tbuckley/cabot-search huggingface dataset:
Response to: ‘Lower anti-drug antibodies with etanercept biosimilar: Can C<sub>trough</sub> explain the differences’ by Shah
Authors: Paul Emery, Jiří Vencovský, Jeehoon Ghil, Jung Won Kang
Journal: Annals of the Rheumatic Diseases (2016)

Response to: 'Lower anti-drug antibodies with etanercept biosimilar: Can C trough explain the differences' by ShahWe appreciate Shah 1 for the interest in and comments on the SB4 phase III study publication and subsequent correspondences regarding immunogenicity results. 2-4 The immunogenicity results in the SB4 phase III study 2 (0.7% in SB4 and 13.1% in reference etanercept (ETN)) was concluded by the Committee for Medicinal Products for Human Use to be uncertain because of the low drug tolerance of the anti-drug antibody (ADA) assay that led to a low sensitivity and potential bias considering the pharmacokinetic (PK) results of our study. 5The trough serum concentration (C trough ) measured in a subset of PK population (41 patients in the SB4 group and 38 in the ETN group) was generally comparable between the SB4 group (ranging from 2.419 to 2.886 μg/mL in weeks 2-24) and the ETN group (ranging from 2.066 to 2.635 μg/mL in weeks 2-24); however, the C trough was relatively higher in SB4 group compared with the ETN group (figure 1) at weeks 4 and 8.We believe that the numerical difference is likely due to an inherent high inter-subject variability; coefficient of variation (CV%) of C trough ranged from 45.2% to 53.8% following SB4 and from 42.4% to 65.7% following ETN.In our phase III study results, the C trough for some patients were higher than the drug tolerance level of the initial ADA assay format used and the ADA incidence could have been underestimated.Based on these results, it is not possible to conclude whether the C trough level affected the detection of ADA.Additional data from the PK population on immunogenicity with a more sensitive assay with regard to drug tolerance have been reported in the response to Marshall et al 6 : 2.4% in SB4 and 21.1% in ETN (results to be published).Together with the SB4 phase I immunogenicity results, 7 which showed that ADA incidence was significantly lower in SB4 (0.0%) compared with European-sourced ETN (15.6%, p=0.006 compared with SB4) or US-sourced ETN (22.7%, p<0.001 compared with SB4) without the concern of drug interference, 6 we hope the data of our study can provide insight into the impact of C trough on ADA.
DIRECT: DNA-mutation Inventory to Refine and Enhance Cancer Treatment—A catalogue of clinically relevant somatic mutations in lung cancer.
Authors: L. Horn, H. Chen, C. M. Lovly, J. Andrews, P. Yeh, M. A. Levy, W. Pao
Journal: Journal of Clinical Oncology (2011)

7575 Background: The treatment of patients with NSCLC in the 21st century has evolved into a complicated algorithm, requiring knowledge of an individual patient’s mutation status prior to initiating therapy. Making mastery of knowledge even more complicated, alterations within a single gene, such as that encoded by the epidermal growth factor receptor (EGFR), can be associated with primary drug sensitivity or resistance, or secondary resistance. Other rarer EGFR mutations are of less clear significance. Methods: We conducted a systematic review of the literature and identified all papers reporting on patients with EGFR mutations. No restrictions were placed on the papers identified provided individual patient data were presented. We recorded demographic data including age, ethnicity, smoking status, EGFR mutation, therapy administered (chemo, TKI), response and survival. General linear modeling was used to assess association between mutation, therapy and response. Results: We reviewed > 1,000 papers and identified 115 papers containing data on 1152individual patients. 91% adenocarcinoma, 62% never smokers, 92% stage IV. 154 different mutations identified: 48% exon 19 deletion, 27% L858R, 3% G719X, 1% L861Q and 21% other. 74% patients had first line EGFR TKI. Compared to patients with del19, patients there was no significant difference in response to EGFR TKI for patients with L858R or L861Q mutation while patients with G719X and other mutations had a significantly worse outcome when treated with EGFR TKIs. Conclusions: This DIRECT database is the start of a larger catalogue of clinically relevant somatic mutations in lung cancer that we are creating to aid physicians within the clinic in their selection of therapies for patients with various mutations and lung cancer. While this project has started with patients with known EGFR mutations, we are expanding the program to incorporate all known mutations with potential clinical significance. We encourage others to contribute data as they emerge. We plan to make this database amenable to query to further enable a genetically-informed approach in the treatment of lung cancer.
Abstract 1089: Cardiac glycosides affect miRNA expression profiles in renal cell carcinoma cell lines
Authors: Elke Nolte, Sven Wach, Izabella T. da Silva, Arif Ekici, Frieder Müller-Uri, Wolfgang Kreis, Julio Vera-Gonzales, Bernd Wullich, Helge Taubert, Xin Lai
Journal: Cancer Research (2016)

