tbuckley/cabot-search huggingface dataset:
Abstract A34: Effect of microvesicles on metalloproteinases secretion by myoepithelial cells
Authors: Gabriel Bernardo Rena, Lucas Novaes Teixeira, Vera Cavalcanti Araújo, Ana Paula Dias Demasi, Elizabeth Ferreira Martinez
Journal: Clinical Cancer Research (2020)

Abstract In tumorigenesis, not only genetic and epigenetic alterations but also stromal cells and soluble factors in the tumor microenvironment can affect the progression of different neoplasms. In salivary gland tumors derived from the intercalated duct, the myoepithelial (Myo) component modulates the neoplastic phenotype positively. Indeed, in carcinoma ex-pleomorphic adenoma (CXPA) where the malignant component is represented only by epithelial cells, the Myo cells present a role in the progression of this neoplasia. Nevertheless, great interest has been taken in the mechanisms of cellular communication mediated by microvesicles (MV). These structures are secreted by different cells and may induce epigenetic modifications. In malignant neoplasia, MV may affect different stages of carcinogenesis, which comprise the modulation of the extracellular matrix components, including metalloproteinases (MMPs). MMPs 2 and 9 exert an essential role in the epithelial-mesenchymal transition, consequently increasing the potential of migration and invasion of plethora tumors, including CXPA. The present in vitro study aimed to characterize MV derived from malignant neoplastic epithelial cell cultures (CAL27 cells) and their effect on the expression of MMPs in benign Myo cell cultures. Malignant epithelial cells (CAL 27 cell line) were cultured until they reached confluence. Then, the culture medium was collected and the MV were extracted. The Myo cultures, derived from pleomorphic adenomas explants, were exposed to MV from CAL 27 for 24 h. After this period, the secretion of MMPs 2, 9 and their inhibitors, TIMP-1 and TIMP-2, was assayed by means of ELISA. The Myo cultures not exposed to MV were used as control. The results indicated that Myo exposed to MV exhibited a significant increase of MMP-2 and MMP-9 expression (p&amp;lt;0.05) and a reduction in TIMP-2 expression (p&amp;lt;0.05). TIMP-1 expression in Myo cultures was not affected by MV (p&amp;gt;0.05). In conclusion, the data suggest that MV can modulate MMP and their inhibitors’ expression in Myo cell, which may promote extracellular matrix degradation and CXPA invasion. Citation Format: Gabriel Bernardo Rena, Lucas Novaes Teixeira, Vera Cavalcanti Araújo, Ana Paula Dias Demasi, Elizabeth Ferreira Martinez. Effect of microvesicles on metalloproteinases secretion by myoepithelial cells [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A34.
Time to End “Manels” in Clinical Trial Leadership
Authors: Tracy Y. Wang, Jacqueline Talea DesJardin
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Probable Evidence of Fecal Aerosol Transmission of SARS-CoV-2 in a High-Rise Building
Authors: Min Kang, Jianjian Wei, Jun Yuan, Juxuan Guo, Yingtao Zhang, Jian Hang, Yabin Qu, Hua Qian, Yali Zhuang, Xuguang Chen, Xin Peng, Tongxing Shi, Jun Wang, Jie Wu, Tie Song, Jianfeng He, Yuguo Li, Nanshan Zhong
Journal: Annals of Internal Medicine (2020)

The role of fecal aerosols in the transmission of severe acute respiratory syndrome coronavirus 2 has been suspected.
Abstract B25: SMARCA4/BRG1 and AP-1 co-regulate an epithelial-like signature in small-cell carcinoma of ovary, hypercalcemic type (SCCOHT)
Authors: Krystal A. Orlando, Jesse R. Raab, Amber K. Douglas, Aierken Abudu, Yemin Wang, Gian Luca Negri, Shane Colborne, Gregg B. Morin, Jessica D. Lang, William P.D. Hendricks, Elizabeth A. Raupach, Patrick Pirrotte, David G. Huntsman, Jeffrey M. Trent, Joel S. Parker, Bernard E. Weissman
Journal: Clinical Cancer Research (2020)

