tbuckley/cabot-search huggingface dataset:
Objective response of first-line chemotherapy in patients with metastatic triple-negative breast cancer confers a better overall survival.
Authors: Ting Li, Jian Zhang, Zhonghua Wang, Biyun Wang, Sheng Zhang, Leiping Wang, Jun Cao, Zhonghua Tao, Jie Xie, JinFeng Zhang, Xi-Chun Hu
Journal: Journal of Clinical Oncology (2016)

e12568 Background: This study sought to determine the overall response rate (ORR) in risk prediction of overall survival (OS) for patients with metastatic triple-negative breast cancer (TNBC) receiving first-line chemotherapy. Methods: The risk prediction model was established and assessed with two independent cohorts, that is the training cohort of 364 patients recruited between April 2005 and November 2013 and the validation cohort of 236 patients recruited between January 2011 and November 2013, as part of a phase 3 trial (CBCSG006). First, univariable and multivariable Cox proportional hazard models were applied to explore associations with progression free survival (PFS) and OS in the training cohort. Then, we validated the risk model in the validation cohort. Results: According to a multivariate analysis, ORR (HR, 0.440, 95% CI 0.344-0.562; P = 0.000) together with ECOG score, menopausal status, disease free survival, number of metastatic organ sites, and platinum-based chemotherapy (PBCT) were observed to be independent predictive factors for PFS, and ORR (HR, 0.507, 95% CI 0.344-0.562; P = 0.000 ) together with disease free survival, number of metastatic organ sites and previous treatment (anthracycline and/or taxane) were observed to be independent predictive factors for OS in training cohort. The PFS and OS risk prediction model built from the training cohort can precisely predict the validation cohort except menopausal status for PFS and previous treatment (anthracycline and/or taxane) for OS. For ORR and non-ORR group, median OS was 22.8 and 13.4 months in 173 and 191 patients in the training cohort (HR, 0.507, p = 0.000), and 26.6 and 14.0 months in 134 and 102 patients in the validation cohort (HR, 0.386, p = 0.000), respectively. By adding ORR in the risk prognostication model of OS, the C-index improved from 0.662 to 0.694 in the training cohort and from 0.646 to 0.714 in the validation cohort. Conclusions: The risk prediction model of OS integrating first-line ORR status with any regimen can precisely predict survival of patients with metastatic TNBC. Thus, in order to achieve objective response in the first-line setting, combination chemotherapy is an option of choice.
Recombinant Nematode Anticoagulant Protein c2 in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome
Authors: Robert P. Giugliano, Stephen D. Wiviott, Peter H. Stone, Daniel I. Simon, Marc J. Schweiger, Alain Bouchard, Massoud A. Leesar, Michael A. Goulder, Steven R. Deitcher, Carolyn H. McCabe, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2007)
Abstract 13: Prehospital Treatment Improves 1-Year Survival of Patients with Acute Myocardial Infarction with ST Segment Elevation
Authors: Fernando Rosell, Francisco J Mellado, Manuel Ruiz-Bailen, Miguel A Paz-Rodriguez, Jesus E Martinez-Faure, Itziar Vivar, Manuela Martinez-Lara, Juan A Garrido, Francisco J Alonso-Urbita
Journal: Circulation (2006)

Our objective is to analyse the prehospital treatment and 1-year survival of patients with acute myocardial infarction with ST segment elevation (STEMI) cared for emergency teams. Methods: Prospect...
Adolescent psychopathology and adult health behaviors in long-term survivors of childhood cancer: Findings from the Childhood Cancer Survivors Study
Authors: K. R. Krull, S. Huang, M. M. Hudson, J. G. Gurney, D. K. Srivastava, J. Klosky, K. K. Ness, W. Leisenring, A. Termuhlen, L. L. Robison
Journal: Journal of Clinical Oncology (2009)

10027 Background: Psychological problems have been identified as important risk factors for poor health behavior in a variety of noncancer populations. We report the association between adolescent psychopathology and future health behaviors in adult survivors of childhood cancer. Methods: Study participants included 1,656 survivors of childhood cancer (50.8% female); 12 - 17 years old and ≥ 5 years post diagnosis at baseline assessment and 18 - 27 years of age at study follow-up. Parents provided medication information and ratings of psychopathology for adolescents at baseline, including symptoms of depression/anxiety, social withdrawal, inattention, and oppositional and antisocial behavior. Survivor self-report of health behavior was collected 6 - 10 years post baseline. Odds ratios (OR) were calculated comparing those with psychopathology to those without on outcomes of obesity, physical activity, smoking, and sunscreen use. Estimates were adjusted for cancer diagnosis, cancer therapy, sex, age, and history of special education. Results: Adult obesity was associated with adolescent social withdrawal (OR 1.5, 95% CI 1.1–2.1) and adolescent use of stimulant medications (OR 1.9, 95% CI 1.1–3.2). Physical inactivity among adults was also associated with adolescent social withdrawal (OR 1.7, 95% CI 1.1–2.5) and to antidepressant use during adolescence (OR 3.2, 95% CI 1.2–8.2). These impacts on obesity and inactivity were above and beyond the risk associated with high body mass index at baseline. Stimulant medication use was associated with decreased likelihood of poor sunscreen use as an adult (OR 0.4, 95% CI 0.2–0.8). Adult smoking was associated with adolescent antisocial behavior (OR 2.6, 95% CI 1.6–4.2). Conclusions: These results suggest that psychological problems in adolescence predict future health behavior in adult survivors of childhood cancer. Furthermore, psychopharmacologic therapy for such problems may increase risk for certain conditions, and decrease risk for others. Increased psychological screening and medication monitoring is warranted to reduce overall risk of poor outcomes. No significant financial relationships to disclose.
Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma
Authors: Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Akifumi Takaori-Kondo, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Journal: Blood (2017)
Concordance between oncologists and dermatologists in the assessment of dermatologic events: A preliminary study.
Authors: Cristian Serna-Tamayo, Claire Marie Reyes-Habito, Viswanath Reddy Belum, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2014)

e20683 Background: Dermatologic adverse events (dAEs) from cancer therapies may impact the dosing, type of therapy and quality of life of patients. Consistency in attribution and need for dose modification of dAEs between dermatologists and oncologists is critical for optimal comprehensive care. In this study, we sought to evaluate the agreement in the attribution of dAEs and the need for dose modification between oncologists and dermatologists. Methods: An IRB approved review of electronic medical records and consult logs of cancer patients seen in December 2012 at the Dermatology outpatient referral service at Memorial Sloan Kettering Cancer Center was performed. The demographics, oncologic and dermatologic attribution, and CTCAE grading of dAEs were reviewed. Concordance was measured by percentage agreement and kappa coefficient (where k < 0.40, poor agreement; k = 0.41-0.75, moderate agreement; k > 0.75, good agreement). Results: There were 41 patient records analyzed: 61% of dAEs were therapy related and 39% were non-therapy related. Most referrals were from the gastrointestinal (14.6%), hematology (14.6%), and breast oncology (12.2%) services. The most common therapy related consult was for acneiform rash (21.9%) and the most common non-therapy related consult was for eczema/dermatitis (14.6%). Therapy related toxicities were mostly from targeted therapies (48%), especially from epidermal growth factor receptor inhibitors (EGFRIs, 24%). Grades of dAEs were grade 1/2 (85%) and grade 3 (15%), with no grade 4 dAEs. When oncologists reported attribution (n = 17), concordance with dermatologists was 88% (k = 0.76). Dose of anticancer agent was maintained in 68% and modified in 24% of patients. In cases in which the dose was modified, agreement between oncologists and dermatologists occurred in 64% of cases (k = 0.27). Conclusions: Urgent dermatologic evaluations are frequently needed both for therapy and non-therapy related events. Our results suggest good concordance in the attribution of these events, but poor agreement regarding the need for dose modification between oncologists and dermatologists. Education of oncologists and dermatologists may enhance collaboration.
Reply to Isabel Heidegger, Renate Pichler, and Andreas Pircher's Letter to the Editor re: Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, et al. Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response. Eur Urol 2017;71:776–87
Authors: Elin Thysell, Erik B. Ylitalo, Emma Jernberg, Anders Bergh, Pernilla Wikström
Journal: European Urology (2017)
Antitumor effect of levetiracetam combined with temozolomide in glioma cell lines.
Authors: Zhong-ping Chen, Qing-wu Wu, Jing Wang
Journal: Journal of Clinical Oncology (2017)

