23 results on '"Zhang, Ti"'
Search Results
2. Drug-related adverse events potentially predict the efficacy of apatinib on advanced hepatocellular carcinoma
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Gu, Xiaoying, Zhang, Su, Yang, Xuejiao, Guan, Tao, Hou, Zhenyu, Cao, Manqing, Li, Huikai, and Zhang, Ti
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- 2022
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3. Mild chronic hypoxia-induced HIF-2α interacts with c-MYC through competition with HIF-1α to induce hepatocellular carcinoma cell proliferation
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Mu, Han, Yu, Ge, Li, Huikai, Wang, Mengmeng, Cui, Yunlong, Zhang, Ti, Song, Tianqiang, and Liu, Changfu
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- 2021
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4. Adjuvant sorafenib therapy in patients with resected hepatocellular carcinoma: evaluation of predictive factors
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Zhang, Wei, Zhao, Gang, Wei, Kai, Zhang, Qingxiang, Ma, Weiwei, Wu, Qiang, Zhang, Ti, Kong, Dalu, Li, Qiang, and Song, Tianqiang
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- 2015
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5. Increased prevalence of regulatory T cells in the tumor microenvironment and its correlation with TNM stage of hepatocellular carcinoma
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Shen, Xiaohong, Li, Na, Li, Hui, Zhang, Ti, Wang, Feng, and Li, Qiang
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- 2010
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6. Surgical Conversion for Initially Unresectable Locally Advanced Hepatocellular Carcinoma Using a Triple Combination of Angiogenesis Inhibitors, Anti-PD-1 Antibodies, and Hepatic Arterial Infusion Chemotherapy: A Retrospective Study.
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Zhang, Jinliang, Zhang, Xihao, Mu, Han, Yu, Ge, Xing, Wenge, Wang, Lu, and Zhang, Ti
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CHEMOEMBOLIZATION ,HEPATOCELLULAR carcinoma ,NEOVASCULARIZATION inhibitors ,CANCER chemotherapy ,ORAL medication ,TREATMENT effectiveness ,IMMUNOGLOBULINS - Abstract
Background: Recent research has shown that selected patients with initially unresectable hepatocellular carcinoma (HCC) are able to achieve conversion to resectable disease through systemic or local therapy. Combination regimens comprised of drugs with different mechanisms of action have shown better outcomes than single-drug or single-approach-based treatments; however, to date, combination regimens investigated as part of conversion therapy strategies have been two drug combinations with reported issues of relatively low surgical conversion and objective response rates. In this study, we investigated the efficacy and safety of triple combination therapy with angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy for surgical conversion of advanced HCC. Methods: This was a single-center, retrospective, single-arm study of patients with unresectable HCC who received at least one cycle of triple combination therapy with an oral anti-angiogenic drug, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy between August 2019 and August 2020. Endpoints included the overall response rate (ORR), surgical conversion rate, time to response and safety. Treatment response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1. Results: In total, 34 patients were included in this study, of whom 25 completed treatment evaluation. The best ORR was 96.0% (24/25); 48.0% (n = 12) had a complete response, 48.0% (n = 12) had a partial response, and 4.0% (n = 1) had stable disease. The median time to response was 50.5 (95% CI, 31.02–64.00) days and the surgical conversion rate was 60% (15/25). Of the 25 patients, 56.0% (n = 14) received surgical resection and 28.0% (n = 7) had a pathologic complete response. Toxic side effects were manageable. Conclusion: A triple combination therapy regimen of angiogenesis inhibitors, programmed death-1 inhibitors and hepatic arterial infusion chemotherapy showed significant therapeutic effect with an extremely high surgical conversion rate in patients with initially unresectable HCC. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Sorafenib combined with cryoablation to treat unresectable hepatocellular carcinoma
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Ni, Hong, Yang, Mao, Guo, Zhi, and Zhang, Ti
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- 2011
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8. The Neutrophil-to-Lymphocyte Ratio (NLR) Predicts the Prognosis of Unresectable Intermediate and Advanced Hepatocellular Carcinoma Treated with Apatinib.
