tbuckley/cabot-search huggingface dataset:
RETRACTED ARTICLE: LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis
Authors: Yiran Liang, Xiaojin Song, Yaming Li, Bing Chen, Wenjing Zhao, Lijuan Wang, Hanwen Zhang, Ying Liu, Dianwen Han, Ning Zhang, Tingting Ma, Yajie Wang, Fangzhou Ye, Dan Luo, Xiaoyan Li, Qifeng Yang
Journal: Molecular Cancer (2020)

Abstract Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown. Methods Based on public databases and integrating bioinformatics analyses, the overexpression of lncRNA BCRT1 in breast cancer tissues was detected and further validated in a cohort of breast cancer tissues. The effects of lncRNA BCRT1 on proliferation, migration, invasion and macrophage polarization were determined by in vitro and in vivo experiments. Luciferase reporter assay and RNA immunoprecipitation (RIP) were carried out to reveal the interaction between lncRNA BCRT1, miR-1303, and PTBP3. Chromatin immunoprecipitation (ChIP) and RT-PCR were used to evaluate the regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on lncRNA BCRT1. Results LncRNA BCRT1 was significantly upregulated in breast cancer tissues, which was correlated with poor prognosis in breast cancer patients. LncRNA BCRT1 knockdown remarkably suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, lncRNA BCRT1 could competitively bind with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes, which further accelerated breast cancer progression. Furthermore, lncRNA BCRT1 was upregulated in response to hypoxia, which was attributed to the binding of HIF-1α to HREs in the lncRNA BCRT1 promoter. Conclusions Collectively, these results reveal a novel HIF-1α/lncRNA BCRT1/miR-1303/PTBP3 pathway for breast cancer progression and suggest that lncRNA BCRT1 might be a potential biomarker and therapeutic target for breast cancer.
OTU-03 Pancreaticobiliary endoscopic ultrasound in england 2007–2017: changing practice, benefits and harms
Authors: Dominic King, Amandeep Dosanjh, Prashant Patel, John Leeds, Manu Nayar, Nigel Trudgill, Kofi Oppong
Journal: Endoscopy (2019)

<h3>Introduction</h3> Population level data on complications and outcomes of pancreaticobiliary (PB) endoscopic ultrasound (EUS) are limited. A perforation rate of 0.03% and attributable morbidity and mortality from pancreatic EUS fine needle aspiration (FNA) of 2.4% and 0.02% respectively are reported. We have examined PB EUS &amp; FNA use in England, how it relates to pancreatic cancer (PC) therapy and associated mortality and adverse events. <h3>Methods</h3> Adults undergoing PB EUS from 2007–17 were identified in Hospital Episode Statistics. A PC diagnosis within 6 months of EUS was required for PC cohort inclusion. EUS and FNA numbers per year, associated 7-day adverse events and 30-day mortality were examined. A logistic regression model examined the impact of variables on mortality and surgical resection. <h3>Results</h3> 79,490 PB EUS in 69,120 subjects were identified. The number per year increased from 2,915 (29% FNA) to 12,764 (35% FNA) over the study period. 8,859 subjects were diagnosed with PC. Bleeding was coded in 0.4% of PB EUS. Perforation was coded in 0.03% and in 0.05% of the PC cohort. 1.6% of PB EUS subjects and 2.8% in the PC cohort died within 30 days of their final EUS. The following factors were associated with increased mortality: increasing age (odds ratio 1.04(95%CI 1.03–1.04),p&lt;0.001); males (1.38(1.22–1.56), p&lt;0.001); increasing co-morbidity (1.49 (1.28–1.75), p&lt;0.001); FNA (2.20 (1.93–2.51), p&lt;0.001); pancreatic cancer (1.37 (1.17–1.60), p&lt;0.001); and low provider total PB EUS volume [baseline &gt;782 EUS] 8–111 (3.99 (2.95–5.38), p&lt;0.001), 112–782 (1.33 (1.13–1.57), p=0.001). Less deprivation was associated with reduced mortality: quintile 5 (0.76 (0.62–0.92), p=0.006). 32.9% of PC subjects had a surgical resection, 43.1% received chemotherapy alone and 33.1% had no active therapy. Increasing age (0.97(95%CI 0.96–0.97), p&lt;0.001), increasing co-morbidity score (0.77(0.60–0.98), p=0.034) and multiple EUS procedures prior to PC diagnosis (0.80(0.66–0.98), p=0.033) were all associated with a lower resection rate. The two least deprived quintiles were associated with an increased resection rate (quintile 4 1.33(1.11–1.59), p=0.002), quintile 5 1.33 (1.11–1.59), p=0.002). <h3>Conclusions</h3> The number of PB-EUS undertaken in England has increased six-fold over the last decade, with an increased proportion of FNA. Deprivation and low provider volume were associated with 30 day mortality. A third of subjects undergoing PB EUS for PC did not receive surgery or chemotherapy. The results of this study support a reappraisal of the provision of and indications for PB EUS.
PTH-056 Hemospray use in acute gastrointestinal bleeding- A 4 year single centre experience
Authors: Tarun Gupta, Farique Leet, Matthew Harborne, Uday Nagesh Shivaji, Ashish Awasthi
Journal: Endoscopy (2018)

