tbuckley/cabot-search huggingface dataset:
Abstract 1924: miR-142-3p is a candidate mediator of chloride intracellular channel 4 (CLIC4) loss during squamous cancer progression
Authors: Brandi L. Carofino, Stuart H. Yuspa
Journal: Cancer Research (2016)

Abstract Chloride intracellular channel 4 (CLIC4) is a broadly expressed protein that has been implicated in multiple cellular processes, including cellular differentiation and apoptosis. As a soluble factor, CLIC4 translocates to the nucleus following exposure to a variety of stimuli, including TGF-β, TNF-α, and etoposide. Nuclear CLIC4 potentiates TGF-β signaling by preventing the dephosphorylation of phospho-SMAD2 and 3 and promotes growth arrest. Although its primary function is as a tumor suppressor, CLIC4 expression is progressively diminished during cancer progression and CLIC4 protein is excluded from the nucleus of many human epithelial neoplasms and squamous cell carcinoma (SCC) cell lines. To date, no gene deletions or mutations have been identified to account for this phenomenon; thus, identifying the mechanism of CLIC4 loss is our primary focus. To determine if epigenetic gene silencing is responsible, we evaluated the methylation status of the CLIC4 promoter in a progression panel (normal, papilloma, SCC) of epithelial cell lines by performing bisulfite sequencing. No differential promoter methylation was found between the cell lines, suggesting that the regulation may be post-transcriptional or post-translational. Because microRNAs (miRNAs) are known to regulate gene expression by mediating the degradation or translational repression of target mRNAs, we performed a bioinformatic analysis of the CLIC4 3’ UTR, which revealed a large number of putative targeting miRNAs. One such miRNA, miR-142-3p, has been predicted to target CLIC4 by multiple algorithms and has been shown to interact with the CLIC4 3’ UTR by high-throughput sequencing and crosslinking immunoprecipitation. We confirmed the functional activity of miR-142-3p against the CLIC4 3’ UTR by using a 3’ UTR luciferase reporter assay and a miR-142-3p mimic. miR-142-3p is high in the tumor tissue and plasma of patients with head and neck SCC and is correlated with worse prognosis, where CLIC4 expression is known to be low. Thus, miR-142-3p may be responsible for mediating CLIC4 loss in squamous lesions and warrants further investigation. Citation Format: Brandi L. Carofino, Stuart H. Yuspa. miR-142-3p is a candidate mediator of chloride intracellular channel 4 (CLIC4) loss during squamous cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1924.
Ophthalmologist who had an affair with patient avoids sanctions because of “unique” surgical skills
Authors: Clare Dyer
Journal: BMJ (2016)

A London consultant ophthalmologist who had an affair with a patient has escaped sanction by the Medical Practitioners Tribunal Service after it ruled that his unique surgical skills made him too important to patients’ welfare to suspend.

John Brookes, 47, a glaucoma expert at London’s Moorfields Eye Hospital, had earned praise for his work with Orbis International, a charity that operates a passenger jet equipped with a mobile operating theatre. Brookes had made several trips to India and Mongolia, saving the sight of children with glaucoma.

He was also considered one of the world’s most skilled paediatric eye surgeons, and brought to his Manchester hearing a …
Abstract 2981: DNA damaging agent-induced apoptosis is controled by MCL-1 phosphorylation and degradation mediated by the Noxa/MCL-1/CDK2 complex
Authors: Wataru Nakajima, June Y. Lee, Nicolas Maxim, Kanika Sharma, Mark A. Hicks, Thien-Trang Vu, Angela Luu, William Andrew Yeudall, Nobuyuki Tanaka, Hisashi Harada
Journal: Cancer Research (2016)

