tbuckley/cabot-search huggingface dataset:
Clinical response to anti-PD1 immunotherapy in a patient with non-seminomatous germ cell tumor and evaluation of the immune landscape in testicular cancer.
Authors: Shalin Shah, James Edward Ward, Riyue Bao, Bruce Brockstein, Jason John Luke
Journal: Journal of Clinical Oncology (2016)

e16040 Background: Anti-PD1 immunotherapy is rapidly becoming a standard of care in multiple cancers and expression of PD-L1 has been described in germ cell tumor specimens. Neither the efficacy of PD1 immunotherapy nor the incidence of an immune-responsive tumor microenvironment has been described in germ cell tumors. Methods: Due to limited diagnostic materials, a patient initially thought to have metastatic melanoma, but who was subsequently determined to have a non-seminomatous germ cell tumor (embryonal cell carcinoma), was treated with a single dose of anti-PD1 antibody (nivolumab). More broadly, we performed an in silico analysis of the testicular cancer cohort of TCGA using a previously published immune signature and a quantitative expression scoring system to divide RNAseq data from individual patient samples into either an inflamed, medium or non-inflamed status. Simultaneously, non-synonymous exonic somatic mutations were retrieved from DNA sequencing data allowing mutational load to be associated with the presence or absence of the T cell-inflamed phenotype in individual samples. Results: The patient treated with a single dose of anti-PD1 immunotherapy experienced clinical resolution of lymphadenopathy, drop in AFP, LDH and beta-hCG as well as greater than 47% tumor reduction by immune-related Response Criteria. Upon recognition of germ cell tumor diagnosis, the patient was referred for curative intent chemotherapy. In silico gene expression analysis suggested that a baseline T cell-inflamed tumor microenvironment was present in more than 50% of testicular cancer specimens of TCGA including both seminoma and non-seminoma individually. Non-synonymous mutational burden did not correlate with the presence of an inflamed gene expression profile. Conclusions: Patients with germ cell tumors can respond to anti-PD1 antibody treatment and gene expression profiling of the tumor-immune microenvironment supports further investigation of immunotherapy in germ cell tumors.
Erlotinib (Tarceva) in patients with non-small-cell lung cancer(NSCLC)): results on 394 patients from Tarceva Registr of CzechRepublic
Authors: Jana Skřičková, Miloš Pešek, Petr Zatloukal, Vítězsla Kolek, Leona Koubková, František Salajka, Milada Zemanová, Marcela Tomíšková, Dimka Sixtová, Tomáš Pavlík
Journal: Journal of Thoracic Oncology (2009)
CD4+ and CD8+ CD28<sup>null</sup> T Cells Are Cytotoxic to Autologous Muscle Cells in Patients With Polymyositis
Authors: Jayesh M. Pandya, Paulius Venalis, Lubna Al‐Khalili, Mohammad Shahadat Hossain, Vanessa Stache, Ingrid E. Lundberg, Vivianne Malmström, Andreas E. R. Fasth
Journal: Arthritis & Rheumatology (2016)

Objective Inflammatory T cell infiltrates in the skeletal muscle tissue of patients with polymyositis are dominated by CD28‐negative effector (CD28 null ) T cells of both the CD4 and CD8 lineage. These cells are potentially cytotoxic, and the aim of the present study was to develop a fully autologous cell culture system in which to investigate the functional contribution of such CD28 null T cells to myotoxicity. Methods In vitro cocultures of autologous skeletal muscle cells and T cell subsets obtained from 5 polymyositis patients were performed. Myotoxicity of T cells was quantified by calcein release and flow cytometric analyses. T cell degranulation was blocked with concanamycin A. Specific blocking of perforin, cytokines, and HLA was performed using antibodies. Results Both CD4+CD28 null and CD8+CD28 null T cells induced more muscle cell death than did their CD28+ counterparts. Differentiated muscle cells (myotubes) were more sensitive to T cell–mediated cell death than were their precursors (myoblasts). Both CD8+ and CD4+ CD28 null T cells displayed perforin polarization toward muscle cells and secreted higher levels of granzyme B and interferon‐γ (IFNγ) in coculture than did CD28+ T cells. The myotoxic effects of CD28 null T cells were reduced upon the blocking of perforin, cytokines, and HLA. Addition of IFNγ or tumor necrosis factor did not induce skeletal muscle cell death in the absence of T cells; however, it did up‐regulate HLA expression on muscle cells. Conclusion Myotoxicity of CD4+ and CD8+ CD28 null T cells is mediated by directed perforin‐dependent killing and can be further influenced by IFNγ‐induced HLA expression on muscle cells. The data suggest that CD28 null T cells are key effector cells that contribute to the muscle cell damage in polymyositis.
Les plans de lutte contre la pandémie de grippe en Europe
Authors: J F Aguilera, W J Paget
Journal: Eurosurveillance (2001)

