tbuckley/cabot-search huggingface dataset:
Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment
Authors: Shuai Shao, Hui Fang, Qingyang Li, Gang Wang
Journal: Theranostics (2020)

Extracellular vesicles (EVs), naturally secreted by almost all known cell types into extracellular space, can transfer their bioactive cargos of nucleic acids and proteins to recipient cells, mediating cell-cell communication. Thus, they participate in many pathogenic processes including immune regulation, cell proliferation and differentiation, cell death, angiogenesis, among others. Cumulative evidence has shown the important regulatory effects of EVs on the initiation and progression of inflammation, autoimmunity, and cancer. In dermatology, recent studies indicate that EVs play key immunomodulatory roles in inflammatory skin disorders, including psoriasis, atopic dermatitis, lichen planus, bullous pemphigoid, systemic lupus erythematosus, and wound healing. Importantly, EVs can be used as biomarkers of pathophysiological states and/or therapeutic agents, both as carriers of drugs or even as a drug by themselves. In this review, we will summarize current research advances of EVs from different cells and their implications in inflammatory skin disorders, and further discuss their future applications, updated techniques, and challenges in clinical translational medicine.
Frequent acquisition of bedaquiline resistance by epidemic extensively drug-resistant Mycobacterium tuberculosis strains in Russia during long-term treatment
Authors: Igor Mokrousov, Gulnora Akhmedova, Vladimir Molchanov, Elena Fundovnaya, Elena Kozlova, Yulia Ostankova, Alexander Semenov, Natalia Maslennikova, Dmitrii Leontev, Viacheslav Zhuravlev, Eugeni Turkin, Anna Vyazovaya
Journal: Clinical Microbiology and Infection (2020)
Abstract 846: Microsatellite instability determined by clinical targeted next generation sequencing
Authors: Ya-Chi Yeh, Chien-Hung Chen, Kuan-Ying Chen, Ying-Ja Chen, Shu-Jen Chen
Journal: Cancer Research (2020)

Abstract Microsatellite instability (MSI)/mismatch repair (MMR) status is a positive predictor for immune checkpoint inhibitors. Conventional detection method for MSI status relies on polymerase chain reaction (PCR) of 5 microsatellite loci. With the advancement of next-generation sequencing (NGS) applied to clinical samples, we developed a MSI prediction algorithm to determine MSI status from large-panel clinical targeted NGS data accounting for more than 500 microsatellite loci. A set of colorectal cancer clinical samples with known MSI status by PCR were used to train a MSI prediction model, which predicts a sample as microsatellite instability high (MSI-H) or microsatellite stable (MSS). The model was constructed based on the change of number of repeats of different lengths from a pooled MSS baseline across microsatellites in a comprehensive cancer genomic panel targeting 440 genes. Using a quantitative measure based on more than 500 microsatellites loci, the model achieves high robustness and efficiency for MSI status detection from NGS data without matched normal. An independent dataset of clinical samples across various cancer types were used to validate the model showing an accuracy of 96.8%. In summary, MSI status can be determined by the MSI prediction model from clinical targeted NGS panel without normal paired sample. Citation Format: Ya-Chi Yeh, Chien-Hung Chen, Kuan-Ying Chen, Ying-Ja Chen, Shu-Jen Chen. Microsatellite instability determined by clinical targeted next generation sequencing [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 846.
Liquid biopsy in the clinical management of hepatocellular carcinoma
Authors: Johann von Felden, Teresa Garcia-Lezana, Kornelius Schulze, Bojan Losic, Augusto Villanueva
Journal: Gut (2020)

With increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field. In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.
Inhibition of the MYC-Regulated Glutaminase Metabolic Axis Is an Effective Synthetic Lethal Approach for Treating Chemoresistant Ovarian Cancers
Authors: Yao-An Shen, Jiaxin Hong, Ryoichi Asaka, Shiho Asaka, Fang-Chi Hsu, Yohan Suryo Rahmanto, Jin-Gyoung Jung, Yu-Wei Chen, Ting-Tai Yen, Alicja Tomaszewski, Cissy Zhang, Nabeel Attarwala, Angelo M. DeMarzo, Ben Davidson, Chi-Mu Chuang, Xi Chen, Stephanie Gaillard, Anne Le, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2020)