Abstract DNA damaging agents, such as cisplatin and etoposide, are employed for the treatment of a wide array of solid tumors, but the prolonged use of chemotherapeutic drugs is limited by their toxicity and by the development of resistance. To overcome these major roadblocks to improved prognosis requires mechanism-based therapeutic strategies that maximize the antitumor effect of drugs while limiting their toxicities. These agents exert anticancer effects via multiple mechanisms, yet their most prominent mode of action involves the generation of DNA lesions followed by activation of the DNA damage response and induction of the BCL-2 family-dependent mitochondrial apoptosis. However, the signaling pathways that connect to BCL-2-family-regulated cell death are not entirely clear. Noxa, a BH3-only pro-apoptotic BCL-2 family protein, causes apoptosis by specifically interacting with the anti-apoptotic BCL-2 family protein MCL-1 to induce its proteasome-mediated degradation. We show here that the DNA damaging agents cisplatin and etoposide upregulate Noxa expression, which is required for the phosphorylation of MCL-1 at Ser64/Thr70 sites, proteasome-dependent degradation, and as a consequence, apoptosis. Noxa-induced MCL-1 phosphorylation at these sites occurs at the mitochondria and is primarily regulated by CDK2. MCL-1 and CDK2 form a stable complex and Noxa binds to this complex to facilitate the phosphorylation of MCL-1. When Ser64 and Thr70 of MCL-1 are substituted with alanine, the mutated MCL-1 is neither phosphorylated nor ubiquitinated, and becomes more stable than the wild-type protein. As a consequence, this mutant can inhibit apoptosis induced by Noxa overexpression or cisplatin treatment. These results indicate that Noxa-mediated MCL-1 phosphorylation followed by MCL-1 degradation is critical for apoptosis induced by DNA damaging agents through regulation of the Noxa/MCL-1/CDK2 complex. Of note, the identified phosphorylation sites are only observed in human MCL-1; thus, the regulatory mechanism shown here may be human-specific. It is of interest in the future to analyze whether CDK2 expression/activity correlates to cisplatin-resistance in patient samples. Citation Format: Wataru Nakajima, June Y. Lee, Nicolas Maxim, Kanika Sharma, Mark A. Hicks, Thien-Trang Vu, Angela Luu, William Andrew Yeudall, Nobuyuki Tanaka, Hisashi Harada. DNA damaging agent-induced apoptosis is controled by MCL-1 phosphorylation and degradation mediated by the Noxa/MCL-1/CDK2 complex. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2981.
Effectiveness of Cetuximab (Cet) and Bevacizumab (Bev) for metastatic colorectal cancer (mCRC) according to primary tumor location (PTL): findings from a ‘real-world’ retrospective analysis
Authors: L. Calvetti, M. Pavarana, A. Auriemma, L. Tondulli, E. Bria, A. Molino, G. Tortora
Journal: Annals of Oncology (2015)
Abstract 5249: Crocin prevents early lesions of liver cancer:system biology approach
Authors: Amr Amin, Alaaeldin A. Hamza, Sayel Daoud, Kamal Khazanehdari, Ala’a Al Hrout, Badriya Baig, Amphun Chaiboonchoe, Thomas E. Adrian, Nazar Zaki, Kourosh Salehi-Ashtiani
Journal: Cancer Research (2016)

Abstract The angiogenesis inhibitor, sorafenib, remains the only available therapy of the poorly diagnosed hepatocellular carcinoma (HCC). Only recently patents of VEGF receptors-3 inhibitors are developed.; hence,Thus, a novel approach against HCC is essential for a better therapeutic outcome. Saffron and its active constituents were reported to have anti-tumor properties. Objective: The aims of this study were to examine the chemopreventive action of saffron's main biomolecule, crocin, against chemically-induced liver cancer in rats, and to explore the mechanisms by which crocin employs its anti-tumor effects. Method: We investigated the anti-cancer effect of crocin on an experimental carcinogenesis model of liver cancer by studying the anti-oxidant, anti-inflammatory, anti-proliferation, pro-apoptotic activities of crocin in vivo. In addition, we provided a network analysis of differentially expressed genes in tissues of animals pre-treated with crocin in comparison to induced-HCC animals’ tissues. To further support our results, in vitro analysis was carried out. We assessed the effects of crocin on HepG2 cells viability by treating them with various concentrations of crocin; in addition, effects of crocin on cell cycle distribution of HepG2 cells were investigated. Results: Findings reported herein demonstrated the anti-proliferative and pro-apoptotic properties of crocin when administrated in induced-HCC model. Crocin exhibited anti-inflammatory properties where NF-kB, among other inflammatory markers, was inhibited. In vitro analysis confirmed crocin's effect in HepG2 by arresting the cell cycle at G2/M phase, inducing apoptosis and down regulating inflammation. Network analysis identified NF-kB as a regulatory hub, and therefore, a candidate therapeutic drug target. Conclusion: Taken together, our findings introduce crocin as a candidate chemopreventive agent against HCC. Citation Format: Amr Amin, Alaaeldin A. Hamza, Sayel Daoud, Kamal Khazanehdari, Ala’a Al Hrout, Badriya Baig, Amphun Chaiboonchoe, Thomas E. Adrian, Nazar Zaki, Kourosh Salehi-Ashtiani. Crocin prevents early lesions of liver cancer:system biology approach. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5249.
Abstract 5264: The National Cancer Institute's biospecimen research database: A community resource for improving specimen quality
Authors: Kelly B. Engel, Sarah R. Greytak, Ping Guan, Helen Moore
Journal: Cancer Research (2016)

