This exploratory study was carried out to determine the expression levels of hepatocyte growth factor (HGF), insulin-like growth factor 1, thyroid-stimulating hormone (TSH), and leptin in serum and tumor samples from patients with uveal melanoma and to investigate the potential association of these expression levels with disease progression and patient survival.
Leptin is a nutritional cytokine encoded by the obesity gene whose concentration in the tumor microenvironment is closely related to the occurrence and progression of cancer.
Vasculogenic mimicry (VM) was an important tumor blood supply to complement the endothelial cell-dependent angiogenesis, while leptin and receptor (ObR) involved in angiogenesis in glioblastoma has been reported on previous study, but the relationship between ObR expression and VM formation in human glioblastoma tissues, as well as their prognostic significance still remains unclear.
Furthermore, pathway analysis of these transcripts demonstrated their association with active inflammation and colon cancer signaling, with leptin and Wnt as the top two transcripts elevated in mouse HFD colon shared with tumors.
Whether or not leptin and leptin receptor expression play a role in the development and/or progression of lipoblastoma and other tumors is not clear to date.Copyrightz1999S.KargerAG, Basel
Collectively, these studies demonstrate that although MDSC protect against some metabolic dysfunction associated with HFD they enhance tumor growth in HFD mice and that leptin is a key regulator linking HFD, chronic inflammation, immune suppression, and tumor progression.
A growing body of evidence suggests an important role of leptin in our major obesity-related health issues such as insulin resistance, hypertension, and neoplasia.
The purpose of this study was to compare the effects of leptin-stimulated colon epithelial cells differing in adenomatous polyposis coli (Apc) genotype (gatekeeper tumor suppressor gene for colon cancer) on angiogenesis.
The results demonstrated a statistically significant increase in the level of leptin in plasma samples from the tumor microenvironment of obese patients with estrogen receptor positive (ER+) breast cancer, compared with peripheral plasma samples.
The profiles were tested on 1) snap-frozen tumors from 133 patients with completely resected stage 1B-2 NSCLC randomized to adjuvant cisplatin and vinorelbine (ACV, n = 71) or no adjuvant treatment (OBS, n = 62) and 2) formalin-fixed paraffin-embedded (FFPE) tumors from 95 patients with completely resected stage 1A-3B NSCLC receiving adjuvant cisplatin and vinorelbine.
Therefore, we hypothesize that over-expression of LEPR, rather than that of LEP has a fundamental role in breast carcinogenesis in particular, and probably for LEP-LEPR associated tumors in general.
Although all the mechanism(s) by which leptin contributes to tumor development are unknown, it appears leptin stimulates an increase in cell numbers, and the expression of VEGF/VEGF-R2.
Significant WLI vs. AC differences were seen in baseline-to-follow-up changes in weight (-3.62 vs. -0.52 kg), %body fat (-1.3 vs. 0%), moderate-to-vigorous physical activity (+224 vs. +115 min/week), caloric density (-0.3 vs. 0 kcal/g), serum leptin (-12.3 vs. -4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle-apoptosis related genes (CC-ARG; all p-values <0.05).
Engineering oncolytic viruses to express leptin in tumor cells induced complete responses in tumor-bearing mice and supported memory development in the tumor infiltrate.
Collectively, the studies suggest that breastfeeding might be negatively associated with promoter methylation of LEP (which encodes an anorexigenic hormone), CDKN2A (involved in tumour suppression) and Slc2a4 genes (which encodes an insulin-related glucose transporter) and positively with promoter methylation of the Nyp (which encodes an orexigenic neuropeptide) gene, as well as influence global methylation patterns and modulate epigenetic effects of some genetic variants.
Expression of either protein was associated with greater neoplasm size (leptin expression, 32.0 +/- 10.7 vs 20.5 +/- 8.4 mm; P = .001; leptin receptor expression, 27.9 +/- 11.5 vs 21.4 +/- 9.0 mm; P = .032).
Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production.
The overexpression of leptin was shown to significantly promote tumor growth and lymph node metastasis in a subcutaneous model and an orthotopic model of human pancreatic cancer, respectively.
Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007).