tbuckley/cabot-search huggingface dataset:
Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation
Authors: Peter Humburg, Narelle Maugeri, Wanseon Lee, Bert Mohr, Julian C. Knight
Journal: Genome Medicine (2016)

The heat shock transcriptional response is essential to effective cellular function under stress. This is a highly heritable trait but the nature and extent of inter-individual variation in heat shock response remains unresolved. We determined global transcription profiles of the heat shock response for a panel of lymphoblastoid cell lines established from 60 founder individuals in the Yoruba HapMap population. We explore the observed differentially expressed gene sets following heat shock, establishing functional annotations, underlying networks and nodal genes involving heat shock factor 1 recruitment. We define a multivariate phenotype for the global transcriptional response to heat shock using partial least squares regression and map this quantitative trait to associated genetic variation in search of the major genomic modulators. A comprehensive dataset of differentially expressed genes following heat shock in humans is presented. We identify nodal genes downstream of heat shock factor 1 in this gene set, notably involving ubiquitin C and small ubiquitin-like modifiers together with transcription factors. We dissect a multivariate phenotype for the global heat shock response which reveals distinct clustering of individuals in terms of variance of the heat shock response and involves differential expression of genes involved in DNA replication and cell division in some individuals. We find evidence of genetic associations for this multivariate response phenotype that involves trans effects modulating expression of genes following heat shock, including HSF1 and UBQLN1. This study defines gene expression following heat shock for a cohort of individuals, establishing insights into the biology of the heat shock response and hypotheses for how variation in this may be modulated by underlying genetic diversity.
DDGP versus SMILE in NK/T-Cell Lymphoma—Letter
Authors: Vineet Govinda Gupta, Ajay Gogia
Journal: Clinical Cancer Research (2016)

We read with interest the randomized controlled trial by Li and colleagues ([1][1]) comparing DDGP (dexamethasone, cisplatin, gemcitabine, pegasparaginase) to SMILE (dexamethasone, methotrexate, ifosfamide, l-asparaginase, etoposide) in patients with stage III–IV NK/T-cell lymphoma (NKTCL). While
Graft-Vs-Lymphoma (GVL) Induction with Allogeneic Hematopoietic Stem Cell Transplantation (SCT) for Primary Cutaneous T Cell Lymphomas (CTCL).
Authors: Vikram R Paralkar, Sunita Dwivedy Nasta, Kelly Morrissey, Jacqueline Smith, Pavel Vassilev, Mary Ellen Martin, Steven C Goldstein, Alison Loren, Alain H Rook, Ellen J Kim, David L Porter
Journal: Blood (2010)
Досвід застосування парентерального харчування в лікуванні печінкової недостатності
Authors: T.D. Nykula, V.O. Moiseienko, E.H. Manzhalii
Journal: GASTROENTEROLOGY (2016)

Наведено дані про позитивний досвід застосування аміноплазмалю гепа 10% як препарату парентерального харчування, що вирівнює співвідношення між амінокислотами з розгалуженим ланцюгом та ароматичними амінокислотами, нормалізує коефіцієнт Фішера, сприяє переходу печінкової енцефалопатії в більш легку стадію, знижує рівень аміаку в крові, забезпечуючи позитивну динаміку астеновегетативного, цитолітичного, холестатичного, геморагічного синдромів.
Anti-CD44 antibodies inhibit both mTORC1 and mTORC2: a new rationale supporting CD44-induced AML differentiation therapy
Authors: S Z Gadhoum, N Y Madhoun, A F Abuelela, J S Merzaban
Journal: Leukemia (2016)

5. After switching between products with the same active substance, more frequent molecular monitoring should be conducted to detect potential differences in effectiveness or side effects early after the switch.There is significant uncertainty for both prescribers and patients concerning the introduction of generic formulations of CML TKIs.More data and guidance are necessary when patients are being switched to alternative, less expensive products, to ensure the procedures are equally safe and that the risk of increased toxicity and/or loss of drug response is minimized.The recommendations from the patient community may provide a basis for discussion by the expert groups for publishing treatment guidelines and recommendations for the management of CML.Previous guidelines such as the European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013 (ref.12) serve as a valuable reference source for patients and physicians seeking to reduce the level of risk and uncertainty for safe administration of generic formulations of CML TKIs.
Sipuleucel-T (sip-T)–induced proliferative CD8+ T-cell responses to immunizing and secondary antigens.
Authors: Emmanuel S. Antonarakis, David I. Quinn, Adam S. Kibel, Daniel Peter Petrylak, Nancy N. Chang, Crystal Cummings, Jason Chinn, Jeff Pufnock, Nadeem Anwar Sheikh, Charles G. Drake
Journal: Journal of Clinical Oncology (2016)

