A basal‐enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer‐enriched miRNA is required for prostate tumorigenesis. We identify miR‐205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR‐205 is not required for normal prostate development and homeostasis, genetic deletion of miR‐205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR‐205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR‐205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR‐205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR‐205 in the progression of Pten null‐induced prostate cancer.     

A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy

BackgroundIsolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.Material and methodsA systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.ResultsOf the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion −5.7, 95% CI [-13.7; 2.3]).ConclusionsSalvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.     

Effects of the Clearing the Lung and Dissipating Phlegm Method in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Objective: The objective of this study is to evaluate the efficacy and safety of the clearing the lung and dissipating phlegm method in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD) and to provide evidence for the treatment of the disease. Materials and Methods: Literature was searched from the United States National Library of Medicine(PubMed), Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database(Wanfang), and the Full?Text Database of Chinese Scientific and Technical Periodicals(VIP).A comprehensive collection was made of randomized controlled trials(RCTs) before June 2018, in which the treatment groups used either the clearing the lung and dissipating phlegm formulas only or combined it with routine Western medicine therapy, and the control group adopted routine Western medicine therapy only for the acute exacerbation of COPD. The Cochrane risk of bias method was used to evaluate the quality of the literature. The data were analyzed and retrieved independently by two reviewers before meta?analysis was carried out with RevMan 5.3 software to evaluate the primary outcome measures, including the total clinical effective rate, and the secondary outcome measures such as the pulmonary function(forced vital capacity [FVC], forced expiratory volume in the 1 s [FEV1], percentage of FEV1 [FEV1%], and FEV1/FVC)and blood gases(PaO_2 and PaCo_2). Results: A total of 13 RCTs involving 990 patients(496 in the treatment group and 494 in the control group)were included in this study. Meta?analysis revealed significant difference in the efficacy of the group that adopted solely the routine Western medicine method and the group that combined the Western medicine with the clearing the lung and dissipating phlegm method. Outcome measures including the pulmonary function(FVC, FEV1, FEV1%, and FEV1/FVC) and the blood gases(PaO_2 and PaCo_2) were significantly improved as compared to the control group(P 0.00001). However, adverse effects in the treatment group using combined traditional Chinese medicine were not reported due to the short observation time of the study. Conclusion: The clearing the lung and dissipating phlegm method can improve the efficacy in the treatment of acute exacerbation of COPD, the outcome measures of the pulmonary function and the blood gases,as well as the life quality of the patients. However, due to the fact that the existing studies are generally of poor quality in which randomization and its implementation were not properly carried out, more high?quality RCTs are necessary to confirm the findings of this study.     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

CT Densitometry and Morphology of Radiofrequency-Ablated Stage IA Non–Small Cell Lung Cancer: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) Trial

PurposeTo evaluate tumor and ablation zone morphology and densitometry related to tumor recurrence in participants with Stage IA non–small cell lung cancer undergoing radiofrequency ablation in a prospective, multicenter trial.Materials and MethodsForty-five participants (median 76 years old; 25 women; 20 men) from 16 sites were followed for 2 years (December 2006 to November 2010) with computed tomography (CT) densitometry. Imaging findings before and after ablation were recorded, including maximum CT attenuation (in Hounsfield units) at precontrast and 45-, 90-, 180-, and 300-s postcontrast.ResultsEvery 1-cm increase in the largest axial diameter of the ablation zone at 3-months’ follow-up compared to the index tumor reduced the odds of 2-year recurrence by 52% (P = .02). A 1-cm difference performed the best (sensitivity, 0.56; specificity, 0.93; positive likelihood ratio of 8). CT densitometry precontrast and at 45 seconds showed significantly different enhancement patterns in a comparison among pretreated lung cancer (delta = +61.2 HU), tumor recurrence (delta = +57 HU), and treated tumor/ablation zone (delta [change in attenuation] = +16.9 HU), (P < .0001). Densitometry from 45 to 300 s was also different among pretreated tumor (delta = −6.8 HU), recurrence (delta = −11.2 HU), and treated tumor (delta = +12.1 HU; P = .01). Untreated and residual tumor demonstrated washout, whereas treated tumor demonstrated increased attenuation.ConclusionsAn ablation zone ≥1 cm larger than the initial tumor, based on 3-month follow-up imaging, is recommended to decrease odds of recurrence. CT densitometry can delineate tumor versus treatment zones.