Amplification and overexpression of the MYC oncogene in tumor cells, including ovarian cancer cells, correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. Here we report that ovarian cancer cells overexpressing glutaminase (GLS), a target of MYC and a key enzyme in glutaminolysis, are intrinsically resistant to platinum-based chemotherapy and are enriched with intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not in low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. These findings suggest consideration of applying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers, especially those with high GLS expression. SIGNIFICANCE: Targeting glutaminase disturbs redox homeostasis and nucleotide synthesis and causes replication stress in cancer cells, representing an exploitable vulnerability for the development of effective therapeutics. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/20/4514/F1.large.jpg.
Early liver transplantation for severe alcoholic hepatitis not responding to medical treatment: results of the French-Belgian prospective study QuickTrans
Authors: Alexandre Louvet, Julien Labreuche, Christophe Moreno, Claire Vanlemmens, Romain Moirand, Cyrille Feray, Jérôme Dumortier, Georges-Philippe Pageaux, Christophe Bureau, Faiza Chermak, Christophe Duvoux, Dominique Thabut, Vincent Leroy, Nicolas Carbonell, Ephrem Salamé, Rodolphe Anty, Jérôme Gournay, Jean Delwaide, Christine Silvain, Guillaume Lassailly, Sebastien Dharancy, Eric Nguyen Khac, Didier Samuel, Alain Duhamel, Philippe Mathurin
Journal: Journal of Hepatology (2020)
Identification of second primary tumors from lung metastases in patients with esophageal squamous cell carcinoma using whole-exome sequencing
Authors: Liyan Xue, Weihua Li, Xinyi Fan, Zitong Zhao, Wei Zhou, Zhimin Feng, Linxiu Liu, Hua Lin, Lin Li, Xuemin Xue, Xuanlin Huang, Peide Huang, Jia Guo, Peina Du, Ning Lu, Lin Li, Qimin Zhan, Yongmei Song
Journal: Theranostics (2020)

Esophageal squamous cell carcinoma (ESCC) patients with a synchronous or metachronous lung tumor can be diagnosed with lung metastasis (LM) or a second primary tumor (SPT), but the accurate discrimination between LM and SPT remains a clinical dilemma. This study aimed to investigate the feasibility of using the whole-exome sequencing (WES) technique to distinguish SPT from LM. Methods: We performed WES on 40 tumors from 14 patients, including 12 patients with double squamous cell carcinomas (SCCs) of the esophagus and lung (lymph node metastases were sequenced as internal controls) diagnosed as LM according to pathological information and 2 patients with paired primary ESCC and non-lung metastases examined as external controls. Results: Shared genomic profiles between esophageal (T) and lung (D) tumors were observed in 7 patients, suggesting their clonal relatedness, thus indicating that the lung tumors of these patients should be LM. However, distinct genomic profiles between T and D tumors were observed in the other 5 patients, suggesting the possibility of SPTs that were likely formed through independent multifocal oncogenesis. Conclusions: Our data demonstrate the limitations and insufficiency of clinicopathological criteria and that WES could be useful in understanding the clonal relationships of multiple SCCs.
Progress in Cancer Research, Prevention, and Care
Authors: Richard L. Schilsky, Sharyl Nass, Michelle M. Le Beau, Edward J. Benz
Journal: New England Journal of Medicine (2020)

Interview with Dr. Richard Schilsky on milestones in the prevention and treatment of cancer in the United States. (16:23)Download Cancer-related mortality has been declining steadily. Treatment advances have reduced death rates for some cancers, but most of the reduction in mortality can be attributed to long-standing efforts related to cancer prevention and early detection.
OC-005 Magnetically assisted capsule endoscopy (mace) of the upper gi tract to select patients for endoscopy and reduce hospital admissions
Authors: H-L Ching, MF Hale, R Sidhu, S Beg, K Ragunath, ME McAlindon
Journal: Gut (2017)

Introduction  Capsule endoscopy might be a suitable non-invasive method to identify patients with suspected upper gastrointestinal (GI) bleeding who need hospital admission and endoscopic therapy.  Method  Stable patients with suspected upper GI bleeding were recruited. After swallowing 1L water with simethicone, MACE was performed using a Mirocam Navi (a single camera device controlled using an external handheld magnet (Intromedic Ltd., Korea)) not less than one hour before gastroscopy (OGD), and findings compared. Prior to OGD, a clinical opinion was documented on whether patients could be discharged based on MACE findings.  Results  The mean duration of oesophagogastric MACE in 15 patients (78.6% M, mean age 60±14.9) was 29.2±17.4mins: duodenal inspection was usually performed after video download. Overall, mucosal visualisation (worst-best:1–5) was good in the gastric cardia (4.1±1.5), gastric body (4.2±2.6), antrum (4.9±0.2) and D2 (5.0±0); less so in oesophagus (2.9±2.4), fundus (3.1±1.2) and D1 (3.3±1.2). Lesions detected by both modalities accounted for 20.5% of pathologies: one case each of oesophagitis, duodenitis, benign gastric polyps, gastric ulcer, oesophageal and gastric varices and two cases of gastritis. 64.1% were only detected by MACE: oesophagitis (n=3), hiatus hernia (n=3), gastritis (n=5), gastric polyps (n=4), gastric angioectasia (n=1), duodenal erosions (n=3) and D1 ulcers (n=3). 26.9% of lesions were only detected by OGD: Barrett’s oesophagus (n=1), gastric erosion (n=1), early gastric antral vascular ectasia (n=1), duodenitis (n=1) and D1 ulcers (n=2). Both cases of D1 ulcers (neither exhibiting stigmata of recent bleed) missed by MACE were due to rapid transit: the edge of one of the lesions could be seen in retrospect. MACE correctly recommended admission for 3/3 patients: one because of poor views and two due to fresh blood in the stomach (no lesion identified at MACE or OGD) or duodenum (DU missed at MACE). The median hospital stay of those for whom MACE suggested discharge (excluding one with 384 hour admission due to recurrent hypoglycaemia) was 53 hours (range 15–103). MACE correctly suggested safe discharge for 12/12 patients. No complications were seen. Post-procedure pain, discomfort and distress scores were all lower with MACE (p  Conclusion  MACE was extremely well tolerated and allowed the identification of patients suitable for out-patient management. Both OGD and MACE missed lesions. Sensitivity of the MiroCam Navi could be improved if the mechanism triggering image capture occurred earlier in the oesophagus and a double-ended camera developed to increase imaging of the fundus and D1.  Disclosure of Interest
Martin Thornton Tanner Bryant
Authors: Maureen Bryant, Michael Ormiston
Journal: BMJ (2020)

Martin Thornton Tanner Bryant was born in Hampstead, north London. His father, a commercial artist, died in a car accident when Martin was 3 years old. His mother, a doctor who founded the Christian Medical Mission (read obituary: https://www.bmj.com/content/316/7137/1096), determined that Martin and two of his sisters should pursue careers in medicine. His third sister became a nurse.

Martin was educated at Epsom College and Millfield School with financial …
High risk pathogens and risk factors for postoperative pancreatic fistula after pancreatectomy; a retrospective case-controlled study
Authors: Kodai Abe, Minoru Kitago, Masahiro Shinoda, Hiroshi Yagi, Yuta Abe, Go Oshima, Shutaro Hori, Takahiro Yokose, Yutaka Endo, Yuko Kitagawa
Journal: International Journal of Surgery (2020)
A Minimal-Invasive Approach for Standardized Induction of Myocardial Infarction in Mice
Authors: Florian Sicklinger, Yunhang Zhang, Kory J. Lavine, Nicolai Simon, Volker Bucher, Manfred Jugold, Lorenz Lehmann, Mathias H. Konstandin, Hugo A. Katus, Florian Leuschner
Journal: Circulation Research (2020)
NickFect type of cell-penetrating peptides present enhanced efficiency for microRNA-146a delivery into dendritic cells and during skin inflammation
Authors: Gemma Carreras-Badosa, Julia Maslovskaja, Kapilraj Periyasamy, Egon Urgard, Kärt Padari, Helen Vaher, Liina Tserel, Maxime Gestin, Kai Kisand, Piret Arukuusk, Chenguang Lou, Ülo Langel, Jesper Wengel, Margus Pooga, Ana Rebane
Journal: Biomaterials (2020)
Abstract 2469: RCC2 promotes esophageal cancer growth by regulating activity and expression of the Sox2 transcription factor
Authors: Ali J. Calderon-Aparicio, Hiroyuki Yamamoto, Humberto de vitto, Tianshun Zhang, Qiushi Wang, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2020)

Abstract RCC2 is a protein located in the centrosome, which ensures that cell division proceeds properly. Previous reports show that RCC2 is overexpressed in some cancers and could play a key role in tumor development, but the mechanisms concerning how this occurs are not understood. Further, no evidence exists regarding its role in esophageal cancer. We studied the relevance of RCC2 in esophageal cancer growth and the mechanisms explaining how this process occurs. RCC2 was highly expressed in mouse and human tissues as well as esophageal cancer cell lines, and this overexpression was associated with tumorigenicity. RCC2 promoted cell proliferation, anchorage-independent growth, and migration. These oncogenic effects were accompanied by overexpression of Sox2, an important transcription factor promoting esophageal cancer. RCC2 upregulated and stabilized Sox2 expression by inhibiting proteasome degradation. Likewise, RCC2 increased the transcriptional activity and promoter binding of Sox2. In vivo studies indicated that RCC2 and Sox2 were overexpressed in esophageal tumors compared to normal controls, and this upregulation occurs in the basal cell layer for both proteins. In conditional knockout mice, RCC2 deletion decreased the tumor nodule formation and progression in the esophagus compared with “wild type” mice. PCNA expression, a cell proliferation marker, was also downregulated in RCC2 knockout mice. Overall, our data show for the first time that RCC2 is an important protein for the stabilization and transcriptional activation of Sox2 and further promotion of malignancy in cancer. Citation Format: Ali J. Calderon-Aparicio, Hiroyuki Yamamoto, Humberto de vitto, Tianshun Zhang, Qiushi Wang, Ann M. Bode, Zigang Dong. RCC2 promotes esophageal cancer growth by regulating activity and expression of the Sox2 transcription factor [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 2469.
Antihypoxic oxygenation agents with respiratory hyperoxia to improve cancer immunotherapy
Authors: Stephen M. Hatfield, Michail V. Sitkovsky
Journal: Journal of Clinical Investigation (2020)

Hypoxia/HIF-1α- and extracellular adenosine/A2 adenosine receptor-mediated immunosuppression protects tissues from collateral damage by antipathogen immune cells. However, this mechanism also protects cancerous tissues by inhibiting antitumor immune cells in hypoxic and extracellular adenosine-rich tumors that are the most resistant to current therapies. Here, we explain a potentially novel, antiimmunosuppressive reasoning to justify strategies using respiratory hyperoxia and oxygenation agents in cancer treatment. Earlier attempts to use oxygenation of tumors as a monotherapy or to improve radiotherapy have failed because oxygenation protocols were not combined with immunotherapies of cancer. In contrast, the proposal for therapeutic use of antihypoxic oxygenation described here was motivated by the need to prevent the hypoxia/HIF-1α-driven accumulation of extracellular adenosine to (a) unleash antitumor immune cells from inhibition by intracellular cAMP and (b) prevent immunosuppressive transcription of cAMP response element- and hypoxia response element-containing immunosuppressive gene products (e.g., TGF-β). Use of oxygenation agents together with inhibitors of the A2A adenosine receptor may be required to enable the most effective cancer immunotherapy. The emerging outcomes of clinical trials of cancer patients refractory to all other treatments provide support for the molecular and immunological mechanism-based approach to cancer immunotherapy described here.
Abstract 535: T-cell recruitment tumor lysis via a novel c-MET/CD3 bispecific antibody
Authors: Lei Huang, Kun Xie, Ruiqin Wang, Hua Gu, Jianmin Fang
Journal: Cancer Research (2020)

