tbuckley/cabot-search huggingface dataset:
Guidelines for the diagnosis of rheumatic fever: Jones criteria, updated 1992: Special writing group of the committee on rheumatic fever, endocarditis, and Kawasaki disease of the council on cardiovascular disease in the young, American Heart Association
Authors: Adnan S. Dajani, Elia Ayoub, Fredrick Z. Bierman, Alan L. Bisno, Floyd W. Denny, David T. Durack, Patricia Ferrieri, Michael Freed, Michael Gerber, Edward L. Kaplan, Adolf W. Karchmer, Milton Markowitz, Shahbudin H. Rahimtoola, Stanford T. Shulman, Gene Stollerman, Masato Takahashi, Angelo Taranta, Kathryn A. Taubert, Walter Wilson
Journal: Circulation (1993)

The Jones criteria for guidance in the diagnosis of acute rheumatic fever were first published by T. Duckett Jones, MD, in 1944 and have been revised over the years by the American Heart Association. The current guidelines are an update of these criteria. For the first time, the guidelines are designed to establish the initial attack of acute rheumatic fever. Major manifestations, minor manifestations, and supporting evidence of antecedent group A streptococcal infection are discussed. These updated guidelines expand on the available tools to diagnose streptococcal pharyngitis and clarify the available antibody tests for detecting antecedent group A streptococcal infection. At the present time echocardiography without accompanying auscultatory findings is insufficient to be the sole criterion for valvulitis in acute rheumatic fever. Finally, this article addresses overdiagnosis of rheumatic fever and lists exceptions to the Jones criteria, including recurrent attacks in individuals with a history of rheumatic fever.
Abstract 4014: Whole-genome microRNA profiling identifies prognostic serum biomarkers of esophageal adenocarcinoma
Authors: Yongyue Wei, Li Su, David C. Christiani
Journal: Cancer Research (2015)

Abstract Background: Cell free circulating microRNAs (cfmiRNAs) have been recognized as robust and stable biomarkers of cancers. However, little is known about the prognostic significance of cfmiRNAs in esophageal adenocarcinoma (EA). In this study, we explored whether specific cfmiRNA profiles could predict EA prognosis and whether H. pylori (HP) infection status could influence the association between cfmiRNAs and EA survival outcomes. Methods: At discovery stage, we profiled 1075 cfmiRNAs in 6 pooled serum samples from 30 EA patients and 30 cancer-free control subjects. After filtration, a total of 589 cfmiRNAs were stably detectable in the serum samples. The most significantly differential expressed cfmiRNAs were then validated the association with overall survival (OS) in an independent cohort of 82 patients, using Log-Rank test and multivariate Cox regression models in overall samples or stratified by HP infection status. qRT-PCR was used for cfmiRNA profiling in validation. HP infection status was determined by immunoblotting assay. Results: We identified a 21-cfmiRNA panel that could distinguish EA patients from cancer-free subjects (multiple response analysis by Hotelling T test, P = 3.0E-12). In validation, the OS analysis among HP-positive subtype patients showed that no cfmiRNA was significantly associated with EA prognosis. In HP-negative patients, however, 9 cfmiRNAs were significantly associated with OS (minimal P = 1.9E-4, all FDR adjusted q-value &amp;lt; 0.05). A risk-score analysis by combining the 9 cfmiRNA biomarkers showed a worse outcome in high-risk group (HR = 12.82, P = 0.0075) that showed better prediction of prognosis than individual cfmiRNA alone. Conclusions: Our findings suggest that deregulated cfmiRNAs may contribute to EA prognosis and HP infection status may modify the association between cfmiRNAs and EA survival. Citation Format: Yongyue Wei, Li Su, David C. Christiani. Whole-genome microRNA profiling identifies prognostic serum biomarkers of esophageal adenocarcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4014. doi:10.1158/1538-7445.AM2015-4014
Abstract 1753: XIAP maintains the characteristics of cancer stem cells and is a therapeutic target in nasopharyngeal carcinoma
Authors: jiao ji, Rong Deng, Wen-Dan Chen, Gong-Kan Feng, Xiao-Feng Zhu, Da-Jun Yang
Journal: Cancer Research (2015)

Abstract Nasopharyngeal carcinoma (NPC) is a common malignancy in South China. Cancer stem cells (CSCs) are thought as the key players in the resistance to chemo- or radio-therapy and are response for tumor recurrence and metastasis, while their ability to escape from the apoptosis pathway may render them the resistant property to the therapies. We show that XIAP is overexpressed in the NPC cell line S18, which have the higher SP populations and CD44+ populations and the stronger abilities of sphere-formation and metastasis. Importantly, XIAP knockdown decreases SP and CD44+ populations, prevents sphere-formation and reduces the ability of invasion and migration. What more, loss of XIAP enhances the sensitivity of cells to conventional chemotherapy drugs CDDP and 5-FU. The primary xenograft tumor formation in vivo found there is a dramatic reduction in tumor formation in the XIAP KD group. They all indicate that XIAP plays an important role in nasopharyngeal cancer stem cell. Further studies show that XIAP limits MAPK signaling and thereby restricts differentiation and maintains the characteristics of cancer stem cells. We designed and synthesized a novel Smac mimetic compound APG-1387 that promotes the rapid degradation of cIAP1/2 and XIAP, and it exerts an antitumor effect on nasopharyngeal carcinoma cancer stem cells. Further studies show that APG-1387 enhances the chemosensitivity and promotes apoptosis in combination with CDDP and 5-FU of NPC in vitro and vivo. Citation Format: jiao ji, Rong Deng, Wen-Dan Chen, Gong-Kan Feng, Xiao-Feng Zhu, Da-Jun Yang. XIAP maintains the characteristics of cancer stem cells and is a therapeutic target in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1753. doi:10.1158/1538-7445.AM2015-1753
Phase I study of everolimus (RAD001) and AMG 479 in patients (pts) with advanced solid tumors and colorectal cancer (CRC).
Authors: M. R. Khawaja, A. Younger, J. M. Funke, M. J. Waddell, D. R. Jones, K. Pollok, N. K. Prasad, W. Berry, G. Sandusky, E. G. Chiorean
Journal: Journal of Clinical Oncology (2011)

TPS157 Background: The insulin growth factor (IGF) axis is overactive in many tumors and affects several downstream signaling pathways including PI3K/Akt/mTOR. Synergism between IGF and mTOR inhibitors has been documented preclinically. The IGF-1 receptor (IGF-1R) or mTOR blockade has shown clinical activity in various solid tumors, but mostly disease stabilization. It is thought that mTOR inhibition up-regulates PI3K/Akt via an IGF-dependent feedback loop, thus the premise of this study is that administration of the IGF-1R inhibitor AMG 479 in conjunction with RAD001 would block this effect, and therefore this drug combination will be clinically synergistic. This study (NCT01122199) is enrolling at Indiana University. Methods: Objectives: determine the safety and toxicity, MTD, pharmacokinetic (PK) and pharmacodynamic (PD) endpoints in mTOR and IGF-1R signaling pathways, as well as preliminary efficacy in refractory CRC pts. Eligibility: pts with solid tumors and CRC, good organ function, ECOG PS 0-1, any numbers of prior therapies, no history of diabetes mellitus, ability to undergo study-related serial tumor biopsies. Design: This is an open-label phase I dose escalation study with a standard “3+3” design. RAD001 is administered orally daily (QD) in doses of 5 or 10 mg, and AMG 479 is dosed at 12 mg/kg iv every 2 weeks (Q2W) in 28-day cycles. During cycle 1 (C1) RAD001 is given as single agent between D1-7 with PKs on C1D1 and D7. AMG 479 is dosed Q2W starting with C1D15, and AMG 479 PKs as single agent are done on C1D15. RAD001 QD continuous dosing starts on C1D16. RAD001 and AMG 479 PK analysis is performed with both drugs at steady state, and concomitant with PD markers, on C3D1. DLTs are assessed during the first 2 cycles. An additional 15 pts with refractory CRC will be enrolled at the MTD. PD evaluations include blood samples at baseline, C1D7, C3D1 and time of progression, and tumor biopsies (baseline and C3D1) for mTOR and IGF1R pathway markers including: pAkt, pS6, p4EBP1, PTEN, IGF-1, IGF-2, pIGF-1R. Cohort 1 completed accrual with 5 pts, among whom 2 were not DLT evaluable due to study discontinuation within 2 cycles with disease progression. Cohort 2 is beginning accrual.
Abstract 1773: MHY-449 induces apoptotic cell death through ROS- and caspase-dependent pathways in AGS human gastric cancer cells
Authors: Yung Hyun Choi, Yong Jung Kang, Seon Hee Kim, Bokyung Sung, Dong Hwan Kim, Seong Yeon Hwang, Minjung Kim, Hyun Sook Lim, Jeong-Hyun Yoon, Hyung Ryong Moon, Hae Young Chung, Nam Deuk Kim
Journal: Cancer Research (2015)