Abstract Background: Renal Cell Carcinoma (RCC) is the ninth most common cancer worldwide, with about 338,000 new cases diagnosed in 2012. Especially metastatic renal cell carcinoma has still despite surgical cytoreduction, VEGF-tyrosine kinase inhibitors, mTOR inhibitors and first promising results of immunotherapies a very poor prognosis what implies an urgent need for additional therapies. Cardiac glycosides have come into the focus as potential cancer treatment option. They can have anti-proliferative and apoptotic characteristics in several cancer cell lines but affect only in a much lesser extent normal cell lines. MicroRNAs are small non-coding RNAs of 17-25 nucleotides length that widely exist and they play an important regulating role in many normal and pathophysiological cellular processes, as cell proliferation, differentiation, induction of apoptosis, tumorigenesis and tumor progression. Material and Methods: Four renal cell carcinoma cell lines were treated with three different cardiac glycosides in the IC50 concentrations during 72h. For the investigation of miRNA expression miRNA microarray expression analyses were performed. In silico target gene and pathway enrichment analyses were performed. Results: An overlap between all treatments and all cell lines could be detected for two mature miRNAs and two premature miRNAs. Pathway enrichment analysis identified MAPK and axon guidance pathways. Moreover, we looked for genes predicted to be regulated by the deregulated miRNAs in all cell lines at all treatments in the MAPK and the axon guidance pathways. Conclusion: The identification and characterization of deregulated miRNAs after cardiac glycoside treatment could give insight in their gene regulation and thus help to clarify the molecular basis of their anti-proliferative and apoptotic effects. Citation Format: Elke Nolte, Sven Wach, Izabella T. da Silva, Arif Ekici, Frieder Müller-Uri, Wolfgang Kreis, Julio Vera-Gonzales, Bernd Wullich, Helge Taubert, Xin Lai. Cardiac glycosides affect miRNA expression profiles in renal cell carcinoma cell lines. [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 1089.
Abstract 3845: A novel selectivity determinant informs the development of next-generation stapled peptide inhibitors of anti-apoptotic BFL-1/A1
Authors: Annissa J. Huhn, Rachel M. Guerra, Gregory H. Bird, Loren D. Walensky
Journal: Cancer Research (2016)

Abstract The development of selective inhibitors for the individual anti-apoptotic BCL-2 family proteins implicated in oncogenesis and chemoresistance remains a formidable but pressing challenge. Precisely tailored compounds would serve as ideal molecular probes and targeted therapies to respectively study and treat human cancers driven by discrete apoptotic blockades. The remarkable potential of this strategy is exemplified by ABT-199, a potent and selective small molecule BCL-2 inhibitor that is proving effective at reactivating apoptosis in BCL-2-dependent cancers. The BCL-2 protein homologue, BFL-1/A1, has emerged as a resistance factor in a series of human cancers, including melanoma, leukemia, and lymphoma, but remains undrugged. To identify binding and specificity determinants for targeting BFL-1/A1, we screened a library of hydrocarbon-stapled BH3 domain helices and identified a subclass of compounds that engage BFL-1/A1 with exquisite selectivity in vitro and in situ. The mechanistic basis for this specificity revealed a unique topographic feature of the BFL-1/A1 binding groove. Leveraging this natural BFL-1/A1 selectivity factor, we designed next-generation stapled peptide inhibitors that block BFL-1/A1's capacity to both bind BH3 domains and suppress BAX-mediated membrane poration. Our studies inform a new pharmacologic strategy for potent and selective inhibition of anti-apoptotic BFL-1/A1 in human cancer. Citation Format: Annissa J. Huhn, Rachel M. Guerra, Gregory H. Bird, Loren D. Walensky. A novel selectivity determinant informs the development of next-generation stapled peptide inhibitors of anti-apoptotic BFL-1/A1. [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 3845.
Disentangling the Causal Association of Plasma Lipid Traits and Type 2 Diabetes Using Human Genetics
Authors: Danish Saleheen, Daniel J. Rader, Benjamin F. Voight
Journal: JAMA Cardiology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
The Mutatome of CBFB/MYH11-rearranged Acute Myeloid Leukemia (AML)
Authors: Sabrina Opatz, Klaus H Metzeler, Tobias Herold, Sebastian Vosberg, Kathrin Bräundl, Bianka Ksienzyk, Nikola P Konstandin, Christine Wang, Alexander Graf, Stefan Krebs, Helmut Blum, Stephanie Schneider, Wolfgang Hiddemann, Karsten Spiekermann, Stefan K Bohlander, Philipp A Greif
Journal: Blood (2014)
Chronic pruritus: evaluation of patient needs and treatment goals with a special regard to differences according to pruritus classification and sex
Authors: S. Steinke, P. Bruland, C. Blome, N. Osada, M. Dugas, F. Fritz, M. Augustin, S. Ständer
Journal: British Journal of Dermatology (2016)

