Pioneer of prostate cancer: past, present and the future of FOXA1

Prostate cancer is the most commonly diagnosed noncutaneous cancers in North American men.While androgen deprivation has remained as the cornerstone of prostate cancer treatment,resistance ensues leading to lethal disease.Forkhead box A1(FOXA1)encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors.Through direct interactions with the Androgen Receptor(AR),FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells.FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition(EMT).In prostate cancer,mutations converge onto the coding sequence and c/s-regulatory elements(CREs)of FOXA1,leading to functional alterations.In addition,FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation.In this review,we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer,pointing to their relevance to guide future clinical interventions.

Radiomics in sarcoma trials:a complement to RECIST for patient assessment

Radiological imaging has a critical role in the diagnosis of sarcomas and in evaluating therapy response assessment.The current gold standard for response assessment in solid tumors is the Response Evaluation Criteria in Solid Tumors,which evaluates changes in tumor size as a surrogate endpoint for therapeutic efficacy.However,tumors may undergo necrosis,changes in vascularization or become cystic in response to therapy,with no significant volume changes;thus,size assessments alone may not be adequate.Such morphological changes may give rise to radiographic phenotypes that are not easily detected by human operators.Fortunately,recent advances in high-performance computing and machine learning algorithms have enabled deep analysis of radiological images to extract features that can provide richer information about intensity,shape,size or volume,and texture of tumor phenotypes.There is growing evidence to suggest that these image-derived or“radiomic features”are sensitive to biological processes such as necrosis and glucose metabolism.Thus,radiomics could prove to be a critical tool for assessing treatment response and may present an integral complement to existing response criteria,opening new avenues for patient assessment in sarcoma trials.

Achieving the Goals of Healthy China 2030 Depends on Increasing Smoking Cessation in China:Comparative Findings from the ITC Project in China,Japan,and the Republic of Korea

Summary Tobacco smoking is the number one preventable cause of disease and death in China as it is globally.Indeed,the toll of smoking in China is much greater than its status as the world’s most populous country.There is a persistent and continuing need for China to implement the measures specified in the global tobacco control treaty,the World Health Organization(WHO)Framework Convention on Tobacco Control(FCTC),which China ratified in 2005.

The Importance of Reducing Smoking in China: To Achieve Healthy China 2030 While Reducing the Severity of the COVID-19 Pandemic

The coronavirus disease 2019(COVID-19)pandemic is the most devastating threat to global health since the 1918 influenza pandemic.As of May 22,2020,there have been 5.1 million cases confirmed,with over 333,000 deaths.And we are just at the beginning of a long struggle.There is a connection between COVID-19—the greatest infectious disease outbreak in a century—and the greatest chronic disease threat in the world today—tobacco smoking.Smoking has been identified by the World Health Organization(WHO)as the“single greatest preventable cause of death in the world”(1).Tobacco smoking kills 7.1 million people a year(2),with an additional 1.2 million dying from secondhand smoke(2).

Local Brand Smoking Among Adult Smokers:Findings from the Wave 5 International Tobacco Control China Survey--China,2015

Summary What is already known about this topic?Branding of cigarettes may play a role in shaping the smoking behaviors of Chinese smokers,and local brand(LB)cigarettes may reflect this influence because of greater tax and non-tax incentives compared to non-LB.Some of these brands are regional flagships that market to smokers using local landmarks or icons.What is added by this report?LB brands were significantly more likely to be the usual brand of smokers residing in provincial-level administrative divisions(PLADs)that produced their own LB cigarettes[adjusted odds ratio(AOR):30.95;95%confidence interval(CI):26.36–36.49]compared to those residing in PLADs that had non-local ventures with non-LB cigarettes.Further,smokers residing in urban areas were found to be less likely to smoke LB cigarettes(AOR:0.79;95%CI:0.67–0.93)compared to those in rural areas.What are the implications for public health practice?These findings suggest that LB smoking may be a result of industry-driven incentives to boost LB sales,fueled by such as supply-side strategies to boost LB sales or targeted cultural/social marketing that appeals to certain demographic groups.Although addressing these incentives to support LBs would be challenging given the nature of China’s tobacco industry,doing so would have potential to reduce cigarette smoking and ultimately the health burden of smoking in China.

Aberrant DNA methylation reprogramming during induced pluripotent stem cell generation is dependent on the choice of reprogramming factors

The conversion of somatic cells into pluripotent stem cells via overexpression of reprogramming factors involvesepigenetic remodeling. DNA methylation at a significant proportion of CpG sites in induced pluripotent stem cells(iPSCs) differs from that of embryonic stem cells (ESCs). Whether different sets of reprogramming factors influencethe type and extent of aberrant DNA methylation in iPSCs differently remains unknown. In order to help resolvethis critical question, we generated human iPSCs from a common fibroblast cell source using either the Yamanakafactors (OCT4, SOX2, KLF4 and cMYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28), and determinedtheir genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all ouriPSCs, we identified Yamanaka-iPSC (Y-iPSC)-specific and Thomson-iPSC (T-iPSC)-specific recurrent aberrations.Strikingly, not only were the genomic locations of the aberrations different but also their types: reprogrammingwith Yamanaka factors mainly resulted in failure to demethylate CpGs, whereas reprogramming with Thomsonfactors mainly resulted in failure to methylate CpGs. Differences in the level of transcripts encoding DNMT3b andTET3 between Y-iPSCs and T-iPSCs may contribute partially to the distinct types of aberrations. Finally, de novoaberrantly methylated genes in Y-iPSCs were enriched for NANOG targets that are also aberrantly methylated insome cancers. Our study thus reveals that the choice of reprogramming factors influences the amount, location,and class of DNA methylation aberrations in iPSCs. These findings may provide clues into how to produce humaniPSCs with fewer DNA methylation abnormalities.