tbuckley/cabot-search huggingface dataset:
Reciprocal Network between Cancer Stem-Like Cells and Macrophages Facilitates the Progression and Androgen Deprivation Therapy Resistance of Prostate Cancer
Authors: Hai Huang, Chao Wang, Fei Liu, Hui-Zhen Li, Guang Peng, Xu Gao, Ke-Qin Dong, Hong-Ru Wang, De-Pei Kong, Min Qu, Li-He Dai, Kai-Jian Wang, Zhe Zhou, Jun Yang, Ze-Yu Yang, Yan-Qiong Cheng, Qin-Qin Tian, Dan Liu, Chuan-Liang Xu, Dan-Feng Xu, Xin-Gang Cui, Ying-Hao Sun
Journal: Clinical Cancer Research (2018)

Purpose: Cancer stem-like cells (CSC) contribute to the progression and androgen deprivation therapy (ADT) resistance of prostate cancer. As CSCs depend on their specific niche, including tumor-associated macrophages (TAM), elucidating the network between CSCs and TAMs may help to effectively inhibit the progression and ADT resistance of prostate cancer.Experimental Design: The underlying intracellular mechanism that sustains the stem-like characteristics of CSCs in prostate cancer was assessed via RNA sequencing, co-immunoprecipitation, chromatin immunoprecipitation, and other assays. A coculture system and cytokine antibody arrays were used to examine the interaction network between CSCs and TAMs. In addition, an orthotopic prostate cancer model was established to evaluate the in vivo effects of the combined targeting of CSCs and their interaction with TAMs on ADT resistance.Results: Autophagy-related gene 7 (ATG7) facilitated the transcription of OCT4 via β-catenin, which binds to the OCT4 promoter, promoting CSC characteristics in prostate cancer, including self-renewal, tumor initiation, and drug resistance. In addition, CSCs remodeled their specific niche by educating monocytes/macrophages toward TAMs, and the CSC-educated TAMs reciprocally promoted the stem-like properties of CSCs, progression and ADT resistance of prostate cancer via IL6/STAT3. Furthermore, the combined targeting of CSCs and their interaction with TAMs by inhibiting ATG7/OCT4 and IL6 receptor effectively ameliorated ADT resistance in an orthotopic prostate cancer model.Conclusions: Targeting CSCs and their niche may prove to be a more powerful strategy than targeting CSCs alone, providing a rational approach to ameliorating ADT resistance in prostate cancer. Clin Cancer Res; 24(18); 4612-26. ©2018 AACR.
Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer
Authors: H. Wang, J. Agulnik, G. Kasymjanova, A. Wang, P. Jiménez, V. Cohen, D. Small, C. Pepe, L. Sakr, P.O. Fiset, M. Auger, S. Camilleri-Broet, M. Alam El Din, G. Chong, L. van Kempen, A. Spatz
Journal: Annals of Oncology (2018)

BackgroundPD-L1 immunohistochemistry (IHC) testing is usually carried out on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay.MethodsA total of 1419 consecutive cases of non-small-cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both. PD-L1 expression was examined by staining with Dako PD-L1 IHC 22C3 pharmDx kit. A Tumor Proportion Score (TPS) was categorized as <1%, 1%–49% and ≥50% tumor cells. A total of 100 viable tumor cells were required for adequacy.ResultsOf the cytology cell blocks, 92% of the specimens had an adequate number of tumor cells, not significantly different from small biopsies. The rate of TPS ≥50% differed between sample types and was observed in 42% of cytology cell blocks versus 36% of small biopsies (P = 0.04), and 29% of surgical resections (P = 0.001). The fixative methods did not affect the immunostaining, with overall PD-L1 high expression (TPS ≥50%) rates of 42% in formalin-fixed specimens versus 40% in specimens with combined fixation by methanol/alcohol and formalin (NS). The PD-L1 high expression rate was not associated with EGFR, ALK or KRAS molecular alterations. Higher stage (IV) was associated with higher PD-L1 TPS (P= 0.001).ConclusionOur results show that when the TPS ≥50% is used as the end point, PD-L1 IHC performs well with cytology cell blocks. Cell blocks should be considered as a valuable resource for PD-L1 testing in advanced NSCLC. The clinical significance of higher PD-L1 IHC scores in cytology specimens needs to be evaluated prospectively.
Extracorporeal CO<sub>2</sub> Removal May Improve Renal Function of Patients with Acute Respiratory Distress Syndrome and Acute Kidney Injury: An Open-Label, Interventional Clinical Trial
Authors: Vito Fanelli, Vincenzo Cantaluppi, Francesco Alessandri, Andrea Costamagna, Paola Cappello, Luca Brazzi, Francesco Pugliese, Luigi Biancone, Pierpaolo Terragni, V. Marco Ranieri
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Angiosarcoma of the scalp responding to nivolumab: a case report
Authors: S. Hofer, K. Zeidler, A. Schipf, W. Kempf, D. Zimmermann, S. Aebi
Journal: British Journal of Dermatology (2018)

