scholarly journals SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Suhong Xia ◽  
Jingwen Wu ◽  
Wangdong Zhou ◽  
Mingyu Zhang ◽  
Kai Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Immune Escape ◽  
Significant Risk ◽  
Suppressor Cells ◽  
Significant Risk Factor ◽  
Solute Carrier Family ◽  
Invasion And Metastasis ◽  
Solute Carrier

AbstractThe main reason for poor prognosis in hepatocellular carcinoma (HCC) patients is high metastasis and recurrence. Cancer progression depends on a tumor-supportive microenvironment. Therefore, illustrating the mechanisms of tumor immunity in underlying HCC metastasis is essential. Here, we report a novel role of solute carrier family 7 member 2 (SLC7A2), a member of the solute carrier family, in HCC metastasis. The reduction of SLC7A2 was an independent and significant risk factor for the survival of HCC patients. Upregulation of SLC7A2 decreased HCC invasion and metastasis, whereas downregulation of SLC7A2 promoted HCC invasion and metastasis. We further found that deficient SLC7A2 medicated the upregulation of CXCL1 through PI3K/Akt/NF-kκB pathway to recruit myeloid-derived suppressor cells (MDSCs), exerting tumor immunosuppressive effect. Moreover, we found that G9a-mediated di-methylation of H3K9 (H3K9me2) silenced the expression of SLC7A2 to suppress HCC metastasis and immune escape. In conclusion, G9a-mediated silencing of SLC7A2 exerts unexpected functions in cancer metastasis by fostering a tumor-supportive microenvironment through CXCL1 secretion and MDSCs recruitment. Thus, SLC7A2 may provide new mechanistic insight into the cancer-promoting property of MDSCs.

Hepatotoxicity during legacy cancer chemotherapy in patients infected with hepatitis C virus: A retrospective cohort study

2021 ◽  
Author(s):  
Jean-Luc Szpakowski ◽  
Lue-Yen Tucker ◽  
David M Baer ◽  
Mary Pat Pauly
Keyword(s):  
Risk Factor ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cancer Progression ◽  
Cancer Chemotherapy ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Hcv Infection ◽  
Grade 3

Background: The rates and causes of significant hepatotoxicity with cancer chemotherapy (CCT) in patients infected with hepatitis C virus (HCV) are incompletely characterized. Methods: We compared rates of grade 3 or 4 hepatotoxicity, defined as elevated transaminases, during CCT in patients who are mono-infected with HCV compared with rates in controls matched on demographics, diagnosis, and rituximab use. We excluded patients with hepatobiliary cancers, hepatitis B virus or human immunodeficiency virus infection. Hepatotoxicity was attributed to a medical cause, cancer progression, or CCT, including HCV flare. Results: Patients with HCV ( n = 196) had a higher rate of cirrhosis than the 1,130 matched controls (21.9% versus 4%; P <0.001). Their higher rate of overall hepatotoxicity (8.7% versus 4.5% of controls, P = 0.01 was due to higher rate of CCT-related hepatotoxicity (4.1% versus 1.2%, P = 0.01). On multivariable analysis, the largest risk factor for overall hepatotoxicity was cirrhosis, and the only risk factor for CCT-related hepatotoxicity was HCV infection. Among those with HCV, the only significant risk factor for hepatotoxicity was rituximab use. Hepatotoxicity caused by CCT delayed or altered treatment in only 3 HCV patients and 1 control (1.5% versus 0.1%, P = 0.01). Conclusions: Most patients with HCV can safely be treated with cancer chemotherapy. Cirrhosis and HCV infection contributed to increased hepatotoxicity in subjects on CCT. Among HCV patients, rituximab use was the major risk factor for increased hepatotoxicity. Hepatotoxicity due to CCT itself rarely altered or delayed CCT. Nonetheless, HCV-positive patients should be monitored carefully during CCT.

scholarly journals CD38 and Regulation of the Immune Response Cells in Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Sanyog Dwivedi ◽  
Erika P. Rendón-Huerta ◽  
Vianney Ortiz-Navarrete ◽  
Luis F. Montaño
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Immune Escape ◽  
Transmembrane Protein ◽  
Suppressor Cells ◽  
Typical Feature ◽  
Metabolic Reprogramming ◽  
Suppressor Activity ◽  
Nad Glycohydrolase ◽  
Cell Mediated Immune Response

