Effect of combinations of drugs on glioma chemotherapy

Patil, Abhijit Arvind (2009) Effect of combinations of drugs on glioma chemotherapy. Masters thesis, University of Central Lancashire.

[thumbnail of Thesis document] PDF (Thesis document) - Submitted Version
Restricted to Repository staff only
Available under License Creative Commons Attribution Non-commercial Share Alike.



Recent developments in chemotherapy have improved the survival rates as well as the quality of life of patients with glioma. Combination chemotherapy regimens along with the use of two or more anticancer agents or with the use of various drug delivery systems have become a major component of various treatment strategies that are used to manage tumours. The
current project underlines the fact that chemotherapeutic agents with different mechanisms of action and mechanisms of resistance can have a greater effect on the tumour cells when used in combination than when used alone. In the current study, human glioma cell lines 132 1N1 and U87-M0 were exposed to different concentrations of anticancer agents, Temozolomide, Cisplatin, and Paclitaxel alone and in combination for a period of 72 hours. Two combination studies involving the combination of Temozolomide and Cisplatin and the combination of Temozolomide and Paclitaxel revealed that Temozolomide when used in combination was significantly more effective than when used alone in vitro. Another study was carried out to test the effect of conjugation of novel generation 3 (03) polyamidoamine (PAMAM) dendrimer to chemotherapeutic agent, Paclitaxel. The cytotoxicity results showed that paclitaxel, when conjugated to the 03 PAMAM dendrimer, was significantly more toxic then when used alone. P-glycoprotein (Pgp) is the major hurdle in the cytotoxic effect of paclitaxel and so a cytotoxicity study was also carried out using P-gp inhibitor, Verapamil Hydrochloride. The study revealed that the cytotoxic effect of Paclitaxel increased in the presence of Verapamil Hydrochloride. In conclusion, the hypothesis that combinations of chemotherapeutic drug are more effective than single agent chemotherapy is in agreement with the results obtained from human glioma cell lines used in the study. This work shows that Temozolomide in combination with other anticancer agents like Cisplatin and Paclitaxel is more effective than used alone. The study also underlines that the 03 PAMAM dendrimer based drug delivery system increases the cytotoxic effect of Paclitaxel on the human glioma cell lines 1321N1 and U87-MG. These experiments also emphasize that use of P-gp inhibitors like Verapamil Hydrochloride can
enhance the cytotoxic effect of Paclitaxel in vitro.

Repository Staff Only: item control page