tbuckley/cabot-search huggingface dataset:
Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation
Authors: Veronica Huber, Chiara Camisaschi, Angela Berzi, Simona Ferro, Luana Lugini, Tiziana Triulzi, Alessandra Tuccitto, Elda Tagliabue, Chiara Castelli, Licia Rivoltini
Journal: Seminars in Cancer Biology (2017)

The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment. At opposite, immunosuppressive components such as myeloid cells and regulatory T cells are engaged by tumor acidity to sustain tumor growth while blocking antitumor immune responses. Local acidity could also profoundly influence bioactivity and distribution of antibodies, thus potentially interfering with the clinical efficacy of therapeutic antibodies including immune checkpoint inhibitors. Hence tumor acidity is a central regulator of cancer immunity that orchestrates both local and systemic immunosuppression and that may offer a broad panel of therapeutic targets. This review outlines the fundamental pathways of acidity-driven immune dysfunctions and sheds light on the potential strategies that could be envisaged to potentiate immune-mediated tumor control in cancer patients.
Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision
Authors: Adi Nosrati, Jacqueline G. Berliner, Shilpa Goel, Joseph McGuire, Vera Morhenn, Juliana R. de Souza, Yildiray Yeniay, Rasnik Singh, Kristina Lee, Mio Nakamura, Rachel R. Wu, Ann Griffin, Barbara Grimes, Eleni Linos, Mary Margaret Chren, Roy Grekin, Maria L. Wei
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> Melanoma in situ (MIS) is increasing in incidence, and expert consensus opinion recommends surgical excision for therapeutic management. Currently, wide local excision (WLE) is the standard of care. However, Mohs micrographic surgery (MMS) is now used to treat a growing subset of individuals with MIS. During MMS, unlike WLE, the entire cutaneous surgical margin is evaluated intraoperatively for tumor cells. <h3>Objective</h3> To assess the outcomes of patients with MIS treated with MMS compared with those treated with WLE. <h3>Design, Setting, and Participants</h3> Retrospective review of a prospective database. The study cohort consisted of 662 patients with MIS treated with MMS or WLE per standard of care in dermatology and surgery (general surgery, otolaryngology, plastics, oculoplastics, surgical oncology) at an academic tertiary care referral center from January 1, 1978, to December 31, 2013, with follow-up through 2015. <h3>Exposure</h3> Mohs micrographic surgery or WLE. <h3>Main Outcomes and Measures</h3> Recurrence, overall survival, and melanoma-specific survival. <h3>Results</h3> There were 277 patients treated with MMS (mean [SD] age, 64.0 [13.1] years; 62.1% male) and 385 treated with WLE (mean [SD] age, 58.5 [15.6] years;<i>P</i> &lt; .001 for age; 54.8% male). Median follow-up was 8.6 (range, 0.2-37) years. Compared with WLE, MMS was used more frequently on the face (222 [80.2%] vs 141 [36.7%]) and scalp and neck (23 [8.3%] vs 26 [6.8%];<i>P</i> &lt; .001). The median (range) year of diagnosis was 2008 (1986-2013) for the MMS group vs 2003 (1978-2013) for the WLE group (<i>P</i> &lt; .001). Overall recurrence rates were 5 (1.8%) in the MMS group and 22 (5.7%) in the WLE group (<i>P</i> = .07). Mean (SD) time to recurrence after MMS was 3.91 (4.4) years, and after WLE, 4.45 (2.7) years (<i>P</i> = .73). The 5-year recurrence rate was 1.1% in the MMS group and 4.1% in the WLE group (<i>P</i> = .07). For WLE-treated tumors, the surgical margin taken was greater for tumors that recurred compared with tumors that did not recur (<i>P</i> = .003). Five-year overall survival for MMS was 92% and for WLE was 94% (<i>P</i> = .28). Melanoma-specific mortality for the MMS group was 2 vs 13 patients for the WLE group, with mean (SD) survival of 6.5 (4.8) and 6.1 (0.8) years, respectively (<i>P</i> = .77). <h3>Conclusions and Relevance</h3> No significant differences were found in the recurrence rate, overall survival, or melanoma-specific survival of patients with MIS treated with MMS compared with WLE.
Prolonged Duration of Systemic Immunosuppression after Allogeneic Hematopoietic Cell Transplantation Associates with the Use of Peripheral Blood Stem Cells, Severe Grade of Chronic Gvhd, Progressive Type Onset of Chronic Gvhd, Grade 2-4 Acute Gvhd and Older Age, but Not with T-Cell Depletion or Conditioning Regimen
Authors: Sita D. Bhella, Elizabeth Shin, Marc Poch Martell, Jieun Uhm, Fotios V. Michelis, Auro Viswabandya, Jeffrey H. Lipton, Hans A. Messner, Dennis Dong Hwan Kim
Journal: Blood (2015)
Myeloid Cells Having NUP98-HOX Fusion Genes with Simultaneous FLT3, NRAS, or WT1 Mutations Confer Growth Advantage, Inhibit Differeniation/Apoptosis, and Augment Self-Renewal
Authors: Takeshi Taketani, Miho Hattori, Mariko Abe, Tomohiro Hirade, Seiji Fukuda, Seiji Yamaguchi
Journal: Blood (2014)
Membrane-Associated Proteinase 3 on Granulocytes and Myeloid Leukemia Mediates Reversible Inhibition of T Cell Proliferation
Authors: Tian-Hui Yang, Karen Clise-Dwyer, Gheath Alatrash, Kathryn Ruisaard, Shoudan Liang, Jeffrey J. Molldrem
Journal: Blood (2011)
Moving care out of hospital is unlikely to save money, new analysis finds
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Moving healthcare out of hospital could improve the quality of care but is unlikely to save the NHS money, a new analysis has concluded.

