tbuckley/cabot-search huggingface dataset:
Immunostimulatory membrane proteins potentiate <i>H. pylori</i>-induced carcinogenesis by enabling CagA translocation
Authors: Matthew G. Varga, Cecily R. Wood, Julia Butt, Mackenzie E. Ryan, Wei-Cheng You, Kaifeng Pan, Tim Waterboer, Meira Epplein, Carrie L. Shaffer
Journal: Gut Microbes (2020)

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations.
Metastasis-on-a-chip reveals adipocyte-derived lipids trigger cancer cell migration via HIF-1α activation in cancer cells
Authors: Jieun Seo, Kyeong Seog Kim, Jong-Wan Park, Joo-Youn Cho, Hak Chang, Junji Fukuda, Ki Yong Hong, Yang-Sook Chun
Journal: Biomaterials (2020)

Although obesity is a newly considered risk factor for cancer, the mechanisms by which adipocyte-derived metabolites accelerate cancer malignancy have yet to be elucidated. To identify the connection among heterogeneous cell types, conventional methods including Transwell assays or conditioned media (CM) have been used; however, these methods do not fully reflect niche effects in the tumor microenvironment (TME). Here, we established an oxygen permeable polydimethylsiloxane (PDMS)-based three-dimensional (3D) culture system to allow direct attachment between human adipocyte derived stem cells (ADSCs) and cancer cells. By doing so, a physiologically bioactive TME was created, which could be used to reveal further the relationships between different cell types. We found that co-culture of cancer cells with ADSCs resulted in a dispersion phenomenon, and the dispersed spheroid was well matched with the enhanced metastatic potential of cancer cells. Lipid profiling and in vitro migration assays suggested that lipids are the driving force for cancer cell migration via HIF-1α upregulation. In addition, the lipid/HIF-1α axis promoted tumor metastasis in a xenograft mouse model. This study presents an in vitro model of a biomimetic TME and provides new mechanistic insights into the effects of ADSC-released fatty acids on cancer cells as oncometabolites.
Liver Stiffness by Transient Elastography to Detect Porto‐Sinusoidal Vascular Liver Disease With Portal Hypertension
Authors: Laure Elkrief, Marie Lazareth, Sylvie Chevret, Valérie Paradis, Marta Magaz, Lorraine Blaise, Laura Rubbia‐Brandt, Lucile Moga, François Durand, Audrey Payancé, Aurélie Plessier, Cendrine Chaffaut, Dominique Valla, Marion Malphettes, Alba Diaz, Jean‐Charles Nault, Pierre Nahon, Etienne Audureau, Vlad Ratziu, Laurent Castera, Juan‐Carlos Garcia Pagan, Nathalie Ganne‐Carrie, Pierre‐Emmanuel Rautou
Journal: Hepatology (2020)

Background and Aims Porto‐sinusoidal vascular liver disease (PSVD) is a rare cause of portal hypertension. PSVD is still often misdiagnosed as cirrhosis, emphasizing the need to improve PSVD diagnosis strategies. Data on liver stiffness measurement using transient elastography (TE‐LSM) in PSVD are limited. The aim of this study was to evaluate the accuracy of TE‐LSM to discriminate PSVD from cirrhosis in patients with signs of portal hypertension. Approach and Results Retrospective multicenter study comparing TE‐LSM in patients with PSVD, according to Vascular Liver Disease Interest Group criteria, with patients with compensated biopsy‐proven cirrhosis associated with alcohol (n = 117), HCV infection (n = 110), or NAFLD (n = 46). All patients had at least one sign of portal hypertension among gastroesophageal varices, splenomegaly, portosystemic collaterals, history of ascites, or platelet count &lt; 150 × 10 9 /L. The 77 patients with PSVD included in the test cohort had lower median TE‐LSM (7.9 kPa) than the patients with alcohol‐associated, HCV‐related, and NAFLD‐related cirrhosis (33.8, 18.2, and 33.6 kPa, respectively; P &lt; 0.001). When compared with cirrhosis, a cutoff value of 10 kPa had a specificity of 97% for the diagnosis of PSVD with a 85% positive predictive value. A cutoff value of 20 kPa had a sensitivity of 94% for ruling out PSVD with a 97% negative predictive value. Of the patients, 94% were well‐classified. Even better results were obtained in a validation cohort including 78 patients with PSVD. Conclusions This study including a total of 155 patients with PSVD and 273 patients with cirrhosis demonstrates that TE‐LSM &lt; 10 kPa strongly suggests PSVD in patients with signs of portal hypertension. Conversely, when TE‐LSM is &gt;20 kPa, PSVD is highly unlikely.
Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up†
Authors: P. Bossi, A.T. Chan, L. Licitra, A. Trama, E. Orlandi, E.P. Hui, J. Halámková, S. Mattheis, B. Baujat, J. Hardillo, L. Smeele, C. van Herpen, A. Castro, J.-P. Machiels
Journal: Annals of Oncology (2020)
VLA4-Targeted Nanoparticles Hijack Cell Adhesion–Mediated Drug Resistance to Target Refractory Myeloma Cells and Prolong Survival
Authors: Francesca Fontana, Michael J. Scott, John S. Allen, Xiaoxia Yang, Grace Cui, Dipanjan Pan, Noriko Yanaba, Mark A. Fiala, Julie O'Neal, Anne H. Schmieder-Atteberry, Julie Ritchey, Michael Rettig, Kathleen Simons, Steven Fletcher, Ravi Vij, John F. DiPersio, Gregory M. Lanza
Journal: Clinical Cancer Research (2020)

