scholarly journals Dissecting the biological diversity of hepatocellular carcinoma: Opening Pandora's Box

2016 ◽  
Vol 2 (4) ◽  
pp. 179
Author(s):  
Omar Abdel-Rahman

<p>Primary liver cancer is one of the most commonly occur-ring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1, 2]. In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3]. Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (e.g., the Barcelona Clinic liver cancer system) [4], exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is ex-pected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic stea-tohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways. In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5]. COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low- to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regulated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward.</p><p>Primary liver cancer is one of the most commonly occurring malignancies, albeit one with a deadly consequence as it ranks second in males and sixth in females as a cause of cancer-related death [1,2]. In this regard, hepatocellular carcinoma (HCC) constitutes almost 90% of confirmed primary liver cancer cases [3].</p><p>Despite the advances in clinical classifications of HCC according to patient-related and disease-related criteria (<em>e.g.</em>, the Barcelona Clinic liver cancer system) [4], exploring the biological diversity of HCC have lagged behind. The biological diversity of HCC is expected to come from a diverse set of etiological factors (Hepatitis-B virus, Hepatitis-C virus, non-alcoholic steatohepatitis, and aflatoxin, among other things), all of which are expected to drive the pathogenesis of HCC via various pathways.</p><p>In the current issue of AMOR, Youssef and co-workers explored the potential involvement of the cofactor of BRCA1 (COBRA1) in HCC pathogenesis [5].  COBRA1 has been incriminated in the pathogenesis of a number of other solid tumors, notably breast cancer. In the current study, the authors investigated the expression of COBRA1 in several HCC cell lines, ranging from low- to high-grade HCC cell lines. Their results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regu- lated in high-grade HCC cell lines. This preliminary study indicates that COBRA1 may indeed play a role in HCC pathogenesis and progression, and should be further investigated moving forward.</p>

2016 ◽  
Vol 63 (2) ◽  
pp. 153-158
Author(s):  
Irina Dinu ◽  
◽  
Mihai Voiculescu ◽  
Andreea Radasan ◽  
◽  
...  

Introduction. Hepatocellular carcinoma is the most common primary liver cancer (90%), the 5th neoplasia in terms of incidence and the 3rd mortality cause worldwide (1). This increased mortality is the consequence of diagnosis in an advanced state and of the fact that most HCC develop based on a chronic hepatic pathology. In Romania, around 7% of the population is affected by chronic hepatitis B, the incidence of this disease being increased in urban areas (2). The sooner the hepatitis B virus infection occurs in life, the higher the probability is, for this to become chronic and to lead to cirrhosis or liver cancer. Hepatitis D only occurs among people who are infected with the Hepatitis B virus because HDV is an incomplete virus that requires the helper function of HBV to replicate. Objective of the study. The main purpose of the surveillance and/or screening is to decrease mortality and morbidity by means of liver cancer for patients diagnosed with hepatitis B and hepatitis D. Matherial and methods. The study was conducted on a number of 102 patients diagnosed with viral hepatitis (HBV, HDV+HBV) admitted at the “Fundeni” Hospital, Bucharest, between 2012-2015. Two batches of patients were taken into account (patients with hepatitis B and hepatitis D). The viral load and chosen treatment were clinically, biochemically and imagistically evaluated. Results. We have noticed a significant increase in patients diagnosed with hepatitis B and D. The existence of the hepatitis D infection in patients diagnosed with hepatitis B significantly increases the occurence potential of liver cancer. The hepatic destruction degree by means of cirrhotic liver occurence respectively hepatic cirrhosisis much higher for patients diagnosed with hepatitis D. Conclusions. The close monitoring of the patients in this research program brings real benefit for the prevention of liver cancer and diagnosing it early, having a much better prognosis on the quality of life.


2016 ◽  
Vol 2 (4) ◽  
pp. 224 ◽  
Author(s):  
Aya Youssef ◽  
Heba Shawer ◽  
Alaa Afify ◽  
Asma Amleh

<p>The cofactor of BRCA1 (COBRA1), which also refers to negative elongation factor polypeptide B (NELF-B), is a negative elongation factor (NELF) subunit that has been implicated in the development and progression of several cancers. While reduced COBRA1 expression has been associated with metastatic breast cancer, COBRA1 negatively regulates the activator protein-1 (AP-1) complex, leading to the down-regulation of trefoil factor-1 (TFF1) expression in gastric cancer cell lines. The involvement of COBRA1 in hepatocellular carcinoma (HCC) tumor formation and progression is not known. Here, we investigated the expression of COBRA1, the AP-1 complex, and TFF1 in several HCC cell lines; ranging from low- to high-grade HCC cell lines generated from patients with different stages of the disease. Our results showed that the COBRA1 protein was highly expressed in the low-grade HCC cell line, while significantly down-regulated in high-grade HCC cell lines. TFF1, previously regarded as a COBRA1 target gene, was only expressed in the low-grade HCC cell line and the control cells. Our results suggest that COBRA1 may play a role in HCC pathogenesis and progression. The TFF1 mRNA expression profile was uncorrelated to that of the AP-1 complex subunit proteins, which suggests the involvement of other regulatory pathways in TFF1 expression; however, this requires further study.</p>


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seiga Komiyama ◽  
Takahiro Yamada ◽  
Nobuyuki Takemura ◽  
Norihiro Kokudo ◽  
Koji Hase ◽  
...  

AbstractLiver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 172
Author(s):  
Elena S. George ◽  
Surbhi Sood ◽  
Anna Broughton ◽  
Georgia Cogan ◽  
Megan Hickey ◽  
...  

Globally, liver cancer is the sixth most common cause of cancer mortality, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. Emerging evidence states that diet is recognised as a potential lifestyle-related risk factor for the development of HCC. The aim of this systematic review is to determine whether there is an association between diet and the development of HCC. Using the PRISMA guidelines, three databases (MEDLINE Complete, CINAHL and Embase) were systematically searched, and studies published until July 2020 were included. Thirty observational studies were selected. The protocol was registered with PROSPERO (CRD42019135240). Higher adherence to the Mediterranean dietary pattern, Alternative Healthy Eating Index-2010, the Urban Prudent Dietary Pattern, the Traditional Cantonese Dietary Pattern, intake of vegetables, wholegrains, fish, poultry, coffee, macronutrients such as monounsaturated fats and micronutrients such as vitamin E, vitamin B9, β-carotene, manganese and potassium were associated with a reduced risk of HCC. The results suggest a potential role of diet in the development of HCC. Further quantitative research needs to be undertaken within a range of populations to investigate diet and the relationship with HCC risk.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3740
Author(s):  
Chunye Zhang ◽  
Ming Yang

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.


2021 ◽  
Vol 22 (8) ◽  
pp. 3956
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Hae June Lee ◽  
Kiwon Song

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.


1985 ◽  
Vol 23 (13) ◽  
pp. 49-51

The hepatitis B virus is the most common cause world-wide of acute hepatitis, and also causes chronic hepatitis, cirrhosis1 and primary liver cancer.2 It can now be prevented by a vaccine. How should this best be used?


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