<h3>Introduction</h3> Upper GI bleeding (UGIB) has a mortality of about 10% in UK despite advances in treatment. The current guidelines recommend dual modality of treatment which could include injection of adrenaline, argon photocoagulation or using endoscopic clips to achieve haemostasis. A recent addition to therapeutic options is Hemospray. Since June 2013, there have been reports from UK that it is useful as an adjunct in treatment of UGIB with most reporting success rates of 77%–85%. It has been suggested that it may not be reliable when used as the only mode of treatment. We report our experience using the product in our centre over 4 years (2013 to 2017). <h3>Methods</h3> A retrospective review of patients using trust endoscopy database (Endosoft) between July 2013 &amp;amp July 2017. We looked at electronic records of patients who underwent an endoscopy and needed Hemospray as a mode of treatment for managing an acute gastrointestinal (GI) bleed. <h3>Results</h3> 45 consecutive patients (M=31), with median age 72 years (range 35–91 years) were included. The mean haemoglobin prior to endoscopy was 92 g/L. 40% were on anticoagulants or anti-platelets on admission. Of all patients who needed Hemospray, 43 had gastroscopies, 1 ERCP and 1 had colonoscopy. The details of diagnosis are in table 1. 23. 39 (86%) patients had Hemospray as adjunct therapy &amp; all patients had complete haemostasis documented at the end of index procedure. 24. It was used as the only modality of therapy successfully in 6 patients (4 with malignancy and 2 iatrogenic bleeds) 25. Overall, 6/45 patients had a documented rebleed after discharge but within 4 weeks; 4 had bleeding vessels and were on warfarin or Ticagrelor; 2 patients had tumour related recurrent bleeding. 26. Forrest classification applicable to 22 patients –1A (n=3, 15%), 1B (n=10, 46%), 2A (n=3, 15%), 2B (n=3, 15%), 2C (n=2, 9%). 27. 100% (n=7) of UGIB related to malignancy responded to Hemospray (adjunct and monotherapy included) 28. 30 day mortality was 24% (n=11) with 3 deaths directly attributed to GI bleeding (4 palliative secondary to malignancy and 4 multifactorial in elderly patients). <h3>Conclusions</h3> Our 4 year experience suggests that Hemospray can be a useful adjunct to conventional endoscopic therapy for acute GI bleed with success rates comparable to previous reports (nearly 85% in our cohort), with a rebleed rate of 14%. Our findings suggest it could be useful as monotherapy for bleeding related to malignancies where other therapy may be impractical. More studies with larger numbers are needed to add to the evidence base.
NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response
Authors: Sandra M. Swain, Gong Tang, Heather Ann Brauer, David S. Goerlitz, Peter C. Lucas, André Robidoux, Brent T. Harris, Hanna Bandos, Yuqi Ren, Charles E. Geyer, Priya Rastogi, Eleftherios P. Mamounas, Norman Wolmark
Journal: Clinical Cancer Research (2020)