Abstract Purpose: In multiple myeloma, drug-resistant cells underlie relapse or progression following chemotherapy. Cell adhesion–mediated drug resistance (CAM-DR) is an established mechanism used by myeloma cells (MMC) to survive chemotherapy and its markers are upregulated in residual disease. The integrin very late antigen 4 (VLA4; α4β1) is a key mediator of CAM-DR and its expression affects drug sensitivity of MMCs. Rather than trying to inhibit its function, here, we hypothesized that upregulation of VLA4 by resistant MMCs could be exploited for targeted delivery of drugs, which would improve safety and efficacy of treatments. Experimental Design: We synthetized 20 nm VLA4-targeted micellar nanoparticles (V-NP) carrying DiI for tracing or a novel camptothecin prodrug (V-CP). Human or murine MMCs, alone or with stroma, and immunocompetent mice with orthotopic multiple myeloma were used to track delivery of NPs and response to treatments. Results: V-NPs selectively delivered their payload to MMCs in vitro and in vivo, and chemotherapy increased their uptake by surviving MMCs. V-CP, alone or in combination with melphalan, was well tolerated and prolonged survival in myeloma-bearing mice. V-CP also reduced the dose requirement for melphalan, reducing tumor burden in association with suboptimal dosing without increasing overall toxicity. Conclusions: V-CP may be a safe and effective strategy to prevent or treat relapsing or refractory myeloma. V-NP targeting of resistant cells may suggest a new approach to environment-induced resistance in cancer.
The Prognostic Value of Cardiac CT After Coronary Artery Bypass Surgery: As Easy as 1, 2, 3?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the view of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Patrick T. O'Gara, Ron Blankstein
Journal: JACC. Cardiovascular imaging (2011)
<i>Brachyspira</i> and IBS with diarrhoea: a <i>Helicobacter pylori</i> moment?
Authors: Robin C Spiller, Jonna Jalanka
Journal: Gut (2020)

<h3>Abstract</h3> Genomic complexity from profound copy-number aberration has prevented effective molecular stratification of ovarian and other cancers. Here we present a method for copy-number signature identification that decodes this complexity. We derived eight signatures using 117 shallow whole-genome sequenced high-grade serous ovarian cancer cases, which were validated on a further 497 cases. Mutational processes underlying the copy-number signatures were identified, including breakage-fusion-bridge cycles, homologous recombination deficiency and whole-genome duplication. We show that most tumours are heterogeneous and harbour multiple signature exposures. We also demonstrate that copy number signatures predict overall survival and changes in signature exposure observed in response to chemotherapy suggest potential treatment strategies.
Myocardial Infarction, Viral Infection, and the Cytoskeleton: Final Common Pathways of a Common Disease?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Jeffrey A. Towbin, Matteo Vatta
Journal: Journal of the American College of Cardiology (2007)
Self‐Adjuvanted Molecular Activator (SeaMac) Nanovaccines Promote Cancer Immunotherapy
Authors: Zichao Luo, Tao He, Peng Liu, Zhigao Yi, Shunyao Zhu, Xiuqi Liang, Entang Kang, Changyang Gong, Xiaogang Liu
Journal: Advanced Healthcare Materials (2020)

