Liver Cancer Cases Research Articles

Analysis of Liver Microenvironment during Early Progression of Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma in Zebrafish.

Liver cancer is currently the thirdleading cause of cancer related death worldwide, and Hepatocellular Carcinoma (HCC) accounts for 75-90% of all liver cancer cases. With the introduction of effective treatments to prevent and treat hepatitis B/C, non-alcoholic fatty liver disease (NAFLD), and the more aggressive form know as non-alcoholic steatohepatitis (NASH), are quickly becoming the number one risk factors to develop HCC in modern societies. To better understand the role NASH has on the development of HCC we designed a NASH-associated HCC zebrafish. The optical clarity and genetic tractability of the zebrafish larvae make them an appealing and powerful model to study the liver microenvironment and immune cell composition using non-invasive fluorescent live imaging. This protocol describes how to use a NASH-associated HCC zebrafish model to investigate the effect of cholesterol surplus in the liver microenvironment and its impact on immune cell composition at early stages of the disease. First, we feed HCC larvae (s704Tg), which express hepatocyte-specific activated beta-catenin, with a 10% high cholesterol diet for 8 days to develop a NASH-associated HCC model. Here we describe how to make use of different transgenic lines to evaluate several early malignancy features in the liver by non-invasive confocal microscopy, such as liver area, cell, and nuclear morphology (hepatocytes area, nuclear area, nuclear:cytoplasmic ratio (N:C ratio), nuclear circularity, micronuclei/nuclear herniation scoring) and angiogenesis. Then, using transgenic lines with tagged immune cells (neutrophils, macrophages, and T cells) we show how to analyze liver immune cell composition in NASH-associated HCC larvae. The described techniques are useful to evaluate liver microenvironment and immune cell composition at early hepatocarcinogenesis stages, but they can also be modified to study such features in other liver disease models.

Hepatocellular Carcinoma Automatic Diagnosis within CEUS and B-Mode Ultrasound Images Using Advanced Machine Learning Methods.

Hepatocellular Carcinoma (HCC) is the most common malignant liver tumor, being present in 70% of liver cancer cases. It usually evolves on the top of the cirrhotic parenchyma. The most reliable method for HCC diagnosis is the needle biopsy, which is an invasive, dangerous method. In our research, specific techniques for non-invasive, computerized HCC diagnosis are developed, by exploiting the information from ultrasound images. In this work, the possibility of performing the automatic diagnosis of HCC within B-mode ultrasound and Contrast-Enhanced Ultrasound (CEUS) images, using advanced machine learning methods based on Convolutional Neural Networks (CNN), was assessed. The recognition performance was evaluated separately on B-mode ultrasound images and on CEUS images, respectively, as well as on combined B-mode ultrasound and CEUS images. For this purpose, we considered the possibility of combining the input images directly, performing feature level fusion, then providing the resulted data at the entrances of representative CNN classifiers. In addition, several multimodal combined classifiers were experimented, resulted by the fusion, at classifier, respectively, at the decision levels of two different branches based on the same CNN architecture, as well as on different CNN architectures. Various combination methods, and also the dimensionality reduction method of Kernel Principal Component Analysis (KPCA), were involved in this process. These results were compared with those obtained on the same dataset, when employing advanced texture analysis techniques in conjunction with conventional classification methods and also with equivalent state-of-the-art approaches. An accuracy above 97% was achieved when our new methodology was applied.

Analysis of clinical characteristics of 481 HBV-related liver cirrhotic patients with low viral load

