Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-7869 (R-flurbiprofen) is a single enantiomer of a racemic nonsteroidal anti-inflammatory drug. E-7869 does not inhibit either cyclooxygenase-1 or cyclooxygenase-2. We used the transgenic adenocarcinoma mouse prostate (TRAMP) mouse, a prostate cancer model, to evaluate the effect of this drug on prostate cancer progression. Sixty 12-week-old male TRAMP mice were placed randomly into five groups. The animals were treated by daily oral gavage with vehicle (1% carboxymethylcellulose) or E-7869 for 18-weeks. During the course of the study, two diets were used. Three groups (vehicle, 15-mg/kg, and 20-mg/kg drug treatments) received a Teklad diet containing 2.4% saturated fat [a high saturated fat (HSF) diet], and two groups (vehicle and 20 mg/kg drug treatment) received an AIN-93G diet containing 1.05% saturated fat [a low saturated fat (LSF) diet]. At necropsy, the urogenital system and periaortic lymph nodes were removed and weighed. The prostate lobes, seminal vesicles, lungs, and periaortic lymph nodes were preserved and sectioned for histological evaluation. The lung and periaortic lymph nodes were graded as to the presence (+) or absence (-) of metastasis; the urogenital tissues were graded on a 1-6 scale for degree of neoplasia/carcinoma. For both diets, the urogenital wet weights and lymph node wet weights in the 20-mg/kg treatment groups were significantly lower as compared to vehicle control groups. In addition, treatment with 20 mg/kg E-7869 in the LSF diet group resulted in a significantly lower primary tumor incidence (P < 0.05) and reduced incidence of metastasis. In this treatment group, the reduced incidence of metastasis was not statistically significant because the LSF diet itself resulted in a remarkably lower incidence of metastasis in the vehicle control group (10% LSF versus 40% HSF). Treatment with 20 mg/kg E-7869 on the HSF diet resulted in a significantly lower incidence of metastasis (P < 0.05) and a reduction in the primary tumor incidence. These results suggest that E-7869 is a promising chemopreventive and treatment for human prostate cancer.
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PMID:E-7869 (R-flurbiprofen) inhibits progression of prostate cancer in the TRAMP mouse. 1078 85

Overexpression of cyclooxygenase-2 (COX-2), characterizes tumors with high potential for local invasion and lymph node involvement. We investigated the expression of COX-2 in primary tumors and metastatic regional lymph nodes (TDL) from untreated and chemotherapy treated cervical cancer, as well as vulvar cancer. Immunostaining of COX-2, expressed as values of COX-2 intensity density (COX-2 IDV) was performed on 57 metastatic TDL and 24 corresponding primary rumors from 14 cervical and 9 vulvar cancer patients admitted to the Department of Obstetrics and Gynecology, Catholic University of Rome. In 6 locally advanced cervical cancer tissue samples, from both primary tumor and TDL, were obtained after chemotherapy treatment. In untreated cervical cancer, COX-2 IDV in tumor cells from positive TDL were significantly lower (median 0.69, range 0.22-0.92) than those from primary tumors (median = 3.84, range 0.19-7.67) (p=0.011). In cervical cancer exposed to chemotherapy, COX-2 IDV in tumor cells from positive TDL were significantly lower (median = 2.06, range 1.48-6.52) than those from primary tumors (median = 6.4, range 4.5-13.7) (p=0.037). In vulvar cancer COX-2 IDV in tumor cells from positive TDL were lower (median = 0.39, range 0.02-6.09) than those from primary tumors (median = 2.49, range 0.71-8.10) (p=0.04). In conclusion, we showed that COX-2 expression is down-regulated in cervical and vulvar tumor cells invading the regional lymph nodes with respect to primary tumors, thus emphasizing the need for deeper insight into the tissue specific relation between tumor cells and node microenvironment.
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PMID:Cyclooxygenase-2 expression in lymph node metastasis of cervical and vulvar cancer. 1453 99

Medullary thyroid cancer (MTC) is a C cell neoplasm-secreting calcitonin. Surgery remains the only treatment as the primary tumor and metastases resist radio- and chemotherapies. MTC produces high amounts of prostaglandins (PGs). Nonsteroidal antiinflammatory drugs have an antitumoral effect, generally related to the decrease of PG levels. We assessed the therapeutic potential of indomethacin in a model of human (TT cells) tumors in nude mice. Indomethacin (1.5 or 2.0 mg/kg body weight.d for 7 wk) inhibited tumor volume by 49 or 77%, respectively, and decreased the plasma level of CT. Although the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling method revealed few apoptotic nuclei, the number of proliferating cells was significantly decreased (Ki-67 antigen study). Immunological effector recruitment and vascular network was not modified by treatment. The inducible synthesis enzyme, cyclooxygenase-2 (COX-2), was revealed only in infiltrating cells, both in treated and control tumors. The expression of the constitutive synthesis enzyme COX-1 was diminished, and the expression of 15-prostaglandin dehydrogenase, the key enzyme catabolizing PGs, was increased in treated tumors. Thus, our results demonstrated the potential of indomethacin, inhibitor of COX-1 and COX-2, to prevent MTC growth. The synthesis enzyme, COX-1, and the catabolism enzyme 15-prostaglandin dehydrogenase, could be involved in MTC development.
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PMID:Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase. 1473 30

