tbuckley/cabot-search huggingface dataset:
Bilateral Same-Day Cataract Surgery: An Idea Whose Time Has Come #COVID-19
Authors: Iqbal Ike K. Ahmed, Warren E. Hill, Steve A. Arshinoff
Journal: Ophthalmology (2020)

The coronavirus disease 2019 (COVID-19) pandemic shut down the world in the spring of 2020. With that, the delivery of healthcare dramatically changed, perhaps forever. The pandemic has led to the need to distance physically, to minimize nonessential exposure, to acquire appropriate personal protective equipment for both providers and patients, to enhance sanitization and hygiene practices, and to cope with the additional costs of doing so. This crisis has made us rethink the status quo and reframe age-old debates.
Brain metastasis PD-L1 and CD8 expression is dependent on primary tumor type and its PD-L1 and CD8 status
Authors: Florian Camy, Georgia Karpathiou, Jean Marc Dumollard, Nicolas Magne, Jean Luc Perrot, Francois Vassal, Tiphanie Picot, Mousa Mobarki, Fabien Forest, Francois Casteillo, Sirine Hathroubi, Marios Froudarakis, Michel Peoc'h
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Brain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features. Methods This is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ 2 test, Cramer’s V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation. Results PD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found. Conclusion PD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.
Abstract 5000: YB-1 based oncolytic virotherapy in combination with small molecular inhibitors for treatment of refractory osteosarcoma
Authors: Charlotte Friederike Middendorf, Sebastian Johannes Schober, Corazón Kordass, Roman Nawroth, Stefan E. Burdach, Per Sonne Holm, Uwe Thiel
Journal: Cancer Research (2020)

Abstract This in vitro study evaluates YB-1 based oncolytic virotherapy in combination with molecular target therapy as a novel therapeutic strategy for refractory osteosarcoma. In vitro combination approaches include CDK4/6-, MDM2- and PARP-inhibitors. The treatment strategy was explored in four established osteosarcoma cell lines (143B, MG-63, SJSA, U2OS). Intracellular YB-1 expression was evaluated by immunofluorescence for oncolytic therapy with YB-1 selective adenovirus XVir-N-31. Efficacy of mono- and combination therapy is assessed using cell survival assays. The Chou Talalay method is used to determine synergistic effects between combinational components. Characterization of molecular pathways associated with oncolytic cytotoxicity is done using cell cycle analysis, western blotting, hexon titer test, sqPCR and ELISA. We observe a potent preclinical anti-tumor effect using XVir-N-31 monotherapy on all tested osteosarcoma cell lines. However, most cell lines were resistant towards inhibitor monotherapy in clinically achievable concentrations. In contrast, all dual combinations resulted in significantly enhanced cytotoxicity. These results require reduced numbers of infectious viral particles and are observed at clinically implementable inhibitor concentrations. Increased oncolytic cytotoxicity is associated with changes of tumor cell cycle regulation due to inhibitor treatment and modulation of infectious viral particle formation. In summary, we determine XVir-N-31 as a potent oncolytic agent for the treatment of refractory osteosarcoma. We provide a strong preclinical rationale for the combination of oncolytic adenovirus with molecular target therapy. A phase I clinical trial with XVir-N-31 in combination with molecular target therapy for refractory childhood sarcoma is planned. Citation Format: Charlotte Friederike Middendorf, Sebastian Johannes Schober, Corazón Kordass, Roman Nawroth, Stefan E. Burdach, Per Sonne Holm, Uwe Thiel. YB-1 based oncolytic virotherapy in combination with small molecular inhibitors for treatment of refractory osteosarcoma [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 5000.
Correspondence on ‘Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case–control study’ by Potere et al
Authors: Leo Buckley
Journal: Annals of the Rheumatic Diseases (2020)

