tbuckley/cabot-search huggingface dataset:
Phase II study of nimotuzumab combination with paclitaxel and cisplatin as the first-line treatment in patients with local advanced or metastatic esophageal squamous cell cancer (ESCC): An interim analysis.
Authors: Xiaodong Zhang, Ming Lu, Jifang Gong, Jing Gao, Xicheng Wang, Xiaotian Zhang, Jie Li, Yan Li, Jian Li, Jun Zhou, Zhihao Lu, Lin Shen
Journal: Journal of Clinical Oncology (2012)

e14604 Background: Nimotuzumab is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. Evidences have shown that nimotuzumab is effective and safe in SCCHN. The combination of paclitaxel/cisplatin (TP) is a standard regimen for advanced or metastatic ESCC. This open uncontrolled phase II study was designed to determine the efficacy and safety of nimotuzumab in combination with TP as the first-line treatment in advanced ESCC. Methods: All patients have histology/cytology confirmed advanced or metastatic ESCC with ECOG PS 0-2. The treatment plan is as the following: paclitaxel administered intravenously (IV) 175 mg/m2 on d1 and cisplatin IV 30-35mg/ m2/d on d1-2, every 21 days for 6 cycles, and nimotuzumab IV 200mg weekly. For patients with stable disease (SD) and better, nimotuzumab will be given continuously after 6 cycles of TP. The primary endpoint is objective response rate (RR) with 56 patients enrollment (target RR &gt;60%); secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety/ tolerability. The coordinations between EGFR and ERCC1 with response of treatment will be analyzed. Results: Up to date, 25 patients (male/female, 20/5; median age 58) have been enrolled. All patients were evaluated for toxicity and 22 are evaluable for response. 14 (63.6%) had a confirmed partial response (PR) and 7 (31.8%) had SD as their best responses with disease control rate of 95.4%. Only one patient had progressive disease (PD). Grade 3 or 4 neutropenia, neutropenic fever and anemia occurred in 52.2%, 4% and 13% respectively. Nonhematological toxicities were generally mild with grade 1 or 2 alopecie, hypodynamia, anorexia, nausea, arthralgia, and itch of skin occurring in 80%, 60.9%, 43.5%, 34.8%, 30.4%, and 21.7%. One patient had a grade 3 haematuria. Conclusions: The interim analysis showed that the combination of nimotuzumab with TP is tolerated reasonably well in patients with advanced or metastatic ESCC and encouraging efficacy. The study is ongoing with coordination of biomarkers and response as well.
Treat the Patient, Not the Angiogram
Authors: J. Aaron Grantham
Journal: Circulation (2017)

illions of people are living with refractory angina and ischemic pain despite maximal medical therapy and are told that they have no revascularization option.The most common reason patients are told that they have no option for revascularization is the presence of a coronary chronic total occlusion (CTO). 1 Although no rigorous data exist, anecdotally, the majority of CTOs are now approachable with percutaneous techniques using drug-eluting stents owing to advances in the techniques that have resulted in improved success rates regardless of anatomy (>85%) and significant relief of ischemic symptoms while maintaining adequate safety.However, attempt rates for CTO percutaneous coronary intervention (PCI) range from 1% to 16% between institutions. 2The question then arises: Among patients with a good indication for revascularization (particularly those with refractory angina and a CTO), why are so many not offered revascularization options?Here, the Canadian Cardiovascular Society Task Force on Refractory Angina provides some insights: "…[T]he nonrevascularization status will be influenced by the local expertise and operator tolerance to risk." 3 Treat the Patient, Not the Angiogram
TCTAP A-007 Predictive Value of Neutrophil to Lymphocyte Ratio in Clinical Outcomes of Acute Myocardial Infarction: A 2-year Follow-Up
Authors: Na Xu, Xiao-fang Tang, Jinqing Yuan, Bo Xu, Runlin Gao, Yuejin Yang, Yi Yao
Journal: Journal of the American College of Cardiology (2017)
구연 : 단일기관에 등록된 2,248명의 간세포암 환자에서 간세포암 가족력과 발병 연령간의 연관성
Authors: 박정화, 송명준, 김진동, 우현영, 권정현, 유찬란, 장정원, 장우임, 김창욱, 남순우, 배시현, 최종영, 윤승규, 조세현, 한준열, 한남익, 양진모, 최상욱, 이영석, 이창돈
Journal: Clinical and Molecular Hepatology (2009)
An Asymptomatic Hyperpigmented Eruption on the Lower Extremities
Authors: Sam Z. Awan, Justin Finch, Arni Kristjansson
Journal: JAMA Dermatology (2017)

A woman in her early 20s presented with 1 year of discrete asymptomatic brown lesions distributed over her lower extremities; she denied any history of trauma or prior lesions at these sites and denied fever, arthralgias, myalgias, or constitutional symptoms. What is your diagnosis?
An inflammatory bowel disease–risk variant in INAVA decreases pattern recognition receptor–induced outcomes
Authors: Jie Yan, Matija Hedl, Clara Abraham
Journal: Journal of Clinical Investigation (2017)

Inflammatory bowel disease (IBD) is characterized by dysregulation in both cytokines and responses to intestinal microbes, and proper regulation of pattern recognition receptor (PRR) signaling is critical for intestinal immune homeostasis. Altered functions for the IBD risk locus containing rs7554511, which encompasses the C1orf106 gene (recently named INAVA), and roles for the protein encoded by the INAVA gene are unknown. Here, we investigated the role of INAVA and INAVA genotype in regulating PRR-initiated outcomes in primary human cells. Both peripheral and intestinal myeloid cells expressed INAVA. Upon PRR stimulation, INAVA was required for optimal MAPK and NF-κB activation, cytokine secretion, and intracellular bacterial clearance. INAVA recruited 14-3-3τ, thereby contributing to recruitment of a signaling complex that amplified downstream signals and cytokines. Further, INAVA enhanced bacterial clearance by regulating reactive oxygen, reactive nitrogen, and autophagy pathways. Macrophages from rs7554511 C risk carriers expressed lower levels of INAVA RNA and protein. Lower expression was attributed in part to decreased transcription mediated directly by the intronic region containing the rs7554511 C variant. In rs7554511 C risk carrier macrophages, lower INAVA expression led to decreased PRR-induced activation of MAPK and NF-κB pathways, cytokines, and bacterial clearance pathways. Thus, IBD-associated polymorphisms in INAVA modulate PRR-initiated signaling, cytokines, and intracellular bacterial clearance, likely contributing to intestinal immune homeostasis.
Sensing Bad: Are Co-stimulatory CAR-Expressing γδ T Cells Safer?
Authors: Robin Parihar
Journal: Molecular Therapy (2017)

Cellular immunotherapy using chimeric antigen receptor (CAR)-bearing T cells has shown promise in early clinical trials, especially for the treatment of CD19+ B cell malignancies.1 Despite impressive remission rates in this clinical setting, associated toxicity has been observed.2 CAR T cells directed against solid tumor antigens have fared less well, with few durable clinical responses but still associated toxicity.3 Toxicity results in part from the "on-target, off-tumor" effects of CAR-T cells, as the tumor-targeting ectodomain of the CAR molecule cannot discern target molecules expressed on tumors versus normal tissues.
A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis.
Authors: Jae-Cheol Jo, Yong Sang Hong, Kyu-Pyo Kim, Jae-Lyun Lee, Jeeyun Lee, Young Suk Park, Sun Young Kim, Jin-Sook Ryu, Jong-Seok Lee, Tae Won Kim
Journal: Journal of Clinical Oncology (2013)

