المؤلفون: Thomas, Emma E., Kelly, Jaimon T., Taylor, Monica L., Mendis, Roshni, Banbury, Annie, Haydon, Helen, Catto, Janessa, Der Vartanian, Carolyn, Smith, Anthony C., Caffery, Liam J.

المصدر: Thomas , E E , Kelly , J T , Taylor , M L , Mendis , R , Banbury , A , Haydon , H , Catto , J , Der Vartanian , C , Smith , A C & Caffery , L J 2023 , ' Telehealth adoption in cancer clinical trials: An Australian perspective ' , Asia Pacific Journal of Clinical Oncology , vol. 19 , no. 4 , pp. 549-558 . https://doi.org/10.1111/ajco.13899Test

مصطلحات موضوعية: cancer, clinical trials, COVID-19, oncology, telehealth, Pandemics, Neoplasms/therapy, Telemedicine, Humans, Australia

الوصف: Introduction Cancer clinical trials have traditionally occurred in-person. However, the COVID-19 pandemic has forced adaptions of all aspects of cancer care (including clinical trials) so they can be delivered remotely. We aimed to quantify and qualify current use of telehealth and how it can be further improved and routinely integrated into cancer clinical trials in Australia. MethodsWe used a mixed-method study design, involving surveys of 14 multi-site Collaborative Cancer Clinical Trial Groups members across Australia (n = 98) and qualitative interviews with trial administrators and clinicians (n = 21). ResultsThe results of our study indicated a strong willingness to use telehealth for certain transactions of clinical trials because it was perceived as a way of increasing efficiency and reach of services. Hybrid models (including telehealth and in-person methods), which considered transaction, cancer type, and patient preferences were most favorable. Additionally, telehealth allowed for greater equity to access and reduced trial burden but interestingly had little effect on increased diversity and recruitment. Factors influencing telehealth service implementation and uptake included communication among trial stakeholders, training, and learning from the experience of others in the clinical trials community. ConclusionMany but not all aspects of clinical trial care are appropriate to be delivered via telehealth. A hybrid approach provides flexibility to trial delivery and may support greater equity of access to trials in the future. Our findings and actionable recommendations support the need for greater planning, training, and guidelines to enable telehealth to be better integrated into clinical trials. Opportunities exist to expand the use of remote patient monitoring to enable more objective data collection from trial participants in the future.

وصف الملف: application/pdf

العلاقة: https://portal.findresearcher.sdu.dk/da/publications/86738a37-fcdb-4459-8512-659e246dd0ccTest

الإتاحة: https://doi.org/10.1111/ajco.13899Test
https://portal.findresearcher.sdu.dk/da/publications/86738a37-fcdb-4459-8512-659e246dd0ccTest
https://findresearcher.sdu.dk/ws/files/221112731/Asia_Pac_J_Clncl_Oncology_2022_Thomas_Telehealth_adoption_in_cancer_clinical_trials_An_Australian_perspective.pdfTest

المؤلفون: Newton, Robert U, Kenfield, Stacey A, Hart, Nicolas H, Chan, June M, Courneya, Kerry S, Catto, James, Finn, Stephen P, Greenwood, Rosemary, Hughes, Daniel C, Mucci, Lorelei, Plymate, Stephen R, Praet, Stephan FE, Guinan, Emer M, Van Blarigan, Erin L, Casey, Orla, Buzza, Mark, Gledhill, Sam, Zhang, Li, Galvão, Daniel A, Ryan, Charles J, Saad, Fred

المصدر: BMJ open. 8(5)

مصطلحات موضوعية: Humans, Disease Progression, Benzamides, Nitriles, Phenylthiohydantoin, Androstenes, Androgen Antagonists, Receptors, Androgen, Exercise Therapy, Quality of Life, United States, Male, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Clinical Trials, Phase III as Topic, Prostatic Neoplasms, Castration-Resistant, disease progression, immune function, inflammation, physical activity, tumour biology, Cancer, Prostate Cancer, Aging, Urologic Diseases, Clinical Trials and Supportive Activities, Pain Research, Chronic Pain, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences

الوصف: IntroductionPreliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC).Methods and analysisParticipants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatment-naïve for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant's fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation.Ethics and disseminationValidation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation.Trial registration numberNCT02730338.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/93g3s30hTest

المؤلفون: Leonardo Pisani, Marco Catto, Giovanni Muncipinto, Orazio Nicolotti, Antonio Carrieri, Mariagrazia Rullo, Angela Stefanachi, Francesco Leonetti, Cosimo Altomare

المصدر: Frontiers in Chemistry, Vol 10 (2022)

مصطلحات موضوعية: cholinesterases, monoamine oxidases, coumarin, neurodegeneration, cancer, Chemistry, QD1-999