Abstract Neoantigen‐based immunotherapy is a promising treatment option for many types of cancer. However, its efficacy and abscopal effect are limited by impotent neoantigens, high treatment costs, and complications due to action of adjuvants. Here, the design and synthesis of nanovaccines are reported, based on self‐adjuvanted, polymer nanoparticles with in vivo neoantigen‐harvesting and molecular activating capabilities. These nanovaccines inhibit tumor growth significantly and prolong the survival of tumor‐bearing mice in both colon carcinoma 26 (CT26) and B16‐F10 tumor models. Mechanistic studies suggest that as‐synthesized nanovaccines can promote dendritic cell maturation and accumulation expeditiously in lymph nodes, leading to the expansion of cytotoxic CD8 + T cells. Moreover, these nanovaccines elicit abscopal effects in CT26 and B16‐F10 tumors without the need for adjuvants or immune checkpoint inhibitors. Combined with an anti‐PD‐L1 antibody, nanovaccines can evoke robust, long‐term memory immune response, as evidenced by tumor growth inhibition and high survival rates (∼ 67%) over 90 days. These results highlight the potential of using self‐adjuvanted nanovaccines as a simple, safe, and affordable strategy to boost neoantigen‐based cancer immunotherapy.
Statistical power in COVID-19 case-control host genomic study design
Authors: Yu-Chung Lin, Jennifer D. Brooks, Shelley B. Bull, France Gagnon, Celia M. T. Greenwood, Rayjean J. Hung, Jerald Lawless, Andrew D. Paterson, Lei Sun, Lisa J. Strug
Journal: Genome Medicine (2020)

Abstract The identification of genetic variation that directly impacts infection susceptibility to SARS-CoV-2 and disease severity of COVID-19 is an important step towards risk stratification, personalized treatment plans, therapeutic, and vaccine development and deployment. Given the importance of study design in infectious disease genetic epidemiology, we use simulation and draw on current estimates of exposure, infectivity, and test accuracy of COVID-19 to demonstrate the feasibility of detecting host genetic factors associated with susceptibility and severity in published COVID-19 study designs. We demonstrate that limited phenotypic data and exposure/infection information in the early stages of the pandemic significantly impact the ability to detect most genetic variants with moderate effect sizes, especially when studying susceptibility to SARS-CoV-2 infection. Our insights can aid in the interpretation of genetic findings emerging in the literature and guide the design of future host genetic studies.
Stoma Formation in Crohn’s Disease and the Likelihood of Antidepressant Use: A Population-Based Cohort Study
Authors: Jonathan Blackwell, Sonia Saxena, Nishani Jayasooriya, Irene Petersen, Matthew Hotopf, Hanna Creese, Alex Bottle, Richard C.G. Pollok
Journal: Clinical Gastroenterology and Hepatology (2020)
癌治療のためのフェノール誘導体からの自己集合ナノ粒子【Powered by NICT】
Authors: Dai Yunlu, Guo Junling, Wang Ting-Yi, Ju Yi, J Mitchell Andrew, Bonnard Thomas, Cui Jiwei, J Richardson Joseph, E Hagemeyer Christoph, Alt Karen, Caruso Frank
Journal: Advanced Healthcare Materials (2017)
Abstract 14986: Modern Prevalence of Familial Chylomicronemia Syndrome
Authors: Vincent A Pallazola, Aparna Sajja, Robert Derenbecker, Oluseye Ogunmoroti, Jihwan Park, Vasanth Sathiyakumar, Seth S Martin
Journal: Circulation (2019)

Introduction: Familial Chylomicronemia Syndrome (FCS) is a rare genetic disorder characterized by elevated fasting triglycerides (TG) >750 mg/dL that presents with recurrent pancreatitis. Prior stu...
Telomerase therapy attenuates cardiotoxic effects of doxorubicin
Authors: Shambhabi Chatterjee, Teresa Hofer, Alessia Costa, Dongchao Lu, Sandor Batkai, Shashi Kumar Gupta, Emiliano Bolesani, Robert Zweigerdt, Diego Megias, Katrin Streckfuss-Bömeke, Christina Brandenberger, Thomas Thum, Christian Bär
Journal: Molecular Therapy (2021)

