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)

There are two isozymes of prostaglandin endoperoxide (PGH) synthase (cyclooxygenase) called PGH synthase-1 and -2 or COX I and II. Both isozymes catalyze the same two reactions: oxygenation of arachidonate to yield PGG2 and reduction of PGG2 to PGH2. PGH synthase-1 is expressed constitutively and is found in most tissues. PGH synthase-2 is undetectable in most cells but can be induced in fibroblasts, endothelial cells, ovarian follicles, and macrophages by various mitogens, cytokines, and tumor promoters. PGH synthase-1 (PGHS-1) has been presumed to be the site of action of nonsteroidal antiinflammatory drugs (NSAIDs). However, the discovery of the second isozyme, PGH synthase-2 (PGHS-2), and its association with inflammation has suggested that this latter enzyme may be the therapeutic target of NSAIDs functioning in their antiinflammatory capacities. We have cloned cDNAs for murine PGHS-1 and PGHS-2, expressed these enzymes in cos-1 cells, and compared the relative sensitivities of the two isozymes to some common NSAIDs. Indomethacin, piroxicam, and sulindac sulfide were found to preferentially inhibit PGHS-1. Ibuprofen and meclofenamate inhibit both enzymes with comparable potencies. 6-Methoxy-2-naphthylacetic acid, the active metabolite of Relafen, inhibits murine PGHS-2 preferentially. Aspirin irreversibly inhibits PGHS-1, preventing this isozyme from forming PGH2 or any other oxygenated product; in contrast, aspirin treatment of PGHS-2 causes this enzyme to form 15-hydroxy-5c,8c,11c,13t-eicosatetraenoic acid (15-HETE) instead of PGH2. Our results indicate mouse PGHS-1 and PGHS-2 are pharmacologically distinct. Thus, it should be possible to develop agents highly selective for each PGHS isozyme. PGHS-2 is not expressed in stomach but is increased by inflammatory cytokines in cells such as macrophages. Thus, a selective inhibitor of PGHS-2 could be an antiinflammatory agent but without being ulcerogenic.
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PMID:Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. 782 62

Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.
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PMID:Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions. 782 59

A retrospective analysis was carried out on 56 pts., (37 M, 19 F), mean age 64 yrs., operated for moderate to severe obstruction due to left colon carcinoma. Clinical and pathological features, treatment and results were compared with those of 108 pts. with left colon cancer who underwent elective surgery. Mean duration of obstructive symptoms was 5.3 days and mean delay between admission and operation was 1.15 days. Site and nature of the obstruction were assessed pre-operatively in 80.3% of the pts. Distribution of tumor localization was similar in the two groups. ASA risk was statistically higher in pts. with obstruction. Staging according to the Astler-Coller (mod. 1978) classification, showed a greater incidence of more advanced stages in the obstructing tumors. In the group with obstruction a three stage surgery was carried out in 18 pts. (32.1%), a two stage in 6 (10.7%), a primary resection in 6 (10.7%) and a decompressive colostomy in 26 (46.5%). Radicality and resectability rates were 50% and 53.6% vs 69.4% and 82.4% in elective surgery. Mean post-operative stay was 42 and 21 days respectively in the two groups. Overall post-operative death rate was 19.6% vs 9.2%, and 3.3% vs 7.8% after resective surgery. Post-operative complications accounted for 21.4% vs 21.3%. 5-year survival rate after curative surgery was 47.8% vs 76.8%. On the basis of their results and on Literature reports the Authors suggest a reevaluation of a staged surgical treatment for obstructing left colon cancer based on primary decompression following an E.L. when needed. Consequent resection and intestinal reconstruction should be performed after 2-3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Surgery of the obstructive complication of carcinoma of the left colon. The clinical problems and the authors' personal experience with 56 surgical cases]. 784 71

The development of two types of tumors in an animal survival-sacrifice experiment can be described by a Markov illness-and-death process with four unknown tumor transition rates and four unknown death rates. Due to the occult nature of tumors, these transition rates cannot be identified through the use of a completely nonparametric model. We propose a semiparametric model that assumes that the four tumor transition rates are proportional to each other and can be described by a known parametric function. We show that these tumor transition rates can be estimated using an ECM algorithm and that inferences about these parameters can be drawn using the likelihood ratio test. We illustrate this model and the algorithm with data from the ED01 study.
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PMID:Estimating multiple tumor transition rates based on data from survival-sacrifice experiments. 808 Oct 51

Immunohistochemical ABC method was used to study the distribution of fibronectin (FN), laminin (LN) and type I, III & IV collagens (Ic, IIIc, IVc) as well as estrogen and progesterone receptors (ER, PgR) in 20 breast carcinomas and 10 benign mammary lesions. LN and IVc were found in vascular and epithelial basement membranes (BMs), and FN was found in BMs and non-BMs. Ic and IIIc were only detected in stroma. LN, IVc and FN displayed continuous linear patterns in benign lesions where Ic and IIIc were sparsely and FN was intensively distributed. BMs in carcinomas were absent in varying degrees, Ic, IIIc and IVc exhibited heterogeneous staining and sparse FN distribution. No differences were noted in ECM staining patterns and ER & PgR levels in patients with and without lymph node metastases. The above data suggest that there is an obvious decrease of BM in breast cancer, and a heterogeneous change in Ic, IIIc and IVc due to stroma-tumor cell reactions, which may play important roles in limiting cancer growth. The immunodetection of BM changes in infiltrating ductal breast carcinoma does not help to evaluate the metastatic potential of tumors and is unrelated to the levels of ER and PgR.
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PMID:[Immunohistochemical detection of extracellular matrix in human breast carcinoma]. 816 85

