tbuckley/cabot-search huggingface dataset:
Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation
Authors: Andrea-Hermina Györfi, Alexandru-Emil Matei, Maximilian Fuchs, Chunguang Liang, Aleix Rius Rigau, Xuezhi Hong, Honglin Zhu, Markus Luber, Christina Bergmann, Clara Dees, Ingo Ludolph, Raymund E. Horch, Oliver Distler, Jiucun Wang, Bertram Bengsch, Georg Schett, Meik Kunz, Jörg H.W. Distler
Journal: The Journal of Experimental Medicine (2021)

Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) is reexpressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and in turn, EN1 mediates the profibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a profibrotic gene expression profile functionally related to cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the reorganization of cytoskeleton during myofibroblast differentiation, in both standard fibroblast culture systems and in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis.
Could intraurethral dexpanthenol be used as a scar-modulating agent post urethroplasty? An experimental study
Authors: M. Hassaan, A. Elkashef, N. Barakat, A. Awadalla, A. Hashem, M. Soltan, F. El-Seddawy, M. Abdel-Maboud
Journal: European Urology (2021)
Anti-inflammatory Agents for Breast Cancer
Authors: Wendy Y. Chen, Jennifer A. Ligibel
Journal: JAMA Oncology (2021)

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Renal functional outcomes at 5 years from radical and partial nephrectomies in normal renal function patients: An untold story of hyperfiltrations
Authors: F. Trevisani, F. Di Marco, G. Rosiello, F. Fiorio, A. Cinque, A. Bettiga, A. Larcher, G. Fallara, D. Cignoli, G. Basile, I. Rowe, D. Canibus, U. Capitanio, A. Salonia, F. Montorsi
Journal: European Urology (2021)
Abstract 16493: Live-Video-Supervised Exercise and Diet Intervention in Pediatric Heart Transplant Patients
Authors: Angela Chen, David Rosenthal, Faustine Ramirez, Katie Jo Stauffer, Samuel Berry, Jerrid Brabender, Nancy McDonald, Donna Lee, Lynsey Barkoff, Susan Nourse, Jeffrey Kazmucha, C. Jason Wang, Inger Olson, Sarah Couch, Elif Seda S Selamet Tierney
Journal: Circulation (2018)

Background: Pediatric heart transplant patients have high-risk cardiovascular profiles that can affect their long-term outcomes. However, non-medical cardiovascular preventive care has not been a m...
Abstract 1153: Targeting CA125 transcription for ovarian cancer treatment
Authors: Er Yue, Guangchao Yang, Yuanfei Yao, Guangyu Wang, Yanqiao Zhang, Edward W. Wang
Journal: Cancer Research (2021)

Abstract CA125 coded by MUC16 gene is highly expressed in most ovarian cancer cells and serves as a tumor marker to monitor disease progression or response to treatment of ovarian cancer patients. However, targeting CA125 for ovarian cancer treatment has never been successful. We performed multiple steps of high-fidelity PCR and obtained a 4.2kb DNA fragment upstream of the human MUC16 gene, which included a region upstream from the transcription start site (TSS) and a region downstream from the TSS that contains both the 5' untranslated region and the first 136bp of the open reading frame. Reporter assays showed that this DNA fragment possesses strong transactivation activity in CA125-high cancer cells, but not in CA125-low cells, indicating that the DNA fragment we cloned contains the transactivation region that controls specific expression of MUC16 gene in ovarian cancer cells. We further refined the promoter and found a 1040bp fragment with similar transcriptional activity and specificity. We used this refined MUC16 promoter to replace the E1A promoter in the adenovirus type 5 genome DNA to control expression of E1A, an essential gene for adenovirus replication, and successfully generated a conditionally replication-competent adenovirus that can replicate in and lyse CA125-high-expressing cancer cells, including CAOV3, Kuramochi, MADH2774, OVCAR3, OVCAR4, and TOV112D cells, but not in CA125-low or -negative cancer cell lines, such as A2780, OVCAR5, PEO4, or SKOV3 cells. In vivo studies showed that intraperitoneal virus injection prolonged survival of NSG mice inoculated intraperitoneally with MADH2774 cells. Preliminary experiment showed that a mouse ovarian cancer cell line, ID8, infected with the virus might elicit a protective immune response to rechallenge of parental cancer cells. Our data indicate that targeting MUC16 transactivation for ovarian cancer treatment by conditionally replicative adenovirus development is feasible and practical. Citation Format: Er Yue, Guangchao Yang, Yuanfei Yao, Guangyu Wang, Yanqiao Zhang, Edward W. Wang. Targeting CA125 transcription for ovarian cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1153.
Abstract 2732: Multiplexed immunohistochemistry and deep learning: a new approach to spatially map the tumor microenvironment
Authors: Kouther Noureddine, Paul Gallagher, Martial Guillaud, Calum MacAulay
Journal: Cancer Research (2021)