L'Organisation Mondiale de la Sante recommande fermement a tous les pays de prevoir des plans pluridisciplinaires de prevention et de lutte contre la prochaine pandemie de grippe. Nous avons mene une enquete sur les methodes de surveillance de la grippe parmi les membres du Reseau europeen de surveillance de la grippe (European Influenza Surveillance Scheme, EISS), incluant une serie de questions sur la plani-fication de la lutte contre la pandemie. Tous les pays sauf un ont active un plan de lutte anti-pandemie ou sont en train de le mettre en œuvre. Une coordination de ces differents plans a un niveau europeen contribuerait probablement a en ameliorer l'efficacite et l'impact.
Effects of the education program for patients with cancer pain.
Authors: Su-Jin Koh, Bhumsuk Keam, Jeong Ju Seo
Journal: Journal of Clinical Oncology (2015)

193 Background: Caner pain is prevalent, burdensome, and undertreated. Barriers to good cancer pain control exist within patients on lack of knowledge or poor attitudes towards pain and opioid analgesics. The objective of this study was to test the effects of an education program on reducing barriers to pain management in oncology. Methods: Participants completed baseline assessments and were randomly allocated to receive an education program or not in addition to standard care. Education materials for the pain management program included the ‘Guideline on cancer pain management for patients’. The average education time took basically 30 minutes, and CRNs implemented the education program using a booklet for an individual patient. Outcome measures at one week included the Barriers Questionnaire (BQ), Brief Pain Inventory. Adherence of analgesia and daily activity score were assessed. Results: 176 participants were recruited from 5 sites over 3 months. Mean average pain and worst pain score (NRS) improved significantly in patients receiving education program 1.40 and 1.61. The addiction subscale of the BQ score was improved by 1.95 (pre: 3.39, post: 1.44, p &lt; 0.001) for participants receiving pain education. In terms of administration of short-acting analgesics due to breakthrough pain, inpatients showed no large difference before/after education in the use of short-acting analgesics but outpatients exhibited an increase from 25.5% before education to 73.5% after education and the difference was statistically significant. Conclusions: A cancer pain education was effective in reducing patient's barriers to pain management, improving pain score and daily activity score of cancer patients, especially using short-acting analgesics for breakthrough pain control in outpatients.
Abstract 3450: Epidemiological factors associated with breast cancer in young women
Authors: Allyson L. Toro, Matthew T. Hueman, Craig D. Shriver, Rachel E. Ellsworth
Journal: Cancer Research (2016)