الوصف: The coumarin core (i.e., 1-benzopyran-2 (2H)-one) is a structural motif highly recurrent in both natural products and bioactive molecules. Indeed, depending on the substituents and branching positions around the byciclic core, coumarin-containing compounds have shown diverse pharmacological activities, ranging from anticoagulant activities to anti-inflammatory, antimicrobial, anti-HIV and antitumor effects. In this survey, we have reported the main scientific results of the 20-years investigation on the coumarin core, exploited by the research group headed by Prof. Angelo Carotti (Bari, Italy) either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fchem.2022.1002547/fullTest; https://doaj.org/toc/2296-2646Test

الوصول الحر: https://doaj.org/article/53ff1d25b4064b7f8ec8c3ec6647bf7dTest

المؤلفون: Robertson, A Gordon, Kim, Jaegil, Al-Ahmadie, Hikmat, Bellmunt, Joaquim, Guo, Guangwu, Cherniack, Andrew D, Hinoue, Toshinori, Laird, Peter W, Hoadley, Katherine A, Akbani, Rehan, Castro, Mauro AA, Gibb, Ewan A, Kanchi, Rupa S, Gordenin, Dmitry A, Shukla, Sachet A, Sanchez-Vega, Francisco, Hansel, Donna E, Czerniak, Bogdan A, Reuter, Victor E, Su, Xiaoping, Carvalho, Benilton de Sa, Chagas, Vinicius S, Mungall, Karen L, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Lu, Yiling, Klimczak, Leszek J, Zhang, Jiexin, Choo, Caleb, Ojesina, Akinyemi I, Bullman, Susan, Leraas, Kristen M, Lichtenberg, Tara M, Wu, Catherine J, Schultz, Nicholaus, Getz, Gad, Meyerson, Matthew, Mills, Gordon B, McConkey, David J, Network, TCGA Research, Albert, Monique, Alexopoulou, Iakovina, Ally, Adrian, Antic, Tatjana, Aron, Manju, Balasundaram, Miruna, Bartlett, John, Baylin, Stephen B, Beaver, Allison, Birol, Inanc, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bowlby, Reanne, Brooks, Denise, Broom, Bradley M, Bshara, Wiam, Burks, Eric, Cárcano, Flavio M, Carlsen, Rebecca, Carvalho, Benilton S, Carvalho, Andre L, Castle, Eric P, Castro, Patricia, Catto, James W, Chesla, David W, Chuah, Eric, Chudamani, Sudha, Cortessis, Victoria K, Cottingham, Sandra L, Crain, Daniel, Curley, Erin, Daneshmand, Siamak, Demchok, John A, Dhalla, Noreen, Djaladat, Hooman, Eckman, John, Egea, Sophie C, Engel, Jay, Felau, Ina, Ferguson, Martin L, Gardner, Johanna, Gastier-Foster, Julie M, Gerken, Mark, Gomez-Fernandez, Carmen R, Harr, Jodi

المصدر: Cell. 171(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Cancer Genomics, Urologic Diseases, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Aged, Cluster Analysis, DNA Methylation, Humans, MicroRNAs, Middle Aged, Muscle, Smooth, RNA, Long Noncoding, Survival Analysis, Urinary Bladder, Urinary Bladder Neoplasms, TCGA Research Network, APOBEC mutation, DNA methylation, basal mRNA subtype, lncRNA transcriptome, luminal mRNA subtype, microRNA, muscle-invasive bladder cancer, neoantigen, neuronal subtype, regulon, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences

الوصف: We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9zq1g0w0Test
https://escholarship.org/content/qt9zq1g0w0/qt9zq1g0w0.pdfTest

المؤلفون: Thomas, EE, Kelly, JT, Taylor, ML, Mendis, R, Banbury, A, Haydon, H, Catto, J, Der Vartanian, C, Smith, AC, Caffery, LJ

مصطلحات موضوعية: Oncology and carcinogenesis, Public health, COVID-19, cancer, clinical trials, oncology, telehealth

الوصف: Introduction: Cancer clinical trials have traditionally occurred in-person. However, the COVID-19 pandemic has forced adaptions of all aspects of cancer care (including clinical trials) so they can be delivered remotely. We aimed to quantify and qualify current use of telehealth and how it can be further improved and routinely integrated into cancer clinical trials in Australia. Methods: We used a mixed-method study design, involving surveys of 14 multi-site Collaborative Cancer Clinical Trial Groups members across Australia (n = 98) and qualitative interviews with trial administrators and clinicians (n = 21). Results: The results of our study indicated a strong willingness to use telehealth for certain transactions of clinical trials because it was perceived as a way of increasing efficiency and reach of services. Hybrid models (including telehealth and in-person methods), which considered transaction, cancer type, and patient preferences were most favorable. Additionally, telehealth allowed for greater equity to access and reduced trial burden but interestingly had little effect on increased diversity and recruitment. Factors influencing telehealth service implementation and uptake included communication among trial stakeholders, training, and learning from the experience of others in the clinical trials community. Conclusion: Many but not all aspects of clinical trial care are appropriate to be delivered via telehealth. A hybrid approach provides flexibility to trial delivery and may support greater equity of access to trials in the future. Our findings and actionable recommendations support the need for greater planning, training, and guidelines to enable telehealth to be better integrated into clinical trials. Opportunities exist to expand the use of remote patient monitoring to enable more objective data collection from trial participants in the future. ; Full Text