Platelets have been hypothesized to contribute to tumor cell metastasis, but the underlying mechanism(s) remain unknown. We demonstrate here that one mechanism whereby platelets may facilitate metastasis is by potentiating tumor cell-induced endothelial cell retraction, a prerequisite for the extravasation of most tumor cell types. The integrity of cultured microvascular endothelial cell (CD3 cells) monolayers was perturbed by 12[S]-hydroxyeicosatetraenoic acid (12(S)-HETE), a lipoxygenase metabolite of arachidonic acid, as well as by tumor cells (i.e., Lewis lung carcinoma cells or 3LL). 3LL cells induced a concentration- and time-dependent retraction of the CD3 monolayers, as assessed by quantitative binding assays as well as by phase-contrast microscopy. In contrast, normal murine fibroblasts (3T3) did not induce endothelial cell retraction. 3LL cell-induced endothelial cell retraction was potentiated, in a dose- and time-dependent manner, by homologous murine platelets while platelets alone did not induce endothelial cell retraction. Platelet-enhanced, tumor cell-induced endothelial cell retraction was inhibited by treating either tumor cells or platelets with the lipoxygenase inhibitors nordihydroguaiaretic acid or N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP) as well as by PGI2 or its analogs iloprost and ZK96.480 (cicaprost), but not by the cyclooxygenase inhibitor aspirin (ASA). Tumor cells, upon adhesion to endothelium, initiated 12(S)-HETE biosynthesis, which was inhibited by pretreating tumor cells with BHPP but not with ASA. Additionally, 12(S)-HETE biosynthesis during tumor cell-endothelial cell adhesion was significantly enhanced by the addition of homologous platelets. Collectively, these results suggest that tumor cell-platelet-endothelial cell interactions lead to enhanced biosynthesis of 12(S)-HETE by tumor cells and/or platelets, which in turn induces endothelial cell retraction, thus facilitating tumor cell extravasation and metastasis.
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PMID:Enhanced endothelial cell retraction mediated by 12(S)-HETE: a proposed mechanism for the role of platelets in tumor cell metastasis. 826 84

The effects of aspirin (acetylsalicylic acid: ASA) on vessel behavior and tumor response were measured during and after photodynamic therapy (PDT). Changes to vessel constriction, macromolecular leakage, tumor interstitial pressure, and tumor response were examined. Animals were randomly placed into treatment groups and injected with 0-25 mg/kg Photofrin and given 0 or 135 J/cm2 light treatment. The light treatment was standardized to 75 mW/cm2 at 630 nm over a 30 min treatment interval (135 J/cm2). The treatment groups were further subdivided to receive Photofrin alone or Photofrin plus 100 mg/kg ASA. A cremaster muscle model in Sprague-Dawley rats was used to directly observe microvascular response and changes in vessel permeability to macromolecules. A tumor interstitial pressure model was designed to measure pressure changes in a chondrosarcoma tumor over time. This model indirectly measures macromolecular leakage, among other factors, in the tumor tissue. Groups of 10-20 rats were implanted subcutaneously with chondrosarcoma and were subjected to PDT to assess tumor response to the various treatments. Statistically significant differences in vessel leakage and changes in interstitial pressure were observed between animals given ASA plus PDT as compared to animals given PDT alone. The administration of ASA significantly inhibited venule leakage of albumin and reduced increases in interstitial pressure after treatment. The use of ASA had no effect on vessel constriction or tumor response after PDT. These findings suggest that the increases in vessel permeability observed during and after PDT, using Photofrin, do not significantly contribute to tumor response.
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PMID:The effects of aspirin on microvasculature after photodynamic therapy. 833 61

Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs.
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PMID:Aspirin use and risk of fatal cancer. 826 25

The metastatic phenotype is of extreme complexity. To complete all the stages of metastasis, the tumor cell must possess a whole series of functional abilities. Multiple biological markers are therefore needed to achieve a deeper understanding of the metastatic phenotype. In the present study we compared primary (PT) to metastatic tumor (MT) cells of two AKR lymphoma variants with respect to several cellular functions relevant to various steps of tumor dissemination. The MT cells of the TAU-44 variant had a higher capacity than the PT cells to attach to endothelial monolayers and ECM, exhibited a more elevated motility and a higher capacity to grow in the spleen as a metastatic target organ. However, the TAU-44-MT cells had a lower ability to grow in the kidney than the PT cells. The TAU-33-MT cells had a higher ability to attach to endothelial cells and to grow in both spleen and kidney but were less motile compared to PT cells. Metastatic cells showed, on the whole, higher ability to perform in most, but not all, stage-specific models than primary tumor cells.
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PMID:Metastasis-related cell functions in primary and metastatic tumor cells of AKR lymphoma. 862 Apr 73

In a retrospective analysis 385 patients with a histologically defined cranial meningioma were studied to analyze the impact of characteristic factors on morbidity and mortality after modern cranial meningioma surgery. Mortality was 4.2% one month and 7.3% six months after operation. 15.6% of the patients stayed more than one month in the hospital (defined as criteria of operative morbidity). Age, poor preoperative clinical condition (ASA score), intra- and postoperative bleeding and CSF disturbances were significantly associated with a subsequent decrease of quality of life. First symptoms like intracranial hypertension, seizures, aphasia and hemiparesis were correlated with an increase of postoperative Karnowsky index. Postoperative quality of life decreased in patients with optic and other cranial nerve disturbances significantly. Tumour size, location (exception: medial sphenoid wing) and histological diagnosis did not influence surgical outcome. This information may be useful in management decisions regarding asymptomatic meningiomas in elderly and high risk patients.
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PMID:Factors influencing morbidity and mortality after cranial meningioma surgery--a multivariate analysis. 873 7


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