Abstract Tissue and blood biospecimens used in cancer research are collected, processed and stored using standard operating procedures (SOPs) that can vary tremendously across institutions. This lack of standardization in biospecimen collection and processing practices across sample sets and institutions can be a contributing source of research variability and can compromise analytical results. In an effort to minimize preanalytical variability and improve the quality of biospecimens used for cancer research, the National Cancer Institute's Biorepositories and Biospecimen Research Branch (BBRB) developed the Biospecimen Research Database (BRD; http://biospecimens.cancer.gov/brd). The BRD is a free and publically accessible online database that aims to (i) improve access to peer-reviewed articles that investigate the impacts that biospecimen collection and handling practices can have on clinical, molecular, and proteomic endpoints, (ii) facilitate transparency between institutions and researchers by promoting SOP sharing and distribution, and (iii) improve the quality of biospecimens through the development of evidence-based procedural guidelines. To date, the BRD houses more than 2,300 articles and 200 SOPs from 30 different participating biobanking institutions. Articles are meticulously categorized and annotated by a team of Ph.D.-level scientists according to the type of biospecimen and technology platform used and the preanalytical factors investigated. Literature contained within the BRD serves as the foundation for internally developed reviewed papers as well as evidence-based procedural guidelines, termed Biospecimen Evidence-Based Practices, which focus on biospecimen collection, preservation, and processing. In addition, more than 90% of the BRD's SOP library was contributed by other government offices, non-profit, private, and international biobanks and institutions. BBRB has invested a substantial and continued level of effort in the establishment of this scientifically accurate and robust database. Ongoing participation by the scientific community in the form of public commenting, article suggestions and SOP submissions is encouraged and will increase both the diversity and value of the BRD. Citation Format: Kelly B. Engel, Sarah R. Greytak, Ping Guan, Helen Moore. The National Cancer Institute's biospecimen research database: A community resource for improving specimen quality. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5264.
Margaret McCartney: Game on for Pokémon Go
Authors: Margaret McCartney
Journal: BMJ (2016)

The game Pokemon Go is a “craze,” a “sensation.” You use a smartphone in a virtual scavenger hunt for cartoon characters, but in real locations. It appeals to youngsters and kidults. Download the app; start walking.

My youngest child is delighted that his mother willingly accompanies him for miles. The middle child is disgusted with our dedication to the cause, but also (I think) impressed with our plans for domination. My eldest is aghast: the popularity of Pokemon Go leads him to infer, just as Donald Trump ascends to presidential candidacy, that we’re at The End of Times.

The …
Revertant mosaicism in recessive dystrophic epidermolysis bullosa due to intragenic crossover in the COL7A1 gene
Authors: N. Almaani, N. Nagy, L. Liu, P. D. C. Dopping-Hepenstal, J. E. Lai-Cheong, S. Clements, T. Techanukul, A. Tanaka, J. E. Mellerio, J. A. McGrath
Journal: British Journal of Dermatology (2010)
Incidence of Acute Respiratory Distress Syndrome
Authors: Ilias I. Siempos, David A. Berlin
Journal: JAMA (2016)

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Impact of the Gather mHealth System on A1C: Primary Results of a Multisite Randomized Clinical Trial Among People With Type 2 Diabetes in India
Authors: Nora J. Kleinman, Avani Shah, Sanjiv Shah, Sanjeev Phatak, Vijay Viswanathan
Journal: Diabetes Care (2016)

Diabetes prevalence in India was 8.7% in 2015 and is rising because of rapid urbanization, increasing life expectancy, and a diet rich in sugar and fat (1). However, less than 20% of people living with diabetes in India achieved target A1C levels in 2011 (2). India’s growing prosperity fuels this epidemic and, through increased mobile phone access, also offers pathways to improve care. A recent review of reviews confirmed the overall benefits of telemedicine in diabetes management (3), but little research has been conducted in developing countries.

A total of 91 people aged 18–65 years with type 2 diabetes, an A1C between 7.5 and 12.5% (58 and 113 mmol/mol), and an Android smartphone were recruited at three sites in Ahmedabad, Chennai, and Mumbai (March–May 2015), randomized 1:1 to the Gather mobile health (mHealth) intervention or usual care, and observed for 6 months. All received free visits, laboratory tests, and test strips and lancets. Intervention participants received the mHealth app and a mobile phone plan stipend. Data were collected through physical measurements, laboratory tests, …
Abstract 3807: Histone deacetylase inhibitors repress hypoxia signaling through affecting Hsp90
Authors: Chunzhang Yang, Zhengping Zhuang
Journal: Cancer Research (2016)