165 Background: Sip-T is an FDA-approved autologous immunotherapy for patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sip-T is manufactured from peripheral blood mononuclear cells cultured with PA2024, a fusion antigen of prostatic acid phosphatase (PAP) conjugated to granulocyte macrophage-colony stimulating factor (GM-CSF). In sip-T–treated pts, T cell and antibody responses to PA2024 or PAP as well as antibody responses to secondary antigens (i.e., antigen spread) correlate with improved overall survival. To explore the biology of this relationship, we further characterized the T cell subpopulations involved in the cellular immune responses to sip-T. Methods: In vitro proliferative CD8+ (cytotoxic T lymphocyte) and CD4+ (T helper) T cell responses to PA2024 and PAP as well as to secondary antigens (PSA, LGALS3, and KRAS) were evaluated using flow cytometry on pt samples from two sip-T–containing clinical trials (STAND [NCT01431391] and STRIDE [NCT01981122]). Results: PA2024-specific CD8+ and CD4+ responses were observed beginning 2 weeks after the first sip-T infusion through week 26 in most evaluable pts. CD8+ and CD4+ responses to PAP were also observed, although the magnitude of this response (to a self-antigen) was smaller when compared with PA2024 responses. Most pts with CD8+ responses to PA2024 also had a CD4+ response, which occurred more frequently than CD8+ responses. Both CD8+ and CD4+ responses to secondary antigens were amplified after sip-T, and these CD8+ proliferative responses to secondary antigens were greater in magnitude compared with CD4+ responses. Conclusions: Here,we report the first evidence of antigen-specific CD8+ responses in pts receiving sip-T, indicating CD8+ T cell involvement in sip-T–mediated immune responses that occur in concert with the expected CD4+ T cell responses to soluble antigens (i.e., PA2024). These CD8+ responses were durable, lasting up to 26 weeks post–sip-T treatment. Importantly, responses to secondary antigens and in particular, CD8+ responses, were also amplified after sip-T treatment, suggesting that antigen spread could be resulting from sip-T–mediated tumor cell lysis. Clinical trial information: NCT01431391 and NCT01981122.
A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma
Authors: N Bolli, Y Li, V Sathiaseelan, K Raine, D Jones, P Ganly, F Cocito, G Bignell, M A Chapman, A S Sperling, K C Anderson, H Avet-Loiseau, S Minvielle, P J Campbell, N C Munshi
Journal: Blood Cancer Journal (2016)

Abstract Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined. Therefore, clinical-grade strategies to investigate the genomic landscape of myeloma samples are needed to integrate new and old prognostic markers. We developed a target-enrichment strategy followed by next-generation sequencing (NGS) to streamline simultaneous analysis of gene mutations, copy number changes and immunoglobulin heavy chain (IGH) translocations in MM in a high-throughput manner, and validated it in a panel of cell lines. We identified 548 likely oncogenic mutations in 182 genes. By integrating published data sets of NGS in MM, we retrieved a list of genes with significant relevance to myeloma and found that the mutational spectrum of primary samples and MM cell lines is partially overlapping. Gains and losses of chromosomes, chromosomal segments and gene loci were identified with accuracy comparable to conventional arrays, allowing identification of lesions with known prognostic significance. Furthermore, we identified IGH translocations with high positive and negative predictive value. Our approach could allow the identification of novel biomarkers with clinical relevance in myeloma.
Prognostic value of tumor-infiltrating lymphocytes (TILs) and expression of PD-L1 in cholangiocarcinoma.
Authors: Yaman Suleiman, Domenico Coppola, Sherma Zibadi, Samir Dalia, TzuHua Juan, Jae K Lee, Mokenge Peter Malafa, Hatem Hussein Soliman, Richard D. Kim
Journal: Journal of Clinical Oncology (2015)

