tbuckley/cabot-search huggingface dataset:
Lung Adenocarcinoma Harboring EGFR 19del/C797S/T790M Triple Mutations Responds to Brigatinib and Anti-EGFR Antibody Combination Therapy
Authors: Xiaofei Wang, Ling Zhou, Jiani C. Yin, Xue Wu, Yang W. Shao, Beili Gao
Journal: Journal of Thoracic Oncology (2019)
Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry
Authors: Hyuna Sung, Rebecca L Siegel, Philip S Rosenberg, Ahmedin Jemal
Journal: The Lancet Public Health (2019)

BackgroundCancer trends in young adults, often under 50 years, reflect recent changes in carcinogenic exposures, which could foreshadow the future overall disease burden. Previous studies reported an increase in early onset colorectal cancer, which could partly reflect the obesity epidemic. We examined age-specific contemporary incidence trends in the USA for 30 common cancers, including 12 obesity-related cancers.MethodsWe obtained incidence data for invasive cancers among people aged 25–84 years diagnosed from Jan 1, 1995, to Dec 31, 2014, for 25 population-based state registries in the USA. All patients in the registry were included in the analyses. We considered the 20 most common cancer types and 12 obesity-related cancers (30 cancer types in total). We used age-period-cohort modelling to estimate average annual percentage change in incidence rates by 5-year age group (25–29 years to 80–84 years in 5-year increments) and incidence rate ratios (IRR) by birth cohort (10-year overlapping birth cohorts from 1910–19 to 1980–89 in 5-year increments). No exclusion criteria were applied after including all invasive cancer cases based on age group and diagnosis year.FindingsFrom 1995 to 2014 there were 14 672 409 incident cases for 30 types of cancer. Incidence significantly increased for six of 12 obesity-related cancers (multiple myeloma, colorectal, uterine corpus, gallbladder, kidney, and pancreatic cancer) in young adults (25–49 years) with steeper rises in successively younger generations. Annual increases ranged from 1·44% (95% CI −0·60 to 3·53) for multiple myeloma to 6·23% (5·32–7·14) for kidney cancer at age 25–29 years, and ranged from 0·37% (0·03–0·72) for uterine corpus cancer to 2·95% (2·74–3·16) for kidney cancer at age 45–49 years. Compared with people born around 1950, IRRs for those born around 1985 ranged from 1·59 (95% CI 1·14–2·21) for multiple myeloma to 4·91 (4·27–5·65) for kidney cancer. Conversely, incidence in young adults increased in successively younger generations for only two cancers (gastric non-cardia cancer and leukaemia), and decreased for eight of the 18 additional cancers, including smoking and HIV infection-associated cancers.InterpretationThe risk of developing an obesity-related cancer seems to be increasing in a stepwise manner in successively younger birth cohorts in the USA. Further studies are needed to elucidate exposures responsible for these emerging trends, including excess bodyweight and other risk factors.FundingIntramural Research Department of the American Cancer Society and the Intramural Research Program of the National Cancer Institute.
Chemotherapy Treatment Doesn't Beneficiate to a Group of Elderly AML Patients with Absence of Complex Karyotype and Circulating Blasts
Authors: Berengere Gruson, Magalie Joris, Olivier Nibourel, Véronique Harrivel, Nathalie Cambier, Pauline Lionne, Bachra Choufi, Celine Rodriguez, Cecile Frimat, Isabelle Plantier, Laure Stalnikiewicz, Maxime Bemba, Céline Berthon, Claude Preudhomme, Pierre Morel, Jean-Pierre Marolleau
Journal: Blood (2018)
Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer
Authors: Ryuma Tokunaga, Joanne Xiu, Curtis Johnston, Richard M. Goldberg, Philip A. Philip, Andreas Seeber, Madiha Naseem, Jae Ho Lo, Hiroyuki Arai, Francesca Battaglin, Alberto Puccini, Martin D. Berger, Shivani Soni, Wu Zhang, Jimmy J. Hwang, Anthony F. Shields, John L. Marshall, Hideo Baba, W. Michael Korn, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2019)

