tbuckley/cabot-search huggingface dataset:
Head and neck cancer (HN) characteristics and outcomes in a human immunodeficiency virus infected (HIV+) patient cohort: A 12-year experience of the Louisiana State University Health Sciences Center (LSUHSC) and Charity Hospital in New Orleans.
Authors: J. Nicholas Bodor, Marco A. Ruiz, Cruz Velasco-Gonzales, Brian C. Boulmay
Journal: Journal of Clinical Oncology (2014)

6069 Background: HIV+ patients (pts) are typically excluded from enrollment on randomized clinical trials for head and neck cancer. Data regarding clinical characteristics and outcomes for HIV+ pts with HN are limited in the medical literature. Despite lack of data, pts with HN and HIV are managed at LSUHSC in a multidisciplinary fashion according to the standards of care established for HIV negative (HIV-) pts. Methods: 15 HIV+ pts with AJCC Stage I (33%), Stage II (0%), Stage III (20%) and Stage IV (47%) squamous cell carcinoma of the head and neck treated from 1/1999 to 6/2011 were retrospectively reviewed. Additional data collected included: tumor primary site, age at diagnosis, gender, ethnicity, time from confirmed HIV infection to HN diagnosis and characteristics of pts HIV status. End points analyzed were progression-free survival (PFS) and overall survival (OS). Results: Oral tongue (26%), tonsil (20%) and larynx (13%) were most common primary sites; mean age at diagnosis was 48 years (yrs) old; 86% of pts were male, 14% were female; 47% of pts were white and 53% were black. Mean time from diagnosis of HIV to HN was 69 months and mean CD4 count nadir at any point prior to HN diagnosis was 93 cells/mm^3. 60% of pts in the cohort had been diagnosed with acquired immune deficiency syndrome (AIDS) before the HN diagnosis; the diagnosis of AIDS occurred a mean of 16 months prior to HN diagnosis. PFS at 3 yrs was 80% and OS at 3 yrs was 40%; median overall survival was 2.1 yrs. Conclusions: A majority of HIV+ pts in this cohort had AIDS diagnosed preceding the HN diagnosis. However, outcomes of HIV+ pts diagnosed with HN treated at our institution are favorable compared to HIV- pts. Our experience would suggest that HIV+ pts be treated according to accepted standards of care with careful management by physicians with HIV expertise.
Use of Intravenous Immune Globulin in Patients with Immune Thrombocytopenia Before and After Romiplostim: Real-World Experience
Authors: Korinne Hamilton, Lisa J. Toltl, Grace Wang, Naushin S Sholapur, Julie Carruthers, Cyrus C. Hsia, Caroline Hamm, Normand Blais, Catherine Girard-Desbiens, Marc-Andre Pearson, Nancy Heddle, Donald M. Arnold
Journal: Blood (2012)
INCLUSION OF WOMEN IN STUDIES OF CATHETER ABLATION FOR ATRIAL FIBRILLATION: FINDINGS FROM THE SMASH-AF META-ANALYSIS STUDY COHORT
Authors: Fahd Yunus, George Leef, Andrew Cluckey, Mariam Askari, Ewoud Schuit, Paul Heidenreich, Mintu Turakhia, Alexander Perino
Journal: Journal of the American College of Cardiology (2017)
MLN0264, an investigational, first-in-class antibody-drug conjugate (ADC) targeting guanylyl cyclase C (GCC): Phase I, first-in-human study in patients (pts) with advanced gastrointestinal (GI) malignancies expressing GCC.