The report, from the healthcare think tank the Nuffield Trust, reviewed existing literature on 27 initiatives in England designed to move care out of hospital, to assess the credibility of the idea that such policies save money.1

That moving care into the community makes financial savings underpins the NHS’s 44 sustainability and transformation plans (http://sandpit.bmj.com/graphics/2016/stpMap), which are aiming to help the NHS make £22bn (€26bn; $27bn) in efficiency savings by 2020-21, by redesigning services. But the authors concluded that some of these STPs were working to “undeliverable expectations” about the economic benefits of shifting more care into the community and would struggle to reduce overall numbers of patients needing hospital treatment without extra money and staff.

The findings echo the conclusions from a recent National Audit Office report that found “no …
Abstract P3-12-05: Estimating costs of relapsing HER2+ breast cancer in Spain
Authors: R Colomer, E Ciruelos, J De la Haba, M Martín, M De Salas-Cansado, B Muñoz-Molina, J Albanell
Journal: Cancer Research (2017)

Abstract OBJECTIVES: The purpose of this study was to describe the economic impact of recurrences (locoregional or unresectable/metastatic recurrences [MR]) in patients with HER2+ breast cancer (BC) in Spain. METHODS: A Delphi panel of 15 Spanish oncologists was carried out to define the clinical management (patients' flow and healthcare resources use) of locoregional recurrences (LR) and unresectable or MR in patients with HER2+ BC. Healthcare resources included medication, medical visits, lab and imaging tests, hospitalizations, surgery, adverse events management and treatment of specific metastases (e.g. bone metastases). Additionally, loss of productivity was also estimated. Local unit costs where used in combination with healthcare resources and workdays lost to estimate both the direct and indirect costs of LR and MR in HER2+ BC patients. A deterministic sensitivity analysis was performed to explore the robustness and assess the critical variables of the study. RESULTS: The estimated distribution of recurrences in HER2+ BC patients was: 90% of MR, 7% of LR and 3% of LR followed by an MR. With respect to MRs, 31% of cases were estimated to receive up to 5 lines of treatment whilst 5% received no treatment (10%, 20% and 21% would receive 2, 3 and 4 treatment lines, respectively, with a median of 3 lines). Treatment regimens including trastuzumab were the most frequently used (in combination with pertuzumab and taxane in 1L, and with other combinations in 4&amp;5L). In 3L, the most common treatment regimen was lapatinib-capecitabine. Total costs, including medical and indirect costs were €235,138, being the direct costs more than 88.7% (€208,682). Both direct and total costs were higher in patients being treated with a higher number of treatment lines, with figures ranging from €38,511 (1L) to €308,869 (5L) and €50,908 (1L) and €358,000 (5L) respectively. CONCLUSIONS: HER2+ BC patients with a MR were estimated to receive a median of 3 treatment lines and almost one third receives 5 treatment lines. The direct and indirect costs of recurrences are high, with a calculated average total cost of €235,138. Using targeted therapies in earlier stages of HER2+ BC that achieve a reduction of recurrences would achieve significant cost savings in Spain. Citation Format: Colomer R, Ciruelos E, De la Haba J, Martín M, De Salas-Cansado M, Muñoz-Molina B, Albanell J. Estimating costs of relapsing HER2+ breast cancer in Spain [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-12-05.
Presidential Address at the Closing Session