The natural history and prognosis of appendiceal adenocarcinomas differ from those of adenocarcinomas arising in other large bowel sites. We aimed to compare the molecular profiles exhibited by appendiceal adenocarcinomas and colorectal cancers, or between the histopathologic subtypes of appendiceal adenocarcinoma.A total of 183 samples from appendiceal adenocarcinoma [46 adenocarcinoma, not otherwise specified (NOS), 66 pseudomyxoma peritonei (PMP), 44 mucinous adenocarcinoma (MU), and 27 signet ring cell carcinoma (SR)], 994 from right-sided colorectal cancer (R-CRC), and 1,080 from left-sided CRC (L-CRC) were analyzed by next-generation sequencing (NGS) and IHC markers. Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS, and programmed death ligand 1 (PD-L1) by IHC.We observed high mutation rates in appendiceal adenocarcinoma samples for KRAS (55%), TP53 (40%), GNAS (31%), SMAD4 (16%), and APC (10%). Appendiceal adenocarcinoma exhibited higher mutation rates in KRAS and GNAS, and lower mutation rates in TP53, APC, and PIK3CA (6%) than colorectal cancers. PMP exhibited much higher mutation rates in KRAS (74%) and GNAS (63%), and much lower mutation rates in TP53 (23%), APC (2%), and PIK3CA (2%) than NOS. Alterations associated with immune checkpoint inhibitor response (MSI-high, TMB-high, PD-L1 expression) showed similar frequency in appendiceal adenocarcinoma compared with L-CRC, but not R-CRC, and those of NOS were higher than other subtypes of appendiceal adenocarcinoma and L-CRC.Molecular profiling of appendiceal adenocarcinoma revealed different molecular characteristics than noted in R-CRC and L-CRC, and molecular heterogeneity among the histopathologic subtypes of appendiceal adenocarcinoma. Our findings may be critical to developing an individualized approach to appendiceal adenocarcinoma treatment.
The Vascular Bone Marrow Niche Influences Outcome in Chronic Myeloid Leukemia
Authors: Parimala Sonika Godavarthy, Stephanie Herkt, Nina Hayduk, Eva Weissenberger, Yosif Manavski, Tina Lucas, Kuan-Ting Pan, Jenna M. Voutsinas, Qian V. Wu, Martin C. Mueller, Thomas Oellerich, Vivian G. Oehler, Jörn Lausen, Daniela S. Krause
Journal: Blood (2018)
Abstract 18011: Vibroacoustic Noninvasive Stimulation (VATS) of Human Coronary Endothelial Cells Induced Syndecan-4, VEGF and KLF2 Mechanosensor Control of eNOS
Authors: Arkady Uryash, Jose A Adams
Journal: Circulation (2017)

Background: Endothelial dysfunction is a hallmark of various cardiovascular diseases. Endothelial Cells (EC) mechanosensor-proteins Syndecan-4 (Syn4), VEGF and KLF2 can translate physical force fro...
Comparative Monitoring of Minimal Residual Disease (MRD) By RT-Quantitative (RT-qPCR) and Digital PCR (dPCR) in Ph+ Chronic Myeloid Leukemia (CML) Patients Treated with TKIs for Recognition of Stable Deep Molecular Response (DMR) and Identification of Best Candidates to TKIs Treatment Discontinuation
Authors: Simona Bernardi, Michele Malagola, Camilla Zanaglio, Alessandra Iurlo, Cristina Bucelli, Nicola Polverelli, Elif Dereli Eke, Massimiliano Bonifacio, Eleonora Toffoletti, Mario Tiribelli, Clara Deambrogi, Gianluca Gaidano, Stefania Stella, Fabio Stagno, Paolo Vigneri, Francesco Di Raimondo, Mirko Farina, Mariella D'Adda, Doriana Gramegna, Elisa Cerqui, Giuseppe Rossi, Micaela Bergamaschi, Marco Gobbi, Luca Franceschini, Maria Teresa Voso, Elisabetta Abruzzese, Malgorzata Monika Trawinska, Domenico Russo
Journal: Blood (2018)
Spitzoid melanoma with ALK copy number gain
Authors: M. Farah, P. Nagarajan, J.L. Curry, Z. Tang, T.‐B. Kim, P.P. Aung, C.A. Torres‐Cabala, A.K. Eterovic, J.A. Wargo, V.G. Prieto, M.T. Tetzlaff
Journal: British Journal of Dermatology (2019)

