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2. Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
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T Richards, S Shaikh, S Rehman, A Khan, J Shah, C Smith, A Brown, S Singh, A P Arnaud, A Young, D Bowen, P Patel, S Williams, J Dunn, J John, M Loubani, A Hainsworth, A Kolias, PJ Hutchinson, R Singh, S Sinha, S Shaw, J Edwards, S Mukherjee, AAB Jamjoom, A Singh, S Saeed, J Martin, S Smith, S Ross, M Mohan, P Hutchinson, G James, RDC Moon, P Brennan, A Williams, S Brown, A Ward, M Lee, K Thompson, S Ali, J Williams, S Reid, U Khan, J Lambert, A Smith, B Singh, M Hassan, N Sharma, J Reynolds, N Wright, T Williams, H Smith, M Ng, M Rahman, A Taylor, P Shah, D Saxena, J Evans, I Omar, M Ali, A Hanson, Z Li, R Andrade, P Cardoso, H Jeong, P Sharma, M Arrieta, J Clark, L Pearce, J McVeigh, V Sharma, B Kim, J Singh, S Newman, J Byrne, A Hassan, A Persad, A Gardner, H Liu, K Shah, I Hughes, S Davison, A Balakrishnan, K Patel, J Hall, S Mistry, J Parry, R Baumber, N McGrath, E Ross, R Mannion, S Murphy, FL Wright, A Rogers, B Rai, M Thomas, R Ribeiro, E Hamilton, J Teixeira, B Davidson, L 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Koutentakis, Syed Nong Chek SAH, M Shinkwin, F Ayeni, H Tustin, M Bordenave, N Manu, N Eardley, OL Serevina, S Roy Mahapatra, K Mohankumar, I Khawaja, A Palepa, T Doulias, Y Premakumar, Y Jauhari, Z Koshnow, A Uberai, F Hirri, BM Stubbs, J Manickavasagam, S Dalgleish, R Kanitkar, CJ Payne, Ng CE, DE Henshall, T Drake, EM Harrison, A Tambyraja, RJE Skipworth, G Linder, R McGregor, J Mayes, R Pasricha, A Razik, S Thrumurthy, D Howden, Z Baxter, L Osagie, M Bence, GE Fowler, N Rajaretnam, A Goubran, JS McGrath, JRA Phillips, DA Raptis, JM Pollok, F Soggiu, S Xyda, C Hidalgo Salinas, H Tzerbinis, T Pissanou, R Mirnezami, N Angamuthu, T Shakir, H Capitelli-McMahon, L Hitchman, A Andronic, A Aboelkassem Ibrahim, J Totty, S Tayeh, T Chase, J Ayorinde, T Cuming, A Trompeter, C Hing, P Tsinaslanidis, MW Benjamin, A Leyte, J Smelt, G Santhirakumaran, A Labib, O Lyons, S Onida, KM Sarraf, S Erridge, S Yalamanchili, A Abuown, D Davenport, S Wheatstone, SM Andreani, MF Bath, A Sahni, L Rigueros Springford, C Sohrabi, J Bacarese-Hamilton, FG Taylor, P Patki, C Tanabalan, ME Alexander, CJ Smart, L Abdeh, M Zeiton, R Advani, S Nikolaou, T Oni, N Ilahi, K Ballantyne, Z Woodward, R Merh, B Robertson-Smith, P Ameerally, JG Finch, C Gnanachandran, I Pop, D Dass, G Thiruchandran, Toh SKC, A Allana, C Bellis, O Babawale, YC Phan, U Lokman, T Koc, L Duggleby, S Shamoon, H Clancy, A Mansuri, A Thakrar, L Wickramarachchi, S Sivayoganathan, E Karam, HV Colvin, A Badran, A Cadersa, A Cumpstey, R Aftab, F Wensley, V Morrison-Jones, GK Sekhon, H Shields, Z Shakoor, T Talbot, A Alzetani, J Rooney, M Rudic, A Aladeojebi, M Kitchen, R Lefroy, P Nanjaiah, AD Rajgor, RJ Scurrah, LJ Watson, T Royle, B Steel, Luk ACO, VG Thiruvasagam, W Marlow, C Konstantinou, D Yershov, A Denning, E Mangos, T Nambirajan, I Flindall, V Mahendran, J De Marchi, NF Davis, A Picciariello, V Papagni, DF Altomare, S Granieri, C Cotsoglou, A Cabeleira, P Serralheiro, T Teles, C Canhoto, J Simões, AC Almeida, O Nogueira, R Athayde Nemésio, MJ Amaral, A Valente da Costa, R Martins, P Guerreiro, A Ruivo, D Breda, JM Oliveira, AL De Oliveira Lopez, M Colino, J De Barros, AP Soares, H Morais, T Revez, MI Manso, JC Domingues, P Henriques, Cardoso N Ribeiro VI, G Martins dos Santos, M Peralta Ferreira, J Ascensão, B Costeira, L Rio Rodrigues, M Sousa Fernandes, P Azevedo, I Lourenço, G Mendinhos, A Nobre Pinto, H Taflin, H Abdou, L O'Meara, Z Cooper, SA Hirji, BU Okafor, V Roxo, CP Raut, JS Jolissaint, DA Mahvi, C Reinke, S Merola, A Ssentongo, P Ssentongo, Oh JS, J Hazelton, J Maines, N Gusani, RCG Martin, N Bhutiani, R Choron, F Soliman, MD E Dauer, E Renza-Stingone, E Gokcen, E Kropf, H Sufrin, J Sewards, J Poggio, K Sanserino, L Rae, M Philp, M Metro, P McNelis, R Petrov, T Pazionis, DB Lumenta, SP Nischwitz, E Richtig, M Pau, P Srekl-Filzmaier, N Eibinger, B Michelitsch, M Fediuk, A Papinutti, TU Cohnert, E Kantor, J Kahiu, S Hosny, A Sultana, M Taggarsi, L Vitone, OP Vaz, I Sarantitis, S Timbrell, A Shugaba, GP Jones, SS Tripathi, MS Greenhalgh, H Emerson, K Vejsbjerg, W McCormick, K Singisetti, Y Aawsaj, R Vanker, M Ghobrial, S Kanthasamy, H Fawi, M Awadallah, J Cheung, S Tingle, F Abbadessa, A Sachdeva, CD Chan, I McPherson, F Mahmoud Ali, S Pandanaboyana, T Grainger, S Nandhra, N Dawe, C McCaffer, J Riches, J Moir, H Elamin Ahmed, C Saleh, RM Koshy, LJ Rogers, PL Labib, N Hope, K Emslie, P Panahi, E Clough, I Enemosah, J Natale, N Raza, JI Webb, M Antar, J Noel, R Nunn, F Eriberto, R Tanna, S Lodhia, C Osório, J Antunes, P Balau, and M Godinho
- Subjects
Medicine - Abstract
Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644
- Published
- 2021
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3. Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study
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Nepogodiev, Dmitri, Siaw-Acheampong, Kwabena, Benson, Ruth A., Bywater, Edward, Chaudhry, Daoud, Dawson, Brett E., Evans, Jonathan P., Glasbey, James C., Gujjuri, Rohan R., Heritage, Emily, Jones, Conor S., Kamarajah, Sivesh K., Khatri, Chetan, Khaw, Rachel A., Keatley, James M., Knight, Andrew, Lawday, Samuel, Li, Elizabeth, Mann, Harvinder S., Marson, Ella J., McLean, Kenneth A., Mckay, Siobhan C., Mills, Emily C., Pellino, Gianluca, Picciochi, Maria, Taylor, Elliott H., Tiwari, Abhinav, Simoes, Joana FF., Trout, Isobel M., Venn, Mary L., Wilkin, Richard JW., Bhangu, Aneel, 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, Arnaud, Alexis P., Augestad, Knut Magne, Ayasra, Faris, Azevedo, José, Bankhead-Kendall, Brittany K., Barlow, Emma, Beard, David, Blanco-Colino, Ruth, Brar, Amanpreet, Minaya-Bravo, Ana, 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Rudic, N, Vallabh, Y, Zhang, G, Harris, G, James, C, Kang, DJ, Lin, AD, Rajgor, T, Royle, R, Scurrah, B, Steel, LJ, Watson, D, Choi, R, Hutchison, V, Luoma, HJ, Marcus, R, May, A, Menon, B, Pramodana, L, Webber, A, Hayes, R, Jones, G, Sivarajah, M, Smith, A, Smrke, D, Strauss, FAM, Abouelela, IA, Aneke, P, Asaad, B, Brown, J, Collis, S, Duff, A, Khan, F, Moura, M, Taylor, B, Wadham, H, Warburton, T, Elmoslemany, Jenkinson, M.D., CP, Millward, R, Zakaria, S, Mccluney, C, Parmar, S, Shah, J, Allison, Babar, M.S., J, Bowen, B, Collard, S, Goodrum, K, Lau, M, Sargent, R, Scott, E, Thomas, H, Whitmore, D, Balasubramaniam, B, Jayasankar, S, Kapoor, A, Ramachandran, C, Semple, A, Elhamshary, SMB, Imam, K, Kapriniotis, V, Kasivisvanathan, J, Lindsay, Rakhshani-Moghadam, S., N, Beech, M, Chand, L, Green, N, Kalavrezos, H, Kiconco, R, McEwen, C, Schilling, D, Sinha, J, Pereca, S, Chopra, D, Egbeare, R, Thomas, S, Arumugam, B, Ibrahim, K, Khan, T, Combellack, G, Hill, S, Jones, M, Kornaszewska, M, Mohammed, G, Tahhan, V, Valtzoglou, N, Blencowe, P, Eskander, K, Gash, L, Gourbault, M, Hanna, TA, Maccabe, B, Main, J, Olivier, C, Newton, S, Roswadowski, N, Ryan, E, Teh, D, West, H, Al-omishy, M, Baig, H, Bates, Taranto