tbuckley/cabot-search huggingface dataset:
Deep Immunoprofiling of the Bone Marrow Microenvironmental Changes Underlying the Multistep Progression of Multiple Myeloma
Authors: Mary H Young, Sam A Danziger, Alison Fitch, Frank Schmitz, Jake Gockley, Mark McConnell, David Reiss, Wilbert B. Copeland, Sarah K Johnson, Katie Newhall, Robert Hershberg, Teri Foy, Alexander Ratushny, Brian A Walker, Andrew Dervan, Gareth Morgan
Journal: Blood (2018)
Predictors of treatment response in colorectal high-grade neuroendocrine carcinomas (HGNEC): A single institution experience.
Authors: Virginia Corbett, Nitya Prabhakar Raj, Virginia Kelly, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2019)

690 Background: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are aggressive tumors; treatment options consist of cis/carboplatin and 5FU-based chemotherapy. To date, choice of systemic therapy and sequencing of these drugs remains poorly understood. We examined clinical and molecular characteristics of colorectal HGNEC to better define predictors of response to cis/carboplatin and 5FU-based treatment. Methods: Patients (pts) with colorectal HGNEC treated at MSKCC from 1990-2018 were identified. MANEC (mixed adeno-neuroendocrine carcinoma) were excluded. Demographics, response to first- and second-line chemotherapy (by radiology report), outcomes, and molecular data (next-generation sequencing of tumor tissue), were collected. Results: 65 pts (mean age 58, 52% male) were identified, 13 (20%) with small cell carcinomas. 52 (79%) metastatic, 13 (20%) locally advanced. 27 (42%) received surgery and 11 (17%) received radiation. 56 pts received cis/carboplatin-based therapy, partial response (PR) in 18 (32%), stable disease (SD) in 4 (7%), and progressive disease (PD) in 31 (55%); 3 (5%) did not tolerate therapy. 28 pts received 5FU-based therapy, 13 PR in (46%), SD in 6 (21%), and PD in 7 (25%); 2 (7%) did not tolerate therapy. Median overall survival was 11.4 months. 21/65 (32%) pts underwent molecular sequencing of tumor; the most common alterations were KRAS 11 (52%), TP53 13 (62%), BRAF 7 (33%), APC 8 (38%), RB1 7 (33%). Most tumors (13/21, 62%) harbored alterations in genes traditionally altered in colorectal adenocarcinoma (KRAS/BRAF/APC) and in HGNEC (TP53/RB1). There was no significant difference in response to cis/carboplatin or 5FU-based chemotherapy based on location of the primary tumor (right vs. left) (p = 0.69/0.85), histologic features of the disease (p = 0.71/0.87), and for response to cis/carboplatin by molecular alterations in KRAS (p = 0.94), BRAF (p = 0.24), APC (p = 0.28), TP53 (p = 0.58), or RB1 (p = 0.28). Conclusions: Colorectal HGNEC are highly aggressive and more effective therapies are desperately needed. In this series, OS was poor. Clinical and molecular characteristics failed to predict response to cis/carboplatin and 5FU-based chemotherapy.
Abstract B024: Family history of prostate cancer and the incidence of ERG- and PTEN-defined prostate cancer
Authors: Dana Hashim, Amparo G. Gonzalez-Feliciano, Thomas U. Ahearn, Andreas Pettersson, Lauren Barber, Claire H. Pernar, Ericka M. Ebot, Stephen Finn, Edward L. Giovannucci, Rosina T. Lis, Massimo Loda, Giovanni Parmigiani, Kathryn L. Penney, Tamara Lotan, Philip W. Kantoff, Lorelei A. Mucci, Rebecca E. Graff
Journal: Cancer Research (2018)

