Search

Yuan Tian,1,* Wenbiao Jin,1,* Honghua Sun,1 Dehao Jin,2 Dongxu Kang,1 Zhiyu Li,1 Longzhen Piao1 1Department of Oncology, The Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People’s Republic of China; 2Department of Radiology, Yanbian Maternal and Child Health Hospital, Yanji, Jilin Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyu Li; Longzhen Piao, Department of Oncology, The Affiliated Hospital of Yanbian University, No. 1327 Juzi Street, Yanji City, Jilin Province, People’s Republic of China, Tel +86 15526771578 ; +86 15526771162, Fax +86 433 2513610, Email 15526771578@163.com; plz1978@126.comBackground: Advanced-stage hepatocellular carcinoma (HCC), especially huge HCC or portal vein tumour thrombus (PVTT), is difficult to treat, and the prognosis is poor. The advantages of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunotherapy for this complex disease are gradually becoming apparent. However, HAIC still has some inevitable disadvantages, such as arterial perfusion therapy requiring a long time, which results in many patients having difficulty completing the procedure. Modified HAIC (mHAIC)-based oxaliplatin and S-1 is a new treatment option for huge HCC or PVTT that can reduce complications and improve patient compliance. We report two cases of huge HCC or PVTT that were successfully treated with mHAIC combined with lenvatinib and camrelizumab. The clinical presentations, treatment strategies, and outcomes of these cases are presented.Case Presentation: Case 1: A 52-year-old female was found to have a huge HCC with a size of 14× 11 cm. She was treated with one cycle of mHAIC combined with transcatheter arterial chemoembolization (TACE), lenvatinib and camrelizumab and 3 cycles of mHAIC in combination with lenvatinib and camrelizumab. The patient’s follow-up maintenance therapy with lenvatinib and camrelizumab has been evaluated for efficacy in achieving complete response (CR). Case 2: A 57-year-old man was diagnosed with advanced HCC in combination with PVTT. He achieved partial remission (PR) after four cycles of mHAIC combined with lenvatinib and camrelizumab. This was followed by treatment with lenvatinib and camrelizumab with an efficacy assessment for CR, and progression-free survival (PFS) was 7 months.Conclusion: For advanced HCC with a large mass or PVTT, mHAIC combined with lenvatinib and camrelizumab is a safe and effective treatment with good patient compliance.Keywords: huge HCC, PVTT, mHAIC, case report

Lihua Piao,1 Haoyue Li,1,2 Ying Feng,1,2 Xiaogang Li,3 Yan Cui,4 Yanhua Xuan1,2 1Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, People’s Republic of China; 2Department of Pathology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, People’s Republic of China; 3Department of Urology, Yanbian University Affiliated Hospital, Yanji 133002, Jilin Province, People’s Republic of China; 4Department of Oncology, Yanbian University Affiliated Hospital, Yanji 133002, Jilin Province, People’s Republic of ChinaCorrespondence: Yanhua XuanDepartment of Pathology, Yanbian University College of Medicine, No. 977, Gongyuan Road, Yanji City 133002, People’s Republic of ChinaTel +86-433-2435107Fax +86-433-2732456Email xuanyh1@ybu.edu.cn Yan CuiDepartment of Oncology, Yanbian University Affiliated Hospital, No. 977, Gongyuan Road, Yanji City 133002, People’s Republic of ChinaTel +86-433-2435107Fax +86-433-2732456Email cuiyan2005@hotmail.comPurpose: The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression.Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffin-embedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting.Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells.Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.Keywords: prostate cancer, leucine zipper-EF-hand containing transmembrane protein 1, epithelial-mesenchymal transition, prognosis

