164 results on '"Xiang-Yuan Wu"'
Search Results
2. Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion
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Xing Li, Jie Chen, Yong-Jian Chen, Yi-Dan Qiao, Li-Yun Zhao, Nan Jiang, Xiang-Yuan Wu, and Yan-Fang Xing
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Biology (General) ,QH301-705.5 - Abstract
Li et al. show that dexamethasone and lactoferrin induced polymorphonuclear myeloid-derived suppressor cells relieve inflammatory conditions in mouse models with minimal effect on tumour growth. This work demonstrates promise for combating inflammatory adverse events during anti-cancer treatments. more...
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- 2021
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Catalog
3. Eukaryotic initiation factor 4A2 promotes experimental metastasis and oxaliplatin resistance in colorectal cancer
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Zhan-Hong Chen, Jing-Jing Qi, Qi-Nian Wu, Jia-Huan Lu, Ze-Xian Liu, Yun Wang, Pei-Shan Hu, Ting Li, Jin-Fei Lin, Xiang-Yuan Wu, Lei Miao, Zhao-Lei Zeng, Dan Xie, Huai-Qiang Ju, Rui-Hua Xu, and Feng Wang more...
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Colorectal cancer ,Eukaryotic initiation factor 4A2 (EIF4A2) ,PDX ,Silvestrol ,ZNF143 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Deregulation of protein translation control is a hallmark of cancers. Eukaryotic initiation factor 4A2 (EIF4A2) is required for mRNA binding to ribosome and plays an important role in translation initiation. However, little is known about its functions in colorectal cancer (CRC). Methods Analysis of CRC transcriptome data from TCGA identified that EIF4A2 was associated with poor prognosis. Immunohistochemistry study of EIF4A2 was carried out in 297 paired colorectal tumor and adjacent normal tissue samples. In vitro and in vivo cell-biological assays were performed to study the biological functions of EIF4A2 on experimental metastasis and sensitivity to oxaliplatin treatment. Bioinformatic prediction, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were carried out to unveil the transcription factor of EIF4A2 regulation. Results EIF4A2 Expression is significantly higher in colorectal tumors. Multivariate analysis suggests EIF4A2 as an independent predictor of overall, disease-free and progression-free survival. Dysfunction of EIF4A2 by genetic knock-down or small-molecule inhibitor silvestrol dramatically inhibited CRC invasion and migration, sphere formation and enhanced sensitivity to oxaliplatin treatment in vitro and in vivo. Notably, EIF4A2 knock-down also suppressed lung metastasis in vivo. qRT-PCR and immunoblotting analyses identified c-Myc as a downstream target and effector of EIF4A2. ChIP and dual-luciferase reporter assays validated the bioinformatical prediction of ZNF143 as a specific transcription factor of EIF4A2. Conclusions EIF4A2 promotes experimental metastasis and oxaliplatin resistance in CRC. Silvestrol inhibits tumor growth and has synergistic effects with oxaliplatin to induce apoptosis in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models. more...
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- 2019
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4. Maximum Somatic Allele Frequency in Combination With Blood-Based Tumor Mutational Burden to Predict the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer: A Pooled Analysis of the Randomized POPLAR and OAK Studies
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Yu-tong Chen, Sharvesh Raj Seeruttun, Xiang-yuan Wu, and Zi-xian Wang
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maximum somatic allele frequency (MSAF) ,blood-based tumor mutational burden (bTMB) ,atezolizumab ,docetaxel ,non-small cell lung cancer (NSCLC) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Blood-based tumor mutational burden (bTMB) was recently found to be suboptimal in predicting overall survival (OS) benefits of atezolizumab over docetaxel among patients with advanced non-small cell lung cancer (NSCLC). The maximum somatic allele frequency (MSAF) is an indicator of the proportion of tumor-derived plasma DNA, which could affect the concordance between bTMB and tissue-based TMB. Therefore, we aimed to evaluate the utility of MSAF, alone or in combination with bTMB, to identify NSCLC patients with or without survival benefit from atezolizumab over docetaxel.Methods: We analyzed the individual patient-level data from the randomized POPLAR and OAK studies. The bTMB and MSAF were derived from the pre-treatment blood-based genomic data.Results: In both the bTMB-high (i.e., bTMB ≥ 13) and bTMB-low subgroups, atezolizumab significantly improved OS compared with docetaxel (hazard ratio [HR] = 0.43 [95% CI, 0.29–0.65], P < 0.001 and HR = 0.73 [95% CI, 0.61–0.87], P < 0.001, respectively). Among patients with a low MSAF (i.e., MSAF < 10.3%), OS significantly favored atezolizumab (HR = 0.59 [95% CI, 0.48–0.72], P < 0.001), whereas OS with atezolizumab was similar to that with docetaxel in the MSAF-high subgroup (HR = 0.91 [95% CI, 0.68–1.20], P = 0.500; interaction test P = 0.017). Among patients from the bTMB-low and MSAF-high subgroup, OS was numerically worse with atezolizumab than with docetaxel (HR = 1.06 [95% CI, 0.78–1.45], P = 0.710); in contrast, OS was significantly improved with atezolizumab compared with docetaxel in those with either a high bTMB or low MSAF (HR = 0.57 [95% CI, 0.47–0.69], P < 0.001; interaction test P < 0.001). Consistent findings were obtained for progression-free survival data.Conclusions: MSAF alone or in combination with bTMB can effectively distinguish patients with or without survival benefit from atezolizumab compared with docetaxel. MSAF and the combined bTMB-MSAF classification may become practical predictive markers for atezolizumab in advanced NSCLC. more...
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- 2019
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5. Cancer-associated fibroblasts from hepatocellular carcinoma promote malignant cell proliferation by HGF secretion.
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Chang-Chang Jia, Tian-Tian Wang, Wei Liu, Bin-Sheng Fu, XueFeng Hua, Guo-Ying Wang, Tuan-Jie Li, Xing Li, Xiang-Yuan Wu, Yan Tai, Jie Zhou, Gui-Hua Chen, and Qi Zhang
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Medicine ,Science - Abstract
Cancer-associated fibroblasts (CAFs) are reported to support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion in most solid tumors. However, the roles of CAFs in the liver cancer microenvironment have not been thoroughly studied. In our previous study, we successfully isolated CAFs from hepatocellular carcinoma (HCC) (H-CAFs) and proved that H-CAFs suppressed the activation of NK cells and thereby created favorable conditions for HCC progression. In our present study, we found that the proliferation of MHCC97L and Hep3B cells was significantly promoted by treatment with conditioned medium from H-CAFs. Pathological analysis also revealed that H-CAFs increased the proportion of Ki-67 (+) malignant cells and prevented them from undergoing necrosis. Moreover, the concentration of hepatocyte growth factor (HGF) cytokine in the conditioned medium of H-CAFs was higher than conditioned medium from normal skin fibroblasts (NSFs). Anti-HGF significantly reduced the proliferation-promoting capability of H-CAFs. In addition, we found that the abundance of H-CAFs correlated positively with tumor size. These results indicate that H-CAFs are an important factor for promoting the growth of HCC in vitro and in vivo, and that HGF plays a key role in HCC proliferation induced by H-CAFs. more...
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- 2013
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6. Beclin 1 deficiency correlated with lymph node metastasis, predicts a distinct outcome in intrahepatic and extrahepatic cholangiocarcinoma.
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Tian-Tian Wang, Qing-Hua Cao, Ming-Yuan Chen, Qing Xia, Xin-Juan Fan, Xiao-Kun Ma, Qu Lin, Chang-Chang Jia, Min Dong, Dan-Yun Ruan, Ze-Xiao Lin, Jing-Yun Wen, Li Wei, Xing Li, Zhan-Hong Chen, Lei Wang, Xiang-Yuan Wu, and Xiang-Bo Wan more...
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Medicine ,Science - Abstract
Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC. more...
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- 2013
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7. Molecular prognostic prediction for locally advanced nasopharyngeal carcinoma by support vector machine integrated approach.
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Xiang-Bo Wan, Yan Zhao, Xin-Juan Fan, Hong-Min Cai, Yan Zhang, Ming-Yuan Chen, Jie Xu, Xiang-Yuan Wu, Hong-Bo Li, Yi-Xin Zeng, Ming-Huang Hong, and Quentin Liu
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Medicine ,Science - Abstract
BACKGROUND:Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers. METHODOLOGY/PRINCIPAL FINDINGS:Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients. CONCLUSIONS/SIGNIFICANCE:Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways. more...
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- 2012
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8. Supplementary Figure from A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study)
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Rui-Hua Xu, Yu-Hong Li, Feng-Hua Wang, Dong-Sheng Zhang, Hui-Yan Luo, Shuang-Zhen Chen, Si-Mei Shi, Ying Guo, Hong Qiu, Zhi-Qiang Wang, Zong-Jiong Mai, Ying Jin, Xiang-Yuan Wu, Zeng-Qing Guo, Qing-Feng Zou, Ying Yuan, Jie-Er Ying, Fu-Xiang Zhou, Zhi-Xiang Zhuang, Yi-Chen Yao, Zhi-Gang Ma, Xiao-Hua Hu, Wei Wang, Yan Zhang, Wei-Jia Fang, Xiang-Lin Yuan, Yan-Qiao Zhang, Jian Xiao, Ming-Ming He, and Feng Wang more...
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Supplementary Figure from A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study) more...
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- 2023
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9. Supplementary Data from A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study)
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Rui-Hua Xu, Yu-Hong Li, Feng-Hua Wang, Dong-Sheng Zhang, Hui-Yan Luo, Shuang-Zhen Chen, Si-Mei Shi, Ying Guo, Hong Qiu, Zhi-Qiang Wang, Zong-Jiong Mai, Ying Jin, Xiang-Yuan Wu, Zeng-Qing Guo, Qing-Feng Zou, Ying Yuan, Jie-Er Ying, Fu-Xiang Zhou, Zhi-Xiang Zhuang, Yi-Chen Yao, Zhi-Gang Ma, Xiao-Hua Hu, Wei Wang, Yan Zhang, Wei-Jia Fang, Xiang-Lin Yuan, Yan-Qiao Zhang, Jian Xiao, Ming-Ming He, and Feng Wang more...
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Supplementary Data from A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study) more...
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- 2023
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10. Aspirin-induced long-term tumor remission in hepatocellular carcinoma with adenomatous polyposis coli stop-gain mutation: A case report
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Haofan Wang, Xiang-Yuan Wu, Mingjun Bai, Xing Li, Mingsheng Huang, and Qu Lin
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Aspirin ,biology ,Adenomatous polyposis coli ,business.industry ,Hepatocellular carcinoma ,Wnt signaling pathway ,Wnt pathway ,General Medicine ,medicine.disease ,Mutation (genetic algorithm) ,Mutation ,Case report ,biology.protein ,medicine ,Cancer research ,business ,medicine.drug - Abstract
BACKGROUND Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma (HCC) may be a promising remedy. CASE SUMMARY The present case involved an advanced hepatocellular carcinoma (HCC) patient who did not receive local regional therapy and was intolerant to sorafenib. Total RNA extracted from the patient’s tumor tissue was used to obtain the gene mutation profile. The c.3676A>T and c.4402A>T stop-gain mutations in adenomatous polyposis coli (APC) were the most prevalent (42.2% and 35.1%, respectively). MutationMapper analysis indicated that the functional domain of APC was lost in the two APC mutant genes. APC is a major suppressor of the Wnt signaling pathway. Thus, the Wnt pathway was exclusively activated due to APC dysfunction, as other elements of this pathway were not found to be mutated. Aspirin has been reported to suppress the Wnt pathway by inducing β-catenin phosphorylation through the activation of glycogen synthase kinase 3 beta via cyclooxygenase-2 pathway inhibition. Therefore, aspirin was administered to the patient, which achieved four years of disease control. CONCLUSION Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC, with aspirin as an effective treatment option. more...
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- 2021
11. FTO downregulation mediated by hypoxia facilitates colorectal cancer metastasis
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Kai Yu, Qi Zhao, Qi Meng, Rui-Hua Xu, Yang Li, Long Bai, Zexian Liu, Ting Li, Huai-Qiang Ju, Junzhong Lin, Min Wang, Dan-Yun Ruan, De Shen Wang, Xiang-Yuan Wu, Li-Zhi Luo, Ying-Nan Wang, and Jin-Fei Lin more...