Authors: Khaldoun Almhanna, Wells A. Messersmith, Jordi Rodon Ahnert, Cristina Cruz, David P. Ryan, JungAh Jung, Adedigbo Fasanmade, Tim Wyant, Thea Kalebic
Journal: Journal of Clinical Oncology (2013)

TPS3646 Background: MLN0264, an investigational ADC that targets GCC, consists of a fully human monoclonal antibody conjugated to the cytotoxic microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. MMAE and the linker technology are licensed from Seattle Genetics. GCC is a cell surface protein expressed by normal intestinal epithelial cells, ~95% of metastatic colorectal cancer (mCRC), and subsets of gastric and pancreatic cancers. In normal tissue, GCC is expressed on the apical side of epithelial cell tight junctions; therefore, systemically delivered GCC-targeting agents are expected to be preferentially delivered to tumor tissue in which cell polarity is disrupted. MLN0264 has demonstrated antitumor activity in mouse xenograft models of GCC-expressing tumors (Veiby et al. EORTC-NCI-AACR, 2012), supporting the scientific rationale for this first-in-human study. Methods: This study (NCT01577758) was designed to evaluate MLN0264 in ~60 adult pts with GI malignancies expressing GCC (≥1+), measurable disease by RECIST, and ECOG PS 0/1. This study is being conducted at 4 centers in the US and EU and is estimated to last ~36–42 months. Pts receive IV MLN0264 on day 1 of 21-day cycles for up to 17 cycles or until disease progression/unacceptable MLN0264-related toxicity. Dose escalation is proceeding via an adaptive Bayesian continual reassessment model approach based on dose-limiting toxicities in cycle 1. Following determination of the maximum tolerated dose (MTD), up to 14 pts each will be enrolled to mCRC and gastric carcinoma expansion groups to further characterize the safety, tolerability, and pharmacokinetics (PK) of MLN0264 and evaluate its clinical activity. The primary objectives are to evaluate the safety and tolerability, determine the MTD, and describe the PK of IV MLN0264. Secondary objectives are to evaluate the antitumor activity and immunogenicity of MLN0264. An exploratory objective is to examine the relationship between levels of GCC protein expression in tumor tissue and clinical response. Enrollment as of Jan 2013 was 12 pts. Clinical trial information: NCT01577758.
High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Support for Relapsed or Refractory Primary CNS Lymphoma - a Prospective Multicentre Trial By the German Cooperative PCNSL Study Group
Authors: Benjamin Kasenda, Gabriele Ihorst, Roland Schroers, Agnieszka Korfel, Ingo GH Schmidt-Wolf, Gerlinde Egerer, Louisa von Baumgarten, Alexander Röth, Stephan Stilgenbauer, Robert Möhle, Mascha Binder, Ulrich Keller, Monika Lamprecht, Hans-Heinrich Wolf, Michael Pfreundschuh, Elke Valk, Heidi Fricker, Schorb Elisabeth, Fritsch Kristina, Jürgen Finke, Gerald Illerhaus
Journal: Blood (2016)
THE ROLE OF PULMONARY FUNCTION TEST IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION: LOOKING BEYOND CHRONIC OBSTRUCTION PULMONARY DISEASE
Authors: Wei Ming Huang, Hao-Min Cheng, Tsu-Hui Shiao, Chen-Huan Chen, Wen-Chung Yu, Shih-Hsien Sung
Journal: Journal of the American College of Cardiology (2017)
Implementation of pediatric population-based cancer registries (PBCR) in Central America (CA).
Authors: Soad Fuentes Alabi, Roberto Vasquez, Federico Antillon, Ana C. Polanco, Elisabeth Orellana, Antonio Perez-Atayde, Irini Albanti, Paola Friedrich, Carlos Rodriguez-Galindo, Karina Ribeiro, A. Lindsay Frazier, Claudia Garrido
Journal: Journal of Clinical Oncology (2015)

e12624 Background: With progress made towards meeting the Millennium Development Goals, cancer is now an important contributor to childhood mortality in CA. Hospital-based data suggests regional differences in cancer incidence compared to estimates in Europe and North America. PBCR are needed for rational cancer planning and to support descriptive and molecular epidemiology research in childhood cancer specific to the region. Methods: Two pediatric PBCR were created in Guatemala (GU) and El Salvador (ES) in 2013. A four-step process was followed. First, training of coordinators and registrars was completed, and CanReg5 was implemented with the support of the International Association of Cancer Registries and the Global Initiative for Cancer Registry Development. Second, the support of health authorities was secured to ensure regulatory compliance and long-term sustainability. Third, involvement of public and private stakeholders (oncologists, pathologists, and laboratories) was sought to ensure access to information sources and registry data. And fourth, variables and coding were defined using the International Classification of Diseases for Oncology third revision (ICD-O-3) and the International Classification of Childhood Cancer (ICCC). Incidence rates were expressed as new cases per 1,000,000 person-years (0-14 years) and compared to estimates produced by IARC in GLOBOCAN 2012. Results: GLOBOCAN reported an age-adjusted incidence rate (AIR) of childhood cancer of 72.36 per million children for ES (133 cases/year) and 57.45 for GU (363 cases/year). In contrast, the PBCR reported a 2014 AIR of 89.76 in ES (165 new cases) and 52.71 in GU (333 new cases). Accordingly, GLOBOCAN shows an underestimation of 24% for ES and overestimation of 8% in GU. Conclusions: Our initiative demonstrates the feasibility of creating pediatric PBCR in CA, and the improved accuracy of estimation compared to GLOBOCAN. Next steps include implementation of methods to assure total case ascertainment in the existing registries and an expansion of the program to Honduras and Nicaragua. The development of pediatric PBCR is a necessary step towards building pediatric cancer epidemiology research in resource-limited settings.
Comprehensive characterization of PDL-1 and CTLA-4 in gastric cancer.
Authors: Hans Anton Schloesser, Uta Drebber, Martin Thelen, Michael Kloth, Sasha Rothschild, Maria Garcia-Marquez, Sharam Zoghi, Alexander Urbanski, Hakan Alakus, Astrid Schauss, Sebastian Theurich, Ute Warnecke-Eberz, Dirk Ludger Stippel, Arnulf Heinrich Hölscher, Thomas Zander, Stefan Paul Moenig, Michael S. von Bergwelt-Baildon
Journal: Journal of Clinical Oncology (2015)

4056 Background: Recently remarkable efficacy of immune checkpoint inhibition has been reported for several kinds of solid cancers. This study is the first comprehensive analysis of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) in gastric cancer and the first study integrating oncogenomic analyses. Methods: PD-L1 and CTLA-4 were stained on paraffin embedded tumor sections of 127 patients with gastric cancer by immunohistochemistry. Genetic driver mutations were identified by next-generation Sequencing and FISH analysis. Expression of PD-1, PD-L1 and CTLA-4 on lymphocytes in tumor sections, lymph nodes and peripheral blood were studied by 10-colour flow cytometry and 4-colour immune-fluorescence microscopy in an additional cohort. Results: PD-L1 and CTLA-4 were expressed on primary tumor cells by 44.9%(57/127) and 86.6%(110/127) of the analyzed gastric cancer samples, respectively. Correlation to clinical and pathological parameters revealed no correlation for PD-L1, whereas CTLA-4-negativity was correlated to higher grading and diffuse type according to Lauren. Positivity of PD-L1 or CTLA-4 on tumor cells was associated with inferior overall survival. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor-infiltrating T cells was significantly elevated compared to peripheral blood lymphocytes. We could identify distinct genotypic profiles comparing the subgroups of checkpoint molecule expression. Conclusions: Our analysis revealed a great impact of PD-1/PD-L1 and CTLA-4 on the biology of gastric cancer. Hence corresponding checkpoint-inhibitors should be evaluated in this disease and approaches combining molecular targeted therapy and checkpoint inhibition could be of additional benefit. An extensive immune monitoring should be included in these studies.