e13530 Background: The antitumor effect oftemozolomide (TMZ) is still remitted for portion of glioma patients, and if anti-epilepcy drug levetiracetam (LEV) may help TMZ for anti-glioma is not clear. Methods: The cell proliferation with Cell Counting Kit-8 (CCK-8) assay was performed in two O 6 -methylguanine DNA methyltransferase (MGMT) positive cell lines (T98G and U138) and two other MGMT negative cell lines (SKMG-4 and U87). The cells were treated with LEV and TMZ alone or in combination. Results: LEV inhibited the proliferation of glioma cell lines but not reach therapeutic effect, especially in U87cell line. The 50% inhibitory concentration (IC50) of TMZ was significantly decreased in cell lines (T98G, U138 and SKMG-4, P&lt; 0.05) which were treated with TMZ and LEV, but no significantly changed in U87 (P&gt; 0.05). Conclusions: LEV may inhibit the proliferation of glioma cell lines (both MGMT- positive and MGMT-negative) and also sensitizes cell lines (T98G, U138 and SKMG-4, but not U87) to TMZ.
An [<sup>18</sup>F]-Positron-Emitting, Fluorescent, Cerebrospinal Fluid Probe for Imaging Damage to the Brain and Spine
Authors: Harikrishna Kommidi, Hua Guo, Nandi Chen, Dohyun Kim, Bin He, Amy P. Wu, Omer Aras, Richard Ting
Journal: Theranostics (2017)

Fluorescein is modified to bear 18F so that it can act as both a positron emitter, and a fluorophore, allowing detection by positron emission tomography (PET), scintillation, and fluorescent imaging (FL). [18F]-2 is injected into the intrathecal space of rats and used to observe the cerebrospinal fluid (CSF) that bathes the brain and spine. Injury in three different applications is visualized with [18F]-2: 1) detection of a 0.7 mm paranasal-sinus CSF leak (CSFL); 2) detection of 0.5 mm puncture damage to the thoracic spine (acute spinal cord injury); and 3) detection of intracerebral hemorrhage/edema because of traumatic brain injury. In all models, the location of injury is visualized with [18F]-2 at high resolution. [18F]-2 PET imaging may be a superior alternative to current clinical contrast myelography and 131I, 111In or 99mTc radionuclide cisternography. Like fluorescein, [18F]-2 may also have other uses in diagnostic or fluorescence guided medicine.
VXM01 phase I study in patients with resectable progression of a glioblastoma.
Authors: Wolfgang Wick, Antje Wick, Martha Nowosielski, Felix Sahm, Dennis Riehl, Marlene Arzt, Andreas von Deimling, Martin Bendszus, Philipp Kickingereder, David Bonekamp, Philipp Beckhove, Friedrich Hubertus Schmitz-Winnenthal, Christine Jungk, Sébastien Wieckowski, Christel Herold-Mende, Heinz Lubenau, Andreas Unterberg, Michael Platten
Journal: Journal of Clinical Oncology (2017)

2061 Background: VXM01 consists of an attenuated Salmonella typhi Ty21a carrying a plasmid encoding for VEGFR-2. The bacterium is serving as a vector via the oral route of administration carrying the plasmid into the Peyer’s plaques. The vaccine construct elicits a systemic T-cell response targeting VEGFR-2. This trial was set up to examine safety and tolerability, clinical and immunogenic response to VXM01 after treatment with at least four vaccinations [10 6 or 10 7 colony-forming units (CFU)] in patients with recurrent glioblastoma who have failed at least radiochemotherapy with temozolomide. Methods: Patients with progressive resctable glioblastoma were subjected to single oral administration of VXM01 each on day 1, 3, 5, and 7. In addition, VXM01 was allowed to be administered in 4-weekly single doses every 4 weeks during the tumor follow-up period after reoperation. Follow-up was done by weekly safety laboratories and physical examinations in the treatment period and 4-weekly thereafter, MRI including perfusion maps (days 15 and 30 and six-weekly thereafter), 12-weekly T-cell immunomonitoring in the peripheral blood, and brain tumor immunohistochemistry. Results: Eight patients have been treated according to the schedule and surgery has been performed in seven of them. Under VXM01 treatment 47 adverse events, mostly unrelated to VXM01, were observed after a median of 7 doses per patient. Four out of eight patients (50%) showed a VEGFR-2 specific T cell response. In four patients there was a relevant increase in cerebral blood volume and apparent diffusion coefficient on post-vaccination MRI. In one patient there was an objective and durable T1 response, whereas three further patients remained stable prior to surgery and thereafter. Evaluation of infiltrating T cells in the tissue from re-operation revealed an increase in CD8+ T-cells in 5 out of 7 patients relative to the primary tumor tissue. Conclusions: VXM01 was safe and produces specific peripheral immune responses as well as enumeration of tumor-infiltrating T-cells in post-vaccine tumor tissue. Post treatment MRI imply vascular normalization and there was one patient with an objective response. As a consequence of this data, an expansion cohort of this trial has been launched. Clinical trial information: NCT02718443.
08.23 Syndecan-4 exerts a protective function in experimental intestinal inflammation
Authors: Mareike Fröhling, Dominik Bettenworth, Sonja Dufentester, Peter Paruzel, Frank Echtermeyer, Andreas Lügering, Thomas Pap, Athanasios Stratis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The ubiquitously expressed transmembrane heparan sulfate proteoglycan Syndecan-4 (Scd4) is crucial in inflammatory diseases, like rheumatoid arthritis. Depending on the tissue, it can either protect or promote an inflammatory process. By its binding of molecules, such as cytokines and growth factors, it can initiate signalling pathways and it has been implicated in cell-matrix adhesion, cell migration, differentiation as well as proliferation. However, the involvement of Sdc4 in intestinal inflammation is unknown so far. Our group revealed a protective function of Sdc4 in experimental intestinal inflammation. <h3>Material and methods</h3> We monitored the course of DSS-induced colitis in Scd4<sup>-/-</sup> and C57BL/6 WT mice and analysed the changes in body weight, colon length, histology and inflammatory cellular infiltrate. We also evaluated Sdc4 protein- and mRNA-level by immunofluorescence staining (IF) and quantitative real-time PCR. Colon-permeability was examined <i>in vivo</i> by using the Evans Blue method and measuring the clearance for <i>Citrobacter rodentium in vivo.</i> Wound healing effects of Scd4 were analysed <i>in vitro</i> by scratch assay analysis with human epithelial colon cell line (T-84) and <i>in vivo</i> by mechanically induced wounds in colonoscopies of Scd4<sup>-/-</sup> compared to WT mice. <h3>Results</h3> The expression of Scd4 is decreased upon the course of colitis and increased during remission. The course of colitis was markedly aggravated in Scd4<sup>-/-</sup> mice, reflected by dramatically loss of body weight, increased mortality rates and histological damage, emphasised by increased invasion of macrophages and granulocytes into the colon. Also colonic epithelial permeability of DSS-treated Scd4<sup>-/-</sup> mice was enhanced associated with an altered expression of tight junction proteins. Furthermore, Sdc4 deficiency resulted in a prolonged intestinal wound healing <i>in vitro</i> and <i>in vivo</i> due to reduced proliferation rates <i>in vitro</i>. <h3>Conclusions</h3> Our data indicates that Scd4 is crucial in experimental intestinal inflammation. It exerts protective effects by maintaining epithelial barrier integrity and regeneration. Further studies are needed to explore the mechanisms of Sdc4-signalling in colitis.
Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma
Authors: Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
Journal: Molecular Cancer (2017)

