Regulation of tumor growth and metastasis: the role of tumor microenvironment.

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body's immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor's surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.

Primary chemotherapy with low-dose prolonged infusion gemcitabine and cisplatin in patients with bladder cancer: a Phase II trial.

BACKGROUND: Gemcitabine is an active agent in the treatment of bladder cancer. The enzyme deoxycytidine kinase catalyzes the phosphorylation of gemcitabine into the active gemcitabine triphosphate. After an infusion during 30 minutes, this enzyme will be saturated, therefore, accumulation of higher intracellular concentrations of the active gemcitabine triphosphate could be achieved by prolonging the infusion time of gemcitabine. PATIENTS AND METHODS: Based on previously published Phase I trials, the efficacy and safety of a combination of cisplatin and gemcitabine given as prolonged infusion were tried in a Phase II study of 57 untreated patients with stage III/IV bladder cancer, which is the most common malignant tumor among Egyptian males. Patients received gemcitabine (250 mg/m(2) during 6-hour infusion) on days 1 and 8, and cisplatin (70 mg/m(2)) on day 2 every 21-day cycle. RESULTS: The 41 males and 16 females had a median age of 55 years (range 37-77). A total of 37 patients had transitional cell, 15 had squamous cell, 2 had adenocarcinoma, and 3 had undifferentiated cell carcinoma. The median number of cycles given to these 57 patients was 4 (range 1-6). Of 54 evaluable patients, 5 (9.4%) had complete remission, and 27 (50%) partial remission, for an overall response rate of 59.4%. These results are comparable to those of a previous Phase II study of the same combination but with gemcitabine given in the standard dose and schedule. Responses were observed at all disease sites. Both hematologic and nonhematologic toxicity were treatable and not severe. CONCLUSIONS: Prolonged infusion of gemcitabine and cisplatin is an effective treatment for advanced bilharzial-related bladder cancer. Toxicity, especially myelosuppression, is surprisingly mild. This combination deserves to be tried in other different disease categories.