Abstract Background: Although breast cancer in young women (YW, &amp;lt;40 years) only accounts for ∼7% of cases diagnosed annually, tumors in young patients have more aggressive characteristics and higher mortality rates. The cost of breast cancer increases significantly with more aggressive tumors in terms of treatment costs, physical and psychosocial effects on the patient and her family, and lost productivity. Improved understanding of factors associated with etiology of breast cancer in YW is critical to developing more effective prevention strategies and improved treatments, reducing the burden of breast cancer in this population. Methods: The Clinical Breast Care Project database was queried to identify all YW with invasive breast cancer or benign breast conditions diagnosed after surgical evaluation between 2001 and 2014 that had questionnaire data available from the time of diagnosis. Epidemiological factors including reproductive and health history and lifestyle choices were using Student's t-tests and chi-square analysis with P&amp;lt;0.05 defining significance. Results: Neither ethnicity nor family history differed significantly between YW with and without breast cancer. Reproductive factors that differed significantly between groups include longer use of oral contraceptives (P&amp;lt;0.001, 93 compared to 66 months), older age at first full-term pregnancy (FFTP, P = 0.002, 24.5 compared to 22.7 years), and longer duration of breastfeeding in parous YW (P = 0.024, 15.1 compared to 10.4 months) in YW with invasive breast cancer compared to those with benign conditions. YW with invasive breast cancer were also significantly more likely to be married (P = 0.043, 78% compared to 68%) and less likely to exercise (P = 0.003, 31% compared to 17%) compared to those with benign breasts. Conclusions: Of the factors evaluated, including reproductive history, lifestyle choices, and co-morbidities, only five differed significantly between YW with and without invasive breast cancer. Paradoxically, breastfeeding, which has been associated with reduced the risk of breast cancer, was higher in YW who developed invasive breast cancer. In contrast, parity and use of oral contraceptives are associated with transient increases in breast cancer risk. The older age at FFTP of YW with invasive breast cancer combined with the significantly longer exposures to oral contraceptives may create an environment within the breast favorable to tumor initiation and progression. Citation Format: Allyson L. Toro, Matthew T. Hueman, Craig D. Shriver, Rachel E. Ellsworth. Epidemiological factors associated with breast cancer in young women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3450.
Abstract 791: Examining the roles of deleterious and potentially damaging variant alleles in African and Caucasian ancestral populations
Authors: Myron K. Gibert, Luisel Ricks-Santi, John T. McDonald
Journal: Cancer Research (2016)

Abstract The purpose of this study was to analyze the overlap between potentially damaging Single Nucleotide Polymorphisms (SNPs) for coding gene regions across African American and Caucasian populations. Allele frequency and genotype data from the International HapMap Project was acquired for ancestral groups from Utah Residents with Northern and Western European Ancestry (CEU), Yoruba in Ibadan, Nigeria (YRI) and African Americans from the Southwest (ASW) resulting in 34,844 unique variants. Using the Variant Effect Predictor, non-synonymous SNPs in overlapping transcripts were filtered and found in 12,367 unique genes. SIFT or Polyphen-2 scores were used to determine which variants were likely to prove damaging to protein function, resulting in 10,917 variants. Functional annotation of biological pathways in genes affected by these variants was analyzed using DAVID. There was enrichment in olfactory pathways/g-protein coupled receptor function, cell membrane function and epidermal growth factor activity. Comparisons of genes affected by these deleterious variants were overlapped with the catalog of published genome-wide association studies (GWAS) with SNP-traits associated with cancer. There were 90 of 463 genes in common with this data that were examined for linkage disequilibrium with the damaging variants. Finally, SNPs with a variant allele frequency differences &amp;gt;±5% between CEU versus YRI or ASW resulted in with 2,381 SNPs with 55.7% overlap between groups. Analysis of patient genotypes found those in the CEU population were more likely to possess a homozygous allele. Using Chi-Squared tests, populations were examined for risk allele frequencies by genotype. This study demonstrated variants with potentially damaging consequences in cancer pathways are disproportionally represented in different ancestral populations. Citation Format: Myron K. Gibert, Luisel Ricks-Santi, John T. McDonald. Examining the roles of deleterious and potentially damaging variant alleles in African and Caucasian ancestral populations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 791.
Retraction Note to: Decreased expression of the long noncoding RNA LINC00261 indicate poor prognosis in gastric cancer and suppress gastric cancer metastasis by affecting the epithelial–mesenchymal transition
Authors: Yu Fan, Yan-fen Wang, Hua-fang Su, Na Fang, Chen Zou, Wen-feng Li, Zheng-hua Fei
Journal: Journal of Hematology & Oncology (2018)

The authors have retracted this article [1] because of significant overlap of text and some images with a previously published article by Xu et al. [2]. A formal investigation by the 1st Affiliated Hospital of Wenzhou Medical University has found that some panels in Fig. 6b [1] are identical with panels in Fig. 5a [2] and some images of mice lungs in Fig. 6c [1] are identical with images in Fig. 3g [2]. The data reported in this article are therefore unreliable. All authors agree to this retraction.
Randomized phase 3 study of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (mCRC): The SALTO study of the Dutch Colorectal Cancer Group.
Authors: Cornelis J. A. Punt, Lieke H Simkens, Johan Van Rooijen, Agnes W Van de Wouw, Olaf Loosveld, Geert-Jan Creemers, Mathijs P Hendriks, Maartje Los, Robbert Jeroen Van Alphen, Marco Polee, Erik W Muller, Ankie Van Der Velden, Thymen Van Voorthuizen, Miriam Koopman, Linda Mol, Johannes J Kwakman, Erik D. van Werkhoven
Journal: Journal of Clinical Oncology (2016)

