scholarly journals An Overview of Bacterial and Viral Inhibitors Involved in Gene Therapy of Hepatocellular Carcinoma (Hcc)

Hepatocellular carcinoma (HCC) is a form of cancer that is very widespread around the world and has a high mortality rate. Extensive evidence suggests that, HCC is a multifactorial disease. Hepatic cirrhosis is present, along with systemic inflammation and viral infections such as hepatitis B or C. Thus, giving rise to genetically and phenotypically heterogeneous hepatocellular carcinoma tumors. Researchers have found that bacterial and viral inhibitors can be used to silence targeted genes in hepatocellular carcinoma. Many bacterial species such as; Salmonella, Listeria, and Escherichia, proved to have anti-tumor properties. Up till now, adenoviral, retroviral, herpes-simplex viral and adeno-associated viral vectors have been modified and are being used for HCC gene therapy. In patients, up regulation of TLR signaling have also been observed showing an interesting influence on HCC’s microenvironment. TLR 4 and TLR 9 have positive relationship with tumor whereas, TLR3 is associated with anti-tumor influence. TLRs can cause an inflammatory response in the presence of foreign pathogens including bacteria and fungi. This review reflects an insight into the biology of HCC suggesting that certain signaling pathways and molecular alterations plays a very significant role in HCC development. As well as new experimental approaches, including; anti-angiogenesis, cancer therapy, oncolytic virotherapy, and suppressing the function of oncogenes, leading to apoptosis are successively being applied. The current challenge for the researchers is to identify a medicament which is selective for tumors specific cells only, having minimal noxiousness and harmless to normal tissue. We have scrutinized research articles based on how to merge viral and bacterial anticancer therapies into a single treatment for HCC.

2020 ◽  
Vol 11 (1) ◽  
pp. 833-850 ◽  
Author(s):  
Katherine E Redd Bowman ◽  
Phong Lu ◽  
Erica R Vander Mause ◽  
Carol S Lim

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death globally, mainly due to lack of effective treatments – a problem that gene therapy is poised to solve. Successful gene therapy requires safe and efficient delivery vectors, and recent advances in both viral and nonviral vectors have made an important impact on HCC gene therapy delivery. This review explores how adenoviral, retroviral and adeno-associated viral vectors have been modified to increase safety and delivery capacity, highlighting studies and clinical trials using these vectors for HCC gene therapy. Nanoparticles, liposomes, exosomes and virosomes are also featured in their roles as HCC gene delivery vectors. Finally, new discoveries in gene editing technology and their impacts on HCC gene therapy are discussed.


2012 ◽  
Vol 153 (25) ◽  
pp. 978-989 ◽  
Author(s):  
Gábor Lendvai ◽  
András Kiss ◽  
Ilona Kovalszky ◽  
Zsuzsa Schaff

The details of molecular alterations occurring during hepatocarcinogenesis have not been revealed yet. Nevertheless, it is known that microRNAs (miRNA), these short RNA molecules regulating gene expression mainly in a negative way, are also involved in this process. Altered miRNA expression levels are present in liver diseases when compared with normal liver tissue, and the observed alterations depend mainly on which is more advantegous for the disease: activation or inhibition of the genes (e.g. oncogenes or tumor suppressor genes) regulated by the altered miRNAs. The miRNA expression pattern described in hepatocellular carcinoma seems to differ the most from that found in the normal liver; however, remarkable alterations at miRNA levels have been published in early stages of hepatic tumor progression such as fibrosis and chronic hepatitis. For example, the expression of miR-21, miR-221, miR-222 and miR-199a showing characteristic alterations in hepatocellular carcinoma also displayed deregulated expressions in these two early stages. The liver characteristic miRNA, miR-122, usually exhibits a decreased expression level upon liver injury as well as miR-122 expression tends to decrease as hepatic carcinogenesis progresses. Besides, miR-122 enhances the replication of hepatitis C virus and the initial low or high level of miR-122 seems to influence the efficiency of interferon therapy. Recently, statistically significant differences have been detected in the expression of several miRNAs being present in the serum of patients with chronic hepatitis, chirrhosis and hepatocellular carcinoma when compared with normal controls. It suggests that serum miRNAs could be potential biomarkers. In this article, the major and recent alterations of microRNA expression patterns in stages of hepatocarcinogenesis such as fibrosis, viral infections (hepatitis), cirrhosis and hepatocellular carcinoma are summarized. Orv. Hetil., 2012, 153, 978–989.


2020 ◽  
Vol 2 (4) ◽  
pp. 469-480
Author(s):  
Bryan Mckiver ◽  
Mohamad Imad Damaj ◽  
Devanand Sarkar

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the fifth most common cancer worldwide. HCC is recognized as the fourth most common cause of cancer related deaths worldwide due to the lack of effective early diagnostic tools, which often leads to individuals going undiagnosed until the cancer has reached late stage development. The current FDA approved treatments for late stage HCC provide a minimal increase in patient survival and lack tumor specificity, resulting in toxic systemic side effects. Gene therapy techniques, such as chimeric antigen receptor (CAR)-T Cells, viral vectors, and nanoparticles, are being explored as novel treatment options in various genetic diseases. Pre-clinical studies using gene therapy to treat in vitro and in vivo models of HCC have demonstrated potential efficacy for use in human patients. This review highlights genetic targets, techniques, and current clinical trials in HCC utilizing gene therapy.


2019 ◽  
Vol 19 (4) ◽  
pp. 272-280 ◽  
Author(s):  
Li Wang ◽  
Min Yao ◽  
Wenjie Zheng ◽  
Miao Fang ◽  
Mengna Wu ◽  
...  

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.


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