Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles.

The vasoactive peptide endothelin-1 (ET-1) has been implicated in promoting the progression of prostate and other cancers though its precise mechanism(s)-of-action remain unclear. To better define the role of ET-1 in prostate cancer progression, we generated prostate cancer cell lines (PC-3 and 22Rv1) that express elevated levels of ET-1. As anticipated, increased ET-1 lead to modest autocrine growth stimulation of PC-3 cells in monolayer culture and increased colony formation in soft agar by both cell lines. Unexpectedly, however, metastatic colonization of 22Rv1 cells expressing elevated levels of ET-1 was reduced, as was the size of subcutaneous tumors produced by both 22Rv1- and PC-3 cells. Based on these data, we hypothesized that high levels of ET-1 may negatively impact the tumor microenvironment. We found that increased ET-1 expression did not consistently inhibit angiogenesis, indicating that this was not the cause of poor tumor growth. As an alternative explanation, we examined whether elevated ET-1 results in local vasoconstriction and thus reduces the blood supply available to the tumor. Consistent with this hypothesis, treatment of mice bearing PC-3 xenografts with a vasodilator increased tumor perfusion and partially restored tumor growth. Moreover, analysis of tumor vascular casts indicated vasoconstriction of tumor-feeding arterioles. Taken together, our data suggest that the local concentration of the ET-1 peptide is critical for determining a balance between its previously unrecognized tumor growth-suppressing activity (vasoconstriction) and known growth-promoting (mitogenesis, survival and angiogenesis) activities. These findings may have implications for the modification of current prostate cancer therapies involving ET-1.

Screening for tuberculosis in the study of the living renal donor in a developing country.

Given the high prevalence of tuberculosis (Tb) in the Mexican population, a strict program to detect Tb in the potential donor is required. Chest x-ray, excretory urogram, urinalysis with microscopic exam of the sediment, urine cultures for M. tuberculosis, and tuberculin skin test (TST) with PPD-RT23 performed for evaluation of 222 living donors were reviewed. Isoniazid prophylaxis before kidney donation was gathered. Donors and recipients were followed up for a minimum of 2 years. According to the TST result, 36.8% of the donors had latent tuberculosis; however, all other studies were normal or negative in all of them. Use of isoniazid prophylaxis in TST-positive donors made no difference in risk of transmission of tuberculosis to the recipient or development of tuberculosis among the donors. Normal chest x-ray and excretory urogram, along with a negative microscopic examination of the urine, safely exclude tuberculosis transmission to recipients.