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

Extrapolation to humans from experimental radioimmunotherapy in nude mouse xenograft models is confounded by large relative tumour size and small volume of distribution in mice allowing tumour uptake of radiolabelled antibodies unattainable in patients. Our large animal model of human tumours in cyclosporin-immunosuppressed sheep demonstrated tumour uptake of targeted radiolabelled monoclonal antibodies comparable with uptakes reported in clinical trials. Sheep immunosuppression with daily intravenous cyclosporin augmented by oral ketoconazole maintained trough blood levels of cyclosporin within the range 1000-1500 ng ml(-1). Human tumour cells were transplanted orthotopically by inoculation of 10(7) cells: SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into ovary and peritoneum. Tumour xenografts grew at all sites within 3 weeks of inoculation, preserving characteristic morphology without evidence of necrosis or host rejection. Lymphatic metastasis was demonstrated in regional nodes draining xenografts of melanoma and ovarian carcinoma. Colonic LS1 74T xenografts produced mucin and carcinoembryonic antigen (CEA). The anti-CEA IgG1 monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% DI g(-1) (percentage of injected dose per gram) and 0.034% DI g(-1) in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% DI g(-1). Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy.
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PMID:Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy. 971 32

Carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from the gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. In the early diagnosis of disease recurrence following surgical resection, a serial increase in CEA level is the first evidence of tumor. In patients with disseminated tumors, serial determinations are useful for monitoring response to therapy. Carcinoembryonic antigen values decrease with effective treatment, while they increase with disease refractory to therapy or progressive metastases, yet the utility of CEA in the management of patients with advanced colorectal cancer remains controversial.
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PMID:Role of carcinoembryonic antigen in the management of advanced colorectal cancer. 978 12

Over the past 25 years and more, very few statistically reliable evaluations dealing with clinicopathologic features of patients with insulinoma and/or hypoglycemic syndrome (HGS), including recently popularized diagnostic modalities, have been published. The aims of this study are threefold: first, to evaluate the clinicopathologic features of patients with insulinoma/HGS from various viewpoints; secondly, to update our knowledge about this subject which has been retained up to date, and thirdly to supply reliable information to investigators working in the specialized field of gut-pancreatic endocrinomas. We collected data from literature on a total of 1085 Japanese patients with insulinoma/HGS and undertook a statistical evaluation. The results are summarized as follows. 1) Association of HGS was recognized in 88.4% of the 1085 patients. 2) Islet B-cell hyperplasia/nesidioblatosis was found in 4.1%; 2.6% in association with insulinoma and 1.6% without it. 3) Patients with small tumors of 20 mm or less comprised 81.1%. 4) The overall rate of metastases was 6.6% (72 patients) and that of malignancy 13.6% (148 patients). 5) Multisecretors immunohistochemically proved were found in 32.4% and multiplicity of tumor growth in 12.6%. 6) The 10-year survival rate after removal of lesions was 90.5% overall; 98.4% in patients with benign lesions and 75.7% in those with malignant tumors. It is expected that the results obtained in the present study will provide extensive and useful information for future investigation.
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PMID:Insulinoma/hypoglycemic syndrome: a statistical evaluation of 1085 reported cases of a Japanese series. 1008 55

Carcinoid tumors are rare neuroendocrine neoplasms that belong to a more general category of tumor called the APUDomas. Ninety percent of carcinoid tumors are located in the gastrointestinal tract. Abdominal carcinoid tumors are categorized according to the division of the primitive gut from which they arise. Carcinoid tumors originating from the foregut develop in the gastric wall, duodenum, and pancreas; those originating from the midgut develop from the small bowel, appendix, and right colon; and those originating from the hindgut develop from the transverse or left colon or from the rectum. This report illustrates the computed tomographic appearance of primary and metastatic carcinoid tumors of the abdomen. Among the different organs that may be involved by metastases from carcinoid tumor, special emphasis is placed on the liver.
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PMID:Carcinoid tumors of the abdomen: CT features. 1022 86

From May 1993 to May 1998 at our hospital 12 classic gastric resections were operated on by laparoscopic procedure. A 2/3 distal Billroth resection was performed in 5 patients, for gastric ulcer (2) and for GIST (3). Other 7 patients were curatively operated on for a malignant disease. Any case was resected by oncosurgical gastrectomy including a D2-lymphadenectomy. The histological diagnoses were an adenocarcinoma in 6 cases, and one highly malignant maltoma. The mean operating time was 230 min in Billroth I resections and 295 min in total gastrectomies. As a complication, we saw postoperatively a duodenal leakage in one case, we could successfully manage also laparoscopically on the day after the operation. All the courses were extremely uncomplicated, connected with rapid mobility, early gut motility, little pain, and a comfortable cosmetic result. The resection result in any case of malignoma was R0, the mean lymphonode amount was 34. Tumour cell dissemination and trokar site metastases we could'nt note either. Oncosurgically, there are no disadvantages in comparison to the open approach.
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PMID:[Initial experience with laparoscopic gastrectomy in benign and malignant tumors]. 1035 92