In this paper the authors present a case history along with results of case series and a literature review to demonstrate the complexity of this condition. The main aim is to increase the awareness among clinicians and the scientist to research in the area of chronic exertional compartment syndrome (CECS). CECS usually refers to myoneural ischaemia due to a reversible increase in tissue pressure within a myofascial compartment. CECS of the leg is well documented in the literature since it was first described by Mavor in 1956. CECS of the foot remains underdiagnosed and has been reported in the literature only on an anecdotal basis. Wood Jones proposed that there were four compartments in the foot but Manoli and Weber suggest that there are nine separate muscle compartments. Clinical signs and symptoms of CECS of the foot remain diverse and lack the consistency of its counter part in the leg. The range of signs and symptoms include swelling, tension, cramps, tightness, paraesthesia, numbness, cyanosis and soft tissue indurations. As a result number of diagnosis is first considered and includes plantar fasciitis, tibialis posterior tendonitis, tarsal tunnel syndrome and medial Lisfranc injury. CECS of the foot remains a diagnosis of exclusion. The most effective treatment is a superficial fasciotomy.
Novel antibiotic-loaded particles conferring eradication of deep tissue bacterial reservoirs for the treatment of chronic urinary tract infection
Authors: Wai K. Lau, Dhanuson Dharmasena, Harry Horsley, Nazila V. Jafari, James Malone-Lee, Eleanor Stride, Mohan Edirisinghe, Jennifer L. Rohn
Journal: Journal of Controlled Release (2020)
Abstract 6206: The xl313 cryptic collagen epitope regulates ovarian tumor growth by a yap dependent mechanism
Authors: Xianghua Han, Jennifer M. Caron, Peter C. Brooks
Journal: Cancer Research (2020)

Abstract Structural changes in the extra cellular matrix (ECM) can lead to the exposure of cryptic regulatory sites that play important roles in angiogenesis, inflammation, tumor growth, and tumor metastasis. Previously, we discovered that a unique cryptic regulatory site (XL313 cryptic epitope) containing the amino acid sequence RGDKGE, is generated during tumor development, and we found that this collagen epitope promotes angiogenesis and inflammation in vivo. Here, we provide the first evidence that ovarian carcinoma cells can bind the XL313 collagen epitope through integrin alpha-V beta-3 and that selectively blocking cellular interactions with the XL313 epitope significantly inhibits ovarian tumor growth and the formation of ascites fluid in vivo. To understand the cellular mechanism(s) by which antagonists of the XL313 epitope inhibit these pathological processes, we examined down-stream signaling events that were altered following blocking ovarian tumor cell interaction with the XL313 collagen epitope. Importantly, selectively targeting the XL313 epitope significantly reduced nuclear accumulation of the transcriptional co-activator YAP. In addition, blocking cellular interaction with the XL313 epitope resulted in enhanced YAP phosphorylation at serine-127. Interestingly, specific targeting of the XL313 epitope also enhanced LATS1 phosphorylation, which is a key effector molecule in the hippo- signaling pathway. Taken together, our data provide new cellular and molecular insight for understanding the role of the XL313 cryptic collagen epitope in controlling ovarian tumor growth, and suggest that selectively targeting the XL313 epitope-integrin-signaling cascade may represent a novel strategy to inhibit ovarian cancer progression. Citation Format: Xianghua Han, Jennifer M. Caron, Peter C. Brooks. The xl313 cryptic collagen epitope regulates ovarian tumor growth by a yap dependent mechanism [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 6206.
Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors
Authors: Noëlle van Egmond, Verena M. Straub, Mario van der Stelt
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (−)- trans-Δ 9 -tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB 1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.
Abstract 1714A: TGF-beta signaling on myeloid cells regulates ECM deposition in mammary carcinoma via adenosine dependent mechanisms
Authors: Georgii Vasiukov, Tatiana Novitskaya, Samantha Schwager, Harold Moses, Timothy Blackwell, Igor Feoktistov, Sergey Novitskiy
Journal: Cancer Research (2020)