Xu Han, 1,* Lianhua Piao, 2,* Xiaoshuang Xu, 2 Fengbao Luo, 1 Zhiwei Liu, 3 Xiaozhou He 1 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China; 2Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou 213001, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaozhou HeDepartment of Urology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, Jiangsu Province, People’s Republic of ChinaTel +86 519 6887 1251Email hxz912@126.comBackground: Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase). The aim of this study was to investigate the biological role of NSD2 in clear cell renal cell carcinoma (ccRCC).Methods: GEO and OncoLnc databases were used to identify NSD2 expression and estimate its clinical value in ccRCC. Immunohistochemistry (IHC) was applied to further evaluate NSD2 protein level in ccRCC tissues. The expression of NSD2 in different cell lines and the transfection efficiency were determined by quantitative real-time PCR and Western blot analysis. The effect of NSD2 and the underlying mechanism in ccRCC progression were investigated via MTT, flow cytometry, Western blotting and xenograft tumor assays.Results: NSD2 was over-expressed in both ccRCC tissues and cell lines. NSD2 expression could discriminate ccRCC samples from normal samples, and moreover, high NSD2 expression was characterized with a short overall survival (OS) time. Additionally, knockdown of NSD2 suppressed proliferation and induced apoptosis of cancer cells by inhibiting Akt/Erk signaling and regulating Bcl-2 and Bax expression. Meanwhile, up-regulation of NSD2 contributed to the opposite effects. Silencing of NSD2 reduced xenograft tumor growth in vivo.Conclusion: NSD2 serves as an oncogenic factor in the progression of ccRCC via activation of Akt/Erk signaling.Keywords: NSD2, renal cancer, proliferation, apoptosis, Akt/Erk signaling

Tao Wen,1,* Aiyun Yang,1,* Lingyu Piao,2 Suisui Hao,1 Lifan Du,1 Jie Meng,1 Jian Liu,1 Haiyan Xu11Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, People’s Republic of China; 2CAS Center for Excellence in Nanoscience, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology, Beijing, 100190, People’s Republic of China*These authors contributed equally to this work Background: Effects of different nanoparticles (NPs) exposure at acutely non-cytotoxic concentrations are particularly worthy to figure out, compare, and elucidate. Objective: To investigate and compare the effect of a small library of NPs at non-cytotoxic concentration on the adherens junction of human umbilical vein endothelial cells (HUVECs), obtaining new insights of NPs safety evaluation. Materials and methods: The HUVECs layer was exposed to NPs including gold (Au), platinum (Pt), silica (SiO2), titanium dioxide (TiO2), ferric oxide (Fe2O3), oxidized multi-walled carbon nanotubes, with different surface chemistry and size distribution. Cellular uptake of NPs was observed by transmission electron microscopy. and the cytotoxicity was determined by Cell Counting Kit-8 assay. The NP-induced variation of intracellular reactive oxygen species (ROS) and catalase (CAT) activity was measured using the probe of 2ʹ7’-dichlorodihydr fluorescein diacetate and a CAT analysis kit, respectively. The level of VE-cadherin of HUVECs was analyzed by Western blot, and the loss of adherens junction was observed with laser confocal microscopy. Results: The acutely non-cytotoxic concentrations of different NPs were determined and applied to HUVECs. The NPs increased the level of intracellular ROS and the activity of CAT to different degrees, depending on the characteristics. At the same time, the HUVECs lost their adherens junction protein VE-cadherin and gaps were formed between the cells. The NP-induced oxidative stress and gap formation could be rescued by the supplementary N-acetylcysteine in the incubation. Conclusion: The increase of intracellular ROS and CAT activity was one common effect of NPs, even at the non-cytotoxic concentration, and the degree was dependent on the composition, surface chemistry, and size distribution of the NP. The effect led to the gap formation between the cells, while could be rescued by the antioxidant. Therefore, the variation of adherens junction between endothelial cells was suggested to evaluate for NPs when used as therapeutics and diagnostics. Keywords: reactive oxygen species (ROS), catalase, HUVEC, VE-cadherin

