Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on the growth factors (primarily IGFs, TGF-alpha and TGB-beta) that control both proliferation and differentiation of the normal intestinal epithelial cells and their involvement in intestinal tumorigenesis. Integrity of the digestive tissue is dependent on continuous coordination between cell growth and maturation along the crypt- villus axis. Beyond an intricate network of various regulatory molecules, such a regulation is essentially in close connection with the opposite biological effects delivered on a same target cell by TGF-alpha and TGF-beta. Growth factors act via regulatory autocrine/paracrine loops that are physiological means to deliver biological signals throughout the normal gut tissue. During tumorigenesis, cell progressively lose their sensitivity towards such extracellular regulatory loops. TGF-alpha insensitivity is linked to constitutive activation of intracellular pathways that induce uncontrolled cell growth. The incapacity to respond to TGF-beta that is due to an alteration of its intracellular pathway does not allow the negative regulation of cell proliferation or the induction of cell differentiation. Concurrently, the disappearance of an IGF-II extracellular autocrine loop appears to be correlated with cells maintained in an undifferentiated state. These alterations lead to a break between the metabolic pathways involved in the delicate control of the proliferation/differentiation balance. This leads to an unscheduled increase of positive proliferative signals which are responsible for an uncoordinated epithelial cell growth that favour tumor cell clone outgrowth. From these experimental data, essentially obtained in vitro, we propose a tentative colorectal tumorigenesis model that links both growth factor pathways and genetic (oncogenes and tumor suppressor genes) alterations. However, such a model only represents a part of the multiple cell and molecular interactions that are set in action in vivo. It remains to decipher their consistency in order to improve new therapeutic strategies.
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PMID:[Growth factors and intestinal cancers]. 142 6

A solitary cervical metastasis of a typical carcinoid tumor was found in the subcutaneous tissue of an asymptomatic 38-yr-old woman. Investigations failed to disclose the primary site until the 5th yr, when she presented with carcinoid syndrome. Multifocal ileal carcinoid tumors were resected and debulking of abdominal metastases performed. Interferon and somatostatin analogue treatment resulted in remission. Solitary cervical metastasis is an exceedingly rare initial manifestation of a mid-gut carcinoid tumor, and poses a therapeutic dilemma. There are no directions in the literature as to whether a "wait-and-see" approach or exploration surgery is the preferred management when one is confronted by a cervical metastasis of typical carcinoid tumor of unknown primary site.
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PMID:Cervical soft tissue metastasis of typical carcinoid tumor preceding diagnosis of ileal primary by 4 years. 144 97

Gastrointestinal (GI) tract neoplasms can be detected, evaluated and staged by computed tomography (CT), especially from high-resolution examinations, but routine CT scanning may occasionally discover GI neoplasms in patients with non-specific symptoms. We therefore evaluated the sensitivity and main signs of CT examinations resulting from routine sessions. In 46 out of 1560 patients who underwent abdominal CT, it was possible to obtain a diagnosis of primitive gastric or colo-rectal tumour by means of barium X-ray and/or endoscopy. The sensitivity rate of CT obtained from the present study was 86% in gastric tumours and 87% in colonic tumours. In gastric lymphoma, infiltrating carcinoma of stomach and rectal carcinoma, the sensitivity rate was 100%. The CT diagnosis of GI neoplasms was based on diffuse or local thickening of the gut on a solid dishomogenous mass showing contrast enhancement. The prevalence of various patterns depends on site of origin and on macroscopic features of the neoplasia. In conclusion the results suggest that abdominal CT, even if performed with a method not specifically devoted to GI tract, has high sensitivity rates and then a high probability of detecting GI neoplasms when unsuspected at time of the examination. In our series 11% of GI neoplasms were initially diagnosed by routine CT examination.
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PMID:Computed tomography detection of gastrointestinal neoplasms. 148 79