10589 Background: There have been reports on responses and prolonged disease stabilizations with imatinib which may be associated with PDGFR-β pathway and KIT mutation in the treatment of aggressive fibromatosis (AF). Sunitinib has not only PDGFRs, KIT, and FLT3 inhibiting activity, but also VEGFRs blockade as antiangiogenesis. The aim of this study is to evaluate the efficacy and safety of sunitinib for patients with advanced AF. Methods: Nineteen patients with pathologically proven AF were accrued between Jun 2008 and Mar 2012. Sunitinib was administered with 37.5 mg/day for 4 weeks without break, comprising one cycle. Primary endpoint was response rate. Results: Ten (53%) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63.2%), and AF associated with familial adenomatous polyposis was observed in 10 (52.6%). With a median 6 cycles per patients (range, 1-47 cycles), 5 (26.3%) achieved a partial response and 8 (42.1%) had stable disease; the overall response rate was 26.3% (95% CI, 6.3-45.7) in intention-to-treat analysis. With median follow-up time of 20.3 months (range, 1.8-50.7), the 2-year progression-free survival and overall survival were 74.7% and 94.4%, respectively. Grade 3 or 4 adverse events of sunitinib with frequency &gt; 5% of patients included neutropenia (33.3%), diarrhea (5.3%), and hand-foot syndrome (5.3%). In 3 patients out of 12 patients with mesenteric AF, mesenteric mass bleeding (n=1), bowel perforation (n=1), and bowel fistula (n=1) with tumor mass necrosis, were observed during an early period of sunitinib. Conclusions: Sunitinib showed potential antitumor activity and was relatively tolerated in patients with AF, especially non-mesenteric AF. Further investigation of sunitinib treatment is necessary in patients with AF.
TCTAP A-052 Effects of Ticagrelor on Neointimal Hyperplasia and Endothelial Function, Compared with Clopidogrel and Prasugrel, in a Porcine Coronary Stent Restenosis Model
Authors: Hyun Kuk Kim, Myung-Ho Jeong, Kyung Seob Lim, Keun-Ho Park
Journal: Journal of the American College of Cardiology (2017)
Abstract P290: Predicting the Change in the Omega-3 Index with Data from 9 Supplementation Studies
Authors: Kristina H Jackson, Rachel Walker, Gregory C Shearer, William S Harris
Journal: Circulation (2017)

