tbuckley/cabot-search huggingface dataset:
Genomic Instability and Clonal Evolution in Chronic Lymphocytic Leukemia: Clinical Relevance
Authors: Adalgisa Condoluci, Davide Rossi
Journal: Journal of the National Comprehensive Cancer Network (2021)

Genomic instability and clonal heterogeneity can influence cancer progression, response to therapy, and relapse. Chronic lymphocytic leukemia (CLL) harbors a variety of clones and subclones that will evolve differently according to intrinsic (microenvironment) and extrinsic (therapy) pressures. Different patterns of clonal evolution have been described, providing insights into the CLL leukemic cell, dynamics, selection, and treatment refractoriness. With the help of genomic technologies allowing a granular resolution of CLL clones, novel synergic therapeutic strategies can be tested with the aim of reaching a genomic-epigenomic ultrapersonalized, tailored approach. These efforts should consider the presence of targetable alterations, continuous cancer reshaping conferring disease refractoriness, and intratumoral clonal equilibrium to possibly avoid clonal selection.
연구논문 : 초치료 만성 B형간염 환자에서 엔테카비어 치료반응 및 관련 인자
Authors: 이명희 ( Myoung Hee Lee ), 임선교 ( Sun Gyo Lim ), 전수진 ( Su Jin Jeon ), 강창준 ( Chang Joon Kang ), 조영주 ( Young Ju Cho ), 김순선 ( Soon Sun Kim ), 이다미 ( Da Mi Lee ), 정재연 ( Jae Youn Cheong ), 조성원 ( Sung Won Cho )
Journal: Clinical and Molecular Hepatology (2009)

목적: 엔테카비어는 만성 B형간염의 초치료 환자에서 강력한 항바이러스 효과 및 낮은 내성률이 보고되고 있다. 본 연구에서는 단일 기관에서 경험한 엔테카비어의 혈청, 생화학, 바이러스반응을 관찰하고 엔테카비어의 치료반응과 연관된 인자를 규명하고자 하였다. 대상과 방법: 12개월 이상 1일 1회 0.5 mg의 엔테카비어를 경구 투여받은 114명의 만성 B형간염 환자를 대상으로 하였다. 초기바이러스반응은 치료 3개월 후 혈청 HBV DNA가 2,000 copies/mL 미만으로 감소한 경우로 정의하였다. 결과: 엔테카비어 투여 후 혈청 ALT값의 정상화는 치료 6개월, 12개월, 24개월에 각각 76명(68.5%), 85명(74.6%), 62명(81.6%)에서, HBV DNA PCR 음전은 각각 50명(43.9%), 81명(71.1%), 65명(85.5%)에서 관찰되었다. HBeAg 혈청소실은 6개월에 17명(36.2%), 12개월에 27명(43.5%), 24개월에 22명(56.4%), 혈청전환은 각각 8명(12.9%), 9명(14.5%), 6명(15.4%)에서 관찰되었다. HBV DNA PCR 음전을 예측할 수 인자는 단변량 분석에서 HBeAg 유무, 치료 전 혈청 AST치, 혈청 HBV DNA치, 초기바이러스반응 유무였고, 다변량 분석에서 초기바이러스반응이 독립적인 인자였다[P<0.001, OR=7.286(2.663~19.932)]. HBeAg의 혈청소실은 혈청 알부민치와 혈소판 수치가 낮은 경우, 혈청 AST치가 높은 경우, 간경변을 동반한 경우와 초기바이러스반응이 있는 경우에 빈번하게 발생하였고, 혈청 알부민[P=0.041, OR=0.232(0.057~0.945)]치와 초기바이러스반응[P=0.005, OR=7.017(1.799~27.378)]이 독립적인 예측인자였다. 결론: 엔테카비어는 만성 B형간염의 초치료 환자에서 우수한 치료반응을 보였으며, 치료 3개월째 초기바이러스반응은 HBV DNA 음전 및 HBeAg 소실의 독립적 예측인자였다.
Lipid metabolism in cancer progression and therapeutic strategies
Authors: Yan Fu, Tiantian Zou, Xiaotian Shen, Peter J. Nelson, Jiahui Li, Chao Wu, Jimeng Yang, Yan Zheng, Christiane Bruns, Yue Zhao, Lunxiu Qin, Qiongzhu Dong
Journal: MedComm (2020)

Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. The enhanced synthesis, storage, and uptake of lipids contribute to cancer progression. The rewiring of lipid metabolism in cancer has been linked to the activation of oncogenic signaling pathways and cross talk with the tumor microenvironment. The resulting activity favors the survival and proliferation of tumor cells in the harsh conditions within the tumor. Lipid metabolism also plays a vital role in tumor immunogenicity via effects on the function of the noncancer cells within the tumor microenvironment, especially immune-associated cells. Targeting altered lipid metabolism pathways has shown potential as a promising anticancer therapy. Here, we review recent evidence implicating the contribution of lipid metabolic reprogramming in cancer to cancer progression, and discuss the molecular mechanisms underlying lipid metabolism rewiring in cancer, and potential therapeutic strategies directed toward lipid metabolism in cancer. This review sheds new light to fully understanding of the role of lipid metabolic reprogramming in the context of cancer and provides valuable clues on therapeutic strategies targeting lipid metabolism in cancer.
Characteristics and outcomes of COVID-19 in patients with autoimmune bullous diseases: A retrospective cohort study
Authors: Hamidreza Mahmoudi, Ali Salehi Farid, Ali Nili, Dorsa Dayani, Soheil Tavakolpour, Tahereh Soori, Amir Teimourpour, Ahdie Isazade, Robabeh Abedini, Kamran Balighi, Maryam Daneshpazhooh
Journal: Journal of the American Academy of Dermatology (2020)
Landscape and Dynamics of the Transcriptional Regulatory Network During Natural Killer Cell Differentiation
Authors: Kun Li, Yang Wu, Young Li, Qiaoni Yu, Zhigang Tian, Haiming Wei, Kun Qu
Journal: Genomics Proteomics & Bioinformatics (2020)

Natural killer (NK) cells are essential in controlling cancer and infection. However, little is known about the dynamics of the transcriptional regulatory machinery during NK cell differentiation. In this study, we applied the assay of transposase accessible chromatin with sequencing (ATAC-seq) technique in a home-developed in vitro NK cell differentiation system. Analysis of ATAC-seq data illustrated two distinct transcription factor (TF) clusters that dynamically regulate NK cell differentiation. Moreover, two TFs from the second cluster, FOS-like 2 (FOSL2) and early growth response 2 (EGR2), were identified as novel essential TFs that control NK cell maturation and function. Knocking down either of these two TFs significantly impacted NK cell differentiation. Finally, we constructed a genome-wide transcriptional regulatory network that provides a better understanding of the regulatory dynamics during NK cell differentiation.
Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer
Authors: Nityam Rathi, Taylor Ryan McFarland, Roberto Nussenzveig, Neeraj Agarwal, Umang Swami
Journal: Drugs (2020)

Immunotherapies have shown remarkable success in the treatment of multiple cancer types; however, despite encouraging preclinical activity, registration trials of immunotherapy in prostate cancer have largely been unsuccessful. Sipuleucel-T remains the only approved immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer based on modest improvement in overall survival. This immune evasion in the case of prostate cancer has been attributed to tumor-intrinsic factors, an immunosuppressive tumor microenvironment, and host factors, which ultimately make it an inert 'cold' tumor. Recently, multiple approaches have been investigated to turn prostate cancer into a 'hot' tumor. Antibodies directed against programmed cell death protein 1 have a tumor agnostic approval for a small minority of patients with microsatellite instability-high or mismatch repair-deficient metastatic prostate cancer. Herein, we present an overview of the current immunotherapy landscape in metastatic castration-resistant prostate cancer with a focus on immune checkpoint inhibitors. We describe the results of clinical trials of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer; either as single agents or in combination with other checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, tyrosine kinase inhibitors, novel hormonal therapies, chemotherapies, and radioligands. Finally, we review upcoming immunotherapies, including novel monoclonal antibodies, chimeric-antigen receptor (CAR) T cells, Bi-Specific T cell Engagers (BiTEs), therapies targeting the adenosine pathway, and other miscellaneous agents.
Abstract 14770: Reduction With Evolocumab in Complex Coronary Disease Requiring Revascularization: Insights From the FOURIER Trial
Authors: Kazuma Oyama, Remo Furtado, Antonio Fagundes, Thomas A Zelniker, Minao Tang, Julia Kuder, Sabina A Murphy, Andrew Hamer, Huei Wang, Anthony C Keech, Terje R Pedersen, Robert Giugliano, Marc S Sabatine, Brian A Bergmark
Journal: Circulation (2020)