Abstract Introduction: Family history is among the strongest known risk factors for prostate cancer. Emerging data suggest unique molecular subtypes of disease, including common somatic genetic aberrations: fusions of androgen-regulated promoters with ERG and, separately, PTEN loss. We examined associations between family history and incidence of these subtypes under the hypothesis that family history could be differentially associated with their occurrence. Methods: We studied 47,115 men in the prospective Health Professionals Follow-up Study from 1986 to 2009. ERG and PTEN status were assessed with immunohistochemistry. Multivariable competing risk models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between self-reported family history of prostate cancer and disease defined by molecular subtypes. Results: During a median follow-up of 22.3 years, 5,606 prostate cancer cases were diagnosed. Among them, 889 and 711 were assayed for ERG status (48% ERG+) and PTEN loss (14% PTEN null), respectively. Prostate cancer family history was positively associated with both ERG+ (HR=1.85; 95% CI: 1.47-2.33) and ERG- (HR=2.20; 95% CI: 1.78-2.72) disease (P-heterogeneity=0.29). High-grade ERG+ disease suggested a pronounced association (HR=2.58; 95% CI: 1.85-3.61; P-heterogeneity versus high-grade ERG-: 0.08). Family history was also positively associated with PTEN null (HR=2.39; 95% CI: 1.53-3.71) and PTEN intact (HR=1.88; 95% CI: 1.54-2.28) prostate cancer (P-heterogeneity=0.34). Conclusion: Prostate cancer family history is positively associated with prostate cancer defined by ERG and PTEN, suggesting a similar role of genetic susceptibility for these subtypes. It is possible that high-grade ERG+ disease could be uniquely associated with positive family history. Citation Format: Dana Hashim, Amparo G. Gonzalez-Feliciano, Thomas U. Ahearn, Andreas Pettersson, Lauren Barber, Claire H. Pernar, Ericka M. Ebot, Stephen Finn, Edward L. Giovannucci, Rosina T. Lis, Massimo Loda, Giovanni Parmigiani, Kathryn L. Penney, Tamara Lotan, Philip W. Kantoff, Lorelei A. Mucci, Rebecca E. Graff. Family history of prostate cancer and the incidence of ERG- and PTEN-defined prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B024.
Characteristics of colorectal cancer (CRC) patients with BRCA1 and BRCA2 mutations.
Authors: Madiha Naseem, Joanne Xiu, Mohamed E. Salem, Richard M. Goldberg, Ari M. Vanderwalde, Axel Grothey, Philip Agop Philip, Andreas Seeber, Alberto Puccini, Ryuma Tokunaga, Francesca Battaglin, Martin D. Berger, Afsaneh Barzi, Diana L. Hanna, Wu Zhang, Jimmy J. Hwang, Anthony Frank Shields, John Marshall, Wolfgang Michael Korn, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2019)

606 Background: Between 3-5% of CRC patients have BRCA1/2 pathogenic mutations. This study aims to identify associations between BRCA1 and BRCA2 mutations and clinical characteristics in CRC. Methods: A total of 6396 CRC tumor samples were tested with Next-Generation Sequencing (NGS) on a 592-gene panel, pathogenic or presumed pathogenic variants were counted as mutations (mt). Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS. Statistical correlations were investigated using ANOVA, Chi-square and t-test. Results: Among tumors sampled, 53% derived from male patients and median age was 60 years. BRCA1 mt were detected in 1.1% (n = 72) of tumors, while BRCA2 in 2.8% (n = 179). BRCA1 mt were more frequent in women (W;65%) than men (M;35%) (p = 0.0019) while no relationship with sex was seen for BRCA2 mt (42% F vs. 58% M). No significant associations with age were noticed. Majority of pathogenic mt in BRCA1 (52%; n = 34) and BRCA2 (62%; n = 103) occurred in MSI-High (MSI-H) cases. MSI-H pts had more frameshift mt in both BRCA1/2 than MSS pts. MSS cases had lower rates of BRCA1 and 2 pathogenic mt (44% and 37%, respectively). Right-sided tumors were significantly associated with BRCA1 (p = 0.0056) and BRCA2 (p &lt; 0.0001) mt in MSI-H cases only. BRCA1/2 mt were associated with higher TMB in all CRCs, including MSI-H and MSS cases (p &lt; 0.001). POLE mt (n = 31) were associated with higher BRCA1/2 mt rates (9.6%, 55% respectively). Among MSS cases with POLE wild-type status, BRCA1 (p = 0.0269) and BRCA2 (p = 0.0151) mt were associated with high TMB and combining both BRCA1/2 mutations led to an even higher TMB (3.6%; p = 0.001). Conclusions: This is the first study to show that BRCA1/2 mutations are more frequent in MSI-H, and independently associated with higher TMB, pathogenic POLE mutations, and right-sided tumors in MSI-H CRCs. Given their relationship with TMB, the presence of BRCA1/2 mutations may be potential predictive biomarkers for checkpoint or PARP inhibitors in CRC, a finding that should be prospectively evaluated.
Evaluation of Clinical Compendia Used for Medicare Part D Coverage Determinations for Off-label Prescribing in Dermatology
Authors: John S. Barbieri, Kayla St Claire, Arash Mostaghimi, Joerg Albrecht
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> When making coverage determinations for off-label prescribing, Medicare Part D recognizes 2 compendia: the American Hospital Formulary Service (AHFS) Drug Information and the DRUGDEX Information System. Deficiencies in the accuracy and completeness of these compendia could result in coverage denials for necessary, effective, evidence-based treatments. <h3>Objective</h3> To evaluate these compendia for dermatologic conditions, with a focus on less common conditions that often require systemic treatment. <h3>Design, Setting, and Participants</h3> This cross-sectional study was conducted from July 1, 2018, through September 30, 2018. To identify diseases for which dermatologists may often need access to off-label systemic treatments, a list of 22 chronic, noninfectious, nonneoplastic diseases with at least 4 systemic therapies (including 1 in the first-line therapies and less than 25% approved by the US Food and Drug Administration) were selected for evaluation. With use of<i>Treatment of Skin Disease, 5th Edition</i>, a list of first-, second-, and third-line medications was created, including the level of evidence for each disease. A search of AHFS and DRUGDEX compendia was performed to evaluate for inclusion of the evidence-based therapies. In addition, the references cited in the compendia to justify inclusion of the therapy were examined qualitatively. <h3>Main Outcomes and Measures</h3> Percentage of treatment options included in each compendium, stratified by level of evidence and position on the therapeutic ladder. Concordance between the 2 compendia was assessed using Cohen κ. <h3>Results</h3> Overall, 73 of 238 treatments (30.7%) evaluated were included in either compendium. Among individual diseases, 10 of 22 (45%) had 1 or fewer treatments included in the DRUGDEX compendium and 15 of 22 (68%) had 1 or fewer treatments included in the AHFS compendium. Discrepancies in which a medication was included in one compendium but not in the other compendium occurred for 53 of the 238 medications (22.3%) evaluated. Literature use did not follow a discernible pattern and was often based on decades-old sources. <h3>Conclusions and Relevance</h3> The findings suggest that treatment options listed in these compendia are incomplete, outdated, idiosyncratic, and unpredictable. To ensure that patients can access treatments for their disease, it appears that policies to reduce the reliance on these compendia for coverage determinations should be developed.
Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering
Authors: Andrew T. Rowley, Raji R. Nagalla, Szu‐Wen Wang, Wendy F. Liu
Journal: Advanced Healthcare Materials (2019)