Min is a fully penetrant dominant mutation that leads to the development of multiple intestinal adenomas throughout the duodenal-to-colonic axis. Min/+ C57BL6/J mice have an average life-span of 120 d. Multi-label immunocytochemical studies of these lesions demonstrate patches of differentiated enterocytes, and scattered enteroendocrine, goblet and Paneth cells. Expression of endogenous marker genes within these differentiated cells can be directly correlated with the position occupied by the adenoma along the duodenal-to-colonic axis and mirrors the regional differentiation of the normal gut epithelium. The presence of multiple lineages in adenomas together with their retention of spatial information suggests that tumorigenesis in Min/+ mice may be initiated in a multipotent stem cell normally located at the base of intestinal crypts. To study the time-dependent properties of these tumors, genetic conditions were sought in which Min/+ animals could survive for up to 300 d. Min is fully penetrant in hybrids with either AKR/J or MA/MyJ. However, the hybrids demonstrate a reduction in the number of intestinal adenomas. Preliminary backcross analysis is consistent with a single major modifier locus unlinked to Min in both the AKR/J and MA/MyJ strains. The increased lifespan of the hybrid animals is also associated with the development of invasive tumors. New tumors do not arise continuously over the lifespan of these animals; instead all adenomas appear to be established by 100 d of age or sooner. These studies indicate that the Min/+ mouse is a powerful model system for analyzing the mechanisms that establish and maintain a balance between proliferation and differentiation in the continuously renewing gut epithelium and for an assessment of the multi-step hypothesis of intestinal neoplasia.
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PMID:The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. 154 40

The effects of glutamine-enriched total parenteral nutrition (TPN+GLN) were studied in tumor-bearing rats because glutamine can benefit host tissues but also may stimulate tumor growth. Rats were implanted with the methylcholanthrene-induced fibrosarcoma (MCA sarcoma) and were studied when the tumor constituted less than 5% of carcass weight (small tumor) and when the tumor constituted 10% of carcass weight (large tumor). Provision of 20% of TPN protein as glutamine produced a significant increase in the arterial glutamine level and maintained the skeletal muscle intracellular glutamine concentration (2.02 +/- 0.1 versus 1.39 +/- 0.07 mumol/g, p less than 0.01). Concurrently, hindquarter GLN fractional release increased nearly threefold (p less than 0.05) in the TPN+GLN group. Glutamine-enriched total parenteral nutrition did not affect carcass weight, tumor weight, tumor DNA content, or tumor glutaminase activity. Furthermore, DNA flow cytometric analysis did not demonstrate any difference in percentage of aneuploid tumor cells within the G1, S, or G2M cell cycles. However, the ratio of aneuploid to diploid cells within the tumor mass increased by 20% in animals receiving glutamine. Glutamine-enriched total parenteral nutrition had no effect on tumor glutathione (GSH) levels. No increase in hepatic GSH levels was observed, but gut mucosal GSH levels were 20% greater in the TPN+GLN group (p less than 0.05). The provision of glutamine-enriched TPN may be beneficial to the host by maintaining skeletal muscle glutamine stores and by supporting gut GSH biosynthesis. In this tumor model, TPN+GLN does not appear to increase tumor size, tumor DNA content, or tumor glutamine metabolism, but the ratio of tumor cells to host infiltrating cells within the tumor mass appears to be increased.
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PMID:The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues. 154 96

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL2) can induce regression of tumor metastases in animal models and in human metastatic malignant melanoma. We investigated the potential of colorectal cancer TIL as a source of killer cells and the effect of tumor necrosis factor alpha (TNF alpha) in combination with IL2 on their cytotoxic activity. Tumor-infiltrating lymphocytes were isolated from surgical specimens using a mechanical and enzymatic dissociation process. Autologous lamina propria mononuclear cells (LPMC) were used as control. Tumor-infiltrating lymphocytes and LPMC were cultured in the presence of IL2 with/without TNF alpha (1000 U/ml each) for 5 to 8 weeks. Cytotoxicity (% lysis) was tested against Daudi target cells in a 4-hr 51Cr-release assay. The combination of IL2 and TNF alpha resulted in a significantly greater-fold expansion of TIL than IL2 alone (P less than 0.01). Lamina propria mononuclear cells expanded less than TIL, and TNF alpha had an inhibitory effect on their growth (P less than 0.05). Tumor-infiltrating lymphocytes and LPMC showed comparable cytotoxicity when cultured with IL2 alone. However, the addition of TNF alpha augmented the killer activity of TIL while inhibiting that of LPMC (P = 0.035). These results indicate that TNF alpha selectively increases the IL2-induced growth and cytotoxic function of colorectal cancer TIL, but not those of gut mucosal lymphoid cells, suggesting that TIL and LMPC differ in their response to TNF alpha. Therefore, this combination of cytokines may hold more promise than single agents for the immunotherapy of colorectal cancers with TIL.
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PMID:Resident research award: tumor necrosis factor alpha selectively enhances growth and cytotoxic activity of tumor infiltrating lymphocytes from human colorectal cancer. 154 66

