ABSTRACT
Aim: This meta-analysis aimed to evaluate the association of HIF-1α expression with clinicopathological features and overall survival (OS) of patients with digestive system malignancies. Background: Numerous studies have demonstrated that hypoxia-inducible factor-1α (HIF-1α) is abnormally expressed in various solid tumors. However, the clinicopathological features and prognostic value of HIF-1α expression in patients with digestive system malignancies remain controversial. Methods: A literature search in PubMed, Web of Science, and Scopus databases was performed to identify all relevant studies published in English until 15 October 2020. The pooled effect was calculated to evaluate the association between HIF-1α expression and clinicopathological features and overall survival in cancer patients. Pooled odds ratios (ORs) or hazard ratios (HRs) with a 95% confidence interval (CI) were calculated using fixed- or random-effects model based on between-study heterogeneity. Results: A total of 44 eligible studies with 5,964 patients were included. The pooled results indicated a positive association of HIF-1α overexpression with poor overall survival (OS) (HR=1.990, 95% CI: 1.615-2.453, p<0.001) and disease-free survival (DFS) (HR=1.90, 95% CI: 1.084-3.329, p=0.043). Meta-analysis results showed that HIF-1α level expression was significantly associated with positive lymph node metastasis (OR=1.869, 95% CI: 1.488-2.248, p<0.001), distance metastasis (OR=2.604, 95% CI: 1.500-4.519, p<0.001), tumor stage (OR=1.801, 95% CI: 1.437-2.257, p<0.001) and tumor size (OR=1.392. 95% CI: 1.068-1.815, p=0.014). Conclusion: This meta-data suggest that HIF-1α expression might serve as an independent prognostic marker and a promising therapeutic target in patients with digestive system malignancies.
ABSTRACT
Myocardial dysfunction, a major component of sepsis-induced multiorgan failure, contributes to the production of massive amounts of pro-inflammatory cytokines. Nitric oxide (NO) is known to act as a precursor of free radicals in inflammation. This research was conducted to assess the effect of aminoguanidine (AG) on lipopolysaccharide (LPS)-induced heart injury. 50 male rats were categorized into five groups (n = 10): (1) control, (2) LPS, (3) LPS-AG50, (4) LPS-AG100, and (5) LPS-AG150. LPS (1 mg/kg) was injected for 5 weeks, and AG (50, 100 and 150 mg/kg) was injected 30 min prior to LPS administration. All drugs were injected intraperitoneally. LPS-evolved cardiovascular toxicity was indicated by the augmentation in the level of nitric oxide (NO) metabolites, interleukin (IL)-6 and malondialdehyde (MDA), as well as reduced contents of total thiol groups, catalase (CAT), and superoxide dismutase (SOD) activity in serum, heart, and aortic tissues. In AG treated groups, noxious effects of LPS were not observed in the serum and harvested tissues. AG reduced MDA, NO metabolites, and IL- 6 and increased total thiol, CAT, and SOD activity in the heart, aorta and serum. As an inhibitor of inducible NO synthase (iNOS), AG further reduced LPS-induced oxidative stress and inflammation, hence considered as cardioprotective.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cardiovascular Diseases/prevention & control , Cardiovascular System/drug effects , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Inflammation/prevention & control , Lipopolysaccharides , Nitric Oxide Synthase Type II/antagonists & inhibitors , Animals , Antioxidants/pharmacology , Cardiotoxicity , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/metabolism , Cardiovascular System/metabolism , Disease Models, Animal , Inflammation/chemically induced , Inflammation/metabolism , Inflammation Mediators/metabolism , Male , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress/drug effects , Rats, WistarABSTRACT
BACKGROUND: Breast cancer is the leading cause of cancer worldwide. The high expenses associated with chemotherapy as well as its side effects make the management of breast cancer a daunting challenge. The most common overexpressed gene in breast cancer is cyclinD1, which induces cell proliferation. Recent investigations into cancer treatment have revealed that curcumin demonstrates potential anti-cancer properties through different pathways. However, the oral bioavailability of curcumin is negligible due to its high hydrophobic structure. Nanotechnology has been employed to overcome this barrier. Nano-formulated curcumin (SinaCurcumin®) has been shown to provide a significantly higher bioavailability for oral consumption. However, the efficacy of this nano-formulated drug in breast cancer has not yet been determined. In relation to the breast cancer cell line, the present study compared nano-curcumin's anti-cancer properties with those of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF). METHODS: After treating MCF7 with nano-curcumin and CAF, the present work assessed cell viability via an MTT assay. The effects of these drugs on cyclinD1 expression were measured by real-time PCR. SPSS 16.0 was used to perform ANOVA and multiple range tests. RESULTS: Nano-curcumin and the CAF regimen both lowered the viability of MCF7. Nano-curcumin decreased cell proliferation by 83.6%, which was more than that achieved by cyclophosphamide (63.31%), adriamycin (70.75%), and 5-fluorouracil (75.04%). In addition, curcumin was able to significantly reduce the expression of cyclinD1, whereas CAF did not alter cyclinD1 expression. CONCLUSION: Nano-curcumin has a relatively high cytotoxic effect on MCF7 breast cancer cells, suppressing the expression of cyclinD1, a critical gene in the development and metastasis of breast cancer. The current study demonstrated that nano-curcumin can be an effective drug in the CAF regimen for the treatment of breast cancer. However, further in vivo research is needed for determining its efficacy and safety in clinical applications.