العلاقة: Asia-Pacific Journal of Clinical Oncology; Thomas, EE; Kelly, JT; Taylor, ML; Mendis, R; Banbury, A; Haydon, H; Catto, J; Der Vartanian, C; Smith, AC; Caffery, LJ, Telehealth adoption in cancer clinical trials: An Australian perspective, Asia-Pacific Journal of Clinical Oncology, 2022; http://hdl.handle.net/10072/421860Test

الإتاحة: https://doi.org/10.1111/ajco.13899Test
http://hdl.handle.net/10072/421860Test

المؤلفون: Boström, Peter J, Bjartell, Anders S, Catto, James WF, Eggener, Scott E, Lilja, Hans, Loeb, Stacy, Schalken, Jack, Schlomm, Thorsten, Cooperberg, Matthew R

المصدر: European Urology. 68(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Aging, Clinical Research, Urologic Diseases, Genetics, Prostate Cancer, Cancer, Human Genome, Prevention, Biotechnology, 4.1 Discovery and preclinical testing of markers and technologies, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Genomics, Humans, Male, Prognosis, Prostatic Neoplasms, Treatment Outcome, Prostate cancer, Prognostic, Predictive, Outcome, Gene panel, Expression panel, Genetic test, RNA, Cell cycle, DNA, Urology & Nephrology, Clinical sciences

الوصف: ContextGiven the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making.ObjectiveTo review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response.Evidence acquisitionSystematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014.Evidence synthesisAn improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points.ConclusionsMajor advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important.Patient summaryWe summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/84n185gnTest

