vasoactive-intestinal-peptide and Neoplasm-Metastasis

We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.

Topics: Active Transport, Cell Nucleus; Animals; beta Catenin; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Nucleus; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Male; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Vasoactive Intestinal Peptide

We report a successful treatment of a patient with heavily metastasized pancreatic vasoactive intestinal polypeptide-secreting tumor, which was unresponsive to high doses of octreotide analog using peptide receptor radionuclide therapy applying a radiolabeled somatostatin analog. After the peptide receptor radionuclide therapy, there was a decrease in vasoactive intestinal polypeptide levels, a significant reduction in somatostatin receptor expression and in molecular tumor volume on 68Ga DOTANOC PET/CT scan, and a complete long-term resolution of symptoms of the patient.

Topics: Dose-Response Relationship, Radiation; Female; Humans; Middle Aged; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Receptors, Somatostatin; Treatment Failure; Vasoactive Intestinal Peptide

Neuroblastoma represents one of the most frequently developing malignant solid tumours in children. At the time of diagnosis, in more than half of the cases, metastatic cells are also present in the bone marrow. The present study was aimed at immunocytochemical analysis of selected neuropeptide manifestation in metastatic cells of neuroblastoma in bone marrow and at comparing the obtained results with the immunophenotype of parental neuroblastoma cells. The studies were performed on bone marrow material obtained from children treated at the Department of Paediatric Haematology and Oncology, University of Medical Sciences, Poznań, Poland, in 1998-2000. Immunocytochemical analysis of nervous tissue markers (employing the immunomax technique) involved 36 bone marrow preparations obtained from 27 children. The analysis included expression of neuron-specific enolase (NSE), PGP 9.5 protein, substance P (SP), chromogranin A (ChA), bombesin (B), galanin (G), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). Close to 90% metastatic cells in bone marrow were found to exhibit NSE+SP+B+ phenotype and over a half of the cells manifested additionally expression of PGP 9.5+ChA+NPY+. Comparison of the obtained results with the immunophenotype of neuroblastoma cells obtained directly from the primary tumour demonstrated high correlation of NSE, SP and PGP 9.5 expression. Due to the relative ease of obtaining the bone marrow material and absence of neuromarkers in bone marrow metastatic cells in solid tumours other than neuroblastoma, determination of immunophenotype of the cells may represent a valuable supplementation in preliminary diagnosis of this tumour in children.

Topics: Adolescent; Biomarkers, Tumor; Biopsy, Needle; Bone Marrow; Child; Child, Preschool; Chromogranin A; Chromogranins; Female; Galanin; Humans; Immunohistochemistry; Immunophenotyping; Male; Neoplasm Metastasis; Neoplasm Staging; Neuroblastoma; Neuropeptide Y; Substance P; Vasoactive Intestinal Peptide

Our goal was to define the incidence of neuroendocrine carcinomas of the colon and rectum, the patterns of neuroendocrine expression, and the cellular subtype within neuroendocrine tumors. We attempted to determine whether differences in neuroendocrine expression or specific cell type influenced survival.. Over a ten-year period, 988 patients had resections for colorectal cancer. Using immunohistochemical staining methods specific for neuroendocrine markers, 39 (3.9 percent) neuroendocrine cancers were identified retrospectively. Tumors were also stained with monoclonal antibody A-80 which is specific for exocrine differentiation. In this way we were able to determine the extent of neuroendocrine differentiation such as pure neuroendocrine, predominant neuroendocrine, and equal neuroendocrine-exocrine expression.. Average patient age was 65.5 (range, 28-89) years; there were 25 males and 14 females. Nineteen tumors were located in the right colon, 11 in the left, and 9 were in the rectum. Three histopathologic patterns were identified: pure neuroendocrine (n = 11), predominantly neuroendocrine (n = 17), and cancers with equal exocrine and neuroendocrine differentiation (n = 7). Three cellular subtypes were seen: small-cell (n = 15), intermediate-cell (n = 15), and well-differentiated neuroendocrine cancers (n = 5). There was one Dukes A cancer, 7 Dukes B, 16 Dukes C, and 15 patients had metastases to distant sites at the time of diagnosis. As a group, neuroendocrine tumors have a poor prognosis: six-month survival was 58 percent, three-year survival was 15 percent, and five-year survival was 6 percent. Survival statistically correlated with tumor stage (P = 0.01) but not with age, sex, tumor location, histopathologic pattern, or neuroendocrine subtypes. Median survival for pure neuroendocrine carcinomas was seven months and for predominantly neuroendocrine carcinomas was five months. Tumors with equal neuroendocrine and exocrine differentiation had a median survival of 22 months (P = 0.3). Small-cell neuroendocrine carcinomas had a median survival of five months, intermediate-cell had 11 months, and well-differentiated had a median survival of 22 months (P = 0.1).. Neuroendocrine differentiation is found in at least 3.9 percent of colon and rectal cancers. Many of these tumors were initially diagnosed as "carcinoids," the diagnosis was changed to "neuroendocrine carcinoma" after immunohistochemical staining. Overall survival is poor especially for small-cell and pure neuroendocrine carcinomas.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Colonic Neoplasms; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Phosphopyruvate Hydratase; Rectal Neoplasms; Serotonin; Survival Rate; Time Factors; Vasoactive Intestinal Peptide

Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Calcitonin; Catecholamines; Child; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Pheochromocytoma; Phosphopyruvate Hydratase; Prognosis; Vasoactive Intestinal Peptide

Topics: Adrenal Gland Neoplasms; Aged; Female; Gastrointestinal Hormones; Humans; Male; Middle Aged; Motilin; Neoplasm Metastasis; Pheochromocytoma; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Five patients with metastatic pancreatic endocrine tumours injected a long acting somatostatin analogue (SMS 201-995) 50 micrograms subcutaneously every 12 hours and were followed up for three to six months. Treatment aimed at controlling excess secretion of hormone by the tumours thereby bringing symptomatic relief. Four patients showed a significant reduction in tumour related hormone concentrations but in none did values return to normal. All five patients, however, noted definite symptomatic improvement and in one this was dramatic (disappearance of life threatening diarrhoea and correction of metabolic acidosis and hypokalaemia within 48 hours). Mild worsening of symptoms and increasing fasting tumour related hormone concentrations after three to six months of treatment were reversed by doubling the 12 hourly dose. The treatment was well tolerated and had no deleterious effect on fasting blood glucose concentrations. This somatostatin analogue seems a promising non-invasive treatment for metastatic pancreatic endocrine tumours.

Topics: Adult; Aged; Blood Glucose; Female; Glucagon; Growth Hormone-Releasing Hormone; Humans; Male; Middle Aged; Neoplasm Metastasis; Octreotide; Pancreatic Neoplasms; Receptors, Opioid; Somatostatin; Vasoactive Intestinal Peptide

A primary duodenal small-cell neuroendocrine carcinoma was found in an elderly man who presented with upper abdominal pain. Although metastatic small-cell carcinoma was documented by liver biopsy, the primary lesion was not identified until postmortem examination. The latter tumor, which ulcerated the duodenal mucosa, was composed of small ovoid cells with sparse cytoplasm and granular chromatin. Electron microscopy revealed cytoplasmic dense-core granules. Immunocytochemical study demonstrated the presence of neuron-specific enolase, Leu 7 antigen, chromogranin, epithelial membrane antigen, and vasoactive intestinal polypeptide within tumor cells. However, there was no evidence of a clinical endocrinopathy. This case emphasizes the need to include the duodenum as a possible primary site when metastatic small-cell neuroendocrine carcinoma is seen in the absence of apparent pulmonary disease.

Topics: Aged; Carcinoma, Small Cell; Duodenal Neoplasms; Duodenal Ulcer; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Neoplasm Metastasis; Vasoactive Intestinal Peptide

Gut endocrine cells in a total of 122 intestinal-tract adenocarcinomas induced in inbred Wistar rats by 1,2-dimethylhydrazine dihydrochloride were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, vasoactive-intestinal polypeptide (VIP), and glicentin (enteroglucagon). Of the 122 tumors, argyrophil cells were detected in 42 tumors (34.3%) comprising 15 tumors of the well differentiated type and 27 tumors of the poorly differentiated type, including signet-ring-cell carcinomas. Of the 27 tumors of the poorly differentiated type, 12 were regarded as endocrine-cell carcinomas composed of numerous argyrophil or argentaffin cells and mucus-containing cells. Immunohistochemically, 7 of the 12 tumors had glicentin and two of these seven tumors also had gastrin and argentaffin cells synchronously. None of the tumors showed immunoreactivity for somatostatin and VIP. Nine of the 12 tumors metastasized to the lung, pancreas, liver, mesenterium, omentum, and lymph nodes. The metastatic foci of these tumors were also shown to have glicentin and argentaffin cells. Ultrastructurally, four types of endocrine granule were found in the tumor cells and amphicrine cells containing endocrine granules and mucous granules were noted. These endocrine-cell tumors were assumed to develop from totipotent immature cells of endodermal origin.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Carcinogens; Chromaffin System; Dimethylhydrazines; Enterochromaffin Cells; Female; Gastrins; Glucagon-Like Peptides; Intestinal Neoplasms; Male; Microscopy, Electron; Neoplasm Metastasis; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Somatostatin; Vasoactive Intestinal Peptide