PREDICTORS OF ANTICOAGULANT PRESCRIPTION IN PATIENTS WITH ATRIAL FIBRILLATION IN NORTH AMERICA: THE GLORIA-AF REGISTRY
Authors: William F. McIntyre, David Conen, Brian Olshansky, Jonathan Halperin, Emil Hayek, Menno Huisman, Gregory Lip, Shihai Lu, Jeff Healey
Journal: Journal of the American College of Cardiology (2017)
Evidence for Induction of a Tumor-Metastasis-Receptive Microenvironment in Bone Marrow and Other Organs As an Unwanted and Underestimated Side Effect of Chemotherapy/Radiotherapy
Authors: Pranesh Gunjal, Gabriela Schneider, Sham Kakar, Magdalena Kucia, Mariusz Z Ratajczak
Journal: Blood (2014)
Simultaneous Supression of CML and GIST by Imatinib in Single Patient.
Authors: Yuko Mishima, Yasuhito Terui, Kengo Takeuchi, Masahiro Yokoyama, Eijiro Nagasaki, Tetsu Fukunaga, Junji Yamamoto, Toshiharu Yamaguchi, Nobuyuki Mizunuma, Yo Kato, Kiyohiko Hatake
Journal: Blood (2004)
A Shift in the Intestinal Microflora towards Pro-Inflammatory Bacteria and Signaling Via Toll-Like-Receptor 2 Triggers Early Onset of Graft-Versus-Host Disease.
Authors: Axel Nogai, Markus M. Heimesaat, Stefan Bereswill, Eckhard Thiel, Ulf B. Goebel, Lutz Uharek
Journal: Blood (2007)
Genetic, tissue, and plasma biomarkers of outcomes from a prospective study of neoadjuvant short course proton-based chemoradiation for resectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Theodore S. Hong, Vikram Deshpande, Marek Ancukiewicz, Beow Y. Yeap, Darrell R. Borger, Jennifer Yon-Li Wo, Yves Boucher, Eunice Lee Kwak, Jeffrey W. Clark, Andrew X. Zhu, Lawrence Scott Blaszkowsky, Harvey J. Mamon, Rakesh K. Jain, David P. Ryan, Thomas F. DeLaney, Carlos Fernandez-del Castillo, Dan G. Duda
Journal: Journal of Clinical Oncology (2013)

4047 Background: The prognosis of resectable PDAC reflects a complex interaction between genotype, growth factor levels, and tumor microenvironment. We performed genetic, plasma, and tissue-based biomarker analysis for a phase I/II study of neoadjuvant short course proton-based chemoradiation. Methods: Patients with radiographically resectable PDAC were treated on an IRB approved, phase I/II trial of neoadjuvant short course-proton-based chemoradiation. Genotyping included KRAS, BRAF, NRAS, TP53, and PIK3CA. Tissue-based IHC on resection specimens included DPC4, CXCR4, CXCR7, and SDF1a in the central and peripheral regions of PDAC. The trial was amended to evaluate plasma biomarkers, drawn before and after chemoradiation, including HGF, VEGF, sVEGFR2, SDF1α, bFGF, PlGF, TNF-α, CAIX, sFLT1, IL-6, IL-8, and IL-1β. Correlation with OS was evaluated by the Wald test in a univariable Cox regression using log-transformed covariates. Results: Surgical specimens from all 38 patients who underwent resection and serial plasma samples from the last 12 patients enrolled were analyzed. Disease-specific results were previously reported (ASCO 2012, abs 4021). DPC4 intact (37% of evaluated patients) was associated with oligometastatic disease (p&lt;0.05) but not OS. KRAS mutation 31/38 patients (82%), did not affect OS (HR=1.57, p=0.88) , but the specific KRAS G12D mutation (14/38, 37%) had a worse OS (HR=2.44, p&lt;0.05). SDF1α and CXCR7 expression was higher and CXCR4 expression was lower in the tumor center versus periphery. Higher CXCR7 expression in the periphery was associated with poor OS (HR=2.29, p&lt;0.05). High baseline plasma HGF was associated with a worse OS (HR=6.60, p&lt;0.05), with a trend for association between high post-treatment plasma HGF and poor OS (HR=9.28, p=0.08). No other biomarker evaluated was significantly associated with OS. Conclusions: In this exploratory analysis, KRAS G12D status, CXCR7 expression, and plasma HGF level were associated with worse OS. DPC4 status correlated with oligometastatic disease. Additional IHC evaluations, including c-MET expression, are ongoing and will be reported. Clinical trial information: NCT00438256.
