tbuckley/cabot-search huggingface dataset:
Abstract 4195: Steviol induces pancreatic cancer cell death <i>via</i> targeting glucose metabolism and protein translation pathways
Authors: Sonam Kumari, Sheema Khan, Mohammed Sikander, Shabnam Malik, Subhash C. Chauhan, Meena Jaggi
Journal: Cancer Research (2020)

Abstract Background Pancreatic cancer is one of the deadliest malignancies, and fourth leading cause of cancer-related deaths in the United States. Aberrant glucose metabolism in cancer cells leads to enhanced tumor growth and aggressiveness. Herein, we have identified an important constituent, steviol from the plant Stevia rebaudiana, which inhibits pancreatic cancer cells via modulation of glucose metabolism and protein translation. Methods Glucose and Lactate assays were performed in pancreatic cancer cells (HPAF-II and AsPC1) using kits purchased from Cayman Chemical. The effect of steviol on the growth, colonization and invasion of pancreatic cancer cells was determined by using in vitro functional assays for cell viability (MTT and xCELLigence), migration (Boyden chambers), invasion (Matrigel) and colonogenicity. The cell cycle study was performed using propidium iodide and analysis done through ModFit software. Immunoblotting was performed to analyze the expression of key proteins associated with translation machinery and apoptotic signaling pathways. Results Our results demonstrate that steviol inhibits proliferation and invasion of pancreatic cancer cells and modulates their glucose uptake and lactate secretion. Steviol treatment regulates the expression of proteins that control the translation machinery in a cell, which include mTOR, 4EBP1, eIF4E, eIF4B and eIF4G. Treatment of cells with steviol was observed to modulate cell cycle regulatory proteins, including p18, p21 and Cyclin D1 and block the cell cycle progression at G1 phase This followed the activation of apoptosis as indicated by upregulation of apoptotic protein, Bax and PARP cleavage. Conclusion: These results suggest that steviol suppresses pancreatic cancer growth and progression by regulating the glucose metabolism and protein translation. This prospects steviol as a promising therapeutic modality for pancreatic cancer prevention and treatment alone or in combination with other existing chemotherapeutic drugs. Citation Format: Sonam Kumari, Sheema Khan, Mohammed Sikander, Shabnam Malik, Subhash C. Chauhan, Meena Jaggi. Steviol induces pancreatic cancer cell death via targeting glucose metabolism and protein translation pathways [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4195.
Abstract 3854: Prevalence and prognostic role of FoxP3regulatory T lymphocytes in cancer: A tissue microarray study on &amp;gt;20,000 cancers
Authors: Tim Mandelkow, Elena Bady, Niclas Blessin, Claudia Hube-Magg, Ronald Simon, Guido Sauter, Christoph Fraune, Maximilian Lennartz, Katharin Möller, Sören Weidemann, Andreas Luebke, Doris Höflmayer
Journal: Cancer Research (2020)