Abstract We previously reported on the anticancer effect of the diastereoisomeric compound MHY-449, a novel dihydrobenzofuro[4,5-b][1,8] naphthyridin-6-one derivative, in various human cancer cells such as HCT116 human colon cancer cells (Int J Oncol 41: 2057-64, 2012) and PC3 human prostate cancer cells (Int J Oncol 44: 905-11, 2014). In this study, we investigated whether MHY-449 has anticancer properties in AGS human gastric cancer cells, and if so, what the molecular mechanisms are. Treatment with MHY-449 inhibited cell growth and induced apoptotic cell death in a concentration-dependent manner. The induction of apoptosis was determined by morphological changes, Hoechst 33342 staining, DNA fragmentation, increase of late apoptosis and sub-G1 DNA which were detected by flow cytometry analysis. Western blot analysis showed that MHY-449 upregulated the levels of Fas, FasL, p53, p21WAF1/CIP1, p27KIP1 and the ratio of Bax/Bcl-2 and downregulated the levels of procaspase-8, -9 and -3 and the cleavage of poly(ADP-ribose) polymerase (PARP). The apoptotic cell death induced by MHY-449 was accompanied by the activation of caspase-8, -9 and -3, which was completely abrogated by the pan-caspase inhibitor, z-VAD-FMK. In addition, treatment with MHY-449 elevated the level of cellular ROS generation. These data were further confirmed by incubating the cells with N-acetyl-L-cysteine (NAC), which is a scavenger of ROS. Pretreatment with NAC protected against MHY-449-induced cytotoxicity. Similarly, pretreatment of NAC abolished MHY-449-induced downregulation of pro-caspase-8, -9 and -3 and PARP cleavage. Taken together, these findings suggest that MHY-449 induces apoptosis via caspase- and ROS-dependent pathways in AGS human gastric cancer cells. Citation Format: Yung Hyun Choi, Yong Jung Kang, Seon Hee Kim, Bokyung Sung, Dong Hwan Kim, Seong Yeon Hwang, Minjung Kim, Hyun Sook Lim, Jeong-Hyun Yoon, Hyung Ryong Moon, Hae Young Chung, Nam Deuk Kim. MHY-449 induces apoptotic cell death through ROS- and caspase-dependent pathways in AGS human gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1773. doi:10.1158/1538-7445.AM2015-1773
Diagnostic value of R-wave amplitude increase during treadmill exercise testing for detecting coronary artery disease.
Authors: Hiroyuki Miyakoda, Hideyuki Kitamura, Toru Kinugawa, Kazuhide Ogino, Akira Hoshio, Hiroshi Kotake, Hiroto Mashiba
Journal: Circulation (1990)

To evaluate the diagnostic value of an exercise-induced increase in R-wave amplitude (RWA) for detecting coronary artery disease (CAD), treadmill testing using the modified Bruce protocol was performed on a CASE II computerized system (Marquette) in 10 healthy young men, 35 patients (pts) with CAD, 22 subjects with normal coronary arteries, and 11 pts with aortic or mitral regurgitation. Based on the analysis of the patterns of serial changes in RWA in lead V5, we proposed new RWA criteria for detecting CAD. (1) During exercise, RWA increases in stage 1 and subsequently increases further or remains unchanged. (2) During exercise, RWA decreases in the early phase of exercise and subsequently increases. (3) In the recovery period, RWA shows a gradual and excessive increase. A combination of the above RWA criteria showed a sensitivity, specificity and accuracy of an equal value of 86%. We conclude that an exercise-induced RWA increase is a useful indicator for detecting CAD, especially when taking the patterns of serial changes into consideration, and that the abnormal RWA increase may be related to an increase in left ventricular (LV) end-diastolic volume due to exercise-induced LV dysfunction.
Abstract 2178: Comparison and interpretation of variants in RNA and DNA from sarcoma cancer sample
Authors: Bodil Øster, Anika Joecker, Rupert Yip, Frank Schacherer, Douglas Basset, Donald Salter, Richard L. Hayward, Ted R. Hupp
Journal: Cancer Research (2015)

