c-peptide and Neoplasm-Metastasis

Insulin-like growth factor (IGF)-I and IGF-II stimulate neoplastic cell growth and inhibit apoptosis, whereas IGF-binding protein-3 (IGFBP-3) inhibits the bioavailability of IGF-I and has independent proapoptotic activity. We examined the influence of baseline plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide on outcome among patients receiving first-line chemotherapy for metastatic colorectal cancer.. The plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide as well as data on prognostic factors and body size were measured at baseline among 527 patients participating in a randomized trial of first-line chemotherapy for metastatic colorectal cancer.. Higher baseline plasma IGFBP-3 levels were associated with a significantly greater chemotherapy response rate (P = 0.03) after adjusting for other prognostic factors, whereas neither IGF-I nor IGF-II levels significantly predicted tumor response. Higher levels of IGF-I, IGF-II, and IGFBP-3 were all univariately associated with improved overall survival (P = 0.0001 for all). In a model that mutually adjusted for IGF-I and IGFBP-3, as well as other prognostic factors, increasing baseline-circulating IGFBP-3 was associated with a significantly longer time to tumor progression (P = 0.03), whereas circulating IGF-I was not associated with disease progression (P = 0.95). Levels of C-peptide were not associated with any measure of patient outcome.. Among colorectal cancer patients receiving first-line chemotherapy, increasing levels of IGFBP-3, an endogenous antagonist to IGF-I, are associated with an improved objective treatment response and a prolonged time to cancer progression. The IGF pathway may represent an important target for future treatment strategies.

Topics: Biomarkers; Body Mass Index; C-Peptide; Colorectal Neoplasms; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Neoplasm Metastasis

Predictors of quality of life (QOL) in patients with metastatic colorectal cancer are lacking. The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer.. We used a cohort of 526 patients with metastatic colorectal cancer treated with combination chemotherapy. Plasma samples of IGF-I, IGF-II, IGF binding protein-3, and C-peptide were collected before initiation of chemotherapy. QOL was measured by the uniscale instrument and the Symptom Distress Scale at baseline and throughout treatment.. Baseline plasma levels of IGF-I and IGF-II before initiation of chemotherapy were significantly associated with several important baseline QOL measures in patients with metastatic colorectal cancer. Patients with lower levels of IGF-I reported increased distress with regard to appearance, appetite, cough, and nausea intensity after adjustment for potential confounders. Similarly, decreased levels of IGF-II were predictive of worse quality related to appearance, appetite, fatigue, nausea frequency and intensity, pain frequency, and composite Symptom Distress Scale score. IGF binding protein-3 and C-peptide were not predictive of baseline QOL. Baseline biomarkers were not associated with subsequent changes in QOL during treatment. Higher body mass index was significantly associated with superior baseline QOL in several areas; nonetheless, the association of IGF-I and IGF-II with baseline QOL measures remained significant even after controlling for baseline body mass index.. Baseline plasma IGF-I and IGF-II are significantly associated with symptom distress. Whether this association is simply reflective of patient nutritional status and/or disease burden or represents an independent biological effect of IGFs on QOL remains uncertain. Nonetheless, these data suggest that molecular biomarkers may be useful predictors of QOL in cancer patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appetite; Biomarkers, Tumor; C-Peptide; Cohort Studies; Colorectal Neoplasms; Fatigue; Female; Humans; Male; Middle Aged; Nausea; Neoplasm Metastasis; Patient Satisfaction; Quality of Life; Somatomedins; Stress, Psychological

Two cases of glucagonoma, one benign and the other malignant, was presented. Benign glucagonoma in a 29-year-old man with multiple endocrine neoplasia type 1 was composed largely of tumor cells with secretory granules ranging from 139 to 417 nm in diameter identical to A cell granules. There were a few tumor cells which contained no A cell granules but smaller granules of approximately 166 nm diameter similar to those of pancreatic polypeptide containing cells. Radioimmunoassay of the tumor extract showed 319 micrograms/g wet weight of glucagon and 0.72 microgram/g wet weight of pancreatic polypeptide. Malignant glucagonoma in a 34-year-old man was a massive tumor of 7 X 6 X 5 cm replacing the tail and body of the pancreas with multiple metastases. The tumor contained 0.2 microgram/g wet weight of glucagon and 0.065 microgram/g wet weight of vasoactive intestinal peptide. The electron microscopic examination revealed that the tumor cells had variable numbers of atypical secretory granules measuring 110 to 200 nm in diameter different from A cell granules. An analysis of plasma glucagon by the gel filtration technique showed the heterogeneity of glucagon molecules indicating the presence of large glucagon. Atypical secretory granules in malignant glucagonoma were considered to represent immature granules containing the precursor or intermediate of glucagon.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Cytoplasmic Granules; Glucagon; Glucagonoma; Humans; Insulinoma; Male; Neoplasm Metastasis; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Radioimmunoassay

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.

Topics: C-Peptide; Celiac Disease; Cholelithiasis; Diabetes Complications; Glucagon; Hormones, Ectopic; Humans; Hypothalamus; Islets of Langerhans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Pituitary Gland; Radioimmunoassay; Somatostatin; Syndrome