3640 Background: Hand-foot syndrome (HFS) is a common side effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients (pts). The Dutch SALTO study (NCT01918852) was designed to compare the incidence of HFS between S-1 and capecitabine as 1stline treatment in mCRC pts. Methods: Previously untreated mCRC pts, WHO performance status (PS) 0-2, and planned treatment with fluoropyrimidine monochemotherapy were randomized between capecitabine 1250 mg/m2 for pts < 70 years of age, and 1000 mg/m2 for pts ≥ 70 years of age, b.i.d. day 1-14 (arm A) and S-1 30 mg/m2 b.i.d.day 1-14 (arm B). Cycles were administered q 3 wks. Cotreatment with bevacizumab 7.5 mg/kg/3wks iv was optional. Pts were stratified for use of bevacizumab, PS, serum LDH, and institution.Toxicity was assessed prior to each cycle by the investigator using NCI CTC 4.0 and by patients using a diary. Tumor response was assessed every 9 wks. Primary endpoint was the incidence of HFS. A total of 150 pts was required to demonstrate a difference in HFS of ≥ 20% with 90% power (α = 0.05, 2-tailed test). Secondary endpoints were grade 3 HFS, other toxicities, progression-free survival (PFS), response rate (RR), overall survival (OS). Results: A total of 161 pts were randomized between January 2014 - July 2015, 81 in arm A and 80 in arm B. Median age is 73 yrs (50-86), 10% of pts have PS2, 58% were planned to receive bevacizumab. Median follow-up is 9.4 months, 39 pts (24%) are still on study. Pts received a median of 6 cycles. In arm A and B the investigator-assessed all grade HFS is 70% and 41% (p .00025), and grade 3 HFS 20% and 4% (p .0025), resp. Other grade ≥ 3 toxicity only differed for anorexia (2.5% and 12.5%, p .018). All grade HFS assessed by 91 pts (preliminary results) is 82% and 57% (p .014), and grade 3 16% and 4% (p .08). Median PFS is 8.3 months and not significantly different between treatment arms (p .88, HR 0.97 [0.67-1.41]). Data on OS are not mature. Conclusions: Treatment with S-1 results in a significantly lower incidence of HFS compared to capecitabine in pts with mCRC, without compromising efficacy. Clinical trial information: NCT01918852.
First-in-class small molecule ONC201 in b-cell malignancies.
Authors: Hun Ju Lee, Michael Andreeff, Cyril Benes, Joshua E. Allen, Lee Schalop, Wolfgang Oster, Michael Wang
Journal: Journal of Clinical Oncology (2016)