Abstract The usual standard of care for assessing if a patient has cancer, its stage and its likely future biological behavior is visual examination of one or more H&amp;E and/or Immunohistochemistry(IHC) stained sections. The paradigm of digital pathology has changed, moving from single-marker IHC towards multiplexed labeling, increasing the need for more advanced techniques that can be easily integrated in routine clinical pathology. Although recent advances in multiple immunostaining have enabled characterization of several parameters on a single tissue section. For a higher dimensional chromogen based methodology, we have developed a multiplexed IHC procedure combining multiple labels per round, enabling analysis of complex immune cell population's on a single slide through consecutive cycles of staining, destaining, hyperspectral imaging and spectral unmixing of the chromogen biomarkers in each round. Not only does this allow us to completely visualize and spatially map the tumor microenvironment(TME), but through the application of AI we can further recognize common histological features present in the tissue. Robust, accurate, segmentation of cell nuclei for overlapping nuclei is one of the most significant unsolved issues in digital pathology. Analyzing the cell-cell interactions between immune and tumor cells and identifying clinically relevant patterns may improve patient outcomes while informing on the likelihood of success of possible treatments. By combining a multiplexed IHC technique which enables the detection of multiple markers on a single slide with deep learning segmentation methods to segment every individual cell nuclei in tissue sections with an accuracy comparable to human annotation, we can improve the accuracy of tissue classification based upon the measured characteristics of these cells and their spatial organization. The two techniques joined can be scaled up to the entire tissue section level, providing an accurate spatial cell level representation of the tissue. Citation Format: Kouther Noureddine, Paul Gallagher, Martial Guillaud, Calum MacAulay. Multiplexed immunohistochemistry and deep learning: a new approach to spatially map the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2732.
Analysis of T‐cell responses directed against the spike and/or membrane and/or nucleocapsid proteins in patients with chilblain‐like lesions during the COVID‐19 pandemic
Authors: C. Cassius, M. Merandet, L. Frumholtz, D. Bergerat, A. Samri, C. Grolleau, L. Grzelak, O. Schwartz, N. Yatim, P. Moghadam, L. Jaume, M. Bagot, J. Legoff, C. Delaugerre, J.‐D. Bouaziz, H. Le Buanec
Journal: British Journal of Dermatology (2021)

Analysis of T-cell responses directed against the spike and/or membrane and/or nucleocapsid proteins in patients with chilblain-like lesions during the COVID-19 pandemic
Abstract 14893: Obesity and Heart-Healthy Dietary Choices in Severe Aortic Stenosis
Authors: Zachary Taylor, Mathew Williams, Zhen-Gang Zhao, Run Du, Cezar Staniloae, Muhamed Saric, Illya Pushkar, Peter Neuburger, Michael Querijero, Alan Vainrib, Kazuhiro Hisamoto, Nicholas Amoroso, Tara Collins, Emily Clark, Danielle Sin, Binita Shah, Hanah Lee, Samantha Vidal, Daniel Bamira, Ricardo Benenstein, Hasan Jilaihawi
Journal: Circulation (2018)

Introduction: Little has been reported on dietary choices and obesity in patients with valvular heart disease. Hypothesis: We hypothesized that obesity is prevalent in patients with aortic stenosis...
Abstract 370: Smoking history as an independent predictor for immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC)
Authors: Xinan Wang, Biagio Ricciuti, Joao V. Alessi, Tom Nguyen, Mark M. Awad, Xihong Lin, Bruce E. Johnson, David C. Christiani
Journal: Cancer Research (2021)