Doxorubicin is one of the most potent chemotherapeutic agents. However, its clinical use is restricted due to the severe risk of cardiotoxicity, partially attributed to elevated production of reactive oxygen species (ROS). Telomerase canonically maintains telomeres during cell division but is silenced in adult hearts. In non-dividing cells such as cardiomyocytes, telomerase confers pro-survival traits, likely owing to the detoxification of ROS. Therefore, we hypothesized that pharmacological overexpression of telomerase may be used as a therapeutic strategy for the prevention of doxorubicin-induced cardiotoxicity. We used adeno-associated virus (AAV)-mediated gene therapy for long-term expression of telomerase in in vitro and in vivo models of doxorubicin-induced cardiotoxicity. Overexpression of telomerase protected the heart from doxorubicin-mediated apoptosis and rescued cardiac function, which was accompanied by preserved cardiomyocyte size. At the mechanistic level, we observed altered mitochondrial morphology and dynamics in response to telomerase expression. Complementary in vitro experiments confirmed the anti-apoptotic effects of telomerase overexpression in human induced pluripotent stem cell-derived cardiomyocytes after doxorubicin treatment. Strikingly, elevated levels of telomerase translocated to the mitochondria upon doxorubicin treatment, which helped to maintain mitochondrial function. Thus, telomerase gene therapy could be a novel preventive strategy for cardiotoxicity by chemotherapy agents such as the anthracyclines.
Development of an animal model that reproduces pulsations for training in esophageal endoscopic submucosal dissection
Authors: Yoshitsugu Misumi, Kouichi Nonaka, Maiko Kishino
Journal: Endoscopy (2020)

In recent years, endoscopic submucosal dissection (ESD) has been increasingly used in early esophageal cancer. ESD is superior to endoscopic mucosal resection in terms of en bloc resection, curative resection, and recurrence rates [1]. However, performing esophageal ESD is technically demanding because of the thin wall and narrow lumen of the esophagus, respiratory fluctuations, and pulsations. The perforation rate is approximately 3.3 % [2]. Because the morbidity of esophageal cancer is lower than that of gastric and colon cancers [3], clinicians have limited opportunities to practice esophageal ESD, and therefore many clinicians consider this technique challenging. Studies to date have reported animal models for esophageal ESD training [4] [5], but these models do not simulate the respiratory fluctuations or pulsations that make the procedure challenging in real-world practice. This report outlines our more realistic novel training model.
Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2
Authors: Kyung Soo Park, Joseph D. Bazzill, Sejin Son, Jutaek Nam, Seung Won Shin, Lukasz J. Ochyl, Jeanne A. Stuckey, Jennifer L. Meagher, Louise Chang, Jun Song, David C. Montefiori, Celia C. LaBranche, Janet L. Smith, Jie Xu, James J. Moon
Journal: Journal of Controlled Release (2020)
Treating low back pain in athletes: a systematic review with meta-analysis
Authors: Jane S Thornton, J P Caneiro, Jan Hartvigsen, Clare L Ardern, Anders Vinther, Kellie Wilkie, Larissa Trease, Kathryn E Ackerman, Kathryn Dane, Sarah-Jane McDonnell, David Mockler, Conor Gissane, Fiona Wilson
Journal: British Journal of Sports Medicine (2020)

To summarise the evidence for non-pharmacological management of low back pain (LBP) in athletes, a common problem in sport that can negatively impact performance and contribute to early retirement. Five databases (EMBASE, Medline, CINAHL, Web of Science, Scopus) were searched from inception to September 2020. The main outcomes of interest were pain, disability and return to sport (RTS). Among 1629 references, 14 randomised controlled trials (RCTs) involving 541 athletes were included. The trials had biases across multiple domains including performance, attrition and reporting. Treatments included exercise, biomechanical modifications and manual therapy. There were no trials evaluating the efficacy of surgery or injections. Exercise was the most frequently investigated treatment; no RTS data were reported for any exercise intervention. There was a reduction in pain and disability reported after all treatments. While several treatments for LBP in athletes improved pain and function, it was unclear what the most effective treatments were, and for whom. Exercise approaches generally reduced pain and improved function in athletes with LBP, but the effect on RTS is unknown. No conclusions regarding the value of manual therapy (massage, spinal manipulation) or biomechanical modifications alone could be drawn because of insufficient evidence. High-quality RCTs are urgently needed to determine the effect of commonly used interventions in treating LBP in athletes.
Biological efficacy of perpendicular type-I collagen protruded from TiO2-nanotubes
Authors: Chia-Yu Chen, David. M. Kim, Cliff Lee, John Da Silva, Shigemi Nagai, Toshiki Nojiri, Masazumi Nagai
Journal: International Journal of Oral Science (2020)

