Assessment of Androgen Receptor Splice Variant-7 as a Biomarker of Clinical Response in Castration-Sensitive Prostate Cancer.

PURPOSE: Therapies targeting the androgen receptor (AR) have improved the outcome for patients with castration-sensitive prostate cancer (CSPC). Expression of the constitutively active AR splice variant-7 (AR-V7) has shown clinical utility as a predictive biomarker of AR-targeted therapy resistance in castration-resistant prostate cancer (CRPC), but its importance in CSPC remains understudied. EXPERIMENTAL DESIGN: We assessed different approaches to quantify AR-V7 mRNA and protein in prostate cancer cell lines, patient-derived xenograft (PDX) models, publicly available cohorts, and independent institutional clinical cohorts, to identify reliable approaches for detecting AR-V7 mRNA and protein and its association with clinical outcome. RESULTS: In CSPC and CRPC cohorts, AR-V7 mRNA was much less abundant when detected using reads across splice boundaries than when considering isoform-specific exonic reads. The RM7 AR-V7 antibody had increased sensitivity and specificity for AR-V7 protein detection by immunohistochemistry (IHC) in CRPC cohorts but rarely identified AR-V7 protein reactivity in CSPC cohorts, when compared with the EPR15656 AR-V7 antibody. Using multiple CRPC PDX models, we demonstrated that AR-V7 expression was exquisitely sensitive to hormonal manipulation. In CSPC institutional cohorts, AR-V7 protein quantification by either assay was associated neither with time to development of castration resistance nor with overall survival, and intense neoadjuvant androgen-deprivation therapy did not lead to significant AR-V7 mRNA or staining following treatment. Neither pre- nor posttreatment AR-V7 levels were associated with volumes of residual disease after therapy. CONCLUSIONS: This study demonstrates that further analytical validation and clinical qualification are required before AR-V7 can be considered for clinical use in CSPC as a predictive biomarker.

Maternal healthcare needs assessment survey at Rabia Balkhi Hospital in Kabul, Afghanistan.

OBJECTIVE: Since the Department of Health and Human Services chose Rabia Balkhi Hospital (RBH) in Kabul, Afghanistan, as a site for intervention in 2002, the status of women's health there has been of interest. This study created a tool to assess accessibility and quality of care of women admitted from May to July, 2005. METHODS: A 39-item questionnaire was created in English and translated into Dari. Hospital staff administered the survey to 292 women admitted to RBH for obstetric and gynecological complaints. RESULTS: Approximately 40% of the women traveled between 1 and 5 hours to reach RBH. Only 54% (158/292) of women reported having their blood pressure monitored during their pregnancy. About one-third of women reported that they had never received an immunization. CONCLUSIONS: This survey tool ascertained that women who received care at RBH traveled great lengths to reach the facility. Preventative measures such as blood pressure checks and immunizations are areas that need improvement.