leptin and Carcinoma--Endometrioid

The expression of NILCO molecules (Notch, IL-1, and leptin crosstalk outcome) and the association with obesity were investigated in types I and II endometrial cancer (EmCa). Additionally, the involvement of NILCO in leptin-induced invasiveness of EmCa cells was investigated.. The expression of NILCO mRNAs and proteins were analyzed in EmCa from African-American (. NILCO molecules were expressed higher in type II EmCa, regardless of ethnic background or obesity status of patients. NILCO proteins were mainly localized in the cellular membrane and cytoplasm of type II EmCa. Additionally, EmCa from obese African-American patients showed higher levels of NILCO molecules than EmCa from lean patients. Notably, leptin-induced EmCa cell invasion was abrogated by NILCO inhibitors.. Type II EmCa expressed higher NILCO molecules, which may suggest it is involved in the progression of the more aggressive EmCa phenotype. Obesity was associated with higher expression of NILCO molecules in EmCa. Leptin-induced cell invasion was dependent on NILCO. Hence, NILCO might be involved in tumor progression and could represent a new target/biomarker for type II EmCa.

Topics: Adenocarcinoma, Papillary; Aged; Antibodies; Asian People; Black People; Carcinoma, Endometrioid; Cell Line, Tumor; Cell Proliferation; Cystadenocarcinoma, Serous; Diamines; Disease Progression; Endometrial Neoplasms; Endometrium; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-1; Leptin; Middle Aged; Neoplasm Staging; Obesity; Protein Isoforms; Receptor, Notch1; Signal Transduction; Thiazoles

Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC.. In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry.. In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC.

Topics: Adult; Aged; AMP-Activated Protein Kinases; Apoptosis; Biomarkers, Tumor; Carcinoma, Endometrioid; Caspase 3; Cell Proliferation; Cytokines; Endometrial Neoplasms; Endometrium; Female; GPI-Linked Proteins; Humans; Hypoglycemic Agents; Immunohistochemistry; Insulin; Insulin-Like Growth Factor I; Ki-67 Antigen; Lectins; Leptin; Metformin; Middle Aged; Mitogen-Activated Protein Kinase 3; Phosphatidylinositol 3-Kinases; Phosphoproteins; Prospective Studies; Proto-Oncogene Proteins c-akt

Since leptin is believed to be a key player in carcinogenesis, a study has been designed to investigate the relationship between leptin levels and endometrial cancer.. A study including 30 patients with endometrial cancer and 30 healthy controls was carried out between November 2008 and July 2009 in Hacettepe University Hospital. All patients with endometrial cancer underwent a complete surgical staging procedure including lymphadenectomy. Preoperative leptin levels of endometrial cancer patients and healthy controls were compared. The relationships between leptin levels and stage, grade, histological type and lymph node status of endometrial cancer cases were evaluated.. The mean serum leptin levels were 16.9 ng/ml among endometrial cancer cases and 19.0 ng/ml among controls (p = 0.32). Of endometrial cancer cases, the mean leptin level was found to be 15.8 ng/ml for Stage I and 18.5 ng/ml for Stage II-IV disease (p = 0.34). The figure was 17.7 ng/ml for endometrioid and 13.2 ng/ml for non-endometrioid type of tumor (p = 0.24). The mean leptin levels of 16.3 ng/ml for grade 1 and 19.9 ng/ml for grade 2-3 tumors were observed (p = 0.07). The cases with positive and negative lymph nodes had leptin levels of 20.2 ng/ml and 16.1 ng/ml, respectively (p = 0.30).. Serum leptin levels in endometrial cancer patients were similar to healthy controls. Leptin did not show any significant correlation with stage, grade, histological type and node metastases in endometrial cancer.

Topics: Adult; Aged; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Leptin; Lymphatic Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging

Signal transducer and activator of transcription (STAT3) maintained invasiveness of endometrial cancer cell line. STAT3 mediated signaling for oncogenic growth stimulated by leptin (Ob) and hypoxia-inducible factor 1 (HIF-1). Therefore, we studied STAT3 in relation with HIF-1alpha, Ob, leptin receptor (ObR) and clinical and pathological variables with immunohistochemistry in 48 human endometrioid adenocarcinomas. Nuclear location was a proof of activity of STAT3 and HIF-1 and it was mainly characteristic for granular anti-STAT3 staining and rarely for diffuse HIF-1alpha expression. HIF-1alpha, Ob and ObR presented cytoplasmic granular immunoreactivities. Positive staining for STAT3, HIF-1, Ob and ObR occurred in 75%, 79%, 60% and 31% of cancers, respectively. Anti-STAT3 staining did not significantly vary with grading, staging and patients' age. STAT3 correlated with Ob (p=0.048, r=0.290) and with HIF-1alpha (p=0.004, r=0.407) in all cancers but it failed to associate with ObR at all. In opposition to the absence of significant relationship between STAT3 and Ob, STAT3 correlated with HIF-1alpha in well differentiated cancers (G1), poorly differentiated tumors (G3), pT1b neoplasms, compound group of pT1c, pT2a, pT2b tumors, and older patients over their sixties. STAT3 mediated signaling pathways that engage leptin and HIF-1alpha could only be partially reflected in correlations between STAT3 and Ob or STAT3 and HIF-1alpha in the examined neoplasms. Nevertheless, STAT3 failed to mark cancer advancement, so progressive significance of STAT3 is questionable in endometrioid adenocarcinomas.

Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Cell Nucleus; Endometrial Neoplasms; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Leptin; Middle Aged; Receptors, Leptin; STAT3 Transcription Factor