Linked Comment:Wollina. Br J Dermatol 2018; 179:257–258.
Hypomethylation of <scp>CYP</scp>2E1 and <scp>DUSP</scp>22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients
Authors: Amanda Mok, Brooke Rhead, Calliope Holingue, Xiaorong Shao, Hong L. Quach, Diana Quach, Elizabeth Sinclair, Jonathan Graf, John Imboden, Thomas Link, Ruby Harrison, Vladimir Chernitskiy, Lisa F. Barcellos, Lindsey A. Criswell
Journal: Arthritis & Rheumatology (2017)

Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients.Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators.Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified.Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.
Ethnic differences in HCV-related HCC outcomes: Report from the Real-world Evidence by the Asia Pacific Rim Liver Consortium for HCC (REAL-HCC)
Authors: D. Prasad, P. Nguyen, J. Guy, M.-L. Yeh, J. Leong, J. Yang, W. Saeed, Y.-C. Hsu, P.-C. Tsai, C.-Y. Dai, J.-F. Huang, Y.-L. Chen, D.W. Jun, L. Roberts, M. Schwartz, M.-L. Yu, E. Gane, M. Nguyen
Journal: Journal of Hepatology (2018)
Epigenetic Regulation of CXCL12 Plays a Critical Role in Mediating Tumor Progression and the Immune Response In Osteosarcoma
Authors: Binghao Li, Zhan Wang, Hao Wu, Mingfeng Xue, Peng Lin, Shengdong Wang, Nong Lin, Xin Huang, Weibo Pan, Meng Liu, Xiaobo Yan, Hao Qu, Lingling Sun, Hengyuan Li, Yan Wu, Wangsiyuan Teng, Zenan Wang, Xingzhi Zhou, Huabiao Chen, Mark C. Poznansky, Zhaoming Ye
Journal: Cancer Research (2018)

Abstract The mechanism by which osteosarcomas metastasize is elusive, and challenges remain regarding its treatment with modalities including immunotherapy. CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12. Here, we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and to impair cytotoxic T-cell homing to the tumor site. Analysis of human osteosarcoma cases further revealed that CXCL12 expression strongly correlated with overall survival. Evaluations on fresh human chemotherapy-free osteosarcoma samples also showed a positive correlation between CXCL12 concentration and the number of intratumoral lymphocytes. Critically, treatment targeting DNMT1 in immunocompetent mouse models significantly elevated expression of CXCL12 in tumors, resulting in a robust immune response and consequently eradicating early lung metastases in addition to suppressing subcutaneous tumor growth. These antitumor effects were abrogated by CXCL12–CXCR4 blockade or CD8+ T-cell depletion. Collectively, our data show that CXCL12 regulation plays a significant role in both tumor progression and immune response, and targeting CXCL12 is promising for therapeutics against osteosarcoma. Significance: Epigenetic regulation of CXCL12 controls metastasis and immune response in osteosarcoma, suggesting epigenetic therapies or therapies targeting CXCL12 have potential for therapeutic intervention in osteosarcoma. Cancer Res; 78(14); 3938–53. ©2018 AACR.
Serum concentrations of Macrophage Migration Inhibitory Factor (MIF) and its soluble receptor CD74 predict transplant-free shortterm survival in patients with acute decompensation of liver cirrhosis
Authors: T. Wirtz, N. Köse, B. Irina, B. Christina, P. Fischer, S. Stengel, Z.H. Wolfgang, K. Ingo, J. Bernhagen, C. Trautwein, A. Stallmach, M.-L. Berres, T. Bruns
Journal: Journal of Hepatology (2018)
Doctors need to give up professional protectionism
Authors: Clifford Mann
Journal: BMJ (2018)

The need for the medical profession to protect its role was, until recently, deemed essential. The notion that others might take on some tasks traditionally thought of as being “doctors’ roles” was regarded as an existential risk to the medical profession.

