Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82

Primary abnormalities of the peritoneum are rare in children. However, there is frequent secondary involvement of the peritoneal cavity and its specialized folds, the mesentery and omentum, in the presence of infectious, neoplastic, and traumatic conditions that originate at other sites in the abdomen or pelvis. Computed tomography (CT) is usually the modality of choice for evaluation of complex abdominal or pelvic pathologic conditions. Peritoneal cavity abnormalities include peritoneal fluid, pneumoperitoneum, and hemoperitoneum; peritoneal abscesses and peritonitis; metastases; and bladder or bowel rupture and solid organ injury. Mesenteric and omental abnormalities include an increase in or infiltration of mesenteric and omental fat; mesenteric lymphadenitis; mid-gut malrotation and bowel herniation; a variety of infections; metastases, lymphoma, and lymphangioma; and mesenteric injury. Knowledge of the spectrum of abnormalities that involve the mesentery, omentum, and peritoneal cavity and the characteristic CT appearances of these abnormalities is essential for improved diagnosis of these conditions.
 ...
PMID:CT of the mesentery, omentum, and peritoneum in children. 789 16

The multiple actions of somatostatin are mediated by specific membrane-bound receptors present in all somatostatin target tissues, such as brain, pituitary, pancreas, gastrointestinal tract, and kidney. For instance, in the human gastrointestinal tract, three different types of tissue compartments express somatostatin receptors: the gastrointestinal mucosa, the peripheral nervous system, and the gut-associated lymphoid tissue, where the receptors are preferentially located in germinal centers. In all these cases, somatostatin binding is of high affinity and specific for bioactive somatostatin analogues. Somatostatin receptors are also expressed in pathological states, such as cancers. A particular abundance is found in neuroendocrine tumors of the gastrointestinal tract. Ninety percent of the carcinoids and a majority of islet cell carcinomas, including their metastases, usually have a high density of somatostatin receptors. Several different somatostatin-receptor subtypes can be expressed by these tumors, the SSTR2 subtype being the most frequently and abundantly expressed. The somatostatin receptors in tumors are identified with in vitro-binding methods, molecular biology techniques, or in vivo-imaging techniques; the latter allow the precise localization of the tumors and their metastases in the patients. Because somatostatin receptors in human gastroenteropancreatic tumors are functional, their identification can be used to predict the therapeutical efficacy of octreotide to inhibit excessive hormone release. Of differential diagnostic importance is the fact that other pathological processes in the gastrointestinal tract may be associated with a high density of somatostatin receptors. Ninety percent of lymphomas, including those with intestinal involvement express somatostatin receptors. Furthermore, a moderate number of colorectal carcinomas contain somatostatin receptors, whereas exocrine pancreatic carcinomas do not. Finally, an increased expression of SS receptors in nonneoplastic conditions, such as in intestinal veins in inflammatory bowel disease, has been recently observed. These observations demonstrate the ability of the human body to regulate SS receptors in a wide number of tissues and conditions.
 ...
PMID:Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. 797 60

The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study. 806 45

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.
 ...
PMID:Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma. 826 71

Hepatocyte growth factor/scatter factor (HGF/SF) is a protein growth factor whose pleiotropic effects on epithelial cells include the stimulation of motility, mitosis and tubulogenesis. These responses are mediated by the cell surface tyrosine kinase receptor c-met. Because both the cytokine and receptor are found in the gastrointestinal tract, we have studied the effects of HGF/SF on transformed gut epithelial cells which express c-met. Here we describe the response of a new transformed human jejunal epithelioid cell line (HIE-7) to HGF/SF. Morphologically HIE-7 cells are immature. Their epithelial lineage was confirmed by reactivity with the epithelial specific antibodies AE1/AE3, Cam 5.2, Ber-EP4 and anti-EMA and is consistent with their expression of c-met mRNA and protein. In addition, electron microscopic analysis revealed the presence of primitive junctions and rudimentary microvilli, but features of polarization were absent. When grown on reconstituted basement membranes, HIE-7 cells formed closely associated multicellular cord-like structures adjacent to acellular spaces. However, the cells did not mature structurally, form lumen-like structures or express disaccharidase mRNA, even in the presence of recombinant HGF (rHGF). On the other hand, rHGF induced HIE-7 cells to scatter and stimulated their rapid migration in a modified wound assay. To determine whether the mitogenic effect caused by rHGF is associated with HIE-7 cell invasiveness across reconstituted basement membranes, a Boyden chamber chemoinvasion assay was performed. rHGF stimulated a 10-fold increase in the number of HIE-7 cells that crossed the basement membrane barrier, while only stimulating a small increase in chemotaxis across a collagen IV matrix, suggesting that the cytokine activates matrix penetration by these cells. rHGF also stimulated the invasion of basement membranes by an undifferentiated rat intestinal cell line (IEC-6) and by two human colon cancer cell lines which are poorly differentiated (DLD-1 and SW 948). In contrast, two moderately well differentiated colon cancer cell lines (Caco-2 and HT-29) did not manifest an invasive response when exposed to rHGF. These results suggest that HGF/SF may play a significant role in the invasive behavior of anaplastic and poorly differentiated gut epithelial tumors.
Clin Exp Metastasis 1994 Mar
PMID:Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line. 830 28