Abstract Anti-receptor tyrosine kinases (RTKs) therapy has been used for the treatment of a number of solid tumors in clinic. C-MET, also known as the hepatocyte growth factor receptor (HGFR), is a representative member of the RTK family. C-MET overexpression is commonly observed in tumor biopsies and associated with poor patient survival. Various kinase inhibitor and monoclonal antibody (e.g. Emibetuzumab and Onartuzumab) have been developed to block the HGF/c-MET interactions, however, those kinase-inhibiting-based therapeutics have shown limited success in clinical trials. There is an urgent need to develop new treatments targeting c-MET to overcome these limitations. Bispecific antibodies that recruit immune cells to the tumor microenvironment have been considered as effective therapeutic candidates. An example of this design strategy is the FDA-approved bispecific antibody blinatumomab. In this study, we have constructed an asymmetric bispecific antibody, which binds both c-MET and CD3, using a novel platform that is monovalent to epitope. Our c-MET/CD3 bispecific antibody showed potent T-cell mediated tumor cells killing in vitro. Meanwhile, this antibody inhibited the phosphorylation of c-MET and downstream signal transduction in tumor cells due to its monovalent nature. In c-MET-overexpressing lung cancer and ovarian cancer xenograft models, c-MET/CD3 bispecific antibody inhibited tumor growth and increased the proportion of activated CD56+ tumor infiltrating lymphocytes. Moreover, in vivo combination therapy with FDA-proved PD-1/PD-L1 antibodies showed higher tumor inhibition than monotherapy in above two tumor models. Collectively, the novel c-MET/CD3 bispecific antibody can provide immunotherapy for c-MET-overexpressing tumors which conventional antibody or small molecular inhibitor might not. These findings also support the immunotherapeutic effects on combination of T-cell dependent bispecific antibody and immune checkpoint blockade. Citation Format: Lei Huang, Kun Xie, Ruiqin Wang, Hua Gu, Jianmin Fang. T-cell recruitment tumor lysis via a novel c-MET/CD3 bispecific antibody [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 535.
THU0227 Osteonecrosis (on) in hiv infection patients: 21affected joints in 9 patients
Authors: M Larrosa, M Cervantes, J Gratacós, M Sala, R Valls, G Gili
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> ON has been described in the setting of HIV infection. No epidemiological studies are available but their incidence seems to be increased and associated to the protease inhibitor (PI) into highly active antiretroviral therapy (HAART). <h3>Objectives</h3> To report the clinical findings of 9 HIV infected patients with ON. <h3>Methods</h3> Nine patients (8M/1W), mean age 40.7 (36–49 years). Review of clinical, biological and radiological characteristics. <h3>Results</h3> All cases were seen after 1998 and 8/9 received PI. In all cases the antiretroviral treatment was successfully (undetectable viral copies: &lt; 200 copies/ml). The diagnosis of the ON was made at 125 days (15–634) after the beginning of symptoms. 3/9 patients showed unilateral hip ON, 3/9 bilateral hip ON and 3/9 bilateral hip and shoulder ON.13/21 ON joints were demonstrated by radiology and 8/21 by IMR. 13/21 joints presented mechanical pain, 4/21 inflammatory pain and 4/21 were silent. Forage was performed in 4/21 and hip arthroplasty in 2/21. 6/9 patients presented hyperlipidaemia (6 hypercholesterolaemia, 4 hypertriglyceridaemia), 8/9 insulin resistance, 4/9 coagulation disturbances (4 deficits of C and S protein, 1 antiphospholipid antibodies), 7/9 haemoglobin &gt;16 g/dl and 5/9 had received steroid therapy. <h3>Conclusion</h3> The ON seems to be a new complication associated to the HIV infection. The ON presented frequently as a polyarticular involvement disease. In most cases its presence is associated with several risk factors, and probably the HAART is one of them.