Authors: T.F. Main, E.J. Anthony, M. Fordham, Anna Freud, Annemarie Dührssen, R.D. Laing, J. Ruesch, M. Boss, G. Benedetti, Elizabeth R. Zetzel, J.D. Sutherland, Dorothy Stock Whitaker, E.K. Schwartz, S.H. Foulkes, F. Knobloch, J. Cumming, Elaine Cumming, Isabel E.P. Menzies, Doreen Weddell, Ch. Mertens de Wilmars, E.L. Trist, D.H. Clark, A.H. Stanton
Journal: Psychotherapy and Psychosomatics (1965)
Abstract P6-11-14: Src homology 2 domain containing transforming protein 1 and steroid receptor coactivator-3 as novel targets for triple-negative breast cancer
Authors: Y-F Chang, Y Wang, GL Greene
Journal: Cancer Research (2017)

Abstract Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases and is more prevalent among young women and African American women. Metastasis and chemoresistance remain significant challenges in TNBC. The development of targeted therapies for TNBC may dramatically improve the survival of patients and the quality of life. An adaptor protein, Src Homology 2 Domain Containing Transforming Protein 1 (SHC1) and steroid receptor coactivator-3 (NCOA3) are found to be overexpressed in breast cancers and important in the regulation of tumor progression and metastasis and drug resistance in ER+ breast cancer. The elevated SHC1 or NCOA3 correlates with poor prognosis in breast cancer patients. However, the biological significance of SHC1 and NCOA3 in TNBC is not well known. In this study, we performed siRNA-mediated knockdown to determine the importance of SHC1 and NCOA3 in the cell proliferation and death of TNBC. The effect of siSHC1 or siNCOA3 on the invasion and chemoresistance was also assayed in vitro. We found that although SHC1 and NCOA3 knockdown slightly inhibited the tumor growth of TNBC cells (MDA-MB-231, BT549, and HS578T), siSHC1 + paclitaxel and siNCOA3 + paclitaxel significantly decreased cell proliferation and increased caspase-3/7 activity in vitro, compared to drug alone. In vivo studies using MDA-MB-231 xenografts and a TNBC PDX model also showed that siSHC1 and siNCOA3 significantly augmented paclitaxel-induced tumor shrinkage. In invasion assays, SHC1 and NCOA3 knockdown significantly decreased the invasion of TNBC cells. These results suggest that targeting SHC1 and NCOA3 is worth investigating for the treatment of TNBC. Citation Format: Chang Y-F, Wang Y, Greene GL. Src homology 2 domain containing transforming protein 1 and steroid receptor coactivator-3 as novel targets for triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-14.
Zoledronic Acid Suppresses Vasculogenesis: A New Effect of Bisphosphonates.
Authors: Haiming Chen, Cathy S. Wang, Jennifer Li, Richard A. Campbell, Mingjie Li, Eric Sanchez, Jeffrey Steinberg, Michael Share, Dror Shalitin, James Wang, Shi-Jason Xie, Yunchao Chang, Benjamin Bonavida, Thomas F. Deuel, James R. Berenson
Journal: Blood (2007)
Regulatory and Activated T Cells in Stem Cell Autografts Collected by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony Stimulating Factor.
Authors: Maud Condomines, Philippe Quittet, Zhao-Yang Lu, Laure Nadal, Pascal Latry, Ernesto Lopez, Marion Baudard, Jean-François Rossi, Karin Tarte, Bernard Klein
Journal: Blood (2005)
HHV-6 Encephalitis in Pediatric Unrelated Umbilical Cord Blood Transplantation: Role for Ganciclovir Prophylaxis?
Authors: Frankie Wai Tsoi Cheng, Vincent Lee, Wing Kwan Leung, Paul Kay Sheung Chan, Ting Fan Leung, Matthew MK Shing, Chi Kong Li
Journal: Blood (2009)
Use of Stereotactic Ablative Radiotherapy (SABR) in Non–Small Cell Lung Cancer Measuring More Than 5 cm
Authors: Hilâl Tekatli, Saar van ’t Hof, Esther J. Nossent, Max Dahele, Wilko F.A.R. Verbakel, Ben J. Slotman, Suresh Senan
Journal: Journal of Thoracic Oncology (2017)
Abstract IA21: Opportunities for integration of PDX models into clinical trials
Authors: Scott Kopetz
Journal: Clinical Cancer Research (2016)

