Concurrent liposomal paclitaxel and cisplatin chemotherapy improved outcomes for locally advanced esophageal squamous cell carcinoma treated with intensity-modulated radiotherapy.

BACKGROUND: To ascertain whether concurrent chemotherapy using liposomal paclitaxel and cisplatin could improve the outcomes of patients with locally advanced esophageal squamous cell carcinoma receiving intensity-modulated radiotherapy (IMRT). METHODS: A total of 72 patients with locally advanced esophageal squamous cell carcinoma, which were admitted to our hospital from October 2011 to December 2013, were retrospectively analyzed in this study. RESULTS: Thirty-six patients (50%) were treated with IMRT alone, while the other 36 patients (50%) were treated by IMRT combined with chemotherapy containing liposomal paclitaxel and cisplatin. Patients treated with chemoradiotherapy showed significantly superior overall survival (OS) and progression-free survival (PFS) compared to patients treated with IMRT alone (median OS: respectively, 29.7 vs. 12.9 months, P=0.0287; median PFS: respectively, 14.0 vs. 6.5 months, P=0.0186). Multivariate Cox analysis confirmed the inclusion of chemotherapy as an independent predictor of favorable OS and PFS. Both chemoradiotherapy and IMRT were well-tolerated in our cohort. CONCLUSIONS: Chemotherapy improved the prognosis of locally advanced esophageal squamous cell carcinoma treated with IMRT. Large prospective studies are needed to confirm the therapeutic value of IMRT combined with chemotherapy in locally advanced esophageal squamous cell carcinoma.

Raltitrexed increases radiation sensitivity of esophageal squamous carcinoma cells.

BACKGROUND: Radiation therapy remains an important therapeutic modality, especially for those patients who are not candidates for radical resection. Many strategies have been developed to increase the radiosensitivity of esophageal cancer, with some success. METHODS: This study was conducted to determine whether raltitrexed can enhance radiosensitivity of esophageal squamous cell carcinoma (ESCC). ESCC cell lines 24 h were incubated with raltitrexed or DMSO with or without subsequent irradiation. Cell Counting Kit assay-8 assay and clonogenic survival assay were used to measure the cell proliferation and radiosensitization, respectively. Flow cytometry was utilized to examine cell apoptosis and cell cycle distribution in different groups. Immunofluorescence analysis was performed to detect deoxyribonucleic acid (DNA) double-strand breaks. In addition, the expression levels of proteins that are involved in radiation induced signal transduction including Bax, Cyclin B1, Cdc2/pCdc2, and Cdc25C/pCdc25C were examined by western blot analysis. RESULTS: The results indicated that raltitrexed enhanced radiosensitivity of ESCC cells with increased DNA double-strand breaks, the G2/M arrest, and the apoptosis of ESCC cells induced by radiation. The sensitization enhancement ratio of 1.23-2.10 was detected for ESCC cells with raltitrexed treatment in TE-13 cell line. In vitro, raltitrexed also increased the therapeutic effect of radiation in nude mice. CONCLUSION: Raltitrexed increases the radiosensitivity of ESCC. This antimetabolite drug is promising for future clinical trials with concurrent radiation in esophageal cancer.

Clinical observation of three dimensional conformal radiotherapy with tamoxifen in treatment of postoperative malignant glioma.

OBJECTIVE: To evaluate the efficacy and adverse effects of three dimensional conformal radiotherapy (3D-CRT) with tamoxifen in treating patients with postoperative malignant glioma. PATIENTS AND METHODS: 60 patients of postoperative malignant glioma were randomly assigned into two groups, 30 patients were treated with 3D-CRT plus tamoxifen (treatment group), and the other 30 patients with 3D-CRT plus temozolomide (control group). All patients were radiated by 6MV X-ray, 2.0 Gy per fraction, once daily, with a total dose (DT) of 56~60 Gy. Tamoxifen was delivered at 60 mg /m2/d, temozolomide was given at 75 mg/m2/d. All patients were treated with concurrent radiotherapy. RESULTS: One, 2, 3 year survival rates of treatment and control group were 63.3%, 30.0%, 23.0% and 70.0%, 33.3%, 26.7%, respectively (χ2=0.01, 0.23, 0.09, P>0.05). The rate of thromboembolism in treatment group was 6.7%. CONCLUSION: Therapeutic efficacy of two groups was similar, but it was more cost- effective in treatment group, and toxicity did not increase.

[Molecular mechanism of radiosensitizing effect of paclitaxel].

BACKGROUND & OBJECTIVE: Paclitaxel is a radiosensitizer which may stabilize microtubules, block the G2/M phase of the cell cycle and thus modulate the radioresponsiveness of tumor cells. However, its potential molecular mechanisms of radiosensitization have not been well understood yet. This study was to investigate the radiosensitizing effect of paclitaxel on human oral epithelium carcinoma (KB) cell line and to explore the molecular mechanism of radiosensitization. METHODS: The survival of KB cells following the treatment with paclitaxel and/or radiation was determined by colony-forming assay. The radiosensitizing effect was evaluated by calculating the sensitizing enhancement ratio (SER) with multi-target single hit model. The cell cycle distribution was analyzed by flow cytometry. Differentially expressed genes related to paclitaxel radiosensitization were screened using human Oligo microarray. Expressions of protein regulating cytokinesis 1 (PRC1) and cyclin B2 genes were confirmed by real-time quantitative PCR. RESULTS: The proliferation of KB cells was significantly inhibited by paclitaxel combined with ionizing radiation. The SERD0 and SERDq were (2.40 +/- 1.87) and (12.23 +/- 2.81) respectively, when the concentration of paclitaxel was 20 nmol/l. After the treatment with paclitaxel in combination with irradiation, the percentage of G1 phase cells decreased from (48.32 +/- 2.40)% to (15.73 +/- 7.00)% (P<0.01), and the percentage of G2/M phase cells increased from (13.66 +/- 2.16)% to (52.51 +/- 5.02)% (P<0.01). In total 176 differentially expressed genes were identified to be related to paclitaxel radiosensitization. Ten genes were found to regulate cell division, two of which were up-regulated and eight were down-regulated after the treatment. Moreover, the expression of PRC1 and cyclin B2 was decreased. CONCLUSION: The radiosensitizing effect of paclitaxel on KB cells may be due to the down-regulated expression of PRC1 and cyclin B2, resulting in inhibition of mitotic spindle formation and cell necrosis.