Cancer is a leading cause of death worldwide. Understanding the functional mechanisms associated with metabolic reprogramming, which is a typical feature of cancer cells, is key to effective therapy. CD38, primarily a NAD + glycohydrolase and ADPR cyclase, is a multifunctional transmembrane protein whose abnormal overexpression in a variety of tumor types is associated with cancer progression. It is linked to VEGFR2 mediated angiogenesis and immune suppression as it favors the recruitment of suppressive immune cells like Tregs and myeloid-derived suppressor cells, thus helping immune escape. CD38 is expressed in M1 macrophages and in neutrophil and T cell-mediated immune response and is associated with IFNγ-mediated suppressor activity of immune responses. Targeting CD38 with anti-CD38 monoclonal antibodies in hematological malignancies has shown excellent results. Bearing that in mind, targeting CD38 in other nonhematological cancer types, especially carcinomas, which are of epithelial origin with specific anti-CD38 antibodies alone or in combination with immunomodulatory drugs, is an interesting option that deserves profound consideration.

scholarly journals Manuscript Impact on Prognosis of Different Anatomical Hepatectomy Approaches for Single Hepatocellular Carcinoma in Segment VI

2019 ◽  
Author(s):  
Jie Mei ◽  
Shao-Hua Li ◽  
Qiao-Xuan Wang ◽  
Liang-He Lu ◽  
Anna Kan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Postoperative Recovery ◽  
Free Survival ◽  
Propensity Score Matching Analysis ◽  
Early Hcc ◽  
The Common ◽  
Preoperative Factors

Abstract Background. Liver resection is effective for hepatocellular carcinoma (HCC). For a single HCC in subsegment 6 (S6), segmentectomy of S6, S5 (S6+5) and segmentectomy of S6, S7 (S6+7) are the common anatomical surgical procedures. However, the benefit of the two resection methods has not been clarified in this patient subgroup. This study aimed to compare the outcomes of S6+5 resection and S6+7 resection for single, early HCC located on S6 of the liver. Methods. In total, 115 patients with single HCC in S6 without vascular invasion and distant metastasis were included in this study. The patients were divided into the S6+5 group (n=73) and S6+7 group (n=42). A one-to-one propensity score-matching analysis (PSM) was performed to minimize the effect of potential confounders. Results. Forty patients from each group were matched. The preoperative factors were balanced between the two groups. The 1-, 2-, and 3-year overall survival (OS) rates in the S6+5 group were 92.3%, 82.1%, and 76.8%, respectively, and in the S6+7 group were 94.5%, 91.6% and 88.6%, respectively (p=0.197). The 1-, 2-, and 3-year recurrence-free survival (RFS) rates in the S6+5 group were 71.9%, 61.6%, and 58.9%, respectively, and in the S6+7 group were 83.5%, 77.7% and 68.8%, respectively (p=0.432). There were no significant differences in the recurrence pattern and postoperative recovery of liver function. The surgical procedure was not a significant risk factor for the OS and RFS in both the uni- and multivariate analyses. Conclusion. S6+5 and S6+7 resection achieved similar outcomes for early-stage solitary HCC in S6.

scholarly journals The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Wentao Jia ◽  
Shufang Liang ◽  
Binbin Cheng ◽  
Changquan Ling
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Stromal Cells ◽  
Immune Escape ◽  
Suppressive Effect ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Heterogeneous Effects ◽  
Chinese Medicine Treatment

Invasion and metastasis are the main reasons for the high mortality of liver cancer, which involve the interaction of tumor stromal cells and malignant cells. Cancer-associated fibroblasts (CAFs) are one of the major constituents of tumor stromal cells affecting tumor growth, invasion, and metastasis. The heterogeneous properties and sources of CAFs make both tumor-supporting and tumor-suppression effects possible. The mechanisms for CAFs in supporting hepatocellular carcinoma (HCC) progression can be categorized into upregulated aggressiveness and stemness, transformed metabolism toward glycolysis and glutamine reductive carboxylation, polarized tumor immunity toward immune escape of HCC cells, and increased angiogenesis. The tumor-suppressive effect of fibroblasts highlights the functional heterogenicity of CAF populations and provides new insights into tumor–stromal interplay mechanisms. In this review, we introduced several key inflammatory signaling pathways in the transformation of CAFs from normal stromal cells and the heterogeneous biofunctions of activated CAFs. In view of the pleiotropic regulation properties of traditional Chinese medicine (TCM) and heterogeneous effects of CAFs, we also introduced the application and values of TCM in the treatment of HCC through targeting CAFs.

