Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer

AIM:To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score(AMLPS) in patients with gastric cancer.METHODS:We retrospectively examined the combination of absolute monocyte count(AMC) and absolute lymphocyte count(ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution.Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis.An AMLPS was generated,which stratified patients into three risk groups:low risk(both low AMC and high ALC),intermediate risk(either high AMC or low ALC),and high risk(both high AMC and low ALC).The primary objective of the study was to validate the impact of AMLPS on both disease-free survival(DFS) and overall survival(OS),and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors.RESULTS:Using data from the entire cohort,the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS.AMLPS risk groups included 158(52.8%) patients in the lowrisk,128(42.8%) in the intermediate-risk,and 13(4.3%) in the high-risk group.With a median followup of 37.2 mo(range:1.7-91.4 mo),five-year DFS rates in the low-,intermediate-,and high-risk groups were 83.4%,78.7%,and 19.8%,respectively.And fiveyear OS rates in the low-,intermediate-,and high-risk groups were 89.3%,81.1%,and 14.4%,respectively.On multivariate analysis performed with patient- and tumor-related factors,we identified AMLPS,age,and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS.CONCLUSION:AMLPS identified patients with a poor DFS and OS,and it was independent of age,pathologic stage,and various inflammatory markers.

Androgen receptor co-regulation in prostate cancer

Prostate cancer(PCa)progression relies on androgen receptor(AR)action.Preventing AR’s ligand-activation is the frontline treatment for metastatic PCa.Androgen deprivation therapy(ADT)that inhibits AR ligand-binding initially induces remission but eventually fails,mainly because of adaptive PCa responses that restore AR action.The vast majority of castration-resistant PCa(CRPC)continues to rely on AR activity.Novel therapeutic strategies are being explored that involve targeting other critical AR domains such as those that mediate its constitutively active transactivation function,its DNA binding ability,or its interaction with co-operating transcriptional regulators.Considerable molecular and clinical variability has been found in AR’s interaction with its ligands,DNA binding motifs,and its associated coregulators and transcription factors.Here,we review evidence that each of these levels of AR regulation can individually and differentially impact transcription by AR.In addition,we examine emerging insights suggesting that each can also impact the other,and that all three may collaborate to induce gene-specific AR target gene expression,likely via AR allosteric effects.For the purpose of this review,we refer to the modulating influence of these differential and/or interdependent contributions of ligands,cognate DNA-binding motifs and critical regulatory protein interactions on AR’s transcriptional output,which may influence the efficiency of the novel PCa therapeutic approaches under consideration,as co-regulation of AR activity.