In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41.Eligible patients had a baseline preadjuvant treatment core biopsy sample, known pCR status, and no withdrawal of consent. We analyzed extracted RNA using the human nCounter Breast Cancer 360 gene expression panel. Gene counts were normalized to housekeeping genes and transformed into logarithmic scale with base 2. To screen for candidate genes and metagene signatures prognostic of pCR, we used univariate logistic regression. Variable selection was done by multivariable logistic regression with lasso regularization.Analyses of data from 130 patients revealed that a composite of gene expression from 19 genes and one gene signature appeared to predict pCR in women with HER2-positive early-stage breast cancer undergoing neoadjuvant chemotherapy with trastuzumab-containing regimens. The identified genes are involved in important pathways such as epithelial-mesenchymal transition, adhesion and migration, estrogen receptor signaling, DNA damage and repair, apoptosis, and proliferation. The AUC from a 10-fold cross-validation on predicting pCR, with these 20 genomic markers in a logistic regression model, was 0.73.The expression level of ERBB2, ESR1, and a few other genomic markers was highly predictive of pCR after trastuzumab-containing regimens. These findings need to be validated and calibrated in future studies.
Somatic Tissue Engineering in Mouse Models Reveals an Actionable Role for WNT Pathway Alterations in Prostate Cancer Metastasis
Authors: Josef Leibold, Marcus Ruscetti, Zhen Cao, Yu-Jui Ho, Timour Baslan, Min Zou, Wassim Abida, Judith Feucht, Teng Han, Francisco M. Barriga, Kaloyan M. Tsanov, Leah Zamechek, Amanda Kulick, Corina Amor, Sha Tian, Katarzyna Rybczyk, Nelson R. Salgado, Francisco J. Sánchez-Rivera, Philip A. Watson, Elisa de Stanchina, John E. Wilkinson, Lukas E. Dow, Cory Abate-Shen, Charles L. Sawyers, Scott W. Lowe
Journal: Cancer Discovery (2020)

Abstract To study genetic factors influencing the progression and therapeutic responses of advanced prostate cancer, we developed a fast and flexible system that introduces genetic alterations relevant to human disease directly into the prostate glands of mice using tissue electroporation. These electroporation-based genetically engineered mouse models (EPO-GEMM) recapitulate features of traditional germline models and, by modeling genetic factors linked to late-stage human disease, can produce tumors that are metastatic and castration-resistant. A subset of tumors with Trp53 alterations acquired spontaneous WNT pathway alterations, which are also associated with metastatic prostate cancer in humans. Using the EPO-GEMM approach and an orthogonal organoid-based model, we show that WNT pathway activation drives metastatic disease that is sensitive to pharmacologic WNT pathway inhibition. Thus, by leveraging EPO-GEMMs, we reveal a functional role for WNT signaling in driving prostate cancer metastasis and validate the WNT pathway as therapeutic target in metastatic prostate cancer. Significance: Our understanding of the factors driving metastatic prostate cancer is limited by the paucity of models of late-stage disease. Here, we develop EPO-GEMMs of prostate cancer and use them to identify and validate the WNT pathway as an actionable driver of aggressive metastatic disease. This article is highlighted in the In This Issue feature, p. 890
Splenic Marginal Zone B-Cell Lymphoma: Clinical Clustering of Immunoglobulin Heavy Chain Repertoires.
Authors: Silvia Zibellini, Luca Arcaini, Francesco Passamonti, Sara Rattotti, Marco Lucioni, Rosangela Invernizzi, Cristina Picone, Elisa Rumi, Michele Merli, Silvia Rizzi, Emanuela Boveri, Marzia Varettoni, Cristiana Pascutto, Marco Paulli, Mario Lazzarino
Journal: Blood (2008)
Acute myocardial infarctions and stroke triggered by laboratory-confirmed respiratory infections in Denmark, 2010 to 2016
Authors: Jessica Ohland, Charlotte Warren-Gash, Ruth Blackburn, Kåre Mølbak, Palle Valentiner-Branth, Jens Nielsen, Hanne-Dorthe Emborg
Journal: Eurosurveillance (2020)

Background Several studies have investigated a possible association between respiratory infection and acute myocardial infarction (MI). As both influenza and pneumococcal infections are vaccine preventable, understanding the populations affected by virus-induced cardiovascular complications is important to guide public health and clinical practice. Aim This observational study aimed to quantify the association between laboratory-confirmed respiratory bacteria or virus infections and risk of first MI or stroke, by using self-controlled case series (SCCS) analysis of anonymised linked electronic Danish health records. Methods The SCCS method was used to determine the relative incidence of the first event of MI and stroke occurring within 28 days after laboratory-confirmed respiratory infections compared with the baseline time period. Results In the age and season adjusted analyses for first acute MI, the incidence ratios (IR) of a MI event occurring during the risk period were significantly elevated following a Streptococcus pneumoniae infection with values of 20.1, 11.0 and 4.9 during 1–3, 4–7 and 8–14 days, respectively and following respiratory virus infection with values of 15.2, 4.5 and 4.4 during 1–3, 8–14 and 15–28 days, respectively. The significantly elevated IRs for stroke following an S. pneumoniae infection were 25.5 and 6.3 during 1–3 and 8–14 days, respectively and following respiratory virus infection 8.3, 7.8 and 6.2 during 1–3, 4–7 and 8–14 days, respectively. Conclusion This study suggested a significant cardiovascular event triggering effect following infection with S. pneumoniae and respiratory viruses (mainly influenza), indicating the importance of protection against vaccine-preventable respiratory infections.
Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas
Authors: Denise Bernhardt, Wolfgang Wick, Stephanie E Weiss, Arjun Sahgal, Simon S Lo, John H Suh, Eric L Chang, Matthew Foote, James Perry, Bernhard Meyer, Peter Vajkoczy, Patrick Y Wen, Christoph Straube, Steffi Pigorsch, Jan J Wilkens, Stephanie E Combs
Journal: Neuro-Oncology (2020)