Abstract The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen (Col-I) from TiO 2 nanotubes (NT-EPF surface). We hypothesized that the NT-EPF surface would play bifunctional roles in stimulating platelet-mediated fibroblast recruitment and anchoring fibroblast-derived Col-I to form a perpendicular collagen assembly, mimicking the connective tissue attachment around natural teeth for the long-term maintenance of dental implants. Ti surface modification was accomplished in two steps. First, TiO 2 nanotubes (NT) array was fabricated via anodization. Diameters and depths of NTs were controlled by applied voltage and duration. Subsequently, an electrophoretic fusion (EPF) method was applied to fuse Col-I into nanotube arrays in a perpendicular fashion. Surface wettability was assessed by contact angle measurement. The bioactivity of modified TiO 2 surfaces was evaluated in terms of NIH3T3 fibroblast attachment, platelet activation, and collagen extension. Early attachment, aggregation, and activation of platelets as well as release of platelet-related growth factors were demonstrated on NT-EPF surfaces. Platelet-mediated NIH3T3 cells migration toward NT-EPF was significantly increased and the attached cells showed a typical fibrous morphology with elongated spindle shape. A direct linkage between pseudopod-like processes of fibroblasts to NT-EPF surfaces was observed. Furthermore, the engineered EPF collagen protrusion linked with cell-derived collagen in a perpendicular fashion. Within the limitation of this in vitro study, the TiO 2 nanotube with perpendicular Col-I surface (NT-EPF) promoted better cell attachment, induced a strong platelet activation which suggested the ability to create a more robust soft tissue seal.
AB0162 THE SIGNIFICANCE OF M1 AND M2 MONOCYTES IN SYSTEMIC SCLEROSIS
Authors: T. Michitsuji, N. Iwamoto, S. Tsuji, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2020)

Background: Recently, the relation between M2 macrophage and fibrosis have been reported in several diseases including systemic sclerosis (SSc). Similar with macrophages, monocytes can be classified into M1 and M2 subset, and the relation of imbalance of these monocytes with disease such as rheumatoid arthritis have been reported 1,2 . Objectives: In this study, we attempted to investigate relationship among M1 or M2 monocytes in SSc. Methods: This study included 23 SSc patients and 20 healthy donors. Using fluorescence-activated cell sorting, we defined CD14, CD68 and CCR2 positive cells as M1 monocytes and CD14, CX3CR1 and CD163 positive cells as M2 monocytes. We examined the ability of cytokines/chemokines secretion of CD14 positive cells from SSc by multiplex bead array assay using MAP human cytokine/chemokine Magnetic Bead Panel which can measure 38 cytokines/chemokines. We next extracted M2 monocytes from CD14-positive cells using FACS, and we used the rest of the CD14 positive cells as M1-dominant monocytes. Then, we evaluated their ability of TGF-β production by multiplex bead array assay. Results: SSc patients had higher M2/M1 ratio as compared with healthy control (7.00 vs 1.63, P&lt;0.05). And, there was tendency that M2/M1 ratio was higher in SSc patients complicated with interstitial pneumonia. Beads array analysis revealed that CCL4 and MCP-1 production from CD14 positive cells which consists M2&gt;M1 (M2/M1 ratio&gt;1) were higher than that from CD14 positive cells which consists M2&lt;M1. Furthermore, the ability of TGF-β secretion of M2 monocytes was higher than that of M1-dominant monocytes. Conclusion: Our present study suggested that the imbalance of M1/M2 monocytes might contribute to pathogenesis of SSc. References: [1]Fadini GP, Simoni F, Cappellari R, et al. Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis. Atherosclerosis 2014; 237 (2): 805-8. [2]Fukui S, Iwamoto N, Takatani A, et al. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis. Front Immunol 2017; 8 : 1958. Disclosure of Interests: None declared