يعرض 1 - 10 نتائج من 10 نتيجة بحث عن '"Prostaglandin-Endoperoxide Synthases"', وقت الاستعلام: 1.04s تنقيح النتائج
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    المؤلفون: Lundholm, Kent, 1945, Daneryd, Peter, 1957, Bosaeus, Ingvar, 1950, Körner, Ulla, 1944, Lindholm, Elisabet, 1946

    المصدر: Cancer. 100(9):1967-77

    الوصف: BACKGROUND: The role of nutrition in the palliative treatment of patients with malignancy-related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition-focused patient care could improve integrated whole-body metabolism and functional outcome in unselected weight-losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]-inhibitory) treatment along with erythropoietin (EPO) support. METHODS: Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15-40,000 units per week) along with specialized, nutrition-focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient-by-patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole-body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2-30 months after treatment initiation). Statistical analyses were performed on 'intention-to-treat' and 'as-treated' bases. RESULTS: Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention-to-treat analysis revealed an improvement in energy balance for nutritionally supported patients (P < 0.03); no other significant differences in outcome between study patients and control patients were observed. As-treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P < 0.01), which was accompanied by improved energy balance (P < 0.001), increasing body fat (P < 0.05), and a greater maximum exercise capacity (P < 0.04). A trend toward increased metabolic efficiency at maximum exercise (P < 0.06) for study patients relative to control patients also was observed. CONCLUSIONS: The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease.

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    المصدر: Cancer. 98:1465-1472

    الوصف: BACKGROUND Although increased expression of cyclooxygenase-2 (COX-2) has been described in association with a variety of neoplasms, including tumors of astrocytic derivation, limited data are available on COX-2 expression in oligodendrogliomas. METHODS The current study retrospectively reviewed 53 oligodendrogliomas and 7 oligodendroglioma-predominant oligoastrocytomas (mixed gliomas) for COX-2 expression and MIB-1 proliferative index (by immunohistochemistry) and for chromosome 1p status (by fluorescence in situ hybridization). RESULTS Patients included 35 males and 25 females, with a mean age of 41 years (range, 12–73 years) at the time of surgery. Forty-four tumor specimens were classified as World Health Organization (WHO) Grade II neoplasms and 16 as WHO Grade III tumors. MIB-1 labeling indices (marker of cell proliferation) ranged from 0 to 22.3 (mean 4.5). Twenty-eight tumor specimens demonstrated allelic loss on chromosome 1p. Positive staining was observed in 17 tumor specimens with COX-2 antibody. COX-2–positive tumor specimens were also evaluated with CD68 (macrophage/microglial cell marker) by coimmunolabeling to confirm that the observed COX-2 immunostaining was not due to immunoreactive macrophages or microglial cells. COX-2 expression, lack of allelic loss at chromosome 1p, and high proliferation indices were associated with decreased survival (P = 0.002, P = 0.009, and P = 0.015, respectively). No correlation with outcome was found with patient gender, age at diagnosis, or histologic grade. CONCLUSIONS Chromosome 1p, COX-2 immunoreactivity, and MIB-1 labeling indices correlated with outcome and were associated with decreased survival. There was not a one-to-one correspondence between COX-2 immunoreactivity and lack of allelic loss at chromosome 1p. Tumors with expression of COX-2 by immunohistochemistry may, in theory, benefit from treatment with therapeutic agents that inhibit COX-2. Cancer 2003;98:1465–72. © 2003 American Cancer Society. DOI 10.1002/cncr.11632

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    المصدر: Cancer. 97:2814-2821