Abstract The extracellular matrix (ECM) is a complex and dynamic structural scaffold for cells within tissues and plays an important role in regulating cell function. Recently it has become appreciated that the ECM contains bioactive motifs that can directly modulate immune responses. This review describes strategies for engineering immunomodulatory biomaterials that utilize natural ECM‐derived molecules and have the potential to harness the immune system for applications ranging from tissue regeneration to drug delivery. A top‐down approach utilizes full‐length ECM proteins, including collagen, fibrin, or hyaluronic acid‐based materials, as well as matrices derived from decellularized tissue. These materials have the benefit of maintaining natural conformation and structure but are often heterogeneous and encumber precise control. By contrast, a bottom‐up approach leverages immunomodulatory domains, such as Arg–Gly–Asp (RGD), matrix metalloproteinase (MMP)‐sensitive peptides, or leukocyte‐associated immunoglobulin‐like receptor‐1(LAIR‐1) ligands, by incorporating them into synthetic materials. These materials have tunable control over immune cell functions and allow for combinatorial approaches. However, the synthetic approach lacks the full natural context of the original ECM protein. These two approaches provide a broad range of engineering techniques for immunomodulation through material interactions and hold the potential for the development of future therapeutic applications.
New Planned Parenthood President: No Politics in the Exam Room
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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Functional profiling of venetoclax sensitivity can predict clinical response in multiple myeloma
Authors: Shannon M. Matulis, Vikas A. Gupta, Paola Neri, Nizar J. Bahlis, Paulo Maciag, Joel D. Leverson, Leonard T. Heffner, Sagar Lonial, Ajay K. Nooka, Jonathan L. Kaufman, Lawrence H. Boise
Journal: Leukemia (2019)
Systematic Literature Review of the Clinical Efficacy and Safety of Treatments in the Relapsed/Refractory Setting for Patients with Follicular Lymphoma or Marginal Zone Lymphoma
Authors: Neerav Monga, Jamie Garside, Peter O'Donovan, Joan Quigley, Amie Padhiar, Lori Parisi, Christoph Tapprich, Loretta Nastoupil
Journal: Blood (2017)
Abstract 19675: 4D Light Sheet Fluorescent Imaging to Elucidate Notch and ErbB2 Signaling in Chemo-Induced Cardiomyopathy and Regeneration
Authors: Junjie Chen, Nelson Jen, Yichen Ding, Michael Chen, Jonathan Gau, Chadi Nahal, René R Packard, Tzung K Hsiai
Journal: Circulation (2017)