Objective: To analyze the clinical characteristics of HBV-related liver cirrhotic patients with low viral load. Methods: A retrospective analysis on 481 inpatients with HBV-related cirrhosis with low viral load [HBV DNA≤2 000 IU/ml (10(4) copies/ml)] general condition, virological indicators, liver function-related indicators, complications, and incidence of complications were analyzed. The t-test was used to compare the average measurement data, and the χ (2) test was used to compare the count data. Results: 481 cases were mainly male (male/female: 324/157), aged 20-83 (53.31 ± 11.67) years old. Han nationality accounted for 71.518%. 386 cases were HBsAg positive. 391 cases were HBeAg positive, and 140 cases were HBV DNA positive. The average value of bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, platelets, and prothrombin were 50.59 ± 91.25 (μmol/L), 33.68 ± 7.5 (g/L), and 60.66 ± 106.95(U/L), 63.37 ± 86.19(U/L), 106.65 ± 83.22(×10(9)/L), 68.82% ± 25.33%, respectively. CTP class A/B/C had 220/150/111 cases. The average values of CTP, MELD, APRI and FIB-4 were 7.61 ± 2.58, 10.98 ± 5.79, 2.34 ± 3.56, 6.91 ± 8.04, respectively. The overall incidence of complications in HBV-related cirrhotic patients with low viral load, HBV DNA negative, HBV DNA positive, HBsAg negative, and HBsAg positive were 80.0%, 82.7%, 73.6%, 85.3%, and 78.8%, respectively. Among them, 283 cases (58.84%), 197 cases (55.77%), 86 cases (61.43%), 52 cases (54.74%) and 231 cases (59.84%) were of hypersplenism, and 267 cases (55.51%), 197 cases (55.77%), 70 cases (50.00%), 56 cases (58.95%), and 211 cases (54.66%) were of esophagogastric varices. There were 59 cases (12.27%), 48 cases (14.08%), 11 cases (7.86%), 12 cases (12.63%), and 47 cases (12.18%) of rupture of esophageal and gastric varices, respectively. 202 cases (42.00%), 147 cases (43.11%), 55 cases (39.29%), 42 cases (44.21%), and 160 cases (41.45%) were of ascites, respectively. 17 cases (3.53%), 12 cases (3.52%), 5 cases (3.5%), 2 cases (2.11%), 15 (3.89%) cases were of hepatic encephalopathy, respectively. There were 6 cases (1.25%), 3 cases (0.88%), 3 cases (2.14%), 0 cases (0%), 6 cases (1.55%) of liver cancer. 29 cases (6.03%), 21 cases (6.16%), 8 cases (5.71%), 9 cases (9.47%) and 20 cases (5.18%) were of portal vein thrombosis. Compared with the overall incidence of complications, 341 HBV DNA-negative patients and 95 HBsAg-negative patients still had higher incidence of complications. The patients were grouped by age, and in < 40 years old, 40-50 years old, and > 50 years old, the overall complications were 80.8% in 42 cases, 76.8% in 116 cases and 81.7% in 227 cases, and the difference was not statistically significant. Conclusion: HBV infection patients with low viral load, and those whose HBsAg has disappeared, are still at risk of developing liver cirrhosis and even serious complications, and whether such population need antiviral therapy and benefit from it deserves further research.

Estimating the risk of aflatoxin-induced liver cancer in Tanzania based on biomarker data.

Evidence about the magnitude of the aflatoxin menace can help policy makers appreciate the importance of the problem and strengthen policies to support aflatoxin mitigation measures. In this study, we estimated aflatoxin-induced liver cancer risk in 2016 for Tanzania and used the information to estimate the health burden due to the aflatoxin exposure in the country. The burden of aflatoxin-induced liver cancer was assessed based on available aflatoxin biomarker data from a previous epidemiology study, hepatitis B virus infection prevalence and population size of Tanzania in 2016. The health burden due to aflatoxin-induced liver cancer was estimated using disability adjusted life years (DALYs). The aflatoxin exposures ranged from 15.0–10,926.0 ng/kg bw/day (median, 105.5 ng/kg bw/day). We estimated that in 2016 there were about 1,480 (2.95 per 100,000 persons) new cases of aflatoxin-induced liver cancer in Tanzania and assumed all of them would die within a year. These morbidity and mortality rates led to a total loss of about 56,247.63 DALYs. These results show, quantitatively, the cases of liver cancer and related deaths that could be avoided, and the healthy life years that could be saved, annually, by strengthening measures to control aflatoxin contamination in Tanzania.