Cyclooxygenase-2 (COX-2) has been identified as a potential target for prevention and therapy of human colorectal cancers (CRC) and other cancers. Because right-sided colon cancers (RSCCs) exhibit clinicopathologic and genetic differences from left-sided colorectal cancers (LSCRCs), determination of COX-2 status in these subsets of CRCs may be clinically relevant in designing COX-2 inhibitor trials for CRC and in subsequent assessment of objective therapeutic response to such therapy. Thirty-six primary CRC resection specimens (18 left, 18 right) from 36 patients were evaluated. Representative tumor sections were subjected to immunohistochemical analysis of COX-2. A semiquantitative system was used to score cytoplasmic COX-2 immunostaining. The tumors were considered COX-2 positive if more than 10% tumor cells showed COX-2 staining. Clinicopathologic and COX-2 data were compared for LSCRCs versus RSCCs. All 18 LSCRCs and 13 of 18 (72%) RSCCs were well to moderately differentiated. Overall rates of COX-2 positivity for the LSCRCs versus RSCCs were 67% (12 of 18) and 33% (6 of 18), respectively (P = 0.04). Furthermore, 11 of 12 (92%) COX-2 positive LSCRCs and 3 of 6 (50%) COX-2 positive RSCCs were stage II-IV at resection. All 12 COX-2 positive LSCRCs were associated with advanced primary tumor and 4 of 12 (33%) LCRCs had distant metastases. These associations could not be evaluated for the RSCCs because of the limited number of COX-2 positive cases. The more frequent expression of COX-2 in LSCRCs as compared with RSCCs supports the hypothesis that COX-2 expression may be related to genetic alterations specific to right- or left-sided CRCs. Further studies are needed to elucidate such relationships. Our data also suggest that stratification of patients with CRC into right- and left-sided subsets may be important in optimal patient selection for COX-2 inhibitor therapy and for subsequent assessment of objective therapeutic response.
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PMID:Cyclooxygenase-2 expression in right- and left-sided colon cancer: a rationale for optimization of cyclooxygenase-2 inhibitor therapy. 1502 97

Large, randomized trials have been conducted in the primary prevention of lung cancer using micronutrients or derivative agents for which epidemiological data suggested a potential role in lung cancer prevention. The disappointing primary prevention trials of beta-carotene, alpha-tocopherol, and retinyl palmitate have led to the development of a more compact, biomarker-driven series of translational trials of lung cancer prevention that target reversal of premalignancy as the primary end point. Serial trials of 13-cis-retinoic acid (isotretinoin) and other retinoids have failed to show a difference in reversal of premalignancy in active smokers or in second primary tumor prevention. However, a trial of 9-cis-retinoic acid, a pan retinoid/rexinoid agonist, showed up-regulation of retinoic acid receptor beta (RAR-beta), a potentially important intermediate marker of response in lung cancer premalignancy. Other planned or ongoing trials currently target important molecular markers of lung carcinogenesis and progression including cyclooxygenase-2, the ras-signaling pathway through farnesyl transferase inhibitors, and the tyrosine kinase/epidermal growth factor receptor pathway (gefitinib, erlotinib). Early results of bioadjuvant trials in head and neck cancer suggest that combination chemoprevention will ultimately be an important option.
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PMID:Molecularly targeted approaches to the chemoprevention of lung cancer. 1521 68

Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in the synthesis of prostaglandins. It is over-expressed in multiple cancers and has been associated with diminished tumor immunity. Dendritic cells (DCs) are considered candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness against established tumors. In this study, we evaluated the effect of short-term administration of the selective COX-2 inhibitor celecoxib on the efficacy of DC-based vaccines in preventing and treating established 4T1 murine mammary tumors. We show that dietary celecoxib alone significantly suppresses the growth of primary tumors and the incidence of lung metastases in the prophylactic setting but is less effective against pre-established tumors. However, we demonstrate that celecoxib administered after primary tumor establishment synergizes with tumor lysate-pulsed DC and the adjuvant, GM-CSF, to improve the antitumor immune response by suppressing primary tumor growth and markedly reducing the occurrence of lung metastases. This triple combination therapy elicits a tumor-specific immune response evidenced by elevated IFN-gamma and IL-4 secretion by CD4+ T cells and results in increased infiltration of CD4+ and CD8+ T cells to the tumor site. In addition, dietary celecoxib inhibits angiogenesis evidenced by decreased vascular proliferation within the tumor and serum vascular endothelial growth factor levels. These studies suggest that short-term celecoxib therapy in combination with DC vaccines may be safely used for treating metastatic breast cancer.
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PMID:Short-term dietary administration of celecoxib enhances the efficacy of tumor lysate-pulsed dendritic cell vaccines in treating murine breast cancer. 1633 15