294 Background: Cholangiocarcinoma is a malignancy arising from the epithelial cells of the biliary tract with poor prognosis. Tumor-infiltrating lymphocytes (TILs) have a prognostic impact in various solid tumors. We aimed to investigate TIL expression and programmed cell death ligand PD-L1 and their clinical relevance in cholangiocarcinoma. Methods: Formalin-fixed paraffin-embedded tumor samples from thirty seven patients with resected and histologically verified cholangiocarcinoma between 1990 and 2011 were identified and immunohistochemically (IHC) stained with anti CD8, anti CD45RO and the anti-PDL1 mouseIgG1 (clone 5H1; Thompson) antibodies on a Leica automated IHC platform. The stains were semiquantitatively analyzed using the AllRed score system (range 1 to 8). Cases with IHC score &gt; 3 were considered positive. The association between PDL1, CD45R0, overall survival (OS) and progressive free survival (PFS) was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results: The median age of patients was 64 (41-85) with 51% male. 25%, 59%, 10% and 5% were stage I, II, III, and IV respectively. CD8 was positive in 10/37 (27%) with median IHC of 5, CD45R0 (specimen with lymph node like structure) was positive in 16/37 (43%) with median IHC score of 4, PD-L1 was positive in 35/37 (94 %) with median IHC score of 8. Pts with tumors exhibiting lymph node (LN) like structures (CD45RO+) has better median OS (63 months vs 18 months, P = 0.0065) and median PFS (29 months vs 14.6 months, P = 0.05) than patients lacking LN like structures (CD45RO-). 5 yrs. OS in CD45RO+ was 64% vs 20% in CD45RO- (P 0.006) whereas 5 yrs. PFS in CD45RO+ was 41% vs. 8% in in CD45RO- pts (P value 0.05). Correlating PDL1 with OS and PFS was not done due to high expression of PD-L1 in most of the samples (94%). Conclusions: Presence of lymph node like structures (CD45RO+) was associated with significant better outcome reflecting the immune-mediated killing of tumor cells. The high expression of PD-L1 on cholangiocarcinoma cells represents a potential therapeutic target which may improve the prognosis for this dismal cancer. Future trials involving PD-L1 inhibitors in cholangiocarcinoma are warranted.
XmAb™2513, an Fc Engineered Humanized Anti-CD30 Monoclonal Antibody, Has Potent In Vitro and In Vivo Activities, and Has the Potential for Treating Hematologic Malignancies.
Authors: Chris E. Lawrence, Phil W. Hammond, Jonathan Zalevsky, Holly Horton, Seung Chu, Sher Karki, John R. Desjarlais, David F. Carmichael
Journal: Blood (2007)
Final report of randomized phase II study of two different outpatient setting regimens, vinorelbine (VNR) with cyclophosphamide (CPA) and temozolomide (TMZ) with etoposide (VP).
Authors: Atsushi Ogawa, Hiroshi Kawamoto, Mari Saito Oba, Ako Hosono, Yoshiyuki Kosaka, Junichi Hara, Yuji Ishida, Kenji Yamada, Katsuyoshi Koh, Yasuhiro Okamoto, Hideo Mugishima, Atsushi Kikuta, Takashi Taga
Journal: Journal of Clinical Oncology (2016)

10550 Background: The efficacy, safety, and feasibility of TMZ with VP (TE) have not been evaluated in pediatric patients (pts) and those of VNR with CPA (VC) have not been confirmed in Japanese pts. Methods: This multicenter, crossover randomized phase II study included children and young adults with recurrent or refractory solid cancer who received disease-specific standard chemotherapies. The study design has been reported in ASCO2010 (TPS328). In group A, VNR (25 mg/m2) and CPA (25 mg/m2) (VC) were administered intravenously on days 1, 8, and 15, and orally on days 1–28, every 28 days, then switched to TMZ (150 mg/m2) and VP (50 mg/m2) (TE) which were administered orally on days 1 - 5 and 1 - 12, every 28 days if they became progressive or intolerant. In group B, TE was given first, then switched to VC. Response was evaluated according to RECIST 1.1. Toxicity and complaints were assessed by using CTCAE v4.0. and face scales, respectively. Results: In group A, 34 pts (median age 15 years, range 3–29) included 8 neuroblastoma (NB), 4 rhabdomyosarcoma (RMS), 7 Ewing sarcoma family tumor (ES), 2 osteosarcoma (OS), 4 CNS tumors (BT), and 9 others. In group B, 33 pts (median age 14 years, range 3–30) included 7 NB, 5 RMS, 6 ES, 8 OS, 3 BT and 4 others. Treatment was well tolerated. No unexpected toxicities were observed. Febrile neutropenia occurred only in VC. In the first regimen, the response rates were 2.9% in VC with 1 PR and 18.2% in TE with 2 CR and 4 PR. The disease control rates were 29.4% in VC with 1 PR, 9 SD and 30.3% in TE with 2 CR, 4 PR and 4 SD. VC and TE improved pain, dyspnea, agitation, fatigue, and anorexia in 40%, 12%, 34%, 43% and 40%, and 38%, 23%, 33%, 28%, 33%, respectively. The 1-year overall survival for groups A and B were 35% (95% CI 21%-51%) and 45% (95% CI 31%-64%). The median survival days for A and B were 271.5 days (95% CI 164-411) and 354 days (95% CI 174-449). The 1-year last progression free survival for A and B were 24% (95% CI 11%-39%) and 21% (95% CI 9%-36%). Conclusions: In recurrent or refractory pediatric solid cancer with poor prognosis, VC, TE and those sequential administration are effective and alleviate tumor associated symptoms without severe toxicity. Clinical trial information: UMIN000003002.
Screening of an Indian cohort with breast and/or ovarian cancer by a next-generation sequencing-based panel to detect a high frequency of mutations.
Authors: Ashraf U Mannan, Jaya Singh, Rupali Gadkari, Ravikiran Lakshmikeshava, Payal Manek, Ravi Ramalingam, Manasa B.P., Suman Kapoor, Jamuna Yadhav, Satish Sankaran, Shanmukh Katragadda, Vamsi Veeramachaneni, Preveen Ramamoorthy, Ramesh Hariharan, Kalyanasundaram Subramanian
Journal: Journal of Clinical Oncology (2015)