    الوصف: BACKGROUND Cyclooxygenase-2 (COX-2) plays a role in progression of colon, breast, pancreas, and lung carcinomas. The authors investigated COX-2 expression in pituitary tumors. METHODS Expression of COX-2 was evaluated in 164 surgically removed human pituitary tumors. Correlation of COX-2 with MIB-1, a cell proliferation marker, as well as angiogenesis, patient age, gender, tumor type, size, invasiveness, and metastatic potential was investigated. RESULTS Cyclooxygenase-2 immunoreactivity was confined to the cytoplasm of tumor cells, whereas the nuclei were unlabeled. Few normal peritumoral adenohypophysial cells showed slight COX-2 cytoplasmic immunoreactivity. The staining intensity and the percentage of immunopositive cells were higher in tumors. Most pituitary tumors (96%) were COX-2–immunopositive. Expression was strong in 60 (44%), moderate in 39 (28%), and weak in 32 (24%). Male gonadotroph adenomas and null cell adenomas showed a high level of COX-2 expression. Growth hormone-producing adenomas, prolactin-producing adenomas, thyrotropic hormone-producing adenomas, female gonadotroph adenomas, silent adrenocorticotropic hormone-producing adenomas, and silent subtype 3 adenomas had a low level of COX-2 expression. Significant correlation was demonstrated with patient age, but not with tumor size, invasiveness, and MIB-1 labeling indices. Expression was medium to high in 76% of macroadenomas and in only 45% of microadenomas. Strong correlations were noted with angiogenesis markers, such as microvessel density and surface density. CONCLUSIONS Correlation with angiogenesis suggests that COX-2 may be involved in the regulation of angiogenesis in pituitary tumors. Phamacologic inhibition of COX-2 activity might suppress angiogenesis in pituitary tumors and may provide a novel approach for medical therapy. Cancer 2003;97:2814–21. © 2003 American Cancer Society. DOI 10.1002/cncr.11387

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    المصدر: Cancer. 91:1876-1881

    الوصف: BACKGROUND Nonsteroidal anti-inflammatory drugs may reduce the incidence of intestinal carcinoma, presumably through inhibition of cyclooxygenase-2 (COX-2). The authors correlated tumor expression of COX-2 with clinicopathologic features in tissues from patients with gastric carcinoma. METHODS Thirty-three surgical specimens, including carcinomas and corresponding noncancerous mucosa, were sampled. Reverse transcription-polymerase chain reaction analysis was performed concomitantly for COX-1 and COX-2. A COX-2 index was determined from the band density ratio of COX-2 to constitutively expressed COX-1. Immunohistochemical staining with COX-2 antibody and routine histologic assessment were performed in the same specimens. RESULTS The COX-2 index in gastric carcinoma was significantly higher than in normal mucosa (3.4 ± 0.7 vs. 2.2 ± 0.7; P < 0.05). COX-2 indices were significantly higher in gastric carcinoma tissues with deep invasion; indices for pT1, pT2, pT3, and pT4 carcinomas were 0.8 ± 0.3, 2.8 ± 0.5, 4.3 ± 1.0, and 8.8 ± 5.5, respectively (P < 0.05). Immunohistochemistry demonstrated COX-2 protein diffusely in the cytoplasm of tumor cells but not in surrounding stroma or in noncancerous mucosa. CONCLUSIONS COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with depth of invasion, indicating that COX-2 is involved in the growth of gastric carcinoma. Cancer 2001;91:1876–81. © 2001 American Cancer Society.

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    المصدر: Cancer. 89:589-596

    الوصف: BACKGROUND Nonsteroidal antiinflammatory drugs inhibiting cyclooxygenase (COX) enzyme activity in both its constitutive (COX-1) and inducible (COX-2) isoforms were shown also to inhibit the development of colon carcinoma in animal models. COX-2 is an inducer of angiogenesis of new blood vessels. The expression of COX-1 and COX-2 in prostate tissues from patients with prostate carcinoma was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. METHODS Tumor specimens were obtained from 28 prostate carcinoma (PC) patients, 8 benign prostatic hyperplasia (BPH) patients, 1 prostatic intraepithelial neoplasia (PIN) patient, and 8 specimens of normal prostate tissue (NP). Affinity-purified COX-1 and COX-2 antibodies were used in immunochemistry. RESULTS Very weak expression of COX-1 and marked expression of immunoreactive COX-2 in tumor cells was obtained. In contrast, expression of both isoforms was very weak in all cases of BPH and in the NP tissues. Immunoreactive COX-1 also was very weak in all cases of benign tissues. The extent and intensity of immunoreactive COX-2 polypeptides in tumor cells was statistically much greater than those of cells from BPH. Immunostaining with normal rabbit immunoglobulin G was completely negative. By RT-PCR analysis, enhanced expression of COX-2, but not COX-1, was observed in PC tissue. BPH displayed faint expression of COX-2. CONCLUSIONS The results of the current study demonstrated that human prostate carcinoma cells generated COX-2, and that COX-2 might play an important role in the proliferation of prostate carcinoma cells. These findings suggest that inhibition of COX-2 development may lead not only to inhibition of the proliferation and metastasis of prostate carcinoma but also to the inhibition of prostate carcinogenesis. Cancer 2000;89:589–96. © 2000 American Cancer Society.

