tbuckley/cabot-search huggingface dataset:
Abstract 947: Effects of methadone on ovarian cancer cell-lines and patient-derived tumor-spheroids
Authors: Heidelinde Fiegl, Judith Hagenbuchner, Michael J. Ausserlechner, Christiana Kyvelidou, Beata Seeber, Sieghart Sopper, Irina Tsibulak, Verena Wieser, Julia Roessler, Elisabeth Reiser, Kaisa Huhtinen, Olli Carpén, Walther Parson, Christian Marth, Alain G. Zeimet
Journal: Cancer Research (2021)

Abstract Background: D,L-Methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. Although the use of this opioid-receptor agonist as an anti-cancer drug is deemed controversial, this drug is gaining popularity in Europe as an “off-label” therapy despite insufficient research to support its benefits. In preclinical glioblastoma and leukaemia cell culture models D,L-methadone showed apoptotic and chemo-sensitizing effects. Its effects in ovarian cancer (OC) are completely unexplored. Methods: We analysed the OPRM mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 192 OC samples and 12 non-neoplastic control tissues. Pro-angiogenetic, cytotoxic and apoptotic effects of D,L-methadone were evaluated in OC cell-lines and four patient-derived tumor-spheroid models. Results: OPRM1 was transcriptionally expressed in 69% of OC-tissues and in five of eight OC cell-lines. D,L-methadone exposure significantly reduced cell-viability in five OC cell-lines irrespective of OPRM1 expression. D,L-methadone, applied alone or combined with cisplatin, showed no significant effects on apoptosis or VEGF secretion in cell-lines. Notably, in two of the four spheroid models, treatment with D,L-methadone resulted in significantly enhanced cell growth (by up to 121%), especially after long-term exposure. This is consistent with the observed attenuation of the inhibitory effects of cisplatin in three spheroid models when adding D,L-methadone. The effect of methadone treatment on VEGF secretion in tumor-spheroids was inconclusive. Conclusions: Our study demonstrates that certain OC samples express OPRM1, which, however, is not a prerequisite for D,L-methadone function. As such, D,L-methadone may exert detrimental effects by stimulating the growth of certain OC-cells and abrogating cisplatin's therapeutic effect. Citation Format: Heidelinde Fiegl, Judith Hagenbuchner, Michael J. Ausserlechner, Christiana Kyvelidou, Beata Seeber, Sieghart Sopper, Irina Tsibulak, Verena Wieser, Julia Roessler, Elisabeth Reiser, Kaisa Huhtinen, Olli Carpén, Walther Parson, Christian Marth, Alain G. Zeimet. Effects of methadone on ovarian cancer cell-lines and patient-derived tumor-spheroids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 947.
Abstract 412: Blockade of beta-catenin pathway combined with Aurora kinase activity inhibition enhances antitumor effects in adrenocortical cancer cells
Authors: Andrea G. Maria, Kleiton S. Borges, Regia C. Lira, Carolina H. Thome, Annabel Berthon, Ludivine Drougat, Fabio R. Faucz, Vitor M. Faca, Luiz G. Tone, Constantine A. Stratakis
Journal: Cancer Research (2021)

Abstract Adrenocortical cancer (ACC) is a rare and aggressive type of endocrine tumor with high risk of recurrence and metastasis. The overall survival of patients diagnosed with ACC is very low and current treatment for metastatic stages remain limited to mitotane, which has low efficiency in advanced stages of the disease and is associated with high toxicity and side effects. Therefore, identification of new biological targets to improve ACC treatment is crucial. Beta-catenin alterations have been found in approximately 30% of ACCs and blockade of Wnt-beta-catenin showed to decrease adrenal steroidogenesis and increase apoptosis of ACC cells, NCI-H295, in vitro and in a mouse model. Aurora kinases are known to play an important role in cell division during G1-M phase and their aberrant expression is correlated with poor prognosis in different types of tumors. Hence, we hypothesized that inhibition of aurora kinase activity combined with beta-catenin pathway blockade could promote better antitumor effects in NCI-H295 cells. We studied the in vitro effects of AMG 900, an aurora kinase activity inhibitor and PNU-74654, a beta-catenin pathway blocker, in proliferation, migration, colony establishment and invasion of NCI-H295 and SW-13 ACC cell lines. Our results show that the combination of AMG 900 with PNU-74654, decreases cell proliferation and viability, compared to either one of the single treatments. Regarding cell invasion and clonogenesis inhibition, AMG 900 was more efficient than PNU-74654, and its combination with the latter did not improve these effects. On the other hand, PNU-74654 was more effective in decreasing cortisol secretion. Taken together, our data suggest that inhibition of aurora kinases activity combined with blockade of the beta-catenin pathway could bring new approaches for designing new drugs to treat certain ACCs. Citation Format: Andrea G. Maria, Kleiton S. Borges, Regia C. Lira, Carolina H. Thome, Annabel Berthon, Ludivine Drougat, Fabio R. Faucz, Vitor M. Faca, Luiz G. Tone, Constantine A. Stratakis. Blockade of beta-catenin pathway combined with Aurora kinase activity inhibition enhances antitumor effects in adrenocortical cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 412.