المؤلفون: Glasbey, James, Ademuyiwa, Adesoji, Adisa, Adewale, AlAmeer, Ehab, Arnaud, Alexis P, Ayasra, Faris, Azevedo, José, Minaya-Bravo, Ana, Costas-Chavarri, Ainhoa, Edwards, John, Elhadi, Muhammed, Fiore, Marco, Fotopoulou, Christina, Gallo, Gaetano, Ghosh, Dhruva, Griffiths, Ewen A, Harrison, Ewen, Hutchinson, Peter, Lawani, Ismail, Lawday, Samuel, Lederhuber, Hans, Leventoglu, Sezai, Li, Elizabeth, Gomes, Gustavo Mendonça Ataíde, Mann, Harvinder, Marson, Ella J, Martin, Janet, Mazingi, Dennis, McLean, Kenneth, Modolo, Maria, Moore, Rachel, Morton, Dion, Ntirenganya, Faustin, Pata, Francesco, Picciochi, Maria, Pockney, Peter, Ramos-De la Medina, Antonio, Roberts, Keith, Roslani, April Camilla, Kottayasamy Seenivasagam, Rajkumar, Shaw, Richard, Simões, Joana Filipa Ferreira, Smart, Neil, Stewart, Grant D, Sullivan, Richard, Sundar, Sudha, Tabiri, Stephen, Taylor, Elliott H, Vidya, Raghavan, Nepogodiev, Dmitri, Bhangu, Aneel, Glasbey, James C, Bhangu, Aneel A, Siaw-Acheampong, Kwabena, Benson, Ruth A, Bywater, Edward, Chaudhry, Daoud, Dawson, Brett E, Evans, Jonathan P, Gujjuri, Rohan R, Heritage, Emily, Jones, Conor S, Kamarajah, Sivesh K, Khatri, Chetan, Khaw, Rachel A, Keatley, James M, Knight, Andrew, Mann, Harvinder S, McLean, Kenneth A, Mckay, Siobhan C, Mills, Emily C, Pellino, Gianluca, Tiwari, Abhinav, Simoes, Joana FF, Trout, Isobel M, Venn, Mary L, Wilkin, Richard JW, Smart, Neil J, Moug, Susan, Di Saverio, Salomone, Vallance, Abigail, Vimalchandran, Dale, Evans, Richard PT, Townend, Philip, McKay, Siobhan, Isaac, John, Satoi, Sohei, Coonar, Aman S, Marchbank, Adrian, Caruana, Edward J, Layton, Georgia R, Patel, Akshay, Brunelli, Alessandro, Ford, Samuel, Desai, Anant, Gronchi, Alessandro, Almond, Max, Tirotta, Fabio, Dumitra, Sinziana, Kolias, Angelos, Price, Stephen J, Fountain, Daniel M, Jenkinson, Michael D, Marcus, Hani J, Piper, Rory J, Lippa, Laura, Servadei, Franco, Esene, Ignatius, Freyschlag, Christian, Neville, Iuri, Rosseau, Gail, Schaller, Karl, Demetriades, Andreas K, Robertson, Faith, Alamri, Alex, Schache, Andrew G, Winter, Stuart C, Ho, Michael, Nankivell, Paul, Rey Biel, Juan, Batstone, Martin, Ganly, Ian, Wilkins, Alex, Singh, Jagdeep K, Thekinkattil, Dinesh, Leung, Elaine YL, Khan, Tabassum, Chiva, Luis, Sehouli, Jalid, Fagotti, Anna, Cohen, Paul, Gutelkin, Murat, Ghebre, Rahel, Konney, Thomas, Pareja, Rene, Bristow, Rob, Dowdy, Sean, Shylasree, TS, Ng, Joe, Fujiwara, Keiichi, Lamb, Benjamin, Narahari, Krishna, McNeill, Alan, Colquhoun, Alexandra, McGrath, John S, Bromage, Steve, Barod, Ravi, Kasivisvanathan, Veeru, Klatte, Tobias, Abbott, Tom EF, Abukhalaf, Sadi, Adamina, Michel, Ademuyiwa, Adesoji O, Agarwal, Arnav, Akkulak, Murat, Alameer, Ehab, Alderson, Derek, Alakaloko, Felix, Albertsmeier, Markus, Alser, Osaid, Alshaar, Muhammad, Alshryda, Sattar, Augestad, Knut Magne, Bankhead-Kendall, Brittany K, Barlow, Emma, Beard, David, Blanco-Colino, Ruth, Brar, Amanpreet, Breen, Kerry A, Bretherton, Chris, Buarque, Igor Lima, Burke, Joshua, Chaar, Mohammad, Chakrabortee, Sohini, Christensen, Peter, Cox, Daniel, Cukier, Moises, Cunha, Miguel F, Davidson, Giana H, Drake, Thomas M, Edwards, John