G, Di, K, Dickson, N, Dunne, C, Gill, D, Howe, D, Jeevan, A, Khajuria, Martin-Ucar, A., K, McEvoy, P, Naredla, S, Robertson, M, Sait, DR, Sarma, S, Shanbhag, T, Shortland, S, Simmonds, J, Skillman, N, Tewari, G, Walton, Akhtar, M.A., A, Brunt, J, McIntyre, K, Milne, MM, Rashid, A, Sgrò, KE, Stewart, A, Turnbull, Abou-Foul, A.K., G, Gossedge, S, O’Donnell, F, Oldfield, S, Thomson, Gonzalez M, Aguilar, S, Talukder, C, Boyle, D, Fernando, K, Gallagher, A, Laird, D, Tham, M, Bath, P, Basnyat, H, Davis, P, Montauban, A, Shrestha, K, Agarwal, T, Arif, C, Magee, T, Nambirajan, S, Powell, R, Vinayagam, I, Flindall, A, Hanson, V, Mahendran, S, Green, M, Lim, L, MacDonald, V, Miu, L, Onos, K, Sheridan, R, Young, F, Alam, O, Griffiths, C, Houlden, VS, Kolli, AK, Lala, S, Leeson, R, Peevor, Z, Seymour, E, Consorti, R, Gonzalez, R, Grolman, Kwan-Feinberg, R., T, Liu, O, Merzlikin, Francisco, San, A, Brown, Z, Cooper, S, Hirji, J, Jolissaint, D, Mahvi, B, Okafor, CP, Raut, V, Roxo, A, Salim, S, Bessen, L, Chen, L, Dagrosa, K, Fay, C, Fleischer, R, Hasson, E, Henderson, M, Leech, A, Loehrer, C, Markey, J, Paydarfar, K, Rosenkranz, K, Telma, N, Tocci, Wilkinson-Ryan, I., M, Bokenkamp, K, Brown, D, Fleming, C, Heron, C, Hill, H, Kay, E, Leede, K, McElhinney, KA, Olson, EC, Osterberg, C, Riley, P, Srikanth, J, Barbour, D, Blazer, GA, DiLalla, O, Fayanju, ES, Hwang, R, Kahmke, H, Kazaure, A, Lazarides, W, Lee, M, Lidsky, C, Menendez, D, Moris, J, Plichta, MC, Pradhan, L, Puscas, HE, Rice, D, Rocke, L, Rosenberger, R, Scheri, Smith, B.D., Stang, M.T., L, Tolnitch, K, Turnage, J, Visgauss, FS, Walton, T, Watts, S, Zani, J, Farma, K, Cardona, MC, Russell, J, Clark, D, Kwon, N, Goel, J, Kronenfeld, B, Bigelow, E, Etchill, Gabre-Kidan, A., H, Jenny, A, Kent, MR, Ladd, C, Long, H, Malapati, A, Margalit, S, Rapaport, J, Rose, K, Stevens, L, Tsai, D, Vervoort, P, Yesantharao, A, Dehal, D, Klaristenfeld, K, Huynh, H, Kaafarani, L, Naar, M, Qadan, L, Brown, I, Ganly, JE, Mullinax, N, Alpert, C, Gillezeau, Miles DDS MD, F.A.C.S.B.A., E, Taioli, DE, Cha, E, Gleeson, C, Horn, U, Sarpel, N, Gusani, J, Hazelton, J, Maines, JS, Oh, A, Ssentongo, P, Ssentongo, A, Bhama, K, Colling, M, Najarian, M, Azam, A, Choudhry, W, Marx, Y, Abedin, G, Arzumanov, R, Chokshi, S, Gabrilovich, N, Glass, E, Kalyoussef, Parvin-Nejad, F.P., D, Roden, J, Stein, Suarez-Ligon, A., G, Tsui, K, Zhao, J, Fleming, A, Fuson, J, Gigliotti, A, Ovaitt, Y, Ying, MK, Abel, V, Andaya, K, Bigay, Boeck, M.A., H, Chern, C, Corvera, El-Sayed, I., A, Glencer, P, Ha, Hamilton, B.C.S., C, Heaton, K, Hirose, Jablons, D.M., KS, Kirkwood, LZ, Kornblith, JR, Kratz, RH, Lee, PN, Miller, EK, Nakakura, Nunez-Garcia, B., RJ, O’Donnell, D, Ozgediz, P, Park, B, Robinson, A, Sarin, B, Sheu, MG, Varma, KC, Wai, R, Wustrack, MJ, Xu, M, Zimel, D, CA) Beswick, J, Goddard, J, Manor, J, Song, Springs/Loveland, Denver/Colorado, A, Cioci, W, Pavlis, K, Rakoczy, G, Ruiz, R, Saberi, T, Fullmer, C, Gaskill, N, Gross, K, Kiong, CL, Roland, SN, Zafar, M, Abdallah, A, Abouassi, E, Aigbivbalu, M, Almasri, J, Eid, B, George, G, Kulkarni, H, Marwan, M, Mehdi, Andrés M, San, J, Sundaresan, SG, Aoun, VS, Ban, HH, Batjer, K, Bosler, J, Caruso, B, Sumer, D, Abbott, A, Acher, T, Aiken, J, Barrett, E, Foley, PB, Schwartz, AT, Hawkins, A, Maiga, NM, Ruzgar, M, Sion, S, Ullrich, J, Laufer, S, Scasso, Al-Naggar, H., Al-Shehari, M., A, Almassaudi, M, Alsayadi, R, Alsayadi, M, Nahshal, S, Shream, S, AL-Ameri, M, Aldawbali, Fotopoulou, Christina, Khan, Tabassum, Bracinik, Juraj, Glasbey, James, Abu-Rustum, Nadeem, Chiva, Luis, Fagotti, Anna, Fujiwara, Keiichi, Ghebre, Rahel, Gutelkin, Murat, Konney, Thomas O., Ng, Joseph, Pareja, Rene, Kottayasamy Seenivasagam, Rajkumar, Sehouli, Jalid, Surappa, Shylasree T.S., and Leung, Elaine
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- 2022
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4. Focal brachytherapy for localized prostate cancer: Mid-term outcomes
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I. Nunes-Silva, M-H. Ta, E. Barret, F. Rozet, P. Macek, A. Mombet, R. Sanchez-Salas, N. Cathala, X. Cathelineau, and J-M. Cosset
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Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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5. New prostate-specific antigen study findings recently were published by F. Rozet and co-researchers
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Analysis ,Research ,Reports ,Antigens -- Reports -- Analysis -- Research ,Body mass index -- Reports -- Analysis -- Research ,Prostate cancer -- Research -- Reports -- Analysis - Abstract
Researchers detail in 'A direct comparison of robotic assisted versus pure laparoscopic radical prostatectomy: a single institution experience,' new data in prostate-specific antigen. According to a study from Paris, France, [...]
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- 2007
6. French AFU Cancer Committee Guidelines - Update 2022-2024: prostate cancer - Management of metastatic disease and castration resistance
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G. Ploussard, G. Roubaud, E. Barret, J.-B. Beauval, L. Brureau, G. Créhange, C. Dariane, G. Fiard, G. Fromont, M. Gauthé, R. Renard-Penna, F. Rozet, A. Ruffion, P. Sargos, R. Mathieu, M. Rouprêt, Clinique La Croix du Sud, Institut Bergonié [Bordeaux], UNICANCER, Institut Mutualiste de Montsouris (IMM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Curie [Paris], National Cystic Fibrosis Reference Center [CHU Necker] (CNR - INSERM U1151), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and CHU Pontchaillou [Rennes]
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Treatment ,Prostate cancer ,Urology ,Recommandations ,[SDV]Life Sciences [q-bio] ,Diagnosis ,Diagnostic ,Cancer de la prostate ,Guidelines ,Traitement - Abstract
International audience; OBJECTIVE: The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the management of prostate cancer. METHODS: A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the elements of therapeutic management of metastatic and castration-resistant prostate cancer (PC), while evaluating the references and their levels of evidence. RESULTS: Androgen deprivation therapy (ADT) remains the standard treatment for metastatic prostate cancer. ADT intensification is now a standard of care in the management of metastatic prostate cancer. This intensification is discussed in relation to the patient and the characteristics of the disease. For all metastatic hormone-sensitive PC (synchronous and metachronous), the overall survival benefit associated with good tolerability makes the combination of ADT and novel hormonal agents (NHA) a standard. For patients with high-volume/high-risk de novo metastatic disease, treatment with docetaxel in addition to ADT + NHA can be discussed for eligible patients. In patients with castration-resistant prostate cancer (CRPC), the contribution of new therapies that have become available in recent years, as well as the advent of precision medicine, help to improve the control of tumour progression and survival, and highlight the value of testing for alterations in DNA repair genes within the tumour tissue or constitutionally. CONCLUSION: This update of the French recommendations should help to improve the management of patients with prostate cancer.
