Carcinomatous meningitis secondary to transitional cell bladder cancer.

We report a patient with carcinomatous meningitis secondary to known transitional cell carcinoma of the bladder. The patient presented with multiple focal neurological signs and symptoms. Diagnosis was suggested by magnetic resonance imaging and confirmed by analysis of the cerebrospinal fluid. He received whole brain radiotherapy despite a poor prognosis. To our knowledge, this is only the fifth reported case of neoplastic meningitis due to bladder cancer with confirmatory imaging and cytology and only the fourth reported case that presented with cranial nerve involvement.

Hyperglycemia-induced thioredoxin-interacting protein expression differs in breast cancer-derived cells and regulates paclitaxel IC50.

PURPOSE: We studied the hyperglycemia-induced expression of thioredoxin-interacting protein (TXNIP) expression and its relevance on the cytotoxic activity of paclitaxel in mammary epithelial-derived cell lines. EXPERIMENTAL DESIGN: Nontumorigenic cells (MCF10A); tumorigenic, nonmetastatic cells (MCF-7/T47D); and tumorigenic, metastatic cells (MDA-MB-231/MDA-MB-435s) were grown either in 5 or 20 mmol/L glucose chronically. Semiquantitative reverse transcription-PCR was used to assess TXNIP RNA expression in response to glucose. Reactive oxygen species were detected by CM-H2DCFDA (5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) and measured for mean fluorescence intensity with flow cytometry. Thioredoxin activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorption. Obtained absorbance values were used to calculate the paclitaxel IC(50) in 5 or 20 mmol/L glucose using the Chou's dose-effect equation. RESULTS: We show that hyperglycemia by itself affects the level of TXNIP RNA in breast cancer-derived cells. TXNIP RNA level differs between nontumorigenic/nonmetastatic, tumorigenic cells (low TXNIP level), and metastatic cells (high TXNIP level). The differences in TXNIP RNA level, in reactive oxygen species level, and in thioredoxin activity are all related. We further show that hyperglycemia is a favorable condition in increasing the paclitaxel cytotoxicity by causing IC(50) 3-fold decrease in metastatic breast cancer-derived MDA-MB-231 cells. The increased paclitaxel cytotoxicity is associated with an additive effect on the hyperglycemia-mediated TXNIP expression more evident in conditions of hyperglycemia than normoglycemia. CONCLUSIONS: Our study opens a new perspective on the relevance of metabolic conditions of hyperglycemia in the biology and treatment of cancer, particularly in view of the epidemic of diabetes.

Phase II trial of gemcitabine as first line chemotherapy in patients with metastatic or unresectable soft tissue sarcoma.

OBJECTIVE: The availability of effective chemotherapy agents or regimens for soft tissue sarcomas (STS) is limited. Response to available first line regimens is generally poor and response to second line regimens is rare. Considering the poor response of STS to available cytotoxic therapy, and the need to adequately evaluate the effectiveness of new agents, first line investigation of promising new agents is justified. Gemcitabine, a relatively new agent, has demonstrated effectiveness in several solid tumors. Limited clinical trials have suggested modest activity in STS. A multi-institutional study of gemcitabine in patients with STS, without prior chemotherapy for metastatic disease, was initiated in the Southwest Oncology Group May 1, 1998 and completed March 15, 1999. MATERIALS AND METHODS: Patients were required to have metastatic or unresectable STS with no prior chemotherapy for metastatic disease. Gastrointestinal leiomyosarcomas and stromal tumors were not eligible. Patients were required to have a performance status of 0-2, measurable disease, adequate renal, hepatic, and hematologic function. The patients were given Gemcitabine 1000 mg/M2 iv over 30 minutes on days 1, 8, and 15, 22, 29, 36, 43, 57, 64, and 71. Dosage reduction was performed for cytopenias and/or other grade 3 or 4 toxicity. RESULTS: Forty-eight patients were registered to the study. The median age was 62 years (range, 30-80) with 21 male and 25 female patients. Two patients were ineligible (1 GI stromal tumor and 1 nerve sheath tumor). Forty-six patients are evaluable for response, toxicity, and survival. There were 2 treatment-related deaths (1 renal failure and 1 hemolytic uremic syndrome). Six additional patients experienced grade 4 toxicity (3 neutropenia, 2 dyspnea, 1 vomiting, and 1 renal failure). Three of the 46 eligible patients had a partial response (7%: 95% confidence interval 1-18%) and 8 patients had stable disease (20%). Nine patients had inadequate assessments to define response. Forty-five patients have died with a median survival of 6 months (95% confidence interval 5-10 months). CONCLUSION: Gemcitabine has minimal activity as a single agent at this dose and schedule in advanced STS. The low response rate does not justify further investigation of gemcitabine as a single agent in STS.