Given the potential for synergistic epigenetic modulation between hydralazine and valproic acid, as well as the safety track record for long-term administration in nononcology patients, we conducted this trial to identify a dose appropriate selleck chemicals llc for chronic administration for lung cancer chemoprevention. The results of our trial support further investigation of epigenetic modification as a new therapeutic strategy. The combination of hydralazine and valproic acid is simple, nontoxic, and lends itself to chemoprevention or combination with other treatments. Future studies will need

to be conducted with pharmacodynamic end points, such as the re-expression of defined panels of tumor suppressor genes as a function of therapy. Furthermore, if hydralazine is used, then study patients will need to be stratified by acetylator phenotype, as it is possible that toxicity, and even efficacy, may be determined by such phenotypic expression. Prospective trials will need to assess the role of epigenetic modification through newly discovered epigenetic

mechanisms of action that could be used as biomarkers of efficacy. We acknowledge the efforts of Valerie Parks (RN), Terry Novak (RN), and Mary Pruess (RN) in providing care to the protocol participants as well as in the monitoring of this trial. “
“Breast cancer (BCa) is the most common malignancy among women around the globe, and it is recognized to be the second most common cause of death in women [1]. Its rate is rising rapidly in Asian women and the developing world. According to the Surveillance, Epidemiology, and End Results database, Asian Indian/Pakistani NVP-BKM120 women residing in the United States seem to have a higher frequency of BCa particularly at a younger age (< 40 years) compared to Caucasians

[2]. The data from South Karachi, a pragmatic representative of the population of Bumetanide Pakistan, revealed that BCa accounted for approximately one third of cancers in women [3]. Hormone receptors such as estrogen (ERs) and progesterone receptors (PRs) play a seminal role in determining the treatment strategy and prognosis of patients with BCa. In addition, human epidermal growth factor receptor type 2 (HER2) has been found to be overexpressed in a subset of invasive BCa and is associated with poor prognosis [4] and [5]. According to Surveillance, Epidemiology and End Results database, Asian Indian/Pakistani women residing in the United States had more ER/PR-negative BCa (30.6%) compared to Caucasians (21.8%) [2]. These data are similar to studies undertaken on samples of BCa from women residing in Pakistan that showed that 60% to 65% of the tumors expressed ER/PR [6] and [7]. Furthermore, frequency of HER2 expression has also found to be higher in Pakistani women with BCa (30%-39%) [6], [8] and [9] in contrast to Caucasians (25%-30%) [4] and [5].