A patient with an islet cell tumor presented initially with a supra-renal mass that histologically had an extensive clear cell component. Electron microscopic and immunocytochemical findings were essential to prove that the extrapancreatic mass with clear cells was an unusual metastatic manifestation of an islet cell tumor. Both the pancreatic and extrapancreatic tumor cells contained neurosecretory granules and produced vasoactive intestinal polypeptide and substance P. The clear cell morphology was due to the accumulation of lipid and glycogen and cytoplasmic swelling.

Topics: Adenoma, Islet Cell; Cytoplasmic Granules; Histocytochemistry; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Substance P; Vasoactive Intestinal Peptide

A 1 1/2 year old child developed profuse watery diarrhoea, shown to be due to excessive plasma vasoactive intestinal peptide (VIP) levels, whilst on treatment for metastatic neuroblastoma. Because it was unresponsive to alternative treatment, an attempt was made to control the diarrhoea with a somatostatin infusion. The attempt failed despite the fact that serum VIP levels were substantially reduced. Possible reasons for failure are discussed and the importance of plasma VIP as a marker for maturation in neuroblastoma emphasised.

Topics: Diarrhea; Female; Gastrointestinal Hormones; Humans; Infant; Neoplasm Metastasis; Neuroblastoma; Somatostatin; Vasoactive Intestinal Peptide

Topics: Gastrointestinal Hormones; Humans; Neoplasm Metastasis; Pancreatic Neoplasms; Preoperative Care; Vasoactive Intestinal Peptide

In animals, the effects of vasoactive intestinal polypeptide (VIP) include peripheral vasodilation, hyperdynamic circulation, hyperglycemia, and hyperventilation. Because these phenomena are noted in patients with cirrhosis, it has been postulated that VIP might be escaping hepatic inactivation and entering the systemic circulatory system and contributing to these abnormalities. The major purpose of this study is to establish whether or not VIP levels are elevated in patients with cirrhosis. Additional goals are to determine if VIP levels are elevated in acute liver disease and in chronic illnesses with secondary liver involvement. The data demonstrate that patients with cirrhosis and those with acute liver disease or chronic illnesses with secondary hepatic involvement have a wide range of VIP levels with mean values significantly above that of normal individuals and patients with chronic illness and no liver involvement.

Topics: Acute Disease; Chronic Disease; Gastrointestinal Hormones; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Neoplasm Metastasis; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Antigens; Calcitonin; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Animals; Diarrhea; Gastrointestinal Hormones; Humans; Neoplasm Metastasis; Pancreatic Neoplasms; Pancreatic Polypeptide; Swine; Syndrome; Vasoactive Intestinal Peptide

Vaso-active intestinal polypeptide (VIP) is a recently discovered polypeptide widely distributed throughout the gastro-intestinal tract and nervous system. Elevated plasma VIP levels are found in gut and neural endocrine tumours producing the watery diarrhoea syndrome. Fifty per cent of these tumours are intrinsically malignant and the mortality rate may be as high as 30% even from the bening growths owing to the serious metabolic sequelae of the syndrome. The plasma VIP level is not elevated in any other non-tumourous diarrhoeal condition. The biological action of VIP closely resembles the clinical features of the Verner-Morrison syndrome and experimental evidence strongly suggests that VIP is the causal agent. The measurement of plasma VIP is of exceptional diagnostic value, since detection of elevated levels enables early removal of the tumour and may be life-saving.

Topics: Adrenal Gland Neoplasms; Diagnosis, Differential; Diarrhea; Ganglioneuroma; Gastrointestinal Hormones; Humans; Hypokalemia; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Syndrome; Vasoactive Intestinal Peptide

A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms.

Topics: Adenoma, Islet Cell; Female; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide