tbuckley/cabot-search huggingface dataset:
PHB2 promotes tumorigenesis <i>via</i> RACK1 in non-small cell lung cancer
Authors: Bin Wu, Ning Chang, Hangtian Xi, Jie Xiong, Ying Zhou, Yingtong Wu, Shuo Wu, Ning Wang, Hongyu Yi, Yun Song, Lihua Chen, Jian Zhang
Journal: Theranostics (2021)

Background: Lung cancer has the highest mortality rate among cancers worldwide, with non-small cell lung cancer (NSCLC) the most common type. Increasing evidence shows that PHB2 is highly expressed in other cancer types; however, the effects of PHB2 in NSCLC are currently poorly understood. Method: PHB2 expression and its clinical relevance in NSCLC tumor tissues were analyzed using a tissue microarray. The biological role of PHB2 in NSCLC was investigated in vitro and in vivo using immunohistochemistry and immunofluorescence staining, gene expression knockdown and overexpression, cell proliferation assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, wound healing assay, Transwell assay, western blot analysis, qRT-PCR, coimmunoprecipitation, and mass spectrometry analysis. Results: Our major finding is that PHB2 facilitates tumorigenesis in NSCLC by interacting with and stabilizing RACK1, which further induces activation of downstream tumor-promoting effectors. PHB2 was found to be overexpressed in NSCLC tumor tissues, and its expression was correlated with clinicopathological features. Furthermore, PHB2 overexpression promoted proliferation, migration, and invasion, whereas PHB2 knockdown enhanced apoptosis in NSCLC cells. The stimulating effect of PHB2 on tumorigenesis was also verified in vivo. In addition, PHB2 interacted with RACK1 and increased its expression through posttranslational modification, which further induced activation of the Akt and FAK pathways. Conclusions: Our results reveal the effects of PHB2 on tumorigenesis and its regulation of RACK1 and RACK1-associated proteins and downstream signaling in NSCLC. We believe that the crosstalk between PHB2 and RACK1 provides us with a great opportunity to design and develop novel therapeutic strategies for NSCLC.
Mind the gap: from neurons to networks to outcomes in multiple sclerosis
Authors: Declan T. Chard, Adnan A. S. Alahmadi, Bertrand Audoin, Thalis Charalambous, Christian Enzinger, Hanneke E. Hulst, Maria A. Rocca, Àlex Rovira, Jaume Sastre-Garriga, Menno M. Schoonheim, Betty Tijms, Carmen Tur, Claudia A. M. Gandini Wheeler-Kingshott, Alle Meije Wink, Olga Ciccarelli, Frederik Barkhof
Journal: Nature Reviews Neurology (2021)
Identifying preventable risk factors for hospitalised asthma in young Aboriginal children: a whole-population cohort study
Authors: Bronwyn Brew, Alison Gibberd, Guy B Marks, Natalie Strobel, Clare Wendy Allen, Louisa Jorm, Georgina Chambers, Sandra Eades, Bridgette McNamara
Journal: Thorax (2021)

Australia has one of the highest rates of asthma worldwide. Indigenous children have a particularly high burden of risk determinants for asthma, yet little is known about the asthma risk profile in this population.To identify and quantify potentially preventable risk factors for hospitalised asthma in Australian Aboriginal children (1-4 years of age).Birth, hospital and emergency data for all Aboriginal children born 2003-2012 in Western Australia were linked (n=32 333). Asthma was identified from hospitalisation codes. ORs and population attributable fractions were calculated for maternal age at birth, remoteness, area-level disadvantage, prematurity, low birth weight, maternal smoking in pregnancy, mode of delivery, maternal trauma and hospitalisations for acute respiratory tract infection (ARTI) in the first year of life.There were 705 (2.7%) children hospitalised at least once for asthma. Risk factors associated with asthma included: being hospitalised for an ARTI (OR 4.06, 95% CI 3.44 to 4.78), area-level disadvantage (OR 1.58, 95% CI 1.28 to 1.94), being born at <33 weeks' gestation (OR 3.30, 95% CI 2.52 to 4.32) or birth weight <1500 g (OR 2.35, 95% CI 1.39 to 3.99). The proportion of asthma attributable to an ARTI was 31%, area-level disadvantage 18%, maternal smoking 5%, and low gestational age and birth weight were 3%-7%. We did not observe a higher risk of asthma in those children who were from remote areas.Improving care for pregnant Aboriginal women as well as for Aboriginal infants with ARTI may help reduce the burden of asthma in the Indigenous population.
OA05.09 Volume Doubling Time and Radiomic Features Predict Tumor Behavior of Screen-Detected Lung Cancers in the National Lung Screening Trial (NLST)
Authors: J. Perez-Morales, I. Tunali, H. Lu, W. Mu, Y. Balagurunathan, R. Gillies, M. Schabath
Journal: Journal of Thoracic Oncology (2021)
PR01.08 Simultaneous Multi-Cancer Detection and Tissue of Origin Prediction Via Targeted Bisulfite Sequencing of Plasma Cell-Free DNA
Authors: K. Kurtzman, G. Oxnard, E. Klein, M. Seiden, E. Hubbell, O. Venn, A. Jamshidi, N. Zhang, J. Beausang, S. Gross, E. Fung, J. Yecies, R. Shaknovich, A. Fields, M. Sekeres, D. Richards, P. Yu, A. Aravanis, A.-R. Hartman, M. Liu
Journal: Journal of Thoracic Oncology (2021)
Learning curves of minimally invasive donor nephrectomy in a high-volume center: A cohort study of 1895 consecutive living donors
Authors: Kosei Takagi, Hendrikus J.A.N. Kimenai, Turkan Terkivatan, Khe T.C. Tran, Jan N.M. Ijzermans, Robert C. Minnee
Journal: International Journal of Surgery (2021)

Few studies have investigated the learning curves of minimally invasive donor nephrectomy (MIDN) using the cumulative sum (CUSUM) analysis. In addition, no study has compared the learning curves of the different surgical MIDN techniques in one cohort study using the CUSUM analysis. This study aims to evaluate and compare learning curves for several MIDN using the CUSUM analysis.A retrospective review of consecutive donors, who underwent MIDN between 1997 and 2019, was conducted. Three laparoscopic-assisted techniques were applied in our institution and included for analysis: laparoscopic (LDN), hand-assisted retroperitoneoscopic (HARP), and robot-assisted laparoscopic (RADN) donor nephrectomy. The outcomes were compared based on surgeon volume to develop learning curves for the operative time per surgeon.Out of 1895 MIDN, 1365 (72.0%) were LDN, 427 (22.5%) were HARP, and 103 (5.4%) were RADN. The median operative time and median blood loss were 179 (IQR, 139-230) minutes and 100 (IQR, 40-200) mL, respectively. The incidence of major complication was 1.2% with no mortality, and the median hospital stay was three (IQR, 3-4) days. The CUSUM analysis resulted in learning curves, defined by decreased operative time, of 23 cases in LDN, 45 cases in HARP, and 26 cases in RADN.Our study shows different learning curves in three MIDN techniques with equal post-operative complications. The LDN and RADN learning curves are shorter than that of the hand-assisted donor nephrectomy. Our observations can be helpful for informing the development of teaching requirements for fellows to be trained in MIDN.
Response to: ‘Correspondence on ‘Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis’’ by Takanashi<i>et al</i>
Authors: Iago Pinal-Fernandez, Maria Casal-Dominguez, Jose Cesar Milisenda, Andrew Lee Mammen
Journal: Annals of the Rheumatic Diseases (2021)

Table 1 Top 10 differentially expressed genes according to the location of the muscle biopsy
Next-Generation Profiling of Medulloblastoma: Old Drugs Are an Elegant Weapon in a Civilized Age
Authors: Carolina Nör, Vijay Ramaswamy
Journal: Cancer Research (2021)

Personalized therapies have remained elusive in medulloblastoma, resulting in treatment paradigms that have been largely stagnant for almost four decades. A recent study by Rusert and colleagues applies a novel integrated approach to the identification of new targets in medulloblastoma by combining genomics, transcriptomics, and high-throughput drug screening across a panel of molecularly characterized patient-derived models. Actinomysin D, a common chemotherapeutic agent, was identified as highly active in the most aggressive form of medulloblastoma, highlighting the power of this approach over genomic paradigms alone.See related article by Rusert et al.; Cancer Res 80(23):5393-407.
Intravascular Ultrasound and Fractional Flow Reserve in Assessment of the Intermediate Coronary Stenosis: What You See Is Not What You Get**Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Goran Stankovic, Milan Dobric
Journal: Journal of the American College of Cardiology (2013)
Checkpoint Blockade in Lymphoma
Authors: Stephen M. Ansell
Journal: Journal of Clinical Oncology (2021)

Article Tools REVIEW ARTICLES Immunotherapy for Hematologic Malignancies Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.20.01522 Journal of Clinical Oncology - published online before print January 12, 2021 PMID: 33434074 Checkpoint Blockade in Lymphoma Stephen M. Ansell , MD, PhD1xStephen M. AnsellSearch for articles by this author Show More 1Division of Hematology, Mayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.20.01522 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveLymphomas typically have an antitumor immune response that is ineffective because of immune suppression or exhaustion. This review discusses the deficiencies in the antitumor immune response in lymphoma and the role of immune checkpoint blockade in addressing the immune dysfunction.Knowledge GeneratedImmune checkpoint ligands are commonly overexpressed in the tumor microenvironment in lymphomas, and immune checkpoint blockade has been explored as treatment for these diseases. Although immune checkpoint blockade has been highly successful in treating patients with Hodgkin lymphoma, the results in other subtypes of lymphomas have been far less encouraging.RelevanceImmune checkpoint blockade is an effective therapy in Hodgkin lymphoma, but to improve upon the results and to increase the efficacy in other lymphomas, future treatment strategies using immune checkpoint blockade will need to use combinations with other immune active agents or with chemotherapy to optimize the antitumor immune response.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTCheckpoint Blockade in LymphomaThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Stephen M. AnsellHonoraria: WebMD, Research to PracticeResearch Funding: Bristol Myers Squibb (Inst), Seattle Genetics (Inst), Affimed Therapeutics (Inst), Regeneron (Inst), Pfizer (Inst), Trillium Therapeutics (Inst), AI Therapeutics (Inst), Celldex (Inst), Regeneron (Inst), ADC Therapeutics (Inst)No other potential conflicts of interest were reported.
Suppressing Nucleotide Exchange to Inhibit KRAS-Mutant Tumors
Authors: Yulei Zhao, Jenny Y. Xue, Piro Lito
Journal: Cancer Discovery (2021)

Guanine nucleotide exchange factors (GEF) control the rate-limiting step of physiologic RAS activation. In this issue of Cancer Discovery, Hofmann and colleagues describe the discovery of a selective inhibitor targeting the GEF, SOS1, along with its preclinical effects in suppressing KRAS-mutant tumor growth.See related article by Hofmann et al., p. 142.
DNA Methylation Patterns in CD4+ T Cells of Naïve and Influenza A Virus-Infected Mice Developmentally Exposed to an Aryl Hydrocarbon Receptor Ligand
Authors: Catherine G. Burke, Jason R. Myers, Christina M. Post, Lisbeth A. Boulé, B. Paige Lawrence
Journal: Environmental Health Perspectives (2021)