Abstract Patient-derived xenograft models (PDX) provide opportunities to evaluate efficacy, pharmacodynamics, response durability, and resistance mechanisms in greater details than traditionally possible with sampling of patient tumors. When PDX models are integrated with patients enrolled in clinical trials, or treated with novel agents, there are opportunities to interrogate aspects of cancer biology not traditionally evaluable, while maintaining clinical relevance. This presentation will explore the strengths and limitations of the models, with examples on how these models are being integrated into clinical trials, validation efforts, and novel insights derived from this approach. The concept of a co-clinical trial has been variously defined, including a definition proposed by the NCI as parallel or sequential trials of combination therapy in patients and in mouse and human-in-mouse models of appropriate genotypes to represent the patients. This concept is being extended for PDX models to incorporate tumor models derived from the same patients participating in the clinical trial, both with a goal of improving translational interrogation of the novel agent efficacy as well as emerging efforts to use the PDX models to guide patient therapy. Validation of the PDX models for treatment response/regression will be demonstrated, including recently completed clinical trials utilizing inhibitors of BRAF and MEK with a comparison of the response of the matched PDX models to radiographic measurements from the treated patients. Cohort based validation will be demonstrated through examples with EGFR targeted therapy and comparison to randomized clinical trial results. Limitations of these approaches will be described. PDX models from clinical trials have been demonstrated to model and replicate mechanisms of resistance in some settings, and examples from colorectal and lung cancer will be used to demonstrate this. Resistance of lung cancer to EGFR tyrosine kinase inhibitors is being explored on PDXs obtained from post-progression biopsies. Tumor heterogeneity as a mechanism of resistance has been successfully modeled in BRAF-mutant colorectal cancer, and has been integrated into prospective clinical trials. Finally, efforts to integrate PDX models as predictors of treatment response are described. These include efforts to use matched PDX models to guide treatment decisions in patients as part of prospective clinical trials. Regulatory, logistic, and biologic limitations of such efforts will be discussed. Citation Format: Scott Kopetz. Opportunities for integration of PDX models into clinical trials. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA21.
PSA screening rates in older men in the United States based on nine-year estimated remaining life expectancy.
Authors: Michael Drazer, Sandip M. Prasad, Dezheng Huo, Mara A Schonberg, Russell Zelig Szmulewitz, William Dale, Scott E. Eggener
Journal: Journal of Clinical Oncology (2013)