Circular RNA circ_0021093 regulates miR-432/Annexin A2 pathway to promote hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a major histological subtype of liver cancer cases. Previous studies showed that circular RNA (circRNA) circ_0021093 was upregulated in HCC, but the regulatory mechanism of circ_0021093 is still rare. The expression levels of circ_0021093, miR-432 and Annexin A2 (ANXA2) were analyzed by real-time quantitative PCR. The relationship between the overall survival time of HCC patients and circ_0021093 level was analyzed with Kaplan-Meier analysis. Cell proliferation, migration and invasion were examined with cell counting kit-8 and transwell assays. Western blot was used to assess the protein expression of epithelial-mesenchymal transition markers and ANXA2. In addition, loss- or gain-of-function experiments and dual-luciferase reporter assay were performed to probe the relationship between miR-432 and circ_0021093 or ANXA2. The influences of circ_0021093 silencing in vivo were measured by using xenograft models. Circ_0021093 was highly expressed in HCC tissues and cells, and its level was associated with poor prognosis of HCC patients. Functional experiments showed that knockdown of circ_0021093 repressed proliferation, migration and invasion in vitro and tumor growth in vivo by regulating miR-432, while upregulation of circ_0021093 reversed these results. Moreover, miR-432 negatively regulated ANXA2 expression in HCC, and introduction of ANXA2 could abolish overexpression of miR-432-induced effects on HCC cells. Collectively, circ_0021093 boosted HCC progression via regulating proliferation, migration and invasion of HCC cells by acting as competing endogenous RNA to sponge miR-432.

The Threat of Multiple Liver Carcinogens in the Population of Laos: A Review

Laos is a landlocked country in South East Asia, ranking fifth for primary liver cancer incidence worldwide. Risk factors that might explain this worrying situation are poorly known. We conducted a review of the literature concerning the etiologies of terminal liver diseases in Laos. A double infectious burden with hepatitis B and C viruses and the liver fluke Opisthorchis viverrini seems to be the main cause of the high liver cancer incidence. Moreover, it was also suggested that mutagenic substances frequently found in tobacco, alcoholic beverages, fermented fish, and mold-contaminated cereals or nuts, which are all substances heavily consumed by Lao people, lead to the accumulation of DNA mutations in the liver cell genome causing tumor processes. However, the respective proportions of liver cancer cases attributable to each category of infections and substances consumed, as well as the histological nature of the neoplasia are still not precisely documented in Laos. The international medical and scientific communities as well as public health stakeholders should urgently consider the alarming situation of liver health in Laos to stimulate both research and subsequent implementation of prevention policies.

Dietary fat intake and liver cancer incidence: A population-based cohort study in Chinese men.

To date, limited studies have focused on the association between dietary fat and liver cancer risk, especially in China. Our study aims to evaluate the association between dietary fat intake and liver cancer incidence risk in men. Dietary fat intake was obtained through a validated food frequency questionnaire in a Chinese prospective cohort. The Cox regression model was utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After exclusion, 59 998 recruitments were finally analyzed with a total follow-up time of 714 339 person-years, 431 incident liver cancer cases were newly identified among them. The adjusted HRs (95% CIs) for the highest vs lowest quartile of total fat, saturated fat, monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) were 1.33 (1.01-1.75), 1.50 (1.13-1.97), 1.26 (0.96-1.65), and 1.41 (1.07-1.86), and the corresponding P-trend values were .008, .005, .034, and .005, respectively. In the secondary analysis among participants tested for hepatitis B virus, we found that higher intakes of saturated fat and PUFA were also associated with increased liver cancer risks. Besides, high risks of per standard deviation alterations of the total fat, saturated fat and MUFA were detected in liver cancer, and these results were similar to those concluded from the full-cohort analysis. In conclusion, dietary intakes of total fat, saturated fat, PUFA, and probably MUFA might increase liver cancer risks. Our study provides suggestive advice to public administration on dietary suggestions, and related measures taken from managing dietary fat intake might reduce liver cancer incidence.

Association of periodontitis and tooth loss with liver cancer: A systematic review.

A number of epidemiological studies have suggested a positive association between periodontal diseases and oro-digestive cancers, including liver cancer. The purpose of the present systematic review was to analyze the current evidence regarding the potential association between periodontitis and/or tooth loss and the risk of liver cancer. A comprehensive search of PubMed, Scopus and Web of Science databases was conducted in August 2019. The inclusion criteria comprised all observational studies that assessed the relationship between periodontitis or tooth loss and liver cancer. Case reports, animal studies, experimental studies, and reviews were excluded. Due to great heterogeneity among the included studies, no meta-analysis was conducted. Six studies (five prospective cohorts and one case-control) comprising 619,834 subjects (including 916 liver cancer cases) were included. The studies were conducted in the United States, Europe, and Asia. Three large-scale cohort studies reported a positive association between periodontitis or tooth loss and the risk of liver cancer. One case-control study found some association between liver cancer and loss of 12-23 teeth, but such association was not replicated in patients with greater number of tooth loss. Contrarily, two studies failed to report any association between periodontitis and/or tooth loss and the risk of liver cancer. The available evidence suggests a possible link between tooth loss/periodontitis and the risk of liver cancer. However, the evidence is not conclusive enough, a fact that drives to conduct more, well-designed, prospective cohort studies to further explore the potential association between periodontitis and the risk of liver cancer.