Radiolabeled somatostatin analogs are potentially of considerable value in both the localization and treatment of somatostatin receptor-bearing tumors. Whole body 123I-labeled Tyr3-octreotide scintigraphy is capable of detecting and localizing primary tumors and metastatic disease that may not be detectable by other methods. Although it is possible that this technique may be applicable to a wide variety of neoplasms, 123I-Tyr3-octreotide scans appear particularly useful for imaging various gut neuroendocrine tumors, meningiomas, and paragangliomas. This primarily reflects the level of expression of somatostatin receptors by these lesions. In addition to whole body scintigraphy, intraoperative localization by receptor identification utilizing a hand-held gamma detector probe may prove to be an effective means of identifying spread and micrometastasis of somatostatin receptor-bearing tumors. Aside from identification and topographic localization of disease, the detection of an 123I-Tyr3-octreotide labeled tumor may be utilized as in vivo assay for the presence of somatostatin receptors. Such observations may prove useful in predicting the susceptibility of an individual tumor to octreotide therapy. Additionally, it may prove possible to deliver a therapeutic dose of radiation to receptor-bearing tumors by the administration of specific radiolabeled somatostatin analogs.
 ...
PMID:Use of radiolabeled somatostatin analogs in the identification and treatment of somatostatin receptor-bearing tumors. 835 74

270 digestive carcinoid tumors have been diagnosed at the Pathology Institute of Lausanne between 1971 and 1990; of these 21 were associated with other, synchronous, tumors: 7 of the carcinoids were from the appendix (33%), 8 from the small bowel (38%), 4 were from the colorectum (25%), one from the duodenum (4.5%) and finally one from the stomach (4.5%). Two thirds (14) were associated with adenocarcinomas of the colon, the rest with 2 gastric tumors, 1 tumor of the appendix, 1 of the gallbladder, 1 of the small gut, 1 of the duodenum and 1 of the peritoneum. The mean age of the patients was 70 years, which correlates with the large proportion of carcinomas of the colon. The males (16) clearly outnumbered the females (5) for no obvious reason. 80% of the carcinoids were discovered during the treatment of the associated tumor. Survival was directly related to the stage and aggressivity of the malignant tumor. The carcinoid itself hardly changed the prognosis, except for one case of liver failure due to metastases from carcinoid of the stomach associated with an adenocarcinoma. The histologic features of the carcinoid tumors were unexceptional. Different hypotheses to explain the associations are formulated.
 ...
PMID:[Digestive carcinoids and synchronous malignant tumors]. 837 37

Midgut carcinoid tumors derive from gut entoderm. These tumors may cause a complex of symptoms comprising the carcinoid syndrome by secreting a wide variety of bioactive agents in addition to serotonin. Such symptoms generally follow metastases to the liver but may also occur in primary ovarian or retroperitoneal tumors. After localization and biochemical characterization, the bioactivity of these tumors should be blocked by octreotide, sometimes in combination with other pharmacologic antagonists, so that primary resection may be performed safely. If curative resection is impossible, then a cytoreductive management scheme should be employed that includes surgical debulking and hepatic arterial embolization, followed by palliation with octreotide.
 ...
PMID:Biology and management of the midgut carcinoid. 842 15

270 digestive carcinoid tumors have been diagnosed at the Pathology Institute of Lausanne between 1971 and 1990; of these 21 were associated with other, synchronous, tumors: 7 of the carcinoids were from the appendix (33%), 8 from the small bowel (38%), 4 were from the colorectum (25%), one from the duodenum (4.5%) and finally one from the stomach (4.5%). Two thirds (14) were associated with adenocarcinomas of the colon, the rest with 2 gastric tumors, 1 tumor of the appendix, 1 of the gallbladder, 1 of the small gut, 1 of the duodenum and 1 of the peritoneum. The mean age of the patients was 70 years, which correlates with the large proportion of carcinomas of the colon. The males (16) clearly outnumbered the females (5) for no obvious reason. 80% of the carcinoids were discovered during the treatment of the associated tumor. Survival was directly related to the stage and aggressivity of the malignant tumor. The carcinoid itself hardly changed the prognosis, except for one case of liver failure due to metastases from carcinoid of the stomach associated with an adenocarcinoma. The histologic features of the carcinoid tumors were unexceptional. Different hypotheses to explain the associations are formulated.
 ...
PMID:[Digestive system carcinoid tumor and synchronous malignant tumors]. 848 Jan 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>