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Wang, Huaqi, Wang, Zhiwei, Hou, Zhenyu, Yang, Xuejiao, Zhu, Keyun, Cao, Manqing, Zhu, Xiaolin, Li, Huikai, and Zhang, Ti
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HEPATOCELLULAR carcinoma ,NEUTROPHIL lymphocyte ratio ,OVERALL survival ,VASCULAR endothelial growth factor receptors ,PROGNOSIS - Abstract
Purpose: Patients with hepatocellular carcinoma (HCC) who might benefit most from anti-angiogenesis therapy remain unknown. In recent years, neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammatory response, has received particular attention in HCC. Herein, we explored the prognostic value of pre-treatment NLR in individuals with unresectable intermediate and advanced hepatocellular carcinoma treated with apatinib, a second-line angiogenesis inhibitor. The findings of this study would assist in precision medicine and provide clinical decision support. Patients and Methods: This is a retrospective study in which 171 HCC patients attending Tianjin Medical University Cancer Institute and Hospital and treated with apatinib between January 2016 and July 2018 were enrolled. The prognosis of the patients based on NLR signatures was then analyzed. Results: Patients with a low pre-treatment NLR (NLR < 2.49) presented a significantly longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.043). Furthermore, a low pre-treatment NLR level could be used to predict a longer OS in patients with non-macrovascular invasion (P < 0.001). Independent of serum alpha-fetoprotein (AFP) levels, a low NLR level in this cohort of patients is associated with a longer OS. Conclusion: Pre-treatment NLR predicts the prognosis of patients with unresectable intermediate and advanced HCC treated with apatinib. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Drug-Related Hypertension Associated with the Efficacy of Apatinib on Hepatocellular Carcinoma.
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Yang, XueJiao, Hou, ZhenYu, Zhu, KeYun, Zhang, Su, Gu, XiaoYing, Wang, ZhiWei, Mu, Han, Zhou, HongYuan, Chen, Ping, Zhu, XiaoLin, Cui, YunLong, Li, Qiang, Li, HuiKai, and Zhang, Ti
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HEPATOCELLULAR carcinoma ,TREATMENT effectiveness ,PROGRESSION-free survival ,HYPERTENSION ,PREVENTIVE medicine - Abstract
Purpose: We retrospectively evaluated the efficacy and safety of apatinib as a first-line treatment for advanced hepatocellular carcinoma (HCC) and explored whether drug-related hypertension (HTN) could predict its efficacy. Patients and Methods: This retrospective analysis included patients with advanced HCC who received oral treatment with apatinib. We evaluated the effectiveness by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease control rate (DCR), and assessed the safety of the drug based on the occurrence of adverse events. In order to explore whether apatinib-related HTN can be used as a predictor of therapeutic effect, patients were divided into an HTN group and a non-HTN group and adjusted for propensity score-matched (PSM) to reduce mixed deviation. Subgroup analyses of negative prognostic factors for advanced HCC were also performed, including alpha-fetoprotein (AFP), Child–Pugh Score, macrovascular invasion, and extrahepatic metastasis. Results: A total of 208 patients were analyzed, of which 40.9% (n =85) developed drug-related HTN. For all patients, the OS was 13.4 months (95% CI, 12.2– 14.6), the PFS was 5.7 months (95% CI, 5.1– 6.3), and the TTP was 6.9 months (95% CI, 6.0– 7.8). The OS of the HTN group and the non-HTN group was 17.4 months (m) and 12.5m (p=0.001), and the PFS was 7.4m and 4.7m (p=0.000), respectively. After PSM, the OS (p=0.001) and PFS (p=0.003) of the HTN group were still significantly better than the non-HTN group. Subgroup analysis suggested that overall survival was significantly longer in patients with HTN when serum AFP ≤ 400 μg/L or extrahepatic metastases. Moreover, OS in the HTN group increased significantly with or without macrovascular invasion. In addition, through the analysis of two groups of patients with PFS> 6m and PFS≤ 6m, we know that the patients with drug-related HTN may develop resistance later, so they have longer survival time. Conclusion: Apatinib demonstrates compelling anti-cancer activity and acceptable safety in advanced HCC. Apatinib-related HTN can potentially predict prolonged survival in patients with advanced HCC. [ABSTRACT FROM AUTHOR]
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- 2020
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10. A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma
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Kong Da-Lu, Wang Jian, Dong Hui, Zhang Ti, and Li Qiang
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Male ,Oncology ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Disease-Free Survival ,Cytokine-Induced Killer Cells ,Risk Factors ,Internal medicine ,Secondary Prevention ,medicine ,Adjuvant therapy ,Carcinoma ,Hepatectomy ,Humans ,Postoperative Care ,Hepatology ,Cytokine-induced killer cell ,business.industry ,Liver Neoplasms ,Gastroenterology ,Immunotherapy ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Radiation therapy ,Hepatocellular carcinoma ,Female ,business ,Adjuvant - Abstract
Background With a resistance to conventional chemotherapy and radiotherapy, hepatocellular carcinoma has a high recurrence rate after radical resection. Adjuvant immunotherapy is a promising treatment for hepatocellular carcinoma. Aim To evaluate the effect of adjuvant immunotherapy with cytokine-induced killer cells on the prognosis of hepatocellular carcinoma after radical resection. Patients and methods From January 2000 to January 2002, we collected 127 patients that met the selection criteria and randomly divided them into 3 groups. After radical resection of the tumor, immunotherapy with cytokine-induced killer cells was performed for 3 courses in 41 patients (CIK-I group) and 6 courses in 43 patients (CIK-II group). The other 43 patients received no postoperative adjuvant therapy (the control group). The 1-, 3-, and 5-year disease free survival rates and the overall survival were compared among the 3 groups. Results The log-rank test showed that the disease-free survival rates were significantly higher in CIK-I group (p = 0.001) and CIK-II group (p = 0.004) than in the control group. No statistical significance was found between CIK-I group and CIK-II group (p = 0.345). Cox regression suggested that treatment modality was a risk factor for recurrence. No statistical significance was found in the overall survival among the three groups. Conclusions Postoperative immunotherapy with cytokine-induced killer cells may prevent recurrence/metastasis after radical resection of hepatocellular carcinoma. However, it cannot improve the overall survival.
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- 2009
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11. Clinical significance of lymph node metastasis in patients undergoing partial hepatectomy for hepatocellular carcinoma
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Cui Yunlong, Shen Xiaohong, Zhang Ti, Li Qiang, Wang Feng, and Li Huikai
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Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Gastroenterology ,Metastasis ,medicine.artery ,Internal medicine ,medicine ,Carcinoma ,Hepatectomy ,Humans ,Lymph node ,Survival rate ,Neoplasm Staging ,Common hepatic artery ,business.industry ,Liver Neoplasms ,medicine.disease ,Survival Analysis ,Surgery ,medicine.anatomical_structure ,Hepatocellular carcinoma ,Lymphatic Metastasis ,Lymph Node Excision ,Lymphadenectomy ,Female ,Lymph Nodes ,business - Abstract
There are few detailed clinical reports about perihepatic lymph node (LN) assessment of hepatocellular carcinoma (HCC). The purpose of the present study was to evaluate the incidence, site, and impact on survival of LN metastasis in patients with HCC amenable to curative liver resection and routine regional lymphadenectomy. From January 2001 to June 2004, a total of 523 HCC patients undergoing curative hepatic resection and routine regional lymphadenectomy were included in this study. The incidence, site of LN metastasis in HCC patients, and its influence on survival were analyzed. A total of 3433 lymph nodes were dissected from the 523 patients enrolled in this study and examined by pathologists. Among these patients, LN metastasis was found in 39 (7.45%) patients. Hepatic pedicle, retropancreatic space, and common hepatic artery stations were conventionally removed. The incidence of LN metastasis in the hepatic pedicle station was higher than that in the other stations (p
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- 2010
12. Decreased expression of acetyl-CoA synthase 2 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.
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Sun, Lin, Kong, Yinlong, Cao, Manqing, Zhou, Hongyuan, Li, Huikai, Cui, Yunlong, Fang, Feng, Zhang, Wei, Li, Jiafeng, Zhu, Xiaolin, Li, Qiang, Song, Tianqiang, and Zhang, Ti
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Metastasis is a serious risk that may occur during the treatment of hepatocellular carcinoma ( HCC), preventing many patients from being surgical candidates and contributing to poor prognosis. Hypoxia has been proved an important factor of metastasis through the epithelial-mesenchymal transition ( EMT) pathway. Acetyl-CoA synthase 2 ( ACSS2) provides an acetyl group for the acetylation of hypoxia-inducible factor ( HIF)-2α, and this epigenetic modification affects the activity of HIF-2α and the subsequent EMT process. Here, we showed that ACSS2 expression was negatively correlated with HCC malignancy. Knockdown of ACSS2 increased the invasion and migration ability of HCC cells and promoted EMT without increasing the total protein level of HIF-2α, even in hypoxic conditions. The immunoprecipitation assay revealed downregulated acetylation levels of HIF-2α after ACSS2 knockdown in hypoxic conditions, which resulted in enhanced HIF-2α activity. Finally, decreased expression of ACSS2 was found to be related to advanced stage and poor overall survival and disease-free survival rates in a cohort of patients with HCC. In conclusion, ACSS2 plays an important role in the acetylation process of HIF-2α, which effectively modifies the activity of HIF-2α under hypoxic conditions and greatly impacts on the prognosis of patients with HCC. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Metformin inhibits the prometastatic effect of sorafenib in hepatocellular carcinoma by upregulating the expression of TIP30.
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Guo, Zhigui, Cao, Manqing, You, Abin, Gao, Junrong, Zhou, Hongyuan, Li, Huikai, Cui, Yunlong, Fang, Feng, Zhang, Wei, Song, Tianqiang, Li, Qiang, Zhu, Xiaolin, Sun, Huichuan, and Zhang, Ti
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We previously found that a low dose of sorafenib had a prometastatic effect on hepatocellular carcinoma (HCC), which was caused by downregulation of TIP30 expression. More recently, metformin has been shown to have potential as a preventive and therapeutic agent for different cancers, including HCC. This study evaluated whether the combination of sorafenib and metformin is sufficient to revert the expression of TIP30, thereby simultaneously reducing lung metastasis and improving survival. Our data show that the combination of sorafenib and metformin inhibits proliferation and invasion in vitro, prolongs median survival, and reduces lung metastasis of HCC in vivo. This effect is closely associated with the upregulation of TIP30, partly through activating AMP-activated protein kinase. Thioredoxin, a prometastasis factor, is negatively regulated by TIP30 and plays an essential role during the process of HCC metastasis. Overall, our results suggest that metformin might be a potent enhancer for the treatment of HCC by using sorafenib. [ABSTRACT FROM AUTHOR]
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- 2016
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14. HIF-2α regulates CDCP1 to promote PKCδ-mediated migration in hepatocellular carcinoma.
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Cao, Manqing, Gao, Junrong, Zhou, Hongyuan, Huang, Jiafei, You, Abin, Guo, Zhigui, Fang, Feng, Zhang, Wei, Song, Tianqiang, and Zhang, Ti
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Overexpression of CUB domain-containing protein 1 (CDCP1), a transmembrane glycoprotein and major substrate of Src family kinases (SFKs), always indicates unfavorable outcomes in various cancers. The characteristics of CDCP1 in hepatocellular carcinoma (HCC) have not been assessed. Most recently, CDCP1 was identified as a specific target gene of HIF-2α in clear cell renal carcinoma (CC-RCC). However, considering the role of HIF-2α in the progression of HCC is highly controversial, it is necessary to figure out whether HIF-2α and CDCP1 play a significant part in the metastasis of HCC. Our results showed that HIF-2α and CDCP1 were both induced by hypoxia, and the activation of CDCP1 was HIF-2α dependent. CDCP1 was governed by HIF-2α at mRNA and protein levels in HCC cell lines. Moreover, knocking down of HIF-2α not only inhibited cell invasion but also impaired the expression of Tyr phosphorylation of protein kinase Cδ (PKCδ) which is a downstream factor of CDCP1 and has been reported to induce malignant migration in various tumors. Analysis of human HCC samples showed a negative correlation of CDCP1 expression with disease-free survival, and CDCP1 was an independent prognostic factors of disease-free survival. Taken together, these data demonstrated that HIF-2α could promote HCC cell migration by regulating CDCP1, and targeting HIF-2α-CDCP1-PKCδ pathway might be effective to inhibit HCC metastasis. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models.
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Rao, Quan, You, Abin, Guo, Zhenglong, Zuo, Bingfeng, Gao, Xianjun, Zhang, Ti, Du, Zhi, Wu, Chenxuan, and Yin, HaiFang
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LIVER transplantation ,LIVER cancer ,LABORATORY mice ,DRUG efficacy ,INTRAVENOUS drug abuse - Abstract
Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters—the latency period, take rates, pathological features and metastatic rates—were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5cm (longitudinal diameter) tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients. Our study demonstrated that orthotopic HCC mouse models established via intrahepatic tissue implantation authentically reflect clinical manifestations in HCC patients pathologically and immunologically, suggesting intrahepatic tissue implantation is a preferable approach for establishing orthotopic HCC mouse models. [ABSTRACT FROM AUTHOR]
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- 2016
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16. The Indications for Hepatectomy for Multinodular Hepatocellular Carcinoma: Experience from a Single Institution.