Because of the increased risk in cancer patients of developing complications caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the competing risks of the negative impact of the pandemic and the primary tumor. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGG) during the coronavirus disease 2019 (COVID-19) pandemic.
Screening for Prostate Cancer
Authors: Thomas H. Lee, Philip W. Kantoff, Mary F. McNaughton-Collins
Journal: New England Journal of Medicine (2009)

In two large randomized trials, researchers examined the effect of annual prostate-specific–antigen (PSA) screening on the rate of death from prostate cancer and found that it was small and was offset by false positive diagnoses. Since screening may have benefits in catching cancers early but may also carry risks including that of unnecessary treatment, professional societies have split on the question of whether to recommend regular PSA screening. In a roundtable discussion moderated by Dr. Thomas Lee, oncologist Philip Kantoff and primary care physician Mary McNaughton-Collins debate the clinical implications of the new findings and the best way to advise . . .
Gene expression analysis of multiple gastrointestinal regions reveals activation of common cell regulatory pathways following cytotoxic chemotherapy
Authors: Joanne Bowen, Rachel Gibson, Anna Tsykin, Andrea Stringer, Richard Logan, Dorothy Keefe
Journal: Clinical Cancer Research (2007)

A70   Introduction: Chemotherapy-induced gastrointestinal mucositis involves many changes at the gene level, affecting epithelial/subepithelial interactions and leading to overt damage. The regional specificity and time course of these changes, and how they relate to subsequent mucositis development however remain unknown. The aim of this study was to determine the early time course of gene expression changes along the gastrointestinal tract of the DA rat following cytotoxic treatment.  Methods: Female DA rats were treated with a single dose of 200 mg/kg irinotecan to induce mucositis, and were killed at short intervals following treatment. Small sections of stomach, jejunum and colon were harvested for analysis of genetic profiles. RNA was hybridised to high density Affymetrix oligonucleotide microarrays. Data analysis was carried out with the freely available software package, TimeCourse, run through Bioconductor.  Results: As early as 1 hour following chemotherapy, expression of hundreds of genes was altered, including those for transcription factors, stress response proteins and protein turnover. These genes are involved in cell proliferation, differentiation and apoptosis along with other cellular processes within the gastrointestinal tract. A preserved subset of altered genes with degrees of change was observed for the three regions investigated. At early time points, there was a significant response involving the mitogen-activated protein kinase pathway, cell cycle regulation and cytokine receptor signalling. At later time points, changes to the complement cascade and TNF/stress pathway became prominent.  Conclusions: We have shown that changes in gene expression following chemotherapy occur by 1 hour, and persist for at least 72 h after treatment. Conserved genes are affected along the length of the gastrointestinal tract and they regulate several of the pathways already implicated in oral mucositis development. Many of these changes are highly likely to be related to the subsequent development of gastrointestinal mucositis and should be investigated further to identify specific biomarkers of damage.
Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients
Authors: Lisa Derosa, Bertrand Routy, Marine Fidelle, Valerio Iebba, Laurie Alla, Edoardo Pasolli, Nicola Segata, Aude Desnoyer, Filippo Pietrantonio, Gladys Ferrere, Jean-Eudes Fahrner, Emmanuelle Le Chatellier, Nicolas Pons, Nathalie Galleron, Hugo Roume, Connie P.M. Duong, Laura Mondragón, Kristina Iribarren, Mélodie Bonvalet, Safae Terrisse, Conrad Rauber, Anne-Gaëlle Goubet, Romain Daillère, Fabien Lemaitre, Anna Reni, Beatrice Casu, Maryam Tidjani Alou, Carolina Alves Costa Silva, Didier Raoult, Karim Fizazi, Bernard Escudier, Guido Kroemer, Laurence Albiges, Laurence Zitvogel
Journal: European Urology (2020)
Disparities in the Use of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma
Authors: Jordan M. Cloyd, Chengli Shen, Heena Santry, John Bridges, Mary Dillhoff, Aslam Ejaz, Timothy M. Pawlik, Allan Tsung
