Expression of mRNAs of urocortin and corticotropin-releasing factor receptors in malignant glioma cell lines.

BACKGROUND: Urocortin and corticotropin-releasing factors (CRFs) and their receptors are expressed in many organs, including the central nervous system. In this study, the expression of mRNAs of urocortin 1, 2, 3, and CRF and CRF receptors 1 and 2 in malignant glioma, was examined. MATERIALS AND METHODS: The RNAs of human and rat glioma cell lines were isolated. Transcripts in these cells were analyzed using cDNA. In addition, the effects of proliferative and cytotoxic stimulation by serum supplementation, ionizing radiation, and the antineoplastic agent temozolomide were investigated. RESULTS: Human and rat cells transcribed urocortin. CRF receptors were detected in human glioma cells. When human KNS42 cells were exposed to stimulation, transcription was altered according to the specific condition. CONCLUSION: Expression of mRNAs of urocortin and CRF receptors was confirmed in human glioma cell lines. Although the quantities of transcripts varied with the proliferative and cytotoxic stimulation, the overall transcription pattern was not influenced by these stimuli.

Phase II clinical trial of second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: AVASIRI trial.

OBJECTIVE: FOLFIRI is a standard chemotherapy regimen for the treatment of metastatic colorectal cancer. Although some studies have shown its efficacy in combination with bevacizumab as first-line chemotherapy, there are no data to support FOLFIRI plus bevacizumab as second-line chemotherapy in patients with this form of cancer. The aim of this study was to evaluate the efficacy and safety of FOLFIRI and bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer. METHODS: Eligible patients were ≥20 years old, previously treated (except with irinotecan [CPT-11] and bevacizumab), with an Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and adequate organ function. Twenty-five eligible patients received FOLFIRI with bevacizumab at a dose of 10 mg/kg given intravenously on day 1. All therapy was administered every 2 weeks until disease progression. The primary endpoint was the response rate. RESULTS: Twenty-five patients were enrolled between February 2008 and March 2009. The median age was 62 (range 38-73) years, the male/female distribution was 20/5, 16 patients had performance status 0 and 9 had performance status 1, and the proportion of patients who were oxaliplatin pretreated/untreated was 16/9. The overall response rate was 32% (90% confidence interval [CI]: 17.0-50.4%), with 8 patients showing partial responses, 15 with stable disease, and 2 with disease progression. Median progression-free survival was 11.6 months (95% CI: 6.9-16.4). Median overall survival was 21.4 months (95% CI: 12.0-30.8). The grade 3/4 adverse events with treatment were neutropenia (64%), leukopenia (16%), diarrhea (8%), anorexia (8%), and febrile neutropenia (8%). The bevacizumab-related grade 3/4 adverse event was hypertension, which was observed in 12% of patients. CONCLUSIONS: The FOLFIRI plus bevacizumab regimen is an active, well-tolerated second-line chemotherapy treatment for patients with metastatic colorectal cancer.

The effect of PTEN on proliferation and drug-, and radiosensitivity in malignant glioma cells.

BACKGROUND: Deletions or mutations of the phosphatase and tensin homolog (PTEN) are frequently observed in malignant glioma and are responsible for progression of the disease. Since the molecule is a promising target for gene therapy, the effects of PTEN on glioma proliferation in combination with the anti-neoplastic agent, temozolomide, and ionizing radiation were investigated. MATERIALS AND METHODS: An adenoviral vector encoding PTEN was used. After infection, changes in proliferation, the cell cycle, as well as drug- and radiosensitivity were investigated. RESULTS: Expression of PTEN led to a 1.21-fold prolongation of the doubling time of the cells. It reduced G(1) and increased G(2)/M populations. Forced PTEN expression conferred sensitivity to temozolomide and/or ionizing radiation. CONCLUSION: In addition to counteracting cell proliferation, expression of PTEN presented advantages in the chemo- and radiosensitivity of glioma cells. Methods for up-regulation of PTEN may have a role in increasing the efficacy of current adjuvant therapies.