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Zhou, Yuan-da, Li, Hui-kai, Cui, Yun-long, Zhang, Ti, and Li, Qiang
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HEPATECTOMY ,SURGICAL excision ,LIVER surgery ,DIAGNOSIS ,PROGNOSIS ,LIVER cancer ,TUMORS - Abstract
Aims: This study was conducted in order to investigate the indications for hepatecomy for multinodular hepatocellular carcinoma (MNHCC) in single institution. Methods: We retrospectively analyzed the medical records from 55 MNHCC patients, mainly with Child-Pugh A liver function, who underwent hepatectomy from January 2006 to December 2008. Both short- and long-term outcomes were analyzed. In addition, the prognostic significance of clinicopathological factors on overall survival (OS) was investigated by univariate analysis using the log-rank test. A Cox proportional hazards model was used in a subsequent multivariate analysis. Results: The perioperative morbidity rate (grade II or higher) was 18.2% (n = 10), and the in-hospital mortality rate was 3.6%. The median OS was 23.9 months (range, 2.5-84 months), whereas the median disease-free survival was 8.75 months (range, 1-65 months). Independent prognostic risk factors of 5-year OS included the number of tumors >2 (p = 0.032) and gross morphology indicating multiple tumor nodules scattered throughout the liver (p = 0.009). Conclusions: The postoperative morbidity and mortality rates were acceptable. The number of tumors >2 and gross morphology indicating multiple tumor nodules scattered throughout the liver were independent prognostic risk factors for patients with MNHCC after hepatectomy. Patients with both of these features had a very poor prognosis and were not considered suitable for surgery. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2015
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17. Silencing thioredoxin induces liver cancer cell senescence under hypoxia.
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Zhang, Ti, Liu, Heping, Zhu, Cihui, Briggs, Katrina, Kang, Ya'an, Fleming, Jason A., and Curley, Steven A.
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THIOREDOXIN , *LIVER cancer , *CANCER cells , *CELLULAR aging , *HYPOXEMIA , *OXIDATION-reduction reaction , *DNA damage , *TUMOR growth - Abstract
Aim: Although thioredoxin 1 (TXN) has pleiotropic cellular functions as a redox-sensitive protein, very little is known about its role in tumor survival and growth under hypoxia. MHCC97H hepatocellular carcinoma cells have a high metastatic potential and high thioredoxin expression levels compared with their parent cell line, MHCC97. Thus, we used this cell line to explore the functional connections between TXN and hypoxia. Methods: MHCC97H cells were cultured under normoxia and hypoxia for specific periods after nucleofection with TXN siRNA or control siRNA. We assessed the β-phenylethyl isothiocyanate (PEITC) sensitivity of the cells, cell proliferation, cell cycle and senescence, and DNA damage response by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony formation assays, flow cytometry, β-galactosidase staining, western blotting, and immunohistochemistry. Results: β-phenylethyl isothiocyanate treatment shifted reduced TXN to oxidized TXN in MHCC97H cells. Although silencing of TXN via siRNA had no effect on the PEITC sensitivity of the cells, it suppressed cell proliferation and colony formation under both normoxia and hypoxia. Under hypoxia, silencing TXN did not induce apoptosis but induced DNA damage response and cellular senescence. Conclusions: High TXN levels in MHCC97H cells protect them from DNA damage and cellular senescence under hypoxia. Targeting TXN might enhance the chemotherapeutic effects of some DNA-damaging agents against hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]
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- 2012
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18. Interferon alpha inhibits hepatocellular carcinoma growth through inducing apoptosis and interfering with adhesion of tumor endothelial cells
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Zhang, Ti, Sun, Hui-Chuan, Zhou, Hong-Yuan, Luo, Jing-Tao, Zhang, Bai-Lin, Wang, Peng, Wang, Lu, Qin, Lun-Xiu, Ren, Ning, Ye, Sheng-Long, Li, Qiang, and Tang, Zhao-You
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INTERFERONS , *LIVER cancer , *APOPTOSIS , *CELL adhesion , *ENDOTHELIUM , *XENOGRAFTS , *GENE expression , *ANTISENSE DNA , *NEOVASCULARIZATION ,TUMOR growth prevention - Abstract