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0301 basic medicine ,Cancer Research ,Adenosine ,medicine.medical_treatment ,Down-Regulation ,Protein degradation ,Biology ,Article ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Genetics ,medicine ,Humans ,Molecular Biology ,Annexin A2 ,Messenger RNA ,Kinase ,Growth factor ,nutritional and metabolic diseases ,RNA-Binding Proteins ,medicine.disease ,Colorectal cancer ,Ubiquitin ligase ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Epigenetics ,Colorectal Neoplasms - Abstract
Fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) demethylase, participates in tumor progression and metastasis in many malignancies, but its role in colorectal cancer (CRC) is still unclear. Here, we found that FTO protein levels, but not RNA levels, were downregulated in CRC tissues. Reduced FTO protein expression was correlated with a high recurrence rate and poor prognosis in resectable CRC patients. Moreover, we demonstrated that hypoxia restrained FTO protein expression, mainly due to an increase in ubiquitin-mediated protein degradation. The serine/threonine kinase receptor associated protein (STRAP) might served as the E3 ligase and K216 was the major ubiquitination site responsible for hypoxia-induced FTO degradation. FTO inhibited CRC metastasis both in vitro and in vivo. Mechanistically, FTO exerted a tumor suppressive role by inhibiting metastasis-associated protein 1 (MTA1) expression in an m6A-dependent manner. Methylated MTA1 transcripts were recognized by an m6A “reader”, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which then stabilized its mRNA. Together, our findings highlight the critical role of FTO in CRC metastasis and reveal a novel epigenetic mechanism by which the hypoxic tumor microenvironment promotes CRC metastasis. more...
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- 2021
12. Synergistic effects of α-Mangostin and sorafenib in hepatocellular carcinoma: New insights into α-mangostin cytotoxicity
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Qi Zhang, Dong-Hao Wu, Xiang-Yuan Wu, Ying-fen Hong, Hui-qiang Huang, Zhan-Hong Chen, Chang-Chang Jia, Tian-Tian Wang, and Yang Li
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Male ,0301 basic medicine ,MAPK/ERK pathway ,Gene Expression ,Apoptosis ,Biochemistry ,Mice ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,RNA-Seq ,Cytotoxicity ,Mice, Inbred BALB C ,TOR Serine-Threonine Kinases ,Liver Neoplasms ,Drug Synergism ,Sorafenib ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,medicine.drug ,Carcinoma, Hepatocellular ,Combination therapy ,MAP Kinase Signaling System ,Ubiquitin-Protein Ligases ,Xanthones ,Biophysics ,Mice, Nude ,Antineoplastic Agents ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,neoplasms ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Cell growth ,business.industry ,Membrane Proteins ,Cell Biology ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,digestive system diseases ,030104 developmental biology ,Cancer research ,business - Abstract
Sorafenib remains the standard first-line treatment for advanced hepatocellular carcinoma (HCC), although other clinical trials are currently underway for treatments that show better curative effects. However, some patients are not sensitive to sorafenib. α-Mangostin, extracted from the pericarp of the mangosteen, which is widely used as a traditional medicine, has anticancer and anti-proliferative properties in various types of cancers, including HCC. In the present study, we found that combining sorafenib and α-Mangostin could be synergistically toxic to HCC both in vitro and in vivo. We then demonstrated that the combination of sorafenib and α-Mangostin enhances the inhibition of cell proliferation in HCC cell lines. Combination therapy leads directly to apoptosis. In xenograft mouse models, the in vivo safety and effectivity was confirmed by a reduction in tumor size after combination treatment. RNA sequencing and protein testing showed that the expression of LRRC8A and RNF181 genes and mTOR and MAPK pathways may be associated with the synergistic effect of the two drugs. In conclusion, our results highlight the synergistic effect of the combination of sorafenib and α-Mangostin, which indicates a potential treatment for advanced HCC for patients that are not sensitive to sorafenib therapy. more...
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- 2021
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13. Intratumoral CD45+CD71+ erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma
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Yi-Dan Qiao, Jian-Liang Xu, Xiang-Yuan Wu, Qing-Jian Ye, Xing Li, Nan Jiang, Hui Zhang, and Jie Chen
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0301 basic medicine ,Cancer Research ,Tumor microenvironment ,medicine.diagnostic_test ,Chemistry ,Cancer ,Transferrin receptor ,Immunofluorescence ,medicine.disease ,Immune tolerance ,03 medical and health sciences ,Paracrine signalling ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,medicine - Abstract
CD45+CD71+ erythroid cells generated through splenic extramedullary erythropoiesis have recently been found to suppress anti-infection and tumor immunity in neonates and adults with malignances. However, their role in tumor microenvironment has not been investigated. In the present study, we found that the number of CD45+CD71+ erythroid cells was significantly elevated in hepatocellular carcinoma (HCC) tissues compared to that in paratumor region and circulation. Additionally, they were more abundant in HCC tissues compared to some immune suppressive cells as well as CD45-CD71+ erythroid cells. CD45+CD71+ erythroid cells suppressed T cells through generation of reactive oxygen species, IL-10, and TGF-β in a paracrine and cell-cell contact manner, and their suppressive effect was stronger than that of myeloid-derived suppressor cells. The abundance of CD45+CD71+ erythroid cells in tumor tissue, as illustrated via immunofluorescence, predicted disease-free survival and overall survival, and its prognostic value was better than that of Cancer of the Liver Italian Program score. This study demonstrated that accumulation of intratumoral CD45+CD71+ erythroid cells in HCC tissues could play a superior immunosuppressive role in tumor microenvironment and may serve as a valuable biomarker to predict recurrence of HCC. more...
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- 2021
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14. Prognostic and immunological role of CD36: A pan-cancer analysis
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Xing Li, Jie Chen, Jing-Yun Wen, Yongjian Chen, Xiang-Yuan Wu, Shao-Zhuo Huang, Dagui Lin, Nan Jiang, Wei-Xin Liao, and Yunfang Yu
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Stromal cell ,Methyltransferase ,medicine.medical_treatment ,Cancer ,hemic and immune systems ,Biomarker ,Immunotherapy ,Biology ,medicine.disease ,Immune checkpoint ,Immune system ,Oncology ,Pan-cancer analysis ,parasitic diseases ,Gene expression ,Cancer research ,medicine ,Biomarker (medicine) ,CD36 ,Research Paper ,circulatory and respiratory physiology - Abstract
CD36 plays a critical role in lipid metabolism, which is closely associated with human immunity. However, the role of CD36 in cancer remains unclear. We performed a pan-cancer analysis to elucidate the potential role of CD36 in cancer by investigating its prognostic value and current predictors for the efficacy of immune checkpoint inhibitors (ICIs) in multiple cancer types. CD36 expression in cancer cell lines, tumor tissue, and their adjacent normal tissues displayed heterogeneity among different cancers. Immunohistochemistry was used to detect CD36 expression and confirmed the results. CD36 expression significantly affects prognosis in the six cancer types. High CD36 expression was marginally associated with poorer prognosis in four of them and improved prognosis in the remaining two types. CD36 expression was significantly correlated with the 6 immune infiltrates in most cancer types. In addition, CD36 gene expression was positively correlated with Stromal score, Immune score, and ESTIMATE score. A total of 47 immune checkpoint genes were collected and their relationship with CD36 expression was analyzed. CD36 expression was significantly associated with multiple stimulatory and inhibitory checkpoint molecules with a disease-specific pattern. As to the genes reported to positively relate to the efficacy of ICIs, CD36 expression was positively correlated with most of them but negatively associated with a small proportion of cancer type-specific patterns. Concerning the genes negatively related to the efficacy of ICIs, CD36 expression was positively correlated with NRP1 and TNFSF15 in multiple cancers. CD36 expression was negatively correlated with tumor neoantigen burden in most cancer types. However, CD36 expression was negatively correlated with tumor mutation burden in most cancer types. The correlation between CD36 expression and the four methyltransferases was also significant in multiple cancers, but also with a cancer type-specific pattern. In summary, the current study found CD36 expression and its prognostic value in multiple cancer types. In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs. The practical application value of CD36 is disease specific. more...
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- 2021
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15. Prognostic value of serum HIF-1α change following transarterial chemoembolization in hepatocellular carcinoma
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Qu Lin, He-Ping Li, Xiang-Yuan Wu, Mingsheng Huang, Xing Li, Xiao-Kun Ma, Zhi-Huan Lin, Jie Chen, and Junrong Jiang
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Treatment response ,Carcinoma, Hepatocellular ,Logistic regression ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Chemoembolization, Therapeutic ,Transcatheter arterial chemoembolization ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hematology ,Proportional hazards model ,business.industry ,Liver Neoplasms ,General Medicine ,Middle Aged ,Hypoxia-Inducible Factor 1, alpha Subunit ,Prognosis ,medicine.disease ,Peripheral blood ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,business ,Follow-Up Studies - Abstract
Transarterial chemoembolization (TACE) induces a change in serum HIF-1α level in patients with hepatocellular carcinoma (HCC). This study investigated the prognostic value of change in serum HIF-1α following TACE treatment in HCC patients. A total of 61 hepatocellular carcinoma patients treated with TACE were included. Peripheral blood samples were collected within 1 week before and after TACE to determine the serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) by enzyme-linked immunosorbent assay (ELISA). Serum HIF-1α change was calculated as follows: ∆HIF-1α = (HIF-1α (pre-TACE) - HIF-1α (post-TACE))/HIF-1α (pre-TACE). Likewise, serum VEG-F change was calculated as follows: ∆VEG-F = (VEG-F (pre-TACE) - VEG-F(post-TACE))/VEG-F (pre-TACE). Based on the cutoffs (0.25) determined by the maximum Youden's index in receiver operating characteristic analysis, the patients were grouped into the low ∆HIF-1α group ( 0.25) and the high ∆HIF-1α group ( 0.25). After TACE treatment, HIF-1α was significantly decreased (pre-TACE 1901.62 vs. post-TACE 621.82 pg/ml, P 0.01) but VEGF-A was significantly increased (pre-TACE 60.80 vs. post-TACE 143.81 pg/ml, P 0.01). Multivariate logistic regression analysis demonstrated that ∆HIF-1α was a prognostic factor (OR = 58.09, 95% CI: 1.59-2127.32, P = 0.027) for the TACE treatment response. Furthermore, multivariate Cox regression analysis revealed that ∆HIF-1α was a prognostic factor for progression-free survival (PFS) (HR = 0.30, 95% CI: 0.14-0.66, P = 0.003) and overall survival (OS) (estimated HR = 0.38, 95% CI: 0.16-0.93, P = 0.034). Kaplan-Meier survival analysis showed that the high ∆HIF-1α group was more likely to have longer PFS (log-rank test, P = 0.004) and OS (log-rank test, P = 0.002) than the low ∆HIF-1α group. The change in serum HIF-1α level following TACE is a prognostic factor associated with the TACE treatment response, PFS, and OS in HCC patients following TACE. more...
- Published
- 2020
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16. Retracted: Demethylation of miR‐195 suppresses prostate cancer cell proliferation, migration and invasion
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Liyuan Zou, Xing Li, Zhan-Hong Chen, Xiang-Yuan Wu, Xiao-Kun Ma, and Li Wei
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Male ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,tumor suppressor ,QH301-705.5 ,Down-Regulation ,DNA Methyltransferase Inhibitor ,Apoptosis ,Biology ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Cell Movement ,medicine ,miR‐195 ,Humans ,Genes, Tumor Suppressor ,Neoplasm Invasiveness ,Biology (General) ,Promoter Regions, Genetic ,Research Articles ,Cell Proliferation ,Cell growth ,Prostatic Neoplasms ,Cancer ,Methylation ,DNA Methylation ,medicine.disease ,prostate cancer ,Demethylation ,MicroRNAs ,030104 developmental biology ,CpG site ,Cell culture ,030220 oncology & carcinogenesis ,PC-3 Cells ,Azacitidine ,Cancer research ,CpG Islands ,methylation ,Research Article ,Signal Transduction - Abstract
Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of tumor‐associated deaths worldwide, with increasing incidence rates over the last 10 years. Recently, miR‐195 was reported to be hypermethylated at its promoter CpG island and down‐regulated in hepatocellular carcinoma. However, the function of miR‐195 and the underlying mechanisms in PCa remain unknown. Here, we report that a significant down‐regulation of microRNA‐195 (miR‐195) in PCa tissues and cell lines was associated with promoter methylation status. Overexpression of miR‐195 significantly suppressed cell proliferation, migration, invasion and epithelial–mesenchymal transition (increased E‐cadherin and decreased N‐cadherin) in PCa cells. We further demonstrated that transfection with a miR‐195 inhibitor reversed the inhibitory effect of the DNA methyltransferase inhibitor 5‐azacytidine on the proliferation, migration and invasion ability of PCa cells. In summary, our findings suggest that miR‐195 may function as a crucial tumor suppressor in PCa., The tumor environment of prostate cancer promotes the methylation of microRNA‐195 (miR‐195) promoter, thereby inhibiting the expression of miR‐195, and the methyltransferase inhibitor 5‐azacytidine can reverse the methylation, promote the expression of miR‐195, and inhibit the proliferation, migration and invasion of tumor cells. more...