A TNFR2-hnRNPK Axis Promotes Primary Liver Cancer Development via Activation of YAP Signaling in Hepatic Progenitor Cells.

Most primary liver cancer (PLC) cases progress mainly due to underlying chronic liver inflammation, yet the underlying mechanisms of inflammation-mediated PLC remain unclear. Here we uncover a TNF receptor II (TNFR2)-hnRNPK-YAP signaling axis in hepatic progenitor cells (HPC) essential for PLC development. TNFR2, but not TNF receptor I (TNFR1), was required for TNFα-induced activation of YAP during malignant transformation of HPCs and liver tumorigenesis. Mechanistically, heterogeneous nuclear ribonuclear protein K (hnRNPK) acted downstream of TNFα-TNFR2 signaling to directly interact with and stabilize YAP on target gene promoters genome-wide, therefore coregulating the expression of YAP target genes. Single-cell RNA sequencing confirmed the association of TNFR2-hnRNPK with YAP expression and the pathologic importance of HPC. Accordingly, expressions of TNFR2, hnRNPK, and YAP were all upregulated in PLC tissues and were strongly associated with poor prognosis of PLC including patient survival. Collectively, this study clarifies the differential roles of TNFRs in HPC-mediated tumorigenesis, uncovering a TNFR2-hnRNPK-centered mechanistic link between the TNFα-mediated inflammatory milieu and YAP activation in HPCs during PLC development. SIGNIFICANCE: This work defines how hnRNPK links TNFα signaling and Hippo pathway transcription coactivator YAP in hepatic progenitor cells during primary liver tumorigenesis.

A long-term follow-up analysis of associations between tooth loss and multiple cancers in the Linxian General Population cohort

Poor oral health, indicated by tooth loss and periodontal disease, may be an important risk factor for various cancers. Prior studies have found inconsistent associations between tooth loss and several cancer types. Here, we examined the relationship between tooth loss and incident cases of multiple cancers in the Linxian General Population Nutrition Intervention Trial cohort. In this large prospective cohort of over 29,000 participants, there were 3101, 1701, 626, 327, 348, and 179 incident esophageal, gastric cardia, gastric noncardia, liver, lung, and colorectal cancer cases, respectively, over 30 years of follow-up. Adjusted Cox proportional hazards regression models with time-varying covariates were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between tooth loss and cancer outcomes during three time intervals: ≤ 5 years (early), > 5 and ≤ 10 years (mid), > 10 years (late). Tooth loss was assessed as quartiles of the number of lost teeth in excess of the loess-smoothed, age-specific median number of teeth lost. For esophageal cancer, the increase in risk associated with the highest quartile of tooth loss was 25% (95% CI: 1.02, 1.52) in the mid time interval, but the association weakened thereafter. For gastric cardia cancer, the increase in risk associated with the highest quartile of tooth loss was 1.34 in both the early (95% CI: 1.06, 1.71) and mid time intervals (95% CI: 1.02, 1.76), with no significant associations in the late interval. Gastric noncardia cancer was only associated with the second quartile of tooth loss in the late time interval (HR = 1.54; 95% CI: 1.16, 2.04). All associations between tooth loss and liver, lung, and colorectal cancers were null. Tooth loss was associated with risk of esophageal and gastric cancers in this updated analysis from the cohort.

Trends in Incidence and Mortality of Primary Liver Cancer in Lithuania 1998-2015.