Abstract Importance: Immune Checkpoint Inhibitors (ICIs) induce durable response in a subset of non-small cell lung cancer (NSCLC) patients. There is an unmet need to develop effective predictors for ICIs in metastatic NSCLC. Objective: Define the predictive impact of smoking history (pack-years) on the clinical outcomes of ICI monotherapy and further to validate the potential clinical utility in metastatic NSCLC. Design, setting, and participants: This study was conducted on 680 metastatic NSCLC patients treated with ICIs between April 2013 and September 2020 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital. Patient TMB and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) were determined by clinical targeted Next Generation Sequencing (NGS) and immunohistochemistry (IHC) and detailed smoking history and clinicopathological characteristics were prospectively collected. Main outcomes and measures: Evaluation of the association of smoking pack-years with objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients treated with ICI monotherapy. Assessment of time-dependent area under the curve (AUC) for predictive models of clinical outcomes. Results: Among 680 metastatic NSCLC patients who received ICI monotherapy: 109 (16.0%) never smokers, 397 (58.4%) former smokers [median 30 pack-years], and 174 (25.6%) current smokers [median 40 pack-years]. Multivariable analysis suggested that doubling of smoking pack-years is significantly associated with better clinical outcomes of ICIs. (ORR OR = 1.20, P &amp;lt; 0.001; PFS HR = 0.92, P &amp;lt; 0.001; OS HR = 0.94, P = 0.01) Predictive models incorporating smoking pack-years yielded additional information and achieved similar model performance compared to the one using TMB. Conclusions and Relevance: This finding suggests that detailed smoking information has a significant predictive value on clinical outcomes of ICI monotherapy independent of PD-L1 TPS. Smoking pack-years could serve as a non-invasive and consistent surrogate for TMB when it is not readily available for treatment-decision in metastatic NSCLC. Citation Format: Xinan Wang, Biagio Ricciuti, Joao V. Alessi, Tom Nguyen, Mark M. Awad, Xihong Lin, Bruce E. Johnson, David C. Christiani. Smoking history as an independent predictor for immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 370.
Mortality Among Persons Entering HIV Care Compared With the General U.S. Population
Authors: Jessie K. Edwards, Stephen R. Cole, Tiffany L. Breger, Jacqueline E. Rudolph, Lindsey M. Filiatreau, Kate Buchacz, Elizabeth Humes, Peter F. Rebeiro, Gypsyamber D’Souza, M. John Gill, Michael J. Silverberg, W. Christopher Mathews, Michael A. Horberg, Jennifer Thorne, H. Irene Hall, Amy Justice, Vincent C. Marconi, Viviane D. Lima, Ronald J. Bosch, Timothy R. Sterling, Keri N. Althoff, Richard D. Moore, Michael Saag, Joseph J. Eron
Journal: Annals of Internal Medicine (2021)

Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population.To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time.Observational cohort study.Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design.82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics.Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function.Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017.Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors.Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population.National Institutes of Health.
Abstract 545: Detection of liver-derived hepatitis B virus-host junction sequences in urine of hepatitis B infected patients for noninvasive disease monitoring
Authors: Selena Lin, Yu-lan Kao, Robin Su, Ting-Tsung Chang, Yih-Jyh Lin, Yixiao Cui, Hie-Won Hann, Grace Park, Wei Song, Ying-Hsiu Su
Journal: Cancer Research (2021)

Abstract Integrated hepatitis B virus (HBV) DNA detected in more than 85% of HBV-infected hepatocellular carcinoma (HBV-HCC) can cause insertional mutagenesis, chromosomal instability, sustained viral protein expression, and/or immune-mediated inflammation leading to HCC carcinogenesis. An opportunistic outcome of HBV DNA integration events, which occur randomly into the host genome, is the creation of a unique HBV-host junction sequence (HBV-JS) in individually infected hepatocytes representing a specific molecular signature of that cell. A noninvasive approach to detect HBV-JS's will enable frequent monitoring and aid in assessing HBV treatment efficacy and HCC disease progression. Here, we assessed the feasibility of detecting HBV-JS's in urine of HBV-infected patients as a proof-of-concept for utilizing urine as a noninvasive HBV-JS liquid biopsy for HBV-related disease monitoring. Utilizing an in-house developed HBV primer extension capture (PEC) NGS assay, we assessed early-stage HBV-patient tumor tissue and matched urine (n=8). Five of 8 urine samples contained detectable HCC tissue-derived HBV-JS's, including a TERT junction sequence. Next, we assessed 32 urine specimens collected from 28 HBV-infected patients including hepatitis (n=5), cirrhosis (n=11), HCC (n=4), and post-HCC (n=8). Interestingly, all urine samples contained HBV-JS sequences with 30 of 32 urines containing integrations in gene-coding regions. Of 351 unique HBV-JS in gene-coding regions identified in urine, 11 HBV-JS's have also been previously reported in tissue of HCC patients, including TERT. All eleven HBV-JS's were identified in cirrhosis or HCC patient cohorts. Furthermore, the distribution of urinary integrated HBV DNA in the HBV genome in all disease categories was found predominantly clustered in HBV DR1-2 (&amp;gt;70%), an integration hotspot, consistent with findings in tissue. Altogether this support the potential of urine as a noninvasive HBV-JS liquid biopsy to monitor HBV-infected patients for disease progression and treatment efficacy. Citation Format: Selena Lin, Yu-lan Kao, Robin Su, Ting-Tsung Chang, Yih-Jyh Lin, Yixiao Cui, Hie-Won Hann, Grace Park, Wei Song, Ying-Hsiu Su. Detection of liver-derived hepatitis B virus-host junction sequences in urine of hepatitis B infected patients for noninvasive disease monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 545.
Presence of Rare Germline Variants in Fanconi Anaemia Pathway Genes Confers a Poor Prognosis Comparable to TP53 Mutations in Therapy-Related Myeloid Neoplasms
Authors: Deepak Singhal, Amilia Wee, Wendy Parker, Sarah Moore, Milena Babic, Jinghua Feng, Andreas Schreiber, Joel Goeghegan, Monika M Kutyna, Rakchha Chhetri, Peter Bardy, Shriram V Nath, Nimit Singhal, Raghvendra Gowda, Luen Bik To, Richard D'Andrea, David M Ross, Ian D Lewis, Christopher N Hahn, Hamish S Scott, Devendra K Hiwase
Journal: Blood (2017)
Abstract 1632: Antibody mediated crosslinking of CD38 triggers costimulatory signaling and promotes T cell effector function
Authors: Mun Kyung Hwang, Anlai Wang, Zhili Song, Shujia Dai, Bailin Zhang, Joachim Theilhaber, Lily Pao, Dmitri Wiederschain, Chen Zhu
Journal: Cancer Research (2021)