Chronic pruritus (CP) is present in approximately one-third of all dermatological patients. Diagnostics and treatment are challenging and impair patients' quality of life.To analyse therapeutic needs in terms of the importance of treatment goals in a large sample of patients with CP.Routine data of 2747 patients with CP were analysed with descriptive methods and significance tests (univariate and multivariate variance analyses). The importance of 27 need items was measured using the Patient Needs Questionnaire of the Patient Benefit Index.The most important needs were to find a clear diagnosis and treatment, to no longer experience itching and to have confidence in the therapy, which were quite or very important to > 90% of the patients. The least important goals concerned a normal working or sex life. Nine needs related mostly to disease and psychological symptoms, and some social needs differed in importance between sexes (P ≤ 0·05). Patients with pruritus on inflamed skin or with chronic scratch lesions judged more than half of all needs as more important than did patients with pruritus on noninflamed skin (P ≤ 0·05). In the multivariate model, age, pruritus intensity and quality of life had a significant effect on the importance of therapeutic needs besides sex and pruritus classification.Patients with CP present high levels of various therapeutic needs with differences by sex and clinical phenotype. The most important needs can be addressed through medical activities such as appropriate itch medication and a trustful doctor-patient relationship.
Reply to Lu Yang, Shi Qiu and Qiang Wei's Letter to the Editor re: Christopher E. Bayne, Stephen B. Williams, Matthew R. Cooperberg, et al. Treatment of the Primary Tumor in Metastatic Prostate Cancer: Current Concepts and Future Perspectives. Eur Urol 2016;69:775–87
Authors: Christopher E. Bayne, -->Stephen B. Williams, Brian F. Chapin
Journal: European Urology (2016)
Abstract 1787A: Puerto Rico BioBank: The first cancer tissue biobank at a US Hispanic-serving institution
Authors: Patricia Casbas-Hernandez, Idhaliz Flores, Edward Seijo, Domenico Coppola, Steve Eschrich, Rodrigo Carvajal-Pelaez, Sonia Abac, Dagmar Correa, Edna Gordian, Teresita Munoz-Antonia
Journal: Cancer Research (2016)

Abstract There are currently 580 million people worldwide considered to be of Hispanic origin. In the US Hispanics represent 17% of the population and its largest ethnic minority. Funded by NIH, Moffitt Cancer Center (Florida) and Ponce School of Medicine (Puerto Rico) initiated a partnership that conducts high-quality research, training, and community outreach focusing on cancer health disparities among Hispanics. A central component to this partnership is the establishment of the first cancer-focused biobank in the island, the Puerto Rico BioBank (PRBB). The PRBB has actively recruited cancer patients since 2009; over these years we have established essential collaborations and a functional infrastructure. Eligible cancer patients provide informed consent and agree to donate blood samples (for DNA) and solid tissue(fresh-frozen &amp; paraffin embedded). Additionally, patients complete a comprehensive questionnaire related to clinical and lifestyle factors. Biospecimen collection at the PHSU follow standard operating procedures that mirror and often exceed NCI biobaking best practices for biospecimens and ensuring patient data confidentiality. Currently, the PRBB has over 1,100 consented patients (65.8% females, 34.2% males) all of Hispanic origin. The most common banked tumors are Breast, Prostate, Lung and Endometrium, although other tumors are represented. All the information and data are entered into a biospecimen management system (BMS) developed by the partnership, which allows for real-time biospecimen inventory management and reporting functionality. In conclusion, the Puerto Rican patient samples banked in the PRBB are a unique resource that can support multiple molecular and population studies. Also, a Hispanic-specific biobank can foster collaborations among local and international researchers that may facilitate the application of novel molecular techniques to solving cancer health disparities among Hispanics. Citation Format: Patricia Casbas-Hernandez, Idhaliz Flores, Edward Seijo, Domenico Coppola, Steve Eschrich, Rodrigo Carvajal-Pelaez, Sonia Abac, Dagmar Correa, Edna Gordian, Teresita Munoz-Antonia. Puerto Rico BioBank: The first cancer tissue biobank at a US Hispanic-serving institution. [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 1787A.
Case 23-1963
Authors: John P. Connelly, Victor J. Rosen
Journal: New England Journal of Medicine (1963)