e12505 Background: Breast and/or ovarian cancer are among the most prevalent forms of hereditary cancers in India causing an increasing societal burden. Early detection and identification of those with a high risk of developing cancer will help in instituting measures for effective surveillance and risk management strategies. NGS (next-generation sequencing) based tests provide an attractive alternative to the traditionally employed sequential testing strategies. With the right combination of test design (multiple genes) and analysis tools, a single NGS test can identify genetic abnormalities arising from single nucleotide variations (SNVs) and/or structural variations (SVs). Methods: 126 unrelated patients and families with breast and/or ovarian cancer were tested using the TruSight Cancer panel (consisting of 94 genes), which includes 13 genes highly associated with risk of inherited breast and/or ovarian cancer. Paired end sequencing was done with an average coverage of > 450X. The data was analyzed using the STRAND NGS software and interpreted using the StrandOmics platform. Results: We were able to detect pathogenic mutations in 40 (32%) cases, out of which 14 were novel mutations. Among all mutations detected, 25% (10/40) of mutations were detected in non-BRCA1/2 genes, namely, TP53, PALB2 and RAD51C. When cases were stratified based on age of diagnosis, in the ≤ 40 years and ≤ 50 years age groups, the detection rate were significantly higher (namely, 47.8% and 46.9%) as compared to the > 50 years age group in which it was 23.5%. Interestingly, 4 BRCA1 mutations were recurrent and accounted for 32.5% of all the mutations seen, highlighting the significance of founder mutations in Indian population. Conclusions: Our study suggests that this NGS based panel increases the sensitivity of the mutation detection rate and helps in identifying patients with a high risk of developing cancer as compared to testing for single genes using reflex testing mode. Our finding has the potential for developing effective strategies for prevention, early detection and better management of hereditary breast and/or ovarian cancer, which will have a positive impact on healthcare in India.
Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepatocellular Circulating Tumor Cells Enrichment
Authors: Shuyi Wang, Chunxiao Zhang, Guozhou Wang, Boran Cheng, Yulei Wang, Fangfang Chen, Yuanyuan Chen, Maohui Feng, Bin Xiong
Journal: Theranostics (2016)