THE EVOLUTION OF ATRIOVENTRICULAR VALVE FUNCTION IN PATIENTS WITH HETEROTAXY SYNDROME: A LONGITUDINAL ASSESSMENT FROM FETUS TO LATE AFTER FONTAN OPERATION
Authors: Masaki Nii, Keisuke Sato, Jun Yoshimoto, Sung-Hae Kim, Norie Mitsushita, Yasuhiko Tanaka
Journal: Journal of the American College of Cardiology (2017)
Polymorphism detection of K-Ras mutations using high-resolution melting analysis in Mexican patients with metastatic colorectal cancer (mCRC)
Authors: H. Astudillo, J. Sanchez-Guillen, P. Romero-Garcia, J. Bastarrachea-ortiz, G. Morgan-Villela, J. M. Salazar, V. M. Vazquez-Rivera, H. Ruiz-Calzada, P. Cortes-Esteban
Journal: Journal of Clinical Oncology (2009)

e15135 Background: Metastatic carcinoma of the colorectum remains a major problem. Nowadays the mutational polymorphism detection of K-ras gene is useful for patients with diagnosis of mCRC especially when an anti-EGFR biological therapy is considered to be used. The purpose of this study was to analyze and establish a molecular method to detect the mutational polymorphism of K-Ras gene in paraffin-embedded biopsies from Mexican patients with mCRC. Methods: The presence and polymorphism of K-ras gene mutations were analyzed in paraffin-embedded biopsies from 156 patients using a real time PCR technique with target specific oligomer competitor shifting the PCR amplification towards the mutated target, thus yielding an enriched PCR product containing variations. Results: K-ras mutations were detected in 89 of 156 patients (59%). There was not evaluated a relationship between the presence of a K-ras mutations and clinicopathological features. 39 of the 89 (42.85%) biopsies with a positive K- ras mutation had a 12G mutation polymorphism, 11 of the 89 (12.08%) biopsies had a 12D mutation polymorphism and 10 of the 89 (10.98%) biopsies had a 12S mutation polymorphism. Of the 64 biopsies without K-ras mutation (wild type), none clinicopathological correlation was determine in this group. The rate of the K-ras mutation was higher than that of the K-ras mutation negative group (wild type). Conclusions: This study demonstrates that the determination of mutational polymorphism of k-ras gene is possible and could be implemented as a predictor response in patients with mCRC to benefit from antibody based anti-EGFR therapies. No significant financial relationships to disclose.
