Biomedical subjects
Publications and source records attributed to R Govindan.
Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours of similar stage remains unclear. We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance.
BACKGROUND: To evaluate the activity and tolerability of gemcitabine plus irinotecan or docetaxel as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients with chemotherapy-naïve stage IIIB or IV NSCLC were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8, plus either irinotecan 100 mg/m2 or docetaxel 40 mg/m2 on days 1 and 8. Treatment was administered every 3 weeks. RESULTS: Of the 80 enrolled patients with stage IIIB or IV NSCLC, 78 were evaluable for activity and safety. Overall response rates, consisting of partial responses, were 12.8% [95% confidence interval (CI) 4% to 35%] for gemcitabine-irinotecan and 23.1% (95% CI 10% to 42%) for gemcitabine-docetaxel. Median overall survival was 7.95 months (95% CI 5.2-10.2) and 12.8 months (95% CI 7.9-17.1) for gemcitabine-irinotecan and gemcitabine-docetaxel, respectively. The corresponding estimated 1-year survivals were 23% and 51%, respectively. The 2-year survival rate in arm A (gemcitabine-irinotecan) is not currently estimable. The 2-year survival rate for arm B (gemcitabine-docetaxel) is 22% (95% CI 6% to 37%). Both combinations were well tolerated; the most common hematological toxicity was neutropenia, which occurred in 26% of patients in each treatment arm. CONCLUSIONS: These results suggest that gemcitabine plus docetaxel or irinotecan is well tolerated in patients with chemotherapy-naïve advanced NSCLC. The survival data with the combination gemcitabine-docetaxel are promising. Gemcitabine-docetaxel combination therapy may be particularly useful for patients who have experienced toxicities with a platinum regimen or in patients who may be more susceptible to platinum-related toxicity.
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BACKGROUND: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies. PATIENTS AND METHODS: Twenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of rubitecan at 0.75 mg/m(2)/day administered orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) administered intravenously on days 1 and 8 of a 21-day cycle. RESULTS: The MTD was defined as rubitecan 1 mg/m(2) administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m(2) administered intravenously over 30 min days 1 and 8, given every 21 days. Dose-limiting toxicity was myelosuppression including neutropenia and thrombocytopenia. Other side effects included diarrhea, nausea, vomiting and fatigue. Five patients with stable disease were observed among 18 evaluable patients. CONCLUSIONS: The recommended phase II dose is rubitecan 1 mg/m(2) given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.
Factor V inhibitors may develop as spontaneous autoantibodies, as alloantibodies after exposure to bovine thrombin preparations, or in factor V-deficient patients after plasma therapy. Clinical manifestations range from asymptomatic laboratory abnormalities to life-threatening hemorrhage. We have characterized the anti-factor V antibodies from 12 patients diagnosed with factor V inhibitors. In 8 patients, hemorrhagic complications (5 autoantibodies and 3 bovine thrombin-induced alloantibodies) developed, and 4 were asymptomatic (2 autoantibodies and 2 alloantibodies). The IgG fractions from all 12 patients immunoprecipitated the factor Va light chain, but only the 8 IgG fractions associated with hemorrhage inhibited factor V activity in a prothrombinase assay. Nine IgG fractions, including the 8 patients with hemorrhage, immunoprecipitated the isolated second C-type domain (C2). The 8 IgG fractions from the symptomatic patients also immunoprecipitated recombinant chimeras containing only the N-terminal third of the factor V C2 domain, and isolated recombinant C2 domain abrogated the inhibitory effect of the antibodies. Five of the inhibitory IgG fractions blocked binding of factor V to phosphatidylserine. These results suggest that inhibitory anti-factor V antibodies are associated with hemorrhagic manifestations and frequently bind to a common region within the C2 domain, whether originating spontaneously or after exposure to bovine thrombin.
Hematopoietic neoplasms involving the breast, although less common than breast carcinoma, are often clinically indistinguishable from other breast tumors. Microscopically, these tumors can mimic primary carcinoma of the breast, especially in limited material such as needle biopsy specimens. Forty-five hematopoietic breast neoplasms including 21 primary non-Hodgkin's lymphomas (NHLs), 19 secondary NHLs, 1 undetermined NHL, 1 lesion secondary to Hodgkin's disease, and 3 granulocytic sarcomas were reviewed with regard to histologic subtype, morphologic features, and immunophenotype. The median age of patients at presentation was 67 years for those with primary NHLs and 61 years for those with secondary NHLs. The majority of lymphomas were intermediate or high grade. Diffuse large cell type was by far the most common histologic subtype. No lymphomas resembling lymphomas of mucosa-associated lymphoid tissue were identified in this series, suggesting that such lymphomas are rare in breast compared with other sites such as the gastrointestinal tract and lung. Four primary NHLs, 2 secondary NHLs, and 1 granulocytic sarcoma were initially misdiagnosed as carcinomas; three patients underwent radical mastectomy, and at least three other patients nearly received surgical treatment. One primary anaplastic large cell lymphoma of B-cell origin was identified that closely resembled poorly differentiated ductal carcinoma. "Single file" or targetoid patterns with extensive sclerosis mimicking invasive lobular carcinoma was common in lymphomas and was seen in one of the granulocytic sarcomas. In addition, two breast lymphomas, one of B-cell phenotype and the other of T-cell phenotype, showed frequent signet ring cells, which potentially could be confused with lobular carcinoma. Despite a number of recent articles on lymphomas of the breast, it appears that these tumors continue to be confused with carcinomas. Histologic features suggestive of lymphomatous involvement include absence of in situ carcinoma, frequent individual karyorrhectic cells, lymphoepithelial lesions, and cellular discohesiveness.
Small cell lung cancer (SCLC) accounts for 20% of all lung cancers. More than two thirds of patients with SCLC present with clinically evident distant metastases. Patients with limited stage disease are treated with a combination of chemotherapy and chest radiation. Patients with extensive stage disease and good performance status are candidates for combination chemotherapy. Almost all patients relapse after an initial response. This article focuses on the common sense approach to the management of SCLC.
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Cardiac autonomic function was evaluated in 23 patients with fibrocalculous pancreatic diabetes (FCPD). Though none of the patients had any symptoms referable to autonomic dysfunction, 5 had abnormal heart rate responses. The variability in the heart rate in response to deep breathing was the earliest abnormality found in our patients. Four of the 5 patients had clinical evidence of neuropathy while all 5 had retinopathy and overt nephropathy. We therefore conclude that the autonomic nervous system can be involved in patients with FCPD even as early as 2 years after the onset of the disease, and thus that evaluation of the autonomic nervous system should be part of the routine evaluation of all patients with FCPD.
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A case of parasellar chondromyxofibroma with ipsilateral total internal carotid artery occlusion is presented. Its radiological appearance and its pathological characteristics are discussed and compared with previously published reports. The rare association with total internal carotid artery occlusion is reviewed.
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