TPS7581 Background: ONC201 is an orally active first-in-class small molecule inducer of the integrated stress response (ISR). Both preclinical tumor sensitivity profiling and mechanism of action studies indicate that B-cell malignancies, including non-Hodgkin’s lymphomas (NHL) and multiple myeloma, are among the most ONC201-sensitive tumor types. The former is based on in vitro and in vivo efficacy evaluations of over 1,000 cancer cell lines and patient samples. The mechanistic congruency is based on PERK-independent induction of the ISR by ONC201 that promotes apoptosis through induction of the ATF4/CHOP signaling axis. Malignant B cells are highly susceptible to ISR-induced apoptosis due to elevated basal ER stress levels driven by immunoglobulin and oncogenic protein production. Methods: Based on these preclinical findings, there are two clinical trials evaluating single agent ONC201 in B-cell malignances. One trial is a phase I/II study in NHL. This study includes adult patients with relapsed and/or refractory mantle cell, diffuse large B-cell, and/or transformed large cell lymphomas who have received < 5 lines of prior therapy. The phase I part of trial is a 3 + 3 dose escalation of ONC201 to establish the recommended phase II dose (RP2D) with once every 1 or 3 week administration. Currently, 3 patients have been enrolled on a once every three-week schedule. Clinical trial information: NCT02420795.
Effect of backing films on the transdermal delivery of cyclobenzaprine patch
Authors: Siji Lv, Peng Quan, Xiaochang Liu, Liang Fang
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The aim of this study was to investigate the effect of backing films on transdermal delivery of cyclobenzaprine patch. Different backing films were chosen to prepare the cyclobenzaprine transdermal patch. The cumulative amount of cyclobenzaprine released from different patches was evaluated in vitro. To investigate the interaction between cyclobenzaprine and backing films, the partitioning experiments and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were performed. The cumulative amount of cyclobenzaprine released from the patch with Cotran™ 9700 as backing film was less than that of other patches with different backing films. Furthermore, the cumulative amount of cyclobenzaprine released from the patch with Cotran™ 9700 as backing film decreased significantly after 7 d storage at room condition. The partitioning experiments indicated a strong adsorption of cyclobenzaprine onto the Cotran™ 9700, which could explain the decrease of cumulative amount of cyclobenzaprine released from the patch with Cotran™ 9700 as backing film. According to the ATR-FTIR results, there was no interaction between Cotran™ 9700 and cyclobenzaprine. The effect of backing films on the release behavior of cyclobenzaprine transdermal patch was attributed to the adsorption of cyclobenzaprine onto the Cotran™ 9700.
The Histone Methyltransferase Ezh2 Is a Crucial Epigenetic Regulator Of Allogeneic T Cell Responses and Graft-Versus-Host Disease In Mice
Authors: Shan He, Fang Xie, Yongnian Liu, Qing Tong, Kazuhiro Mochizuki, Philip E Lapinski, Pavan Reddy, Izumi Mochizuki, Arul M. Chinnaiyan, Shin Mineishi, Philip D King, Yi Zhang
Journal: Blood (2013)
Transcriptomic profiling of collecting duct carcinoma to reveal metabolic and immune aberrations.
Authors: Gabriel G. Malouf, Eva Comperat, Hui Yao, Roger Mouawad, Veronique Lindner, Nathalie Rioux-Leclercq, Virginie Verkarre, Xavier Leroy, Linda Dainese, Marion Classe, Jean-Luc Descotes, Philippe Barthelemy, Mokrane Yacoub, Morgan Roupret, Jean-Christophe Bernhard, Chad J. Creighton, Jean-Philippe Spano, Xiaoping Su, David Khayat
Journal: Journal of Clinical Oncology (2016)

4572 Background: Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggest an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Furthermore, the transcriptomic profile of CDC is not fully known. Methods: CDC samples (n = 15) collected from several French institutions were centrally reviewed by a national expert pathologist. As a control, muscle-invasive UTUC samples (n = 10) were also analyzed. RNA sequencing of CDC was performed and compared to that of urothelial (UTUC and bladder) and renal cell carcinoma (RCC) subtypes (clear-cell, papillary, translocation and chromophobe). Tumor infiltrating lymphocytes (TIL) were also analyzed using CD4, CD8 and CD3 staining. Results: CDC displays a unique transcriptomic signature among kidney cancer subtypes, with a putative cell of origin in the distal convoluted tubules. Hierarchical unsupervised clustering reveals that the CDC signature is closer to that of other RCC subtypes than to UTUC, which is similar to that of bladder carcinoma. CDC is characterized by a metabolic shift, with impairment of oxidoreductase activity, pyruvate metabolism and the tricarboxlyic acid cycle, as well as an immunogenic response. We found that the overall median TIL percentage in CDC assessed using CD3 staining was 22% (range: 0%-50%), with a higher statistically significant percentage in metastatic versus non-metastatic tumors (p = 0.04). Similarly, the median CD8 TIL percentage was 11% (range: 0%-25%), with a trend toward a higher percentage in metastatic versus non-metastatic tumors (p = 0.08). Genes and pathways differentially altered between CDC and UTUC point to a basal-like phenotype of CDC in contrast to the luminal-like signature of UTUC. Finally, we identified a set of genes wich might be used in clinic to differentiate between CDC and UTUC with good accuracy. Conclusions: CDC is unique among RCC subtypes that display a pathognomonic transcriptomic signature. Furthermore, CDC is both immunogenic and a metabolic disease, indicating that targeting these processes might provide therapeutic options for patients with CDC.