scholarly journals Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yixi Zhang ◽  
Xiaojing Luo ◽  
Jianwei Lin ◽  
Shunjun Fu ◽  
Pei Feng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Tumour Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth in vivo was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105–2.373, P<0.001) and DFS (HR = 1.744, 95% CI = 1.205–2.523, P=0.003). Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.

scholarly journals Pan-Cancer Analysis of the Solute Carrier Family 39 Genes in Relation to Oncogenic, Immune Infiltrating, and Therapeutic Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Yuan Qu ◽  
Rong-Yan Guo ◽  
Meng-Ling Luo ◽  
Quan Zhou
Keyword(s):  
Tumor Cell ◽  
Cancer Progression ◽  
Therapeutic Targets ◽  
Genetic Mutation ◽  
Functional Enrichment ◽  
Solute Carrier Family ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Solute Carrier ◽  
Pan Cancer

Background: Emerging pieces of evidence demonstrated that the solute carrier family 39 (SLC39A) members are critical for the oncogenic and immune infiltrating targets in multiple types of tumors. However, the precise relationship between the SLC39A family genes and clinical prognosis as well as the pan-cancer tumor cell infiltration has not been fully elucidated.Methods: In this study, the pan-cancer expression profile, genetic mutation, prognostic effect, functional enrichment, immune infiltrating, and potential therapeutic targets of the SLC39A family members were investigated by analyzing multiple public databases such as the Oncomine, TIMER, GEPIA, cBioPortal, KM-plotter, PrognoScan, GeneMANIA, STRING, DAVID, TIMER 2.0, and CellMiner databases.Results: The expression levels of most SLC39 family genes in the tumor tissues were found to be significantly upregulated compared to the normal group. In mutation analysis, the mutation frequencies of SLC39A4 and SLC39A1 were found to be higher among all the members (6 and 4%, respectively). Moreover, the overall mutation frequency of the SLC39A family genes ranged from 0.8 to 6% pan-cancer. Also, the function of the SLC39A highly related genes was found to be enriched in functions such as zinc II ion transport across the membrane, steroid hormone biosynthesis, and chemical carcinogenesis. In immune infiltration analysis, the expression level of the SLC39A family genes was found to be notably related to the immune infiltration levels of six types of immune cells in specific types of tumors. In addition, the SLC39A family genes were significantly related to the sensitivity or resistance of 63 antitumor drugs in a variety of tumor cell lines.Conclusion: These results indicate that the SLC39 family genes are significant for determining cancer progression, immune infiltration, and drug sensitivity in multiple cancers. This study, therefore, provides novel insights into the pan-cancer potential targets of the SLC39 family genes.

scholarly journals Comparison of open liver resection and RFA for the treatment of solitary 3-5 cm hepatocellular carcinoma: a retrospective study

2019 ◽  
Author(s):  
Jianyong Lei ◽  
LN Yan ◽  
DJ Li ◽  
WT Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Cox Regression ◽  
Survival Rates ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Small Hepatocellular Carcinoma ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Resection Group

Abstract Aim: The goal of this study was to compare the postoperative results of liver resection and radiofrequency ablation (RFA) for the treatment of small hepatocellular carcinoma (HCC) (3-5 cm). Patients and methods: We retrospectively collected 122 patients with small solitary HCC treated at our center from Jan 2011 to Dec 2015, with diameters in the range of 3-5 cm. According to the treatment program received at our center, they were divided into the liver resection group (72 patients) and the RFA group (50 patients). Result : In comparison with the RFA group, the resection group had a longer operative time, and greater intra-operative blood loss (P<0.01), more hepatic inflow occlusion , and longer postoperative hospital stay (P<0.01). The 1-, 3-, and 5-year expected overall survival rates and tumor-free survival rates were comparable between the two groups. Cox regression analysis showed that resection or RFA was not a significant risk factor for overall or tumor-free survival for HCC. Conclusions : For solitary HCC of 3-5 cm in diameter, RFA can achieve better in-hospital clinical results and similar long-term outcomes, and RFA can be considered for wide application, especially for central cases.

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