Medical societies, colleges, unions, and regulators approached proposals of clinical practice by other health professionals with deep suspicion. Concerns were often couched hubristically in terms of patient safety. But the prime motive was a fear that the profession would be diminished in size and stature.

If there were a shortage of work for doctors to do, then such attitudes would be a rational response. But these protectionist attitudes persisted long after the workload per doctor had become excessive. They have continued even when doctors’ workloads have become impossible. New clinician roles have not arisen out of some grand plot to do doctors down but from the need to deal with the workload crisis.

A junior doctor is a pluripotential clinician, …
TRAF1 Is Critical for Regulating the BRAF/MEK/ERK Pathway in Non–Small Cell Lung Carcinogenesis
Authors: Qiushi Wang, Ge Gao, Tianshun Zhang, Ke Yao, Hanyong Chen, Mi Hee Park, Hiroyuki Yamamoto, Keke Wang, Weiya Ma, Margarita Malakhova, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2018)

Abstract Tumor necrosis factor receptor (TNFR)–associated factor 1 (TRAF1) is a unique TRAF protein that can interact directly or indirectly with multiple TNFR family members, regulatory proteins, kinases, and adaptors that contribute to its diverse functions in specific tissues. However, the role of TRAF1 in non–small cell lung cancer (NSCLC) remains unknown. In this study, we report that TRAF1 is overexpressed in human lung cancer cells and tissues. TRAF1 expression level inversely correlated with patient survival probability. Loss of TRAF1 decelerated tumor invasion in a urethane-induced lung carcinogenesis mouse model. Furthermore, TRAF1 expression affected TRAF2-mediated BRAF Lys48–linked ubiquitination, which was followed by the inhibition of growth and differentiation, and the induction of death in lung cancer cells. Overall, our work suggests that TRAF1 plays a novel role in the regulation of the BRAF/MEK/ERK signaling pathway in NSCLC and offers a candidate molecular target for lung cancer prevention and therapy. Significance: These findings identify TRAF1 as a new therapeutic target for NSCLC. Cancer Res; 78(14); 3982–94. ©2018 AACR.
FOXM1 is a critical driver of lung fibroblast activation and fibrogenesis
Authors: Loka R. Penke, Jennifer M. Speth, Vijaya L. Dommeti, Eric S. White, Ingrid L. Bergin, Marc Peters-Golden
Journal: Journal of Clinical Investigation (2018)

While the transcription factor forkhead box M1 (FOXM1) is well known as a proto-oncogene, its potential role in lung fibroblast activation has never been explored. Here, we show that FOXM1 is more highly expressed in fibrotic than in normal lung fibroblasts in humans and mice. FOXM1 was required not only for cell proliferation in response to mitogens, but also for myofibroblast differentiation and apoptosis resistance elicited by TGF-β. The lipid mediator PGE2, acting via cAMP signaling, was identified as an endogenous negative regulator of FOXM1. Finally, genetic deletion of FOXM1 in fibroblasts or administration of the FOXM1 inhibitor Siomycin A in a therapeutic protocol attenuated bleomycin-induced pulmonary fibrosis. Our results identify FOXM1 as a driver of lung fibroblast activation and underscore the therapeutic potential of targeting FOXM1 for pulmonary fibrosis.
Preclinical and first-in human development of SGM-1019, a first-in-class novel small molecule modulator of inflammasome activity for the treatment of nonalcoholic steatohepatitis (NASH)
Authors: K. Dabbagh, G. Steven Dodson, L. Yamamoto, B. Baeza-Raja, A.W. Goodyear
Journal: Journal of Hepatology (2018)
A Bizarre Bone Scan of Fibrodysplasia Ossificans Progressiva
Authors: Tzyy-Ling Chuang, Kuo-Wei Ho, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2018)

