Far-infrared rays control prostate cancer cells _in vitro_ and _in vivo_

We introduce a new effective method to control hormone refractory prostate cancer cells by using an activated rubber/resin form (RB), far-infrared ray emitter, with or without sodium butyrate (SB). The growth of three human prostate cancer cell lines (Du145, PC-3 and LNCaP) was suppressed _in vitro_ and _in vivo_ by using RB, and the cells were eradicated with RB + 3 mM SB. G1 arrest and apoptotic pathway proteins were induced by RB with intensified expressions of apoptosis - related mRNA on cDNA microarray. RB radiates the infra-red rays of the 4 to 25 [mu]m wavelengths to an object which exert a favorable influence on a cancer control. These results may render us a new therapeutic modality in hormone refractory prostate cancer

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Background & Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH‐2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha‐fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post‐hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). Methods: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH‐2. Kaplan‐Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression‐free survival (PFS), time to progression (TTP) and patient‐reported outcomes (Functional Hepatobiliary System Index‐8 [FHSI‐8] score). Results: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581‐0.975), ≥65 to <75 years (0.602; 0.419‐0.866) and ≥75 years (0.709; 0.420‐1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI‐8 with ramucirumab was observed in all subgroups. Conclusions: In this post‐hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years

Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Background & Aims: The albumin-bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC. Methods: Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2weeks. Datawere analysed by trial and as a meta-analysis of individual patientlevel data (pooled population) from REACH (alpha-fetoprotein>− 400 ng/ml) and REACH-2. Patients from REACHwith Child-Pugh class Bwere analysed as a separate cohort. The ALBI grades and scoreswere calculated at baseline and before each treatment cycle. Results: Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13-1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445-0.824]) and ALBI grade 2 (HR 0.814 [0.630-1.051]. Conclusions: Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade

The oncoprotein and stem cell renewal factor BMI1 associates with poor clinical outcome in oesophageal cancer patients undergoing preoperative chemoradiotherapy

Abstract Background The polycomb group (PcG) family BMI1, acting downstream of the hedgehog (Hh) pathway, plays an essential role in the self-renewal of haematopoietic, neural, and intestinal stem cells, and is dysregulated in many types of cancer. Our recent report has demonstrated that Hh signalling activation can predict very earlier relapse of oesophageal cancers. As data were not available on the clinical role of BMI1 expression in oesophageal cancers after chemoradiotherapy (CRT), we analysed whether it could be also used to predict disease progression and prognosis in oesophageal cancer patients undergoing trimodality therapy of preoperative CRT and oesophagectomy. Methods Expressions of BMI1 and p16INK4A, a downstream target of PcG, were analysed in 78 patients with histologically confirmed oesophageal squamous cell carcinoma (ESCC) after preoperative CRT by immunohistochemical staining. The association of BMI1 and p16INK4A expression with clinicopathologic characteristics was analysed by χ2-test. Survival analysis was carried out by the log-rank test using Kaplan-Meier method. Results Among 78 ESCC patients, 24 patients (30.8%) showed BMI1 positivity, mainly localised in the nuclei of tumour cells. Patients harbouring BMI1-positive tumour cells showed significantly poorer prognoses than those without such cells or residual tumours (mean disease-free survival (DFS) time 16.8 vs 71.2 months; 3-yr DFS 13.3% vs 49.9%, P=0.002; mean OS time 21.8 vs 76.6 months; 3-yr OS 16.2% vs 54.9%, P=0.0005). There was no significant correlation between p16INK4A expression and BMI1 expression. Conclusions Our study shows that BMI1 expression is a predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that BMI1 signal activation might be involved in promoting cancer regrowth and progression after CRT, and might be indicative of emergence of ‘more aggressive’ cancer progenitor cells.</p