tbuckley/cabot-search huggingface dataset:
PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling
Authors: Bomiao Cui, Jiao Chen, Min Luo, Yiying Liu, Hongli Chen, Die Lü, Liwei Wang, Yingzhu Kang, Yun Feng, Libin Huang, Ping Zhang
Journal: International Journal of Oral Science (2021)

Abstract Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.
The De-adoption of Low-Value Health Care
Authors: Alberto Donzelli
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Multimodal biomarkers overcome sampling bias to predict presence of aggressive localized prostate cancer.
Authors: David Monty Berman, Anna YW Lee, Robert Lesurf, Palak Patel, Walead Ebrahimizadeh, Jane Bayani, Nadia Boufaied, Tamara Jamaspishvili, Karl-Philippe Guerard, Dan Dion, Laura A Lee, Vasundara Venkateswaran, Simone Chevalier, Fadi Brimo, Ralph Buttyan, Axel A Thomson, Paul C Park, Jacques Lapointe, Paul Christopher Boutros, John Bartlett
Journal: Journal of Clinical Oncology (2021)

209 Background: Histopathologic investigation of diagnostic prostate biopsies both confirms the presence of disease and estimates its potential for distal spread via tumour grade. The accuracy of biopsy grading is limited by intra-tumoral heterogeneity, inter-observer variability, and other factors. To improve risk stratification at the time of diagnosis, we sought to create objective molecular biomarkers of radical prostatectomy grade that are resistant to sampling error and should be useful when applied to biopsy tissue. Methods: We developed and validated a robust objective biomarker of prostate cancer grade using pathologic grading of prostatectomy tissues as the gold standard. We created training (333 patients) and validation (202 patients) cohorts of Cancer of the Prostate Risk Assessment (CAPRA) low- and intermediate-risk prostate cancer patients. To address intra-tumoral heterogeneity, each tumor was sampled at two locations. We profiled the abundance of 342 mRNAs complemented by 100 canonical DNA copy number aberration loci (CNAs) and 14 hypermethylation events. Using the training cohort with cross-validation, we evaluated models for training classifiers of pathologic Grade Group ≥2, Restricting to strategies resulting in true negative rates ≥0.5, true positive (TP) rates ≥0.8, we selected two strategies to train classifiers, PRONTO-e and PRONTO-m. Results: The PRONTO-e classifier comprises 353 mRNA and CNA features, while the PRONTO-m classifier comprises 94 mRNA, CNA, methylation and clinical features. Both classifiers (PRONTO-e, PRONTO-m) validated in the independent cohort, with respective TP rates of 0.809 and 0.760, false positive rates of 0.429 and 0.262, F1 scores of 0.709 and 0.724, and AUCs of 0.792 and 0.818. Conclusions: Two classifiers were developed and validated in separate cohorts, each achieved excellent performance by integrating different types of molecular data. Implementation of classifiers with these performance characteristics could markedly improve current active surveillance approaches without increasing patient morbidity and may help better inform patients on their individual need for definitive therapy versus active surveillance.
RUNX3: Promoter 1 methylation status
Authors: Connie C. Cortez, Gangning Liang, Anna Van Rietschoten, Li Jia, Yvonne C. Tsai, Gerda Egger, Peter A. Jones
Journal: Cancer Research (2006)

1576  RUNX3 is a transcription factor that is involved in hematopoiesis and the TGF-beta signaling pathway. The RUNX3 gene can either work to activate or repress the transcription of genes. It is regulated by two promoters which code for two separate proteins that differ at the N terminus by 19 amino acids. Promoter 1 (P1) is a non CpG dense promoter, whereas promoter 2 (P2) lies within a 3000 bp CpG island. In mouse, RUNX3 P2 is expressed in almost all tissues and P1 expression is limited to a few lineages or physiological states (activated T cells), which show there is differential promoter usage. It has been reported that in various cancers there is P2 hypermethylation and loss of expression of this transcript. Not much focus is put on the methylation of areas with a low density of CpG sites in gene promoters; therefore the methylation status of RUNX3 P1 has not been studied. We hypothesize that DNA methylation plays a role in the limited expression of this non CpG dense promoter. In our study, the methylation status of RUNX3 P1 was examined in normal human tissues, including EBV-transformed B cells, and blood-fractionated lymphocytes and granulocytes. RUNX3 P1 was highly methylated in most normal tissues studied, however there were lower methylation levels in granulocytes, EBV-transformed B cells, and bone marrow. Interestingly, lymphocytes were devoid of methylation. This suggests a lineage specific methylation pattern in these tissues and blood cell types. Moreover, the EBV-transformed B cells were shown by bisulfite sequencing to either have completely methylated or unmethylated strands in a 1:1 ratio. This data suggests monoallelic methylation in B cells. Based on these findings, methylation may play a role in the expression of RUNX3 P1 in normal tissues.
DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801)—A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation.
Authors: Tamim Niazi, Scott Williams, Ian D. Davis, Martin R. Stockler, Andrew James Martin, Karen Bracken, Felicia Roncolato, Lisa Horvath, Jarad Martin, Tee Sin Lim, Simon Hughes, Raymond S. McDermott, James WF Catto, Paul J. Kelly, Sean Matthew McBride, Wendy R. Parulekar, Scott Carlyle Morgan, Ricardo A. Rendon, Christopher Sweeney
Journal: Journal of Clinical Oncology (2021)

