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Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been clearly established and the role of leptin in accelerating tumor growth is unclear. Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin. We injected 1 × 106 B16F10 melanoma cells subcutaneously into lean wild type (WT), obese melanocortin receptor 4 knockout (MC4R−/−), which have high leptin levels, obese leptin-deficient(ob −/−), pair fed lean ob−/−, and lean ob+/− mice. Mean body weights were 29.7 ± 0.3 g (WT), 46.3 ± 1.9 g (MC4R−/−), 63.7 ± 0.9 g (ob−/−), 30.5 ± 1.0 g (pair fed ob−/−) and 31.6 ± 1.7 g (ob+/−). Tumors were much larger in the obese leptin deficientob−/− (5.1 ± 0.9 g) and obese MC4R−/− (5.1 ± 0.7 g) than in lean WT (1.9 ± 0.3 g) and ob+/− (2.8 ± 0.7 g) mice. prevention of obesity by pair feeding ob−/− mice dramatically reduced tumor weight (0.95 ± 0.2 g) to a level that was significantly lower than in WT mice of the same weight. Tumor VEGF levels were the highest in the obese mouse tumors (p < 0.05), regardless of the host leptin levels. Except for the lean ob+/−, MC4R−/− and ob−/− melanomas had the highest VEGF receptor 1 and VEGF receptor 2 protein expression (p < 0.01 and p < 0.05), respectively. These results indicate that obesity markedly increases melanoma tumor growth rate by mechanisms that may involve upregulation of VEGF pathways. although tumor growth does not require host leptin, melanoma tumor growth may be accelerated by leptin.

More sensitive biomarker is urgently needed to reduce the mortality caused by the worldwide prevalent liver cancer. This study aims to assess whether quantitative measurement of heat shock protein 90alpha (Hsp90α) in plasma can improve the diagnosis accuracy and monitor treatment response of liver cancer patients. We analyzed the data from an official (registered at ClinicalTrial.gov: NCT02324127), large-scale (1647 enrollments), and multicenter (three independent hospitals) clinical trial, which quantitatively measured plasma Hsp90α by ELISA for patients with liver cancer, patients with at-risk liver diseases (including hepatitis, liver cirrhosis, focal nodular hyperplasia), and healthy individuals. Diagnostic performance of plasma Hsp90α was evaluated by the calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). ROC curve showed plasma Hsp90α can discriminating liver cancer with a sensitivity of 92.7% and specificity of 91.3% from non-liver cancer control. Similar results were noted in detecting early-stage liver cancer (sensitivity 91.4%, specificity 91.3%). In a parallel study compared with AFP20, plasma Hsp90α exhibited a significantly higher diagnostic performance (sensitivity 93.3% vs 61.1%) in discriminating hepatocellular carcinoma (HCC) from the control. Furthermore, plasma Hsp90α measurement maintained distinctly excellent diagnostic accuracy in distinguishing AFP-negative HCC patients (sensitivity 93.9%, specificity 91.3%) and AFP-limited liver cancer (sensitivity 96.6%, specificity 90.3%). In the efficacy monitoring study, levels of plasma Hsp90α were dramatically decreased after surgery (P = 0.005), and correlated significantly with tumor size during interventional therapy (P ≤ 0.05). These findings highlight that plasma Hsp90α as a biomarker for the diagnosis of liver cancer, and can be used to evaluate the therapeutic efficacy of liver cancer patients underwent surgery, or interventional therapy.

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Patients developing HRS type 1 in the absence of high MELD score and low serum sodium would benefit from LT.