Spitzoid melanoma is an uncommon melanoma (type of skin cancer) that can occur at any age, and can resemble a harmless mole called a ‘Spitz nevus’. This similarity can make it difficult to diagnose. Spitzoid tumours (Spitz nevi) have recently begun to be categorized according to their genetic profile, meaning the genes found in them, and certain molecular alterations were found to link to changes to the structure of the nevus as could be seen when examined under a microscope. For example, Spitz tumours can have what is called an anaplastic lymphoma kinase (ALK) gene rearrangement. ALK is a gene that tells your body how to make proteins that help cells talk to each other. ALK rearrangement means that part of this gene is broken and attached to another gene. Spitz tumours with ALK rearrangement have been shown to have a distinctive “plexiform pattern”. Humans have two copies of most genes, but occasionally alterations can lead to the gain or a loss of one copy. When it is a gain of one copy this is called copy gain. In this report, authors from the US discuss a case of an 87‐year‐old man with a 3cm tumour on his back, and conclude that ALK copy gain represents an additional mechanism of ALK activation among Spitzoid tumours and shows the same plexiform pattern seen among ALK‐rearranged Spitz tumours.
Assessment of Percentage of Women in the Dermatology Workforce Presenting at American Academy of Dermatology Annual Meetings, 1992-2017
Authors: Hannah Stratman, Erik J. Stratman
Journal: JAMA Dermatology (2019)

This study assesses the percentage of female speakers at American Academy of Dermatology conferences from 1992 through 2017 and compares it with the overall percentages of board-certified female dermatologists.
HGCSG 1603: Phase II study of ramucirumab and irinotecan combination therapy as second-line treatment in patients with metastatic or advanced gastric cancer.
Authors: Atsushi Ishiguro, Yasuyuki Kawamoto, Satoshi Yuki, Yoshimitsu Kobayashi, Kazuaki Harada, Susumu Sogabe, Yasushi Tsuji, Shintaro Nakano, Kentaro Sawada, Tetsuhito Muranaka, Hiroshi Nakatsumi, Masayoshi Dazai, Takahide Sasaki, Kazunori Eto, Michio Nakamura, Osamu Muto, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2019)

TPS183 Background: As second-line chemotherapy for gastric cancer, a survival benefit has been shown in several clinical trials. Irinotecan and taxanes are recommended as second-line regimen. However, therapeutic outcomes have remained unsatisfactory and more effective treatment are expected. Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody that prevents ligand binding of VEGF-A, VEGF-C, and VEGF-D and the receptor-mediated pathway activation in endothelial cells, subsequently inhibiting neovascularization. In the REGARD study, RAM monotherapy for previously treated advanced gastric or gastro-esophageal junction adenocarcinoma improved median overall survival (mOS) compared with placebo. Moreover, in the RAINBOW study, RAM plus paclitaxel (PTX) versus placebo plus PTX, mOS showed significantly longer in RAM plus PTX group than in placebo plus PTX group. In contrast, there are no data on the efficacy of RAM and irinotecan in the second-line treatment for gastric cancer. The WJOG 4007 study demonstrated an equivalent efficacy between irinotecan and PTX. In this study, we propose to examine the efficacy of RAM plus irinotecan. Methods: This study is carried out as a multicenter, non-randomized, single arm, prospective, phase II study. The patients with metastatic or advanced gastric cancer that is refractory or intolerance to primary chemotherapy are eligible for this study. RAM and irinotecan combination therapy is administered every two weeks, which is continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint is progression-free survival rate at six months, and the secondary endpoints are OS, progression-free survival, response rate, safety, and dose intensity for each drug. A total of 35 cases areplanned for registration. This study is registered with the University Hospital Medical Information Network. Clinical trial information: UMIN000030372.
Peritoneal carcinomatosis (PC) in well-differentiated (WD) small-intestinal neuroendocrine tumor (SI-NET) patients (Pts) with mesenteric tumor deposits (MTDs).
Authors: Satya Das, Chanjuan Shi, Tatsuki Koyama, Yi Huang, Raul S. Gonzalez, Kamran Idrees, Christina Edwards Bailey, Jordan Berlin
Journal: Journal of Clinical Oncology (2019)