Abstract Regulatory FoxP3+ lymphocytes function as suppressors of T-cell activity. The clinical impact of high FoxP3+ cell density in cancers is not fully understood, as some studies have linked high FoxP3+ cell density to good prognosis and others to poor prognosis in tumor cohorts with associated clinical data. While some data suggest that these variable data are due to biological differences between tumor entities, it is also possible that methodological differences have caused these discrepancies. This study was undertaken to analyze the density of FoxP3+ cells in various different cancer types by employing standardized methods. Tissue microarrays and large sections made from &amp;gt;20,000 prostate, breast, colorectal, ovarian, pancreatic, bladder and stomach cancers were analyzed together with various normal and inflamed tissues by conventional brightfield FoxP3 immunohistochemistry. Samples were also analyzed by fluorescent multiplex immunohistochemistry to assess the fraction of Ki67+ FoxP3+ cells. Our results indeed suggested a variable role of FoxP3+ cells in different tumor types. High FoxP3+ density was linked to high Gleason grade (p=0.0003) and early biochemical recurrence (p&amp;lt;0.0001) in 16923 prostate cancers, but to low tumor stage (p=0.027) and prolonged survival (p=0.0029) in 1341 breast cancers, and to low tumor stage (p&amp;lt;0.0001) in 744 colorectal cancers. No significant associations were found to tumor phenotype in 549 ovarian, 574 pancreatic, 549 bladder and 346 stomach cancers. Multiplex fluorescence IHC analysis of FoxP3 and Ki67 revealed comparable fractions of proliferating FoxP3+ cells in healthy tissues (average 12.3%, range 5.8-18.5%) and inflammatory conditions (average 7.6%, range 2.6-17.2%). Interestingly, the rate of Ki67+FoxP3+ cells was markedly higher in 36 bladder cancers (average 14.2%, range 0-49.3%) suggesting active expansion of FOXP3+ cells in cancer. Our data demonstrate an inverse prognostic impact of the FoxP3+ cell density in prostate and breast cancers. The increased proliferation rate of immune-regulatory FoxP3+ cells in some bladder cancer is interesting in the light of the variable response of these tumors to immune checkpoint inhibitors. Citation Format: Tim Mandelkow, Elena Bady, Niclas Blessin, Claudia Hube-Magg, Ronald Simon, Guido Sauter, Christoph Fraune, Maximilian Lennartz, Katharin Möller, Sören Weidemann, Andreas Luebke, Doris Höflmayer. Prevalence and prognostic role of FoxP3regulatory T lymphocytes in cancer: A tissue microarray study on &amp;gt;20,000 cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3854.
Evaluation of Drug Labels Following the 2015 Pregnancy and Lactation Labeling Rule
Authors: John J. Byrne, Alexander M. Saucedo, Catherine Y. Spong
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The US Food and Drug Administration (FDA) Pregnancy and Lactation Labeling Rule (PLLR), implemented in 2015, includes information on pregnancy, lactation, and women and men with reproductive potential. <h3>Objectives</h3> To identify the drugs that have adhered to the new PLLR format; to shed light on the continued need for implementation of pregnancy, lactation, and reproduction into clinical studies; and to evaluate how many new therapeutic products have human and animal data specific to pregnancy and lactation. <h3>Design, Setting, and Participants</h3> This cross-sectional study of 290 new therapeutic drugs reviewed labeling data for newly FDA-approved therapeutic products from January 2010 to December 2019. Therapeutic products submitted on or after June 30, 2015, were required to be in PLLR format; those approved from June 30, 2007, to June 29, 2015, had until June 30, 2019, to be in PLLR format. Approval data and subsequent labeling revision were evaluated for pregnancy and lactation data (human and animal), pregnancy registry, black-box warnings, and inclusion of PLLR labeling format. <h3>Exposures</h3> Date of new drug approval by FDA. <h3>Main Outcomes and Measures</h3> Compliance with PLLR; presence of animal or human data; presence of pregnancy registries; and presence of information regarding female and male reproductive potential. <h3>Results</h3> A total of 290 new molecular entities or therapeutic products were approved by the FDA between 2010 and 2019 in 19 categories. Black-box warnings occurred in 89 drugs (30.7%; 95% CI, 25.4%-36.3%), with 3 (3.4%; 95% CI, 0.7%-9.5%) involving pregnancy. All products submitted after June 30, 2015, were in PLLR format; however, of the 138 submitted between 2010 and that date, 45 (32.6%; 95% CI, 24.9%-41.1%) were not in PLLR format by June 30, 2019. During the 10 years of data analyzed, significantly more were in PLLR format (<i>P </i>for trend &lt; .001). Most approved therapeutic products have pregnancy data derived from animal studies (260 products; 89.7%; 95% CI, 85.6%-92.9%) but only 31 (10.7%; 95% CI, 7.4%-14.8%) derived data from human studies. Only 148 therapeutic products (51.0%; 95% CI, 45.1%-56.9%) had any data associated with lactation, 143 (49.3%; 95% CI, 43.4%-55.2%) originating from animal studies and 8 (2.8%; 95% CI, 1.2%-5.4%) from human studies. <h3>Conclusions and Relevance</h3> The results of this study show that with the implementation of PLLR in the last decade, new therapeutic products were in compliance with the new rules; however, more than one-third of labels remain out of PLLR compliance. Human data on pregnancy and lactation are available in less than 20% of new product labeling.
Cell Phone Activity in Categories of Places and Associations With Growth in Cases of COVID-19 in the US
Authors: Shiv T. Sehra, Michael George, Douglas J. Wiebe, Shelby Fundin, Joshua F. Baker
Journal: JAMA Internal Medicine (2020)