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- 2022
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7. French AFU Cancer Committee Guidelines - Update 2022-2024: prostate cancer - Diagnosis and management of localised disease
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G. Ploussard, G. Fiard, E. Barret, L. Brureau, G. Créhange, C. Dariane, G. Fromont, M. Gauthé, R. Mathieu, R. Renard-Penna, G. Roubaud, F. Rozet, A. Ruffion, P. Sargos, J.-B. Beauval, M. Rouprêt, Clinique La Croix du Sud, Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Institut Mutualiste de Montsouris (IMM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut Curie [Paris], National Cystic Fibrosis Reference Center [CHU Necker] (CNR - INSERM U1151), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Bergonié [Bordeaux], UNICANCER, Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), and Hospices Civils de Lyon (HCL)
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Treatment ,Prostate cancer ,Urology ,Recommandations ,[SDV]Life Sciences [q-bio] ,Diagnosis ,Diagnostic ,Cancer de la prostate ,Guidelines ,Traitement - Abstract
International audience; OBJECTIVE: The objective of the French Urology Association Cancer Committee is to propose an update of the recommendations for the diagnosis and management of prostate cancer (PC). METHODS: A systematic review of the literature from 2020 to 2022 was conducted by the CCAFU on the diagnosis and therapeutic management of localised PC, while evaluating the references and their levels of evidence. RESULTS: The recommendations specify the genetics, epidemiology and means of diagnosing prostate cancer, as well as the notions of screening and early detection. MRI, the gold standard imaging examination for localised cancer, is recommended before prostate biopsies are performed. The transperineal approach reduces the risks of infection. The therapeutic methods are described and recommended according to the clinical context. Active surveillance is the gold standard of treatment for tumours with a low risk for progression. Early salvage radiotherapy is recommended in case of biochemical recurrence after radical prostatectomy. Imaging, particularly molecular imaging, helps to guide the decision-making in the event of biochemical recurrence after local treatment, but should not delay early salvage radiotherapy in the event of biological recurrence after radical prostatectomy. CONCLUSION: This update of the French recommendations should help to improve the management of patients with PC.
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- 2022
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8. Feedback from Operative Performance to Improve Training Program of Laparoscopic Radical Prostatectomy.
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R. Gupta, X. Cathelineau, F. Rozet, and G. Vallancien
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- 2004
9. Transperitoneal or Extraperitoneal Approach for Laparoscopic Radical Prostatectomy: A False Debate Over a Real Challenge.
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X. CATHELINEAU, D. CAHILL, H. WIDMER, F. ROZET, H. BAUMERT, and G. VALLANCIEN
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- 2004
10. Polymers used in pharmaceutical industry for oral delivery: insight to synthesis, structure–activity relationship, and recent applications.
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Mori, Dhaval, Dudhat, Kiran, Soniwala, Moinuddin, Parmar, Ramesh, Suthar, Devi, Jayani, Rutvi, Shah, Sunny, Borkhataria, Chetan, Patel, Kalpesh, and Dudhrejiya, Ashwin
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SOLID dosage forms ,RESEARCH personnel ,PHARMACEUTICAL industry ,POLYMERS ,CELLULOSE - Abstract
For a long time, polymers have played a critical role in the pharmaceutical industry for developing safe, effective, and deliverable dosage forms. Among all the dosage forms oral dosage form remains the most widely used, prescribed, and produced ones. The present review articles comprehensively describe various natural, semi-synthetic, and synthetic polymers used to prepare oral solid dosage forms. Along with describing a method for isolation and preparation of all the polymers, this article also explains in detail the key physicochemical properties that make them suitable for the particular dosage form. The article specifically deals with the formulation of conventional tablets, sustained-release matrix tablets, solid dispersions, and other miscellaneous dosage forms such as microspheres and oral gels. Furthermore, the article also provides a detailed discussion of the factors that influence the selection of the appropriate polymer and formulation method. This review article is expected to be a valuable resource for researchers, scientists, and professionals in the pharmaceutical industry who are interested in using polymers for developing effective and safe oral solid dosage forms. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Evaluation of the application effect of the continuous care model after radical prostatectomy based on IKAP theory.
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Wang, Lixia, Hu, Yuanchao, Wang, Shunfeng, Hu, Dongping, and Wang, Yajun
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NURSING models ,RADICAL prostatectomy ,POSTOPERATIVE care ,URINARY incontinence ,SELF-evaluation ,PATIENT compliance - Abstract
Objective: This study aims to evaluate the effectiveness of a continuous nursing model based on the information-knowledge-attitude-practice (IKAP) theory for patients after radical prostatectomy. Methods: Data were collected from July 2022 to August 2023, involving 104 patients from the Department of Urology at a hospital in Dongyang, Zhejiang Province. Patients were divided into IKAP and routine groups, each starting with 52 individuals and concluding with 47 effective cases. The routine group received standard postoperative care, while the IKAP group received care through a continuous nursing model based on the IKAP theory in addition to routine care. We compared disease awareness scores (acceptance, helplessness, and perception), prostate symptoms [International Prostate Symptom Score (IPSS)], urinary incontinence status (ICIQ-SF score), anxiety levels [Self-Rating Anxiety Scale (SAS) score], quality of life (SF-12 score), self-management efficacy [Strategies Used by People to Promote Health (SUPPH) score], and compliance behaviors (medication adherence, daily exercise, functional exercise, and regular follow-up) between the two groups. Results: The acceptance and perception scores of the IKAP group after nursing were higher than those in the conventional group, and the scores of helplessness were lower than those in the conventional group, with both P < 0.05. The IPSS score and ICI-Q-SF score after nursing care in the IKAP group were lower than those in the conventional group, with P < 0.05. The SAS score after nursing care in the IKAP group was lower than that in the conventional group, and the SF-12 score was higher than that in the conventional group, with a P < 0.05. The scores of positive attitude, self-stress reduction, and self-decision-making on the SUPPH scale after nursing care in the IKAP group were higher than those in the conventional group, with all P < 0.05. The implementation rates of medication compliance, daily exercise, functional exercise, and regular follow-up in the IKAP group were higher than those in the conventional group, with a P < 0.05. Conclusion: The continuous nursing model based on IKAP theory significantly improves disease cognition, reduces prostate symptoms and urinary incontinence, alleviates anxiety, enhances quality of life, boosts self-management efficacy, and improves medical compliance behaviors in patients after radical prostatectomy. This model is highly effective in promoting postoperative recovery and is worthy of promotion and application. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Recombinant Slit2 Requires Heparin Sulphate to Inhibit TGF-ß Induced Tumor Proliferation in Lung Cancer and Glioblastoma.
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Amjad, Quratulain and Shakoori, Abdul Rauf
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Slit and roundabout homologs have emerged as important players in signaling cascades of tumor metastasis. In previous reports it is stated that the interactions between Slit2 and Robo1 are facilitated by heparan sulphate that is abundantly expressed on cell surface and extracellular matrix. Slit2 reduces tumor proliferation in lung cancer and glioblastoma cells whereas TGF-ß is a well-described tumor inducer. The present study was aimed at deciphering the role of heparan sulphate in Slit2 mediated inhibition of cancer metastasis. Cancer proliferation was induced by TGF-ß in lung cancer cells (H1650) and glioblastoma cells (SF767) and then the anti-proliferative role of Slit2 was analyzed in presence and absence of heparan sulfate. The data revealed that, heparan sulfate plays important role in enhancing tumor inhibition by Slit2 in cancer cells as there was further reduction in cell proliferation when Slit2 was administered along with heparin. [ABSTRACT FROM AUTHOR]
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- 2024
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13. 712Laparoscopic assisted cystectomy: Experience after 72 cases
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X., Cathelineau, F., Rozet, C., Arroyo, E., Barret, and G., Vallancien
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- 2005
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14. ENO2, a Glycolytic Enzyme, Contributes to Prostate Cancer Metastasis: A Systematic Review of Literature.
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Zhou, Yuhan, Zeng, Feier, Richards, Gareth Owain, and Wang, Ning
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ENZYME metabolism ,OSTEOBLAST metabolism ,RISK assessment ,CASTRATION-resistant prostate cancer ,GLYCOLYSIS ,PROSTATE tumors ,ENZYMES ,METASTASIS ,SYSTEMATIC reviews ,MEDLINE ,GENE expression ,CELL lines ,NEUROENDOCRINE tumors ,ONLINE information services ,TUMOR classification ,DISEASE risk factors - Abstract
Simple Summary: This paper reviews the role of ENO2, a protein involved in sugar metabolism, in advanced prostate cancer. Analysing five studies, we found that ENO2 levels tend to be higher in aggressive forms of prostate cancer, particularly those that have spread or become resistant to hormone therapy. This increased presence might be linked to how prostate cancer cells change their energy production as the disease progresses, shifting to rely more on sugar breakdown in advanced stages. The study also suggests that ENO2 can be influenced by the tumour's environment, such as low hormone levels or the presence of bone cells, which is relevant, as prostate cancer often spreads to bones. While not proving a direct causal relationship, the research indicates that ENO2 could be an important marker for aggressive disease and potentially a target for future treatments, warranting further investigation into its role in prostate cancer progression, especially in bone metastasis. Prostate cancer (PCa) is the second leading cause of male cancer deaths in the UK and the fifth worldwide. The presence of distant PCa metastasis can reduce the 5-year survival rate from 100% to approximately 30%. Enolase 2 (ENO2), a crucial glycolytic enzyme in cancer metabolism, is associated with the metastasis of multiple cancers and is also used as a marker for neuroendocrine tumours. However, its role in PCa metastasis remains unclear. In this study, we systematically reviewed the current literature to determine the association between ENO2 and metastatic PCa. Medline, Web of Science, and PubMed were searched for eligible studies. The search yielded five studies assessing ENO2 expression in PCa patients or cell lines. The three human studies suggested that ENO2 expression is correlated with late-stage, aggressive PCa, including castrate-resistant PCa (CRPC), metastatic CRPC, and neuroendocrine PCa (NEPC). This was further supported by two in vitro studies indicating that ENO2 expression can be regulated by the tumour microenvironment, such as androgen deprived conditions and the presence of bone-forming osteoblasts. Therefore, ENO2 may functionally contribute to PCa metastasis, possibly due to the unique metabolic features of PCa, which are glycolysis dependent only at the advanced metastatic stage. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Solid Lipid Nanoparticles for the Delivery of Plant-derived Bioactive Compounds in the Treatment of Cancer Disorders -- A Review.