Abstract Mutations in SMARCA4 (BRG1), one of the two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex, occur in &amp;gt;95% of small cell carcinomas of the ovary, hypercalcemic type (SCCOHT), a rare and aggressive form of ovarian cancer. Because of its apparent role as a driver for SCCOHT, we performed integrative multi-omic analyses in a SCCOHT cell line +/- BRG1 re-expression to identify its role in SCCOHT tumorigenesis. After re-expression, BRG1 was recruited to both distal and promoter regions. We also observed increased chromatin accessibility at distal sites enriched for transcription factor binding motifs for AP-1 family members. Of interest, BRG1 re-expression induced an epithelial-like gene and protein expression concomitant with enrichment of AP-1 motifs at the TSS of highly upregulated epithelial genes. To determine the biologic relevance of these changes at AP-1 binding sites, we used a dominant negative AP-1 cell line to demonstrate that the necessity of AP-1 DNA binding activity and BRG1 re-expression for the protein expression of epithelial genes. Our study demonstrates that BRG1 loss may drive SCCOHT tumorigenesis by diminishing an epithelial-like gene and protein signature of its cell of origin driven by altered AP-1 binding. Citation Format: Krystal A. Orlando, Jesse R. Raab, Amber K. Douglas, Aierken Abudu, Yemin Wang, Gian Luca Negri, Shane Colborne, Gregg B. Morin, Jessica D. Lang, William P.D. Hendricks, Elizabeth A. Raupach, Patrick Pirrotte, David G. Huntsman, Jeffrey M. Trent, Joel S. Parker, Bernard E. Weissman. SMARCA4/BRG1 and AP-1 co-regulate an epithelial-like signature in small-cell carcinoma of ovary, hypercalcemic type (SCCOHT) [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B25.
Abstract 4985: PD-L1 and diacylglycerol kinase alpha (DGKA) expression in melanoma, nsclc and bladder cancers
Authors: Rachel M. Gonzalez, Tianli Qu, Xiaomin Hu, Qi Ren, Qiankun Zhang, Zhaoying Guo, Young-Hwan Kim, Yiran Wang, Xuan Liu, Wei Fu
Journal: Cancer Research (2020)

Abstract Diacylglycerol kinase alpha (DGKA) functions as lipid kinase to phosphorylate the lipid diacylglycerol (DAG). DGKA has been characterized to negative regulate the Ras-MAPK pathway in T lymphocytes. A 2018 study using crispr knockouts of DGKA have shown the anti tumor activity of T-cells continue to increase in the presence of PD-L1 positive tumor cells. Little is known about the expression patterns of DGKA in human cancer. In our previous study, we explore the tumor micro environment with a number of immune cell markers such as CD3, CD8A, CD20, CD68, TIM3 and LAG3 with PD-L1 expression in melanoma, NSCLC, and bladder cancer and found a few unique signatures for these cancers. In this study, we evaluate expression pattern of DGKA in various cancers by immunohistochemistry to elucidate the signature profile of DGKA expression with PD-L1 and other markers in the PD-L1 tumor micro environment. Citation Format: Rachel M. Gonzalez, Tianli Qu, Xiaomin Hu, Qi Ren, Qiankun Zhang, Zhaoying Guo, Young-Hwan Kim, Yiran Wang, Xuan Liu, Wei Fu. PD-L1 and diacylglycerol kinase alpha (DGKA) expression in melanoma, nsclc and bladder cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4985.
Ian B Pearson
Authors: Tamsin Pearson
Journal: BMJ (2020)

Ian B Pearson started his career in Sheffield in the 1950s with junior hospital posts in paediatrics, medicine, surgery, and obstetrics, then general practice—where he recalled his introduction to two huge drums: one of red pills, one of blue pills. If a patient presented with pain, he was to give them one week’s supply of red pills. If they came back, he should give them one week’s supply of blue pills. What was in the pills? Aspirin. Identical.