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    المصدر: Cancer. 100(9)

    الوصف: The role of nutrition in the palliative treatment of patients with malignancy-related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition-focused patient care could improve integrated whole-body metabolism and functional outcome in unselected weight-losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]-inhibitory) treatment along with erythropoietin (EPO) support.Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15-40,000 units per week) along with specialized, nutrition-focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient-by-patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole-body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2-30 months after treatment initiation). Statistical analyses were performed on 'intention-to-treat' and 'as-treated' bases.Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention-to-treat analysis revealed an improvement in energy balance for nutritionally supported patients (P0.03); no other significant differences in outcome between study patients and control patients were observed. As-treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P0.01), which was accompanied by improved energy balance (P0.001), increasing body fat (P0.05), and a greater maximum exercise capacity (P0.04). A trend toward increased metabolic efficiency at maximum exercise (P0.06) for study patients relative to control patients also was observed.The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease.

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    المصدر: Cancer. 94(5)

    الوصف: BACKGROUND The objective of this study was to investigate COX-2 expression in intraductal papillary-mucinous tumor of the pancreas (IPMT) using immunohistochemical staining (IH) and in situ hybridization (ISH). METHODS Immunohistochemical staining of COX-2 was performed using samples from 42 patients with IPMT (hyperplasia, 10; adenoma, 13; noninvasive adenocarcinoma, 13; invasive adenocarcinoma, 6) and from 10 patients with ductal pancreatic adenocarcinoma, 10 with chronic pancreatitis, and 6 normal pancreatic tissues as controls. Also, COX-2 was determined in five patients with IPMT noninvasive adenocarcinoma, in whom all histologic types, hyperplasia, adenoma, and adenocarcinoma were observed in the same excised specimens. Furthermore, IH of proliferating cell nuclear antigen (PCNA) was performed, and the labeling index (LI) was calculated to investigate the correlation with COX-2. To confirm COX-2 mRNA, the authors performed ISH in 20 IPMT patients. RESULTS COX-2 was positive in 0%, 0%, and 10% of pancreatic duct epithelial cells from normal pancreatic tissue, chronic pancreatitis, and IPMT hyperplasia, respectively. Whereas it was positive in 69%, 77%, 67%, and 80% of IPMT adenoma, IPMT noninvasive adenocarcinoma, IPMT invasive adenocarcinoma, and ductal pancreatic adenocarcinoma, respectively, showing significant differences between IPMT hyperplasia and IPMT adenoma or IPMT adenocarcinoma (noninvasive and invasive adenocarcinoma). In the same patient, COX-2 was negative in the hyperplasia region but positive in adenoma and adenocarcinoma regions, showing results reflecting the progression of the disease. In the COX-2 negative group, PCNA-LI was 19.2 ± 17.9%, and 33.5 ± 15.7% in the positive group, a significant difference. On ISH, COX-2 mRNA was expressed in three of four and seven of eight COX-2 positive patients with IPMT adenoma and adenocarcinoma, respectively. CONCLUSIONS COX-2 was highly expressed in adenoma and adenocarcinoma in IPMT, showing a relation to the histologic grade of IPMT. Cancer 2002;94:1565–73. © 2002 American Cancer Society. DOI 10.1002/cncr.10358

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    المصدر: Cancer. 94(4)