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Samanthula, Kumara Swamy, Obbalareddy, Satya, Thatipelli, Ravi Chander, and Bairi, Agaiah Goud
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CANCER chemotherapy ,ANTIARTHRITIC agents ,MEDICAL practice ,BIOACTIVE compounds ,MOLECULES ,CASTRATION-resistant prostate cancer ,MARINE natural products ,EPICATECHIN - Published
- 2024
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16. The Diagnostic Value of Plasma Small Extracellular Vesicle-Derived CAIX Protein in Prostate Cancer and Clinically Significant Prostate Cancer: A Study on Predictive Models.
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Chen H, Pang B, Liu Z, Li B, Wang Q, Fan B, Han M, Gong J, Zhou C, Chen Y, Li Y, and Jiang J
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Background: Current diagnostic tools are inaccurate and not specific to prostate cancer (PCa) diagnosis. Cancer-derived small extracellular vehicles (sEVs) play a key role in intercellular communication. In this study, we examined the diagnostic value of plasma sEV-derived carbonic anhydrase IX (CAIX) protein for PCa and clinically significant prostate cancer (csPCa) diagnosis and avoiding unnecessary biopsies., Methods: Plasma samples (n = 230) were collected from the patients who underwent prostate biopsy with elevated prostate-specific antigen (PSA) levels. sEVs were isolated and characterized, and sEV protein CAIX was measured using an enzyme-linked immunosorbent assay. Independent predictors of csPCa (Gleason score ≥ 7) were identified, and a predictive model was established. A Nomogram for predicting csPCa was developed using data from the training cohort., Results: The expression of sEV protein CAIX was significantly higher in both PCa and csPCa compared to benign patients and nonsignificant PCa (nsPCa) (Gleason score < 7, p < 0.001). sEV protein CAIX performed well in distinguishing PCa from benign patients. The predictive model defined by sEV protein CAIX and PSA density (PSAD) demonstrated the highest discriminative ability for csPCa (AUC = 0.895), with diagnostic sensitivity and specificity of 82.5% and 85.8%, respectively. Furthermore, sEV protein CAIX is an effective predictor of 2-year biochemical recurrence (BCR) in PCa patients (p = 0.013), and its high expression is significantly associated with poorer BCR-free survival (p < 0.05)., Conclusions: Our findings demonstrate the excellent performance of sEV protein CAIX in PCa and csPCa diagnosis. The Nomogram-based csPCa predictive model incorporating sEV protein CAIX and PSAD exhibits strong predictive value. Additionally, assessing plasma sEV protein CAIX expression levels can further aid in evaluating patient prognosis and provide a basis for making effective treatment decisions., (© 2025 The Author(s). The Prostate published by Wiley Periodicals LLC.)
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- 2025
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17. MCTP1 increases the malignancy of androgen-deprived prostate cancer cells by inducing neuroendocrine differentiation and EMT.
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Liu, Yen-Nien, Chen, Wei-Yu, Yeh, Hsiu-Lien, Chen, Wei-Hao, Jiang, Kuo-Ching, Li, Han-Ru, Dung, Phan Vu Thuy, Chen, Zi-Qing, Lee, Wei-Jiunn, Hsiao, Michael, Huang, Jiaoti, and Wen, Yu-Ching
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PROSTATE cancer ,NEUROENDOCRINE cells ,CANCER cells ,ANDROGEN deprivation therapy ,CANCER cell migration ,ANDROGEN receptors - Abstract
Neuroendocrine prostate cancer (PCa) (NEPC), an aggressive subtype that is associated with poor prognosis, may arise after androgen deprivation therapy (ADT). We investigated the molecular mechanisms by which ADT induces neuroendocrine differentiation in advanced PCa. We found that transmembrane protein 1 (MCTP1), which has putative Ca
2+ sensing function and multiple Ca2+ -binding C2 domains, was abundant in samples from patients with advanced PCa. MCTP1 was associated with the expression of the EMT-associated transcription factors ZBTB46, FOXA2, and HIF1A. The increased abundance of MCTP1 promoted PC3 prostate cancer cell migration and neuroendocrine differentiation and was associated with SNAI1-dependent EMT in C4-2 PCa cells after ADT. ZBTB46 interacted with FOXA2 and HIF1A and increased the abundance of MCTP1 in a hypoxia-dependent manner. MCTP1 stimulated Ca2+ signaling and AKT activation to promote EMT and neuroendocrine differentiation by increasing the SNAI1-dependent expression of EMT and neuroendocrine markers, effects that were blocked by knockdown of MCTP1. These data suggest an oncogenic role for MCTP1 in the maintenance of a rare and aggressive prostate cancer subtype through its response to Ca2+ and suggest its potential as a therapeutic target. Editor's summary: Androgen deprivation therapy is used to treat prostate cancer but can induce its differentiation into an aggressive neuroendocrine subtype with poor clinical outcomes. Liu et al. uncovered a role for the putative Ca2+ sensor MCTP1 in neuroendocrine differentiation in prostate cancer. MCTP1 was abundant in human prostate tumors, and its expression in prostate cancer cells was stimulated by the transcription factors ZBTB46, FOXA2, and HIF1A in a hypoxia-dependent manner. MCTP1 expression promoted tumor progression and epithelial-to-mesenchymal transition, thus suggesting that targeting MCTP1 could prevent neuroendocrine differentiation in prostate cancer. —Amy E. Baek [ABSTRACT FROM AUTHOR]- Published
- 2024
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18. Ultrasound-mediated drug-free theranostics for treatment of prostate cancer.
- Author
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Perera, Reshani Himashika, Berg, Felipe Matias, Abenojar, Eric Chua, Nittayacharn, Pinunta, Youjoung Kim, Xinning Wang, Basilion, James Peter, and Exner, Agata
- Published
- 2024
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19. Strategies for the Nuclear Delivery of Metal Complexes to Cancer Cells.
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Huynh, Marie, Vinck, Robin, Gibert, Benjamin, and Gasser, Gilles
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- 2024
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20. Development and Characterisation of a New Patient-Derived Xenograft Model of AR-Negative Metastatic Castration-Resistant Prostate Cancer.
- Author
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Turnham, Daniel J., Mullen, Manisha S., Bullock, Nicholas P., Gilroy, Kathryn L., Richards, Anna E., Patel, Radhika, Quintela, Marcos, Meniel, Valerie S., Seaton, Gillian, Kynaston, Howard, Clarkson, Richard W. E., Phesse, Toby J., Nelson, Peter S., Haffner, Michael C., Staffurth, John N., and Pearson, Helen B.
- Subjects
CASTRATION-resistant prostate cancer ,ANDROGEN receptors ,LUTEINIZING hormone releasing hormone ,PROSTATE cancer - Abstract
As the treatment landscape for prostate cancer gradually evolves, the frequency of treatment-induced neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC) that is deficient for androgen receptor (AR) and neuroendocrine (NE) markers has increased. These prostate cancer subtypes are typically refractory to AR-directed therapies and exhibit poor clinical outcomes. Only a small range of NEPC/DNPC models exist, limiting our molecular understanding of this disease and hindering our ability to perform preclinical trials exploring novel therapies to treat NEPC/DNPC that are urgently needed in the clinic. Here, we report the development of the CU-PC01 PDX model that represents AR-negative mCRPC with PTEN/RB/PSMA loss and CTNN1B/TP53/BRCA2 genetic variants. The CU-PC01 model lacks classic NE markers, with only focal and/or weak expression of chromogranin A, INSM1 and CD56. Collectively, these findings are most consistent with a DNPC phenotype. Ex vivo and in vivo preclinical studies revealed that CU-PC01 PDX tumours are resistant to mCRPC standard-of-care treatments enzalutamide and docetaxel, mirroring the donor patient's treatment response. Furthermore, short-term CU-PC01 tumour explant cultures indicate this model is initially sensitive to PARP inhibition with olaparib. Thus, the CU-PC01 PDX model provides a valuable opportunity to study AR-negative mCRPC biology and to discover new treatment avenues for this hard-to-treat disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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21. Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.
- Author
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Martin-Caraballo, Miguel
- Subjects
ANDROGEN receptors ,PROSTATE cancer ,CASTRATION-resistant prostate cancer ,CANCER cell growth ,AURORA kinases ,BIOMARKERS - Abstract
Androgen receptor signaling regulates the normal and pathological growth of the prostate. In particular, the growth and survival of prostate cancer cells is initially dependent on androgen receptor signaling. Exposure to androgen deprivation therapy leads to the development of castration-resistant prostate cancer. There is a multitude of molecular and cellular changes that occur in prostate tumor cells, including the expression of neuroendocrine features and various biomarkers, which promotes the switch of cancer cells to androgen-independent growth. These biomarkers include transcription factors (TP53, REST, BRN2, INSM1, c-Myc), signaling molecules (PTEN, Aurora kinases, retinoblastoma tumor suppressor, calcium-binding proteins), and receptors (glucocorticoid, androgen receptor-variant 7), among others. It is believed that genetic modifications, therapeutic treatments, and changes in the tumor microenvironment are contributing factors to the progression of prostate cancers with significant heterogeneity in their phenotypic characteristics. However, it is not well understood how these phenotypic characteristics and molecular modifications arise under specific treatment conditions. In this work, we summarize some of the most important molecular changes associated with the progression of prostate cancers and we describe some of the factors involved in these cellular processes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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22. ORAI Ca 2+ Channels in Cancers and Therapeutic Interventions.
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Zhang, Qian, Wang, Chen, and He, Lian
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CALCIUM ions ,POST-translational modification ,CALCIUM channels ,SMALL molecules ,IMMUNOLOGIC diseases ,HOMEOSTASIS ,CELLULAR signal transduction - Abstract
The ORAI proteins serve as crucial pore-forming subunits of calcium-release-activated calcium (CRAC) channels, pivotal in regulating downstream calcium-related signaling pathways. Dysregulated calcium homeostasis arising from mutations and post-translational modifications in ORAI can lead to immune disorders, myopathy, cardiovascular diseases, and even cancers. Small molecules targeting ORAI present an approach for calcium signaling modulation. Moreover, emerging techniques like optogenetics and optochemistry aim to offer more precise regulation of ORAI. This review focuses on the role of ORAI in cancers, providing a concise overview of their significance in the initiation and progression of cancers. Additionally, it highlights state-of-the-art techniques for ORAI channel modulation, including advanced optical tools, potent pharmacological inhibitors, and antibodies. These novel strategies offer promising avenues for the functional regulation of ORAI in research and may inspire innovative approaches to cancer therapy targeting ORAI. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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23. An insight into the diagnostic, prognostic, and taxanes resistance of double zinc finger and homeodomain factor's expression in naïve prostate cancer.
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Said, Rahma, Hernández-Losa, Javier, Jenni, Rim, de Haro, Rosa Somoza Lopez, Moline, Teresa, Zouari, Skander, Blel, Ahlem, Rammeh, Soumaya, Derouiche, Amine, and Ouerhani, Slah
- Subjects
GENE expression ,PROSTATE cancer ,DIGITAL rectal examination ,ZINC-finger proteins ,TAXANES ,LUTEINIZING hormone releasing hormone ,LYMPHATIC metastasis - Abstract
Currently, clinical biomarkers are urgently needed to improve patient management to guide personal therapy for cancer. In this study, we investigate the deregulation of Zeb-1 in prostate cancer (PC) Tunisian patients. Expression patterns of the Zeb-1 were investigated in prostate adenocarcinoma and benign prostate biopsies using quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) and 2-ΔΔCt method. Statistical analysis was used to identify differences across groups depending on gene expression level. Furthermore, we exploited a follow-up over 15 years to correlate Zeb-1 deregulation and clinical outcomes in PC patients. Based on ROC curve analyses, the AUC was found in discriminating PC patients from controls (AUC = 0.757; p < 0.001). In addition, the higher expression level was significantly associated with PSA, Digital Rectal Examination, Gleason score, tumor stage, and distant lymph node metastases. Moreover, Zeb-1 overexpression was correlated with shorter overall survival (OS) (p = 0.042), poor progression-free survival (PFS) (p = 0.007), and with resistance to taxanes (p = 0.012). Our data provide the aberrant expression of Zeb-1 in PC patients suggesting its potential diagnostic, prognostic, and theranostic role. Further functional studies are mandatory to strengthen these results and to uncover the molecular mechanism of this neoplasm. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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24. Variable effects of periprostatic adipose tissue on prostate cancer cells: Role of adipose tissue lipid composition and cancer cells related factors.
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Cancel, Mathilde, Crottes, David, Bellanger, Dorine, Bruyère, Frank, Mousset, Coralie, Pinault, Michelle, Mahéo, Karine, and Fromont, Gaëlle
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- 2024
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25. The Effect of Microcrystalline Cellulose–CaHPO 4 Mixtures in Different Volume Ratios on the Compaction and Structural–Mechanical Properties of Tablets.
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Mohylyuk, Valentyn, Paulausks, Artūrs, Radzins, Oskars, and Lauberte, Liga
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CALCIUM phosphate ,MIXTURES ,SURFACE area ,CELLULOSE ,CELLULOSE fibers - Abstract
Using microcrystalline cellulose (MCC) with plastic behaviour and calcium phosphate anhydrous (CaHPO
4 ) with brittle behaviour under compaction is very popular in the pharmaceutical industry for achieving desirable structural–mechanical properties of tablet formulations. Thus, mixtures of specific grades of MCC and CaHPO4 were tested in volume proportions of 100-0, 75-25, 50-50, 25-75, and 0-100 at a constant weight-by-weight concentration of sodium stearyl fumarate lubricant, utilizing a state-of-the-art benchtop compaction simulator (STYL'One Nano). Tablet formulations were prepared at 100, 150, 250, 350, 450, and 500 MPa, and characterized by tabletability profile, ejection force profile, proportion–tensile strength relationship, proportion–porosity relationship, pressure–displacement, and elastic recovery profiles, as well as by in-/out-of-die Heckel plots and yield pressures. Interestingly, the 25-75 formulation demonstrated a two-stage out-of-die Heckel plot and was additionally investigated with X-ray micro-computed tomography (µCT). By post-processing the µCT data, the degree of brittle CaHPO4 particles falling apart, along with the increasing compression pressure, was quantified by means of the surface area to volume (S/V) ratio. For the 25-75 formulation, the first stage (up to 150 MPa) and second stage (above the 150 MPa) of the out-of-die Heckel plot could be attributed to predominant MCC and CaHPO4 deformation, respectively. [ABSTRACT FROM AUTHOR]- Published
- 2024
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26. Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.
- Author
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Lin, Shao-Long, Chen, Yan-Song, Liu, Ruo-Yu, Zhu, Mei-Ying, Zhu, Tian, Wang, Ming-Qi, and Liu, Bao-Quan
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- 2024
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27. Reconstructing axion-like particles from beam dumps with simulation-based inference.
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Morandini, Alessandro, Ferber, Torben, and Kahlhoefer, Felix
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PARTICLE beams ,PHOTON pairs ,PLASMA beam injection heating ,MACHINE learning ,EXPERIMENTAL design - Abstract
Axion-like particles (ALPs) that decay into photon pairs pose a challenge for experiments that rely on the construction of a decay vertex in order to search for long-lived particles. This is particularly true for beam-dump experiments, where the distance between the unknown decay position and the calorimeter can be very large. In this work we use machine learning to explore the possibility to reconstruct the ALP properties, in particular its mass and lifetime, from such inaccurate observations. We use a simulation-based inference approach based on conditional invertible neural networks to reconstruct the posterior probability of the ALP parameters for a given set of events. We find that for realistic angular and energy resolution, such a neural network significantly outperforms parameter reconstruction from conventional high-level variables while at the same time providing reliable uncertainty estimates. Moreover, the neural network can quickly be re-trained for different detector properties, making it an ideal framework for optimizing experimental design. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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28. Correlation between E‐cadherin/β‐catenin, Vimentin expression, clinicopathologic features and drug resistance prediction in naïve prostate cancer: A molecular and clinical study.
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Said, Rahma, Hernández‐Losa, Javier, Derouiche, Amine, Moline, Teresa, de Haro, Rosa Somoza Lopez, Zouari, Skander, Blel, Ahlem, Rammeh, Soumaya, and Ouerhani, Slah
- Published
- 2024
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29. ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling.
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Zhang, Jinxiong, Chen, Zhihao, Mao, Yongxin, He, Yijun, Wu, Xin, Wu, Jianhong, and Sheng, Lu
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CELL differentiation ,FIBROBLAST growth factors ,IN vitro studies ,IN vivo studies ,CELL receptors ,CELLULAR signal transduction ,JANUS kinases ,DNA-binding proteins ,RESEARCH funding ,ANDROGEN receptors ,PROSTATE tumors ,DRUG resistance in cancer cells ,PHENOTYPES - Abstract
Simple Summary: Androgen receptor-negative prostate cancer is one of the important mechanisms of castration resistant prostate cancer. The application of next generation androgen receptor signaling pathway inhibitors (ARPIs) has led to a gradual increase of AR-negative prostate cancer in the clinic. In this paper, we demonstrated the potential promotional role of ID2 in androgen receptor-negative prostate cancer through extensive bioinformatics analysis and experimental studies. Through transcriptome sequencing and downstream functional enrichment analysis, we found that ID2 can activate neuroendocrine or stemness-related pathways and inhibit androgen receptor signaling pathways. ID2 can activate JAK/STAT signaling pathway as well as FGFR signaling pathway to promote the acquisition of prostate cancer lineage plasticity, which in turn leads to androgen receptor-negative prostate cancer. Through cell function experiments and mouse experiments, we reveal that ID2 can promote prostate cancer evolution. Using transcriptome sequencing and publicly available clinical data, we generated ID2-related gene signatures to help determine clinical prognosis. The use of androgen receptor pathway inhibitors (ARPIs) has led to an increase in the proportion of AR-null prostate cancer, including neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC), but the mechanism underlying this lineage transition has not been elucidated. We found that ID2 expression was increased in AR-null prostate cancer. In vitro and in vivo studies confirmed that ID2 promotes PCa malignancy and can confer resistance to enzalutamide in PCa cells. We generated an ID2 UP50 signature, which is capable of determining resistance to enzalutamide and is valuable for predicting patient prognosis. Functional experiments showed that ID2 could activate stemness-associated JAK/STAT and FGFR signaling while inhibiting the AR signaling pathway. Our study indicates a potentially strong association between ID2 and the acquisition of a stem-like phenotype in adenocarcinoma cells, leading to resistance to androgen deprivation therapy (ADT) and next-generation ARPIs in prostate cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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30. Neuroendocrine gene subsets are uniquely dysregulated in prostate adenocarcinoma.
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Naranjo, Nicole M., Kennedy, Anne, Testa, Anna, Verrillo, Cecilia E., Altieri, Adrian D., Kean, Rhonda, Hooper, D. Craig, Yu, Jindan, Zhao, Jonathan, Abinader, Oliver, Pickles, Maxwell W., Hawkins, Adam, Kelly, William K., Mitra, Ramkrishna, and Languino, Lucia R.
- Abstract
Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP is enriched in small extracellular vesicles (sEVs) derived from plasma of PRAD patients, but it is absent in sEVs derived from plasma of healthy donors. Similarly, classical sEV markers are enriched in sEVs derived from plasma of prostate cancer patients, but weakly detectable in sEVs derived from plasma of healthy donors. Overall, our results pave the way to explore new strategies to diagnose these diseases based on the neuroendocrine gene expression in patient tumors or plasma sEVs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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31. Molecular Anatomy of Prostate Cancer and Its Implications in Active Surveillance and Early Intervention Strategies.