It is unknown how well cell phone location data portray social distancing strategies or if they are associated with the incidence of coronavirus disease 2019 (COVID-19) cases in a particular geographical area.
Virtual care models for cancer survivorship
Authors: Quynh Pham, Jason Hearn, Bruce Gao, Ian Brown, Robert J. Hamilton, Alejandro Berlin, Joseph A. Cafazzo, Andrew Feifer
Journal: npj Digital Medicine (2020)

Abstract Virtual care models for cancer survivorship are needed to support patients living with the chronic effects of cancer treatment, while increasing health system capacity. Characteristics that may be critical to their success have not been adequately studied. This scoping review summarizes previous efforts to virtualize survivorship care to inform future innovations in the field. Four databases were searched for articles published before January 2020, and 24 articles that met selection criteria were included in this analysis. Rationale for pursuing virtual models of care shared two common objectives: (1) the need for sustainable survivorship care, and (2) the opportunity to improve survivorship outcomes. Breast cancer ( N = 10) and prostate cancer ( N = 4) were the most targeted cancers for virtual survivorship care. The implemented technologies included web platforms ( N = 15), telephone calls ( N = 12), and smartphone or tablet applications ( N = 5). A variety of healthcare professionals were effectively involved in the provision of virtual care. Future virtual care models may benefit from integrating with existing health systems and services, repurposing common technologies, involving allied health professionals, and engaging patients and caregivers from diverse communities in the design of virtual services.
Abstract 6330: DPP4 modulates ACSL4 to promote lipid peroxidation and regulate ferroptosis in pancreatic cancer
Authors: Xiang Zhou, Weiming Wang, Baofu Zhang, Zixia Lin, Yi Wang, Gang Chen
Journal: Cancer Research (2020)

Abstract BACKGROUND and AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the highest mortality rate cancers with almost no curative chemotherapeutic treatment. Ferroptosis is a recently recognized regulated necrotic cell death and that has emerged to play an important role in cancer biology. Recent discoveries have highlighted the important role of Dipeptidyl-peptidase-4 (DPP4) in TP53-deficient cancer cells. PDAC Patients with a lower DPP4 level have a poorer postoperative survival. We investigated whether DPP4 contributes to ferroptosis in pancreatic cancer. METHODS: DPP4 expression status was evaluated in PDAC tissues using tissue chip immunohistochemistry. The effects of DPP4 re-expression or knockdown on cell proliferation, the cell cycle and energy metabolism were determined. DPP4 interacting protein was identified by mass spectrometry and DPP4-related cancer pathways by RNA-seq analyses. The clinical impact of DPP4 in driving ferroptosis and enhancing gemcitabine sensitivity was assessed in patient-derived xenograft tumours (PDX), subcutaneous, and DPP4 knock-down (KD) or knock-in (KI) mice orthotopic xenograft models of PDAC. RESULTS: DPP4 was commonly low expression in PDAC. DPP4 significantly inhibited cell proliferation by causing G1-S cell cycle arrest, inhibiting energy metabolism and promoting erastin-induced ferroptosis in vitro, and suppressed xenograft tumour growth in both subcutaneous and orthotopic xenograft mouse models (both p&amp;lt;0.001). Mechanistically, DPP4 facilitated ferroptosis by binding ACSL4 and the DPP4-ACSL4 interaction stabilized ACSL4 by inhibiting its ubiquitin-mediated degradation, and subsequent lipid peroxidation. This interaction inactivated their downstream key elements of NF2-YAP signalling cascades. Importantly, the DPP4-ACSL4 pathway dictated ferroptosis sensitivity and promoted the anticancer activity of gemcitabine. Activating of the DPP4-ACSL4 pathway enhanced gemcitabine sensitivity by disinhibiting ferroptosis in vitro and in PDX, subcutaneous, and DPP4 KD or KI orthotopic xenograft models of PDAC. CONCLUSIONS: Collectively, these findings identify a novel role of DPP4 in ferroptosis and suggest a potential therapeutic strategy for overcoming gemcitabine resistance. Citation Format: Xiang Zhou, Weiming Wang, Baofu Zhang, Zixia Lin, Yi Wang, Gang Chen. DPP4 modulates ACSL4 to promote lipid peroxidation and regulate ferroptosis in pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6330.
Community use of face masks and similar barriers to prevent respiratory illness such as COVID-19: a rapid scoping review
Authors: Julii Brainard, Natalia R. Jones, Iain R Lake, Lee Hooper, Paul R Hunter
Journal: Eurosurveillance (2020)