Introduction: Although PCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall, their ability to specifically reduce the risk of complex coronary atherosclerosis requiring revascularization has not been explored. Methods: FOURIER was a randomized trial of the PCSK9 inhibitor evolocumab vs. placebo in 27,564 patients with ASCVD on statin therapy (median achieved LDL-C 32 mg/dL vs. 89 mg/dL) followed for a median of 2.2 years. The study database was blindly reviewed to assess characteristics of coronary revascularization procedures. Complex revascularization was the composite of complex PCI (per GLOBAL LEADERS criteria, at least one of: multivessel PCI, 3 or more stents implanted, 3 or more lesions treated, bifurcation PCI with 2 or more stents, or total stent length &gt;60 mm) or CABG. PCI complications included no-reflow, side branch loss, thrombus formation, major dissection, or perforation. The effects of evolocumab on types of revascularization and PCI complications were evaluated using Cox proportional hazards models. Results: 1724 patients underwent revascularization procedures during follow-up. Evolocumab reduced the risk of non-complex PCI by 22% (HR 0.78; 95%CI 0.70-0.88; P&lt;0.001) and the risk of complex revascularization by 29% (HR 0.71; 95%CI 0.61-0.84; P&lt;0.001), including complex PCI by 33% (HR 0.67; 95%CI 0.54-0.84; P&lt;0.001) and CABG by 24% (HR 0.76; 95%CI 0.60-0.96; P=0.019; Figure). The incidence of reported PCI complications tended to be lower with evolocumab (HR 0.74; 95% CI 0.49-1.11). Conclusions: Adding evolocumab to statin therapy reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. Together with prior coronary imaging findings, these data suggest very aggressive LDL-C lowering to &lt;1 mmol/L has beneficial effects on coronary atherosclerosis burden, anatomical complexity, and the need for intervention.
Cytotoxic T-Lymphocyte–Associated Antigen-4
Authors: F. Stephen Hodi
Journal: Clinical Cancer Research (2007)

Abstract Previously, the development of immune-based therapies has primarily focused on vaccines and cytokines, yielding benefit in a small percentage of patients. Recent advances in our understanding of the function of costimulatory molecules have revitalized enthusiasm in the development of immune therapies for cancer. This family of proteins possesses properties involved in both lymphocyte activation and immune-inhibitory functions. The costimulatory molecule with the greatest translation into the clinic thus far is CTL-associated antigen-4 (CTLA-4). CTLA-4 engagement leads to T-cell inhibition by two principle mechanisms. The first involves competitive binding with CD28 for B7 on the antigen-presenting cell. The second is direct intracellular inhibitory signals mediated by the CTLA-4 cytoplasmic tail. Numerous clinical trials testing the blockade of CTLA-4 signaling with fully human monoclonal antibodies have treated a variety of cancers, with the most experience in the treatment of metastatic melanoma. Significant antitumor activity as well as potential autoimmune-related toxicities have been observed. Further clinical investigation with CTLA-4 blockade, planned clinical trials testing manipulation of other costimulatory molecules, and continued improvement in understanding of costimulatory pathways present a new era of immune therapies for cancer patients.
Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET
Authors: Marc Garcia-Moure, Marisol Gonzalez-Huarriz, Sara Labiano, Elizabeth Guruceaga, Eva Bandres, Marta Zalacain, Lucia Marrodan, Carlos de Andrea, Maria Villalba, Naiara Martinez-Velez, Virginia Laspidea, Montse Puigdelloses, Jaime Gallego Perez-Larraya, Ignacio Iñigo-Marco, Renata Stripecke, Jennifer A. Chan, Eric H. Raabe, Marcel Kool, Candelaria Gomez-Manzano, Juan Fueyo, Ana Patiño-García, Marta M. Alonso
Journal: Clinical Cancer Research (2020)

Atypical teratoid/rhabdoid tumors (AT/RT) and central nervous system primitive neuroectodermal tumors (CNS-PNET) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus, Delta-24-RGD, which selectively replicates in and kills tumor cells.
COVID-19 and Kidney Transplant Outcomes
Authors: Vinay Nair, Nicholas Jandovitz, Mersema Abate, Madhu C. Bhaskaran, Gayatri D. Nair, Ernesto P. Molmenti
Journal: Journal of the American Society of Nephrology (2020)