Through the 1960s Ian was a Wellcome Trust research fellow in the department of pharmacology and therapeutics at Sheffield University, then a registrar in psychiatry at …
The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19
Authors: Alessandro Gozzetti, Enrico Capochiani, Monica Bocchia
Journal: Leukemia (2020)

With great interest, we had the opportunity to read the paper by La Rosée F et al. [1] in which between March 30th and April 15th, 2020, using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signaling by the Janus Kinase (JAK) 1/2 inhibitor ruxolitinib (Rux).Fourteen patients were treated up to 14 days with Rux at 7.5 mg per day (at an intermediate dose between GvHD, 5 mg bid, and hemophagocytic lymphohistiocytosis, 15 mg bid) with a CIS ≥ 10 out of 16 points.The authors reported that 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with a sustained clinical improvement in 11/14 patients.We would like to report our results in COVID-19 patients with acute respiratory distress syndrome (ARDS) while employing a different Rux schedule at higher doses than those reported by La Rosée.The Ruxolitinib for the treatment of ARDS (RESPIRE, NCT04361903) study was approved by the National Ethics Committee.For each patient treated with Rux, parameters of inflammation and organ function were measured before treatment and again every 12, 24, or 48 h.Between March 10th and April 7th we treated 18 hospitalized patients (12 males/6 females; median age 62.5 years, range 28-86) with Rux 20 mg bid for the first 48 h and subsequent two-step de-escalation at 10 mg bids and 5 mg bids for a maximum of 14 days of treatment.Major endpoint of the treatment was to avoid respiratory worsening and progression to mechanical ventilation.Main inflammatory laboratory findings at baseline were: Fibrinogen (g/L) 4.4 (2.1-21.6)Ferritin (ng/mL) 841 (321-3348) CRP (mg/L) 17.8 (4-82) PCT (ng/ml) 0.6 (0.1-3.3) LDH (IU/L) 301 (189-506) ALT (U/L) 55
Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network
Authors: G.D. Demetri, C.R. Antonescu, B. Bjerkehagen, J.V.M.G. Bovée, K. Boye, M. Chacón, A.P. Dei Tos, J. Desai, J.A. Fletcher, H. Gelderblom, S. George, A. Gronchi, R.L. Haas, N. Hindi, P. Hohenberger, H. Joensuu, R.L. Jones, I. Judson, Y.-K. Kang, A. Kawai, A.J. Lazar, A. Le Cesne, R. Maestro, R.G. Maki, J. Martín, S. Patel, F. Penault-Llorca, C. Premanand Raut, P. Rutkowski, A. Safwat, M. Sbaraglia, I.-M. Schaefer, L. Shen, C. Serrano, P. Schöffski, S. Stacchiotti, K. Sundby Hall, W.D. Tap, D.M. Thomas, J. Trent, C. Valverde, W.T.A. van der Graaf, M. von Mehren, A. Wagner, E. Wardelmann, Y. Naito, J. Zalcberg, J.-Y. Blay
Journal: Annals of Oncology (2020)