The omega-3 index (O3I; erythrocyte EPA+DHA % of total fatty acids) is directly associated with favorable cardiovascular and cognitive outcomes. In spite of its utility as a biomarker of omega-3 status, there remains unexplained variability in its response to EPA+DHA supplementation. De-identified data (n=841) from 9 published intervention studies were used to predict changes in the O3I. All studies provided data on EPA+DHA supplementation dose and duration, pre- and post-O3I values, and standard demographic factors. Stepwise regression analysis was performed to select variables and create a predictive model, using % change as the outcome variable. The mean age and weight of the participants was 48 ± 16 years and 83 ± 18 kg (BMI: 29 ± 5). The cohort was 49% (n=409/841) male and 86% (n=722/841) white. Treatment groups took an average of 2115 ± 1048 mg/day of EPA+DHA (range: 300 - 3600 mg/day; placebo groups took 0 mg/day) for 11.5 ± 4.0 weeks (range: 4 - 20 weeks). The O3I increased from 5.28 ± 1.58% to 9.27 ± 2.59% in the supplemented individuals (n=434), and was unchanged in the placebo groups (5.30 ± 1.52% to 5.30 ± 1.50%; n=407; P&lt;0.0001). Variables that were selected into the model were age, sex, weight, dose of DHA, dose of EPA, duration, baseline O3I and an interaction between weight and age. The model R 2 was 0.75 and the root mean square error was 0.18. The correlation between the predicted and observed O3I changes was 0.84 (P&lt;0.0001; Figure). The model predicts individual changes in the O3I with reasonable accuracy, and may be useful for selecting the appropriate supplemental EPA+DHA doses and duration for clinical research studies that aim to reach a target O3I level.
Analysis of Long-Term Survival in Multiple Myeloma Patients after First-Line Autologous Stem Cell Transplantation: Impact of Clinical Risk Factors and Duration of Response
Authors: Nicola Lehners, Natalia Becker, Axel Benner, Maria Pritsch, Elias Karl Mai, Jens Hillengass, Hartmut Goldschmidt, Marc S. Raab
Journal: Blood (2016)
Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy
Authors: Prasanna Sooriakumaran, Tommy Nyberg, Olof Akre, Anders Widmark, Freddie Hamdy, Markus Graefen, Stefan Carlsson, Gunnar Steineck, N. Peter Wiklund
Journal: European Urology (2017)
TCTAP A-168 Quantification of Incompletely-apposed Gap after Transcatheter Aortic Valve Replacement Using Patient-specific Models for Understanding the Mechanism of Paravalvular Leak
Authors: Saeko Sasuga, Yutaka Tanaka, Azuma Takahashi, Kazuto Obama, Yusuke Aoyama, Umezu Mitsuo, Shigeru Saito, Kiyotaka Iwasaki
Journal: Journal of the American College of Cardiology (2017)
Abstract 400: Regulated Levels of Sarcolemmal Membrane Protein Isoform 3 Impact Cardiac Function in Mice
Authors: Jana Mlynarova, Mayra Trentin-Sonoda, Maysoon Salih, Fernanda Gaisler da Silva, Jennifer L Major, Marcela Sorelli Carneiro-Ramos, Balwant S Tuana
Journal: Circulation Research (2015)

The sarcolemmal membrane-associated proteins (SLMAPs) are a family of tail-anchored membrane proteins generated by alternative splicing of the SLMAP gene. A ubiquitously expressed SLMAP isoform 3 encompasses an N-terminal FHA domain with extended coiled-coil structure and has been implicated in cell cycle control. Heart function in transgenic mice with cardiac-specific overexpression of SLMAP3 cDNA driven by α myosin heavy chain promoter was evaluated by echocardiography. qPCR and western blot were used to analyze gene and protein expression respectively. Structure and fibrosis was analyzed by H&amp;E and Masson’s Trichrome staining. Function analysis showed a 15% (p&lt;0.05) decrease in ejection fraction and 19% (p&lt;0.05) decrease in fractional shortening in transgenic mice as early as 5 weeks and persisted into old age at 44 weeks. Transgenic mice presented a mild systolic dysfunction and a trend towards dilated cardiomyopathy without any premature death. Natriuretic peptide ANP and BNP levels were not changed and there was no difference in left ventricular mass or activation of the hypertrophic factor Akt1 in SLMAP3 expressing myocardium. However, significant changes in calcium handling proteins with a significant decrease in phosphorylation of phospholamban ser16 (p&lt;0.05) along with a down-regulation of sarco-endoplasmic reticulum Ca2+ ATPase protein and increased ryanodine receptor 2 phosphorylation ser2808 (p&lt;0.05) were noted at 5 weeks of age in transgenic hearts. These data indicate that increased SLMAP3 levels did not influence cardiac remodeling or hypertrophic growth but did impact membrane biology of calcium transport systems in myocardium leading to depressed contractility. Thus regulated levels of SLMAP3 are important to support normal heart function.
Kaposiform Lymphangiomatosis with Human Papillomavirus Infection
Authors: Elżbieta Radzikowska, Katarzyna Błasińska-Przerwa, Małgorzata Szołkowska, Agnieszka Miąsko, Włodzimierz Kupis, Elżbieta Wiatr
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Genomic Instability in Cancer: Teetering on the Limit of Tolerance
Authors: Noemi Andor, Carlo C. Maley, Hanlee P. Ji
Journal: Cancer Research (2017)