- Author
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Figiel, Sandy, Cancel-Tassin, Géraldine, Mills, Ian G., Lamb, Alastair D., Fromont, Gaelle, and Cussenot, Olivier
- Subjects
PROSTATE cancer ,MOLECULAR oncology ,CARCINOGENESIS ,EARLY medical intervention ,ANDROGEN receptors - Abstract
Understanding prostate carcinogenesis is crucial not only for identifying new treatment targets but also for developing effective strategies to manage the asymptomatic form of the disease. There is a lack of consensus about predicting the indolent form of the disease prostate cancer, leading to uncertainties regarding treatment initiation. This review aims to enhance the assessment and management of early prostate cancer by providing a comprehensive picture of the molecular anatomy of the prostate, synthesising current evidence, highlighting knowledge gaps, and identifying future directions. It presents evidence for the efficacy of active surveillance as an alternative treatment strategy and its potential benefits in specific patient groups through androgen receptor disruption. Overall, an improved understanding of prostate carcinogenesis and its molecular underpinnings can pave the way for tailored and precise management approaches for this common cancer. Further development and validation of molecule-based assessment tools are needed. Integrating genomic, proteomic, and phenotypic models, as well as functional approaches, can help predict outcomes. This facilitates selecting candidates for active surveillance and targeting interventions for higher-risk cases, contributing to more precise management strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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32. Polyploid Giant Cancer Cells Generated from Human Cytomegalovirus-Infected Prostate Epithelial Cells.
- Author
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Bouezzedine, Fidaa, El Baba, Ranim, Haidar Ahmad, Sandy, and Herbein, Georges
- Subjects
MYCOPLASMA ,FLOW cytometry ,CELL culture ,CYTOMEGALOVIRUS diseases ,CULTURE media (Biology) ,MICROSCOPY ,ONCOGENES ,COLONY-forming units assay ,GIANT cell tumors ,MANN Whitney U Test ,DESCRIPTIVE statistics ,RESEARCH funding ,EPITHELIAL cells ,CELL lines ,PROSTATE tumors - Abstract
Simple Summary: Prostate cancer remains a leading cause of death in men worldwide. Polyploid giant cancer cells (PGCCs) and chromosomal instability have been proposed to drive the progression of cancer. Given that HCMV infection has been implicated in malignant diseases from different cancer entities, in the present study, we assessed its transformation potential in vitro and evaluated the obtained cellular and molecular phenotypes of prostate epithelial cells (PECs) using HCMV high-risk clinical strains, DB and BL, which were previously isolated in our laboratory. HCMV-induced PGCC formation, Myc and EZH2 upregulation, as well as the stemness and epithelial–mesenchymal transition features verified the transformation process of PECs. Our research work deserves to be distributed among the scientific community, as it paves the way for upcoming studies targeting the potential role of HCMV and PGCCs in prostate cancer development and treatment. Background: Prostate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men worldwide. Chromosomal instability (CIN) and polyploid giant cancer cells (PGCCs) have been considered predominant hallmarks of cancer. Recent clinical studies have proven the association of CIN, aneuploidy, and PGCCs with poor prognosis of prostate cancer (PCa). Evidence of HCMV transforming potential might indicate that HCMV may be involved in PCa. Methods: Herein, we underline the role of the high-risk HCMV-DB and -BL clinical strains in transforming prostate epithelial cells and assess the molecular and cellular oncogenic processes associated with PCa. Results: Oncogenesis parallels a sustained growth of "CMV-Transformed Prostate epithelial cells" or CTP cells that highly express Myc and EZH2, forming soft agar colonies and displaying stemness as well as mesenchymal features, hence promoting EMT as well as PGCCs and a spheroid appearance. Conclusions: HCMV-induced Myc and EZH2 upregulation coupled with stemness and EMT traits in IE1-expressing CTP might highlight the potential role of HCMV in PCa development and encourage the use of anti-EZH2 and anti-HCMV in PCa treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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33. Uncovering the Quality Deficiencies with Potentially Harmful Effects in Substandard and Falsified PDE-5 Inhibitors Seized by Belgian Controlling Agencies.
- Author
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Vanhee, Celine, Jacobs, Bram, Mori, Marcella, Kamugisha, Angélique, Debehault, Loïc, Canfyn, Michael, Ceyssens, Bart, Van Der Meersch, Hans, van Hoorde, Koenraad, Deconinck, Eric, and Willocx, Marie
- Subjects
DRUGS of abuse ,HEALTH risk assessment ,MASS spectrometry ,MICROBIOLOGY ,PATHOGENIC bacteria - Abstract
Illicit PDE-5 inhibitors are frequently encountered by regulatory agencies. Self-medicating with substandard and falsified (SF) PDE-5 inhibitors could be dangerous as they are likely taken without any medical supervision and might be of poor quality which could result in adverse reactions. In order to provide an overview of the quality deficiencies present in recently seized illicit PDE-5 samples that may pose health risks, we set out to identify the products' different chemical and/or biological risks. Our results indicate that 38% of the samples harbored a chemical risk including the significant exceedance of the maximum recommended dosage, a large heterogeneity in API content between the different tablets in the same package or blister and the presence of only 40% of the claimed dosage. Moreover, our results also demonstrate that 16 of the 32 samples were not compliant with the internationally set microbiological quality standards. Startlingly, two samples were severely contaminated with potentially pathogenic bacteria, which could result in a gastrointestinal illness upon oral intake. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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34. The Development and Validation of a Targeted LC-HRAM-MS/MS Methodology to Separate and Quantify p -Synephrine and m -Synephrine in Dietary Supplements and Herbal Preparations.
- Author
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Vanhee, Celine, Barhdadi, Sophia, Kamugisha, Angélique, Van Mulders, Tanika, Vanbrusselen, Kevin, Willocx, Marie, and Deconinck, Eric
- Subjects
STRUCTURAL isomers ,MASS spectrometry ,GOVERNMENT agencies ,TANDEM mass spectrometry ,FOOD adulteration - Abstract
Dietary supplements containing Citrus aurantium or p-synephrine remain very popular in Europe and the United States of America (USA). They are primarily sold as weight loss enhancers, although their efficacy and the safety are still under scrutiny. To this end, several countries have set maximum threshold levels of p-synephrine that are permitted in dietary supplements. Moreover, there have also been reports of possible chemical adulteration of these supplements with the synthetic positional isomer, m-synephrine, known to be used as a medicinal product. Therefore, it is pivotal for regulatory agencies to be able to discriminate between the two positional isomers and also quantify the amount of each when encountered in dietary supplements. Here, we present the development and the validation of a simple and fast "dilute and shoot" procedure, employing liquid chromatographic (LC) separation in combination with high-resolution accurate mass (HRAM) tandem mass spectroscopy (LC-HRAM-MS/MS) to separate these two isomers and subsequently quantify them. The quantification methodology has been validated using the "total error approach", applying accuracy profiles, and is consequently compliant with ISO17025. Moreover, ten real-life samples, either purchased online or encountered by Belgian regulatory agencies, were analyzed using the described procedure. Startlingly, only one sample out of ten was compliant with Belgian legislation in terms of labeling, the presence of a batch number, expiration date and dosage (with a tolerated error of ±20%). Moreover, three samples also contained banned substances such as yohimbine and sibutramine. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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35. Operative and oncological outcomes of salvage robotic radical and partial nephrectomy: a multicenter experience.
- Author
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Okhawere, Kennedy E., Grauer, Ralph, Zuluaga, Laura, Meilika, Kirolos N., Ucpinar, Burak, Beksac, Alp Tuna, Razdan, Shirin, Saini, Indu, Abramowitz, Chiya, Abaza, Ronney, Eun, Daniel D., Bhandari, Akshay, Hemal, Ashok K., Porter, James, Stifelman, Michael D., Menon, Mani, and Badani, Ketan K.
- Abstract
We aim to describe the perioperative and oncological outcomes for salvage robotic partial nephrectomy (sRPN) and salvage robotic radical nephrectomy (sRRN). Using a prospectively maintained multi-institutional database, we compared baseline clinical characteristics and perioperative and postoperative outcomes, including pathological stage, tumor histology, operative time, ischemia time, estimated blood loss (EBL), length of stay (LOS), postoperative complication rate, recurrence rate, and mortality. We identified a total of 58 patients who had undergone robotic salvage surgery for a recurrent renal mass, of which 22 (38%) had sRRN and 36 (62%) had sRPN. Ischemia time for sRPN was 14 min. The median EBL was 100 mL in both groups (p = 0.581). One intraoperative complication occurred during sRRN, while three occurred during sRPN cases (p = 1.000). The median LOS was 2 days for sRRN and 1 day for sRPN (p = 0.039). Postoperatively, one major complication occurred after sRRN and two after sRPN (p = 1.000). The recurrence reported after sRRN was 5% and 3% after sRPN. Among the patients who underwent sRRN, the two most prevalent stages were pT1a (27%) and pT3a (27%). Similarly, the two most prevalent stages in sRPN patients were pT1a (69%) and pT3a (6%). sRRN and sRPN have similar operative and perioperative outcomes. sRPN is a safe and feasible procedure when performed by experienced surgeons. Future studies on large cohorts are essential to better characterize the importance and benefit of salvage partial nephrectomies. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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36. A prognostic model for use before elective surgery to estimate the risk of postoperative pulmonary complications (GSU-Pulmonary Score): a development and validation study in three international cohorts.