A 27-year-old woman had progressive bony ankylosis over both hands since she was 5 years old. Bony ankylosing over the peripheral joints and spine slowly progressed, and scoliosis surgery was performed at age 14. Recently, she developed difficulty walking, changing position, and opening her mouth. A neurologist was consulted and ruled out the suspicion of narcolepsy. Chest CT showed ankylosing spondylitis. A bone scan showed a bizarre pattern with radiouptake to the left maxilla, bilateral sacroiliac joints, left middle third femur, and soft tissue uptake over bilateral arms, legs, and pelvis. Regional radiograph suggested fibrodysplasia ossificans progressiva.
The role of SOD, CAT and CYP1A1/1A2 in human gastric neoplasm.
Authors: Marta Monari, Jurgen Foschi, Carlo Calabrese, Anna Fabbri, D. Zahalane, Giulio Di Febo, Vitaliano Tugnoli, M. R. Tosi, Andrea Trinchero, Gian Paolo Serrazanetti
Journal: Gut (2006)
Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia
Authors: Joseph A. Fraietta, Simon F. Lacey, Elena J. Orlando, Iulian Pruteanu-Malinici, Mercy Gohil, Stefan Lundh, Alina C. Boesteanu, Yan Wang, Roddy S. O’Connor, Wei-Ting Hwang, Edward Pequignot, David E. Ambrose, Changfeng Zhang, Nicholas Wilcox, Felipe Bedoya, Corin Dorfmeier, Fang Chen, Lifeng Tian, Harit Parakandi, Minnal Gupta, Regina M. Young, F. Brad Johnson, Irina Kulikovskaya, Li Liu, Jun Xu, Sadik H. Kassim, Megan M. Davis, Bruce L. Levine, Noelle V. Frey, Donald L. Siegel, Alexander C. Huang, E. John Wherry, Hans Bitter, Jennifer L. Brogdon, David L. Porter, Carl H. June, J. Joseph Melenhorst
Journal: Nature Medicine (2018)
Revisiting Blood Safety Practices Given Emerging Data about Zika Virus
Authors: Evan M. Bloch, Paul M. Ness, Aaron A.R. Tobian, Jeremy Sugarman
Journal: New England Journal of Medicine (2018)

Zika Virus and Blood-Product Safety The rapid emergence and dissemination of Zika virus across the Americas over the past 2 years has aroused serious concern regarding the safety of blood transfusion. The authors discuss the challenges associated with securing blood-product safety.
Extension of French vaccination mandates: from the recommendation of the Steering Committee of the Citizen Consultation on Vaccination to the law
Authors: Daniel Lévy-Bruhl, Jean-Claude Desenclos, Sylvie Quelet, François Bourdillon
Journal: Eurosurveillance (2018)

On 4 December 2017, French parliamentarians passed a law extending the vaccination mandates for children up to 2 years of age from three vaccinations (against diphtheria, tetanus and poliomyelitis) to 11 by adding vaccinations against pertussis, Haemophilus influenza b (Hib), hepatitis B, pneumococcal diseases, meningococcal C diseases, measles, mumps and rubella. This vote follows a recommendation made by the Steering Committee of the Citizen Consultation on Vaccination that took place in 2016. The law applies to all children born after 1 January 2018. Parents who do not fulfil the mandate will not be fined but non-vaccinated children will not be admitted to any collective child services such as nurseries or schools. No exemption other than for medical reasons will be considered. Here we describe the historical background of this evolution and its main epidemiological, sociological and policy drivers. They mainly refer to insufficient vaccine coverage, persistence of a preventable burden for some diseases and growing vaccine hesitancy in the French population. We also discuss some of the challenges and conditions of success.
Designing effective graphs to get your message across
Authors: Maarten Boers
Journal: Annals of the Rheumatic Diseases (2018)

Research is of little use if its results are not effectively communicated. Data visualised in graphs (and tables) are key components in any scientific report, but their design leaves much to be desired. This viewpoint focuses on graph design, following two general principles: clear vision and clear understanding. Clear vision is achieved by maximising the signal to noise ratio. In a graph, the signal is the data in the form of symbols, lines or other graphic elements, and the noise is the support structure necessary to interpret the data. Clear understanding is achieved when the story in the data is told effectively, through organisation of the data and use of text. These principles are illustrated by original and improved graphs from recent publications, completed by tutorial material online (appendices, web pages and film clips). The popular matrix form (multiple graphs in one frame) is discussed as a special case. Differences between publication (including the proofing stage) and presentation are outlined. Suggestions are made for better peer review and processing of graphs in the publication stage.
An orthotopic glioblastoma animal model suitable for high-throughput screenings
Authors: Linda Pudelko, Steven Edwards, Mirela Balan, Daniel Nyqvist, Jonathan Al-Saadi, Johannes Dittmer, Ingrid Almlöf, Thomas Helleday, Lars Bräutigam
Journal: Neuro-Oncology (2018)