G, Emile, Sameh, Farik, Shebani, Fitzgerald, J Edward, Garmanova, Tatiana, Grecinos, Gustavo, Gruendl, Magdalena, Halkias, Constantine, Harrison, Ewen M, Hisham, Intisar, Hutchinson, Peter J, Hwang, Shelley, Isik, Arda, Jonker, Pascal, Kaafarani, Haytham MA, Keller, Debby, Kruijff, Schelto, Litvin, Andrey, Loehrer, Andrew, Löffler, Markus W, Lorena, Maria Aguilera, Modolo, Maria Marta, Major, Piotr, Mashbari, Hassan N, Metallidis, Symeon, Mohan, Helen M, Moszkowicz, David, Ng-Kamstra, Joshua S, Maimbo, Mayaba, Negoi, Ionut, Niquen, Milagros, Olivos, Maricarmen, Oussama, Kacimi, Outani, Oumaima, Parreno-Sacdalanm, Marie Dione, Rivera, Carlos Jose Perez, Pinkney, Thomas D, van der Plas, Willemijn, Qureshi, Ahmad, Radenkovic, Dejan, Richards, Toby, Roslani, April C, Rutegård, Martin, Segura-Sampedro, Juan José, Santos, Irène, Sayyed, Raza, Schache, Andrew, Schnitzbauer, Andreas A, Seyi-Olajide, Justina O, Sharma, Neil, Shaw, Catherine A, Shu, Sebastian, Soreide, Kjetil, Spinelli, Antonino, Sund, Malin, Tsoulfas, Georgios, van Ramshorst, Gabrielle H, Vimalachandran, Dale, Warren, Oliver J, Wedderburn, Duane, Wright, Naomi, EuroSurg, null, Booth, Lesley, Runigamugabo, Emmy, Barker, Margaret, Barker, Neil, Cooke, Shirley, Doré, Suzanne, Horwood, Nigel, Tierney Weir, Carrie, Dajti, I, Allemand, C, Boccalatte, LA, Figari, M, Lamm, M, Larrañaga, J, Marchitelli, C, Noll, F, Odetto, D, Perrotta, M, Saadi, J, Zamora, L, Ballester, AM, Tapper, KE, Zeff, N, Valenzuela, JI, Alurralde, C, Anastasio, J, Apas Perez de Nucci, A, Caram, EL, Eskinazi, D, Mendoza, JP, Usandivaras, M, Badra, R, Esteban, A, García, JS, García, PM, Gerchunoff, JI, Lucchini, SM, NIgra, MA, Vargas, L, Hovhannisyan, T, Stepanyan, A, Vasey, CE, Watson, EGR, Ip, C, Kealey, J, Lim, CSH, Sengupta, S, Ward, S, Wong, E, Gould, T, Gourlay, R, Griffiths, B, Gananadha, S, McLaren, M, Cecire, J, Joshi, N, Salindera, S, Sutherland, A, Ahn, JH, Charlton, G, Chen, S, Gauri, N, Hayhurst, R, Jang, S, Jia, F, Mulligan, C, Yang, W, Ye, G, Zhang, H, Ballal, M, Gibson, D, Hayne, D, McMillan, H, Moss, J, Pugliese, MJ, Richards, T, Seow, YTN, Thian, A, Viswambaram, P, Vo, UG, Bennetts, J, Bright, T, Brooke-Smith, M, Fong, R, Gricks, B, Huang, L, Lam, YH, Nathan, A, Ong, BS, Ooi, E, Szpytma, M, Watson, D, Bagraith, K, Caird, S, Chan, E, Dawson, C, Ho, D, Hui, N, Izwan, S, Jeyarajan, E, Jordan, S, Liang, R, Lim, A, Nolan, GJ, Oar, A, Parker, D, Puhalla, H, Quennell, A, Rutherford, L, Sommerville, C, Townend, P, Von Papen, M, Wullschleger, M, Dawson, AC, Drane, A, Blatt, A, Cope, D, Egoroff, N, Fenton, M, Gani, J, Lott, N, Pockney, P, Shugg, N, Elliott, M, Phung, D, Phan, D, Townend, D, Bong, C, Gundara, J, Frankel, A, Bowman, S, Guerra, GR, Gerns, N, McGeorge, S, Riddell, A, Roberts, M, Rukin, N, Bolt, J, Buddingh, K, Dudi-Venkata, NN, Jog, S, Kroon, HM, Sammour, T, Smith, R, Stranz, C, Batstone, M, Lah, K, McGahan, W, Mitchell, D, Morton, A, Pearce, A, Sheahan, G, Swinson, B, Waldron, A, Walker, P, Alam, N, Banting, S, Chong, L, Choong, P, Clatworthy, S, Foley, D, Fox, A, Hii, MW, Knowles, B, Mack, J, Read, M, Rowcroft, A, Wright, G, Lun, EWY, Lanner, M, Burtscher, J, Trivik-Barrientos, F, Königsrainer, I, Bauer, M, Freyschlag, C, Kafka, M, Messner, F, Öfner, D, Tsibulak, I, Holawe, S, Zimmermann, M, Emmanuel, K, Grechenig, M, Gruber, R, Harald, M, Öhlberger, L, Presl, J, Wimmer, A, Namazov, I, Samadov, E, Barker, D, Boyce, R, Corbin, S, Doyle, A, Eastmond, A, Gill, R, Haynes, A, Millar, S, O'Shea, M, Padmore, G, Paquette, N, Phillips, E, St. John, S, Walkes, K, Abeloos, J, De