Abstract TGF-beta plays a crucial role in tumor microenvironment by regulating cell-cell and cell-stroma interactions. We previously demonstrated that TGF-beta signaling on myeloid cells regulates expression of CD73, a key enzyme for production of adenosine, a pro-tumorigenic metabolite implicated in regulation of tumor cell behaviors, immune response and angiogenesis. Using MMTV-PyMT mouse mammary tumor model, we discovered that deletion of TGF-beta signaling on myeloid cells (PyMT/TGFbRII-LysM) affects ECM formation in tumor tissue, specifically increases collagen and decreases fibronectin deposition, and these changes associate with mitigated tumor growth and reduced metastases. Using multiplexed five-color immunofluorescent staining and spatial analysis on a single-cell level, we discovered that reduced TGF-beta signaling on fibroblasts associates with their proximity to CD73 positive myeloid cells in tumor tissue. Consistent with these findings, in vitro gel contraction assay and Western blotting for Collagen I and pSMAD proteins confirmed that adenosine significantly downregulates TGF-beta signaling on fibroblasts. Using in vitro pharmacological approach, we found that this effect is regulated by A2a and A2b adenosine receptors. TCGA data base analysis revealed that patients with triple negative breast cancer and basal type have similar signature of adenosine and ECM profiles: high expression of A2b adenosine receptors correlates with decreased expression of Col1 and is associates with poor outcome. Taken together, our studies reveal a new role for TGF-beta signaling on myeloid cells in tumorigenesis. Discovered crosstalk between TGF-beta/CD73 on myeloid cells and TGF-beta signaling on fibroblasts can contribute to ECM remodeling and pro-tumorigenic actions of CAFs. Citation Format: Georgii Vasiukov, Tatiana Novitskaya, Samantha Schwager, Harold Moses, Timothy Blackwell, Igor Feoktistov, Sergey Novitskiy. TGF-beta signaling on myeloid cells regulates ECM deposition in mammary carcinoma via adenosine dependent mechanisms [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 1714A.
Janus Kinase Inhibition in the Aicardi–Goutières Syndrome
Authors: Adeline Vanderver, Laura Adang, Francesco Gavazzi, Katherine McDonald, Guy Helman, David B. Frank, Nicole Jaffe, Sabrina W. Yum, Abigail Collins, Stephanie R. Keller, Pierre Lebon, Jean-François Meritet, Jullie Rhee, Asako Takanohashi, Thais Armangue, Nicole Ulrick, Omar Sherbini, Jamie Koh, Kyle Peer, Constance Besnier, Carly Scher, Katherine Boyle, Holly Dubbs, Julia Kramer-Golinkoff, Amy Pizzino, Sarah Woidill, Justine Shults
Journal: New England Journal of Medicine (2020)

JAK Inhibition in the Aicardi–Goutieres Syndrome Patients with the Aicardi–Goutieres syndrome, an autosomal recessive disorder that affects the central nervous system, immune system, and skin, have...
Abstract 1859: Elucidating the role of KMT2D as a novel therapeutic target for resistant HER2+ breast cancer
Authors: EMILY MA, Andrei Zlobin, Debra Wyatt, Jeffrey Ng, Andrew Dingwall, Clodia Osipo
Journal: Cancer Research (2020)