Nair, Vinay; Jandovitz, Nicholas; Abate, Mersema; Bhaskaran, Madhu C.; Nair, Gayatri D.; Molmenti, Ernesto P. Author Information
Fast and Robust Identity-by-Descent Inference with the Templated Positional Burrows–Wheeler Transform
Authors: William A Freyman, Kimberly F McManus, Suyash S Shringarpure, Ethan M Jewett, Katarzyna Bryc, Adam Auton
Journal: Molecular Biology and Evolution (2020)

Abstract Estimating the genomic location and length of identical-by-descent (IBD) segments among individuals is a crucial step in many genetic analyses. However, the exponential growth in the size of biobank and direct-to-consumer genetic data sets makes accurate IBD inference a significant computational challenge. Here we present the templated positional Burrows–Wheeler transform (TPBWT) to make fast IBD estimates robust to genotype and phasing errors. Using haplotype data simulated over pedigrees with realistic genotyping and phasing errors, we show that the TPBWT outperforms other state-of-the-art IBD inference algorithms in terms of speed and accuracy. For each phase-aware method, we explore the false positive and false negative rates of inferring IBD by segment length and characterize the types of error commonly found. Our results highlight the fragility of most phased IBD inference methods; the accuracy of IBD estimates can be highly sensitive to the quality of haplotype phasing. Additionally, we compare the performance of the TPBWT against a widely used phase-free IBD inference approach that is robust to phasing errors. We introduce both in-sample and out-of-sample TPBWT-based IBD inference algorithms and demonstrate their computational efficiency on massive-scale data sets with millions of samples. Furthermore, we describe the binary file format for TPBWT-compressed haplotypes that results in fast and efficient out-of-sample IBD computes against very large cohort panels. Finally, we demonstrate the utility of the TPBWT in a brief empirical analysis, exploring geographic patterns of haplotype sharing within Mexico. Hierarchical clustering of IBD shared across regions within Mexico reveals geographically structured haplotype sharing and a strong signal of isolation by distance. Our software implementation of the TPBWT is freely available for noncommercial use in the code repository (https://github.com/23andMe/phasedibd, last accessed January 11, 2021).
Blood-based kinase activity profiling: a potential predictor of response to immune checkpoint inhibition in metastatic cancer
Authors: Daan P Hurkmans, Els M E Verdegaal, Sabrina A Hogan, Rik de Wijn, Lies Hovestad, Dianne M A van den Heuvel, Rob Ruijtenbeek, Marij J P Welters, Mandy van Brakel, Edwin A Basak, Herbert M Pinedo, Cor H J Lamers, Harmen J G van de Werken, John P Groten, Reno Debets, Mitchell P Levesque, Reinhard Dummer, Ellen Kapiteijn, Ron H J Mathijssen, Joachim G J V Aerts, Sjoerd H van der Burg
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Many cancer patients do not obtain clinical benefit from immune checkpoint inhibition. Checkpoint blockade targets T cells, suggesting that tyrosine kinase activity profiling of baseline peripheral blood mononuclear cells may predict clinical outcome. Methods Here a total of 160 patients with advanced melanoma or non-small-cell lung cancer (NSCLC), treated with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) or anti-programmed cell death 1 (anti-PD-1), were divided into five discovery and cross-validation cohorts. The kinase activity profile was generated by analyzing phosphorylation of peripheral blood mononuclear cell lysates in a microarray comprising of 144 peptides derived from sites that are substrates for protein tyrosine kinases. Binary grouping into patients with or without clinical benefit was based on Response Evaluation Criteria in Solid Tumors V.1.1. Predictive models were trained using partial least square discriminant analysis (PLS-DA), performance of the models was evaluated by estimating the correct classification rate (CCR) using cross-validation. Results The kinase phosphorylation signatures segregated responders from non-responders by differences in canonical pathways governing T-cell migration, infiltration and co-stimulation. PLS-DA resulted in a CCR of 100% and 93% in the anti-CTLA-4 and anti-PD1 melanoma discovery cohorts, respectively. Cross-validation cohorts to estimate the accuracy of the predictive models showed CCRs of 83% for anti-CTLA-4 and 78% or 68% for anti-PD-1 in melanoma or NSCLC, respectively. Conclusion Blood-based kinase activity profiling for response prediction to immune checkpoint inhibitors in melanoma and NSCLC revealed increased kinase activity in pathways associated with T-cell function and led to a classification model with a highly accurate classification rate in cross-validation groups. The predictive value of kinase activity profiling is prospectively verified in an ongoing trial.
Red dichromatic imaging helps in detecting exposed blood vessels in gastric ulcer induced by endoscopic submucosal dissection
Authors: Shuichi Miyamoto, Ryo Sugiura, Satoshi Abiko, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Naoya Sakamoto
Journal: Endoscopy (2020)