The clinicopathological, ultrastructural and immunohistochemical characteristics of four primary tumors of the middle ear are reported. These neoplasms showed a striking, heterogeneous aspect ranging from solid-trabecular (Type I) to tubulo-glandular (Type II) growth patterns. Secretory activity of the tumor cells was evaluated by immunohistochemistry and electron microscopy. Based on these procedures, three cell types were found, mainly limited to tumors with a tubulo-glandular (Type II) growth pattern. Most frequent were B-cells with an abundant pale cytoplasm containing neuroendocrine granules, both cytokeratin and vimentin as well as several endocrine marker substances. Less frequent were A-cells, which are slender, darkly staining and line the glandular lumina. They showed exocrine activity only and stained strongly with a polyclonal cytokeratin antibody. Finally, least frequent were amphicrine cells, which were characterized by both lumina and neuroendocrine granules in their cytoplasm and were interpreted as the link between A and B cells. Although this morphological description closely resembles that of carcinoids and adenocarcinoids of the respiratory tract and gut, the clinical behaviour of these middle ear tumors nevertheless seems different, with no recurrence or metastasis after a follow-up of 1 to 14 years (median 78 months). Therefore, some authors suggest that these tumors should be classified as middle ear adenomas or adenomatous tumors. However, we strongly feel that these tumours represent a distinct entity and can be classified as adenocarcinoids or amphicrine tumors, i.e. demonstrating both exocrine and endocrine activities. Further work is required to evaluate the exact proportion of neuroendocrine and amphicrine tumors in the heterogeneous group of adenomas and in the rarely described group of adenocarcinomas.
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PMID:Adeno-carcinoid or amphicrine tumors of the middle ear a new entity? 159 87

The implications of profound and sustained suppression of acid secretion are of increasing concern. Short-term inhibition of acid secretion by H2-receptor blockade or proton pump inhibition alters the gastric luminal flora and increases the risk of nosocomial pneumonia in critically ill patients who are receiving prophylaxis for stress gastritis. Long-term suppression alters gut flora, carcinogen levels in the gastric lumen, and the hormonal milieu, leading to proliferative changes in the fundic mucosa. Previous reports have noted a significant incidence of gastric malignancies in the achlorhydric environment of atrophic gastritis and pernicious anemia. Concern has also been expressed regarding the possibility of gastric neoplasia that arises after vagotomy and distal gastrectomy. The exact risk of gastric epithelial and endocrine hyperplasia or neoplasia in patients receiving potent antisecretory agents is not yet known, but such risks cannot be dismissed until long-term follow-up studies are available. The relationship between sustained suppression of acid secretion and the proliferation of epithelial and endocrine elements may provide insight into processes that regulate replication and growth of cells in the gastric mucosa.
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PMID:Implications of sustained suppression of gastric acid secretion. 159 43

The SRIF analog octreotide (SMS 201-995) has been in clinical use for over 6 yr in the treatment of acromegaly and metastatic endocrine pancreatic and carcinoid tumors. The use of the analog in the treatment of acromegaly and TSH-secreting tumors is beyond the scope of this clinical review. Patient acceptance of the analog, given chronically by the sc route, has been excellent and side effects have been few with the exception of the development of gallstones. In endocrine pancreatic and carcinoid tumors the hypersecretion of hormones such as VIP, glucagon, and gastrin and the secretory products of carcinoid tumors (e.g. 5-hydroxytryptamine and tachykinins) and their clinical effects may be successfully blocked. This allows excellent palliation of such tumors and often enables the patients to return home and lead normal social lives. Initial hopes that long-term octreotide therapy would be an effective antitumor drug, reducing tumor growth, based on experimental animal models and human tumor cell lines, have not been born out in clinical practice. A reduction in gut tumor bulk due to octreotide, rarely or never occurs as a sustained phenomenon. Eventually a decrease in, and finally an absence of, clinical effectiveness occurs despite the reintroduction of other treatment modalities.
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PMID:Clinical review 23: The use of the long-acting somatostatin analog octreotide in the treatment of gut neuroendocrine tumors. 164 13

Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption. The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)-binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property. Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but still retain anti-collagenase activity. The first of these CMTs, 4-de-di-methylaminotetracycline, was found not to produce a major side-effect of antimicrobial tetracycline therapy--its administration to experimental animals did not result in the emergence of tetracycline-resistant microorganisms in the oral flora and gut. Numerous examples of the clinical potential of this non-antimicrobial property of tetracyclines in the treatment of periodontal and several medical diseases (e.g., sterile corneal ulcers, rheumatoid arthritis, skin bullous lesions, tumor-induced angiogenesis and metastasis) are discussed.
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PMID:Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. 165 39


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