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- 2020
17. MicroRNA-126 Inhibit Viability of Colorectal Cancer Cell by Repressing mTOR Induced Apoptosis and Autophagy
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Na Cheng, Zhan-Hong Chen, Li Wei, Xiang-Yuan Wu, Dong-Hao Wu, Min Dong, Jie Chen, and Xing Li
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0301 basic medicine ,Autophagy ,Cell ,Transfection ,Biology ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,microRNA ,medicine ,Cancer research ,Pharmacology (medical) ,Viability assay ,Carcinogenesis ,PI3K/AKT/mTOR pathway - Abstract
Objective Colorectal cancer (CRC) is a fatal disease, and tumor development is a complex cellular event involving a multistep cascade process involving proliferation, invasion, and migration. In recent years, it has been shown that microRNA-126 (miR-126) plays a key role in the tumorigenesis of CRC, but further studies are required to investigate the regulatory mechanisms through which this miRNA affects cell viability, autophagy, and apoptosis in CRC. We aimed to study the effect of miR-126 in gene regulation in CRC HCT116 cells. Methods CRC biopsy samples and normal colorectal tissue samples were used for miRNA profiling. Real-time quantitative PCR and WB were utilized to detect RNA and protein levels. MTT and colony formation assays were performed to examine cell viability. Furthermore, an immunofluorescence assay and Annexin V/PI flow cytometry were performed to detect autophagy and apoptosis, respectively. Results The expression of miR-126 was downregulated in CRC biopsies and cell lines compared with that in normal cells and tissues. The upregulation of miR-126 resulted in impaired viability and growth of CRC cells. Furthermore, with the overexpression of miR-126, cell autophagy was increased, as evidenced by LC3-I/II transformation and p62 degradation. Meanwhile, apoptosis induction was also observed because of the increased miR-126 levels. The autophagy inhibitor Bafilomycin A1 (BafA1) repressed both autophagy and apoptosis, indicating that miR-126 induced autophagy was responsible for the induction of apoptosis. A dual-luciferase reporter assay (DLRA) and bioinformatics prediction revealed that miR-126 silenced the mTOR gene by targeting the 3'-UTR. mTOR mRNA levels in CRC biopsy tissues and cell lines were upregulated to a greater extent than that in normal cells and tissues. Furthermore, HCT116 cells transfected with an miR-126 mimic showed a decreased expression of mTOR. In addition, the overexpression of mTOR counteracted miR-126 on autophagy and apoptosis. Conclusion Our study demonstrated that miR-126-induced can regulate the activity of CRC cells via autophagy and apoptosis and suggested a new mechanism of miR-126-mTOR interaction in CRC pathogenesis. more...
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- 2020
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18. A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study)
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Feng Wang, Ming-Ming He, Jian Xiao, Yan-Qiao Zhang, Xiang-Lin Yuan, Wei-Jia Fang, Yan Zhang, Wei Wang, Xiao-Hua Hu, Zhi-Gang Ma, Yi-Chen Yao, Zhi-Xiang Zhuang, Fu-Xiang Zhou, Jie-Er Ying, Ying Yuan, Qing-Feng Zou, Zeng-Qing Guo, Xiang-Yuan Wu, Ying Jin, Zong-Jiong Mai, Zhi-Qiang Wang, Hong Qiu, Ying Guo, Si-Mei Shi, Shuang-Zhen Chen, Hui-Yan Luo, Dong-Sheng Zhang, Feng-Hua Wang, Yu-Hong Li, and Rui-Hua Xu more...
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Bevacizumab ,Cancer Research ,Oncology ,Rectal Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Colonic Neoplasms ,Leucovorin ,Humans ,Antineoplastic Agents ,Ascorbic Acid ,Fluorouracil ,Glucosephosphate Dehydrogenase ,Colorectal Neoplasms - Abstract
Purpose: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). Patients and Methods: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. Results: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70–1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50–0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. Conclusions: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation. more...
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- 2022
19. Inhibition of Autophagy Improves the Efficacy of Abiraterone for the Treatment of Prostate Cancer
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Zhan-Hong Chen, Xing Li, Ze-Xiao Lin, Xiang-Yuan Wu, Xiao-Kun Ma, and Liyuan Zou
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Androgen deprivation therapy ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Cell Line, Tumor ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Autophagy ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Initial therapy ,Pharmacology ,business.industry ,Adenine ,Standard treatment ,General Medicine ,medicine.disease ,Prostatic Neoplasms, Castration-Resistant ,Abiraterone ,030104 developmental biology ,Castration ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Androstenes ,Drug Screening Assays, Antitumor ,business - Abstract
Although androgen deprivation therapy remains the standard treatment for the initial therapy of advanced prostate cancer (PC), castration does not eliminate persistent intratumoral androgens within the prostate tumor microenvironment, which is capable of activating androgen receptor. Abiraterone effectively target adrenal and tumor androgen production in castration-resistant PC (CRPC). However, abiraterone-resistant CRPC is now common challenge in clinic via multiple mechanisms.In this study, human CRPC cell line PC3 and androgen-sensitive cells LNCaP were used. The authors investigated the role of autophagy during the therapy of abiraterone in CRPC by analysis of transmission electron microscopy (TEM), Western blot and immunofluorescence assay. Cell cycle and apoptosis using flow cytometry analysis.The analysis of TEM showed more autophagic vesicles (AVs) in PC3 cell line than that in LNCaP cell line and indicated the high basic cellular autophagy in CRPC cell line PC3, which was confirmed by the upregulation of autophagy-related protein LC3, Atg5, and Beclin1. Interestingly, the treatment of abiraterone reduced the level of autophagic vesicles in two cell lines and inhibited the expressions of autophagic markers LC3, Atg5 and Beclin1 in parallel with decreased cell vitality and induced G2/M arrest in PC3 cell line and LNCaP cell line. Moreover, the addition of the autophagy inhibitor 3-methyladenine to the treatment of abiraterone inhibited the formation of AVs with downregulated autophagic markers, and inhibition of autophagy promoted the efficiency of cytotoxicity of abiraterone with further impaired cell vitality and G2/M arrest.These data suggested that inhibition of autophagy by its inhibitor benefits the treatment of abiraterone for CRPC patients. more...
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- 2019
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20. Intratumoral CD45
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Jie, Chen, Yi-Dan, Qiao, Xing, Li, Jian-Liang, Xu, Qing-Jian, Ye, Nan, Jiang, Hui, Zhang, and Xiang-Yuan, Wu
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Adult ,Male ,Carcinoma, Hepatocellular ,T-Lymphocytes ,Primary Cell Culture ,Kaplan-Meier Estimate ,Risk Assessment ,Disease-Free Survival ,Young Adult ,Hepatitis B, Chronic ,Erythroid Cells ,Antigens, CD ,Receptors, Transferrin ,Tumor Microenvironment ,Hepatectomy ,Humans ,Cells, Cultured ,Aged ,Retrospective Studies ,Liver Neoplasms ,Middle Aged ,Prognosis ,Coculture Techniques ,Italy ,Liver ,Hematopoiesis, Extramedullary ,Leukocyte Common Antigens ,Female ,Tumor Escape ,Neoplasm Recurrence, Local ,Follow-Up Studies - Abstract
CD45
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- 2020
21. Modified CLIP score with the albumin-bilirubin grade retains prognostic value in HBV-related hepatocellular carcinoma patients treated with trans-catheter arterial chemoembolization therapy
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Xiao-Ping Zhang, Min Dong, Zhan-Hong Chen, Meng-Meng Liu, Si-Dong Xie, Qu Lin, Xiu-Rong Cai, Xiao-Kun Ma, Jing-Yun Wen, Jin-Xiang Lin, Xiang-Yuan Wu, and Jie Chen
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medicine.medical_specialty ,Multivariate analysis ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Transcatheter arterial chemoembolization ,Hepatic encephalopathy ,Univariate analysis ,Receiver operating characteristic ,business.industry ,Cancer ,CLIP ,albumin-bilirubin grade ,hepatocellular carcinoma ,medicine.disease ,digestive system diseases ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Liver function ,prognosis ,business ,hepatitis B virus ,Research Paper ,transcatheter arterial chemoembolization - Abstract
Background: The Cancer of the Liver Italian Program (CLIP) score is commonly used for prognosis prediction of hepatocellular carcinoma (HCC). The CLIP includes the Child-Pugh grade, which is relatively subjective, for hepatic encephalopathy assessment. A newly developed scoring system called albumin-bilirubin grade (ALBI grade), consists of albumin and bilirubin to assess liver function reserve objectively. Here, we substituted the ALBI grade for the Child-Pugh grade to establish the ALBI-CLIP scoring system and validated its prognostic value in hepatitis B virus (HBV)-related HCC patients treated with trans-catheter arterial chemoembolization (TACE) therapy. Methods: We retrospectively analyzed HBV-related HCC patients who received TACE therapy. Baseline characteristics were collected and evaluated to classify patients according to ALBI-CLIP, CLIP and TNM systems. Univariate analyses using the Kaplan-Meier method and the log-rank test, as well as multivariate analysis using the Cox proportional hazards regression model, were conducted to detect independent prognostic factors for overall survival. Receiver operating characteristic (ROC) curves and a likelihood ratio test (LRT) were both utilized to compare the values of ALBI-CLIP, CLIP and TNM staging systems in predicting survival. Results: With a total of 389 patients included in the current study, 301 (77.4%) and 88 (22.6%) were classified as Child-Pugh grade A and B, respectively. However, 152 (39.1%), 227 (58.4%) and 10 (2.5%) patients were correspondingly classified into ALBI grade 1, 2 and 3. The areas under the curves of ALBI-CLIP, CLIP and TNM systems were 0.804, 0.778 and 0.734, respectively, for predicting 3-month survival; 0.796, 0.778 and 0.733, respectively, for 6-month survival; 0.697, 0.687 and 0.644, respectively, for 1-year survival; and 0.618, 0.612 and 0.569, respectively, for 2-year survival. The LRT indicated that the ALBI-CLIP and the CLIP had similar values of χ2 and Akaike information criterion (AIC) while the TNM system had the smallest χ2 value (χ2 = 12.1, 11.9, 10.5; AIC = 2620.2, 2620.5, 2621.1 for ALBI-CLIP, CLIP and TNM, respectively). Conclusions: In conclusion, our present study suggested that the ALBI-CLIP scoring system retained the prognostic value of the CLIP in HBV-related HCC treated with TACE therapy. more...
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- 2018
22. The Predictive Value of Albumin-to-Alkaline Phosphatase Ratio for Overall Survival of Hepatocellular Carcinoma Patients Treated with Trans-Catheter Arterial Chemoembolization Therapy
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Zhan Hong Chen, Si Dong Xie, Rui-Hua Xu, Xiao-Ping Zhang, Qu Lin, Xiang Yuan Wu, Xiao Kun Ma, Jin Xiang Lin, Jie Chen, Meng meng Liu, Xiu Rong Cai, Jing Yun Wen, and Min Dong
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medicine.medical_specialty ,Multivariate analysis ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,albumin-to-alkaline phosphatase ratio ,prognostic factor ,Univariate analysis ,Receiver operating characteristic ,business.industry ,trans-catheter arterial chemoembolization therapy ,Area under the curve ,Univariate ,hepatocellular carcinoma ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,serum biomarker ,Cohort ,Alkaline phosphatase ,030211 gastroenterology & hepatology ,business ,Research Paper - Abstract
Background: We have previously reported the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) for advanced hepatocellular carcinoma (HCC) patients who are not receiving any standard anticancer therapy. However, the prognostic value of the AAPR for HCC patients treated with trans-catheter arterial chemoembolization therapy (TACE) was not investigated. Methods: We retrospectively analysed 372 HCC patients treated with TACE (the training cohort) and applied receiver operating characteristic curves (ROC curves) to identify the best cut-off value for the AAPR in this cohort. Then, univariate analyses by the Kaplan-Meier method and multivariate analysis by a Cox proportional hazards regression model were conducted. Both comparisons of the ROC curves and the likelihood ratio test (LRT) were employed to evaluate the abilities of different factors in predicting the survival of patients in this cohort. Finally, the prognostic value of the AAPR was validated in two cohorts: one included 202 HCC patients treated with supportive care (validation cohort I), and the other included 82 HCC patients treated with TACE (validation cohort II). Results: We identified 0.439 as the best cut-off value of the AAPR by ROC curve analysis. An AAPR > 0.439 was significantly correlated with a lower frequency of Child-Pugh grade B, portal vein tumour thrombus (PVTT), T3-4 and lymph node metastasis (P < 0.05). The median overall survival (OS) of the patients with an AAPR > 0.439 was significantly longer than that of those with an AAPR ≤ 0.439 (58.4 m vs 17.8 m, respectively, P < 0.001). The AAPR was identified as an independent prognostic factor after univariate and multivariate analyses (HR = 0.636, P = 0.003). The independent prognostic value of the AAPR was also confirmed in validation cohorts I and II. Additionally, we substituted the AAPR for the Child-Pugh grade in the CLIP system and integrated the AAPR into the TNM system. We found that the area under the curve (AUC) of the AAPR-CLIP system was significantly larger than that of the CLIP and the TNM when predicting 3-month, 6-month, 1-year and 2-year survival (P < 0.05). There was no significant difference between the AUCs for the AAPR-CLIP and the AAPR-TNM. The LRT suggested that both AAPR-CLIP and AAPR-TNM had significantly larger χ2 values and smaller AIC values than that of their corresponding primary system (P < 0.05). Conclusions: The AAPR was an independent prognostic index for the HCC patients treated with TACE. Both AAPR-CLIP and AAPR-TNM outperformed their corresponding primary system in predicting OS in the current study. more...