Background Evidence for face-mask wearing in the community to protect against respiratory disease is unclear. Aim To assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base. Methods We systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described. Results 33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75–1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32–2.27; OR: 0.39; 95% CI: 0.18–0.84 and OR: 0.61; 95% CI: 0.45–0.85 for cohort, case–control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48–1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality. Conclusion Wearing face masks may reduce primary respiratory infection risk, probably by 6–15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.
Abstract A09: Activation of the CD45 receptor on leukocytes by the C24D peptide results in immune-mediated head and neck squamous cell carcinoma apoptosis
Authors: Aviram Mizrachi, Elad Hikri, Amit Ritter, Julia Dick-Lipovetsky, Sivan Simchi, Aron Popovtzer, Rinat Yerushalmi, Gideon Bachar, Anat Raiter
Journal: Clinical Cancer Research (2020)

Abstract Objectives: CD45 is a highly conserved receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes. C24D, a novel 24-amino acid dimer peptide, previously shown to activate immune-modulated breast cancer cell killing, binds to CD45, triggering leukocyte activation against cancer cells. The aim of this study was to evaluate the efficacy of C24D in activating leukocytes against head and neck squamous cell carcinoma (HNSCC). Methods: We performed a series of in vitro studies using 3 HNSCC cell lines (Cal33, FaDu, and A431). HNSCC cells were cocultured with peripheral blood mononuclear cells (PBMC) from healthy donors and subsequently treated with either C24D peptide or a scrambled control version. C24D activity was evaluated by tumor cell density and apoptosis analysis. Leukocyte activation by the peptide was evaluated by interferon gamma (IFN-γ) secretion. Results: Cocultures of HNSCC cells and PBMCs treated with C24D resulted in a substantial decrease in tumor cell density and increased apoptosis. IFN-γ levels were significantly elevated in the C24D treated PBMCs cocultured with HNSCC, suggesting leukocyte activation. Conclusions: C24D peptide activates leukocytes via CD45, causing immune cell-mediated killing of HNSCC cell lines. Citation Format: Aviram Mizrachi, Elad Hikri, Amit Ritter, Julia Dick-Lipovetsky, Sivan Simchi, Aron Popovtzer, Rinat Yerushalmi, Gideon Bachar, Anat Raiter. Activation of the CD45 receptor on leukocytes by the C24D peptide results in immune-mediated head and neck squamous cell carcinoma apoptosis [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A09.
Competition indices and monetary advantage index of intercropping maize (Zea mays L.) with legumes under supplementary irrigation in Tselemti District, Northern Ethiopia
Authors: Tesfahun Mekuanint
Journal: Journal of Clinical Oncology (2020)

An understanding of competitive and monetary indices such as land equivalent ratio (LER), land equivalent coefficient (LEC), relative crowding coefficient (K) and monetary advantage index (MAI) is critical in recommending cropping systems in a given area. To appreciate this, an experiment was conducted in Tselemti, Tigray region, Northern Ethiopia. Maize (Zea mays L.) was intercropped with Soybean and Mung bean in a 50:50 ratio under rainfed conditions and supplemented with irrigation in the 2016/17 season to determine the effect of leguminous competition on maize and the economic viability of the intercropping system over sole cropping. The experiment was laid in a split-plot design in three replications with intercropping taking the main plots and supplementary irrigation to sub-plots. The LER values were generally greater than one which indicated the yield advantages of intercropping over sole cropping. LEC was well above 25% and this means that intercropping was more productive. The highest value of LEC was recorded in wheat-lentil mixtures. The relative crowding coefficient (K) showed that the legumes were more dominant over maize. Although both maize-soybean and maize-mungbean mixtures showed economic advantage, as recorded by positive MAI, maize-soybean intercropping system proved more profitable under rainfed conditions whereas under supplementary irrigation, maize-Mungbean recorded a higher value of MAI. Conclusively, it was demonstrated that maize-soybean combinations were more advantageous in terms of yield and monetary advantage for smallholder farmers in Tselemti area who depend on rainfed farming.

