Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly ( P < 0.05 ); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly ( P < 0.05 ) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly ( P < 0.05 ); YAP and MMP9 mRNA expression increased significantly ( P < 0.05 ) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.

Disruptores endocrinos y su camino hacia el desequilibrio metabólico

El presente artículo de revisión tiene como objetivo presentar, de forma resumida, la evidencia que existe sobre las repercusiones metabólicas a nivel de obesidad y diabetes, que se genera como consecuencia de la exposición a sustancias químicas exógenas, denominadas disruptores endocrinos (DE), a las cuales nos exponemos de forma cotidiana y que afectan nuestra salud y la de nuestra descendencia. Adicionalmente, con la presente revisión hacemos un llamado no solo a la comunidad médica, sino a los sectores involucrados en la producción, distribución y reglamentación del uso de estas sustancias, pues cada vez hay más evidencia de los efectos nocivos que pueden generar y debemos evitar su uso. Los datos se obtuvieron de estudios clínicos aleatorizados y de una revisión en idioma español e inglés de los últimos 15 años, que incluyó los términos DeCS: disruptores endocrinos, con alternativa DeCS: sustancias disruptoras endocrinas y efecto disruptor endocrino, así como términos MeSH: endocrine disruptors y alternativas MeSH: disruptors, endocrine; endocrine disrupting chemicals; chemicals, endocrine disrupting; endocrine disruptor effect; disruptor effect, endocrine; effect, endocrine disruptor; endocrine disruptor effects; disruptor effects, endocrine; effects, endocrine disruptor.

Diagnostic and prognostic value of immune indicators of inflammation in the course and progression of gastroesophageal reflux disease and autoimmune thyroiditis in young people

Cytokines are considered as “microendocrine system” due to the fact that they have a triple mechanism of action. First, they affect the cell-producer (autocrine effect); secondly, they influence neighboring (adjacent) cells (paracrine effect); thirdly, they affect the distant cells of organs and tissues (endocrine effect). Most cytokines have a wide range of biological activity, which is associated with their synthesis and secretion of various types of cells. Aim of study was to determine the role and prognostic values of tumor necrosis factor (TNF) α, interleukin (IL) 1β and IL-18 in young patients with autoimmune thyroiditis (AIT) and gastroesophageal reflux disease (GERD). Materials and methods. Study involved 83 patients (students) with GERD and AIT. The average age for the group was 22.1±2.11 years. The comparison group was represented by 30 patients of similar age with isolated GERD. The enzyme immunoassay was used to study the content of TNF-α, IL-1β and IL-18. Results. Upon evaluating the complaints of patients, it was found that the main manifestation of GERD was heartburn of varying severity, duration and frequency of occurrence. It has been shown that the course of GERD occurs against the background of the development of a systemic inflammatory reaction (increased synthesis of proinflammatory cytokines IL-1β and TNF-α), and also depends on the form of esophagitis: more pronounced in the erosive variant of the mucous membrane of the esophagus. At the same time, there was an increase in the synthesis of IL-18, which, with isolated GERD, is associated with a general inflammatory reaction, and with the addition of AIT, the inclusion of immune mechanisms. Relationship between the level of TNF-α in peripheral blood and the content of thyroid-stimulating hormone was studied. However, unlike the results of other scientists, the authors have not identified such a relationship.

Adipokines and the Female Reproductive Tract

It is well known that adipose tissue can influence puberty, sexual maturation, and fertility in different species. Adipose tissue secretes molecules called adipokines which most likely have an endocrine effect on reproductive function. It has been revealed over the last few years that adipokines are functionally implicated at all levels of the reproductive axis including the gonad and hypothalamic-pituitary axis. Many studies have shown the presence and the role of the adipokines and their receptors in the female reproductive tract of different species. These adipokines regulate ovarian steroidogenesis, oocyte maturation, and embryo development. They are also present in the uterus and placenta where they could create a favorable environment for embryonic implantation and play a key role in maternal-fetal metabolism communication and gestation. Reproductive functions are strongly dependent on energy balance, and thereby metabolic abnormalities can lead to the development of some pathophysiologies such as polycystic ovary syndrome (PCOS). Adipokines could be a link between reproduction and energy metabolism and could partly explain some infertility related to obesity or PCOS.

Association of response to neoadjuvant chemotherapy (NAC) in premenopausal patients with hormone receptor-positive early breast cancer with chemotherapy-induced ovarian function suppression by NAC.

e11017 Background: The purpose of this study is to assess the additive endocrine effect by chemotherapy-induced ovarian function suppression (CIOS) for premenopausal women with early breast cancer in neoadjuvant chemotherapy (NAC). Methods: We retrospectively compared the clinical efficacy to NAC between premenopausal and postmenopausal patients with early breast cancer to evaluate the endocrine effect by CIOS. One-hundred twenty two patients received NAC with anthracycline-containing regimen and/or taxane in Kumamoto University Hospital between April 2004 and March 2011. Results: Objective response rate by NAC in premenopausal ER-positive/HER2-negative patients is greater than that in postmenopausal ER-/HER2+ patients (premenopausal 93% vs. postmenopausal 63%, p=0.0121). Reduction rate of primary tumor by NAC on imaging studies in premenopausal ER+/HER2- patients is greater than that in postmenopausal ER-/HER2+ patients (premenopausal 54% vs. postmenopausal 40%, p=0.006). However, no significant difference in response rate between in premenopausal patients with other subtypes and postmenopausal patients with those was found (ER+/HER2+; premenopausal 50% vs. postmenopausal 48%, ER-/HER2+; premenopausal 43% vs. postmenopausal 77%, Triple-negative; premenopausal 86% vs. postmenopausal 65%). All of premenopausal women were suppressed ovarian function within two months after initiation of NAC. Expression levels of progesterone receptor on primary tumor in premenopausal ER+ cancer were significantly decreased after NAC compared with that in postmenopausal ER+ cancer (premenopausal -40.3% vs. postmenopausal +3.6%, p<0.001). Conclusions: These data suggests that CIOS by NAC contributes the additive effects through the endocrine fashion in premenopausal patients with ER+/HER2- breast cancer.