    الوصف: Cyclooxygenase (Cox) is the main target enzyme for the nonsteroidal antiinflammatory drugs that have been shown to suppress carcinogenesis in both experimental models and epidemiologic studies.To evaluate its utility as an intermediate biomarker in bronchial chemoprevention trials, the authors examined Cox 1 and Cox 2 expression in normal and premalignant bronchial epithelial cells and nonsmall cell lung carcinoma (NSCLC) samples using an immunohistochemical staining technique. Included in the current study were 101 NSCLC samples and 77 bronchial biopsy samples obtained from 15 healthy smokers.In the normal bronchial epithelium, Cox 2 expression was found to be completely negative whereas Cox 1 expression was noted in a few scattered cells. The areas of basal cell hyperplasia and squamous metaplasia demonstrated the same pattern. There were relatively more Cox 2-positive tumors, as defined by positive staining in10% of tumor cells, than Cox 1-positive tumors (30 of 101 tumors [30%] vs. 14 of 101 tumors [14%]; P = 0.01). When tumor types were considered, there were more Cox 2-positive adenocarcinomas compared with squamous cell carcinomas (21 of 51 adenocarcinomas [41%] vs. 9 of 46 squamous cell carcinomas [20%]; P = 0.03). In contrast, fewer adenocarcinomas tended to show Cox 1 expression compared with squamous cell carcinomas (4 of 51 adenocarcinomas [8%] vs. 9 of 46 squamous cell carcinomas [20%]; P = 0.14). Although smokers tended to have more Cox 2-positive tumors than nonsmokers (29 of 91 tumors in the smokers [32%] vs. 1 of 10 tumors in the nonsmokers [10%]; P = 0.15), there was no statistically significant relation found between Cox 1 or Cox 2 expression and smoking status or prognostically significant clinicopathologic features.The results of the current study suggest that Cox 1 and Cox 2 expression may not be a useful intermediate biomarker in bronchial chemoprevention trials. Nevertheless, considering the patterns of Cox 1 and Cox 2 expression in tumor cells, Cox expression status may be a useful parameter when designing treatment strategies for a subset of NSCLC patients.

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    المصدر: Cancer. 92(1)

    الوصف: BACKGROUND Expression of the inducible form of cyclooxygenase (COX)-2 is known to correlate with development of transitional cell carcinoma (TCC) of the human urinary bladder. However, the clinical significance of COX-2 expression with respect to clinicopathologic findings and patient survival is unknown. METHODS COX-2 expression was examined immunohistochemically in tumor tissues obtained from 108 patients who underwent radical cystectomy for TCCs, without knowledge of clinicopathologic findings. Correlation between COX-2 expression and clinicopathologic findings and patient survival was determined. RESULTS COX-2 expression was detected in 34 of 108 (31%) tumors but in none of 10 normal uroepithelial samples. Univariate logistic regression analysis showed a significant correlation between COX-2 expression and local invasion, infiltration pattern, lymphatic invasion, and venous invasion. However, multivariate logistic regression analysis revealed that only local invasion correlated significantly with COX-2 expression (P = 0.047). Cox proportional hazards regression analysis showed that both local invasion (P = 0.008) and lymph node metastasis (P = 0.001) were independent prognostic factors; however, COX-2 expression (P = 0.16) was not. CONCLUSIONS The authors showed that COX-2 overexpression plays a role in development and invasion of TCCs, but not prognosis of patients with TCC. COX-2 inhibitors may be useful for chemoprevention of TCCs and treatment of invasive disease. Cancer 2001;92:188–93. © 2001 American Cancer Society.

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    المصدر: Cancer. 91(2)

    الوصف: BACKGROUND Cyclooxygenase-2 (COX-2) is thought to be linked to carcinogenesis; however, very little is known about its expression in pancreatic neoplasms. The authors studied the expression of COX-2 in human pancreatic neoplasms and investigated the effect of COX inhibitors on the growth of human pancreatic carcinoma cells. METHODS Expression of COX-2 protein was immunohistochemically examined in 42 human pancreatic duct cell carcinomas (PDCs) and in 29 intraductal papillary mucinous tumors (IPMTs [adenomas, 19; carcinomas, 10]) of the pancreas that were resected surgically at the National Cancer Center Hospital in Tokyo. The growth of four human pancreatic carcinoma cell lines also was evaluated in the presence of COX inhibitors. RESULTS Marked COX-2 expression was observed in 57% (24 of 42) of PDCs, in 58% (11 of 19) of adenomas, and in 70% (7 of 10) of adenocarcinomas of IPMTs. However, there was no correlation between COX-2 expression and clinicopathologic indices of the patients. All four pancreatic cancer cell lines expressed COX-2 protein weakly or strongly, and the inhibitory effect of aspirin on cell growth was correlated with the expression of COX-2. CONCLUSIONS COX-2 was expressed in adenomas of IPMTs as well as in carcinomas and might have played a role in the development of pancreatic tumors. In this study, COX inhibitors, as nonsteroidal anti-inflammatory drugs, were shown to be possible preventive agents against pancreatic neoplasms. Cancer 2001;91:333–8. © 2001 American Cancer Society.