Background: Early life environmental exposures can have lasting effects on the function of the immune system and contribute to disease later in life. Epidemiological studies have linked early life exposure to xenobiotics that bind the aryl hydrocarbon receptor (AhR) with dysregulated immune responses later in life. Among the immune cells influenced by developmental activation of the AhR are CD4+ T cells. Yet, the underlying affected cellular pathways via which activating the AhR early in life causes the responses of CD4+ T cells to remain affected into adulthood remain unclear. Objective: Our goal was to identify cellular mechanisms that drive impaired CD4+ T-cell responses later in life following maternal exposure to an exogenous AhR ligand. Methods: C57BL/6 mice were vertically exposed to the prototype AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), throughout gestation and early postnatal life. The transcriptome and DNA methylation patterns were evaluated in CD4+ T cells isolated from naïve and influenza A virus (IAV)-infected adult mice that were developmentally exposed to TCDD or vehicle control. We then assessed the influence of DNA methylation-altering drug therapies on the response of CD4+ T cells from developmentally exposed mice to infection. Results: Gene and protein expression showed that developmental AhR activation reduced CD4+ T-cell expansion and effector functions during IAV infection later in life. Furthermore, whole-genome bisulfite sequencing analyses revealed that developmental AhR activation durably programed DNA methylation patterns across the CD4+ T-cell genome. Treatment of developmentally exposed offspring with DNA methylation-altering drugs alleviated some, but not all, of the impaired CD4+ T-cell responses. Discussion: Taken together, these results indicate that skewed DNA methylation is one of the mechanisms by which early life exposures can durably change the function of T cells in mice. Furthermore, treatment with DNA methylation-altering drugs after the exposure restored some aspects of CD4+ T-cell functional responsiveness. https://doi.org/10.1289/EHP7699
Batting against mental health in elite cricket
Authors: Hassan Jamaal Sadiq Mahmood, Daniel Jonah Friedman
Journal: British Journal of Sports Medicine (2021)

Elite athletes have always struggled with mental health. This is not news. But it does seem to be featured more often in newspapers and newsfeeds. Although sport is protective for mental health, athletes suffer from similar rates of anxiety, depression and substance abuse as the general population.1 Just as the sport and exercise medicine community are calling for more athlete mental health support through international consensus statements,2 the public are also waking up to athletes’ daily battles on and off the pitch. Now is the time to ensure cricket is not left behind.

In many countries, cricket is inseparable from religion and culture; players are worshipped by billions . The select few who represent their nation carry incredible responsibility—and failure leads to ultimate shame and financial insecurity. Cricket shines an unforgiving spotlight on individual players who can spend 300 days a year away from home.3 Statistical analysis of individual performance combined with extended time alone to reflect on errors likely predisposes cricketers to anxiety, depression and burnout.4 

To make matters worse, ubiquitous and relentless social media prevents cricketers …
The Evolving Immunotherapy Landscape and the Epidemiology, Diagnosis, and Management of Cardiotoxicity
Authors: Lili Zhang, Kerry L. Reynolds, Alexander R. Lyon, Nicolas Palaskas, Tomas G. Neilan
Journal: JACC CardioOncology (2021)

Immune checkpoint inhibitors (ICIs) are newer therapies being applied to an increasing number of patients with cancer. Data suggest that up to 36% of cancer patients may be eligible for immunotherapy and, in late 2019, there were more than 3,362 clinical trials initiated to evaluate the effectiveness of immunotherapy, either as single agents or in combination with other immunotherapy, targeted therapies, or traditional cytotoxic or radiation therapy. With the combination of both immune and non-immune treatment approaches, the complexity in making the diagnosis of cardiotoxicity related to an ICI will increase substantially. Here, we summarize the published data on the epidemiology, diagnosis, and management of cardiotoxicity of ICIs. This is a rapidly evolving field, and as our understanding continues to evolve, previously considered hypotheses may not prove to be entirely correct. Research and continued collaborations are urgently needed to provide evidence-based cardiovascular care for this rapidly expanding and vulnerable cohort of patients. (J Am Coll Cardiol CardioOnc 2021;3:35-47) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Skin immunization for effective treatment of multifocal melanoma refractory to PD1 blockade and Braf inhibitors
Authors: Xingxing Hao, Louis D Falo III, Guo Chen, Jiying Zhang, Cara D Carey, Walter J Storkus, Louis D Falo Jr, Zhaoyang You
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Despite the remarkable benefits associated with the interventional treatment of melanomas (and other solid cancers) with immune checkpoint and Braf inhibitors (Brafi), most patients ultimately progress on therapy. The presence of multifocal/disseminated disease in patients increases their mortality risk. Hence, the development of novel strategies to effectively treat patients with melanomas that are resistant to anti-PD1 mAb (αPD1) and/or Brafi, particularly those with multifocal/disseminated disease remains a major unmet clinical need. Methods Mice developing induced/spontaneous Braf V600E /Pten −/− melanomas were treated by cutaneous immunization with a DNA vaccine encoding the melanoma-associated antigen TRP2, with Brafi or αPD1 alone, or with a combination of these treatments. Tumor progression, tumor-infiltration by CD4 + and CD8 + T cells, and the development of TRP2-specific CD8 + T cells were then monitored over time. Results Vaccination led to durable antitumor immunity against PD1/Brafi-resistant melanomas in both single lesion and multifocal disease models, and it sensitized PD1-resistant melanomas to salvage therapy with αPD1. The therapeutic efficacy of the vaccine was associated with host skin-resident cells, the induction of a systemic, broadly reactive IFNγ + CD8 + T cell repertoire, increased frequencies of CD8 + TIL and reduced levels of PD1 hi/int CD8 + T cells. Extended survival was associated with improved TIL functionality, exemplified by the presence of enhanced levels of IFNγ + CD8 + TIL and IL2 + CD4 + TIL. Conclusions These data support the use of a novel genetic vaccine for the effective treatment of localized or multifocal melanoma refractory to conventional αPD1-based and/or Brafi-based (immune)therapy.
Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
Authors: Yu-Pei Chen, Jia-Wei Lv, Yan-Ping Mao, Xiao-Min Li, Jun-Yan Li, Ya-Qin Wang, Cheng Xu, Ying-Qin Li, Qing-Mei He, Xiao-Jing Yang, Yuan Lei, Jia-Yi Shen, Ling-Long Tang, Lei Chen, Guan-Qun Zhou, Wen-Fei Li, Xiao-Jing Du, Rui Guo, Xu Liu, Yuan Zhang, Jing Zeng, Jing-Ping Yun, Ying Sun, Na Liu, Jun Ma
Journal: Molecular Cancer (2021)