e16006 Background: PSA screening for prostate cancer (PCa) is controversial, but informed decision making is recommended for men with an estimated 10 years of remaining life expectancy (RLE). The association between screening of men 65+ and estimated 9-year life expectancy is unknown. Our purpose was to determine the association between predicted 9-year life expectancy and PCa screening in 2005 and 2010. Methods: Data were extracted from the 2005 and 2010 National Health Interview Survey. Men 65+ without prostate known PCa were divided into quartiles with a validated index estimating 9-year RLE (&lt;27%, 27-52%, 53-75%, and &gt;75%). The proportions of men screened in 2005 and 2010 were determined. Logistic regression was used to compare screening in 2005 and 2010. Results: Screening rates for men 65+ were 48.3% (95% CI, 45.6-50.9%) in 2005 and 48.5% (95% CI, 45.5-51.6%) in 2010 (p = 0.9). There were no differences in screening between cohorts by age and predicted mortality for 65-74 (all p &gt; 0.05 for &lt;27%, 27-52%, 53-75%, and &gt;76% predicted mortality) and 75+ year olds (all p&gt; 0.05). The most screened group were 65-74 year olds with a &lt;27% chance of 9-year mortality, with 58.3% (95% CI, 53.6–63.1) and 56.1% (95% CI, 50.6-61.5) screened in 2005 and 2010. Conclusions: PSA-based PCa screening did not differ between 2005 and 2010 for men 65+. Over 35% and 33% of older men with limited estimated 9-year RLE were screened in 2005 and 2010 despite minimal clinical benefit. [Table: see text]
Endothelial Microparticles (EMP) Bind and Complex with Unusually-Large Multimers of Von Willebrand Factor (ULvWf) and Act as Potent Inducers of Platelet Adhesion and Aggregation.
Authors: Wenche Jy, Joaquin J. Jimenez, Pengyu Cheng, Lucia M. Mauro, Lawrence L. Horstman, Eugene R. Ahn, Carlos J. Bidot, Yeon S. Ahn
Journal: Blood (2004)
Thank You to <i>JAMA</i> Authors, Peer Reviewers, and Readers
Authors: Phil B. Fontanarosa, Howard Bauchner, Robert M. Golub
Journal: JAMA (2017)

Biomedical journals serve numerous constituencies, the most important of which are authors (who provide content for the journal), peer reviewers (who evaluate the quality and validity of the content),1 and readers (who use the content to expand their knowledge and improve patient care). We hereby express our deepest appreciation to the members of these important groups for their ongoing contributions to, support of, and interest in JAMA.
Increase of Sensitivity to Chemotherapy and NK-Mediated Cytotoxicity of Leukemic Stem Cell by a Farnesyltransferase Inhibitor.
Authors: Miaorong She, Jinggao Li, Xilin Chen, Xingqing Niu, Kunyuan Guo, Xin Du, Maohua Zhou, Yanjie He, Yi Le
Journal: Blood (2009)
Lenalidomide Consolidation Appears to Prolong Time to Retreatment After First-Line Chemoimmunotherapy for Patients with Previously Untreated CLL,
Authors: Tait D. Shanafelt, Han Tun, Curtis A. Hanson, Clive S. Zent, Jose F. Leis, Timothy G Call, Betsy R. LaPlant, Deborah Bowen, EmilyS S Pavey, Diane F. Jelinek, Neil Kay
Journal: Blood (2011)
Exploring the Functional Relevance of BTK Beyond Chronic Lymphocytic Leukemia (CLL) Cells: BTK Expression in Non-Malignant Immune Cells of the Microenvironment Mediates CLL Development and Progression In Vivo
Authors: Fabienne McClanahan, Sean D. Reiff, Daphne Guinn, Minh Tran, Larry Beaver, Samantha McWorther, Rose Mantel, Lisa L. Smith, Amy J. Johnson, John C. Byrd, Jennifer A. Woyach
Journal: Blood (2016)
Injuries in elite Korean fencers: an epidemiological study
Authors: Ki Jun Park, Song Brian Byung
Journal: British Journal of Sports Medicine (2017)