Abstract HER2 targeted agents have improved clinical outcomes for women with HER2+ breast cancer. However, drug resistance remains a critical challenge for curing HER2+ disease. Cancer stem cells (CSCs)-enriched during anti-HER2 therapy promote resistance and recurrence. Therefore, novel targets that drive survival of CSCs are needed. Recently, the histone-lysine N-methyltransferase 2D (KMT2D) has been shown to be a prognostic marker for poor recurrence free survival in women with HER2+ breast cancer. Preliminary data showed that KMT2D RNA was increased in HER2+ CSC-enriched mammospheres compared to bulk cells. Further, KMT2D protein is increased in resistant compared to sensitive cells. These data suggest that KMT2D is necessary for survival of CSCs and resistance to anti-HER2 therapy. To address this hypothesis, RNAi-mediated knockdown of KMT2D was performed in trastuzumab sensitive and resistant cells. KMT2D depletion in sensitive cells resulted in almost complete blockade of proliferation in 2-D culture and CSC survival in 3-D culture. In contrast, proliferation and CSC survival was only moderately inhibited by KMT2D depletion in resistant cells. ChIP studies confirmed that KMT2D is enriched on the MYC enhancer in sensitive cells but only moderately in resistant cells. Based on these data, KMT2D is necessary for growth of HER2+ breast cancer and is possibly inactivated during acquisition of resistance. To determine the mechanism, RNA sequencing was performed in both sensitive and resistance cells expressing or depleted for KMT2D. Several differentially expressed genes that were positively or negatively regulated by KMT2D were identified. Specifically, transcript levels of ITGB6 and CLIC3 were decreased upon KMT2D knockdown, while PGR and AR transcripts were increased. Initial results showed that ITGB6 depletion resulted in decreased bulk cell proliferation and survival of CSCs similar to KMT2D knockdown. These results suggest that ITGB6 could be a direct target gene of KMT2D and thus mediates the phenotypic effects of KMT2D. Overall, our results suggest that KMT2D is necessary for both proliferation and CSC survival in HER2+ breast cancer sensitive to anti-HER2 therapy and a combination approach of targeting both HER2 and KMT2D could prevent enrichment of CSCs and acquired resistance. Citation Format: EMILY MA, Andrei Zlobin, Debra Wyatt, Jeffrey Ng, Andrew Dingwall, Clodia Osipo. Elucidating the role of KMT2D as a novel therapeutic target for resistant HER2+ breast cancer [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 1859.
Correction to: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
Authors: Cheng-Cao Sun, Wei Zhu, Shu-Jun Li, Wei Hu, Jian Zhang, Yue Zhuo, Han Zhang, Juan Wang, Yu Zhang, Shao-Xin Huang, Qi-Qiang He, De-Jia Li
Journal: Genome Medicine (2021)

An amendment to this paper has been published and can be accessed via the original article.
Abstract 639: Acute promyelocytic leukemia
Authors: Ravinder Singh Chale, Joaquin J. Jimenez
Journal: Cancer Research (2020)

Abstract Introduction: Acute Promyelocytic Leukemia (APL) accounts for 10%-15% of all acute myeloid leukemia's. The use of All-Trans Retinoic Acid/ Arsenic trioxide (ATRA/ATO) in the treatment regimens of low to intermediate-risk patients has led to remarkable cure rates (~80%). However, treatment guidelines of high-risk patients (WBC count≥ 10 x 109/L) remain unclear and these patients are at an increased risk of relapse. Design: Due to ambiguous treatment guidelines for high-risk APL patients as well as limited options for patients with arsenic resistant disease we sought to analyze clinical outcomes in this subset of patients. We conducted a literature search through Pubmed, EBSCO, and JSTOR to identify original articles that evaluated treatment protocols as well as outcomes for high-risk/refractory APL patients. We also evaluated the literature for clinical data involving patients who had arsenic resistant APL. Only relevant articles from 2000 to 2019 were included. Clinical trials where patients did not receive ATRA/ATO treatment were excluded. High risk patients have an increased mortality and decreased overall survival compared to intermediate and low risk patients. Although early death resulting from bleeding complications remains an important clinical hindrance, cases of arsenic resistant disease are becoming more prevalent. Resistant/refractory APL is a rare occurrence; however, no effective treatment exists to overcome resistance in this subset of patients. Of particular interest is the identification of variant translocations in APL; those that differ from the classical PML-RARA (~95%). 12 non-characteristic rearrangements have so far been described; of these, the ZBTB16-RARA and STAT5b-RARA are the most common variants. Both ZBTB16-RARA &amp; STAT5b-RARA are insensitive to ATRA/ATO combination therapy, leaving these patients with limited options. Clinical outcomes have recently been described in a subset of 13 patients with arsenic resistant disease. Of these 13 patients with arsenic resistant disease, 11 eventually died. Mutations in a particular region of the PML protein have been shown to mediate arsenic resistant disease in both in vitro and in vivo models, suggesting a potential benefit of molecular screening to improve clinical outcomes. Neither ATO nor cytotoxic chemotherapy was successful in inducing remissions in this particular subset of patients. Conclusion: Well-defined treatment guidelines in high-risk APL and the need for alternative agents in patients resistant to ATO therapy are needed to improve clinical efficacy and outcomes. 1. Zhu, H.H.; Qin, Y.Z.; Huang, X.J. Resistance to arsenic therapy in acute promyelocytic leukemia. N Engl J Med 2014, 370, 1864-1866, doi:10.1056/NEJMc1316382. Citation Format: Ravinder Singh Chale, Joaquin J. Jimenez. Acute promyelocytic leukemia [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 639.
Abstract 3962: Differential extracellular matrix remodeling induced by VEGF-A and TGF-β activated fibroblasts
Authors: Muriel A. Nuñez, Javier Cerda-Infante, Francisco Nualart, Gustavo Cerda, Isabel M. Yussef, Viviana P. Montecinos
Journal: Cancer Research (2020)