Soy isoflavones and breast cancer risk among Chinese women in Singapore: A cohort analysis
Authors: Woon-Puay Koh, Anna Wu, Renwei Wang, Hin-Peng Lee, Mimi Yu
Journal: Cancer Research (2008)

4160  A large number of in-vitro experiments and studies in animals have shown that phytoestrogens such as isoflavones from soy foods may have a chemopreventive role in breast cancer. Although the collective evidence from numerous case-control studies has suggested that a high intake of soy products may reduce breast cancer risk, evidence from population-based prospective studies is very sparse. We examined the relationship between intake of soy isoflavones and breast cancer risk in the Singapore Chinese Health Study, a population-based prospective cohort of 63,257 middle-aged and older Chinese men and women enrolled between 1993 and 1998. Detailed information on current diet, assessed via a validated food frequency questionnaire, medical history and lifestyle factors were obtained through an in-person interview at enrollment. The cohort has been continuously followed, both actively through re-interviews and passively through computer linkage to population-based death and cancer registries. Loss to follow-up has been negligible. All breast cancer cases identified from the cancer registry were subsequently verified through manual review of pathological reports and medical records. As of 31 December 2005, 629 women had developed incident breast cancer among the 34,028 women participants. We used the Cox regression methods to examine soy intake in relation to breast cancer risk with adjustment for age at and year of study enrollment, dialect group, level of education, family history of breast cancer, age when period became regular, number of livebirths, body mass index and n-3 fatty acid intake. High (above median value for all female participants) versus low dietary soy isoflavones was associated with a statistically significant, 18% reduction in breast cancer risk (relative risk [RR], 0.82; 95% confidence interval [CI], 0.70-0.97). When subjects were stratified by duration of follow-up, the soy-risk association was strongest among those with the longest (>10 years) duration of follow-up (RR, 0.48; 95% CI, 0.30-0.79). Earlier, in a case-control study, we noted that the protective effect of dietary soy in Asian American women is stronger for adolescent versus adulthood consumption (Wu et al., 2006). Thus, the present findings are consistent with our previous observation, both indicating that time of dietary soy exposure is an important codeterminant of breast cancer risk, with earlier exposure relating to a greater degree of risk reduction.
