ABSTRACT
This study aims to examine the effects of verapamil and/or Doxorubicin [DOX] treatment on the Matrix metalloproteinase [MMPs] expression and DNA damage in murine tumor cells. Tummbearing mice treated with DOX [2mg/kg I. P. every other day X3] and/or verapamil [20 mg/kg I. P. daily for 5 days]. After last injection Ehrlich ascites carcinoma cells [EAC-cells] were withdrawn tot preparation of protein lysate and DNA. Gelatin zymographic analysis [GZA] and DNA agarose gel electrophoresis, used for this determination of MMPs expression and DNA damage, respectively. DOX treatment showed 34.1 days median survival time with 20% long-term survivors. However, administration of verapamil before DOX increased the long-term survivors to 60% with medium survival time of 44.4 days. Verapamil pretreatment increased the cellular level of DOX at all time points tested with maximum level appeared at 6 hours after treatment, 5.5 micro g/10[8] cells compared to 3.4 micro g/10[8] cells for DOX alone]. Using verapamil or DOX induced metalloproteinase activity and DNA damage, whereas their combination induced metalloproteinase isomer with low molecular weight at 24 hours which disappeared at 48 and 72 hours. Also combination of verapamil and DOX increased the amount of DNA degradation
Conclusion: Verapamil potentiates DOX-cytotoxicity against EAC-cells by increasing MMPs expression and DNA degradation with the consequent increase in DOX cellular uptake and cytotoxicity
ABSTRACT
This study was conducted upon 98 subjects, 20 acted as controls and 78 patients having lympho-proliferative malignancies. The patients group included 31 cases of acute lymphoblastic leukemia [ALL], 10 cases of chronic lymphatic leukemia [CLL], 15 patients having Hodgkin disease [HD]. 16 subjects with non-Hodgkin lymphoma [LPL]. The number of glucocorticoid receptors [GR] on peripheral blood lymphoid cells were determined before any therapy. After receiving chemotherapy, that included steroids, patients were followed for a maximum of one year to evaluate the response to treatment by examining both peripheral blood and bone marrow cells. The study revealed that, in lympho- proliferative malignancy, GR number on peripheral blood cells has no significant difference from those of normal controls except in NHL where there was a significant increase in the receptor content of peripheral lymphocytes. In addition the number of these GR was not correlated to the response to various chemotherapies given in lymphatic leukemias and lymphomas