neuropeptide-y and Stomach-Neoplasms

Cancer cachexia (CC), a syndrome characterized by anorexia and body weight loss due to low fat-free mass levels, including reduced musculature, markedly worsens patient quality of life. Although stomach cancer patients have the highest incidence of cachexia, few experimental models for the study of stomach CC have been established. Herein, we developed stomach CC animal models using nude rats subcutaneously implanted with two novel cell lines, i.e., MKN45c185, established from the human stomach cancer cell line MKN-45, and 85As2, derived from peritoneal dissemination of orthotopically implanted MKN45c185 cells in mice. Both CC models showed marked weight loss, anorexia, reduced musculature and muscle strength, increased inflammatory markers, and low plasma albumin levels; however, CC developed earlier and was more severe in rats implanted with 85As2 than in those implanted with MKN45cl85. Moreover, human leukemia inhibitory factor (LIF), a known cachectic factor, and hypothalamic orexigenic peptide mRNA levels increased in the models, whereas hypothalamic anorexigenic peptide mRNA levels decreased. Surgical removal of the tumor not only abolished cachexia symptoms but also reduced plasma LIF levels to below detectable limits. Importantly, oral administration of rikkunshito, a traditional Japanese medicine, substantially ameliorated CC-related anorexia and body composition changes. In summary, our novel peritoneal dissemination-derived 85As2 rat model developed severe cachexia, possibly caused by LIF from cancer cells, that was ameliorated by rikkunshito. This model should provide a useful tool for further study into the mechanisms and treatment of stomach CC.

Topics: Agouti-Related Protein; Animals; Cachexia; Cell Line, Tumor; Corticotropin-Releasing Hormone; Cytokines; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Hypothalamic Hormones; Hypothalamus; Leukemia Inhibitory Factor; Male; Melanins; Nerve Tissue Proteins; Neuropeptide Y; Oxygen Consumption; Pituitary Hormones; Pro-Opiomelanocortin; Rats; Rats, Nude; RNA, Messenger; Stomach Neoplasms

To investigate the plasma NPY concentration in patients with gastric and colorectal carcinomas in relation to tumor progression.. Blood samples were obtained from patients with gastric cancer (n = 18) and colorectal cancer (n = 20). Plasma NPY concentration was determined by radioimmunoassay.. The average plasma NPY level in the 38 patients studied (125.3 +/- 31.5 pg/ml) was significantly(P < 0.001) lower than that in 28 healthy control individuals (145.1 +/- 44.1 pg/ml). Decreased NPY levels were correlated with loss (> 3 kg) of body weight (P < 0.01) and tumor size (> 5 cm) (P < 0.05). The stage of gastric cancer, but not that of colorectal cancer, was negatively correlated with plasma NPY level. Plasma NPY level did not correlate with sex, age, blood pressure, depth of tumor invasion, degree of differentiation, lymph node metastasis, hemoglobin and albumin concentrations.. Plasma NPY level is decreased in patients with gastric and colorectal carcinomas, but it reflects only in part the progression of gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Staging; Neuropeptide Y; Radioimmunoassay; Rectal Neoplasms; Stomach Neoplasms