Abstract Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection, and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared with intermediate levels under this threshold. This has been observed in clonal subpopulations of larger size, especially when genomic instability is shared among a limited number of clones. We hypothesize that cancers with extreme levels of genomic instability may be teetering on the brink of a threshold where so much of their genome is adversely altered that cells rarely replicate successfully. Another possibility is that tumors with high levels of genomic instability are more immunogenic than other cancers with a less extensive burden of genetic aberrations. Regardless of the exact mechanism, but hinging on our ability to quantify how a tumor's burden of genetic aberrations is distributed among coexisting clones, genomic instability has important therapeutic implications. Herein, we explore the possibility that a high genomic instability could be the basis for a tumor's sensitivity to DNA-damaging therapies. We primarily focus on studies of epithelial-derived solid tumors. Cancer Res; 77(9); 2179–85. ©2017 AACR.
Combination of Imatinib and Hypusination Inhibitors Represents a Novel Therapeutic Strategy in Bcr-Abl Positive Leukemias.
Authors: Stefan Balabanov, Artur Gontarewicz, Patrick Ziegler, Ulrike Hartmann, Mhairi Copland, Ute Brassat, Ilona Hauber, Lothar Kanz, Carsten Bokemeyer, Alfred Nordheim, Joachim Hauber, Tessa L. Holyoake, Tim H. Brummendorf
Journal: Blood (2006)
TCTAP C-016 Left Main Coronary Artery to Left Anterior Descending Artery Percutaneous Coronary Intervention in Acute Anterior Myocardial Infarction Complicated by Ostial Left Circumflex Artery Plaque Shift: Make it Complex or Keep it Simple
Authors: Jiyen Kam, Benjamin Leo Cheang Leng, Hou Tee Lu, Chuey Yan Lee
Journal: Journal of the American College of Cardiology (2017)
Alzheimer's Disease: Hematite-Based Photoelectrode Materials for Photoelectrocatalytic Inhibition of Alzheimer's β-Amyloid Self-Assembly (Adv. Healthcare Mater. 8/2017)
Authors: Kayoung Kim, Byung Il Lee, You Jung Chung, Woo Seok Choi, Chan Beum Park
Journal: Advanced Healthcare Materials (2017)

The self-assembly of β-amyloid peptides into aggregates is a major pathological hallmark of Alzheimer's disease that affects more than 11% of the population aged over 65. In article number 1601133, Chan Beum Park and co-workers show that β-amyloid self-assembly can be suppressed effectively via photoelectrocatalytic mechanism using a hematite-based photoelectrode platform.
Development and Internal Validation of a Novel Model to Identify the Candidates for Extended Pelvic Lymph Node Dissection in Prostate Cancer
Authors: Giorgio Gandaglia, Nicola Fossati, Emanuele Zaffuto, Marco Bandini, Paolo Dell’Oglio, Carlo Andrea Bravi, Giuseppe Fallara, Francesco Pellegrino, Luigi Nocera, Pierre I. Karakiewicz, Zhe Tian, Massimo Freschi, Rodolfo Montironi, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2017)
Defects in DNA replication hit NK cells and neutrophils
Authors: Klaus Ley
Journal: Journal of Clinical Investigation (2017)