Abstract Introduction: Tumor progression is modulated by the presence within the tumor microenvironment of activated fibroblasts called cancer-associated fibroblasts (CAFs). CAFs exhibit an increase in the production of collagen (COL), tenascin C (TNC) and fibronectin (FN), resulting in a remodeling of the extracellular matrix (ECM) within the tumor mass. CAFs-derived ECM guides the cancer cells to migrate directionally increasing metastasis. TGF-β and VEGF-A are highly express in tumors and promote progression, however, their role in ECM remodeling is poorly understood. This study seeks to analyze the ECM protein remodeling mediated by TGF- β o VEGF-A activated fibroblasts. Materials and methods: In vitro and in vivo ECM protein remodeling mediated by TGF- β o VEGF-A activated fibroblasts was analyzed through expression of TNC, FN and COL using immunofluorescence and second harmonic generation (SHG); alignment and thickness of the fibers; Organoleptic invasion and 2D migration assay were conducted to study the effect of the stiffness of collagen gels generated by VEGF-A and TGF-β activated fibroblasts in the migration/invasion of tumor cells. Results and discussion: ECM derived from VEGF-A and TGF-β activated fibroblasts have differential ECM remodeling patterns, including differences in the secretion of TNC, FN, and COL; alignment and thickness of the fibers, and migration/invasion rate. These changes results in a differential stiffness of the ECM, which would alter the directional migration of cancer cells within tumor microenvironment. Citation Format: Muriel A. Nuñez, Javier Cerda-Infante, Francisco Nualart, Gustavo Cerda, Isabel M. Yussef, Viviana P. Montecinos. Differential extracellular matrix remodeling induced by VEGF-A and TGF-β activated fibroblasts [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 3962.
Poor Graft Function Following Autologous Stem Cell Transplant (ASCT): A Retrospective Analysis over Two Decades at a Transplant Center
Authors: Forat Lutfi, William Paul Skelton, Emma Rosenau, Nosha Farhadfar, Hemant S. Murthy, W. Stratford May, John W. Hiemenz, Christopher R. Cogle, Randy A. Brown, Sarah Wheeler, John R. Wingard, Maxim Norkin
Journal: Blood (2017)
ニューロピリン1は胸腺由来のナチュラル調節性T細胞上では発現するが,粘膜産生の誘導性Foxp3 + の制御性T細胞では発現しない | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: M Weiss Jonathan, M Bilate Angelina, Gobert Michael, Ding Yi, DE Lafaille Maria A. Curotto, N Parkhurst Christopher, Xiong Huizhong, Dolpady Jayashree, B Frey Alan, Ruocco Maria Grazia, Yang Yi, Floess Stefan, Huehn Jochen, OH Soyoung, O Li Ming, E Niec Rachel, Y Rudensky Alexander, L Dustin Michael, R Littman Dan, J Lafaille Juan
Journal: The Journal of Experimental Medicine (2012)