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: Current guidelines support either immediate surgical resection or neoadjuvant therapy (NT) for patients with resectable pancreatic ductal adenocarcinoma (PDAC). However, which patients are selected for NT and whether disparities exist in the use of NT for PDAC are not well understood. Methods: Using the National Cancer Database from 2004 through 2016, the clinical, demographic, socioeconomic, and hospital-related characteristics of patients with stage I/II PDAC who underwent immediate surgery versus NT followed by surgery were compared. Results: Among 58,124 patients who underwent pancreatectomy, 8,124 (14.0%) received NT whereas 50,000 (86.0%) did not. Use of NT increased significantly throughout the study period (from 3.5% in 2004 to 26.4% in 2016). Multivariable logistic regression analysis showed that travel distance, education level, hospital facility type, clinical T stage, tumor size, and year of diagnosis were associated with increased use of NT, whereas comorbidities, uninsured/Medicaid status, South/West geography, left-sided tumor location, and increasing age were associated with immediate surgery (all P &lt;.001). Based on logistic regression–derived interaction factors, the association between NT use and median income, education level, Midwest location, clinical T stage, and clinical N stage significantly increased over time (all P &lt;.01). Conclusions: In addition to traditional clinicopathologic factors, several demographic, socioeconomic, and hospital-related factors are associated with use of NT for PDAC. Because NT is used increasingly for PDAC, efforts to reduce disparities will be critical in improving outcomes for all patients with pancreatic cancer.
Low rate of severe acute respiratory syndrome coronavirus 2 spread among health-care personnel using ordinary personal protection equipment in a medium-incidence setting
Authors: E. Durante-Mangoni, R. Andini, L. Bertolino, F. Mele, M. Bernardo, M. Grimaldi, N. Cuomo, C. Tiberio, E. Falco, A. Di Spirito, M. Raffone, M.G. Russo, L. Atripaldi, R. Zampino
Journal: Clinical Microbiology and Infection (2020)
Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme
Authors: Rachel L. Manthe, Maximilian Loeck, Tridib Bhowmick, Melani Solomon, Silvia Muro
Journal: Journal of Controlled Release (2020)

The interaction of drug delivery systems with tissues is key for their application. An example is drug carriers targeted to endothelial barriers, which can be transported to intra-endothelial compartments (lysosomes) or transcellularly released at the tissue side (transcytosis). Although carrier targeting valency influences this process, the mechanism is unknown. We studied this using polymer nanocarriers (NCs) targeted to intercellular adhesion molecule-1 (ICAM-1), an endothelial-surface glycoprotein whose expression is increased in pathologies characterized by inflammation. A bell-shaped relationship was found between NC targeting valency and the rate of transcytosis, where high and low NC valencies rendered less efficient transcytosis rates than an intermediate valency formulation. In contrast, an inverted bell-shape relationship was found for NC valency and lysosomal trafficking rates. Data suggested a model where NC valency plays an opposing role in the two sub-processes involved in transcytosis: NC binding-uptake depended directly on valency and exocytosis-detachment was inversely related to this parameter. This is because the greater the avidity of the NC-receptor interaction the more efficient uptake becomes, but NC-receptor detachment post-transport is more compromised. Cleavage of the receptor at the basolateral side of endothelial cells facilitated NC transcytosis, likely by helping NC detachment post-transport. Since transcytosis encompasses both sets of events, the full process finds an optimum at the intersection of these inverted relationships, explaining the bell-shaped behavior. NCs also trafficked to lysosomes from the apical side and, additionally, from the basolateral side in the case of high valency NCs which are slower at detaching from the receptor. This explains the opposite behavior of NC valency for transcytosis vs. lysosomal transport. Anti-ICAM NCs were verified to traffic into the brain after intravenous injection in mice, and both cellular and in vivo data showed that intermediate valency NCs resulted in higher delivery of a therapeutic enzyme, acid sphingomyelinase, required for types A and B Niemann-Pick disease.