- Subjects
- Humans, Female, Prognosis, Middle Aged, Male, Prospective Studies, Aged, Risk Assessment methods, Adult, Machine Learning, Risk Factors, Lung Diseases etiology, Cohort Studies, Elective Surgical Procedures adverse effects, Postoperative Complications epidemiology, COVID-19 epidemiology
- Abstract
Background: Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery., Methods: Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a composite of pneumonia, acute respiratory distress syndrome, and unexpected mechanical ventilation. Model development with candidate predictor variables was done in the GlobalSurg-CovidSurg Week dataset (global; October, 2020). Two structured machine learning techniques were explored (XGBoost and the least absolute shrinkage and selection operator [LASSO]), and the model with the best performance (GSU-Pulmonary Score) underwent internal validation using bootstrap resampling. The discrimination and calibration of the score were externally validated in two further prospective cohorts: CovidSurg-Cancer (worldwide; February to August, 2020, during the COVID-19 pandemic) and RECON (UK and Australasia; January to October, 2019, before the COVID-19 pandemic). The model was deployed as an online web application. The GlobalSurg-CovidSurg Week and CovidSurg-Cancer studies were registered with ClinicalTrials.gov, NCT04509986 and NCT04384926., Findings: Prognostic models were developed from 13 candidate predictor variables in data from 86 231 patients (1158 hospitals in 114 countries). External validation included 30 492 patients from CovidSurg-Cancer (726 hospitals in 75 countries) and 6789 from RECON (150 hospitals in three countries). The overall rates of pulmonary complications were 2·0% in derivation data, and 3·9% (CovidSurg-Cancer) and 4·7% (RECON) in the validation datasets. Penalised regression using LASSO had similar discrimination to XGBoost (area under the receiver operating curve [AUROC] 0·786, 95% CI 0·774-0·798 vs 0·785, 0·772-0·797), was more explainable, and required fewer covariables. The final GSU-Pulmonary Score included ten predictor variables and showed good discrimination and calibration upon internal validation (AUROC 0·773, 95% CI 0·751-0·795; Brier score 0·020, calibration in the large [CITL] 0·034, slope 0·954). The model performance was acceptable on external validation in CovidSurg-Cancer (AUROC 0·746, 95% CI 0·733-0·760; Brier score 0·036, CITL 0·109, slope 1·056), but with some miscalibration in RECON data (AUROC 0·716, 95% CI 0·689-0·744; Brier score 0·045, CITL 1·040, slope 1·009)., Interpretation: This novel prognostic risk score uses simple predictor variables available at the time of a decision for elective surgery that can accurately stratify patients' risk of postoperative pulmonary complications, including during SARS-CoV-2 outbreaks. It could inform surgical consent, resource allocation, and hospital-level prioritisation as elective surgery is upscaled to address global backlogs., Funding: National Institute for Health Research., Competing Interests: Declaration of interests The CovidSurg and GlobalSurg studies were funded by a National Institute for Health Research (NIHR) Global Health Research Unit grant (NIHR 16.136.79). The funder has approved the submission of this report for publication. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the UK Department of Health and Social Care. STARSurg Collaborative is supported by an unrestricted educational partnership with BJS Society. JCG is funded through a doctoral research fellowship from the NIHR Academy (NIHR300175). LB is funded by the Wellcome Trust 4-year studentship programme in Mechanisms of Inflammatory Disease (MIDAS; grant number 215182/Z/19/Z, part of 108871/B/15/Z). SC is supported by Experimental Cancer Medicine Centre Birmingham (Cancer Research UK and NIHR) funding. GVG acknowledges support from the NIHR Birmingham ECMC, NIHR Birmingham SRMRC, Nanocommons H2020-EU (731032), MAESTRIA (grant agreement 965286), HYPERMARKER (grant agreement 101095480), PARC (grant agreement 101057014), and the MRC Heath Data Research UK (HDRUK/CFC/01), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. BB has received a grant from NIHR Global Health Research Group on Perioperative and Critical Care (NIHR133850) and is a board member of SAMRC and Safe Surgery South Africa. MWSH has received honoraria for lectures from Olympus UK and is a council member of BAOMS QOMS., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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37. Evaluating the Effect of Microcrystalline Cellulose Variations on Tablet Quality of Natural Plant Product Using a Design of Experiment Approach.
- Author
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Zhao, Haiyue, Shi, Chuting, Liu, Zhenda, Zhao, Lijie, and Shen, Lan
- Abstract
Microcrystalline cellulose (MCC) of different grades from different manufacturers differ in particulate and powder properties significantly. The choice of MCC is important to the development of a tablet formulation with satisfactory quality. In this study, the effects of five different MCCs (KG 802, Pharmacel 102, MC 302, M 200, and PH 112) that had different compactibility and tablet disintegration on the tablet quality of two different natural plant products (NPPs) were evaluated systematically, including CrataegiFolium ethanol extract (CF-E) and SarcandraeHerba water extract (SH-W). The result of D-optimal mixture designs demonstrated that KG 802 showed the best ability to improve compression properties and tensile strength, followed by Pharmacel 102, MC 302, and M 200. PH 112 did the weakest. However, MCCs of different grades had no different influence on the disintegration of NPP tablets. Similar results were found in the experiments of the two different NPP powders, suggesting the generalization of the finding. Moreover, KG 802-containing CF-E formulations showed the largest optimum region size, that is, the lowest production risk. The design space sizes of SH-W were hardly sensitive to the change of MCCs, due to the better tabletability. In conclusion, the properties of MCCs could transfer to the high NPP loading (70%) formulations, leading to the variations on the compression properties and tablet quality. The poorer the tabletability of NPP, the more obvious the variation. The result is promising for the use of MCC and the manufacturing of high drug-loading NPP tablets by direct compression. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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38. THE MODELING OF CHANGES IN THE SPECIFIC ACTIVITY OF TRITIUM IN PLANTS.
- Author
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Kryazhych, Olha, Kovalenko, Oleksandr, Itskovych, Victoria, and Iushchenko, Kateryna
- Subjects
TRITIUM ,BIRCH ,RADIOISOTOPES ,BIOACCUMULATION in plants ,HUMIDITY - Abstract
Birch juice is a drink made of birch sap of medium-sized wild trees at the springtime. It is popular especially in northern Europe and Asia on territories with occasionally waterlogged permeable soils. However, some of these areas coincide with highest tritium leakage ever recorded (Kyshtym, Chernobyl and Fukushima). Robust analyses on tritium levels (scintillation method) in the birch sap were carried out in location with a constant load of tritiated water between 2003 and 2016. Sampling the birch sap was carried out annually in season (usually from the final week of February to the first-week of April. Sampling of birch sap was usually has been carried out during the period when the daytime air temperature was within +(5-8) °C minimum for 3 days. During this period, began intensive sap flow. Data obtained is put in relation to air temperature and humidity in order to contribute to the understanding basic mechanisms of tritium intake via birch. Findings confirmed that tritium easily penetrates via water into any organism and it can accumulate there for much longer than its half-decay times. It was firstly revealed that it is possible to predict the concentration of this dangerous pollutant in the birch sap based on the temperature and humidity dynamics. And with continuous input of tritium into the environment, the concentration of tritium in free water increases polynomial. The specific tritium activity values due to the gradient of tritium concentration in the atmosphere-plant-ground system of the change in temperature and humidity. For the organization of monitoring and control, the possibility of radioecological safety for the affected areas was determined. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
39. Quality by design approach with multivariate analysis and artificial neural network models to understand and control excipient variability.
- Author
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Kim, Ji Yeon and Choi, Du Hyung
- Published
- 2023
- Full Text
- View/download PDF
40. Novel candidate theranostic radiopharmaceutical based on strontium hexaferrite nanoparticles conjugated with azacrown ligand.
- Author
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Khabirova, Sofia, Aleshin, Gleb, Anokhin, Evgeny, Shchukina, Anna, Zubenko, Anastasia, Fedorova, Olga, Averin, Aleksey, Trusov, Lev, and Kalmykov, Stepan
- Subjects
STRONTIUM ,SILANE coupling agents ,MAGNETIC nanoparticles ,FERRITES ,RADIOPHARMACEUTICALS ,CARBOXYL group - Abstract
In this article, we report to the best of our knowledge the first modification of NPs with ligands for combined radiopharmaceuticals. Nanoparticles with suitable magnetic properties can be used both for diagnostics as a contrast for MRI and for therapy, including the insufficiently studied magneto-mechanical therapy. Strontium hexaferrite is one of the few hard-magnetic materials for which stable biocompatible colloidal solutions can be obtained. Strontium hexaferrite nanoparticles coated with silicon dioxide (SHF@SiO
2 ) were modified with an amino silane coupling agent (3-aminopropyl)triethoxysilane and azacrown ether derivatives with six heteroatoms in rings were covalently linked to the amine group through the carboxyl group. The hard magnetic nanoparticles were then radiolabeled with207 Bi with a labelling yield of up to 99.8%. In vitro experiments showed that the complex SHF@SiO2 -APTES-L2-207 Bi is stable enough to be a potential theranostic radiopharmaceutical. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
41. Comparison of Perioperative, Functional, and Oncological Outcomes of Transperitoneal and Extraperitoneal Laparoscopic Radical Prostatectomy.