Background: Recently, reports have suggested that rates of liver cancer have increased during the last decades in developed countries; increasing hepatocellular carcinoma and cholangiocarcinoma rates were reported. The aim of this study was to examine time trends in incidence and mortality rates of liver cancer for the period of 1998–2015 in Lithuania by sex, age, and histology. Methods: We examined the incidence of liver cancer from 1998 to 2015 using data from the Lithuanian Cancer Registry. Age-standardized incidence rates were calculated by sex, age, and histology. Trends were analyzed using the Joinpoint Regression Program to estimate the annual percent change. Results: A total of 3086 primary liver cancer cases were diagnosed, and 2923 patients died from liver cancer. The total number of liver cancer cases changed from 132 in 1998 to 239 in 2015. Liver cancer incidence rates changed during the study period from 5.02/100,000 in 1998 to 10.54/100,000 in 2015 in men and from 2.43/100,000 in 1998 to 6.25/100,000 in 2015 in women. Annual percentage changes (APCs) in the age-standardized rates over this period were 4.5% for incidence and 3.6% for mortality. Hepatocellular cancer incidence rates were stable from 1998 to 2005 (APC −5.9, p = 0.1) and later increased by 6.7% per year (p < 0.001). Intrahepatic ductal carcinoma incidence increased by 8.9% per year throughout the study period. The rise in incidence was observed in all age groups; however, in age groups < 50 and between 70 and 79 years, observed changes were not statistically significant. For mortality, the significant point of trend change was detected in 2001, where after stable mortality, rates started to increase by 2.4% per year. Conclusions: Primary liver cancer incidence and mortality increased in both sexes in Lithuania. The rise om incidence was observed in both sexes and main histology groups. The increasing incidence trend may be related to the prevalence of main risk factors (alcohol consumption, hepatitis B and C infections. and diabetes).

Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that is responsible for a growing fraction of cirrhosis and liver cancer cases worldwide. Changes in the gut microbiome have been implicated in NASH pathogenesis, but the lack of suitable murine models has been a barrier to progress. We have therefore characterized the microbiome in a well-validated murine NASH model to establish its value in modeling human disease. The composition of intestinal microbiota was monitored in mice on a 12- or 24-week NASH protocol consisting of high fat, high sugar Western Diet (WD) plus once weekly i.p injection of low-dose CCl4. Additional mice were subjected to WD-only or CCl4-only conditions to assess the independent effect of these variables on the microbiome. There was substantial remodeling of the intestinal microbiome in NASH mice, characterized by declines in both species diversity and bacterial abundance. Based on changes to beta diversity, microbiota from NASH mice clustered separately from controls in principal coordinate analyses. A comparison between WD-only and CCl4-only controls with the NASH model identified WD as the primary driver of early changes to the microbiome, resulting in loss of diversity within the 1st week. A NASH signature emerged progressively at weeks 6 and 12, including, most notably, a reproducible bloom of the Firmicute order Erysipelotrichales. We have established a valuable model to study the role of gut microbes in NASH, enabling us to identify a new NASH gut microbiome signature.

Clinical Study on Efficacy and Treg Cell Changes in Peripheral Blood of Massive Liver Cancer Treated with Gelfoam Microparticles (GSMs) TACE Combined with Surgical Resection

Objective: Observe the clinical efficacy and safety of using absorbable GSMs embolization agent to embolize massive liver cancer, and to observe the changes in the changes of Treg cells in peripheral blood. Methods: During 2018-2019 GSMs-TACE combined with conventional resection of liver cancer treatment of 7 cases of massive liver cancer. GSMs particle of 150-350, mixed with 50 mg doxorubicin, 30 days later underwent conventional surgery. Flow cytometry is used to test the content of Treg cells in peripheral blood before , 10 days after GSMs-TACE and before conventional surgical. Results: The average resection month after GSMs-TACE (14-48 days) was one month in 7 patients, and the volume of tumor necrosis after GSMs-TACE was more than 50%, among which 5 cases were more than 90%. After embolization, the tumor volume decreased by 20.2%, and the right hemihepatic resection was performed in 6 cases and the middle hepatic resection was performed in 1 case. There were no sever complications. The survival rates at 6 months and 12 months after resection were 100% (7/7) and 100% (5/5). The Treg cells in peripheral blood was 11.72 ±0.91%, 8.62 ±1.43%, and 10.34 ±1.12%, before, 10 days and 30 days after GSMs-TACE. Conclusions: GSMs-TACE combined with surgical resection in the treatment of massive liver cancer has a good safety and clinical efficacy, GSMs-TACE has a positive regulatory effect on the body´s immune function.GSMs-TACE 15 to 30 days after surgery is the best time for surgical resection.

Mechano-Signaling Aspects of Hepatocellular Carcinoma.