Abstract 151: An improved computational pipeline for tumor somatic alterations detection
Authors: Cheng Yan, Yingjiang Ye, Weihua Guo, Junhui Yang, Yufei Yang
Journal: Cancer Research (2021)

Abstract Background: As high throughput sequencing (HTS) technique advances, it has been widely used in cancer research. More specifically, HTS enables genome-wide detection of somatic alterations which implicate the dynamic of cancer development as well as therapeutic strategy. However, a number of complications, such as sample tissue lesion, imperfect experimental procedure and nucleotide polymorphism between individual, often induce non-somatic noise and jeopardize the detection of somatic alterations. We present a validated computational pipeline that allows accurate somatic alteration identification. Method: We created a number of cell line mixture samples and sequenced at averagely 1500x depth. Each mixture sample was composed of cell lines with pre-specified proportion in order to represent distinct tumor purity and clonality. Prior to mixture creation, variant candidates in each cell line sample were labeled as one of three categories: germline variant of high confidence, artifact or blacklist (excluded from future assessment). The categorization was based on HaplotypeCaller results followed by a series of quality control. The allele frequency distribution of germline variants from each cell line was validated in mixture samples. We used MuTect as prototype pipeline and implemented further optimization on a number of parameter settings in a supervised fashion. Lastly, the optimized pipeline was evaluated using an independent dataset and its performance was compared with a number of alternative variant callers. Result: Our benchmark showed that default parameter setting of ‘alt_allele_in_normal' and ‘nearby_gap_events' in MuTect were over-strict. 73% of variants rejected by these parameters were actually real somatic variants. We believed that, instead of using constant as parameter settings, the optimum parameters should be trained on data with similar sequencing depth. We therefore re-configured the parameters using logistic regression. Furthermore, minimum supporting depth and minimum allele frequency were determined by AUROC. With optimized pipeline, we were able to achieve 96% sensitivity and 2/M false positive rate (FPR) compared with 90% sensitivity and 8/M FPR using default parameters. We further tested the optimized pipeline in an independent dataset and compared the performance with several well-known variant callers including MuSE, VarScan2, Strelka, LoFreq, VarDict and MuTect2. The performance of each caller was ranked as following: our optimized pipeline &amp;gt; MuTect &amp;gt; MuTect2/Strelka/LoFreq &amp;gt; Muse &amp;gt; VarScan2/VarDict. Citation Format: Cheng Yan, Yingjiang Ye, Weihua Guo, Junhui Yang, Yufei Yang. An improved computational pipeline for tumor somatic alterations detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 151.
Abstract 2164: Overexpression of the TERT binding proteins GABPA/B in Glioblastoma
Authors: Marco Timmer, Efthymios Papazacharias, Roland Goldbrunner
Journal: Cancer Research (2021)

Abstract Enhanced expression of TERT in gliomas is a result of two hotspot mutations, C228T and C250T, at the promoter region. GA-binding proteins selectively bind at these positions, respectively causing an activation of the promoter and overexpression of TERT. GABP is a multimeric protein consisting of GABPA and GABPB with its isoforms GABPB1, GABPB1-L, GABPB1-S, GABPB2. In this study, we investigated the mRNA expression and association between TERT and GABPA/B isoforms in tumor samples of different glioma grades. The expression was determined by quantitative real-time PCR and the results were statistically analyzed. We present that TERT is mainly expressed in primary glioblastomas. All GA-binding proteins progress through the glioma grades and have the highest expression levels in secondary glioblastomas. In secondary glioblastomas after chemotherapy, GABPB1 and GABPB1-L are lower expressed than without treatment. In high grades, TERT and GABPA, GAPB1, GABPB1-L, GABPB1-S are upregulated compared to low grades. Between primary and secondary glioblastomas with and without chemotherapy, TERT is elevated in the former while GABPB1 is increased in the secondary glioblastomas. GABPA and GABPB1, GABPB1-L and GABPB1-S positive correlate in primary glioblastomas. The present study confirms the upregulation of TERT in primary glioblastomas while all GABP proteins rise with the malignancy of the gliomas. TERT and all GABP proteins seem to play a key role in the gliomagenesis. Citation Format: Marco Timmer, Efthymios Papazacharias, Roland Goldbrunner. Overexpression of the TERT binding proteins GABPA/B in Glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2164.