Abstract Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.
Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation
Authors: Yansen Xiao, Min Cong, Jiatao Li, Dasa He, Qiuyao Wu, Pu Tian, Yuan Wang, Shuaixi Yang, Chenxi Liang, Yajun Liang, Jili Wen, Yingjie Liu, Wenqian Luo, Xianzhe Lv, Yunfei He, Dong-dong Cheng, Tianhao Zhou, Wenjing Zhao, Peiyuan Zhang, Xue Zhang, Yichuan Xiao, Youcun Qian, Hongxia Wang, Qiang Gao, Qing-cheng Yang, Qifeng Yang, Guohong Hu
Journal: Cancer Cell (2021)

Lung metastasis is the major cause of breast cancer-related mortality. The neutrophil-associated inflammatory microenvironment aids tumor cells in metastatic colonization in lungs. Here, we show that tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating recruitment of neutrophils and formation of neutrophil extracellular traps (NETs). CTSC enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to facilitate interleukin-1β (IL-1β) processing and nuclear factor κB activation, thus upregulating IL-6 and CCL3 for neutrophil recruitment. In addition, the CTSC-PR3-IL-1β axis induces neutrophil reactive oxygen species production and formation of NETs, which degrade thrombospondin-1 and support metastatic growth of cancer cells in the lungs. CTSC expression and secretion are associated with NET formation and lung metastasis in human breast tumors. Importantly, targeting CTSC with compound AZD7986 effectively suppresses lung metastasis of breast cancer in a mouse model. Overall, our findings reveal a mechanism of how tumor cells regulate neutrophils in metastatic niches and support CTSC-targeting approaches for cancer treatment.
Ferroptosis as a novel therapeutic target for cardiovascular disease
Authors: Xiaoguang Wu, Yi Li, Shuchen Zhang, Xiang Zhou
Journal: Theranostics (2021)

Cell death is an important component of the pathophysiology of cardiovascular disease. An understanding of how cardiomyocytes die, and why regeneration of cells in the heart is limited, is a critical area of study. Ferroptosis is a form of regulated cell death that is characterized by iron overload, leading to accumulation of lethal levels of lipid hydroperoxides. The metabolism of iron, lipids, amino acids and glutathione tightly controls the initiation and execution of ferroptosis. Emerging evidence shows that ferroptosis is closely associated with the occurrence and progression of various diseases. In recent years, ferroptosis has been found to play critical roles in cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, and heart failure. This article reviews the mechanisms by which ferroptosis is initiated and controlled and discusses ferroptosis as a novel therapeutic target for various cardiovascular diseases.