Patients who present with unique immunological phenotypes provide an opportunity to better understand defect-driving mutations. In this issue of the JCI, Cottineau and colleagues characterize 5 individuals who exhibited growth restriction, facial deformities, and a history of bacterial and viral infection. Further characterization revealed that these patients were neutropenic and NK cell deficient. These phenotypes were unexpectedly linked to mutations in the gene encoding a subunit of the Go-Ichi-Ni-San (GINS) complex, which is essential for DNA replication prior to cell division. Together, the results of this study lay the groundwork for future studies to explore the role of DNA replication in immune cell generation and function.
Novel autoantibody against the β2‐glycoprotein I/human leucocyte antigen– <scp>DR</scp> complex in patients with refractory cutaneous ulcers
Authors: N. Arase, K. Tanimura, H. Jin, T. Yamaoka, M. Kishibe, M. Nishioka, E. Kiyohara, M. Tani, S. Matsuoka, K. Ohmura, K. Takasugi, T. Yamamoto, H. Murota, H. Arase, I. Katayama
Journal: British Journal of Dermatology (2017)
Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior
Authors: Yuki Fujita, Koji Masuda, Masashige Bando, Ryuichiro Nakato, Yuki Katou, Takashi Tanaka, Masahiro Nakayama, Keizo Takao, Tsuyoshi Miyakawa, Tatsunori Tanaka, Yukio Ago, Hitoshi Hashimoto, Katsuhiko Shirahige, Toshihide Yamashita
Journal: The Journal of Experimental Medicine (2017)

Abnormal epigenetic regulation can cause the nervous system to develop abnormally. Here, we sought to understand the mechanism by which this occurs by investigating the protein complex cohesin, which is considered to regulate gene expression and, when defective, is associated with higher-level brain dysfunction and the developmental disorder Cornelia de Lange syndrome (CdLS). We generated conditional Smc3-knockout mice and observed greater dendritic complexity and larger numbers of immature synapses in the cerebral cortex of Smc3+/- mice. Smc3+/- mice also exhibited more anxiety-related behavior, which is a symptom of CdLS. Further, a gene ontology analysis after RNA-sequencing suggested the enrichment of immune processes, particularly the response to interferons, in the Smc3+/- mice. Indeed, fewer synapses formed in their cortical neurons, and this phenotype was rescued by STAT1 knockdown. Thus, low levels of cohesin expression in the developing brain lead to changes in gene expression that in turn lead to a specific and abnormal neuronal and behavioral phenotype.
Barst RJ, McGoon M, McLaughlin V, Tapson V, Oudiz R, Shapiro S, Robbins IM, Channick R, Badesch D, Rayburn BK, Flinchbaugh R, Sigman J, Arneson C, Jeffs R, for the Beraprost Study Group. Beraprost Therapy for Pulmonary Arterial Hypertension.
Journal: Journal of the American College of Cardiology (2003)
Visualising early lung disease in CF: the emergence of MRI
Authors: Jane C Davies
Journal: Thorax (2017)

The potential of magnetic resonance imaging (MRI) in lung imaging appears to be increasing year-on-year;1 having previously been considered a tool unlikely suitable for an air-filled organ, both hyperpolarised gas and more standard approaches are generating new interest within the field of cystic fibrosis (CF). The lack of radiation involved is an attractive feature, but are new outcome measures really needed, and if so, in which particular groups?

There is now widespread recognition that lung disease begins early in CF, but can remain undetected and therefore potentially inadequately treated. In particular, forced expiratory manoeuvres …
<i>CIC-DUX4</i> Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma
Authors: Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R. Antonescu, Takuro Nakamura
Journal: Cancer Research (2017)

CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). However, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here, we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA. Recipient mice transplanted with eMC-expressing CIC-DUX4 rapidly developed an aggressive, undifferentiated sarcoma composed of small round to short spindle cells. Gene-expression profiles of CDS and eMC revealed upregulation of CIC-DUX4 downstream genes such as PEA3 family genes, Ccnd2, Crh, and Zic1 IHC analyses for both mouse and human tumors showed that CCND2 and MUC5AC are reliable biomarkers to distinguish CDS from ES. Gene silencing of CIC-DUX4 as well as Ccnd2, Ret, and Bcl2 effectively inhibited CDS tumor growth in vitro The CDK4/6 inhibitor palbociclib and the soft tissue sarcoma drug trabectedin also blocked the growth of mouse CDS. In summary, our mouse model provides important biological information about CDS and provides a useful platform to explore biomarkers and therapeutic agents for CDS. Cancer Res; 77(11); 2927-37. ©2017 AACR.