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- 2018
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23. Combination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma
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Qu Lin, Zhan-Hong Chen, Jing-Yun Wen, Xing Li, Xiao-Kun Ma, Xiang-Yuan Wu, Dong-Hao Wu, Dan-Yun Ruan, Chang-Chang Jia, and Tian-Tian Wang
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cohort Studies ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Autophagy-Related Protein-1 Homolog ,Humans ,Progression-free survival ,Stage (cooking) ,Survival analysis ,Pharmacology ,Tissue microarray ,business.industry ,Liver Neoplasms ,Autophagy ,Intracellular Signaling Peptides and Proteins ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,Hepatocellular carcinoma ,Biomarker (medicine) ,Female ,business ,Microtubule-Associated Proteins ,Follow-Up Studies - Abstract
Background Autophagy involves in both prevention and promotion in cancer, and its role probably changed during tumor development. Defined the dynamic function of autophagy in cancer may advance precision diagnostics, treatment, and guide drug design. Autophagy related protein ULK1 is key regulator of autophagy, and its role in hepatocellular carcinoma (HCC) was still unclear. This study aims to investigate ULK1’s capacity along with other autophagic markers in predicting prognosis of HCC and explore position of these biomarkers in dynamic function of autophagy during HCC progression. Methods The expression of ULK1 and other autophagic marker (LC3B) were test by Tissue microarray-based immunohistochemistry in 156 operable HCC patients. Survival analysis and correlation analysis were used to analysis influence of ULK1 and combined biomarker on clinical characteristics and prognosis. Results The expression level of ULK1 was not related to all clinicopathological features, however, high expression of the ULK1 as well as LC3B overexpression suggested large tumor size (P = 0.035), high levels of serum AFP (P = 0.049), more frequency of node metastasis (P = 0.015), later TNM stage (P = 0.009). Survival analysis showed that ULK1 expression were negatively correlated with PFS rather than OS in HCC patients (P = 0.021), while LC3B were suggested to be negatively related with patients’ PFS, However, Simultaneous high expression of ULK1 and LC3B had a poorer 5-year overall survival (OS) rate (P = 0.002) and shorter 5-year progression free survival (PFS)(P = 0.003), Further multivariate analysis revealed that the two combined biomarkers were independent factors to predict the prognosis of OS and PFS in all patients, while ULK1 alone or LC3B alone were only an independent predict factor for OS or PFS respectively. Conclusion ULK1 were demonstrated to be an important prognostic factor for HCC patient, and it combined LC3B would improve prognosis assessment of the patients. Combined autophagic biomarkers would better represent dynamic stage of autophagy and It might provide a potential therapeutic way that how to interfere autophagy in HCC. more...
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- 2018
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24. Elevated baseline serum lactate dehydrogenase indicates a poor prognosis in primary duodenum adenocarcinoma patients
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Rui-Hua Xu, Miao Zhen Qiu, Zhao Lei Zeng, Yun Wang, Feng Wang, Jia Huan Lu, Zhan Hong Chen, Qi Nian Wu, Xiao Li Wei, and Xiang Yuan Wu
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0301 basic medicine ,medicine.medical_specialty ,Poor prognosis ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Lactate dehydrogenase ,Medicine ,Radical surgery ,Stage (cooking) ,business.industry ,Cancer ,lactate dehydrogenase ,primary duodenum adenocarcinoma ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,serum biomarker ,Duodenum ,Adenocarcinoma ,prognosis ,business ,Serum lactate dehydrogenase ,Research Paper - Abstract
Purpose: Tumour cells produce energy through glycolysis and lactate dehydrogenase (LDH) is a key part of glycolysis. Elevation of serum LDH may indicate poor prognosis in primary duodenum adenocarcinoma. We aim to explore the prognostic significance of LDH in this disease. Methods and materials: Two hundred forty-four patients diagnosed with primary duodenum adenocarcinoma who were treated at the Sun Yat-sen Cancer Center from February 1996 to January 2016 were retrospectively analysed. We collected routine clinical data, including baseline LDH. Patients were classified into a normal LDH group (≤ 245U/L) and higher LDH group (>245U/L). Correlations of the LDH level and other clinicopathological characteristics were explored using the Chi-square test. Prognostic factors for overall survival were identified using univariate and multivariate analyses. Results: Two hundred seven patients (84.9%) had normal LDH levels, while 37 patients (15.1%) had abnormally high LDH levels. Higher LDH levels were significantly associated with more distant metastasis, node metastasis, poor differentiation and TNM stage Ⅲ-Ⅳ (P more...
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- 2018
25. Identification of the prognostic value of lymphocyte-to-monocyte ratio in patients with HBV-associated advanced hepatocellular carcinoma
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Dan‑Yun Ruan, Jing Yun Wen, Ze‑Xiao Lin, Ying‑Fen Hong, Jie Chen, Zhan Hong Chen, Xing Li, Li Wei, Tian-Tian Wang, Xiao Kun Ma, Qu Lin, Xiang Yuan Wu, Min Dong, Xiu Rong Cai, and Dong‑Hao Wu
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,lymphocyte-to-monocyte ratio ,chronic hepatitis B virus infection ,medicine.disease_cause ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Ascites ,Medicine ,Hepatitis B virus ,Tumor microenvironment ,Receiver operating characteristic ,business.industry ,Proportional hazards model ,Cancer ,Articles ,medicine.disease ,digestive system diseases ,030104 developmental biology ,inflammation ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,prognosis ,advanced hepatocellular carcinoma ,medicine.symptom ,business - Abstract
The inflammatory microenvironment serves an important function in the progression of hepatocellular carcinoma (HCC). Peripheral blood lymphocyte-to-monocyte ratio (LMR), as a novel inflammatory biomarker combining an estimate of host immune homeostasis with the tumor microenvironment, has been identified to be a predictor of clinical outcomes in a number of malignancies. The present study aimed at investigating the prognostic value of LMR in patients with hepatitis B virus (HBV)-associated advanced HCC. A total of 174 patients with HBV-associated advanced HCC, without fever or signs of infections, were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival time. Univariate and multivariate analysis was performed using Cox's proportional hazards model. A threshold value was determined using a time-dependent receiver operating characteristic curve. Univariate and multivariate analysis identified LMR as an independent prognostic factor in overall survival (OS) time in patients with HBV-associated advanced HCC (P2.22). The OS time of the high LMR group was significantly longer compared with the low LMR group (P more...
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- 2017
26. Validation and ranking of seven staging systems of hepatocellular carcinoma
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Ze‑Xiao Lin, Jie Chen, Jing Yun Wen, Rui-Hua Xu, Li Wei, Qu Lin, Dong‑Hao Wu, Xiao Kun Ma, Jin-Xiang Lin, Min Dong, Xiang Yuan Wu, Tian-Tian Wang, Xing Li, Dan‑Yun Ruan, Zhan Hong Chen, and Ying‑Fen Hong more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,neoplasm staging ,Survival analysis ,Tumor size ,Receiver operating characteristic ,business.industry ,Cancer ,Articles ,hepatocellular carcinoma ,medicine.disease ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Absolute neutrophil count ,030211 gastroenterology & hepatology ,prognosis ,Liver cancer ,business ,hepatitis B virus - Abstract
The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622, respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575, respectively. For 3-month mortality, the prognostic value of CLIP ranked highest, followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked highest, followed by JIS. No significant difference between the AUCs of CLIP and CIS (P>0.05) in their predictive value for 3-month mortality was observed. The AUC of CLIP was significantly higher compared with that of the other staging systems (P more...
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- 2017
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27. Advance directives: cancer patients' preferences and family-based decision making
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Qu Lin, Yan-Fang Xing, Xing Li, Xiao-Kun Ma, Jin-Xiang Lin, Xiang-Yuan Wu, Liang-Hong Yin, Li Wei, Jie Chen, and Dong-Hao Wu
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Decision Making ,Alternative medicine ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,medicine ,cancer ,Humans ,Family ,030212 general & internal medicine ,Patient participation ,China ,patients’ preference ,Aged ,business.industry ,Cancer ,Patient Preference ,Awareness ,Middle Aged ,Patient Acceptance of Health Care ,Medical decision making ,medicine.disease ,Directive ,Chinese people ,advance directive ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,medical decision making ,Female ,Patient Participation ,Advance Directives ,business ,Research Paper - Abstract
// Yan-Fang Xing 1, 2, 3, * , Jin-Xiang Lin 4, * , Xing Li 4, * , Qu Lin 4, * , Xiao-Kun Ma 4, * , Jie Chen 4 , Dong-Hao Wu 4 , Li Wei 4 , Liang-Hong Yin 1, 2 , Xiang-Yuan Wu 4 1 Department of Nephrology, First Affiliated Hospital of Jinan University, Guangzhou 510630, People’s Republic of China 2 School of Medicine, Jinan University, Guangzhou 510632, People’s Republic of China 3 Department of Nephrology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, People’s Republic of China 4 Department of Medical Oncology, Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China * These authors contributed equally to this work Correspondence to: Liang-Hong Yin, email: 13725251458@126.com Xiang-Yuan Wu, email: wuxiangy@mail.sysu.edu.cn Keywords: advance directive, medical decision making, cancer, patients’ preference Received: February 08, 2017 Accepted: March 21, 2017 Published: April 28, 2017 ABSTRACT Background: Advance directives are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, and these decisions might violate patients’ personal will. Objectives: This study aimed to examine the acceptance of advance directives among Chinese cancer patients and their families and patient participation in this procedure and, finally, to analyze the moral risk involved. Results: While 246 patients and their family members refused official discussion of an advance directive, the remaining 166 patients and their families accepted the concept of an advance directive and signed a document agreeing to give up invasive treatment when the anti-cancer treatment was terminated. Of these, only 24 patients participated in the decision making. For 101 patients, anti-cancer therapy was ended prematurely with as many as 37 patients not told about their potential loss of health interests. Materials and Methods: Participants were 412 adult cancer patients from 9 leading hospitals across China. An advance directive was introduced to the main decision makers for each patient; if they wished to sign it, the advance directive would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients’ awareness of their disease, and participation in an advance directive. Conclusions: Advance directives were not widely accepted among Chinese cancer patients unless anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an advance directive. more...
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- 2017
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28. Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value for hepatocellular carcinoma patients
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Jie Zhou, Ai-Hua Lei, Xiang-Yuan Wu, Zhi-Huan Lin, Xing Li, Yan-Fang Xing, Qiang Xiao, and Ying-Fen Hong
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Adult ,Male ,0301 basic medicine ,Oncology ,Nephrology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Neutrophils ,medicine.medical_treatment ,Peripheral blood mononuclear cell ,Targeted therapy ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,neutrophil counts ,Internal medicine ,medicine ,Humans ,Aged ,Proportional hazards model ,business.industry ,Liver Neoplasms ,hepatocellular carcinoma ,Middle Aged ,Prognosis ,medicine.disease ,myeloid derived suppressor cell ,030104 developmental biology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Immunology ,Myeloid-derived Suppressor Cell ,Absolute neutrophil count ,Female ,business ,Research Paper ,patient selection - Abstract
// Xing Li 1, 2, 3 , Yan-Fang Xing 4 , Ai-Hua Lei 1, 2 , Qiang Xiao 1, 2 , Zhi-Huan Lin 3 , Ying-Fen Hong 3 , Xiang-Yuan Wu 3 , Jie Zhou 1, 2 1 Program in Immunology, Affiliated Guangzhou Women and Children’s Medical Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China 2 Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China 3 Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China 4 Department of Nephrology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Correspondence to: Xiang-Yuan Wu, email: wuxiangy@mail.sysu.edu.cn Jie Zhou, email: zhouj72@mail.sysu.edu.cn Keywords: neutrophil counts, hepatocellular carcinoma, patient selection, prognosis, myeloid derived suppressor cell Received: October 07, 2016 Accepted: February 06, 2017 Published: February 17, 2017 ABSTRACT Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r 2 = 0.2875, p < 0.0001), neutrophils (r 2 = 0.3630, p < 0.0001) and platelet counts (r 2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) ( p = 0.000, HR 1.065, 95% CI 1.028–1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy. more...
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- 2017
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29. The Association of Incidence of Face-Touching Behaviors with Masks Wearing Rates During the Coronavirus Disease 2019 Pandemic
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Xing Li, Jing-Yun Wen, Yong-Jian Chen, Xiang-Yuan Wu, Jian-Liang Xu, Jie Chen, Gang Qin, and Hai Li
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education.field_of_study ,Family planning ,Informed consent ,Incidence (epidemiology) ,Population ,Pandemic ,Face (sociological concept) ,East Asia ,Psychology ,education ,China ,Demography - Abstract
Background: Mandatory mask wearing policy for general population in public areas were the most controversial mitigative measure for the coronavirus disease 2019 (COVID-19) pandemic. Thus, it was imperative to investigate its influence on the incidence of face touching behaviors. Methods: Videos displaying mask-wearing and face-touching behaviors of general population in public areas were analyzed. Period before the COVID-19 epidemic were defined as January 2018 to October 2019, and those during the pandemic were from February 2020 to August 2020 in East Asia, and March to August 2020 in Europe and United States (US). Findings: 37 videos (4699 individuals) before the pandemic with 135 videos (8217 individuals) were included. The mask wearing rates all increased significantly during the pandemic. However, the incidence of face touching behaviors maintained. The incidence of eyes, nose and mouth touching behaviors decreased in East Asia and Europe, instead of US. Mask wearing rates was negatively related to incidences of face touching behaviors, especially in East Asia. Surprisingly, when mask wearing rates were >0% and more...