The emergence of NTRK gene fusions as clinically actionable biomarkers marks a new era in precision oncology, with the tumor-agnostic approvals of larotrectinib and entrectinib representing milestones in drug development. TRK inhibitors provide new personalized treatment options with the potential to extend survival and improve quality of life in some patients with sarcoma harboring NTRK gene fusions. Integrating NTRK fusion testing into the current diagnostic workup of patients with sarcoma is particularly challenging due to the rarity of this biomarker. Here, we propose a diagnostic strategy to address this that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.
The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signalling
Authors: Antoine David, Simone Zocchi, Alexis Talbot, Caroline Choisy, Ashley Ohnona, Julien Lion, Wendy Cuccuini, Jean Soulier, Bertrand Arnulf, Jean-Christophe Bories, Michele Goodhardt, David Garrick
Journal: Leukemia (2020)
Management of idiopathic childhood nephrotic syndrome in sub-Saharan Africa: Ibadan consensus statement
Authors: Christopher Esezobor, Adebowale D. Ademola, Adewale E. Adetunji, Emmanuel A. Anigilaje, Anthony Batte, Fatima N. Jiya-Bello, Francis F. Furia, Uzoamaka Muoneke, Mignon McCulloch, Peter Nourse, Patience Obiagwu, Odutola Odetunde, Perditer Okyere, Adaobi Solarin, Elliot K. Tannor, Damien Noone, Rasheed Gbadegesin, Rulan S. Parekh, Gloria Ashuntantang, Guemkam Georgette, Dwamoa Adu, Victoria May Adabayeri, Vincent Boima, Charlotte Osafo, Elliot Koranteng Tannor, Perditer Okyere, Sampson Antwi, Jacob Plange-Rhule, Manmak Mamven, Samuel Ajayi, Emmanuel Anigilaje, Ogochukwu Okoye, Ofejiro Okperi, Okiroro Ighosewe, Ifeoma Ulasi, Uzoamaka Muoneke, Odutola Odetunde, Henrietta U. Okafor, Babatunde Salako, Adebowale Ademola, Kemi Amodu, Yemi Raji, Asinobi O. Adanze, Fatiu Arogundade, Wasiu Olowu, Timothy Olusegun Olanrewaju, Olanrewaju Adedoyin, Patience Obiagwu, Aliyu Abdu, Adaobi Solarin, Oluwatoyin Amira, Christopher Esezobor, Charles Odenigbo, Nonyelum Jisieike-Onuigbo, Adesola Musa, Rosemary Audu, Olanrewaju Jinadu, Adewale E. Adetunji, Muhammad Makusidi, Fatima Nma Jiya Bello, Jacob Olugbenga Awobusuyi, Mignon McCulloch, Peter Nourse, Francis Frederick Furia, Paschal Ruggajo, Jacqueline Shoo, Robert Kalyesubula, Grace Kansiime, Anthony Batte, Rulan S. Parekh, Damien Noone, Jovanka Vasilevska-Ristovska, Tonny H.M. Banh, Akinlolu O. Ojo, Jillian Wilson, Donna Smith, Titilayo Ilori, Rasheed Gbadegesin
Journal: Kidney International (2020)
LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer
Authors: Biao Zheng, Jianhua Qu, Kenoki Ohuchida, Haimin Feng, Stephen Jun Fei Chong, Zilong Yan, Yicui Piao, Peng Liu, Nan Sheng, Daiki Eguchi, Takao Ohtsuka, Kazuhiro Mizumoto, Zhong Liu, Shazib Pervaiz, Peng Gong, Masafumi Nakamura
Journal: Theranostics (2020)

Rationale: Pancreatic cancer is one of the most difficult cancers to manage and its poor prognosis stems from the lack of a reliable early disease biomarker coupled with its highly metastatic potential. Liver metastasis accounts for the high mortality rate in pancreatic cancer. Therefore, a better understanding of the mechanism(s) underlying the acquisition of the metastatic potential in pancreatic cancer is highly desirable. Methods: Microarray analysis in wild-type and highly liver metastatic human pancreatic cancer cell lines was performed to identify gene expression signatures that underlie the metastatic process. We validated our findings in patient samples, nude mice, cell lines and database analysis. Results: We identified a metastasis-related gene, laminin subunit alpha 4 (LAMA4), that was upregulated in highly liver metastatic human pancreatic cancer cell lines. Downregulation of LAMA4 reduced the liver metastatic ability of pancreatic cancer cells in vivo. Furthermore, LAMA4 expression was positively correlated with tumor severity and in silico analyses revealed that LAMA4 was associated with altered tumor microenvironment. In particular, our in vitro and in vivo results showed that LAMA4 expression was highly correlated with cancer-associated fibroblasts (CAFs) level which may contribute to pancreatic cancer metastasis. We further found that LAMA4 had a positive effect on the recruitment and activity of CAFs. Conclusions: These data provide evidence for LAMA4 as a possible biomarker of disease progression and poor prognosis in pancreatic cancer. Our findings indicate that LAMA4 may contribute to pancreatic cancer metastasis via recruitment or activation of CAFs.
Primary care networks: the impact of covid-19 and the challenges ahead
Authors: Luisa M Pettigrew, Stephanie Kumpunen, Nicholas Mays
Journal: BMJ (2020)