Abstract CD38 is a multi-functional ecto-enzyme that regulates NAD+ metabolism. Monoclonal antibodies against CD38, including daratumumab and isatuximab have been successfully developed to treat patients with multiple myeloma, a cancer known to express high levels of CD38. However, CD38 is also expressed by normal immune cells, including B, NK, myeloid and T cell subsets. Using monoclonal antibodies against CD38, we show that CD38 crosslinking can augment T cell antigen receptor signaling, leading to enhanced T cell proliferation and cytokine production. Gene profiling analysis supports the contention that anti-CD38 ligation promotes T cell activation. Studies of CD38 mutants demonstrate that the co-stimulatory effect of anti-CD38 is independent of the ecto-enzymatic activity of CD38. Further analysis of activated CD4 T cells by mass spectrometry shows that CD38 is in close proximity with multiple adhesion and co-stimulatory molecules, including LFA-1, ICOS and OX40. These data support a role for CD38 as a co-stimulatory molecule in T cells, independent of its enzymatic activity. Citation Format: Mun Kyung Hwang, Anlai Wang, Zhili Song, Shujia Dai, Bailin Zhang, Joachim Theilhaber, Lily Pao, Dmitri Wiederschain, Chen Zhu. Antibody mediated crosslinking of CD38 triggers costimulatory signaling and promotes T cell effector function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1632.
The Prognostic Role of <i>MYC</i> Structural Variants Identified by NGS and FISH in Multiple Myeloma
Authors: Neeraj Sharma, James B. Smadbeck, Nadine Abdallah, Cinthya Zepeda-Mendoza, Moritz Binder, Kathryn E. Pearce, Yan W. Asmann, Jess F. Peterson, Rhett P. Ketterling, Patricia T. Greipp, P. Leif Bergsagel, S. Vincent Rajkumar, Shaji K. Kumar, Linda B. Baughn
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Structural variants (SV) of the MYC gene region are common in multiple myeloma and influence disease progression. However, the prognostic significance of different MYC SVs in multiple myeloma has not been clearly established. Experimental Design: We conducted a retrospective study of multiple myeloma comparing MYC SV subtypes identified by next-generation sequencing (NGS) and FISH to MYC expression and disease survival using 140 cases from Mayo Clinic and 658 cases from the MMRF CoMMpass study. Results: MYC SVs were found in 41% of cases and were classified into nine subtypes. A correlation between the presence of a MYC SV and increased MYC expression was identified. Among the nine MYC subtypes, the non-immunoglobulin (non-Ig) insertion subtype was independently associated with improved outcomes, while the Ig insertion subtype, specifically involving the IgL gene partner, was independently associated with poorer outcomes compared with other MYC SV subtypes. Although the FISH methodology failed to detect approximately 70% of all MYC SVs, those detected by FISH were associated with elevated MYC gene expression and poor outcomes suggesting a different pathogenic role for FISH-detected MYC subtypes compared with other MYC subtypes. Conclusions: Understanding the impact of different MYC SVs on disease outcome is necessary for the reliable interpretation of MYC SVs in multiple myeloma. NGS approaches should be considered as a replacement technique for a more comprehensive evaluation of the multiple myeloma clone.