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- 2020
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30. Neutrophil-to-Apolipoprotein A1 Ratio Predicted Overall Survival in Hepatocellular Carcinoma Receiving Transarterial Chemoembolization
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Zi-Ming Liang, Nan Jiang, Xing Li, Yongjian Chen, Zhuo Liu, Xiang-Yuan Wu, Ming-Jun Bai, Jian-Liang Xu, Jie Chen, and Yan-Fang Xing
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Neutrophils ,Gastroenterology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Chemoembolization, Therapeutic ,Retrospective Studies ,biology ,Apolipoprotein A-I ,business.industry ,Proportional hazards model ,Liver Neoplasms ,Cancer ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cohort ,biology.protein ,Apolipoprotein A1 ,Hepatobiliary ,business ,Lipoprotein - Abstract
Purpose The purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE). Patients and Methods We investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1–positive (LOX-1+) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated. Results Multivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR ( Conclusion This study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level. Implications for Practice The present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1–positive polymorphonuclear myeloid-derived suppressor cells. more...
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- 2019
31. Maximum Somatic Allele Frequency in Combination With Blood-Based Tumor Mutational Burden to Predict the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer: A Pooled Analysis of the Randomized POPLAR and OAK Studies
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Sharvesh Raj Seeruttun, Zi-Xian Wang, Xiang-Yuan Wu, and Yu-tong Chen
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0301 basic medicine ,Oncology ,atezolizumab ,Cancer Research ,medicine.medical_specialty ,Somatic cell ,Concordance ,non-small cell lung cancer (NSCLC) ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Atezolizumab ,Internal medicine ,medicine ,docetaxel ,Lung cancer ,Allele frequency ,Original Research ,business.industry ,Hazard ratio ,maximum somatic allele frequency (MSAF) ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,blood-based tumor mutational burden (bTMB) ,030104 developmental biology ,Docetaxel ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Background: Blood-based tumor mutational burden (bTMB) was recently found to be suboptimal in predicting overall survival (OS) benefits of atezolizumab over docetaxel among patients with advanced non-small cell lung cancer (NSCLC). The maximum somatic allele frequency (MSAF) is an indicator of the proportion of tumor-derived plasma DNA, which could affect the concordance between bTMB and tissue-based TMB. Therefore, we aimed to evaluate the utility of MSAF, alone or in combination with bTMB, to identify NSCLC patients with or without survival benefit from atezolizumab over docetaxel.Methods: We analyzed the individual patient-level data from the randomized POPLAR and OAK studies. The bTMB and MSAF were derived from the pre-treatment blood-based genomic data.Results: In both the bTMB-high (i.e., bTMB ≥ 13) and bTMB-low subgroups, atezolizumab significantly improved OS compared with docetaxel (hazard ratio [HR] = 0.43 [95% CI, 0.29–0.65], P < 0.001 and HR = 0.73 [95% CI, 0.61–0.87], P < 0.001, respectively). Among patients with a low MSAF (i.e., MSAF < 10.3%), OS significantly favored atezolizumab (HR = 0.59 [95% CI, 0.48–0.72], P < 0.001), whereas OS with atezolizumab was similar to that with docetaxel in the MSAF-high subgroup (HR = 0.91 [95% CI, 0.68–1.20], P = 0.500; interaction test P = 0.017). Among patients from the bTMB-low and MSAF-high subgroup, OS was numerically worse with atezolizumab than with docetaxel (HR = 1.06 [95% CI, 0.78–1.45], P = 0.710); in contrast, OS was significantly improved with atezolizumab compared with docetaxel in those with either a high bTMB or low MSAF (HR = 0.57 [95% CI, 0.47–0.69], P < 0.001; interaction test P < 0.001). Consistent findings were obtained for progression-free survival data.Conclusions: MSAF alone or in combination with bTMB can effectively distinguish patients with or without survival benefit from atezolizumab compared with docetaxel. MSAF and the combined bTMB-MSAF classification may become practical predictive markers for atezolizumab in advanced NSCLC. more...
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- 2019
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32. EBV-miR-BART10-3p and EBV-miR-BART22 promote metastasis of EBV-associated gastric carcinoma by activating the canonical Wnt signaling pathway
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Chun-kui Shao, Xiao-fang Zhang, Min Dong, Yi-wang Zhang, Da-yang Hui, Jian-Ning Chen, Li-ping Gong, Xiao-xiao Zhao, and Xiang-yuan Wu
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0301 basic medicine ,Male ,Cancer Research ,Herpesvirus 4, Human ,Adenomatous polyposis coli ,Biology ,Deep sequencing ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Stomach Neoplasms ,Cell Line, Tumor ,microRNA ,medicine ,Gene silencing ,Humans ,Neoplasm Invasiveness ,Neoplasm Metastasis ,Wnt Signaling Pathway ,Cell Proliferation ,Base Sequence ,Wnt signaling pathway ,Cell migration ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,DKK1 ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Cancer research ,biology.protein ,Disease Progression ,Molecular Medicine ,Female - Abstract
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) constitutes the largest subpopulation in EBV-associated tumors worldwide. To date, 44 mature EBV-encoded microRNAs (EBV miRNAs) have been identified, but their roles in EBVaGC development are still poorly understood. In this study, we aimed to investigate the roles and targets of ebv-miR-BART10-3p (BART10-3p) and ebv-miR-BART22 (BART22) in EBVaGC. EBV miRNA expression in EBVaGCs was evaluated by deep sequencing and qRT-PCR, and relationships between BART10-3p or BART22 expression and clinicolpathological characteristics and survival rates of patients with EBVaGC were analyzed. The roles of BART10-3p and BART22 and their underlying mechanisms were further investigated through exogenous overexpression or silencing in EBVaGC cells, and validated in clinical EBVaGC tissue samples. BART10-3p and BART22 were found to be highly expressed in the EBVaGC cell lines SNU719 and YCCEL1. Higher expression of BART10-3p or BART22 in primary EBVaGC samples was significantly associated with lymph node metastasis and a worse 5-year overall survival. BART10-3p and BART22 promoted cell migration and invasion by targeting adenomatous polyposis coli (APC) and Dickkopf 1 (DKK1), thereby activating the Wnt signaling pathway and, consequently, upregulating downstream Twist and downregulating downstream E-cadherin. In 874 primary gastric carcinoma samples, APC and DKK1 were found to be lower expressed in EBVaGC than in EBV-negative samples, and their expression levels were inversely correlated with those of BART10-3p and BART22 in 71 EBVaGC samples. From our data we conclude that BART10-3p and BART22 play vital roles in promoting EBVaGC metastasis by targeting APC and DKK1 and, subsequently, activating the Wnt signaling pathway, thereby providing novel prognostic biomarkers and potential therapeutic targets for EBVaGC. more...
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- 2019
33. Eukaryotic initiation factor 4A2 promotes experimental metastasis and oxaliplatin resistance in colorectal cancer
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Lei Miao, Huai-Qiang Ju, Dan Xie, Jing-Jing Qi, Jia-huan Lu, Zhan-Hong Chen, Zhao-Lei Zeng, Ting Li, Rui-Hua Xu, Yun Wang, Zexian Liu, Xiang-Yuan Wu, Jin-Fei Lin, Qi-Nian Wu, Pei-Shan Hu, and Feng Wang more...
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0301 basic medicine ,Male ,Cancer Research ,Colorectal cancer ,Transcriptome ,Mice ,0302 clinical medicine ,Cell Movement ,Eukaryotic initiation factor ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Immunohistochemistry ,ZNF143 ,Oxaliplatin ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Female ,Colorectal Neoplasms ,medicine.drug ,Adult ,Antineoplastic Agents ,Biology ,lcsh:RC254-282 ,Silvestrol ,03 medical and health sciences ,Eukaryotic translation ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Transcription factor ,Eukaryotic initiation factor 4A2 (EIF4A2) ,PDX ,Aged ,Cell Proliferation ,Research ,medicine.disease ,Survival Analysis ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,030104 developmental biology ,Drug Resistance, Neoplasm ,Eukaryotic Initiation Factor-4A ,Cancer research ,Chromatin immunoprecipitation ,Biomarkers - Abstract
Background Deregulation of protein translation control is a hallmark of cancers. Eukaryotic initiation factor 4A2 (EIF4A2) is required for mRNA binding to ribosome and plays an important role in translation initiation. However, little is known about its functions in colorectal cancer (CRC). Methods Analysis of CRC transcriptome data from TCGA identified that EIF4A2 was associated with poor prognosis. Immunohistochemistry study of EIF4A2 was carried out in 297 paired colorectal tumor and adjacent normal tissue samples. In vitro and in vivo cell-biological assays were performed to study the biological functions of EIF4A2 on experimental metastasis and sensitivity to oxaliplatin treatment. Bioinformatic prediction, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were carried out to unveil the transcription factor of EIF4A2 regulation. Results EIF4A2 Expression is significantly higher in colorectal tumors. Multivariate analysis suggests EIF4A2 as an independent predictor of overall, disease-free and progression-free survival. Dysfunction of EIF4A2 by genetic knock-down or small-molecule inhibitor silvestrol dramatically inhibited CRC invasion and migration, sphere formation and enhanced sensitivity to oxaliplatin treatment in vitro and in vivo. Notably, EIF4A2 knock-down also suppressed lung metastasis in vivo. qRT-PCR and immunoblotting analyses identified c-Myc as a downstream target and effector of EIF4A2. ChIP and dual-luciferase reporter assays validated the bioinformatical prediction of ZNF143 as a specific transcription factor of EIF4A2. Conclusions EIF4A2 promotes experimental metastasis and oxaliplatin resistance in CRC. Silvestrol inhibits tumor growth and has synergistic effects with oxaliplatin to induce apoptosis in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Electronic supplementary material The online version of this article (10.1186/s13046-019-1178-z) contains supplementary material, which is available to authorized users. more...
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- 2019
34. Safety and efficacy of apatinib as third or later line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma: A post-marketing phase IV study
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Xiaoyan Lin, Jin Li, Lu Wen, Guifang Zhang, Zhiguo Hou, Junsheng Wang, Wenying Deng, Yi Ba, Tongfu Jia, Jun Zhao, Shukui Qin, Ying Sun, Yifu He, Yuxian Bai, Weijian Guo, Xiang-Yuan Wu, Da Jiang, Feng Gao, Haijun Zhong, and Jianwei Yang more...
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Cancer Research ,medicine.drug_class ,business.industry ,High selectivity ,Advanced gastric cancer ,Gastroesophageal Junction Adenocarcinoma ,Small molecule ,Tyrosine-kinase inhibitor ,chemistry.chemical_compound ,Oncology ,chemistry ,Cancer research ,medicine ,Apatinib ,business - Abstract
e16034 Background: Apatinib, a small molecule multi-target tyrosine kinase inhibitor with high selectivity for VEGFR-2, has been approved for the treatment of advanced gastric cancer or gastroesophageal adenocarcinoma in China by significantly improving progression-free survival (PFS) and overall survival (OS). Here, we report safety and efficacy data from an open-label, single-arm, multicenter, phase IV trial of apatinib as a third-line or later line treatment for advanced gastric cancer. Methods: Eligible patients had histologically or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate haematological and hepatic function; and failure of at least two lines of chemotherapy. Patients received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included PFS and OS. Results: The intention-to-treat population (ITT) included 2004 patients. At baseline, the median age was 59 (range, 19-85) years, ECOG performance status of 0/1/2 (%) was 15.4/68.8/15.1, and stage III/IV was 3.5/96.4; 98.8% had metastases, and among which metastatic foci≤2/ > 2 was 64.5/34.2 (%), respectively. 89.6% of the patients were given apatinib 500mg as the initial does and the median treatment duration was 56 days. After a median follow-up of 126.5 days, adverse events (AEs) occurred in 95.1% of the patients and 70.3% were grade ≥3. 87.9% of the patients experienced treatment-related AEs (TRAEs), of which 51% had grade ≥3, 12.3% and 16.8% reduced dose and discontinued the treatment, respectively. 57 (2.9%) TRAEs-related deaths were reported, mainly because of gastrointestinal bleeding (16 cases), upper gastrointestinal haemorrhage (7), cerebral haemorrhage (2), and gastric perforation (1). The incidence of TRAEs of special interest was 74.3%; 38.1% of patients developed grade≥3, mainly including hypertension (26.3%), bleeding (5.1%), proteinuria (4.5%), and hand-foot syndrome (3.1%). In an ITT population, median PFS was 2.7 months (95%CI 2.23-2.79) and median OS was 5.8 months (95% CI 5.42-6.11). Conclusions: This study confirms that apatinib has a well-established and manageable safety profile and survival benefit as third or later line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma. Clinical trial information: NCT02426034. more...