Abstract Histone deacetylase inhibitors (HDACis) are among the most promising recently developed anti-cancer agents. Recent work suggests that HDACis suppress both malignant cell metabolism and progression by interfering with the hypoxia-inducible factor (HIF) signaling, which plays a key role in tumor progression in both actual and falsely perceived cellular hypoxia (pseudohypoxia). However, the precise biochemical mechanism of HDACis repression of HIFs function remains unclear. In this study, we demonstrated that the class-2 histone deacetylase inhibitor SAHA potently inhibits hypoxia signaling via interfering with heat shock protein 90 (Hsp90). HDACis increase in the acetylation of Hsp90, resulting in less HIF-α recognition and nuclear translocation. Accumulated cytoplasmic HIF-α is not transcriptionally active and degradaded through proteosomal pathway. Finally, we demonstrated that SAHA remarkably reduces hypoxia signaling and decreases tumor growth in vivo. These findings provide insight into new possible therapeutic strategies for using HDACis in tumors with known HIF pathway aberrations. Citation Format: Chunzhang Yang, Zhengping Zhuang. Histone deacetylase inhibitors repress hypoxia signaling through affecting Hsp90. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3807.
Former Johnson and Johnson executives are convicted over off label marketing
Authors: Owen Dyer
Journal: BMJ (2016)

Two former executives at Acclarent, a division of Johnson and Johnson, have been convicted of selling medical devices against Food and Drug Administration (FDA) recommendations but acquitted of graver felony charges of fraud and conspiracy.

William Facteau, former chief executive officer of Acclarent, and Patrick Fabian, former vice president of sales, launched the Relieva Stratus Microflow Spacer as a steroid delivery device after the FDA had expressly rejected that application and approved it only as a device for maintaining open sinuses, federal prosecutors said.

The two men hoped to rapidly boost the value of the company to find a buyer and hid the nature of their marketing from prospective buyers including Ethicon, the Johnson and Johnson device maker that bought Acclarent for …
Abstract 2565: Prostate cancer GWAS from more than 89,000 men identifies more than 30 novel prostate cancer susceptibility loci
Authors: Fredrick R. Schumacher, Ali A. Al Olama, Sonja I. Berndt, Fredrik Wiklund, David V. Conti, Mahbubl Ahmed, Sarah Benlloch, Douglas F. Easton, Peter Kraft, Stephen J. Chanock, Brian E. Henderson, Zsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles
Journal: Cancer Research (2016)

Abstract Genome-wide association studies (GWAS) and fine-mapping efforts have identified over 100 loci associated with prostate cancer susceptibility. Combined multiplicatively, these loci capture 33% of the familial risk for prostate cancer among European-ancestral populations. In order to identify novel prostate cancer susceptibility loci we conducted a GWAS involving over 53,000 prostate cancer cases and 36,000 controls using the OncoArray that includes a 260K GWAS backbone and a custom portion of 310K SNPs developed from previous GWAS and fine-mapping studies of multiple cancer types (http://epi.grants.cancer.gov/oncoarray/). Following standard quality control procedures, the prostate cancer OncoArray genotyped data were imputed using the October 2014 release of the 1000 genomes project data as a reference and analyzed by participating study for overall and advanced prostate cancer using logistic regression. The study-specific results were combined using inverse variance fixed effect meta-analysis. Regions surrounding previously associated variants (+/- 500kb of the reported index variant) were excluded to identify novel associations. In the OncoArray meta-analysis, we identified more than 30 novel loci significantly associated (P&amp;lt;5.0×10-8) with overall, advanced (Gleason ≥8, death from PrCa, PSA&amp;gt;100, or disease stage “Distant”), or early-onset (≤55 years of age) prostate cancer. Previous GWAS of prostate cancer are being imputed to the latest release of the 1000 genomes project to enhance our statistical power for novel discovery. In total our overall meta-analysis will incorporate over 176,000 individuals of European ancestry - more than 95,000 prostate cancer cases and 79,000 controls. The current results, as well as the larger ongoing meta-analysis, provide further insight into the underlying mechanisms of prostate cancer carcinogenesis and will improve the utility of genetic risk scores for targeted screening and prostate cancer prevention. Citation Format: Fredrick R. Schumacher, Ali A. Al Olama, Sonja I. Berndt, Fredrik Wiklund, David V. Conti, Mahbubl Ahmed, Sarah Benlloch, Douglas F. Easton, Peter Kraft, Stephen J. Chanock, Brian E. Henderson, Zsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles. Prostate cancer GWAS from more than 89,000 men identifies more than 30 novel prostate cancer susceptibility loci. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2565.