194 Background: Although WD SI-NETs are typically biologically indolent, they tend to metastasize. PC is a dreaded regional metastatic complication in pts with SI-NETs and contributes to significant morbidity and mortality. Risk factors for PC development in these pts are not well studied, however one factor may be MTD presence. Our analysis is the first to suggest an association between MTD presence and PC in this pt subgroup. Methods: We performed a retrospective analysis on 191 WD SI-NET samples from Vanderbilt University Medical Center with mesenteric masses identified on gross pathology or radiographic review. Of 138 samples with suspected MTDs, 79 were confirmed definitively by detailed pathologic review and 59 were considered likely based on descriptions from surgical pathology reports. We assessed whether pts in our cohort with MTDs had greater rates of PC compared to those without MTDs. We also assessed what other patient determinants were associated with PC and the prognostic role of these determinants. Results: Pts with suspected MTDs had an odds ratio (OR) of 3.9 for PC compared to pts without MTDs. Rates of PC in pts with definitive MTDs and those with likely MTDs were not significantly different (OR 1, p = 1.00). Although suspected MTD presence was not associated with poorer OS (p = 0.97), pts with confirmed MTDs had a trend toward poorer overall survival (OS) than pts with likely MTDs (p = 0.05). PC was a negative prognostic factor in all pts with regards to OS (p = 0.044). Conclusions: SI-NET pts with MTDs appear to have significantly increased rates of PC compared to those without mesenteric deposits. We believe this observation merits prospective evaluation given its potential therapeutic implications. If confirmed prospectively, pts with MTDs could benefit from earlier use of cytoreductive therapies to hinder development of PC. [Table: see text]
ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment
Authors: Magnus T. Dillon, Katharina F. Bergerhoff, Malin Pedersen, Harriet Whittock, Eva Crespo-Rodriguez, Emmanuel C. Patin, Alex Pearson, Henry G. Smith, James T.E. Paget, Radhika R. Patel, Shane Foo, Galabina Bozhanova, Chanthirika Ragulan, Elisa Fontana, Krisha Desai, Anna C. Wilkins, Anguraj Sadanandam, Alan Melcher, Martin McLaughlin, Kevin J. Harrington
Journal: Clinical Cancer Research (2019)

Abstract Purpose: ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor microenvironment. Experimental Design: We used an immunocompetent mouse model of HPV-driven malignancies to investigate the ATR inhibitor AZD6738 in combination with fractionated radiation (RT). Gene expression analysis and flow cytometry were performed posttherapy. Results: Significant radiosensitization to RT by ATRi was observed alongside a marked increase in immune cell infiltration. We identified increased numbers of CD3+ and NK cells, but most of this infiltrate was composed of myeloid cells. ATRi plus radiation produced a gene expression signature matching a type I/II IFN response, with upregulation of genes playing a role in nucleic acid sensing. Increased MHC I levels were observed on tumor cells, with transcript-level data indicating increased antigen processing and presentation within the tumor. Significant modulation of cytokine gene expression (particularly CCL2, CCL5, and CXCL10) was found in vivo, with in vitro data indicating CCL3, CCL5, and CXCL10 are produced from tumor cells after ATRi + RT. Conclusions: We show that DNA damage by ATRi and RT leads to an IFN response through activation of nucleic acid–sensing pathways. This triggers increased antigen presentation and innate immune cell infiltration. Further understanding of the effect of this combination on the immune response may allow modulation of these effects to maximize tumor control through antitumor immunity.
The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity
Authors: Sanjivan Gautam, Jessica Fioravanti, Wei Zhu, John B. Le Gall, Philip Brohawn, Neal E. Lacey, Jinhui Hu, James D. Hocker, Nga Voong Hawk, Veena Kapoor, William G. Telford, Devikala Gurusamy, Zhiya Yu, Avinash Bhandoola, Hai-Hui Xue, Rahul Roychoudhuri, Brandon W. Higgs, Nicholas P. Restifo, Timothy P. Bender, Yun Ji, Luca Gattinoni
Journal: Nature Immunology (2019)
Sequential Infusion of Tcrαβ- and CD45RA-Depleted Haploidentical Progenitor Cells Is Safe and Allows for Rapid Immune Reconstitution in Pediatric Patients with Recurrent Hematological Malignancies
Authors: Ali Y Suliman, Ying Li, David Cullins, Amanda J Sooter, Janice Riberdy, Madden Renee, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma, Ashok Srinivasan, Aimee Talleur, Anusha Sunkara, Guolian Kang, Stephen Gottschalk, Brandon Triplett
Journal: Blood (2018)
Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7)
Authors: Malgorzata Mikulska, Simone Cesaro, Hugues de Lavallade, Roberta Di Blasi, Sigrun Einarsdottir, Giuseppe Gallo, Christina Rieger, Dan Engelhard, Thomas Lehrnbecher, Per Ljungman, Catherine Cordonnier
Journal: The Lancet Infectious Diseases (2019)
Abstract 19888: Improved Longitudinal Low Density Lipoprotein Cholesterol Goal Achievement Among Familial Hypercholesterolemia Patients in the CASCADE FH Patient Registry
Authors: P. Barton Duell, Rolf L Andersen, Thomas Knickelbine, Lars Anderson, Eugenia Gianos, Emily C O’Brien, Iris Kindt, Peter Shrader, Dervilla McCann, Seth Baum, Linda C Hemphill, Catherine D Ahmed, Seth S Martin, Karol E Watson, Iftikhar J Kullo, John A Larry, Michael Murray, Robert Fishberg, John Guyton, Katherine Wilemon, Matthew T Roe, Daniel J Rader, Christie M Ballantyne, James A Underberg, Paul Thompson, Zahid S Ahmad, David Whellan, MacRae F Linton, Patrick M Moriarty, Michael D Shapiro, Joshua W Knowles
Journal: Circulation (2017)