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- 2021
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35. Combination therapy with vincristine, immunoglobulin and glucocorticosteroid (VIG regimen) is very effective for the management of grade 3/4 or steroid-refractory immune-related adverse events (irAE) secondary to PD-1 blockade
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Zhan-Hong Chen, Tian-Tian Wang, Li Wei, Qu Lin, and Xiang-Yuan Wu
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Oncology ,Cancer Research ,medicine.medical_specialty ,Vincristine ,Combination therapy ,biology ,business.industry ,Regimen ,Immune system ,Internal medicine ,medicine ,biology.protein ,Pd 1 blockade ,Antibody ,Steroid refractory ,Adverse effect ,business ,medicine.drug - Abstract
e14577 Background: The management of grade 3/4 or steroid-refractory immune related adverse events (irAE) is based on a paucity of retrospective data analysis. Our initial experience with the combination therapy with Vincristine (VCR), immunoglobulin (IVIG) and glucocorticosteroid (VIG regimen) showed clinical improvement in a wide variety of irAEs. As a result, we recommend the use of VIG regimen for the management of grade 3/4 or steroid-refractory irAEs. Methods: The character and clinical course of irAEs were abstracted from the medical record and analyzed. The components of VIG regimens are as follows: Methylprednisolone (MP) 2-10mg/kg for 3days, VCR 1.4mg/m2 (≤2mg) continuous infusion for 4-8 hours on day 3 once a week with Immunoglobulin (IVIG) 0.4g/kg for 3-5 days. The dose of MP and IVIG will be reduced quickly after irAE improves. VCR 1.4mg/m2 once a week will be used for 1 to 3 times according to the improvement. Clinical improvement was defined as either: documentation of resolution of symptoms and normalisation of biochemical tests or hospital discharge within 14 days. Results: A total of 25 patients had grade3/4 or steroid-refractory irAEs after receiving immune checkpoint inhibitors and then received VIG regimen. Among them, 22 patients have been significantly improved, with an improvement rate of 88%. Twenty-three patents were treated in the inpatient setting (92%). The index grade 3/4 irAE was pneumonitis in 28%, immune mediated hepatotoxicity(IMH) in 28%, rash/SJS/TEN in 24%, cerebritis in 8 % and one case each of ITP, Near blindness and severe oral mucositis. In 7 patients with severe IMH, the range of total bilirubin was 80-481umol/L and ALT 35-5000u/L. Six patients with IMH recover well but one patient did not recover to normal due to IMH complicated with pneumonitis and TEN . Clinical improvement was noted in 22/25 patients (88%), 11 patients (44%) required a single dose, while 12 patients (48%) required two doses, 2 patients(8%) required three doses of VCR 1.4mg/m2 continuous infusion for 4-8 hours. What is impressive is that the two patients with encephalitis were significantly relieved within 2 weeks after using the VIG regimen. One patient with TEN (SCORETEN 3)was significantly improved and discharged from our hospital 11 days after using the VIG regimen. A patient with near-blind eyesight recovered to normal 3 days after using the VIG regimen. Conclusions: VIG regimen may be an effective therapeutic option for the management of grade3/4 or steroid-refractory irAEs secondary to immune checkpoint blockade. However, randomized trials are needed to better elucidate the efficacy and safety of VIG regimen. more...
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- 2021
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36. Nomogram for preoperative estimation of long-term survival of patients who underwent curative resection with hepatocellular carcinoma beyond Barcelona clinic liver cancer stage A1
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Tian-Tian Wang, Hui Zhao, Min Dong, Ze-Xiao Lin, Xiang-Yuan Wu, Yang Li, Dong-Hao Wu, Jie Chen, Dan-Yun Ruan, and Qu Lin
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Barcelona clinic liver cancer stage ,Adult ,Male ,Curative resection ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,genetic structures ,Kaplan-Meier Estimate ,survival ,Risk Assessment ,Disease-Free Survival ,Resection ,nomogram ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Long term survival ,medicine ,Hepatectomy ,Humans ,resection ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,business.industry ,Proportional hazards model ,Liver Neoplasms ,Retrospective cohort study ,hepatocellular carcinoma ,Middle Aged ,Nomogram ,Prognosis ,medicine.disease ,Surgery ,Survival Rate ,Nomograms ,Oncology ,Barcelona Clinic Liver Cancer Stage ,Spain ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,business ,Research Paper ,Follow-Up Studies - Abstract
// Dan-Yun Ruan 1, * , Ze-Xiao Lin 1, * , Tian-Tian Wang 1, * , Hui Zhao 2 , Dong-Hao Wu 1 , Jie Chen 1 , Min Dong 1 , Qu Lin 1 , Xiang-Yuan Wu 1 , Yang Li 2 1 Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China 2 Department of Liver Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China * These authors contributed equally to this work Correspondence to: Yang Li, email: Liyang840920@hotmail.com Xiang-Yuan Wu, email: Wuxiangy@mail.sysu.edu.cn Keywords: hepatocellular carcinoma, Barcelona clinic liver cancer stage, resection, nomogram, survival Received: April 10, 2016 Accepted: August 10, 2016 Published: August 17, 2016 ABSTRACT Background and Aims: This retrospective cohort study developed a prognostic nomogram to predict the survival of hepatocellular carcinoma (HCC) patients diagnosed as beyond Barcelona clinic liver cancer stage A1 after resection and evaluated the possibility of using the nomogram as a treatment algorithm reference. Results: The predictors included in the nomogram were total tumour volume, Child-Turcotte-Pugh class, plasma fibrinogen and portal vein tumour thrombus. Patients diagnosed as beyond A1 were stratified into low-, medium- and high-risk groups using nomogram scores of 0 and 51 with the total points of 225. Patients within A1 exhibited similar recurrence-free survival (RFS) and overall survival (OS) rates compared with the low-risk group. Patients in the medium-risk group exhibited a similar OS but a worse RFS rates compared with patients within A1. The high-risk group was associated with worse RFS and OS rates compared with the patients within A1 (3-year RFS rates, 27.0% vs. 60.3%, P < 0.001; 3-year OS rates, 49.2% vs. 83.1%, P < 0.001). Methods: A total of 352 HCC patients undergoing curative resection from September 2003 to December 2012 were included to develop a nomogram to predict overall survival after resection. Univariate and multivariate survival analysis were used to identify prognostic factors. A visually orientated nomogram was constructed using a Cox proportional hazards model. Conclusions: This user-friendly nomogram offers an individualized preoperative recurrence risk estimation and stratification for HCC patients beyond A1 undergoing resection. Resection should be considered the first-line treatment for low-risk patients. more...
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- 2016
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37. Expression and prognostic roles of PIK3CA, JAK2, PD-L1, and PD-L2 in Epstein-Barr virus–associated gastric carcinoma
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Xiang-yuan Wu, Jian-ning Chen, Hong Du, Yi-wang Zhang, Xiao-xiao Zhao, Yan Huang, Chun-kui Shao, Hai-gang Li, Ling Xue, Hai-yan Wang, and Min Dong
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Male ,0301 basic medicine ,China ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Class I Phosphatidylinositol 3-Kinases ,Kaplan-Meier Estimate ,In situ hybridization ,Adenocarcinoma ,Biology ,B7-H1 Antigen ,Virus ,Pathology and Forensic Medicine ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,Epstein-Barr virus associated gastric carcinoma ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Stomach Neoplasms ,PD-L1 ,Biomarkers, Tumor ,medicine ,Humans ,Clinical significance ,neoplasms ,Epstein–Barr virus infection ,In Situ Hybridization ,Proportional Hazards Models ,Chi-Square Distribution ,Janus Kinase 2 ,Middle Aged ,Prognosis ,Programmed Cell Death 1 Ligand 2 Protein ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,030220 oncology & carcinogenesis ,DNA, Viral ,Multivariate Analysis ,Cancer research ,biology.protein ,RNA, Viral ,Female - Abstract
As a special subtype of gastric carcinoma, Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. The Cancer Genome Atlas Research Network revealed that EBVaGC also has distinct molecular features: PIK3CA mutations, DNA hypermethylation, and JAK2, PD-L1, and PD-L2 amplification. Here, we evaluated PIK3CA, JAK2, PD-L1, and PD-L2 expression in 59 EBVaGC and 796 EBV-negative gastric carcinoma (EBVnGC) cases using immunohistochemistry and found that PIK3CA, JAK2, PD-L1, and PD-L2 were highly expressed in 75.9% and 48.8% (P more...
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- 2016
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38. Comparison of Face-Touching Behaviors Before and During the Coronavirus Disease 2019 Pandemic
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Xing Li, Ding-Yun Feng, Yongjian Chen, Xiang-Yuan Wu, Jian-Liang Xu, Jie Chen, and Gang Qin
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Mainland China ,Cross-sectional study ,Pneumonia, Viral ,Population ,law.invention ,Betacoronavirus ,Habits ,law ,Pandemic ,Disease Transmission, Infectious ,Humans ,China ,education ,Pandemics ,education.field_of_study ,Asia, Eastern ,SARS-CoV-2 ,business.industry ,Incidence (epidemiology) ,Masks ,COVID-19 ,General Medicine ,United States ,Europe ,Cross-Sectional Studies ,Geography ,Transmission (mechanics) ,Touch ,Face ,Public transport ,Coronavirus Infections ,business ,Demography - Abstract
There is insufficient evidence on the efficacy of masks in the general population for the prevention of coronavirus disease 2019 (COVID-19) in public areas. Therefore, it is imperative to investigate the association of mandatory mask-wearing policies with behaviors associated with the transmission of COVID-19.To assess the association of mask wearing with face-touching behavior among the general population in public areas.This cross-sectional study used videos recorded in public transportation stations, streets, and parks among the general population in China, Japan, South Korea, Western Europe (ie, England, France, Germany, Spain, and Italy), and the US to analyze mask-wearing and face-touching behavior in public areas. Videos before the COVID-19 pandemic were defined as those recorded from January 2018 to October 2019, and those during the COVID-19 pandemic were defined as those recorded during February 2020 to March 2020 in China, Japan, and South Korea and during March 2020 in Western Europe and the US. Individuals who clearly displayed their face and face-touching behavior were included, and those whose behaviors were influenced by filming or public events were excluded.Mandatory mask-wearing policies enacted at various time points in China, Japan, South Korea, Western Europe, and the US.Proportion of individuals wearing masks and incidence of face touching.This study included 4699 individuals before the COVID-19 pandemic and 2887 individuals during the pandemic. During the periods studied, mask wearing increased in all regions except the US, from 20 of 1745 individuals (1.1%) to 1090 of 1097 individuals (99.4%) in mainland China (P .001), 44 of 1422 individuals (3.1%) to 346 of 893 individuals (38.7%) in Japan (P .001), 6 of 717 individuals (0.8%) to 277 of 324 individuals (85.5% ) in South Korea (P .001), 1 of 546 individuals (0.2%) to 6 of 379 individuals (1.6%) in Western Europe (P = .02), and 1 of 269 individuals (0.4%) to 4 of 194 individuals (2.1%) in the US (P = .17). Surgical masks were predominant in China (989 masks [89.1%]), and fabric masks were predominant in the other regions (Japan: 371 masks [95.1%]; South Korea: 240 masks [84.8%]; Western Europe: 6 masks [85.7%]; US: 5 masks [100%]). Face-touching behaviors decreased from before COVID-19 to during COVID-19 among individuals in China (72 incidences of 1745 observations [4.1%] to 12 incidences of 1097 observations [1.1%]; P .001), South Korea (80 incidences of 717 observations [11.2%] to 7 incidences of 324 observations [2.2%]; P .001), and Europe (62 incidences of 546 observations [11.4%] to 23 incidences of 379 observations [6.1%]; P = .01). Logistic regression found that mask wearing was associated with a reduction in face touching in China (odds ratio [OR], 3.91; 95% CI, 2.11-7.24) and South Korea (OR, 6.69; 95% CI, 2.69-16.69) and of touching the nose, mouth, and eyes (China: OR, 8.60; 95% CI, 2.65-27.86; South Korea: OR, 29.27; 95% CI, 1.79-478.22).The findings of this cross-sectional study suggest that mandatory mask-wearing policies were associated with increased mask wearing during the COVID-19 pandemic. Mask wearing was associated with reduced face-touching behavior, especially touching of the eyes, nose, and mouth, which may prevent contact transmission of COVID-19 among the general population in public areas. more...
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- 2020
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39. A phase III study of comparing FOLFOX+/-bevacizumab with FOLFOX+/-bevacizumab+ high-dose intravenous vitamin C as first-line therapy in patients with advanced colorectal cancer
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Feng Wang, Yanqiao Zhang, Rui-Hua Xu, Xiaohua Hu, Zhixiang Zhuang, Xiang-Yuan Wu, Weijia Fang, S. Chen, Wei Wang, Xianglin Yuan, Jieer Ying, Ying Guo, Fuxiang Zhou, Qing-Feng Zou, Ying Yuan, Ming-Ming He, Zengqing Guo, and Jian Xiao more...
