Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined.
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PMID:Cardiac disturbances during the administration of taxol. 167 81

Superoxide dismutases (SOD) and their changes in diabetes, aging, ischemia and cancer were studied, Cu, Zn-SOD undergoes glycation reaction in vitro and in vivo and loses its activity by formation of Amadori compounds. Two lysine residues of Cu, Zn-SOD, Lys-122 and Lys-128 are primary glycated sites which are located on the surface of the molecule. The sites are also located on the active site liganding loop which plays a major role in the activity. The glycated Cu, Zn-SOD increased in the red cells of diabetic patients, especially those with diabetic complications. Mn-SOD appears in the serum of patients with acute myocardial infarction in a biphasic manner. The enzyme appears in sera 16 hr and 108 hr after the attack as determined by ELISA. The Mn-SOD levels are also increased in the serum of patients with epithelial ovarian cancer and it is a good marker for detecting and monitoring this cancer. Mn-SOD may play an important role in the ischemic and cancer tissues.
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PMID:[Superoxide dismutases: significances in aging, diabetes, ischemia and cancer]. 223 47

Heat shock proteins (Hsp) are cytoplasmic proteins that act as molecular chaperones for protein molecules in various intra-cellular processes. They play an important role in protein-protein interactions, including folding and conformation, and prevention of inappropriate protein aggregation. They are called "heat shock proteins" since they were first discovered in cells exposed to high temperatures. However, their synthesis is also accentuated under other stress conditions, such as exposure of the cell to inflammation, infection, ischemia, toxins, cytotoxic drugs and malignant transformation. Hsp have been classified into families according to their molecular weight. In ovarian carcinoma, over-expression of Hsp27 was associated with increased resistance to chemotherapy and a worse prognosis. In endometrial carcinoma, over-expression of Hsp70 was associated with poorly differentiated tumors and a worse prognosis, whereas over-expression of Hsp27 and Hsp90 were associated with well-differentiated tumors and better prognosis. The association between increasing expression of Hsp90 and better differentiation and prognosis seems to reflect high levels of sex steroid receptors in well-differentiated endometrial carcinomas. In cervical carcinoma, the presence of Hsp70 was associated with a worse outcome. Since Hsp are highly antigenic, their property to bind with tumor proteins and proteins produced by viruses may be used for the development of vaccines against cancers and viral diseases. It is speculated that examination of the lower genital tract secretions for IgA antibodies against Hsp will contribute to early detection of malignancies. Since Hsp may affect the growth of the tumor and its response to chemotherapy, it is speculated that using drugs that inhibit Hsp in combination with conventional chemotherapy may contribute to the improvement of the treatment results.
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PMID:[Heat shock proteins and malignancies of the female genital tract]. 1247 32

Adrenomedullin (ADM) is a potent hypotensive peptide produced by macrophages and endothelial cells during ischemia and sepsis. The molecular mechanisms that control ADM gene expression in tumor cells are still poorly defined. It is known, however, that hypoxia potently increases ADM expression by activation of the transcription factor complex hypoxia inducible factor 1 (HIF-1). Proinflammatory cytokines produced by tumor invading macrophages likewise activate expression of ADM. Herein, we show that apart from hypoxia, the proinflammatory cytokine interleukin 1beta (IL-1beta) induced the expression of ADM mRNA through activation of HIF-1 under normoxic conditions and enhanced the hypoxia-induced expression in the human ovarian carcinoma cell line OVCAR-3. IL-1beta significantly increased accumulation and nuclear translocation of HIF-1alpha under normoxic conditions and amplified hypoxic HIF-1 activation. IL-1beta treatment affected neither HIF-1alpha mRNA levels nor the hydroxylation status of HIF-1alpha and, thus, stability of the protein. Instead cycloheximide effectively prevented the increase in HIF-1alpha protein, indicating a stimulatory effect of IL-1beta on HIF-1alpha translation. Finally, treatment of HIF-1alpha with short interfering RNA revealed a significant role for HIF-1 in the IL-1beta-dependent stimulation of ADM expression.
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PMID:The proinflammatory cytokine interleukin 1beta and hypoxia cooperatively induce the expression of adrenomedullin in ovarian carcinoma cells through hypoxia inducible factor 1 activation. 1593 Feb 87