Abstract Identification and interpretation of somatic variants using DNA from matched tumor/normal pairs is crucial for understanding the mechanisms behind cancer. Studies have shown that a large proportion of variants present in the DNA are not present in the RNA and vice versa due to RNA-editing and other unknown molecular processes. In addition, recent publications show that RNA-editing plays an important role in cancer. These findings can have strong implications for clinical diagnostics where correct identification and interpretation of somatic variants from matched tumor/normal samples is essential. In this study we will investigate somatic variants that are only present in the DNA or the RNA of pleomorphic undifferentiated sarcoma. For this approach we will first identify somatic variants in the DNA using Exome Sequencing data and in the RNA using RNA-Seq data from a matched tumor/normal pair. Somatic variants in DNA as well as RNA are then again filtered for germline variants using the DNA of the normal sample and the RNA of the normal sample. Somatic variants found in only DNA or only RNA are further investigated using Ingenuity's large Knowledge Base as well as HGMD and PGMD. We will show which class of proteins is mainly affected by the RNA editing events and which pathways are mainly affected. We will also highlight implications for clinical diagnostics using DNA only. The complete analysis will be done using the new integrated QIAGEN tool suite of CLC Cancer Research Workbench, Ingenuity Variant Analysis and Biobase Genome Trax. Citation Format: Bodil Øster, Anika Joecker, Rupert Yip, Frank Schacherer, Douglas Basset, Donald Salter, Richard L. Hayward, Ted R. Hupp. Comparison and interpretation of variants in RNA and DNA from sarcoma cancer sample. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2178. doi:10.1158/1538-7445.AM2015-2178
Primary intramedullary spinal cord lymphoma: a population-based study
Authors: Wuyang Yang, Tomas Garzon-Muvdi, Maria Braileanu, Jose L. Porras, Justin M. Caplan, Xiaoming Rong, Judy Huang, George I. Jallo
Journal: Neuro-Oncology (2016)

Primary intramedullary spinal cord lymphoma (PISCL) is a rare diagnosis with poorly understood disease progression. Clarification of the factors associated with survival in PISCL patients is warranted.We conducted a population-based cohort study utilizing prospectively collected data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with histological diagnosis of primary lymphoma in spinal cord (C72.0) from 1973 to 2012 in the SEER database were included. Multivariable survival analysis between patient, lesion characteristics, and PISCL-related death was performed to adjust for confounding factors.We included 346 PISCL patients in our study. Average age was 56.5 ± 17.8 years, with 62.7% being male. Racial distribution of these patients was white (87.6%), black (8.0%), and other (4.3%). More than half (55.8%) of patients were married. The most prevalent histology of PISCL was diffuse B-cell (46.2%), and the majority (55.2%) were low stage (Ann Arbor stage I/II). Most patients (67.9%) received radiation therapy. Average survival interval of patients with PISCL-related death (n=135, 39.0%) was 27.8 months. General cumulative survival probability at 1 year, 2 years, and 5 years was 73.8%, 67.9%, and 63.1%, respectively. Multivariable accelerated failure time (AFT) regression showed follicular lymphoma (HR:0.25, P=.008) and more recent diagnosis (HR:0.96, P<.001) was positively associated with PISCL-related survival. Conversely, nonwhite race (HR:1.69, P=.046), older age (HR:1.02, P<.001), unmarried status (HR:2.14, P<.001), and higher stage (HR:1.54, P=.022) were negatively associated with survival.Age, race, marital status, tumor histology, tumor stage, and year of diagnosis were associated with survival of PISCL. While most PISCL-related deaths occur within a 1-year period, subsequent slow progression was observed after the first year of survival.
Medical oncology services in cyber space: Benefits of the Townsville teleoncology project.
Authors: S. S. Sabesan, S. Varma
Journal: Journal of Clinical Oncology (2011)