Circulating tumor cells (CTCs) have been considered as the origin of cancer metastasis.Thus, detection of CTCs in peripheral blood is of great value in different types of solid tumors.However, owing to extremely low abundance of CTCs, detection of them has been technically challenging.To establish a simple and efficient method for CTCs detection in patients with hepatocellular carcinoma (HCC), we applied biocompatible and transparent HA/CTS (Hydroxyapatite/chitosan) nanofilm to achieve enhanced topographic interactions with nanoscale cellular surface components, and we used sLex-AP (aptamer for carbohydrate sialyl Lewis X) to coat onto HA/CTS nanofilm for efficient capture of HCC CTCs, these two functional components combined to form our CTC-BioT Chip platform.Using this platform, we realized HCC CTCs' capture and identification, the average recovery rate was 61.6% or more at each spiking level.Importantly, our platform identified CTCs (2±2 per 2 mL) in 25 of 42 (59.5%)HCC patients.Moreover, both the positivity rate and the number of detected CTCs were significantly correlated with tumor size, portal vein tumor thrombus, and the TNM (tumor-node-metastasis) stage.In summary, our CTC-BioT Chip platform provides a new method allowing for simple but efficient detection of CTCs in HCC patients, and it holds potential of clinically usefulness in monitoring HCC prognosis and guiding individualized treatment in the future.
Recombinant Thrombomodurin For The Treatment Of Transplantation-Associated Coagulopathy After Allogeneic Stem Cell Transplantation
Authors: Kazuyoshi Ishii, Shosaku Nomura, Tomoki Ito, Yuta Katayama, Taiichi Kyo, Shuichi Ota, Masanori Seki, Shigeru Chiba, Yoshinobu Maeda, Mitsune Tanimoto, Takayuki Ikezoe, Hideo Yagi, Yoji Ishida, Naohito Fujishima, Kenichi Sawada
Journal: Blood (2013)
Silicone Gel Breast Implants
Authors: Yank D. Coble
Journal: JAMA (1993)

AT THE 1991 Annual Meeting, Resolution 259 was referred by the Board of Trustees to the Council on Scientific Affairs (CSA) for a report on the evaluation of the safety of breast implants. The recommendations of Report M prepared by the CSA were adopted as amended by the American Medical Association (AMA) House of Delegates at the Interim Meeting in 1991 in lieu of Resolution 259 (A-91) and Resolution 521 (I-91) and the remainder of the Report was filed (Policy 525.984,<i>AMA Policy Compendium</i>). Report M described the Food and Drug Administration (FDA) regulatory history of breast implant devices through August 1991. Because of continuing developments, including a voluntary moratorium on their use by the FDA in November 1991, the Council elected to provide a follow-up report (Report C) on this subject. Report C covers the continuing FDA regulatory history through October 1992 and See also pp 2607 and 2608.
Screening of Telomere Length in Peripheral Blood Lymphocytes From Patients with Aplastic Anemia by Flow-Fluorescence in Situ Hybridization.
Authors: Nobuhiro Nishio, Yoshiyuki Takahashi, Hideki Muramatsu, Asahito Hama, Toshihito Nagata, Seiji Kojima
Journal: Blood (2009)
Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) and Decitabine in Patients with Relapsed, Refractory or Poor Prognosis Leukemia.
Authors: Farhad Ravandi, Stefan Faderl, Deborah Thomas, Jan Burger, Charles Koller, Guillermo Garcia-Manero, Gail Morris, Ritva Torma, Hagop Kantarjian, Jean-Pierre Issa
Journal: Blood (2007)
Laying the foundation for evonomics
Authors: David Sloan Wilson
Journal: Behavioral and Brain Sciences (2016)

The target article is a major step toward integrating the biological and human-related sciences. It is highly relevant to economics and public policy formulation in the real world, in addition to its basic scientific import. My commentary covers a number of points, including avoiding an excessively narrow focus on agriculture, the importance of multilevel selection and complex systems theory, and utopic versus dystopic scenarios for the future.
Standardized MRD Flow and ASO IGH RQ-PCR for MRD Quantification in CLL Patients after Rituximab-Containing Immunochemotherapy – a Comparative Analysis in 574 Samples from the Randomized GCLLSG CLL8 Trial
Authors: Sebastian Boettcher, Stephan Stilgenbauer, Raymonde Busch, Monika Brüggemann, Thorsten Raff, Kirsten Fischer, Günter Fingerle-Rowson, Anna-Maria Fink, Christiane Pott, Hartmut Döhner, Michael Hallek, Michael Kneba, Matthias Ritgen
Journal: Blood (2008)
The Ecology of Medical Care
Authors: Kerr L. White, T. Franklin Williams, Bernard G. Greenberg
Journal: New England Journal of Medicine (1961)

CURRENT discussions about medical care appear largely concerned with two questions: Is the burgeoning harvest of new knowledge fostered by immense public investment in medical research being delivered effectively to the consumers? Is the available quantity, quality and distribution of contemporary medical care optimum in the opinion of the consumers? In addition, it may be asked: Whose responsibility is it to examine these questions and provide data upon which sound judgments and effective programs can be based?The traditional indexes of the public's health, such as mortality and morbidity rates, are useful for defining patterns of ill-health and demographic characteristics . . .