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Oncology ,Cancer Research ,medicine.medical_specialty ,Vitamin C ,Bevacizumab ,business.industry ,digestive system diseases ,Advanced colorectal cancer ,First line therapy ,FOLFOX ,Internal medicine ,Medicine ,In patient ,business ,medicine.drug - Abstract
TPS4115 Background: Previous studies showed that high dose vitamin C especially when administered intravenously might have anti-cancer effect. A recent preclinical study found that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high dose vitamin C. Our phase I dose-escalation and expansion study has shown that high dose (up to 1.5g/kg) intravenous vitamin C with FOLFOX or FOLFIRI is well tolerated in patients with colorectal or gastric cancer. This trial is a randomized, multicenter, phase Ⅲ study of high dose vitamin C infusion combined with FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab as first-line therapy in patients with advanced colorectal cancer. Methods: This study has enrolled patients with histologically confirmed metastatic adenocarcinoma of colorectum, normal G6PD status and no prior treatment for metastatic disease. 432 patients are randomized 1:1 into one of two groups. Patients in the control group are treated with mFOLFOX6 (oxaliplatin 85 mg/m² d1 concurrent with leucovorin 400 mg/m², followed by bolus 5FU 400 mg/m² d1, followed by infusional 5FU 2400 mg/m² over 46 hours) with or without bevacizumab (5mg/kg, d1) every 2 weeks. Patients in the experimental group are treated with vitamin C intravenously (1.5g/kg/day, d1-3) in combination with mFOLFOX6 with or without bevacizumab every 2 weeks. Randomization is stratified by the location of primary site (left-sided or right-sided) and treatment with bevacizumab (with or without). The primary endpoint is progression free survival (assessed by investigator per RECIST v1.1). Secondary endpoints are overall survival, response rate, assessment of treatment-related adverse events, progression free survival and overall survival in RAS or BRAF mutant patients. Genome, microbiome and metabolome are also assessed. Clinical trial information: NCT02969681 . more...
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- 2020
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40. The Prognostic Value of aspartate aminotransferase to lymphocyte ratio and systemic immune-inflammation index for Overall Survival of Hepatocellular Carcinoma Patients Treated with palliative Treatments
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Jingjing Qi, Xiang-Yuan Wu, Jing-Yun Wen, Xiao-Kun Ma, Min Dong, Pei-Shan Hu, Meng-Meng Liu, Zhan-Hong Chen, Zhao-Lei Zeng, Qu Lin, Jin-Xiang Lin, Dong-Hao Wu, Li-Yun Zhao, Jie Chen, Xiao-Ping Zhang, Dong-dong Yang, and Dan-Yun Ruan more...
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0301 basic medicine ,medicine.medical_specialty ,Multivariate analysis ,Lymphocyte ,PREDICTS PROGNOSIS ,DIAGNOSIS ,Gastroenterology ,nomogram ,03 medical and health sciences ,0302 clinical medicine ,CLIP SCORE ,Internal medicine ,Ascites ,medicine ,FIBROSIS ,CURATIVE RESECTION ,ALRI ,CIRRHOSIS ,Univariate analysis ,Science & Technology ,Receiver operating characteristic ,business.industry ,palliative treatment ,prognostic factors ,hepatocellular carcinoma ,Nomogram ,medicine.disease ,Thrombosis ,CANCER ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,medicine.symptom ,business ,Life Sciences & Biomedicine ,Research Paper - Abstract
Background: Lymphocytes were reported to play a significant part in host anticancer immune responses and influence tumour prognosis. Few studies have focused on the prognostic values of aspartate aminotransferase (AST) to lymphocyte ratio (ALRI), aspartate aminotransferase to platelet count ratio index (APRI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) treated with palliative treatments. Methods: Five hundred and ninety-eight HCC patients treated with palliative therapies were retrospectively analysed. We randomly assigned patients into the training cohort (429 patients) and the validation cohort I (169 patients). Receiver operating characteristic (ROC) curves were used to identify the best cut-off values for the ALRI, APRI and SII in the training cohort and the values were further validated in the validation cohort I. Correlations between ALRI and other clinicopathological factors were also analysed. A prognostic nomogram including ALRI was established. We validated the prognostic value of the ALRI, SII and APRI with two independent cohorts, the validation cohort II of 82 HCC patients treated with TACE and the validation cohort III of 150 HCC patients treated with curative resection. In the training cohort and all the validation cohorts, univariate analyses by the method of Kaplan-Meier and multivariate analysis by Cox proportional hazards regression model were carried out to identify the independent prognostic factors. Results: The threshold values of ALRI, APRI and SII were 86.3, 1.37 and 376.4 respectively identified by ROC curve analysis in the training cohort. Correlation analysis showed that ALRI>86.3 was greatly associated with higher rates of Child-Pugh B&C, portal vein tumor thrombosis (PVTT) and ascites (P < 0.05). Correspondingly, ALRI level of HCC patients with Child-Pugh B&C, PVTT and ascites was evidently higher than that of HCC patients with Child-Pugh A, without PVTT and without ascites (P < 0.001). In the training cohort and the validation cohort I, II, III, the OS of patients with ALRI >86.3 was obviously shorter than patients with ALRI ≤86.3 (P more...
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- 2019
41. Efficacy of cytokine-induced killer cell-based immunotherapy for hepatocellular carcinoma
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Chang-Chang, Jia, Yun-Hao, Chen, Xiu-Rong, Cai, Yang, Li, Xiao-Fang, Zheng, Zhi-Cheng, Yao, Li-Yun, Zhao, Dong-Bo, Qiu, Shu-Juan, Xie, Wen-Jie, Chen, Chang, Liu, Qiu-Li, Liu, Xiang-Yuan, Wu, Tian-Tian, Wang, and Qi, Zhang more...
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Original Article - Abstract
In attempts to delay tumor progression after surgery or minimally invasive local treatments, multidisciplinary strategies have been broadly studied in patients with hepatocellular carcinoma (HCC). The objective of this present study was to evaluate the efficacy of autologous transplantations of cytokine-induced killer (CIK) cells as an adjuvant therapy for patients with HCC. A total of 264 patients with HCC were enrolled in this retrospective study. Of these patients, 165 received either CIK cell therapy alone or as adjuvant therapy to surgery, transcatheter arterial chemoembolization (TACE), or TACE-based comprehensive treatments (CT). The remaining 99 patients received only surgery or TACE. Kaplan-Meier analysis and the Chi-squared test were used to analyze the overall survival (OS), progression-free survival (PFS), and clinical characteristics of the patients in the different treatment subgroups. Kaplan-Meier analysis suggested that patients in the Surgery+CIK group had a significantly improved OS compared with those in the other three groups (P < 0.001). Furthermore, patients who developed a fever after the CIK cell treatments manifested a likely better OS (P = 0.028). Subgroup analysis indicated that patients in the Surgery+CIK group likely had an improved PFS but a similar OS compared with the patients in the Surgery-alone group (P = 0.055 for PFS, and P = 0.746 for OS). Further subgroup analysis showed that the OS in both the TACE+CIK and CT+CIK groups was prolonged significantly compared with that in the TACE-alone group (P = 0.015 and P = 0.018, respectively). However, similar OS was observed between the TACE+CIK and CT+CIK groups (P = 0.686). Autologous transplantation of CIK cells as an adjuvant therapy was associated with better survival for patients with HCC, especially for those who had also undergone TACE. A fever reaction might be a potential event for assessing the curative effect of the CIK treatment. more...
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- 2018
42. Efficacy of Prophylactic Entecavir for Hepatitis B Virus-Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization
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Zhan-Hong Chen, Dong-Hao Wu, Ze-Xiao Lin, Tian-Tian Wang, Jing-Yun Wen, Xing Li, Xiang-Yuan Wu, Xiao-Kun Ma, Li Wei, Xiang Zhong, Dan-Yun Ruan, Qu Lin, Min Dong, Jie Chen, and Yan-Fang Xing
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Male ,Cancer Research ,Epidemiology ,medicine.disease_cause ,Gastroenterology ,Hepatic Artery ,0302 clinical medicine ,Child ,Aged, 80 and over ,Liver Neoplasms ,Lamivudine ,Entecavir ,Middle Aged ,Hepatitis B ,Prognosis ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,medicine.drug ,Adult ,Hepatitis B virus ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Guanine ,Adolescent ,Antiviral Agents ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Chemoembolization, Therapeutic ,Transcatheter arterial chemoembolization ,Aged ,Neoplasm Staging ,Retrospective Studies ,Hepatitis ,Performance status ,business.industry ,Public Health, Environmental and Occupational Health ,medicine.disease ,digestive system diseases ,Surgery ,Case-Control Studies ,Virus Activation ,Liver function ,business ,Follow-Up Studies - Abstract
Background and aims Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients. more...
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- 2016
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43. MicroRNA-34a-5p enhances sensitivity to chemotherapy by targeting AXL in hepatocellular carcinoma MHCC-97L cells
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Qi Zhang, Qu Lin, Dan‑Yun Ruan, Xiang Yuan Wu, Xiao‑Yun Li, Chang Chang Jia, Min Dong, Xiao Kun Ma, Zhi‑Yong Xiong, Wei Liu, Ze‑Xiao Lin, Jie Chen, Dong‑Hao Wu, Li Wei, Yan Tai, Tian-Tian Wang, Jing Yun Wen, Zhan Hong Chen, and Xing Li more...
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Cancer Research ,Pathology ,medicine.medical_specialty ,Cell ,cisplatin ,microRNA ,medicine ,microRNA34a-5p ,Cisplatin ,Oncogene ,business.industry ,chemoresistance ,AXL ,Articles ,hepatocellular carcinoma ,Transfection ,Cell cycle ,medicine.disease ,digestive system diseases ,medicine.anatomical_structure ,Oncology ,MicroRNA 34a ,Hepatocellular carcinoma ,Cancer research ,business ,medicine.drug - Abstract
Mature microRNA (miRNA) 34a-5p, which is a well-known tumor suppressor in hepatitis virus-associated hepatocellular carcinoma (HCC), plays an important role in cell processes, such as cell proliferation and apoptosis, and is therefore an optimal biomarker for future clinical use. However, the role of miRNA-34a-5p in chemoresistance has yet to be identified. In the present study, the expression of miRNA-34a-5p was assessed by an in situ hybridization assay in HCC tissues and was found to be significantly decreased compared with the pericarcinomatous areas of the tissue specimens, which consisted of samples obtained from 114 patients with HCC. High expression of miRNA-34a-5p was found to be associated with a favorable overall survival time in HCC patients. Functional tests performed by transfecting miRNA-34a-5p mimics or inhibitors into MHCC-97L cells illustrated that miRNA-34a-5p inhibited proliferation, elevated apoptosis and decreased chemoresistance to cisplatin in HCC cells. AXL is the direct target of miRNA-34a-5p, as confirmed by sequence analysis and luciferase assay. Transfection of the cells with small interfering RNA for AXL (siAXL) increased the apoptosis ratio of the MHCC-97L cell line. Transfection with siAXL led to similar biological behaviors in the MHCC-97L cells to those induced by ectopic expression of miRNA-34a-5p. Thus, it was concluded that miRNA-34a-5p enhanced the sensitivity of the cells to chemotherapy by targeting AXL in hepatocellular carcinoma. In addition, low expression of miRNA-34a-5p in HCC tissues yielded an unfavorable prognosis for patients with HCC that received radical surgery, due to the promotion of proliferation and an increase in chemoresistance in HCC cells. more...