e16545 Background: Current models of rural outreach cancer care are inadequate since patients and specialists spend significant amount of time in costly long distance travels for consultations and treatment. Clinics conducted using videoconferencing technology eliminates unnecessary travel while providing subspecialist services closer to rural homes. Townsville Cancer Centre (TCC) in Queensland, Australia provides all its medical oncology services including supervision of chemotherapy delivery, in patient consultations and ward rounds exclusively on videoconferencing for most rural cancer patients in their health districts. Distances between TCC and rural towns range from 400 to 1200 km. Overall clinic model and patient satisfaction are described elsewhere. Clinics are run weekly, ward rounds and in patient consultations are conducted on demand. Aim of this report is to describe the benefits of our model of care. Methods: Data on clinics conducted between May 2007 and December 2010 was extracted from the oncology information system of the TCC. Results: A Total of 150 patients were reviewed in 609 consultations in 44 months. Median age was 58 (20-86) and males were 46% and females 54%. 24 patients were from indigenous communities. Last 77 patients were cared for without seeing in person. Most common cancer types were breast (37%), colorectal (21%) and lung (22%). Total of 81 patients received a total of 431 cycles of chemotherapy. Examples of chemotherapy regimens include TAC, BEP, FOLFOX, methotrexate infusion etc. One patient died of severe pneumonia after one cycle of capeciatbine, one patient suffered a stroke after 4 cycles of EOX and one suffered non fatal cardiac arrest after herceptin. Other side effects and admission rates were similar to TCC figures. 10 patients were seen urgently and received urgent chemotherapy, thus avoiding transfer to TCC. 6 admitted patients were seen on regular ward rounds during their in patient admission. Conclusions: Provision of comprehensive medical oncology services via videoconferencing is feasible and is a safe and efficient model of care for rural, remote and indigenous patients of North Queensland. Given its many benefits, our model could become part of standard practice.
Validation of International Staging System (ISS) for Multiple Myeloma: A Retrospective Analysis of 487 Patients at 8 Brazilian Centers.
Authors: Vania T.M. Hungria, Angelo Maiolino, Gracia Martinez, Gisele Colleoni, Luciana Oliveira, Erika O.M. Coelho, Lais Rocha, Rosane Bittencourt, Adriana Quero, Karina Ribeiro
Journal: Blood (2005)
The Activity of Combined Topoisomerase Inhibitors Is Augmented by Octreotide in the Treatment of Lymphoid Leukemias.
Authors: Dimitrios T.P. Trafalis, Konstantinos Lilakos, Daphne Koumbi, Panayiotis Dalezis, Maria K. Angelopoulou, Athanasios E. Athanassiou, Athanasios Papageorgiou, Gerassimos A. Pangalis
Journal: Blood (2005)
Abstract 4762: ITPKA expression in lung and other cancers, regulated via gene body methylation, functions as an oncogene
Authors: Yi-Wei Wang, Xiaotu Ma, Yu-An Zhang, Mei-Jung Wang, Yasushi Yatabe, Stephen Lam, Luc Girard, Jeou-Yuan Chen, Adi F. Gazdar
Journal: Cancer Research (2015)

Abstract Inositol-Trisphosphate 3-Kinase A (ITPKA), a kinase with limited tissue distribution, is involved in inositol phosphate metabolism. We identified ITPKA as up-regulated in lung and many other types of cancers. Using gain-of-function and loss-of-function approaches, we demonstrated by in vitro and in vivo assays that ITPKA functions as an oncogene to drive the development of lung cancer. We further showed that methylation level in the ITPKA gene body is significantly higher in various types of primary tumors than in corresponding non-malignant tissues, which was positively correlated with its expression. Our study revealed that DNMT3B-mediated methylation of the CpG island in ITPKA gene body regulates its expression via modulation of the binding of transcription activator SP1 to the ITPKA promoter. During the multistage pathogenesis of lung carcinoma, ITPKA gene body methylation first appeared at the in situ carcinoma stage and increased during disease progression. Thus ITPKA expression functions as an oncogene in lung and other cancers. Highly specific and sensitive expression and methylation of ITPKA was present in a wide range of tumor types, suggesting that deregulation of ITPKA may function as a universal or near universal hallmark of malignancy. Citation Format: Yi-Wei Wang, Xiaotu Ma, Yu-An Zhang, Mei-Jung Wang, Yasushi Yatabe, Stephen Lam, Luc Girard, Jeou-Yuan Chen, Adi F. Gazdar. ITPKA expression in lung and other cancers, regulated via gene body methylation, functions as an oncogene. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4762. doi:10.1158/1538-7445.AM2015-4762
Immunotherapy for Lymphoma Using T Cells Targeting Multiple Tumor Associated Antigens
Authors: Ann Leen, Ifigeneia Tzannou, Munu Bilgi, Hao Liu, Juan F Vera, Ulrike Gerdemann, Rammurti T Kamble, Carlos A. Ramos, Bambi Grilley, Adrian P. Gee, Catherine M. Bollard, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, George Carrum
Journal: Blood (2015)