This study was designed to investigate the potential key genes of ADP-ribosylation factor-like 15 (ARL15) regulating glycolysis and lipogenesis in colon cancer. Hematoxylin-eosin (HE) staining and immunohistochemistry were used to observe the expression of ARL15 in 10 normal colon tissues and 10 colon cancer tissues. Immunofluorescence staining was used to observe the expression position of ARL15 in normal human colorectal mucosa cells (FHC) and colon cancer cells (HCT116 and SW620) with a confocal microscope. The ARL15 plasmid and small interfering RNA (siRNA) were constructed. After transfection, the expression levels of glycolysis and lipogenesis regulatory enzymes and messenger RNA (mRNA) transcription of ARL15 in over-expressed and silenced colon cancer cells were detected by Western blotting and real-time quantitative PCR (qRT-PCR). High expression of ARL15 in colon cancer tissue and low expression in normal colon tissue, and all expression are in the cytosol. The expression position of ARL15 in the FHC, HCT116, and SW620 cells was consistent and mainly distributed in the cytosol. After the pCMV-3Tag-2-ARL15 plasmid was transfected in HCT116, the protein expressions of FASN, AKT, P-AKT, P-GSK, SREBP-1 (p125) (p<0.01), and AMPK (p<0.001) were higher than those in the control group. The mRNA transcription level of FASN, GSK, AMPKa1, and SREBP-1 gene was higher than control group after the over-expression of ARL15. After the ARL15-siRNA was transfected in HCT116, the protein expression levels of PKM2, PFK, FASN, AKT, P-AKT, P-GSK, and AMPK decreased compared with the control group, (p<0.05). The mRNA transcription level of FASN, GSK, AMPKa1 gene was lower than control group after the low-expression of ARL15 (p<0.05). After adding 2 µM JIB-04, ARL15 in HCT116 showed statistical differences compared with the control group at 12 h, 24 h and 36 h (p<0.05). After adding 2 µM JIB-04, the protein expression levels of AKT, p-GSK, FASN, AMPK and SREBP-1 in HCT116 cells decreased significantly after 24 h. It was also found that the expression levels of AKT, P-GSK, FASN, AMPK and SREBP-1 genes in the dose-adding group were significantly lower than those in the control group. In summary, ARL15 may promote the occurrence of colon cancer by increasing the expression of protein kinase B/AMP-activated protein kinase (AKT/AMPK) downstream regulatory enzymes for glycogenesis and lipogenesis. JIB-04 can target ARL15 and affect its expression as well as the expressions of glucose and lipid metabolity-related proteins in AKT and AMPK signaling pathways. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore whether plasmacytoma variant translocation 1 (PVT1) could regulate glioblastoma multiforme (GBM) progression via microRNA-1301-3p (miR-1301- 3p) and transmembrane BAX inhibitor motif containing 6 (TMBIM6) axis. MATERIALS AND METHODS: Expression patterns of PVT1 and RMBIM6 in GBM patients were analyzed using GEPIA, an online gene expression analysis tool. Levels of PVT1 in GBM cells and normal cells were analyzed with quantitative real-time PCR method. Cell Counting Kit-8 (CCK- 8), transwell invasion assay, and flow cytometry assay were applied to detect cell viability and apoptosis. Connections of PVT1 or TMBIM6 with miR-1301-3p were validated with bioinformatic tool and luciferase activity reporter assay. RESULTS: PVT1 was significantly expressed in GBM tissues and cells. PVT1 promotes GBM cell proliferation and invasion but inhibits apoptosis in vitro. TMBIM6 was significantly expressed in GBM tissues. The knockdown of TMBIM6 reversed the stimulation effects of PVT1 on GBM cell malignancy behaviors with miR- 1301-3p as a bridge. CONCLUSIONS: Collectively, we showed PVT1 elevated TMBIM6 expression mediated by miR-1301-3p and thus to promote GBM progression. [ABSTRACT FROM AUTHOR]