<h3>Background</h3> Recent evidence has linked early repolarisation pattern (ERP) to sudden cardiac death (SCD) in patients without structural heart disease. However, no studies have clarified the prognostic value of ERP in people at high risk for atherosclerotic heart disease. <h3>Methods</h3> We prospectively assessed the prognostic significance of ERP on ECGs in a community-based population of 18 231 subjects with atherosclerotic risk factors (49.3% men, mean age 64.0 years). Mean follow-up was 7.6 years. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. <h3>Results</h3> Compared with those without ERP, subjects with ERP had a significantly increased risk of developing SCD (HR 1.91, 95% CI 1.30 to 2.82), death from coronary heart disease (CHD) (HR 1.80, 95% CI 1.45 to 2.22) and death from any cause (HR 1.35, 95% CI 1.22 to 1.50). ERP was not associated with an increased risk of non-sudden CHD death and non-CHD death. ERP with J wave pattern in inferior leads, high amplitude of J wave pattern, notching configuration and horizontal or descending ST segment indicated a higher risk for SCD. ERP was associated with an absolute risk increase of 52.3 additional SCDs per 100 000 person-years in the population at high risk for atherosclerotic heart disease. <h3>Conclusions</h3> ERP is associated with a significantly increased risk for SCD, CHD death and death from any cause in people with atherosclerotic risk factors. The observed association between ERP and all-cause mortality appears to be driven by an association with CHD death, in particular SCD.
Abstract 1821: Reversal of <i>PD-L1</i>-mediated chemoresistance by MCL-1/BCL-2 antagonism in colon cancer cells
Authors: Lei Sun, Arpad Patai, Bo Qin, Frank A. Sinicrope
Journal: Cancer Research (2020)

Abstract Background: PD-L1 is an immune checkpoint protein that may display intrinsic, non-immune functions in human cancer cells. Previously, we discovered that PD-L1 is regulated by BRAFV600E via YAP and c-Jun, and whose deletion can confer chemoresistance due to a decrease in the BH3-only BIM protein in colorectal cancer (CRC) cells. Here, we hypothesize that release of pro-apoptotic BIM from its sequestration by MCL-1 or BCL-2 can overcomes drug resistance mediated by depletion of PD-L1. Materials and Methods: Parental and PD-L1 knockout human (RKO) and murine (MC38) CRC cells with or without reconstituted PD-L1 were utilized. RKO cells with knockdown of MCL-1 or BCL-2 by shRNA were generated. Cells were treated with the MCL-1 selective inhibitor AZD5591 or the BCL-2/BCL-xL inhibitor ABT-263 alone or combined with the MEK inhibitor, cobimetinib. Apoptosis was measured by immunoblotting of cleaved caspase-3 and by Annexin V labeling using FACS. Clonogenic cell survival assay was performed. Protein/protein interaction was analyzed by immunoprecipitation assay. Results: BIM induction by cobimetinib was insufficient to overcome chemoresistance due to loss of PD-L1. Using a potent and selective inhibitor of MCL-1 (AZD-5591), we demonstrate that concurrent antagonism of MCL-1 and MEK can overcome apoptosis resistance in both human and murine PD-L1 knockout CRC cells. Specifically, inhibition of MCL-1 by AZD-5591 or gene knockdown combined with cobimetinib suppresses clonogenic cell survival and enhances apoptosis in cells with PD-L1 knockout, wild type or those with reconstituted PD-L1. Mechanistically, the interaction of BIM with MCL-1 is increased in PD-L1 knockout (versus wild-type cells) in the presence of cobimetinib, and enhanced binding of BIM to MCL-1 is associated with BIM phosphorylation at Thr116. Targeting MCL-1 using AZD-5591 or MCL-1 shRNA releases BIM from its sequestration by MCL-1 and results in enhanced apoptotic signaling induced by cobimetinib to an equivalent extent in wild type and PD-L1 knockout cells with or without reconstitution of PD-L1. Similarly, targeting BCL-2 by ABT-263 or by BCL-2 shRNA releases BIM from its binding to BCL-2, and enhances apoptosis induction by cobimetinib independent of PD-L1 status. Enhanced binding of BIM to BCL-2 was also associated with BIM phosphorylation at Thr116. Conclusion: Chemoresistance mediated by loss of PD-L1 can be reversed by the use of BH3 mimetic drugs combined with MEK inhibition in CRC cells to exploit their apoptotic dependency on BIM expression. Citation Format: Lei Sun, Arpad Patai, Bo Qin, Frank A. Sinicrope. Reversal of PD-L1-mediated chemoresistance by MCL-1/BCL-2 antagonism in colon cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1821.