Introduction: The advent of Light Sheet Fluorescent Microscopy (LSFM) offers deep axial resolution with large dynamic range, rapid data acquisition, and reduced photobleaching for live imaging. Zeb...
Endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors and pancreatic cystic neoplasms: a prospective multicenter study
Authors: Marc Barthet, Marc Giovannini, Nathalie Lesavre, Christian Boustiere, Bertrand Napoleon, Stéphane Koch, Mohamed Gasmi, Geoffroy Vanbiervliet, Jean-Michel Gonzalez
Journal: Endoscopy (2019)

Abstract Background Pancreatic neuroendocrine tumors (NETs) and intraductal pancreatic mucinous neoplasia (IPMN) with worrisome features are surgically managed. Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) has recently been developed. The safety of EUS-RFA was the primary end point of this study, its efficacy the secondary end point. Methods This was a prospective multicenter study that was planned to include 30 patients with a 1-year follow-up with either a NET &lt; 2 cm or a pancreatic cystic neoplasm (PCN), either a branch duct IPMN with worrisome features or a mucinous cystadenoma (MCA). EUS-RFA was performed with an 18G RFA cooling needle. Results 12 patients had 14 NETs (mean size 13.1 mm, range 10 – 20 mm); 17 patients had cystic tumors (16 IPMNs, 1 MCA; mean size 28 mm, range 9 – 60 mm). Overall three adverse events occurred (10 %), two of these in the first two patients (one pancreatitis, one small-bowel perforation). After these initial patients, modifications in the protocol resulted in a decrease in complications (3.5 %), with one patient having a pancreatic ductal stenosis. Among the 14 NETs, at 1-year follow-up 12 had completely disappeared (86 % tumor resolution), with three patients having a delayed response. Among the 17 PCNs, at 12 months, there were 11 complete disappearances and one diameter that decreased by &gt; 50 % (significant response rate 71 %). All 12 mural nodules showed complete resolution. Conclusions EUS-RFA of pancreatic NETs or PCNs is safe with a 10 % complication rate, which can be decreased by improved prophylaxis for the procedure.
Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection.
Authors: Kabsoo Shin, In-Ho Kim
Journal: Journal of Clinical Oncology (2019)

160 Background: The aim of this study is to compare capecitabine and oxaliplatin (XELOX) with S-1 based on disease-free survival, and to define the clinical impact of lymph node ratio to select a regimen. Methods: Patients who had curative resection and received either S-1 or XELOX as adjuvant chemotherapy for gastric cancer between Jan. 2011 and Dec. 2015, were analyzed using propensity score matching (PSM). Of the 412 patients enrolled, 301 received S-1 and 111 received XELOX and after PSM, the sample size of each group was 111 patients. And the groups were classified according to stage and lymph node ratio (0, &gt; 0-0.1, &gt; 0.1-025, &gt; 0.25) and three-year disease-free survival (DFS) was evaluated. Results: In post-PSM analysis of all 222 patients, The three-year DFS rates in XELOX group was higher than in the S-1 group in all stage 3 (78% vs. 66.1%, p = 0.036), stage IIIC (64.1% vs. 42.0%, p = 0.038) and LNR &gt; 0.25 (67.7.1% vs. 26.1%, p = 0.002). The hazard ratio of XELOX for recurrence compared with S-1 for stage IIIC and LNR &gt; 0.25 was respectively 0.479 (95% CI 0.238~0.985, p = 0.046) and 0.351 (95% CI 0.162~0.758, p = 0.008). Conclusions: Adjuvant XELOX was more effective than S-1 for stage IIIC and LNR &gt; 0.25 in gastric cancer after D2 dissection.
Is it time to reevaluate prenatal mental health? – Author's reply
Authors: Tom A McAdams, Laurie J Hannigan, Espen Moen Eilertsen, Line C Gjerde, Ted Reichborn-Kjennerud, Thalia C Eley, Fruhling V Rijsdijk, Eivind Ystrom
Journal: The Lancet Psychiatry (2019)
Impact of Homozygous Conserved Extended HLA Haplotypes on Cord Blood Transplantation: Implications for Induced Pluripotent Stem Cell Banking and Transplantation
Authors: Yasuo Morishima, Satoko Morishima, Makoto Murata, Nobuyoshi Arima, Naoyuki Uchida, Yuji Ohno, Satoshi Takahashi, Yoshiko Matsuhashi, Makoto Onizuka, Tetsuya Eto, Yoshiko Atsuta, Takahiro Fukuda, Tatsuo Ichinohe, Shunichi Kato, Junya Kanda
Journal: Blood (2018)
Abstract 10553: APD418, A Selective Beta3-Adrenergic Receptor Antagonist Enhances Cardiac Positive Inotropic and Lusitropic Responses to Dobutamine in Conscious, Chronically-Instrumented Dogs With Pacing-Induced Heart Failure: Assessment by Pressure-Volume Analysis
Authors: Xiaowei Zhang, Zhi Zhang, Tiankai Li, Heng-Jie Cheng, Dwight D Deal, James E Jordan, John Adams, Che Ping Cheng
Journal: Circulation (2018)