A new human malignant rhabdoid tumor (MRT) cell line (designated FRTK-1) was established from MRT of the kidney of an 18-month-old boy. The cell line is maintained for over 24 months with more than 100 passages. FRTK-1 cells in vitro showed 2 different growth patterns, adherent and non-adherent patterns. The FRTK-1 cells showed the same morphological and immunophenotypical characteristics as primary tumor cells of kidney. Cytogenetic and molecular analyses revealed a non-sense mutation in the hSNF5/INI1 gene and loss of expression of hSNF5/INI1 gene product protein. Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were expressed in the FRTK-1 cells. Until now, there has been no report of MRT cell lines with expression of COX-2. Therefore, FRTK-1 cell line might be useful for investigating biological behavior and developing new molecular targeting antitumor drugs for MRT with expression of EGFR or COX-2.
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PMID:Establishment and characterization of a new cell line, FRTK-1, derived from human malignant rhabdoid tumor of the kidney, with overexpression of epidermal growth factor receptor and cyclooxygenase-2. 1682 Sep 1

We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.
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PMID:Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO. 1688 1

Increased cyclooxygenase-2 expression has been reported to be a poor prognostic indicator in a number of cancers. In this study we investigated the relationship between COX-2 expression in squamous cell carcinoma of the esophagus and tumor characteristics and patient survival. The study group consisted of 90 men and 48 women who underwent esophagectomy for squamous cell carcinoma of the esophagus between October 1984 and May 1985. COX-2 expression was measured by immunohistochemistry in 138 primary cancers, 23 metastatic lymph nodes and 21 normal esophageal stumps. The relationship between the extent of staining for COX-2 and clinicopathological features and survival was determined. The extent of staining for COX-2 in both primary and metastatic cancers was higher than in normal squamous epithelia (P = 0.002 and P < 0.0001 respectively), and the grade of staining in the primary tumor correlated positively with the finding of lymph node metastases (P = 0.03). The 5-year survival rate in patients with less than 10% COX-2 positive cells was 47.5% compared to 23.2% in patients with more than 10% COX-2 positive cells (P = 0.0036). The relationship between survival and COX-2 staining was not due to COX-2 being a surrogate marker for TNM stage. Our results show that the expression of COX-2 is elevated in squamous cell carcinoma of the esophagus compared to normal epithelium and correlates with lymph node metastases. Survival was longer in those patients whose tumors expressed lower levels of COX-2.
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PMID:Cyclooxygenase-2 expression in squamous cell carcinoma of the esophagus. 1698 31

To evaluate the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in thyroid neoplasms in a Korean population, we studied a total of 154 cases: papillary carcinoma of classical type (PTC), 86; follicular adenoma (FA), 21; follicular carcinoma (FC), 35; medullary carcinoma (MC), 3; undifferentiated carcinoma (UC), 5; and Hurthle cell neoplasm (HN), 4. Using immunohistochemical staining, COX-2 expression was detected in 62 (72.1%) PTC specimens, 5 (23.8%) FA specimens, 10 (28.6%) FC specimens, 0 (0.0%) MC specimens, 1 (20.0%) UC specimen, and 3 (75%) HN specimens. iNOS expression was detected in 66 (76.7%) PTC specimens, 4 (19.0%) FA specimens, 13 (37.1%) FC specimens, 0 (0.0%) MC specimens, 3 (60.0%) UC specimens, and 4 (100%) HN specimens. The results showed that COX-2 and iNOS were frequently expressed in the PTC and HN specimens, and iNOS was more frequently overexpressed in the FC specimens than in the FA specimens. In PTC, COX-2 and iNOS were significantly overexpressed in patients over 45 yr of age (p=0.029, p=0.041), and iNOS expression was increased in patients with a large primary tumor (p=0.028). These results suggest that the upregulation of COX-2 and iNOS may contribute to the tumor progression of thyroid gland, particularly in PTC and HN, and iNOS may play an adjuvant role during the tumor progression of FC.
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PMID:Cyclooxygenase-2 and inducible nitric oxide synthase expression in thyroid neoplasms and their clinicopathological correlation. 1717 88


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