Abstract: The aim of this study was to observe the effect of interferon alpha (IFNα) on tumor endothelial cells (TECs) in highly metastatic hepatocellular carcinoma (HCC) model, and to investigate the underlying mechanism. Nude mice with HCC xenograft were treated with IFNα. Gene expression profiles of TECs were analyzed by utilizing cDNA microarray. The differentiation of tumor blood vessels was evaluated by CD31/αSMA dual immunohistochemistry. Apoptosis of TECs was determined by CD31/TUNEL double staining. The functions of TECs in adhesion and uptake of acetylated low-density lipoprotein were observed in vitro. Results showed that IFNα effectively inhibited HCC tumor growth, with decreased microvessel density, increased apoptosis in TECs and normalized tumor blood vessels. cDNA microarray analysis revealed differential gene expression patterns in TECs under the treatment of IFNα. The cell-cell contact distribution of VE-Cadherin and uptake of acetylated low-density lipoprotein were significantly inhibited by IFNα in cultivated TECs. These results suggest that IFNα may induce apoptosis and interfere with hemophilic adhesion of TECs. The changes of gene expression in TECs contribute essentially to its effect of anti-angiogenesis and the subsequent inhibition of tumor progression. [Copyright &y& Elsevier]
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- 2010
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19. Thioredoxin facilitates hepatocellular carcinoma stemness and metastasis by increasing BACH1 stability to activate the AKT/mTOR pathway.
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Wang, Chengmeng, Zhang, Lu, Cao, Manqing, Fu, Zhou, Wang, Huaqi, Zhang, Su, Zhu, Keyun, Hou, Zhenyu, Cui, Jinfang, Yue, Ping, Guo, Hua, and Zhang, Ti
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Thioredoxin (TXN) is essential for preserving balance and controlling the intracellular redox state. Most studies have focused on the function of TXN in redox reactions, which is critical for tumor progression. Here, we showed that TXN promotes hepatocellular carcinoma (HCC) stemness properties in a non‐redox‐dependent manner, which has rarely been reported in previous studies. TXN exhibited upregulated expression in human HCC specimens, which was associated with a poor prognosis. Functional studies showed that TXN promoted HCC stemness properties and facilitated HCC metastasis both in vitro and in vivo. Mechanistically, TXN promoted the stemness of HCC cells by interacting with BTB and CNC homology 1 (BACH1) and stabilized BACH1 expression by inhibiting its ubiquitination. BACH1 was positively correlated with TXN expression and was significantly upregulated in HCC. In addition, BACH1 promotes HCC stemness by activating the AKT/mammalian target of rapamycin (mTOR) pathway. Furthermore, we found that the specific inhibition of TXN in combination with lenvatinib in mice significantly improved the treatment of metastatic HCC. In summary, our data demonstrate that TXN plays a crucial role in HCC stemness and BACH1 plays an integral part in regulating this process by activating the AKT/mTOR pathway. Thus, TXN is a promising target for metastatic HCC therapy. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Pulmonary metastasis of hepatocellular carcinoma: pathogenesis and therapeutic advances
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GUAN Tao, ZHANG Ti, WANG Lu
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hepatocellular carcinoma ,pulmonary metastasis ,tumor microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Surgery ,RD1-811 - Abstract
In recent years, the survival of patients increased with development of treatment modalities for hepatocellular carcinoma(HCC). However, the incidence of distant metastasis was gradually increasing to make the prognosis of patients with HCC worse. Lungs are the most common distant metastatic organs from HCC. Therapy of pulmonary metastasis from HCC was still disappointing with the median overall survival less than 1 year for individual differences in patients and tumor heterogeneity. Currently, there was without standard treatment for pulmonary metastases from HCC, and the patients were treated according to the treatment guidelines of advanced HCC combined with lung cancer. Although studies on invasion and metastasis of HCC emerged in a few decades, the detail pathogenesis of lung metastasis remains unclear. This article will summarize the pathogenesis and therapeutic advances of pulmonary metastasis from HCC and emphasize the importance of intrahepatic lesion control and management of pulmonary metastases.
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- 2022
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21. Angiotensin-converting enzyme inhibitors have adverse effects in anti-angiogenesis therapy for hepatocellular carcinoma.
