Partial association of restriction polymorphism of the ligand binding domain of human androgen receptor in prostate cancer

Background: Human androgen receptor [AR] functions as a steroid-hormone activated transcription factor. The receptor binds to its ligand [testosterone or dihydrotestosterone] and is translocated to the nucleus to stimulate the transcription of androgen responsive genes. Mutations in the ligand binding domain [LBD] impair the receptor activity and play a crucial role in the development and progression of prostate cancer [PCa]

Materials and methods: This work was designated to investigate the restriction integrity of the LBD and its association with benign prostatic hyperplasia [BPH] and prostate cancer. Exons of this domain [exons: 4-8] were amplified from prostate tissue of BPH and PCa patients and the restriction polymorphism was investigated by SmlI, HphI and Tsp45I restriction enzymes in both BPH and PCa groups

Results: Data revealed the integrity of exons 4-6 in both BPH and PCa patients. Exons 7 and 8, however have kept their constitutional pattern only in BPH patients. Hph1 site showed an abnormal restriction pattern in 40% and 26.7% of PCa patients. Also, Tsp45I demonstrated restriction polymorphism in 20% and 13% of PCa patients

Conclusion:Our results indicate that the loss of the restriction integrity in the C-terminal part [exons: 7 and 8] of the LBD is associated with the progression of benign prostatic hyperplasia to prostate cancer

Nitric oxide, matrix metalloproteinases [2,9] and tissue inhibitor of matrix metalloproteinases-1 levels in hepatocellular carcinoma of egyptian patients

The aim of this study was to examine the relationship between the levels of NO, MMP-2 and 9 and TIMP-1 and the behavior of this carcinoma which may be helpful in disease management. For this purpose, the sera of 74 hepatocellular carcinoma cases as well as 74 normal cases were subjected for the analysis of the above mentioned parameters using ELISA technique and the results were correlated with the different clinicopathological data. The results revealed a significant enhancement in the levels of all the parameters examined in the hepatocellular cases rather than the normal ones. Almost, the same parameters showed no significant changes in their levels associated with the histopathological types of the disease. However, a significant change was obtained when the levels of NO, MMP-2, 9 and TIMP-1 were matched with the different tumor grades. All the parameters examined showed no significant difference with the tumor size [/<2 cm or >cm].Only the nitrite level was significantly changed with the C-virus infection and LN involvement; while the other parameters were not. The results suggested that analysis of NO, MMP-2. 9 and TIMP-1 may be helpful in disease management of patients with hepatocellular carcinoma

Matrix metalloproteinase 2,9 expression and DNA damage during treatment with verapamil and /or doxorubicin in murine tumor cells

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