Backer, T, De Ceulaer, J, Dick, C, Diez-Fraile, A, Lamoral, P, Spaas, C, Ceelen, W, Pattyn, P, Van de putte, D, Van Nieuwenhove, Y, Van Ramshorst, G, Willaert, W, Bazzett-Matabele, L, Chiyapo, SP, Ramogola-Masire, D, 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Adishesh, M, Atherton, R, Baxter, K, Brocklehurst, M, Chaudhury, M, Krishnamohan, N, McAleer, J, Owens, G, Parkin, E, Patkar, P, Phang, I, Aladeojebi, A, Ali, M, Barmayehvar, B, Gaunt, A, Gowda, M, Halliday, E, Kitchen, M, Mansour, F, Nanjaiah, P, Zakai, D, Abbassi-Ghadi, N, Assalaarachchi, H, Currie, A, Flavin, M, Frampton, A, Hague, M, Hammer, C, Hopper, J, Horsnell, J, Humphries, S, Kamocka, A, Madhuri, TK, Preston, S, Singh, P, Stebbing, J, Tailor, A, Walker, D, Coomber, E, Jaunoo, S, Kennedy, L, Airey, A, Bunni, J, Crowley, R, Fairhurst, K, Frost, J, George, R, Lee, S, Mitchell, S, Phull, J, Richards, S, Aljanadi, F, Campbell, A, Glass, A, Hraishawi, I, Jones, M, McIlmunn, C, McIntosh, S, Mhandu, P, O'Donnell, C, Turkington, R, Al-Ishaq, Z, Bhasin, S, Bodla, AS, Burahee, A, Crichton, A, El-Ghobashy, A, Fossett, R, Pigadas, N, Rahman, E, Snee, D, Vidya, R, Yassin, N, Fountain, D, Hasan, MT, Karabatsou, K, Laurente, R, Pathmanaban, O, Barlow, C, Ding, D, Foster, J, Longstaff, L, 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المساهمون: Glasbey, Jame, Ademuyiwa, Adesoji, Adisa, Adewale, AlAmeer, Ehab, Arnaud, Alexis P, Ayasra, Fari, Azevedo, José, Minaya-Bravo, Ana, Costas-Chavarri, Ainhoa, Edwards, John, Elhadi, Muhammed, Fiore, Marco, Fotopoulou, Christina, Gallo, Gaetano, Ghosh, Dhruva, Griffiths, Ewen A, Harrison, Ewen, Hutchinson, Peter, Lawani, Ismail, Lawday, Samuel, Lederhuber, Han, Leventoglu, Sezai, Li, Elizabeth, Gomes, Gustavo Mendonça Ataíde, Mann, Harvinder, Marson, Ella J, Martin, Janet, Mazingi, Denni, McLean, Kenneth, Modolo, Maria, Moore, Rachel, Morton, Dion, Ntirenganya, Faustin, Pata, Francesco, Picciochi, Maria, Pockney, Peter, Ramos-De la Medina, Antonio, Roberts, Keith, Roslani, April Camilla, Kottayasamy Seenivasagam, Rajkumar, Shaw, Richard, Simões, Joana Filipa Ferreira, Smart, Neil, Stewart, Grant D, Sullivan, Richard, Sundar, Sudha, Tabiri, Stephen, Taylor, Elliott H, Vidya, Raghavan, Nepogodiev, Dmitri, Bhangu, Aneel, Glasbey, James C, Bhangu, Aneel A, Siaw-Acheampong, Kwabena, Benson, Ruth A, Bywater, Edward, Chaudhry, Daoud, Dawson, Brett E, Evans, Jonathan P, Gujjuri, Rohan R, Heritage, Emily, Jones, Conor S, Kamarajah, Sivesh K, Khatri, Chetan, Khaw, Rachel A, Keatley, James M, Knight, Andrew, Mann, Harvinder S, McLean, Kenneth A, Mckay, Siobhan C, Mills, Emily C, Pellino, Gianluca, Tiwari, Abhinav, Simoes, Joana FF, Trout, Isobel M, Venn, Mary L, Wilkin, Richard JW, Smart, Neil J, Moug, Susan, Di Saverio, Salomone, Vallance, Abigail, Vimalchandran, Dale

