neuropeptide-y and Rectal-Neoplasms

Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial.. Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA.. Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes.. Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.

Topics: Aged; Biomarkers, Tumor; Chemoradiotherapy; Circulating Tumor DNA; Clinical Trials, Phase III as Topic; Disease Progression; DNA Methylation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neuropeptide Y; Prognosis; Prospective Studies; Rectal Neoplasms; Survival Rate

The immunohistochemical expression of various neuropeptides, including substance P (SP), and the substance P receptor (SPR), was examined in irradiation-induced enteropathy in man. Samples from irradiated and non-irradiated patients operated on for rectal carcinoma were examined. The samples were from the sigmoid and corresponded macroscopically to non-cancerous sigmoid colon. There was a marked atrophy, ulcerations and inflammatory reactions in the irradiation-influenced mucosa. In this mucosa, there was a very pronounced innervation of varicose nerve fibers showing SP-like immunoreactivity (LI). The degree of SP-LI in the ganglionic cells of the submucous plexus was increased as compared to non-irradiated patients. There were only few or no nerve fibers showing immunoreaction for other neuropeptides examined (CGRP, enkephalin, NPY) in the irradiation-influenced mucosa. A marked SPR immunoreaction was detected in cells in the lamina propria which were interpreted as representing polymorphonuclear leukocytes. The marked expression of SP in the irradiation-damaged mucosa and the presence of SPR immunoreactive leukocytes suggest that SP is highly involved in the inflammatory reactions that occur in response to radiotherapy. The observations also suggest that SP, but not NPY, CGRP and enkephalin, has an important role in the reorganisation processes that take place in the mucosa in irradiation-induced enteropathy.

Topics: Calcitonin Gene-Related Peptide; Colon; Enkephalins; Female; Humans; Intestinal Mucosa; Male; Neuropeptide Y; Rectal Neoplasms; Substance P

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