	 

	Key words: Competition, mungbean, intercropping, supplementary irrigation, soybean, maize.
The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia
Authors: George A. Keepers, Laura J. Fochtmann, Joan M. Anzia, Sheldon Benjamin, Jeffrey M. Lyness, Ramin Mojtabai, Mark Servis, Art Walaszek, Peter Buckley, Mark F. Lenzenweger, Alexander S. Young, Amanda Degenhardt, Seung-Hee Hong
Journal: American Journal of Psychiatry (2020)

V Resumen
Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation
Authors: Ken Okumura, Masaharu Akao, Tetsuro Yoshida, Masahito Kawata, Osamu Okazaki, Shintaro Akashi, Kenichi Eshima, Kimihiko Tanizawa, Masayuki Fukuzawa, Takuya Hayashi, Masahiro Akishita, Gregory Y.H. Lip, Takeshi Yamashita
Journal: New England Journal of Medicine (2020)

Implementation of appropriate oral anticoagulant treatment for the prevention of stroke in very elderly patients with atrial fibrillation is challenging because of concerns regarding bleeding.
Abstract 2618: Tumor multicomponent targeting nanoparticle for synergistic killing of drug resistant renal cell carcinoma
Authors: Kushal Vanamala, Samaresh Sau, Shivani Naik, Arun K. Rishi, Arun Iyer
Journal: Cancer Research (2020)

Abstract Targeted therapy in renal cell carcinoma (RCC) has limited clinical response due to the development of drug resistance. Drug resistance can be acquired through multiple pathways including, impairment of apoptosis, overexpression of hypoxia promoting carbonic anhydrase 9 (CA9), and infiltration of folate receptor (FR) positive tumorigenic macrophages. Our hypothesis was to overcome the drug resistance by developing a tumor stimuli-responsive nanoparticle (NP) that can carry combination drugs, such as Cabozantinib (CB) and CFM 4.16 in RCC. The rationale of choosing the CB in combination with CFM4.16 was to induce synergistic anti-RCC effect by modulating the multiple tumor survival pathways, such as caspase 3, Akt/p-Akt, MET. One of the major challenges of the CB and CFM4.16 combination therapy is their poor water solubility and limited targetability to cancer. Thus, we came up with a smart strategy of developing dual folate receptor (FR) and carbonic anhydrase-9 (CA9) biomarker directed nanoparticles that can target the tumor stroma and hypoxia of RCC, respectively. In this proof of concept study, we synthesized SMA-TPGS and SMA polymer (PL) comprising of FR and CA9 dual targeting ligand, namely, FR-CA9-OL using reagent free ‘click' chemistry. FR-CA9-PL was encapsulated either with CFM4.16 or with CB to obtain nanoparticles, called FR-CA9-C4.16 and FR-CA9-CB respectively. The nanoparticles were prepared by using a co-solvent dialysis method that resulted in small-particle size with a range of 80-100 nm diameter, narrow polydispersity index of ∼ 0.15 and high drug loading of 30% (wt./wt.). The homogenous and high drug loading characteristics of nanoparticles are optimal for penetrating hypoxia of RCC. The IC50 of FR-CA9-C4.16 was improved by 60-fold as compared to CFM4.16 treatment and IC50 of FR-CA9-CB is improved by 16-fold compared to CB treatment in aggressive Everolimus-resistant (Evr-res) A498 RCC cells. The combination of FR-CA9-C4.16 with FR-CA9-CB demonstrated synergistic killing of Evr-res-A498 with CI value 0.1-0.5. The signature characteristic and superior anticancer effect of nanoparticles in Evr-resistant RCC provide a worthwhile strategy for overcoming drug resistance in RCC. Citation Format: Kushal Vanamala, Samaresh Sau, Shivani Naik, Arun K. Rishi, Arun Iyer. Tumor multicomponent targeting nanoparticle for synergistic killing of drug resistant renal cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2618.