ACOSOG Z0011:センチネルリンパ節転移陽性の臨床病期T1-2 N0 M0 乳癌女性における腋窩リンパ節切除の無作為化試験
Authors: A E Giuliano, L M Mccall, P D Beitsch, P W Whitworth, M Morrow, P W Blumencranz, A M Leitch, S Saha, K Hunt, K V Ballman
Journal: Journal of Clinical Oncology (2010)
Pentafecta achievement comparison between open and robot-assisted radical cystectomy with totally intracorporeal urinary diversion: Results from a randomized controlled trial
Authors: R. Mastroianni, G. Tuderti, U. Anceschi, A.M. Bove, A. Brassetti, M. Ferriero, L. Misuraca, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2021)
Prevalence of chronic diseases in older Palestinian adults and common pharmacological interventions: a cross-sectional study
Authors: Anas Najjar, Beesan Warasna, Islam Kitaneh, Salam Abu-Sharar, Maryam Sawalha, Abrar Jamous, Muhannad Qiq, Wafa Amro, Enas Makharzeh, Yazan Amro, Bayan Subb Laban, Ahmad Amro
Journal: The Lancet (2021)
In patients with AMI and anemia, a restrictive vs. liberal blood transfusion strategy was noninferior for 30-d MACE
Authors: Debbie Jiang, David Garcia
Journal: Annals of Internal Medicine (2021)

Source Citation Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, et al. Effect of a restrictive vs liberal blood transfusion strategy on major cardiovascular events among patients with acute myocardial infarction and anemia: the REALITY randomized clinical trial. JAMA. 2021;325:552-60. 33560322
External validation of a nomogram for predicting 68Ga-PSMA PET/CT detection rate in patients with prostate cancer recurrence. A clinical tool to guide physicians before suggesting 68Ga-PSMA PET/CT
Authors: L. Bianchi, F. Ceci, M. Droghetti, P. Castellucci, C. Artigas, J. Leite, P. Corona, A. Farolfi, Q.A. Shagera, R. Moreira, C. Gonzàles, M. Queiroz, F.D.G. Barbosa, R. Schiavina, E. Brunocilla, D. Deandreis, S. Fanti
Journal: European Urology (2021)
In overweight or obese adults without diabetes, semaglutide increased weight loss and GI disorders
Authors: Selvi Rajagopal, Lawrence J. Cheskin
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubJuly 2021In overweight or obese adults without diabetes, semaglutide increased weight loss and GI disordersSelvi Rajagopal, MD, MPH, Lawrence J. Cheskin, MDSelvi Rajagopal, MD, MPHJohns Hopkins University, Baltimore, Maryland, USA (S.R.), Lawrence J. Cheskin, MDGeorge Mason University and John Hopkins University, Fairfax, Virginia, and Baltimore, Maryland, USA (L.J.C.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202107200-080 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationWilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989. https://pubmed.ncbi.nlm.nih.gov/33567185Clinical Impact RatingsGIM/FP/GP: Endocrinology: Public Health: References1 Tak YJ, Lee SY. Long-term efficacy and safety of anti-obesity treatment: where do we stand? Curr Obes Rep. 2021;10:14-30. [PMID: 33410104] Google Scholar2 O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018;392:637-49. [PMID: 30122305] Google Scholar3 Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397:971-84. [PMID: 33667417] Google Scholar Author, Article, and Disclosure InformationAffiliations: Johns Hopkins University, Baltimore, Maryland, USA (S.R.)George Mason University and John Hopkins University, Fairfax, Virginia, and Baltimore, Maryland, USA (L.J.C.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7318.This article was published at Annals.org on 6 July 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics July 2021Volume 174, Issue 7Page: JC80KeywordsBody mass indexDrugsHemoglobinNauseaObesityOverweightPrevention, policy, and public healthSafetyType 2 diabetesWeight loss ePublished: 6 July 2021 Issue Published: July 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Guidance for Health Care Leaders During the Recovery Stage of the COVID-19 Pandemic
Authors: Jaason M. Geerts, Donna Kinnair, Paul Taheri, Ajit Abraham, Joonmo Ahn, Rifat Atun, Lorena Barberia, Nigel J. Best, Rakhi Dandona, Adeel Abbas Dhahri, Louise Emilsson, Julian R. Free, Michael Gardam, William H. Geerts, Chikwe Ihekweazu, Shanthi Johnson, Allison Kooijman, Alika T. Lafontaine, Eyal Leshem, Caroline Lidstone-Jones, Erwin Loh, Oscar Lyons, Khalid Ali Fouda Neel, Peter S. Nyasulu, Oliver Razum, Hélène Sabourin, Jackie Schleifer Taylor, Hamid Sharifi, Vicky Stergiopoulos, Brett Sutton, Zunyou Wu, Marc Bilodeau