Abstract Background The plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways. Methods A chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness. The oncogenic effects of microRNA-455-3p (miR-455-3p) on ESCC chemoresistance and tumorigenesis were examined by in vivo and in vitro chemoresistance, tumorsphere formation, side-population, and in vivo limiting dilution assays. The roles of miR-455-3p in activation of the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad pathways were determined by luciferase and RNA immunoprecipitation assays. Results We found that miR-455-3p played essential roles in ESCC chemoresistance and tumorigenesis. Treatment with a miR-455-3p antagomir dramatically chemosensitized ESCC cells and reduced the subpopulations of CD90 + and CD271 + T-ICs via deactivation of multiple stemness-associated pathways, including Wnt/β-catenin and TGF-β signaling. Importantly, miR-455-3p exhibited aberrant upregulation in various human cancer types, and was significantly associated with decreased overall survival of cancer patients. Conclusions Our results demonstrate that miR-455-3p functions as an oncomiR in ESCC progression and may provide a potential therapeutic target to achieve better clinical outcomes in cancer patients.
Clinical Pathways: Recommendations for Putting Patients at the Center of Value-Based Care
Authors: Edward Abrahams, Alan Balch, Patricia Goldsmith, Marcia Kean, Amy M. Miller, Gilbert Omenn, Ellen Sonet, John Sprandio, Courtney Tyne, Kimberly Westrich
Journal: Clinical Cancer Research (2017)

Two major trends that have been affecting the provision of oncology care in the United States are a shift from volume-based to value-based care and a push toward patient-centered healthcare. However, these two trends are not always completely aligned with each other. Value-based payment models, including clinical pathways, are one strategy being implemented by oncology stakeholders to help encourage the uptake of value-based oncology care. If structured with the patient in mind, they can improve quality of care for patients with cancer, decrease inappropriate care while enabling appropriate personalization of care, and constrain rising prices by demanding a stronger link between cost and value. If not structured appropriately, they can limit patient choice, impede access to innovative treatments, and encourage one-size-fits-all oncology care. Clin Cancer Res; 23(16); 4545-9. ©2017 AACR.
The impact of the 21-gene assay in the Czech Republic on adjuvant chemotherapy (CT) recommendations and costs in estrogen receptor positive (ER+) early stage breast cancer (ESBC) patients with grade 2 tumors and risk factors.
Authors: Katarina Petrakova, Lubos B. Petruzelka, Milos Holanek, Tomas Svoboda, Marketa Palacova, Iveta Kolarova, Zuzana Bielcikova, Zuzana Zbozinkova
Journal: Journal of Clinical Oncology (2016)

e12061 Background: Conventional clinical risk factors are imprecise for determining recurrence risk. Multigene classifiers may provide useful information to resolve treatment decisions in the presence of these risk factors. We assessed the impact of the 21-gene assay on frequency and cost of CT usage in ESBC patients with risk factors in Czech medical centers. Methods: Eligible patients had ER+, HER2-, N0, grade 2 tumors and one secondary risk factor (high Ki67, micrometastatic disease, low/negative progesterone receptor expression). Following surgery, a treatment recommendation was formulated, then the 21-gene assay was ordered. Following receipt of the assay results, the treatment recommendation was reevaluated. Changes in treatment decision and influence of the assay result on treatment decision were recorded. Results: The study recruited 200 consecutive patients at 13 centers, with Recurrence Score data available for 196 (109 (55.6%) low, 75 (38.3%) intermediate, and 12 (6.1%) high Recurrence Score results). Overall, 63.7% of treatment recommendations changed after receipt of the assay result (62.2% switched from CHT to HT and 1.5% switched from HT to CHT). Most physicians agreed (59.5%) or strongly agreed (33.5%) that the 21-gene assay influenced their decision. Budget impact analysis in this patient population at the current 23% rate of testing, showed that utilization of the 21-gene assay results in a total budget impact of $183,019 in 2016 increasing to $279,806 in 2020. Conclusions: In this population of ESBC patients with grade 2 tumors the 21-gene assay reduced CT use by more than 60%, with >90% of physicians indicating that it influenced their treatment decision. The total budget impact of usage of the 21-gene assay in the Czech Republic is expected to be almost $282,851 per year in 2020, with part of the assay reimbursement cost compensated for by reduced CT usage. Further health economic studies are warranted to evaluate cost effectiveness. After 21-Gene Assay HT CHT Total Before 21-Gene Assay HT 42 (21.4%) 3 (1.5%) 45 CHT 122 (62.2%) 29 (14.8%) 151 Total 164 32 196
Rectus Femoris Tear Presenting as an Unusual Cause of a Subcutaneous Mass
Authors: Christina M. Murphy, Christen M. Mowad, Thomas Bowen, Timothy J. Murphy
Journal: JAMA Dermatology (2017)

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