Showing papers by "Jaishree Jagirdar published in 2000"

Response and Determinants of Sensitivity to Paclitaxel in Human Non-Small Cell Lung Cancer Tumors Heterotransplanted in Nude Mice

Abstract: The lack of tumor models that can reliably predict for response to anticancer agents remains a major deficiency in the field of experimental cancer therapy. Although heterotransplants of certain human solid tumors can be successfully grown in nude mice, they have never been appropriately explored for prediction of in vivo chemosensitivity to anticancer agents. We determined the tumor response rate and studied the influence of several biological and molecular tumor parameters on the in vivo sensitivity to paclitaxel in a series of heterotransplanted human non-small cell lung cancer (NSCLC) tumors. One hundred consecutive resected NSCLC tumors were heterotransplanted s.c. in nude mice. The in vivo sensitivity to i.v. paclitaxel (60 mg/kg every 3 weeks) was studied in 34 successfully grown heterotransplants. Treatment started when the tumors reached a size of 5 mm in diameter, and strict standard clinical criteria (>50% shrinkage in tumor weight or cross-sectional surface) were used to define tumor response. Baseline multidrug resistance protein (MRP), Her-2/neu, and epidermal growth factor receptor (EGFR) expression, and pre- and posttherapy bax and bcl-2 expression were determined by Western blot analysis. p53 status was determined by sequencing. The overall take rate was 46% (95% confidence interval, 36-56%) and was significantly higher (P < 0.05) for squamous carcinoma tumors (75%) than for adenocarcinoma tumors (30%) and bronchoalveolar tumors (23%). The heterotransplants were morphologically very similar to the original tumors. The response rate to paclitaxel was 21% (95% confidence interval, 9-38%). Baseline tumor parameters associated with response were no Her-2/neu expression (none of the responding tumors expressed Her-2/neu versus 48% of the nonresponding tumors, P = 0.05) and baseline bcl-2 expression (all responding tumors expressed bcl-2 versus only 43% of the nonresponding tumors, P = 0.02). There was a trend toward a higher response rate in bax-positive tumors, and MRP- and EGFR-negative tumors, but it was not statistically significant. The response was independent of baseline p53 status and baseline mitotic index. Responding tumors had a higher bax/bcl-2 ratio 24 h after therapy, but the difference was only marginally significant (2.8 for responding tumors versus 1.1 for nonresponding tumors, P = 0.07). The extent of mitotic arrest at 24 h after therapy was not associated with response. Human NSCLC heterotransplants are morphologically identical to the original tumors and have a response rate to paclitaxel that is equivalent to that reported in Phase II studies in patients with advanced NSCLC treated with single-agent paclitaxel. NSCLC heterotransplants deserve to be explored to evaluate new agents for lung cancer and to predict clinical response on an individual basis in selected groups of patients.

Calretinin staining pattern aids in the differentiation of mesothelioma from adenocarcinoma in serous effusions

Abstract: BACKGROUND. The differentiation between malignant mesothelioma and adenocarcinoma based on morphology alone can be a diagnostic challenge. The majority of the available antibodies recognize molecules expressed by adenocarcinoma whereas to the authors' knowledge specific markers for mesothelial cells are lacking. Calretinin, a calcium-binding protein, has been reported to be a selective marker for mesothelioma and largely is absent from adenocarcinoma on histologic material. The results with cytologic preparations have been inconsistent. METHODS. To evaluate the specificity of calretinin in differentiating mesothelioma from adenocarcinoma in cytologic preparations, 21 paraffin embedded cells blocks of serous effusions from 15 patients with metastatic adenocarcinoma and 16 cell blocks from 9 patients with malignant mesothelioma were stained with a monoclonal antibody against calretinin. The immunoreactivity was evaluated blindly by two observers. Positive staining was defined as nuclear and cytoplasmic staining with or without intense membranous decoration. The former resulted in a characteristic fried egg appearance. RESULTS. Calretinin staining was positive in all but 2 cases of mesothelioma (14 of 16 cases; 87.5%). The latter contained predominantly spindle-shaped neoplastic mesothelial cells in the cell block preparations. All adenocarcinoma specimens were classified as negative for calretinin staining; 9 (42.9%) lacked any immunoreactivity and 12 (57.1%) showed weak, sparse, coarse, granular cytoplasmic staining without nuclear or membranous staining. Benign reactive mesothelial cells, when observed in association with adenocarcinoma, also showed the characteristic fried egg appearance. The difference in the staining pattern of calretinin between cells of mesothelial origin and adenocarcinoma cells was statistically significant. CONCLUSIONS. Calretinin is a useful marker in differentiating mesothelioma of the epithelial type from adenocarcinoma in serous effusions. The fried-egg appearance or cytoplasmic and nuclear staining pattern is characteristic of cells of mesothelial origin.

BK virus infection in AIDS

Abstract: The BK virus (BKV) belongs to the family of the polyoma group, which contains three species: JC, which is responsible for progressive multifocal leukoencephalopathy in acquired immunodeficiency syndrome (AIDS); simian virus 40 (SV40), which is a simian virus of little pathologic significance in humans; and BKV, which is usually not pathogenic and is found in the urine of asymptomatic individuals. Recently BKV has been reported to cause symptomatic infection in renal transplant patients. The authors report a rare case of a 14-year-old boy with AIDS who developed a BKV infection of the lung and kidney that progressed to diffuse alveolar damage and death. The infected type II pneumocytes in the lung and the tubular epithelial cells in the kidney showed large, homogenous purple intranuclear inclusions. The absence of necrosis and destruction made it possible to distinguish BKV infection from herpes simplex. The size of the infected cells and the lack of a halo around the nuclear inclusion helped rule out cytomegalovirus as the cause of infection. Electron microscopy detected the presence of 40-nm intranuclear viral particles compatible with BKV, and in situ hybridization established the diagnosis.