TPS266 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high- risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or adjuvant therapy for very high-risk PC. Methods: This study is a randomized (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localized PC; or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: RP; use of adjuvant docetaxel; pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.
Risk of urinary morbidity associated with photoselective vaporization of the prostate (PVP) in prostate cancer patients undergoing a combined radiotherapy regimen consisting of dynamic adaptive radiotherapy (DART) and brachytherapy boost.
Authors: Michael J. Dattoli, Joseph M Kaminski, Gregory Lawrence, Daniel Kaplon
Journal: Journal of Clinical Oncology (2021)

231 Background: Recent studies have shown PVPs to be associated with diminished perioperative and postoperative complications compared to transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). This is the first study to evaluate the timing of PVP intervention and post-treatment morbidity related to a combined regimen of DART and Pd-103 brachytherapy for treatment of prostate cancer. Methods: Between 12/05 and 04/20, 51 consecutive patients underwent Greenlight Laser (GLL) or Olympus Plasma Button (OPB) PVP after DART (median dose: 45 Gy) and before Pd-103 brachytherapy (median dose: 90 Gy). 27 patients received GLL PVP and 24 patients received OPB PVP. Peripheral seed loading designs were utilized to achieve optimal urethral sparing. The time from DART to PVP ranged from 1 to 81 days (median: 18 days). For 12 patients, the interval between DART and PVP was ≤7 days. The time from PVP to seed implant ranged from 0 to 55 days (median: 18 days). For 13 patients, the interval between PVP and implant was ≤7 days. American Urological Association (AUA) symptom scores were compiled prior to PVP and on the last post-brachytherapy follow-up. Post-implant follow-up ranged from 6 months to 15 years (median: 6.4 years). Results: No patient experienced post-implant urinary retention or incontinence. Morbidity was limited to RTOG grade 1-2 symptoms, with the exception of one patient who experienced protracted dysuria, which was identified to be secondary to a pre-existing prostate anomaly (steep urethral curvature). Only that patient required dilation for urethral stricture. AUA scores improved or remained the same in 43 of 51 patients. Only 1 patient of the remaining 8 experienced an increase in AUA &gt; 8 points. Conclusions: In our experience, there have been remarkably few adverse urinary sequelae following Pd-103 implantation in patients with prior PVP and DART. In contrast to TURPs, PVPs are safe even with short intervals between DART and brachytherapy. Based upon these results, pre-implant PVP is preferred, rather than PVPs or TURPs in the post-implant setting.
A prospective phase 2/3 study of PSMA-targeted <sup>18</sup>F-DCFPyL-PET/CT in patients (pts) with prostate cancer (PCa) (OSPREY): A sub-analysis of disease staging changes in PCa pts with recurrence or metastases on conventional imaging.
Authors: Jeremy C. Durack, Ajjai Shivaram Alva, Mark A Preston, Frederic Pouliot, Lawrence Saperstein, Peter R. Carroll, Kenneth J. Pienta, Steven P. Rowe, Akash Patnaik, Stephan Probst, Nancy Stambler, Jessica Jensen, Vivien Wong, Barry A. Siegel, Michael J. Morris
Journal: Journal of Clinical Oncology (2021)

e17003 Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18 F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18 F-DCFPyL on staging of pts with high-risk PCa have been previously reported. Here we report on the impact of 18 F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18 F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18 F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18 F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18 F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18 F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18 F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18 F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18 F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.
Abstract PO-036: A sophisticated bioinformatics framework for integrative study of radiomics and genomics profiles of tumors
Authors: Shrey S. Sukhadia, Shivashankar H. Nagaraj, Olivier Gevaert, Sivakumaran Theru Arumugam, Aayush Tyagi, Pritam Mukherjee, A.P. Prathosh
Journal: Clinical Cancer Research (2021)