Somatostatin is known to inhibit the secretory release of other peptide hormones. Somatostatinomas associated either with or without somatostatinoma (inhibitory) syndrome are rare neoplasms among gut-pancreatic endocrinomas. Collected from international literature, this study aimed to perform a statistical analysis on 173 patients with somatostatinoma/inhibitory syndrome. The evaluation further attempted to provide investigators in this particular field of research with extensive and precise information on the present situation of somatostatinoma. The 173 patients consisted of 81 with pancreatic somatostatinomas and 92 with extrapancreatic somatostatinomas. Most of the latter were found to have originated in the duodenum and may be termed as carcinoid somatostatinoma. Where data were considered to be adequate, a comparative study was carried out between two groups, pancreatic and duodenal, each consisting of 81 patients. A statistically significant difference between these two groups was found in the incidence of inhibitory syndrome (18.5% versus 2.5%) and von Recklinghausen's disease (1.2% versus 43.2%), large size of tumor (>20 mm) (85.5% versus 41.4%), multisecretory activities (33.3% versus 16.3%), and presence of psammoma bodies (2.5% versus 49.4%). There was no statistically significant difference in the rate of metastases and malignancy between the two groups. The average postoperative 5-year survival rate was 75.2% in 90 patients overall, 59.9% in 44 with metastases and 100.0% in 46 without metastases. Compared with the other pancreatic endocrinomas, including PPomas, glucagonomas, vipomas, gastrinomas, and insulinomas, somatostatinomas were characterized by the low rate of the relevant syndrome and multiple endocrine neoplasia syndrome type 1. There was a low rate of multiplicity, and a high incidence of psammoma bodies in the duodenal group particularly with von Recklinghausen's disease. A high rate of malignancy was recorded, resulting in a low postoperative survival rate of patients with metastases. In conclusion, somatostatinomas exhibited characteristic features quite different from those of the other pancreatic endocrinomas regarding multiple points.
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PMID:Somatostatinoma/inhibitory syndrome: a statistical evaluation of 173 reported cases as compared to other pancreatic endocrinomas. 1037 71

We have come to understand apoptosis as not merely a single form of cell death, but as a fundamental theme in cell biology that has far-reaching implications in the fields of physiology and pathology. At the present time, however, the mechanism of apoptosis is not clearly understood, as research into apoptosis is still at the initial stages. Nevertheless, the links between apoptosis and a variety of pathological conditions are gradually becoming clearer. In this article, we will provide a simple explanation of apoptosis and its mechanism as a novel concept of cell death and discuss the way in which apoptosis has been linked to a variety of pathological conditions. WHAT IS APOPTOSIS?: In normal tissue, cells that are no longer needed are rapidly eliminated without affecting the overall function of the tissue. In this process cells undergo an active and spontaneous suicide called programmed cell death. In fact, the majority of physiological cell deaths take the form of apoptosis. The word apoptosis is used, in contrast to necrosis, to describe the situation in which a cell actively pursues a course toward death upon receiving certain stimuli [1]. The morphological changes of apoptosis found in most cell types first involve contraction in cell volume and condensation of the nucleus. When this happens the intracellular organelles such as the mitochondria retain their normal morphology. As apoptosis proceeds, blebbing of the plasma membrane occurs, and the nucleus becomes fragmented. Finally, the cell itself fragments to form apoptotic bodies that are engulfed by nearby phagocytes. With respect to biochemical changes, it is known that the chromosomes become fragmented into nucleosome units, and DNA forms characteristic ladder patterns when subjected to agarose gel electrophoresis. MECHANISM OF APOPTOSIS: It has been reported that apoptosis is induced in various cells by many kinds of irritations, but the precise mechanism is still unclear. Cell injuries that induce apoptosis include those that cause DNA damage such as radiation and anticancer drugs, those that are mediated by the TNF receptor and Fas receptor (the so-called "death signal receptors"), and the deprivation of cytokines that supply survival signals such as IL-3 and erythropoietin. The tumor suppressor gene p53 plays a very important role in apoptosis induced by damage to DNA. This has been demonstrated by studying resistance to apoptosis of cells derived from p53 knockout mice [2]. Other than the irritations that induce apoptosis, molecules that have been strongly implicated as major players in the drama of apoptosis include the Bcl-2 family proteins and the IL-1 converting enzyme (ICE) and its homolog proteases (caspase family). Both groups of proteins show homology with proteins that affect cell death in nematodes. It is believed that molecules that contribute to cell death have been well conserved in multicellular organisms all the way from the relatively primitive nematodes to mammals including humans. It was discovered that Bcl-2 suppressed apoptosis induced in IL-3 dependent cells by deprivation of IL-3 [3]. It has since become the gene around which apoptosis research revolves. Recently, it has become clear that cell death involving the Bcl-2 protein is under the control of similar proteins from the same family [4]. It is interesting that the phenomenon of cell death may be regulated by the balance of the molecules involved in it. APOPTOSIS ABNORMALITIES AND DISEASE: Physiological cell death plays a major role in the growth and permanent maintenance of the human body [5]. In the process of forming the nervous system, neurons that do not form proper connections die. Physiological cell death also accompanies the removal of virus-infected cells by cytotoxic T cells, the elimination of autoreactive immune cells, the formation of the gut, the reconstitution of cartilage and bone, etc. When physiological cell death that normally should occur is inhibited, inappropriate physiological cell death may occur that is harmful to the body and forms the basis of disease. For example, in patients with neural degenerative disorders such as Alzheimer's disease and Parkinson's disease, we can find premature cell death in a particular subset of neurons. The death of T cells in AIDS patients is also a form of physiological cell death. Inhibition of cell death in the immune system enables the survival of autoreactive B cells and T cells, and is therefore a cause of autoimmune disorders. Apoptosis has been particularly linked to cancer. Normal cells are programmed for death if they are subjected to many types of non-physiological stress such as anticancer drugs or radiation, if they become isolated from surrounding cells and are unable to receive their tissue-specific survival signals [6], or if oncogenes are expressed haphazardly [7]. On the other hand, it is believed that the ability to survive is enhanced in transformed cancer cells because they are more resistant to apoptosis, they exhibit resistance to anticancer drugs, they are no longer dependent on survival signals, and they can metastasize. Therefore, the cancer progresses as the cancer cells maintain the proliferative superiority they acquire from their oncogenes. In other words, when cancer cells become resistant to apoptosis, they become resistant to treatment, metastasize, and proliferate destructively. The concept that the malignancy of cancer is due to its resistance to apoptosis is a relatively new one and is worthy of further study.
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PMID:Physician Education: Apoptosis. 1038 21

