Study of the Role of Insulin Resistance as a Risk Factor in Hcv Related Hepatocellular Carcinoma

Ibrahim, Amany Ahmad; Aleem, Mostafa Hamed Abdel; Abdella, Heba M.

doi:10.12816/0010856

Cited by 4 publications

(5 citation statements)

References 20 publications

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“…With one exception [68] , studies robustly and consistently indicated that obesity [63] , steatosis [64,65] , visceral fat [66] , diabetes [67] , obesity and diabetes [69] , and MetS [76] were risk factors for HCC in selected cohorts (i.e., those with HCV infection, and those with recurrent HCC) and unselected population studies. The pathomechanisms sustaining this link include leptin [85] , elevated insulin/insulin resistance [72,73] , and sarcopenia [74] . Interestingly, metabolic factors, including steatosis, (visceral) obesity, and DM, also play a role in risk factors of HCC developing in the setting of alcoholic cirrhosis [71] and viral hepatitis [77][78][79][80][81][82][83][84] , suggesting that these dysmetabolic traits are consistently associated with increased HCC risk across a broad spectrum of clinical scenarios.…”

Section: Metanalytic Studiesmentioning

confidence: 99%

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

Lugari¹,

Baldelli²,

Lonardo³

2023

Metab Target Organ Damage

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Primary liver cancer (PLC) is a heterogeneous group of disorders arising with the background of chronic liver disease (CLD) owing to varying etiologies. PLC carries a high lethality rate and a substantial epidemiological, clinical, and financial burden, which is projected to escalate. The two most common PLC histotypes in adults are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC); the latter is sub-classified as either intrahepatic CC or extrahepatic CC. Over recent decades, there has been a decline of viral CLD accompanied by an increase in dysmetabolic CLD, resulting in PLC becoming relatively more common in Western countries. Metabolic co-morbidities are risk factors and co-factors for HCC and (increasingly) CC. Complex immunological, cellular, pro-inflammatory, molecular, and genetic processes in the systemic dysmetabolic milieu increase PLC risk. Improved understanding of these mechanisms requires close surveillance and early diagnosis of at-risk patients while paving the way for personalized medicine, chemoprevention, and innovative management of metabolic PLC.

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Section: Metanalytic Studiesmentioning

confidence: 99%

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

Lugari¹,

Baldelli²,

Lonardo³

2023

Metab Target Organ Damage

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“…However, the occurrence of drug resistance is a thorny problem in HCC therapy in clinical practice, and tumor cells that escape death appear in a lot of cases that are associated with acquired resistance to apoptosis induced by anticancer drugs. 7,8 Tumors acquired resistance to apoptosis though early stage apoptosis or incomplete apoptotic responses to oncolytic treatments of anticancer drugs and late stage apoptosis frequently led to death of tumor cells. Anti-cancer drugs inhibited tumor growth through decreasing apoptosis resistance and inducing apoptosis of tumor cells, which further led to decreasing of neoplasm invasion.…”

Section: Introductionmentioning

confidence: 99%

A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma

Zhang

Wang

2017

Tumour Biol.

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The abilities to escape apoptosis induced by anticancer drugs are an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this study, we identified hTERTR-FAM96A (human telomerase reverse transcriptasefamily with sequence similarity 96 member A) as a new efficient agent for apoptosome-activating and anti-tumor protein and investigated the potential tumor suppressor function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was constructed by genetic engineering and its anticancer function of hTERTR-FAM96A was explored in vitro and in vivo by investigating the possible preclinical outcomes. Effects of hTERTR-FAM96A on improvement of apoptotic sensitivity and inhibition of migration and invasion were examined in cancer cells and tumors. Our results showed that the therapeutic effects of hTERTR-FAM96A were highly effective for inhibiting tumor growth and inducing apoptosis of hepatocellular carcinoma cells in H22-bearing nude mice. The hTERTR-FAM96A fusion protein could specifically bind with Apaf-1 and hTERT, which further induced apoptosis of hepatocellular carcinoma cells and improved apoptosis sensitivity. Our results indicated that hTERTR-FAM96A treatment enhanced cytotoxic effects by upregulation of cytotoxic T lymphocyte responses, interferon-γ release, and T lymphocyte infiltration. In addition, hTERTR-FAM96A led to tumor-specific immunologic cytotoxicity through increasing apoptotic body on hepatocellular tumors. Furthermore, hTERTR-FAM96A dramatically inhibited tumor growth, reduced death rate, and prolonged mice survival in hepatocellular carcinoma mice derived from three independent hepatocellular carcinoma mice cohorts compared to control groups. In summary, our data suggest that hTERTR-FAM96A may serve as an efficient anti-tumor agent for the treatment of hepatocellular carcinoma.

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“…These cellular signal pathways presented key signal transduction for various extracellular growth factors and receptors of HCC cells. However, the high occurrence (62–82%) of drug resistance is a major issue in clinical HCC therapy ( 10 , 11 ). Tumors have been demonstrated to acquire apoptotic-resistance during early stage apoptosis or incomplete apoptotic responses to oncolytic treatments and anticancer drugs, and the consequent requirement for long-term medical therapy presented a major clinical problem in HCC ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Combination therapy of hTERTR and FAM96A for hepatocellular carcinoma through enhancing apoptosis sensitivity

Wang

Gao

2017

Exp Ther Med

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Avoidance of apoptosis induced by anticancer drugs is an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. Human telomerase reverse transcriptase receptor (hTERTR) is a potential anti-cancer agent for inhibiting tumor growth. Family with sequence similarity 96 member A (FAM96A) is a ubiquitous, conserved protein and possesses apoptosome-activating and pro-apoptotic tumor suppressor potential in hepatocellular carcinoma (HCC). In the present study, hTERTR and FAM96A were identified as efficient anti-cancer agents for activating apoptosomes and reducing tumor growth. The potential tumor suppressor function of combination treatment with hTERTR and FAM96A in HCC was also investigated. hTERTR and FAM96A proteins were expressed by genetic engineering and their anti-cancer function was explored in vitro and in vivo. Effects of hTERTR and FAM96A on improvement of apoptotic sensitivity and inhibition of migration and invasion were examined in cancer cells and in a mouse model. The present results demonstrated that the therapeutic effects of hTERTR and FAM96A were effective for inhibiting tumor growth and inducing apoptosis of HCC cells in H22-bearing nude mice compared with single agent treatment. hTERTR and FAM96A were found to bind with apoptotic protease activating factor 1 and human telomerase reverse transcriptase, which enhanced the apoptosis of tumor cells and apoptosis sensitivity. In addition, hTERTR and FAM96A therapy enhanced cytotoxic effects by cytotoxic T lymphocyte responses, interferon-γ release, T lymphocytes infiltration and apoptosis on tumor cells. Furthermore, hTERTR and FAM96A protein inhibited tumor growth in HCC mice. In conclusion, the present findings suggested that combination therapy with hTERTR and FAM96A may serve as novel tumor suppressor agents.

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Study of the Role of Insulin Resistance as a Risk Factor in Hcv Related Hepatocellular Carcinoma

Cited by 4 publications

References 20 publications

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma

Combination therapy of hTERTR and FAM96A for hepatocellular carcinoma through enhancing apoptosis sensitivity

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