Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer frequently expresses cyclooxygenase-2 (COX-2) enzyme. In preclinical studies, COX-2 inhibition results in decreased cell proliferation and potentiation of chemotherapy and radiation. We report preliminary results of a phase II study conducted by the Hoosier Oncology Group in patients with potentially resectable esophageal cancer. All patients received cisplatin at 75 mg/m2 given on days 1 and 29 and fluorouracil (5-FU) at 1000 mg/m2 on days 1 to 4 and 29 to 32 with radiation (50.4 Gy beginning on day 1). Celecoxib (Celebrex) was administered at 200 mg orally twice daily beginning on day 1 until surgery and then at 400 mg orally twice daily until disease progression or unexpected toxicities, or for a maximum of 5 years. Esophagectomy was performed 4 to 6 weeks after completion of chemoradiation. The primary study endpoint was pathologic complete response (pCR). Secondary endpoints included response rate, toxicity, overall survival, and correlation between COX-2 expression and pCR. Thirty-one patients were enrolled from March 2001 to July 2002. Respective grade 3/4 toxicities were experienced by 58%/19% of patients, and consisted of granulocytopenia (16%), nausea/vomiting (16%), esophagitis (10%), dehydration (10%), stomatitis (6%), and diarrhea (31%). Seven patients (24%) required initiation of enteral feedings. There have been seven deaths so far, resulting from postoperative complications (2), pulmonary embolism (1), pneumonia (1), and progressive disease (3). Of the 22 patients (71%) who underwent surgery, 5 had pCR (22%). We conclude that the addition of celecoxib to chemoradiation is well tolerated. The pCR rate of 22% in this study is similar to that reported with the use of preoperative chemoradiation in other trials. Further follow-up is necessary to assess the impact of maintenance therapy with celecoxib on overall survival.
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PMID:Cisplatin, fluorouracil, celecoxib, and RT in resectable esophageal cancer: preliminary results. 1568 29

Right ventricular (RV) damage contributes to poor clinical outcome after pulmonary embolism (PE). Our studies show that neutrophils contribute to RV dysfunction in rat PE. Present studies examine effects of the nonsteroidal anti-inflammatory drug, ketorolac, upon RV inflammation and dysfunction. RV inflammatory gene expression significantly increased 6 and 18 hours after PE [cytokine-induced neutrophil chemoattractant-1 (CINC-1) 18-fold and 24-fold; cyclooxygenase-2 21-fold and 32-fold]. Eighteen hours after PE, there was significant upregulation of adhesion molecules (selectin E 18-fold; intercellular adhesion molecule 1 14-fold), influx of neutrophils (myeloperoxidase activity 21-fold), depressed RV function (RV peak systolic pressure = 24 +/- 3 vs. 40 +/- 1 mm Hg; maximum rate of pressure development = 444 +/- 79 vs. 1533 +/- 146; maximum rate of pressure decrease = -357 +/- 50 vs. -651 +/- 44), and release of cardiac troponin I (7.8 +/- 1.9 ng/mL) compared with vehicle. Ketorolac (10 mg/kg, intraperitoneally) significantly reduced expression of CINC-1, cyclooxygenase-2, selectin E, and intercellular adhesion molecule 1, lowered neutrophil influx, improved RV function (RV peak systolic pressure was 34 +/- 3 mm Hg; maximum rate of pressure development = 1288 +/- 146; maximum rate of pressure decrease = -611 +/- 92), and marginally reduced cardiac troponin I release (P < 0.07) compared with PE alone. Ketorolac reduced CINC-1 stimulated chemotaxis of isolated neutrophils. PE converted cardiac tissue into a proinflammatory phenotype. Ketorolac reduced RV inflammatory genes, reduced neutrophil influx, and improved RV function in rat PE.
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PMID:Proinflammatory events in right ventricular damage during pulmonary embolism: effects of treatment with ketorolac in rats. 1962 Aug 82