مصطلحات موضوعية: COVID-19, Oncology, cancer, surgery

الوصف: Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20-60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926. Findings: Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16-30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77-0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50-0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80-0·88; p<0·001), and full lockdowns (0·57, 0·54-0·60; p<0·001), remained independently ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34624250; info:eu-repo/semantics/altIdentifier/wos/WOS:000716464100026; volume:22; issue:11; firstpage:1507; lastpage:1517; numberofpages:11; journal:THE LANCET ONCOLOGY; https://hdl.handle.net/11585/834674Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85119114788; https://www.sciencedirect.com/science/article/pii/S1470204521004939?via=ihubTest

الإتاحة: https://doi.org/10.1016/S1470-2045Test(21)00493-9
https://hdl.handle.net/11585/834674Test
https://www.sciencedirect.com/science/article/pii/S1470204521004939?via=ihubTest

المؤلفون: Thorsson V., Gibbs D. L., Brown S. D., Wolf D., Bortone D. S., Ou Yang T. -H., Porta-Pardo E., Gao G. F., Plaisier C. L., Eddy J. A., Ziv E., Culhane A. C., Paull E. O., Sivakumar I. K. A., Gentles A. J., Malhotra R., Farshidfar F., Colaprico A., Parker J. S., Mose L. E., Vo N. S., Liu J., Liu Y., Rader J., Dhankani V., Reynolds S. M., Bowlby R., Califano A., Cherniack A. D., Anastassiou D., Bedognetti D., Mokrab Y., Newman A. M., Rao A., Chen K., Krasnitz A., Hu H., Malta T. M., Noushmehr H., Pedamallu C. S., Bullman S., Ojesina A. I., Lamb A., Zhou W., Shen H., Choueiri T. K., Weinstein J. N., Guinney J., Saltz J., Holt R. A., Rabkin C. S., Caesar-Johnson S. J., Demchok J. A., Felau I., Kasapi M., Ferguson M. L., Hutter C. M., Sofia H. J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J. C., Zhang J. J., Chudamani S., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D. I., Kim J., Lawrence M. S., Lin P., Meier S., Noble M. S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Knijnenburg T., Kramer R., Leinonen K., Miller M., Reynolds S., Shmulevich I., Zhang W., Akbani R., Broom B. M., Hegde A. M., Ju Z., Kanchi R. S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G. B., Ng K. -S., Ryan M., Wang J., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W. K., de Bruijn I., Gao J., Gross B. E., Heins Z. J., Kundra R., La K., Ladanyi M., Luna A., Nissan M. G., Ochoa A., Phillips S. M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S. O., Sun Y., Taylor B. S., Anur P., Peto M., Spellman P., Benz C., Stuart J. M., Wong C. K., Yau C., Hayes D. N., Wilkerson M. D., Ally A., Balasundaram M., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S. J. M., Kasaian K., Lee D., Ma Y., Marra M. A., Mayo M., Moore R. A., Mungall A. J., Mungall K., Robertson A. G., Sadeghi S., Schein J. E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A. C., Beroukhim R., Cibulskis C., Gabriel S. B., Ha G., Meyerson M., Schumacher S. E., Shih J., Kucherlapati M. H., Kucherlapati R. S., Baylin S., Cope L., Danilova L., Bootwalla M. S., Lai P. H., Maglinte D. T., Van Den Berg D. J., Weisenberger D. J., Auman J. T., Balu S., Bodenheimer T., Fan C., Hoadley K. A., Hoyle A. P., Jefferys S. R., Jones C. D., Meng S., Mieczkowski P. A., Perou A. H., Perou C. M., Roach J., Shi Y., Simons J. V., Skelly T., Soloway M. G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P. W., Bellair M., Chang K., Covington K., Creighton C. J., Dinh H., Doddapaneni H., Donehower L. A., Drummond J., Gibbs R. A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D. A., Xi L., Zhao F., Hess J., Appelbaum E. L., Bailey M., Cordes M. G., Ding L., Fronick C. C., Fulton L. A., Fulton R. S., Kandoth C., Mardis E. R., McLellan M. D., Miller C. A., Schmidt H. K., Wilson R. K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J. M., Gerken M., Leraas K. M., Lichtenberg T. M., Ramirez N. C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A. L., de Carvalho A. C., Fregnani J. H., Longatto-Filho A., Reis R. M., Scapulatempo-Neto C., Silveira H. C. S., Vidal D. O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M. L., Castro P. D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E. R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C. P., Malykh A., Barnholtz-Sloan J. S., Barrett W., Devine K., Fulop J., Ostrom Q. T., Shimmel K., Wolinsky Y., Sloan A. E., De Rose A., Giuliante F., Goodman M., Karlan B. Y., Hagedorn C. H., Eckman J., Harr J., Myers J., Tucker K., Zach L. A., Deyarmin B., Kvecher L., Larson C., Mural R. J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S. M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M. -H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D. J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J. J., Owonikoko T., Pickens A., Ramalingam S., Shin D. M., Sica G., Van Meir E. G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K. E., Zwarthoff E. C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W. J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W. G., Kalkanis S., Mikkelsen T., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A. L., Van Bang N., Hanh P. T., Phu B. D., Tang Y., Colman H., Evason K., Dottino P. R., Martignetti J. A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K. J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A. H., Castle E., Chandan V., Cheville J., Copland J. A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J. -P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B. P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R. H., Torbenson M., Yang J. D., Zhang L., Brimo F., Ajani J. A., Gonzalez A. M. A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Lazar A. J., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch O., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T. A., Ghossein R., Gopalan A., Levine D. A., Reuter V., Singer S., Singh B., Tien N. V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J. -W., Hung N. P., Kebebew E., Linehan W. M., Metwalli A. R., Pacak K., Pinto P. A., Schiffman M., Schmidt L. S., Vocke C. D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D. M., Rintoul R. C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A. -P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N. A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J. A., Liptay M. J., Pool M., Seder C. W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M. C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K. -F., Janssen K. -P., Slotta-Huspenina J., Abdel-Rahman M. H., Aziz D., Bell S., Cebulla C. M., Davis A., Duell R., Elder J. B., Hilty J., Kumar B., Lang J., Lehman N. L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W. E., Sexton K. C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S. L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P. R., Chan J. M., Disaia P., Glenn P., Kelley R. K., Landen C. N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A. K., Madan R., Rosenthal H. G., Adebamowo C., Adebamowo S. N., Boussioutas A., Beer D., Giordano T., Mes-Masson A. -M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E. M. M., Quintero-Aguilo M., Carlotti C. G., Dos Santos J. S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C. S., Godwin E. M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K. M., Yang I., Korst R., Rathmell W. K., Fantacone-Campbell J. L., Hooke J. A., Kovatich A. J., Shriver C. D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M. A., Lee J. I., Aredes N. D., Mariamidze A., Serody J. S., Demicco E. G., Disis M. L., Vincent B. G.

المساهمون: Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Ou Yang, T. -H., Porta-Pardo, E., Gao, G. F., Plaisier, C. L., Eddy, J. A., Ziv, E., Culhane, A. C., Paull, E. O., Sivakumar, I. K. A., Gentles, A. J., Malhotra, R., Farshidfar, F., Colaprico, A., Parker, J. S., Mose, L. E., Vo, N. S., Liu, J., Liu, Y., Rader, J., Dhankani, V., Reynolds, S. M., Bowlby, R., Califano, A., Cherniack, A. D., Anastassiou, D., Bedognetti, D., Mokrab, Y., Newman, A. M., Rao, A., Chen, K., Krasnitz, A., Hu, H., Malta, T. M., Noushmehr, H., Pedamallu, C. S., Bullman, S., Ojesina, A. I., Lamb, A., Zhou, W., Shen, H., Choueiri, T. K., Weinstein, J. N., Guinney, J., Saltz, J., Holt, R. A., Rabkin, C. S., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. J., Chudamani, S., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., Defreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Knijnenburg, T., Kramer, R., Leinonen, K., Miller, M., Reynolds, S., Shmulevich, I., Zhang, W., Akbani, R., Broom, B. M., Hegde, A. M., Ju, Z., Kanchi, R. S.

مصطلحات موضوعية: immune, cancer, methods

الوصف: (Immunity 48, 812–830.e1–e14; April 17, 2018) In the originally published version of this article, the authors neglected to include Younes Mokrab and Aaron M. Newman as co-authors and misspelled the names of authors Charles S. Rabkin and Ilya Shmulevich. The author names have been corrected here and online. In addition, the concluding sentence of the subsection “Immune Signature Compilation” in the Method Details in the original published article was deemed unclear because it did not specify differences among the gene set scoring methods. The concluding sentences now reads “Gene sets from Bindea et al., Senbabaoglu et al., and the MSigDB C7 collection were scored using single-sample gene set enrichment (ssGSEA) analysis (Barbie et al., 2009), as implemented in the GSVA R package (Hänzelmann et al., 2013). All other signatures were scored using methods found in the associated citations.”