Carcinoid tumours are the most commonly occurring gut endocrine tumours; they are characterized by relatively slow rate of growth, local spread and distant metastases as compared with other malignant neoplasms. The carcinoid syndrome occurs in less than 10% of patients with carcinoid tumours when liver metastases are present. The combination of symptoms, humoral markers and imaging techniques provide an optimal means for the identification of carcinoid tumours and their metastases.
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PMID:Clinical aspects of carcinoid tumours. 1060 19

Bombesin-like peptides and their receptors are widely distributed throughout the gut and are potential mitogens for a number of gastrointestinal (GI) cancers. We have analysed the expression of bombesin-like peptides and their receptor subtypes in normal and neoplastic colorectal tissue. Expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) using receptor and ligand subtype-specific primers and then expression localized by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR product. Colorectal cancer tissue and matched normal mucosa from 23 patients were studied. Two of these patients had synchronous adenomatous polyps and two had synchronous hepatic metastases which were also studied. An additional two patients with adenomatous polyps were studied along with matched normal mucosa. Gastrin releasing peptide (GRP) receptor and ligand expression was present in all samples but with overall greater expression in the tumour samples. Neuromedin B (NMB) receptor expression was not detectable. NMB ligand was detected in all but one mucosal sample with overall overexpression in the tumour samples. Bombesin receptor subtype 3 (BRS-3) receptor expression was not detectable. These data support the possibility that GRP may be an autocrine growth factor in colorectal cancer.
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PMID:Bombesin family receptor and ligand gene expression in human colorectal cancer and normal mucosa. 1063 78

BACKGROUND: Carcinoid tumors are the most frequently encountered endocrine tumors of the gastrointestinal tract. They are most often found in the appendix, although they can arise in any location of the gut. Carcinoid tumors may secrete a variety of bioactive substances, which can cause the complex of symptoms associated with the carcinoid syndrome. METHODS: The authors reviewed the pathology, clinical presentation, and management of carcinoid tumors with an emphasis on the surgical management. RESULTS: The primary treatment for a carcinoid tumor located anywhere in the gut is surgical. Those who have widely metastatic disease or who are anatomically unresectable may undergo cytoreductive surgical debulking and/or hepatic arterial embolization followed by palliation of symptoms with octreotide, the long-acting somatostatin analog. CONCLUSIONS: The prognosis for patients with carcinoid tumors that are fully resected is excellent. Those with hepatic metastases and the carcinoid syndrome have a less favorable prognosis.
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PMID:Carcinoid Tumors of the Gut. 1076 99


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