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The COVID-19 pandemic is the greatest global test of health leadership of our generation. There is an urgent need to provide guidance for leaders at all levels during the unprecedented preresolution recovery stage. <h3>Objective</h3> To create an evidence- and expertise-informed framework of leadership imperatives to serve as a resource to guide health and public health leaders during the postemergency stage of the pandemic. <h3>Evidence Review</h3> A literature search in PubMed, MEDLINE, and Embase revealed 10 910 articles published between 2000 and 2021 that included the terms<i>leadership</i>and variations of<i>emergency</i>,<i>crisis</i>,<i>disaster</i>,<i>pandemic</i>,<i>COVID-19</i>, or<i>public health</i>. Using the Standards for Quality Improvement Reporting Excellence reporting guideline for consensus statement development, this assessment adopted a 6-round modified Delphi approach involving 32 expert coauthors from 17 countries who participated in creating and validating a framework outlining essential leadership imperatives. <h3>Findings</h3> The 10 imperatives in the framework are: (1) acknowledge staff and celebrate successes; (2) provide support for staff well-being; (3) develop a clear understanding of the current local and global context, along with informed projections; (4) prepare for future emergencies (personnel, resources, protocols, contingency plans, coalitions, and training); (5) reassess priorities explicitly and regularly and provide purpose, meaning, and direction; (6) maximize team, organizational, and system performance and discuss enhancements; (7) manage the backlog of paused services and consider improvements while avoiding burnout and moral distress; (8) sustain learning, innovations, and collaborations, and imagine future possibilities; (9) provide regular communication and engender trust; and (10) in consultation with public health and fellow leaders, provide safety information and recommendations to government, other organizations, staff, and the community to improve equitable and integrated care and emergency preparedness systemwide. <h3>Conclusions and Relevance</h3> Leaders who most effectively implement these imperatives are ideally positioned to address urgent needs and inequalities in health systems and to cocreate with their organizations a future that best serves stakeholders and communities.
Abstract 2886: The mechanistic effect of DHA on FABP7 associated membrane lipid order &amp; nanodomain distribution in glioblastoma migration
Authors: Xia Xu, Yixiong Wang, Wonshik Choi, Roseline Godbout
Journal: Cancer Research (2021)

Abstract Glioblastoma (GBM) is the most common primary brain malignancy. Brain fatty acid binding protein (B-FABP, FABP7) promotes glioblastoma (GBM) migration and correlates to dismal prognosis in GBM patients. Long chain polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and arachidonic acid (AA) are abundant in brain cell membranes. DHA and AA are preferred ligands of FABP7, with DHA having the stronger affinity for FABP7. Previous studies have shown that DHA inhibits GBM migration in an FABP7-dependent manner. In the current study, we have demonstrated that DHA dramatically altered membrane FABP7 nanoscale distribution pattern, which resulting from plasma membrane lipid ordered domain disruption in GBM cells and neurosphere cultures. We used quantitative membrane order assay to show that FABP7-expressing cells has increased membrane lipid order which is tightly correlated with higher GBM migration property. Using stimulated emission depletion (STED) microscopy, we observed lipid ordered domain was associated with FABP7 nanoscale domain formation. Interestingly, super-resolution microscopy quantitative image analysis revealed that FABP7 membrane nanodomains distribution was dramatically altered upon DHA treatment, which is associated with DHA inhibitory effect on membrane lipid order. Furthermore, STED microscopy has also revealed that reduced FABP7 nanodomain formation in slow migrating GBM cells are similar as FABP7-expressing GBM cells upon DHA treatment. Therefore, we hypothesize that these alterations are likely to be the mechanism of FABP7-mediated DHA inhibitory role in GBM migration. Citation Format: Xia Xu, Yixiong Wang, Wonshik Choi, Roseline Godbout. The mechanistic effect of DHA on FABP7 associated membrane lipid order &amp; nanodomain distribution in glioblastoma migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2886.