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31433971; info:eu-repo/semantics/altIdentifier/wos/WOS:000482088500021; volume:51; issue:2; firstpage:411; lastpage:412; numberofpages:2; journal:IMMUNITY; http://hdl.handle.net/11573/1347368Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85070213901

الإتاحة: https://doi.org/10.1016/j.immuni.2019.08.004Test
http://hdl.handle.net/11573/1347368Test

المؤلفون: Hendrik Van Poppel, James N'Dow, Manfred P. Wirth, James W.F. Catto, Christopher R. Chapple, Monique J. Roobol, Arnulf Stenzl, Jens Sønksen

المصدر: European Urology. 80:703-711

مصطلحات موضوعية: Male, medicine.medical_specialty, Package insert, business.industry, Urology, Mortality rate, Prostatic Neoplasms, Cancer, Prostate-Specific Antigen, medicine.disease, Prostate cancer, Prostate-specific antigen, medicine.anatomical_structure, Quality of life, Prostate, Quality of Life, medicine, Humans, Overdiagnosis, business, Early Detection of Cancer

الوصف: Background Recommendations against prostate-specific antigen (PSA) testing in 2012 have increased advanced-stage diagnosis and prostate cancer–specific mortality rates. Objective To present the position of the European Association of Urology (EAU) in 2021 and provide recommendations for the use of PSA testing as part of a risk-adapted strategy for the early detection of prostate cancer. Evidence acquisition The authors combined their review of relevant literature, including the EAU prostate cancer guidelines 2021 update, with their own knowledge to provide an expert opinion, representing the EAU’s position in 2021. Evidence synthesis The EAU has developed a risk-adapted early prostate cancer detection strategy for well-informed men based on PSA testing, risk calculators, and multiparametric magnetic resonance imaging, which can differentiate significant from insignificant prostate cancer. This approach largely avoids the overdiagnosis/overtreatment of men unlikely to experience disease-related symptoms during their lifetime and facilitates an early diagnosis of men with significant cancer to receive active treatment. It also reduces advanced-stage diagnosis, thereby potentially reducing prostate cancer–specific mortality and improving quality of life. Education is required among urologists, general practitioners, radiologists, policy makers, and healthy men, including endorsement by the European Commission to adapt the European Council’s screening recommendations in its 2022 plan and requests to individual countries for its incorporation into national cancer plans. Conclusions This risk-adapted approach for the early detection of prostate cancer will reverse current unfavourable trends and ultimately save lives. Patient summary The European Association of Urology has developed a patient information leaflet and algorithm for the early diagnosis of prostate cancer. It can identify men who do not need magnetic resonance imaging or a biopsy and those who would not show any symptoms versus those with more aggressive disease who require further tests/treatment. We need to raise awareness of this algorithm to ensure that all well-informed men at risk of significant prostate cancer are offered a prostate-specific antigen test. Take Home Message A risk-adapted early prostate cancer detection strategy, incorporating prostate-specific antigen testing, multiparametric magnetic resonance imaging, risk calculators, and biomarkers, will avoid overdiagnosis/overtreatment of insignificant cancers and ensure early detection and treatment of significant cancers, thereby improving quality of life and reducing prostate cancer–related deaths.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b441c1bfe16560e987cf68308faf2b1Test
https://doi.org/10.1016/j.eururo.2021.07.024Test

المؤلفون: Napolitano L, Scalise M, Koyioni M, Koutentis P, Catto M, Eberini I, Parravicini C, Palazzolo L, Pisani L, Galluccio M, Console L, Carotti A, Indiveri C.

المساهمون: L. Napolitano, M. Scalise, M. Koyioni, P. Koutenti, M. Catto, I. Eberini, C. Parravicini, L. Palazzolo, L. Pisani, M. Galluccio, L. Console, A. Carotti, C. Indiveri

مصطلحات موضوعية: LAT1 inhibitors 1,2,3-Dithiazoles 1,2,4-Dithiazine, mechanism of inhibition, pharmacological target, cancer, Settore BIO/10 - Biochimica, Settore BIO/14 - Farmacologia

الوصف: The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly over- expressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithi- azine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [3H]histidine in exchange with intralipo- somal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100 mM concentration, were subjected to dose-response analysis. Two of them exhibited IC50 lower than 1 mM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular dock- ing of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000412969200004; volume:143; firstpage:39; lastpage:52; numberofpages:14; journal:BIOCHEMICAL PHARMACOLOGY; http://hdl.handle.net/2434/548337Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85024491522

الإتاحة: https://doi.org/10.1016/j.bcp.2017.07.006Test
http://hdl.handle.net/2434/548337Test