Delayed bleeding is one of the postoperative complications of gastric endoscopic submucosal dissection (ESD) [1]. The clipping of exposed blood vessels after ESD completion is effective in preventing delayed bleeding [2] [3]. However, the exposed blood vessels are sometimes difficult to detect. Herein we report the effectiveness of a novel image-enhanced endoscopic technology called red dichromatic imaging (or dual red imaging) for detecting exposed blood vessels and preventing delayed bleeding after gastric ESD.
Is the Association Between Beverage Taxes and Reductions in Sales Driven by Communication of Health Consequences in Addition to Price Increases?
Authors: Anna H. Grummon, Christina A. Roberto, James W. Krieger
Journal: JAMA Network Open (2020)

August 2, 2017, Cook County, Illinois, became the sixth US jurisdiction to implement a sweetened beverage tax.Four months later, the county commissioners repealed the
Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials
Authors: Romain Cohen, Julien Taieb, Jack Fiskum, Greg Yothers, Richard Goldberg, Takayuki Yoshino, Steven Alberts, Carmen Allegra, Aimery de Gramont, Jean-Francois Seitz, Michael O'Connell, Daniel Haller, Norman Wolmark, Charles Erlichman, Alberto Zaniboni, Sara Lonardi, Rachel Kerr, Axel Grothey, Frank A. Sinicrope, Thierry André, Qian Shi
Journal: Journal of Clinical Oncology (2020)

In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain.Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors.MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses.Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.
NK-Cell Alloreactivity Is Associated with Acute Gvhd and Decreased Relapse Incidence after T-Replete Haplo-Identical Allotransplant with High-Dose Post-Transplant Cyclophosphamide
Authors: Christelle Retiere, Catherine Willem, Nolwenn Legrand, Thierry Guillaume, Katia Gagne, Pierre Peterlin, Alice Garnier, Marie C Bene, Amandine Le Bourgeois, Patrice Chevallier
Journal: Blood (2017)
Total body photography for the diagnosis of cutaneous melanoma in adults: a systematic review and meta‐analysis*
Authors: A. Ji‐Xu, J. Dinnes, R.N. Matin
Journal: British Journal of Dermatology (2020)

Early detection of melanoma is essential to reduce mortality. Total body photography (TBP) can facilitate the detection of melanoma in high-risk individuals. However, the accuracy of TBP in diagnosing melanoma remains unclear.To determine the diagnostic accuracy of TBP for the detection of melanoma in adults.MEDLINE, Embase, Cochrane and Centre for Reviews databases were searched from inception to 26 May 2020. Studies that included TBP for diagnosing melanoma with at least one follow-up appointment were eligible for inclusion in the systematic review if they provided data to calculate at least one diagnostic accuracy measure. Two authors independently screened articles, extracted data and assessed quality. Disagreements were resolved by a third reviewer.In total, 10 studies were included, comprising 41 703 patients who underwent TBP and 6203 biopsies. Melanoma in situ (MIS) was diagnosed in 315 (5·1%) lesions and invasive melanoma was diagnosed in 187 (3·0%) lesions biopsied. Summary estimates for TBP in diagnosing melanoma were calculated as follows: mean percentage of biopsies positive for MIS or melanoma was 15% [95% confidence interval (CI) 10-21], number needed to biopsy (NNB) was 8·6 (range 2·3-19·6), naevus : melanoma ratio was 7·6 (range 1·3-18·6), and MIS : melanoma ratio was 1·7 (1·0-3·5). Regression analysis showed a negative correlation between NNB and MIS : melanoma ratio.Available data regarding the diagnostic accuracy of TBP are heterogeneous, owing to variability in the risk profile of cohorts and TBP protocols. Best current estimates suggest that TBP for diagnosing melanoma has an acceptable NNB in high-risk patients. However, prospective diagnostic test accuracy studies are needed to gauge the diagnostic accuracy of TBP.
Plant roots employ cell-layer-specific programs to respond to pathogenic and beneficial microbes
Authors: Christian Fröschel, Jaqueline Komorek, Agnès Attard, Alexander Marsell, William A. Lopez-Arboleda, Joëlle Le Berre, Elmar Wolf, Niko Geldner, Frank Waller, Arthur Korte, Wolfgang Dröge-Laser
Journal: Cell Host & Microbe (2020)