The association between malignancy and venous thrombotic events is well established. However, arterial thrombosis among cancer patients is extremely rarely reported. There are several mechanisms of arterial thrombosis or embolism in malignancy. Important mechanisms in arterial thrombogenesis are shear stress-induced platelet aggregation and platelet-derived microparticles. Both of these are induced by major abdominal surgery. A major abdominopelvic surgery followed by adjuvant platinum-based combined chemotherapy is routinely performed for epithelial ovarian cancer which is the leading cause of death among all gynecologic malignancies. These patients have a greater risk of arterial thrombosis at the postoperative period. If the affected arteries are relatively larger, clinical findings will be evident due to limb ischemia or fatal organ infarctions. However, thrombosis of the small arteries disturbs the tissue circulation which is extremely important for the chemotherapeutic agents to reach the residual tumor cells. When the thrombosis of small arteries is prevented, these drugs will reach all of the residual macroscopic or microscopic tumoral tissues and so the prognosis of the patients may be improved. Therefore, we hypothesize that anti-platelet therapy with aspirin is needed to be initiated during the postoperative period of epithelial ovarian cancer patients and be continued as long as chemotherapy goes on. Such an approach might have a role in optimizing the oncological prognosis of these patients via increasing the effectiveness of cytotoxic therapy since some of the recurrences may be caused by some microscopic tumor foci which were not affected by cytotoxic drugs because of subclinical small arterial thromboses.
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PMID:Use of anti-thrombotic agents during chemotherapy for epithelial ovarian cancer. 1644 52

The ovulatory process is extraordinary in that it constitutes a hormone-induced injury. Gonadotropin delivered via the follicular vascular wreath stimulates secretion of plasminogen activator by contiguous ovarian surface epithelial cells. A consequent elevation in interstitial plasmin activates collagenases and cleaves tumor necrosis factor alpha from its anchors on endothelium. Collagen fibril degradation and cellular death at the apex of the preovulatory follicle are hallmarks of impending ovulation. Follicular contractions rupture the weakened fabric at the apex, and the ovum, which has been disconnected from the underlying granulosa, is expelled; these components of the cascade are prostaglandin-mediated. Ovulation is required for fertility; unfortunately, it imparts a cancer risk to the ovarian surface epithelium. DNA-damaging reactive oxygen species are generated by inflammatory cells attracted into the vicinity of the ovulatory stigma. An ischemia-reperfusion flux coincident with ovulation and wound repair also contributes to genotoxicity. Potentially mutagenic lesions in DNA are normally reconciled by TP53 tumor suppressor-dependent cell-cycle arrest and base excision repair mechanisms; it is a unifocal escape that could be problematic. Epithelial ovarian cancer is a deadly insidious disease because it typically remains asymptomatic until it has metastasized to vital abdominal organs.
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PMID:Mechanisms and pathobiology of ovulation. 2175 73

Calpains, also called calcium activated neutral proteases (CANP), are expressed ubiquitously. They are intracellular, non-lysosomal cytoplasmic cysteine endopeptidases. Calcium is required for their activation. Their endogenous specific inhibitor is calpastatin, which is expressed ubiquitously and coexists within cells besides calpain. When calcium is present, calpastatin and calpain attach to each other inhibiting the protease. The calpain system plays an important role in many processes including apoptosis, necrosis, ischemia formation and exocytosis. So far, many reports exist on studies about the influence of calpains in different tumors (skin, breast, renal cell and prostate cancers). The role of calpains in pathogenesis or further tumor progression has always been proved in related studies, but their exact function could not be demonstrated. So far, no studies on calpains being involved in the pathogenesis of ovarian cancer have been published. In our study we focused on the expression of the enzymes calpain 1, calpain 2 and their inhibitor calpastatin in normal and malign ovarian tissue. Therefore, we performed immunohistochemical stainings of paraffin slices and evaluated staining intensity (SI), percentage of positive cells (PP) and immunoreactive score (IRS). We evaluated the correlation between enzyme expression in malign and benign ovarian tissues. In malignant ovarian tissue, we found decreased expression, staining intensity and immunoreactive score of calpastatin. With higher grading of the ovarian carcinoma, staining intensity and immunoreactive score of calpain 1 decreased. Staining intensity of calpain 2 in ovarian carcinoma decreased with increasing lymph node status. We clearly demonstrated differences between enzyme expressions in malign and benign tissue. This study could not find any specific function of calpains. Only few studies in the literature have been found that deal with calpain evaluation of ovarian cancer. Additional studies including more patients are required to elucidate the functional role and impact of calpain in tumors in detail.
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PMID:Immunhistochemical analysis for expression of calpain 1, calpain 2 and calpastatin in ovarian cancer. 2233 24

We present an unusual case of advanced ovarian carcinoma with postoperative complications of ischemia and perforation of the rectum as a result of tumor embolism. The interval progression from ischemia to infarction of the rectum was captured in repeated sigmoidoscopies. A brief discussion on tumor embolism and management of this case is also included.
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PMID:An Unusual Case of Ovarian Carcinomatosis with Microscopic Tumor Embolism Leading to Rectal Ischemia and Perforation. 2946 44