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Neoadjuvant Chemotherapy for transitional cell carcinoma.of the Bladder： A Single Centre Experience

Journal of Life Sciences 2016年第2期10卷 85-90页

作者： Gauhar Sultan Babar Malik Syed Najeeb Niamatullah Altaf Hashmi Asad Shehzad Mubarak M SyedAdeeb ul Hassan Rizvi Department of Medical Oncology Sindh Institute of Urology & Transplantation Karachi Pakistan Department of Pathology Sindh Institute of Urology & Transplantation KarachL Pakistan

Urothelial cancers usually recur distantly rather than loco-regionally. In patients with pT2 and pT3/pT4 tumors, local recurrence has been observed in 3-4% and 11-16%, respectively, whereas distant failure has occurred in 10-27% and 19-35%, respectively. Despite local therapy most patients with muscle invasive transitional cell carcinoma.（TCC） of the bladder die of systemic relapse, indicating a need for effective adjunctive systemic treatment. We determined whether neoadjuvant chemotherapy improved overall survival. This study evaluated the role of neoadjuvant combination chemotherapy with gemcitabine/cisplatin （GC） in improving the outcome of this group of patients. A total of 44 patients （84% Male, 16% Female） with newly diagnosed bladder cancer （T3-4, N0-2, M0） were subjected to initial 3 cycles of GC, then managed according to response. Patients were assessed clinically after each cycle and by Interim CT scan after 3 cycles of chemotherapy and those who achieved complete or partial response underwent radical cystectomy. We enrolled 63 patients, 19 of whom were found to be ineligible; thus, 44 were assigned to receive neoadjuvant chemotherapy followed by surgery. Average size of the largest tumor was greater that 30mm in 77% patients. According to Computed Tomographic findings 70% patients belonged to Stage T4A. The overall response rate to GC was 50%, and incomplete response was achieved in 25% whereas 25% patients were lost to follow up. Twenty two patients who had complete response, underwent cystectomy and diversion. It was observed that those patients who underwent radical cystectomy with ureterosigmoidostomy had an increased serum creatinine in comparison to patients who had ileal conduit. The size of the effect is modest and combination chemotherapy can be administered safely without adverse outcomes resulting in delayed local therapy. Further efforts to identify the patients most likely to benefit from neoadjuvant therapy are necessary to optimize its us

关键词： Bladder cancer neoadjuvant chemotherapy cystectomy transitional cell carcinoma.

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Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

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cell Research 2001年第2期11卷 107-115页

作者： SUN HONG ZHI, SHU FANG WU, ZENG HONG TU Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Istrel. Tel: 009728-9343182. E-mail: hongzhi@wicc.weizmann.ac.il Fax: 00972-8-9344116 State Key Laboratory of Drug Research, Shang Department of Biological Regulation Weizmann Institute of Science Rehovot Israel State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China

A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace leve1s; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.

关键词： IGF-1R signaling autocrine drug resistance apoptosis transitional cell carcinoma.

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