HCC is one of the leading causes of cancer related death worldwide and comprises about 90% of the cases of primary liver cancer. It is generally accompanied by chronic liver fibrosis characterised by deposition of collagen fibres, which, in turn, causes enhanced stiffness of the liver tissue. Changes of tissue stiffness give rise to alterations of signalling pathways that are associated to mechanical properties of the cells and the extracellular matrix, and that can be subsumed as “mechano-signaling pathways”, like, e.g., the YAP/TAZ pathway, or the SRF pathway. Stiffness of the liver tissue modulates mechanical regulation of many genes involved in HCC progression. However, mechano-signaling is still rather underrepresented in our concepts of cancer in comparison to “classical” biochemical signalling pathways. This review aims to give an overview of various stiffness induced mechano-biological aspects of HCC.

POSSIBLE TREATMENT APPROACHES FOR HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide. HCC patients are diagnosed in advanced stages, due to its poor prognosis. Currently, immunotherapy and chemotherapy are the best treatment options in &gt;90 cases of liver cancer. Therefore, new treatment options are urgently needed for the cure of liver cancer. Use of nanotechnology and/or some natural compounds may become better options for liver cancer patients with minimum side effects and lower toxicity. This review focuses on present available treatment approaches for the management of liver cancer in patients.

Dietary fat intake and liver cancer risk: A prospective cohort study in Chinese women.

Objective:This study aimed to determine whether dietary fat intake increased liver cancer risk in Chinese women from a prospective population-based cohort.Methods:A total of 72,704 Chinese women were followed up from the time of baseline recruitment (1996–2000) to the end of 2016. Dietary fat intake was calculated using a validated food frequency questionnaire. The Cox regression model was used to assess the hazard ratio (HR) and 95% confidence intervals (CI) for dietary fat intake and liver cancer risk.Results:We identified 252 incident liver cancer cases out of 1,267,845 person-years during the overall follow-up time. Null associations, neither in quartiles nor per standard deviation (SD) increment, were detected between liver cancer risk and dietary total fat, fat subtypes and subtype ratios, and food sources. The HR (95% CI) of the 1-SD increment was 1.03 (0.90–1.17) for total fat, 1.06 (0.93–1.20) for saturated fat, 1.06 (0.93–1.21) for monounsaturated fat, and 1.00 (0.89–1.13) for polyunsaturated fat. Similar null associations were observed in stratification analyses according to body mass index and menopausal status.Conclusions:In our prospective cohort study, no significant association was observed in Chinese women between dietary fat and liver cancer risk, and in stratification and sensitivity analyses.

CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway.

Purpose: The incidence of hepatocellular carcinoma (HCC) is extremely high, and China accounts for approximately 50% of global liver cancer cases. Previous studies reported that CDC20 is involved in the occurrence and progression of a variety of malignant tumors. So, whether CDC20 will affect the development of HCC, we have conducted in-depth research on this.Methods: We selected Hep3B and HepG2 for cell culture, and performed siRNA transfection, lentiviral infection, western blot, MTS determination, cell cycle determination, apoptosis test, immunodeficiency test, clone survival test and subcutaneous parthenogenesis in nude mice.Results: Knockdown of CDC20 greatly enhanced the radiation efficacy on the growth retardation in HepG2, and protein level of CDC20 was decreased for the activation of P53 by radiation. Downregulation of CDC20 combined with radiation can inhibit proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of HCC cells was gradually reduced with radiation dose increased in P53 mutated Hep3B cells. After knocking down CDC20 in HCC, Bcl-2 was down-regulated and Bax expression increased. Down-regulation of CDC20 can inhibit further invasion by promoting the radiosensitivity of HCC.Conclusion: In this study, we found that that CDC20 was highly expressed in HCC and participated in radio resistance of HCC cells with P53 mutation Bcl-2/Bax via signaling pathway. This study is the first to present evidence that CDC20 may play a role in improving the efficacy of radiotherapy in HCC.

Chemical Risk Factors of Primary Liver Cancer: An Update.