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- 2015
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44. Endoplasmic reticulum stress induced LOX‐1+ CD15+ polymorphonuclear myeloid‐derived suppressor cells in hepatocellular carcinoma
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Ze-Xiao Lin, Xiang-Yuan Wu, Yumei He, Qing-Jian Ye, Xiao-Kun Ma, Jia-Rong Cai, Xing Li, Jian-Xin Tang, Jie Chen, Dan-Yun Ruan, Hui-Min Dong, Bo Hu, Xiu-Rong Cai, Yan-Fang Xing, and Jiang Nan
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0301 basic medicine ,Carcinoma, Hepatocellular ,T cell ,T-Lymphocytes ,Immunology ,Lewis X Antigen ,Lymphocyte Activation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Immunology and Allergy ,Humans ,Cells, Cultured ,Cell Proliferation ,NADPH oxidase ,biology ,Arginase ,Cell growth ,Chemistry ,Endoplasmic reticulum ,Myeloid-Derived Suppressor Cells ,Liver Neoplasms ,Original Articles ,medicine.disease ,Endoplasmic Reticulum Stress ,Fucosyltransferases ,Scavenger Receptors, Class E ,Coculture Techniques ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Case-Control Studies ,biology.protein ,Myeloid-derived Suppressor Cell ,Cancer research ,Unfolded protein response ,Interferons ,Reactive Oxygen Species ,Signal Transduction - Abstract
A recent study indicated that Lectin‐type oxidized LDL receptor‐1 (LOX‐1) was a distinct surface marker for human polymorphisms myeloid‐derived suppressor cells (PMN‐MDSC). The present study was aimed to investigate the existence LOX‐1 PMN‐MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty‐seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX‐1(+) CD15(+) PMN‐MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX‐1(+) CD15(+) PMN‐MDSC in circulation were positively associated with those in HCC tissues. LOX‐1(+) CD15(+) PMN‐MDSCs significantly reduced proliferation and IFN‐γ production of T cells with a dosage dependent manner with LOX‐1(−) CD15(+) PMNs reached negative results. The suppression on T cell proliferation and IFN‐γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX‐1 (+)CD15(+) PMN were higher in LOX‐1(+) CD15(+) PMN‐MDSCs than LOX‐1(−) CD15(+) PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX‐1(+) CD15(+) PMN‐MDSCs displayed significantly higher expression of spliced X‐box ‐binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX‐1 expression and suppressive function for CD15(+) PMN from health donor. For HCC patients, LOX‐1(+) CD15(+) PMN‐MDSCs were positively related to overall survival. Above all, LOX‐1(+) CD15(+) PMN‐MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients. more...
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- 2017
45. Comparison of five staging systems in predicting the survival rate of patients with hepatocellular carcinoma undergoing trans‑arterial chemoembolization therapy
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Li Wei, Xiang-Wei Chen, Jing Yun Wen, Dan‑Yun Ruan, Tian-Tian Wang, Ying‑Fen Hong, Rui-Hua Xu, Ze‑Xiao Lin, Xing Li, Dong‑Hao Wu, Min Dong, Jie Chen, Jin-Xiang Lin, Xiao Kun Ma, Qu Lin, Zhan Hong Chen, and Xiang Yuan Wu more...
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,trans-arterial chemoembolization ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Survival rate ,Performance status ,Receiver operating characteristic ,business.industry ,model to estimate survival for hepatocellular carcinoma ,Area under the curve ,Cancer ,Articles ,hepatocellular carcinoma ,Hepatitis B ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,hepatitis B ,prognosis ,Trans arterial chemoembolization ,business - Abstract
The majority of patients with unresectable hepatocellular carcinoma (HCC) undergo trans-arterial chemoembolization (TACE). However, the prognosis of HCC remains poor. In the present study, five staging systems were compared to predict the survival rate of patients with HCC undergoing TACE treatment. A total of 220 patients with HCC were examined according to the model to estimate survival for hepatocellular carcinoma (MESH), hepatoma arterial embolization prognostic score (HAP), modified HAP (mHAP), performance status combined Japan Integrated Staging system (PSJIS) and tumor-node-metastasis (TNM) staging systems. The endpoints of the study were 3-month survival, 6-month survival, 1-year survival and overall survival (OS) rates. Receiver operating characteristic curve analysis indicated that the area under the curve of MESH, HAP, mHAP, PSJIS and TNM was 0.858, 0.728, 0.690, 0.688 and 0.699, respectively, in predicting 3-month survival rates; 0.822, 0.747, 0.720, 0.722 and 0.715, respectively, in predicting 6-month survival rates and 0.725, 0.664, 0.672, 0.645 and 0.654, respectively, in predicting 1-year survival rates. Discriminatory ability, homogeneity, monotonicity and prognostic stratification ability was evaluated using a likelihood ratio test and Akaike information criterion values among the five staging systems, and revealed that the MESH system was the optimal prognostic staging system for HCC. In conclusion, the results of the present study suggest that the MESH system is the most accurate prognostic staging system of 3-month survival, 6-month survival, 1-year survival and OS rates among the five systems analyzed in patients with HCC who have received TACE treatment. more...
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- 2017
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46. Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma
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Zhan Hong Chen, Jing Yun Wen, Li Wei, Tian-Tian Wang, Ze‑Xiao Lin, Dong‑Hao Wu, Min Dong, Xing Li, Xiao Kun Ma, Jie Chen, Qu Lin, Xiao‑Yun Li, Xiang Yuan Wu, and Dan‑Yun Ruan
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Oncology ,Cancer Research ,medicine.medical_specialty ,Cirrhosis ,Oncogene ,Cancer ,Diagnostic marker ,Articles ,Cell cycle ,Biology ,medicine.disease ,Molecular medicine ,digestive system diseases ,03 medical and health sciences ,0302 clinical medicine ,Apoptosis ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Internal medicine ,medicine ,030211 gastroenterology & hepatology - Abstract
Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P more...
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- 2017
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47. MicroRNA-195 regulates docetaxel resistance by targeting clusterin in prostate cancer
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Qu Lin, Xing Li, Liyuan Zou, Zhan-Hong Chen, Xiang-Yuan Wu, and Xiao-Kun Ma
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0301 basic medicine ,Male ,Docetaxel ,Metastasis ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Vasculogenesis ,DU145 ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Gene Silencing ,Pharmacology ,Gene knockdown ,Clusterin ,biology ,Base Sequence ,Chemistry ,Prostatic Neoplasms ,General Medicine ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Apoptosis ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Taxoids - Abstract
MicroRNAs (miRNAs) have been implicated in neoplasm growth, metastasis, vasculogenesis, and drug resistance. It has been validated that abnormal miR-195 expression was related with poor survival of prostate cancer (PC); however, its role in the resistance to chemotherapeutic drugs docetaxel (DOC) in PC is still acquainted scarcely. In our study, the lower expression of miR-195 was appeared in DOC-resistant PC cells (DU145/DOC) rather than DOC-sensitive DU145 cells. The up-regulation of miR-195 lowered the IC50 of DOC, facilitated the apoptosis and inhibited the colony formation ability in DU145/DOC cells. Moreover, we also found that miR-195 had the binding site with clusterin (CLU) by the online TargetScan database mining. Luciferase tests revealed that miR-195 binds to the 3'-UTR of CLU. MiR-195 overexpression decreased the amassment of CLU in DU145/DOC cells. Knockdown of CLU diminished the IC50 of DOC and enhanced the apoptosis of DU145/DOC cells, which was consistent with the influence of miR-195 on DOC-induced cell apoptosis. Taken together, our results illuminated that miR-195 improved the sensitivity of resistant PC cells to DOC by suppressing CLU. Hence, miR-195 may be a potentially promising molecular target for drug resistance of PC. more...
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- 2017
48. Albumin-to-Alkaline Phosphatase Ratio as an Independent Prognostic Factor for Overall Survival of Advanced Hepatocellular Carcinoma Patients without Receiving Standard Anti-Cancer Therapies
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Jing-Yun Wen, Xiao-Kun Ma, Ze-Xiao Lin, Dong-Hao Wu, Jie Chen, Tian-Tian Wang, Xiang-Yuan Wu, Xiu-Rong Cai, Li Wei, Zhan-Hong Chen, Xiang-Wei Chen, Min Dong, Xing Li, Dan-Yun Ruan, Ming-Jun Bai, and Qu Lin more...
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Oncology ,medicine.medical_specialty ,Multivariate analysis ,hepatic function reserve ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Ascites ,medicine ,albumin-to-alkaline phosphatase ratio ,Univariate analysis ,Receiver operating characteristic ,business.industry ,Univariate ,Cancer ,medicine.disease ,biomarkers ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Liver function ,advanced hepatocellular carcinoma ,prognosis ,medicine.symptom ,business ,Research Paper - Abstract
Background Albumin-to-Alkaline Phosphatase Ratio (ALB/ALP ratio, AAPR), a newly developed index of liver function, has been rarely discussed about its prognostic value in malignancies. The current study attempted to evaluate the prognostic prediction of AAPR in advanced HCC. Methods 237 advanced HCC patients who refused any standard anti-cancer therapies were retrospectively analyzed. The threshold value of AAPR was determined by receiver operating characteristic (ROC) curve. Univariate analyses using Kaplan-Meier method and log-rank test, and multivariate analysis using Cox proportional hazards regression model were conducted. Comparisons of ROC curves and likelihood ratio test (LRT) were utilized to compare the value of different factors in predicting survival. Results ROC curve analysis confirmed 0.38 as the optimal cutoff value of AAPR in evaluating overall survival (OS). Patients with an AAPR > 0.38 exhibited significantly lower frequencies of ascites, portal vein tumor thrombus, Child-Pugh grade B & C, and KPS < 70 (all P < 0.05). These patients also displayed a longer median survival time than those with an AAPR ≤ 0.38 (5.8 m vs 2.4 m, P < 0.01). Univariate and multivariate analyses identified AAPR as an independent prognostic indicator (HR = 0.592, P = 0.007). Furthermore, we integrated AAPR with TNM system and found that area under curve of AAPR-TNM system was significantly larger than that of TNM system when predicting 3-month survival (0.670 vs 0.611, P < 0.01). Moreover, LRT indicated that AAPR-TNM system had a significantly larger χ2 (26.4 vs 16.4, P < 0.01) and a significantly smaller Akaike information criterion value (1936 vs 1948, P < 0.01) comparing with TNM system. Conclusions Our study implied that AAPR was a potentially valuable prognostic index for advanced HCC patients without receiving any standard anti-cancer therapies. AAPR-TNM system preceded TNM system in predicting overall survival in this study. more...
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- 2017
49. Hepatitis B Virus DNA Negativity Acts as a Favorable Prognostic Factor in Hepatocellular Carcinoma Patients
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Tian-Tian Wang, Xiang Zhong, Yan-Fang Xing, Zhan-Hong Chen, Li Wei, Dan-Yun Ruan, Xiao-Kun Ma, Jie Chen, Qu Lin, Min Dong, Xing Li, Dong-Hao Wu, Ze-Xiao Lin, Xiang-Yuan Wu, and Jing-Yun Wen
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Adult ,Male ,Hepatitis B virus ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Guanine ,Cirrhosis ,Adolescent ,Epidemiology ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Disease-Free Survival ,Young Adult ,Hepatitis B, Chronic ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Chemoembolization, Therapeutic ,Child ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hepatitis ,business.industry ,Liver Neoplasms ,Public Health, Environmental and Occupational Health ,Lamivudine ,Entecavir ,Middle Aged ,Hepatitis B ,medicine.disease ,digestive system diseases ,Oncology ,Hepatocellular carcinoma ,DNA, Viral ,Immunology ,Reverse Transcriptase Inhibitors ,Female ,business ,medicine.drug - Abstract
Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients. more...
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- 2014
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50. Platelet-to-lymphocyte ratio acts as a prognostic factor for patients with advanced hepatocellular carcinoma
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Tian-Tian Wang, Yun Deng, Xing Li, Ze-Xiao Lin, Li Wei, Xiao-Kun Ma, Yan-Fang Xing, Xiang-Yuan Wu, Zhan-Hong Chen, Dong-Hao Wu, Jin-Yun Wen, Jie Chen, Min Dong, Dan-Yun Ruan, and Qu Lin
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Adult ,Blood Platelets ,Male ,Oncology ,Sorafenib ,medicine.medical_specialty ,Pathology ,Carcinoma, Hepatocellular ,Kaplan-Meier Estimate ,Liver disease ,Internal medicine ,Carcinoma ,medicine ,Humans ,Lymphocytes ,Survival rate ,Aged ,Aged, 80 and over ,Receiver operating characteristic ,Platelet Count ,business.industry ,Proportional hazards model ,Liver Neoplasms ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,digestive system diseases ,Blood Cell Count ,body regions ,Hepatocellular carcinoma ,Female ,business ,medicine.drug - Abstract
The platelet count, as an inflammation marker, is involved in the progress of tumor invasion. However, the prognostic value of platelet counts and the platelet-to-lymphocyte ratio (PLR) has not been investigated in patients with advanced hepatocellular carcinoma (HCC). This study aimed to determine the prognostic value of platelet counts and PLR in HCC patients. A total of 243 ethnic Chinese advanced HCC patients from two major hospitals, not receiving systemic sorafenib, were analyzed retrospectively. The prognostic value of differential blood cell counts and PLR for overall survival (OS) was determined by integrating the Cancer of the Liver Italian Program (CLIP) score system and model for end-stage liver disease by using a stepwise model of multivariate Cox regression. The Kaplan-Meier method and receiver operating characteristic (ROC) curves were utilized accordingly. PLR was confirmed to be an independent predictor for OS (p 0.01), while the remaining parameters had no predictive value. Then, advanced HCC patients were dichotomized into two groups based on the PLR value (≤111.23 or111.23), according to ROC analysis. Patients with a high PLR had a lower 3-month survival rate (37.6 vs. 57.6%) compared with patients with a low PLR. PLR was associated with aggressive malignant behavior, characterized by distant metastasis and portal vein thrombosis. Additionally, PLR was not associated with the CLIP score and Child-Pugh grade. PLR was identified as an independent prognostic factor for advanced HCC patients not receiving systemic sorafenib; the predictive ability of PLR partially relies on its association with the aggressive nature of HCC. more...
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- 2014
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