Introduction: Familial hypercholesterolemia (FH) is associated with 10-20 fold increased CHD risk and requires aggressive low density lipoprotein cholesterol (LDL-C) lowering, ideally initiated at a young age. Late diagnosis and inability to achieve LDL-C goals impede care and portend worse outcomes. The FH Foundation CASCADE FH patient registry consists of data from lipid specialty clinics and was analyzed prospectively. Hypothesis: LDL-C goal achievement improved among FH patients in the registry over time, particularly after availability of anti-PCSK9 drugs beginning mid-2015. Methods: Out of 3910 FH patients in the registry, 958 with longitudinal data collected between 4/14-2/17 were analyzed for changes in health status and LDL-C (Chi-squared tests for categorical and Kruskal Wallis for continuous variables). Results: Mean entry age was 57 ± 15 yr; mean follow-up was 12.5 ± 6 months with 1.2 ± 0.5 visits; LDL-C was 256 ± 85 mg/dl untreated (n=676) and 140 ± 65 mg/dl at entry to registry; CHD was pres...
Abstract 18435: Development and Validation of a Risk Score Predicting 5-Year Mortality after Percutaneous Coronary Intervention for Selecting Suitable Patients for Bioresorbable Stents
Authors: Nick van Boven, Isabella Kardys, Ron T van Domburg, Joost Daemen, Victor A Umans, Robert-Jan van Geuns, Eric Boersma
Journal: Circulation (2014)

Introduction: It is a defendable strategy to restrict the use of bioresorbable stents to patients with a life expectancy that exceeds the stent dissolution time. However, selection tools for the broad population of percutaneous coronary intervention (PCI) patients are lacking. Hypothesis: We aimed to develop and validate a risk score predicting 5-year all-cause mortality after PCI, which might help selecting suitable patients for bioresorbable stents. Methods: A total of 19532 patients were included, who underwent PCI for any indication in our hospital during 2000 - 2012. Patients were randomly divided into a balanced training (n=13090) and validation (n=6442) cohort. Mortality data were obtained via the Civil Registry. Cox proportional hazards models with backward selection were used to identify risk factors for 5-year mortality. Results: Median age was 63 years (IQR 54-72) and 72% were men. Five-year mortality was 12.9%. In the training set, age, body mass index <25, diabetes mellitus, renal insufficien...
Abstract 19020: Brief Hand-Held Echocardiography Teaching Improves Diagnosis of Valvular Heart Disease by Medical Students: A Controlled Study in the 2nd Year Cardiovascular Curriculum
Authors: David A Vorchheimer, Robert S Copeland-Halperin, M. Urooj Zafar, Paul Trubin, Matthew Seigerman, Erik Popil, Jagat Narula, Jonathan L Halperin
Journal: Circulation (2014)

Background: As clinical examination skills by standard teaching methods decline, Hand-Held Echo (HHE) can augment medical student physical diagnosis. Methods: We studied whether the addition of bri...
New Deep Brain Stimulation Target for Mood Disorders
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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