Primary liver cancer has the sixth highest incidence and fourth highest cancer mortality worldwide. Hepatitis B is the leading cause of liver cancer, though its incidence is decreasing with vaccination. Alcohol is the leading cause of liver transplant, cirrhosis, and cancer in the developed world, and is projected to surpass hepatitis B as the leading hepatic cancer etiology worldwide. Tobacco smoking has shown a positive association with liver cancer in a majority of studies, though not all. Aflatoxin, a mycotoxin produced by Aspergillus, is estimated to account for 3–20% of global liver cancer cases, 40% of which occur in sub-Saharan Africa. These statistics are confounded by the prevalence of hepatitis B, which may have a synergistic effect on hepatic carcinogenesis. Aflatoxin is ingested and likely inhaled from agricultural products, placing farmers, food processors, and textile workers in developing nations at risk. Vinyl-chloride is used in the production of PVC plastics and causes rare liver angiosarcoma, hepatocellular carcinoma, and other neoplasms. Arsenic and cadmium are naturally-occurring, hepatocarcinogenic metals with high occupational exposure in industries involving coal, metals, plastics, and batteries. Millions of laborers in waste-disposal and manufacturing are exposed to organic solvents and N-nitrosamines, which vary from carcinogenic (group 1) to possibly carcinogenic (group 2B) in their IARC designation. Insecticide DDT is possibly hepatocarcinogenic (group 2B), though continues to be used for malaria control in the developing world. While suggested by case reports, anabolic steroids and oral contraceptives have not been shown to increase liver cancer risk in large studies.

Toxicological Risk Associated with Consumption of Rice Sold in Uganda

Previous studies have reported the presence of aflatoxins (AFB1, AFB2, AFG1 and AFG2), heavy metals (As, Cd and Pb) and organochlorine pesticide residues (OCPs) in rice sold in Uganda. However, the potential health effects associated with consumption of rice have not been evaluated. The aim of this study was to evaluate the health risk of consuming rice sold in Uganda. A total of 45 packed and 30 open traded rice samples were randomly collected from retail outlets in the main rice trading areas of Uganda. Rice was analysed for AFB1, AFB2, AFG1 and AFG2, As, Cd, Pb and OCPs using AOAC standard methods. Dietary exposure of the consumers to contaminants was assessed using the estimated daily intake (EDI). The Hazard index (HI) and the incremental lifetime cancer risk (ILCR) were determined to define the non-carcinogenic and carcinogenic risk from contaminants, respectively. The potency of liver cancer cases in Uganda was 1.02E-5 and 1.05E-5 adults/year/100,000, and 6.50E-4 and 6.72E-5 infants /year/100,000 for open traded and packed rice, respectively. The values obtained for the ILCR for Arsenic detected in rice were 1.14E-2 and 7.28E-2 for adults and infants, respectively. The ILCR of all detected OCPs in adults and infants were higher than 1.0E-4, in both open traded and packed rice. This study established a potential carcinogenic risk from consumption of rice sold in Uganda in both infants and adults at the current level of contamination and consumption rate. Establishment of a monitoring system along the entire rice value chain; enforced by a national regulatory body can provide timely feedback on the levels of contamination and the progress in reducing the contamination burden.

Review on the Aflatoxins’ Contamination of Foods and Public Health Effects among Nigerian Population

Aflatoxin in foods and feeds need adequate monitoring on account of their severe toxicity and carcinogenicity to both humans and animals. This review was aimed at examining the public health risks attributed to chronic exposure of aflatoxins in foods within Nigeria. Both the reported cases of aflatoxins in foods and biomarkers in Nigeria signified increase in dietary exposure. Aflatoxins contamination levels ranges from 1.3 ng/g to 51,192ng/g in foods with an estimated dietary exposure of 0.00017 ng/kgbw/day to 9, 880.56 ng/kgbw/day. The percentage incidence of primary liver cancer cases (PLCC) attributable to the dietary aflatoxin exposure for every 100,000 Nigerians per year ranges from 0.0024 to 708.13% between 1998 to 2008 which increases to 0.0046 to 45,602% between 2009 to 2018. The percentage incidence of PLCC signified by urine aflatoxin M1 (AFM1) levels in adults was around 0.23 – 1.29% per 100,000 population per year. In children, the estimated PLCC and stunting due to aflatoxin exposure via breast milk were 0.0019 to 237.71 cancers per 100,000 populations per year and mild to severe stunting with height-for-age z-score (HAZ) value above -3 HAZ reductions. Hence, there is need for additional monitoring of the marketed foods and implementing more stringent control and prevention strategies that reduce dietary exposure levels in Nigeria.