Presentation of CaseA nine-year-old boy was referred to the hospital because of pain in the abdomen.The child was the product of a normal pregnancy and delivery and exhibited normal growth and development. He had had digestive trouble, as manifested by vomiting and abdominal discomfort, since infancy; episodes of abdominal pain occurred after the ingestion of fatty foods, including cream, ice cream, peanut butter and fried foods. The pain, which was sudden in onset and lasted for about an hour, was severe, nonradiating, constant and noncolicky. It was localized in the epigastrium and right upper quadrant and was often . . .
Abstract 2636: Myc vs. Akt therapy in RapidCap, a GEM model for metastatic prostate cancer
Authors: Carlos E. Stahlhut, Kaitlin E. Watrud, Alexandra J. Ambrico, Hyejin Cho, Lily Wang, Jun Qi, Lewis C. Cantley, James Bradner, Lloyd C. Trotman
Journal: Cancer Research (2015)

Abstract Metastasis is a major driver of mortality and morbidity in prostate cancer, the most common cancer type in men and the second leading cause of cancer-related deaths in the western world. To recapitulate the process in genetically engineered mice, we have developed the RapidCaP system, which uses prostate-directed viral infection to trigger focal loss of Pten and Trp53. The system provides a powerful platform for identification and validation of candidate driver genes and for efficient testing of novel therapeutics. Using this approach, we have recently identified Myc as a critical, spontaneously activated driver in Pten-negative metastatic prostate cancer. In agreement, our previous trials indicated that the Myc-suppressing Brd4 inhibitor JQ1 is ineffective towards primary disease, but causes metastatic regression. Mechanistically, this specificity correlates with the switch from Akt-driven primary to Myc-driven metastatic disease. Intriguingly, however, advanced metastases in RapidCaP do not express the androgen receptor, in spite of being of epithelial origin as shown by the Nkx3.1 prostate marker. As a consequence, metastatic disease often shows little to no response to castration therapy and invariably results in lethal disease. Therefore, we will discuss how, when and why targeting of Myc using JQ1 and the PI 3-Kinase pathway using NVP-BKM120 are best used to treat naïve or castration-resistant metastatic disease. Citation Format: Carlos E. Stahlhut, Kaitlin E. Watrud, Alexandra J. Ambrico, Hyejin Cho, Lily Wang, Jun Qi, Lewis C. Cantley, James Bradner, Lloyd C. Trotman. Myc vs. Akt therapy in RapidCap, a GEM model for metastatic prostate cancer. [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 2636. doi:10.1158/1538-7445.AM2015-2636
Characterization of the Poplar Pan-Genome by Genome-Wide Identification of Structural Variation
Authors: Sara Pinosio, Stefania Giacomello, Patricia Faivre-Rampant, Gail Taylor, Veronique Jorge, Marie Christine Le Paslier, Giusi Zaina, Catherine Bastien, Federica Cattonaro, Fabio Marroni, Michele Morgante
Journal: Molecular Biology and Evolution (2016)

Many recent studies have emphasized the important role of structural variation (SV) in determining human genetic and phenotypic variation. In plants, studies aimed at elucidating the extent of SV are still in their infancy. Evidence has indicated a high presence and an active role of SV in driving plant genome evolution in different plant species. With the aim of characterizing the size and the composition of the poplar pan-genome, we performed a genome-wide analysis of structural variation in three intercrossable poplar species: Populus nigra, Populus deltoides, and Populus trichocarpa. We detected a total of 7,889 deletions and 10,586 insertions relative to the P. trichocarpa reference genome, covering respectively 33.2 Mb and 62.9 Mb of genomic sequence, and 3,230 genes affected by copy number variation (CNV). The majority of the detected variants are inter-specific in agreement with a recent origin following separation of species. Insertions and deletions (INDELs) were preferentially located in low-gene density regions of the poplar genome and were, for the majority, associated with the activity of transposable elements. Genes affected by SV showed lower-than-average expression levels and higher levels of dN/dS, suggesting that they are subject to relaxed selective pressure or correspond to pseudogenes. Functional annotation of genes affected by INDELs showed over-representation of categories associated with transposable elements activity, while genes affected by genic CNVs showed enrichment in categories related to resistance to stress and pathogens. This study provides a genome-wide catalogue of SV and the first insight on functional and structural properties of the poplar pan-genome.