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Zhang, Su, Cao, Manqing, Hou, Zhenyu, Gu, Xiaoying, Chen, Yongzi, Chen, Lu, Luo, Yi, Chen, Liwei, Liu, Dongming, Zhou, Hongyuan, Zhu, Keyun, Wang, Zhiwei, Zhang, Xihao, Zhu, Xiaolin, Cui, Yunlong, Li, Huikai, Guo, Hua, and Zhang, Ti
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HEPATOCELLULAR carcinoma , *DIABETIC nephropathies , *LIVER cancer , *CANCER invasiveness , *TUMOR growth , *PROTEINURIA - Abstract
At present, anti-angiogenic drugs (AADs) are widely used in the systemic treatment of hepatocellular carcinoma (HCC) or other types of cancer, and have achieved good anti-cancer effect, whereas treatment-related proteinuria can affect the routine use of AADs, which in turn abates the overall efficacy. Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria according to diabetic nephropathy guidelines or expert recommendations. However, the efficacy of ACEIs in reducing AAD-related proteinuria and its effect on the anticancer effect of AADs is unknown. Our clinical data showed that some HCC patients experienced tumor progression by ACEIs administration for the treatment of proteinuria caused by AADs. Here, we confirmed that in different tumor-bearing mouse models, ACEIs did not delay the appearance of proteinuria or alleviate proteinuria caused by AADs but compromised the anticancer efficacy of AADs. This effect is unrelated to the change in the VEGF signaling pathway. Our data showed that the combination of ACEIs and AADs flared the production of kidney-derived erythropoietin (EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. In conclusion, for the treatment of proteinuria caused by AADs, ACEIs have no efficacy while also promoting AADs resistance. This finding is of great significance to guide clinical standardized management of side effects of anti-angiogenic therapy for cancer patients. • ACEIs cannot reduce or delay proteinuria caused by AADs. • ACEIs alone do not promote tumor growth of liver cancer subcutaneous tumor. • High doses of AADs easily induce stable proteinuria, but the anticancer effect is better. • Proteinuria caused by AADs is reversible after withdrawal. • ACEIs promotes the production of kidney-derived EPO and reduces the anticancer efficacy of AADs. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Cross talk between oxidative stress and hypoxia via thioredoxin and HIF‐2α drives metastasis of hepatocellular carcinoma.
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Cao, Man‐Qing, You, A‐Bin, Cui, Wei, Zhang, Su, Guo, Zhi‐Gui, Chen, Lu, Zhu, Xiao‐Dong, Zhang, Wei, Zhu, Xiao‐Lin, Guo, Hua, Deng, Da‐Jun, Sun, Hui‐Chuan, and Zhang, Ti
- Abstract
Oxidative stress and hypoxia are two opposite microenvironments involved in HCC metastasis. Thioredoxin (TXN) and hypoxia‐inducible factor 2α (HIF‐2α) are typical proteins involved in these two different microenvironments, respectively. How these two factors interact to influence the fate on tumor cells remains unknown. Hypoxia facilitated HCC cells withstood oxidative stress and eventually promoted HCC cells metastasis, in which TXN and HIF‐2α were mostly involved. Upregulation of TXN/HIF‐2α correlated with poor HCC prognosis and promoted HCC metastasis both in vitro and in vivo. Epithelial‐mesenchymal transition (EMT) process was involved in TXN/HIF‐2α‐enhanced invasiveness of HCC cells. Additionally, the stability and activity of HIF‐2α were precisely regulated by TXN via SUMOylation and acetylation, which contributed to HCC metastasis. Our data revealed that the redox protein TXN and HIF‐2α are both associated with HCC metastasis, and the fine regulation of TXN on HIF‐2α contributes essentially during the process of metastasis. Our study provides new insight into the interaction mechanism between hypoxia and oxidative stress and implies potential therapeutic benefits by targeting both TXN and HIF‐2α in the treatment of HCC metastasis. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Retraction notice to "Protective autophagy induced by physcion suppresses hepatocellular carcinoma cell metastasis by inactivating the JAK2/STAT3 Axis" [Life Sci. 214 (2018) 124–135].
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Pan, Xiaoping, Wang, Chen, Li, Yan, Zhu, Lida, and Zhang, Ti
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HEPATOCELLULAR carcinoma , *METASTASIS - Published
- 2020
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