Background: Attenuation of heart failure (HF) response to positive inotropic agents such as dobutamine (DOB) represents a major clinical problem. The regulation of cardiac function by catecholamine...
Abstract P2-06-10: Withdrawn
Authors: AK Sood, A Mukhopadhyay, J Wang
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Sood AK, Mukhopadhyay A, Wang J. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-10.
Characteristic gene alterations in primary gastrointestinal T- and NK-cell lymphomas
Authors: Gunho Lee, Hyang Joo Ryu, Ji Woon Choi, Hyundeok Kang, Woo Ick Yang, In Seok Yang, Mi-kyoung Seo, Sangwoo Kim, Sun Och Yoon
Journal: Leukemia (2019)
Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities
Authors: Craig A. Elmets, Craig L. Leonardi, Dawn M.R. Davis, Joel M. Gelfand, Jason Lichten, Nehal N. Mehta, April W. Armstrong, Cody Connor, Kelly M. Cordoro, Boni E. Elewski, Kenneth B. Gordon, Alice B. Gottlieb, Daniel H. Kaplan, Arthur Kavanaugh, Dario Kivelevitch, Matthew Kiselica, Neil J. Korman, Daniela Kroshinsky, Mark Lebwohl, Henry W. Lim, Amy S. Paller, Sylvia L. Parra, Arun L. Pathy, Elizabeth Farley Prater, Reena Rupani, Michael Siegel, Benjamin Stoff, Bruce E. Strober, Emily B. Wong, Jashin J. Wu, Vidhya Hariharan, Alan Menter
Journal: Journal of the American Academy of Dermatology (2019)
Abstract B34: Pyrimidobenzimidazoles as a potential new drug to treat human melanoma
Authors: Jéssica Gonçalves Azevedo, Iago Carvalho Schultz, Jacqueline Fraga de Souza Santos, Silvya Stuchi Maria-Engler, Guido Lenz, Marcia Rosângela Wink
Journal: Clinical Cancer Research (2018)

Abstract Melanoma is the most aggressive skin tumor due to its high capacity to metastasize and resistance to therapy, leading to poor prognosis and high mortality rates. Thus, the aim of this study was to investigate a possible antitumoral action of pyrimidobenzimidazole compounds in human melanoma lineages, SK-Mel-103, SK-Mel-28, and SK-Mel-28 resistant to vemurafenib. Using acute treatment (72 hours) it was possible to select two, among the seven compounds tested, by their effectiveness in decrease the cell viability, by MTT assay, in low concentrations. Further, using chronic assay (120 hours) it was possible to find the IC50 of the best compounds, PBZs 1 and 4. For cell line SK-Mel-103 the IC50 value was 3.2 µM and 4.0 µM, for the two more potent compounds respectively, and for cell line SK-Mel-28 IC50 of 9.7 µM and 9.6 µM was obtained for PBZ01 and PBZ04, respectively. These compounds, alone or in combination with DTIC, were used to analyze the cumulative population doubling, in an attempt to simulate the treatment cycle used for patients. The results show that PBZs 1 and 4, especially when in combination with dacarbazine, were able to cause a significant decrease in the population growth rate and in the number of colonies in clonogenic assay, of the SK-Mel-28, better than dacarbazine alone and in lower concentration. Also, it is important to highlight that the effect of PBZs was selective to melanoma, considering that it did not cause relevant effect in melanocyte and in the proliferative nontumoral cell line, MRC5. The cell cycle analysis showed that the treatment alters the cell complexity, increasing the size (FSC) and granularity (SSC). Furthermore, when vemurafenib-resistant cells were treated with PBZ (cotreatment with vemurafenib), there were a population decrease in the population doubling assay more than vemurafenib alone. These results are important and encourage the study of the mechanism by which these compounds affect the melanomas' viability as well as the development of a preclinical model to confirm their effectiveness in vivo. Citation Format: Jéssica Gonçalves Azevedo, Iago Carvalho Schultz, Jacqueline Fraga de Souza Santos, Silvya Stuchi Maria-Engler, Guido Lenz, Marcia Rosângela Wink. Pyrimidobenzimidazoles as a potential new drug to treat human melanoma [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B34.