Final analysis of a multicenter, randomized phase II trial comparing three different chemoradiotherapy regimens in the treatment of patients with locally advanced, nonmetastatic pancreatic cancer
Authors: R. Wilkowski, S. Boeck, S. Ostermaier, R. Sauer, M. Herbst, R. Fietkau, M. Flentje, C. J. Bruns, H. G. Rau, V. Heinemann
Journal: Journal of Clinical Oncology (2009)

4610 Background: To date, no standard treatment approach for patients (pts) with non-resectable, locally advanced pancreatic cancer (PC) is defined. Methods: Within a prospective phase II trial treatment-naive pts with locally advanced PC and adequate organ function were randomly assigned to three different CRT regimens; all pts received a conventionally fractionated radiotherapy of 50 Gy (with a daily dose of 2.0 Gy) and were randomized to either concurrent 5-FU as a 24h-infusion (350 mg/m 2 /d on each day of radiotherapy, RT-5FU arm), concurrent low-dose gemcitabine 300 mg/m 2 and cisplatin 30 mg/m 2 on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by a sequential chemotherapy with full- dose gemcitabine (1000 mg/m 2 ) and cisplatin (50 mg/m 2 ) every two weeks (RT-GC+GC arm). Treatment duration in the RT- GC+GC arm was upon disease progression or unacceptable toxicity. The primary study endpoint was the overall survival (OS) rate after 9 months (mo); secondary endpoints included response rate (WHO criteria), progression-free survival (PFS), resectability and toxicity. Results: Ninety-five patients (median age 64 years, 54% male, 50% KPS 90–100%) were recruited from 12 German centers. Seventy patients were evaluable for objective response: the intent-to-treat response rate (CR+PR) was 19% in the RT-5FU arm, 22% in the RT-GC arm and 13% in the RT-GC+GC arm, respectively. Overall, 18 pts (19%) underwent surgical resection after initial CRT (R0 in 8 pts). After a median follow-up of 8.6 mo, median PFS was estimated with 4 mo (RT-5FU), 5.6 mo (RT-GC) and 6 mo (RT- GC+GC), respectively (p=0.21). The corresponding median OS times were 9.6 mo, 9.3 mo and 7.3 mo (p=0.61). Hematological grade 3/4 toxicities were higher in the two gemcitabine/cisplatin-containing arms, but no grade 3/4 febrile neutopenia was observed. Regarding non-hematological toxicity, nausea/vomiting were more frequently in the RT-GC and RT-GC+GC arm, whereas diarrhea was more frequent in the RT-5FU arm. Conclusions: Based on these data, gemcitabine/cisplatin-based CRT does not achieve a higher clinical efficacy compared to RT-5FU, and is associated with increased hematological toxicity. [Table: see text]
Increased Number of Driver Mutations Is a Predictor of Response to Hypomethylating Agents in Patients with Myelodysplastic Syndromes
Authors: Guillermo Montalban-Bravo, Ana Alfonso Pierola, Feng Wang, Song Xingzhi, Elias J. Jabbour, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes, Courtney D DiNardo, Naval Daver, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Graciela M. Nogueras-Gonzalez, Xuelin Huang, Carlos E Bueso-Ramos, Keyur Patel, Andrew Futreal, Hagop M. Kantarjian, Koichi Takahashi, Guillermo Garcia-Manero
Journal: Blood (2016)
ADJUSTED ODDS OF INPATIENT MORTALITY FOR NON-ST ELEVATION MYOCARDIAL INFARCTION IS NOT AFFECTED BY DAY OF ADMISSION: A NATIONWIDE ANALYSIS
Authors: Farid Gholitabar, Shawn Lee, Alejandro Lemor, Carlos Gongora, Abel Casso Dominguez, Eyal Herzog
Journal: Journal of the American College of Cardiology (2017)
Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation
Authors: Aoife M. Murphy, Amandine Thomas, Sophie J. Crinion, Brian D. Kent, Murtaza M. Tambuwala, Aurelie Fabre, Jean-Louis Pepin, Helen M. Roche, Claire Arnaud, Silke Ryan
Journal: European Respiratory Journal (2017)

Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role. We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort. IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA. Providing mechanistic insight, IH induced a pro-inflammatory phenotype of visceral adipose tissue in mice with pro-inflammatory M1 macrophage polarisation correlating with the severity of insulin resistance. Complimentary in vitro analysis demonstrated that IH led to M1 polarisation of THP1-derived macrophages. In subjects without comorbidities (n=186), OSA was independently associated with insulin resistance. Furthermore, we found an independent correlation of OSA severity with the M1 macrophage inflammatory marker sCD163. This study provides evidence that IH induces a pro-inflammatory phenotype of the adipose tissue, which may be a crucial link between OSA and the development of insulin resistance.