Abstract The potential for radiomics to support oncology decision-making has grown substantially in recent years, as these scanning techniques have been found to offer unique information regarding the tumor phenotype and microenvironment that is distinct from that provided by genomic or proteomic assays. Radiomic and genomic (or proteomic) data can be correlated with one another, thereby facilitating radiogenomic efforts. Radiogenomically-informed biopsies have the potential to yield better pathological outcomes and can aid in the planning of more appropriate treatment strategies for cancer patients. However, the field lacks a unified software platform wherein radiomic and genomics/proteomic data could be brought together to conduct a variety of correlational analyses and build robust artificial intelligence models that would aid the prediction of genomic/proteomic profiles of tumors from their radiological images. We have built such a comprehensive platform that could be utilized by scientists and clinicians globally to conduct radiogenomic studies for a variety of cancer types, and further validate and deploy it in clinics to aid effective monitoring, diagnosis, and treatment of cancer patients. Citation Format: Shrey S. Sukhadia, Shivashankar H. Nagaraj, Olivier Gevaert, Sivakumaran Theru Arumugam, Aayush Tyagi, Pritam Mukherjee, A.P. Prathosh. A sophisticated bioinformatics framework for integrative study of radiomics and genomics profiles of tumors [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-036.
Stopping smoking may improve mental health, Cochrane review finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

People who stop smoking are not likely to experience a long term worsening in mood and may see improvements in their mental health, such as reduced symptoms of anxiety and depression, a Cochrane review has found.1

The review, which brought together the results from 63 studies that measured changes in mental health symptoms during smoking cessation, reported that people who stopped smoking for at least six weeks experienced less depression, anxiety, and stress than people who continued to smoke. Evidence also …
Abstract 10199: Atrial Fibrillation is Associated With Impaired Exercise Capacity and Adverse Prognosis in Heart Failure Patients With Mid-range Ejection Fraction
Authors: Yu Sato, Akiomi Yoshihisa, Yu Hotsuki, Koichiro Watanabe, Yusuke Kimishima, Takatoyo Kiko, Yuki Kanno, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Introduction: Exercise capacity represented by peak oxygen uptake (VO2) is an independent predictor of cardiac event in heart failure (HF) patients with reduced ejection fraction. However, factors ...
Role of extracellular vesicles in chronic lung disease
Authors: Anne Trappe, Seamas C Donnelly, Paul McNally, Judith A Coppinger
Journal: Thorax (2021)

To explore the role of extracellular vesicles (EVs) in chronic lung diseases. EVs are emerging as mediators of intercellular communication and possible diagnostic markers of disease. EVs harbour cargo molecules including RNA, lipids and proteins that they transfer to recipient cells. EVs are intercellular communicators within the lung microenvironment. Due to their disease-specific cargoes, EVs have the promise to be all-in-one complex multimodal biomarkers. EVs also have potential as drug carriers in chronic lung disease. Descriptive discussion of key studies of EVs as contributors to disease pathology, as biomarkers and as potential therapies with a focus on chronic obstructive pulmonary disorder (COPD), cystic fibrosis (CF), asthma, idiopathic pulmonary fibrosis and lung cancer. We provide a broad overview of the roles of EV in chronic respiratory disease. Recent advances in profiling EVs have shown their potential as biomarker candidates. Further studies have provided insight into their disease pathology, particularly in inflammatory processes across a spectrum of lung diseases. EVs are on the horizon as new modes of drug delivery and as therapies themselves in cell-based therapeutics. EVs are relatively untapped sources of information in the clinic that can help further detail the full translational nature of chronic lung disorders.
COVID-19 Rates Increased Where In-Person College Classes Were Held: The Journal of the American Medical Association
Authors: Bridget M. M. S. J. Kuehn
Journal: JAMA (2021)

Coronavirus disease 2019 (COVID-19) incidence increased by 56% in counties where colleges held in-person classes after the start of the fall 2020 school year, the US CDC reported  As COVID-19 incidence generally declined in US counties in early August 2020, incidence rates increased among young adults aged 18 to 22 years  Such increases have been identified as a driving force of infection among adults older than 60 years, who are at increased risk of severe illness and death  To determine whether large universities' instructional format--in-person or remote classes--was associated with COVID-19 incidence in the surrounding communities, CDC investigators analyzed data from 101 counties where classes started between July 27 and August 28, 2020
Extracellular Tuning of Mitochondrial Respiration Leads to Aortic Aneurysm
Authors: Jorge Oller, Enrique Gabandé-Rodríguez, María Jesús Ruiz-Rodríguez, Gabriela Desdín-Micó, Juan Francisco Aranda, Raquel Rodrigues-Diez, Constanza Ballesteros-Martínez, Eva María Blanco, Raquel Roldan-Montero, Pedro Acuña, Alberto Forteza Gil, Carlos E. Martín-López, J. Francisco Nistal, Christian L. Lino Cardenas, Mark Evan Lindsay, José Luís Martín-Ventura, Ana M. Briones, Juan Miguel Redondo, María Mittelbrunn
Journal: Circulation (2021)

Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the