Abstract Background Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies, and clinically relevant orthotopic zebrafish models have been developed. However, currently available GBM orthotopic zebrafish models do not support high-throughput drug discovery screens. Methods We transplanted both GBM cell lines as well as patient-derived material into zebrafish blastulas. We followed the behavior of the transplants with time-lapse microscopy and real-time in vivo light-sheet microscopy. Results We found that GBM material transplanted into zebrafish blastomeres robustly migrated into the developing nervous system, establishing an orthotopic intracranial tumor already 24 hours after transplantation. Detailed analysis revealed that our model faithfully recapitulates the human disease. Conclusion We have developed a robust, fast, and automatable transplantation assay to establish orthotopic GBM tumors in zebrafish. In contrast to currently available orthotopic zebrafish models, our approach does not require technically challenging intracranial transplantation of single embryos. Our improved zebrafish model enables transplantation of thousands of embryos per hour, thus providing an orthotopic vertebrate GBM model for direct application in drug discovery screens.
TIPS placement improves sarcopenia and modifies fat distribution: A monocentric retrospective study
Authors: F. Artru, M. Xavier, A. Mustapha, N. Amelie, T. Pierre, E. Olivier, G. Lassailly, S. Dharancy, S. Geraldine, P. Mathurin, A. Louvet
Journal: Journal of Hepatology (2018)
Temporal changes in recurrent incidences after curative therapies in early stage hepatocellular carcinoma
Authors: A. Kurosugi, S. Ogasawara, Y. Ooka, M. Inoue, T. Chiba, E. Suzuki, M. Yokoyama, T. Maeda, T. Wakamatsu, K. Kobayashi, S. Kiyono, M. Nakamura, T. Saito, S. Nakamoto, S. Yasui, A. Tawada, M. Arai, T. Kanda, H. Maruyama, S. Kuboki, M. Miyazaki, O. Yokosuka, M. Ohtsuka, N. Kato
Journal: Journal of Hepatology (2018)
Neural Circuits of Sexual Behavior in <i>Caenorhabditis elegans</i>
Authors: Scott W. Emmons
Journal: Annual Review of Neuroscience (2018)

The recently determined connectome of the Caenorhabditis elegans adult male, together with the known connectome of the hermaphrodite, opens up the possibility for a comprehensive description of sexual dimorphism in this species and the identification and study of the neural circuits underlying sexual behaviors. The C. elegans nervous system consists of 294 neurons shared by both sexes plus neurons unique to each sex, 8 in the hermaphrodite and 91 in the male. The sex-specific neurons are well integrated within the remainder of the nervous system; in the male, 16% of the input to the shared component comes from male-specific neurons. Although sex-specific neurons are involved primarily, but not exclusively, in controlling sex-unique behavior-egg-laying in the hermaphrodite and copulation in the male-these neurons act together with shared neurons to make navigational choices that optimize reproductive success. Sex differences in general behaviors are underlain by considerable dimorphism within the shared component of the nervous system itself, including dimorphism in synaptic connectivity.
Abstract 18035: Left Ventricular Remodeling After Long-term Right Ventricular Pacing is Predicted by Electrical and Mechanical Dyssynchrony, but not Pacing Site
Authors: Ngai Y Chan, Ho C Yuen, Chi C Choy, Ngai S Mok, Chee W Wu, Ping T Tsui, Chun L Lau, Ying K Lo, Pui S Chu, Hoi F Chow, Yan Y Cheung, Suet T Lau
Journal: Circulation (2010)

Introduction: Long-term right ventricular apical (RVA) pacing has been shown to cause adverse left ventricular (LV) remodeling and clinical outcomes. We investigated the predictors of LV remodeling...
ACC inhibitor demonstrates potent anti-fibrotic activity in vitro and in vivo
Authors: J. Bates, S. Ghoshal, L. Wei, D. Hollenback, K. Liu, S. Kusam, M. Sulfab, H. Liu, R. Brockett, D. Newstrom, I. Mikaelian, T. Wang, G. Harriman, W.F. Westlin, J. Rocnik, H.J. Harwood, R. Kapeller, A. Ray, D. Breckenridge, B.C. Fuchs
Journal: Journal of Hepatology (2018)