We aimed to assess the risk of injury associated with training activities in a population of elite Korean fencers training for the Olympic games.We analysed the incidence of sports injuries, based on data prospectively collected over an 8-year period (January 2008 to December 2015) at the National Training Center in Seoul, Korea. The population of elite fencing athletes was stratified according to fencing category (sabre, epee and foil), sex, injury location (body region and site) and injury severity (mild or level I injury, requiring treatment for 1-3 days; moderate or level II injury, requiring treatment for 4-7 days; and severe or level III injury, requiring treatment for ≥8 days).A total of 1176 injuries were recorded during the study period, with an average of 3.3 injuries per athlete annually. Of these, over half (52.6%) were mild injuries, with most injuries occurring in the lower extremity (47.2%), followed by injuries to the upper extremity (26.4%), trunk (21.4%), and head and neck area (5.0%). For all weapon categories, there was a significant difference between male and female athletes in terms of injury location and severity (p≤0.005).We hope that our data describing injury location and severity according to weapon category and sex can help one understand the circumstances that lead to injuries in elite Korean fencers and can be used in the development of programmes to reduce the incidence of sports injuries and enhance athletic performance.
A Prospective Clinical Trial of a Novel Epstein-Barr Virus (EBV) PCR Panel in Patients with EBV Associated Malignancies.
Authors: Marin F. Xavier, Dale Frank, Sunita Nasta, Stephen Schuster, Charalambos Andreadis, Sharon Arnoldi, Eric Sherman, Sigrid Berg, Anthony Mato, Benjamin Musher, Lisa Downs, David Porter, Edward Stadtmauer, Steven Goldstein, Ellen Kim, Donald Tsai
Journal: Blood (2007)
Towards a global cancer knowledge network: dissecting the current international cancer genomic sequencing landscape
Authors: D.J. Vis, J. Lewin, R.G. Liao, M. Mao, F. Andre, R.L. Ward, F. Calvo, B.T. Teh, A.A. Camargo, B.M. Knoppers, C.L. Sawyers, L.F.A. Wessels, M. Lawler, L.L. Siu, E. Voest
Journal: Annals of Oncology (2017)

While next generation sequencing has enhanced our understanding of the biological basis of malignancy, current knowledge on global practices for sequencing cancer samples is limited. To address this deficiency, we developed a survey to provide a snapshot of current sequencing activities globally, identify barriers to data sharing and use this information to develop sustainable solutions for the cancer research community.
Early Mixed T-Lymphocyte and Myeloid Chimerism Is Predictive of Disease Recurrence Following Allogeneic Stem Cell Transplantation for AML/MDS.
Authors: Hans C. Lee, Rima M. Saliba, Gabriela Rondon, Julianne Chen, Yasmeen Charafeddine, L. Jeffrey Medeiros, Marcos De Lima, Borje S Andersson, Partow Kebriaei, Betul Oran, Richard E. Champlin
Journal: Blood (2012)
A survey on deep learning in medical image analysis
Authors: Geert Litjens, Thijs Kooi, Babak Ehteshami Bejnordi, Arnaud Arindra Adiyoso Setio, Francesco Ciompi, Mohsen Ghafoorian, Jeroen A.W.M. van der Laak, Bram van Ginneken, Clara I. Sánchez
Journal: Medical Image Analysis (2017)
Outcomes for Unrelated Donor Hematopoietic Cell Transplantation (URD-HCT) for Patients with Acute Lymphoblastic Leukemia (ALL) Using Fractionated Total Body Irradiation (FTBI) and Etoposide (VP16).
Authors: Margaret O’Donnell, P Parker, A Dagis, ML Slovak, D Snyder, A Stein, R. Spielberger, A Pawlowska, J Rosenthal, J Palmer, N. Kogut, S. J Forman
Journal: Blood (2008)