Anti-Cancer Effects of Lycopene in Animal Models of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION: Globally, hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer and the third important cause of cancer-related death. As there are only two targeted drugs for the treatment of advanced HCC-that merely extend survival by a few months-the need for alternative treatments is inevitable. Lycopene, a carotenoid that is known to be most abundant in red tomatoes and tomato-based products, has been investigated for its anticancer activity in various types of cancers including HCC. This review was conducted to evaluate the effects of lycopene on HCC from animal models to pave the way for further clinical studies. METHODS: Electronic databases and search engines including PubMed, EMBASE, and Google Scholar were searched for original records addressing the anticancer effect of lycopene in animal models of HCC. Data were extracted using a format prepared in Microsoft Excel and exported to Stata 15.0 for analyses. A meta-analysis was performed using a random-effects model at a 95% confidence level for the outcome measures: tumor incidence, number, and growth (tumor volume and size). The presence of publication bias between studies was evaluated using Egger's test and funnel plot. The study protocol was registered in the PROSPERO database with reference number: CRD42019159312. RESULTS: The initial database search yields 286 articles, of which 15 studies met the inclusion criteria. The characteristics of the included studies were a bit diversified. The studies involved a total of 644 animals (312 treatment and 332 control groups) and mice shared the majority (488) followed by rats (117) and ferrets (39). The meta-analysis showed that lycopene significantly reduced the incidence [RR 0.8; 95% CI 0.69, 0.92 (p=0.00); I2 = 30.4%, p=0.16; n=11], number [SMD-1.83; 95% CI -3.10, -0.57 (p=0.01); I2 = 95.9%, p=0.00; n=9], and growth [SMD -2.13; 95% CI -4.20, -0.04 (p=0.04); I2 = 94.6%, p=0.00; n=4] of HCC. CONCLUSIONS: Administration of lycopene appears to inhibit the initiation and progression of cancer in animal models of HCC. However, more controlled and thorough preclinical studies are needed to further evaluate its anti-HCC effects and associated molecular mechanisms.

Aflatoxins as a risk factor for liver cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Liver cirrhosis is characterized by fibrosis and nodule formation in the liver, due to a chronic injury, and subsequent alteration of the normal architecture of the liver. Even though there is a huge effort to elucidate the possible etiologic factors of liver cirrhosis, a significant number of cases are cryptogenic, especially in Sub Saharan Africa, where there is a high burden of aflatoxin exposure. Aflatoxins are known to cause hepatocellular carcinoma, which share similar etiologic factors with liver cirrhosis. This study aimed to assess the association between aflatoxin exposure and the risk of liver cirrhosis. METHODS: Relevant studies were identified through systematic searches conducted in Ovid MEDLINE, PubMed and Google Scholar. Also, by searching the references of retrieved articles. The abstracts and full text were screened for eligibility and the risk of bias was assessed for each study using Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. The extracted data from included studies using Microsoft Excel were exported to Stata software version 15.0 for analyses. The overall pooled estimation of outcomes was calculated using a random-effects model of DerSimonian-Laird method at a 95% confidence level. The heterogeneity of studies was determined using I2 statistics. The presence of publication bias between studies was evaluated using the Begg's and Egger's tests and funnel plot. The protocol of this systematic review and meta-analysis was registered in the Prospero database with reference number ID: CRD42019148481. RESULTS: A total of 5 studies published between the years 2005 and 2018 that met the pre-defined inclusion and exclusion criteria were included. The meta-analysis showed that a significant increase in the risk of liver cirrhosis is associated with aflatoxin exposure (unadjusted pooled odds ratio (OR) = 3.35, 95% CI: 2.74-4.10, p = 0.000; I2 = 88.3%, p = 0.000; adjusted OR = 2.5, 95% CI: 1.84-3.39, p = 0.000; I2 = 0%, p = 0.429). CONCLUSIONS: The present meta-analysis suggests that aflatoxin exposure is associated with a higher risk of liver cirrhosis.

Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies. It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus. OBJECTIVE: A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients. METHODS: Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018. In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting. Heterogeneity among the studies was evaluated using I 2 statistics. Publication bias was evaluated using the funnel plot asymmetry test. The Newcastle-Ottawa scale (NOS) was used to assess the study quality. RESULTS: A total of 8 cohort studies were included in the meta-analysis. Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR = 0.74, 95% CI: 0.55-0.99, I 2 = 97.89%, p < 0.00001; adjusted RR = 0.76, 95% CI: 0.54-1.07, I 2 = 98.12%, p < 0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting. CONCLUSIONS: According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes. This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.