- Author
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Bejrananda, Tanan, Karnjanawanichkul, Watid, and Tanthanuch, Monthira
- Abstract
Purpose. +is study aimed to compare the oncological, functional, and perioperative outcomes of localized and locally advanced prostate cancer treated with intraperitoneal or extraperitoneal laparoscopic radical prostatectomy (LRP). Methods. From April, 2008, through December, 2020, 266 patients underwent laparoscopic radical prostatectomy, 168 cases with an extraperitoneal approach (E-LRP) and 98 cases using a transperitoneal approach (T-LRP). +e clinical, perioperative, functional, and oncological outcomes were collected and compared between these groups. At the 3-, 12- and 24-monthfollow-ups, the functional outcomes tested were urinary function (urinary domain of EPIC) and sexual function (sexual domain of EPIC). +e oncological outcomes of biochemical recurrence, biochemical recurrence-free survival, and positive surgical margin status were evaluated. Univariable and multivariable Cox regression analyses were used to identify factors predictive for biochemical recurrence. All statistical analyses used the R program. Results. +e patient characteristics were similar between the E-LRP and T-LRP groups except for higher prostatic-speci
- Published
- 2023
- Full Text
- View/download PDF
42. CRAC and SK Channels: Their Molecular Mechanisms Associated with Cancer Cell Development.
- Author
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Tiffner, Adéla, Hopl, Valentina, and Derler, Isabella
- Subjects
POTASSIUM metabolism ,CALCIUM metabolism ,ION channels ,CANCER invasiveness ,METASTASIS ,MOLECULAR biology ,CELLULAR signal transduction ,CELL motility ,CELL proliferation ,CELL lines ,CALCIUM-binding proteins - Abstract
Simple Summary: Cell fate is ultimately determined by the precisely coordinated action of the Ca
2+ -signaling machinery. During carcinogenesis, Ca2+ signaling is significantly remodeled due to mutations and/or ectopic expression. Here, we summarize current knowledge on how alterations in Ca2+ signaling contribute to the development of different cancer hallmarks. Emphasis is placed on the structure/function relationship of the well-studied store-operated Ca2+ channel, i.e., Orai1, and the Ca2+ -activated K+ channel, i.e., SK3, alongside their individual and joint roles in cancer. This review lays out the current state of knowledge of Ca2+ -signaling effectors and proteins as potential targets for the treatment of certain cancer types, with Orai1 and SK3 presented as emerging therapeutic targets. Cancer represents a major health burden worldwide. Several molecular targets have been discovered alongside treatments with positive clinical outcomes. However, the reoccurrence of cancer due to therapy resistance remains the primary cause of mortality. Endeavors in pinpointing new markers as molecular targets in cancer therapy are highly desired. The significance of the co-regulation of Ca2+ -permeating and Ca2+ -regulated ion channels in cancer cell development, proliferation, and migration make them promising molecular targets in cancer therapy. In particular, the co-regulation of the Orai1 and SK3 channels has been well-studied in breast and colon cancer cells, where it finally leads to an invasion-metastasis cascade. Nevertheless, many questions remain unanswered, such as which key molecular components determine and regulate their interplay. To provide a solid foundation for a better understanding of this ion channel co-regulation in cancer, we first shed light on the physiological role of Ca2+ and how this ion is linked to carcinogenesis. Then, we highlight the structure/function relationship of Orai1 and SK3, both individually and in concert, their role in the development of different types of cancer, and aspects that are not yet known in this context. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
43. The impact of genomic biomarkers on a clinical risk prediction model for upgrading/upstaging among men with favorable-risk prostate cancer.
- Author
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Braun AE, Chan JM, Neuhaus J, Cowan JE, Kenfield SA, Van Blarigan EL, Tenggara I, Broering JM, Simko JP, Carroll PR, and Cooperberg MR
- Subjects
- Humans, Male, Middle Aged, Aged, Risk Assessment, Prostate-Specific Antigen blood, Neoplasm Staging, Prostatectomy, Genomics methods, ROC Curve, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Prostatic Neoplasms blood, Neoplasm Grading, Biomarkers, Tumor genetics
- Abstract
Background: The challenge of distinguishing indolent from aggressive prostate cancer (PCa) complicates decision-making for men considering active surveillance (AS). Genomic classifiers (GCs) may improve risk stratification by predicting end points such as upgrading or upstaging (UG/US). The aim of this study was to assess the impact of GCs on UG/US risk prediction in a clinicopathologic model., Methods: Participants had favorable-risk PCa (cT1-2, prostate-specific antigen [PSA] ≤15 ng/mL, and Gleason grade group 1 [GG1]/low-volume GG2). A prediction model was developed for 864 men at the University of California, San Francisco, with standard clinical variables (cohort 1), and the model was validated for 2267 participants from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (cohort 2). Logistic regression was used to compute the area under the receiver operating characteristic curve (AUC) to develop a prediction model for UG/US at prostatectomy. A GC (Oncotype Dx Genomic Prostate Score [GPS] or Prolaris) was then assessed to improve risk prediction., Results: The prediction model included biopsy GG1 versus GG2 (odds ratio [OR], 5.83; 95% confidence interval [CI], 3.73-9.10); PSA (OR, 1.10; 95% CI, 1.01-1.20; per 1 ng/mL), percent positive cores (OR, 1.01; 95% CI, 1.01-1.02; per 1%), prostate volume (OR, 0.98; 95% CI, 0.97-0.99; per mL), and age (OR, 1.05; 95% CI, 1.02-1.07; per year), with AUC 0.70 (cohort 1) and AUC 0.69 (cohort 2). GPS was associated with UG/US (OR, 1.03; 95% CI, 1.01-1.06; p < .01) and AUC 0.72, which indicates a comparable performance to the prediction model., Conclusions: GCs did not substantially improve a clinical prediction model for UG/US, a short-term and imperfect surrogate for clinically relevant disease outcomes., (© 2024 American Cancer Society.)
- Published
- 2024
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- View/download PDF
44. COenzyme Q10 ameliorates bisphinol A induced reproductive male toxicity: A transmission electron microscopic and immunohistochemistry study.
- Author
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Barghash, Samia, Farrag, Islam, Abd El-Hakam, Fatma, Ali, Somia, and Aly, Eman
- Published
- 2022
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- View/download PDF
45. Nutritional and metabolic signalling through GPCRs.
- Author
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Pardella, Elisa, Ippolito, Luigi, Giannoni, Elisa, and Chiarugi, Paola
- Subjects
CELL receptors ,AMINO acids ,LACTATES ,FATTY acids - Abstract
Deregulated metabolism is a well‐known feature of several challenging diseases, including diabetes, obesity and cancer. Besides their important role as intracellular bioenergetic molecules, dietary nutrients and metabolic intermediates are released in the extracellular environment. As such, they may achieve unconventional roles as hormone‐like molecules by activating cell surface G‐protein‐coupled receptors (GPCRs) that regulate several pathophysiological processes. In this review, we provide an insight into the role of lactate, succinate, fatty acids, amino acids as well as ketogenesis‐derived and β‐oxidation‐derived intermediates as extracellular signalling molecules. Moreover, the mechanisms by which their cognate metabolite‐sensing GPCRs integrate nutritional and metabolic signals with specific intracellular pathways will be described. A better comprehension of these aspects is of fundamental importance to identify GPCRs as novel druggable targets. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
46. Fast and credible likelihood-free cosmology with truncated marginal neural ratio estimation.
- Author
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Cole, Alex, Miller, Benjamin K., Witte, Samuel J., Cai, Maxwell X., Grootes, Meiert W., Nattino, Francesco, and Weniger, Christoph
- Published
- 2022
- Full Text
- View/download PDF
47. Tritium from the Molecule to the Biosphere. 1. Patterns of Its Behavior in the Environment.
- Author
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Antonova, E. V., Antonov, K. L., Vasyanovich, M. E., and Panchenko, S. V.
- Subjects
TRITIUM ,THERMONUCLEAR fusion ,BIOSPHERE ,FUEL cycle ,NUCLEAR industry ,NUCLEAR weapons testing ,CONTROLLED fusion - Abstract
The beta-emitter tritium (
3 H, the half-life is 12.32 ± 0.02 years) contained in the environment has a natural and technogenic origin. The equilibrium global content of natural tritium is estimated at (1.0–2.6) × 1018 Bq. The total activity of technogenic tritium that was formed as a result of nuclear and thermonuclear weapon tests in 1945–1975 and during the normal and emergency operation of nuclear fuel cycle enterprises reaches 1020 Bq. Anthropogenic tritium serves as a unique marker for generalizing data on the behavior of this radionuclide in different environmental components. This is especially important in view of the intensification of research and development works in the field of controlled thermonuclear fusion in recent years. Promi-sing fusion power reactors, in which it is planned to use a significant amount of3 H as fuel, can become an additional source of impact on the biosphere. Their safety should be assessed, justified, and ultimately ensured based on proper technology and infrastructure. We have analyzed the dynamics of the number of publications on3 H over the period from 1951 to 2021 from the Google Scholar and Clarivate Analytics databases. The main characteristics and chemical forms of tritium are given. The methodology for assessing the content of different forms of3 H in environmental components is given taking into account interlaboratory intercalibration. Pathways of tritium entry into the environment (atmosphere and aquatic and terrestrial ecosystems) as a result of routine and emergency releases and discharges from nuclear industry enterprises are analyzed. Seasonal fluctuations in tritium activity with the maximum level in spring, as well as the effect of climatic factors and distance from the emission source on the spatial distribution of3 H, are shown. The role of soil organic acids in the behavior of tritium in ecosystems is noted. Based on the concept of reference plant and animal species, we have analyzed publications to assess the accumulation of different forms of3 H by biota during laboratory experiments and monitoring studies of natural ecosystems. A number of topical issues that need to be addressed in the near future have been revealed. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
48. MiR-4763-3p targeting RASD2 as a Potential Biomarker and Therapeutic Target for Schizophrenia.
- Author
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Jiao Wang, Wenxin Qi, Hongwei Shi, Lin Huang, Fujiang Ning, Fushuai Wang, Kai Wang, Haotian Bai, Hao Wu, Junyi Zhuang, Huanle Hong, Haicong Zhou, Hu Feng, Yinping Zhou, Naijun Dong, Li Liu, Yanyan Kong, Jiang Xie, and Chunhua Zhao, Robert
- Subjects
SCHIZOPHRENIA treatment ,BIOMARKERS ,RAP1 proteins - Abstract
Existing diagnostic methods are limited to observing appearance and demeanor, even though genetic factors play important roles in the pathology of schizophrenia. Indeed, no molecular-level test exists to assist diagnosis, which has limited treatment strategies. To address this serious shortcoming, we used a bioinformatics approach to identify 61 genes that are differentially expressed in schizophrenia patients compared with healthy controls. In particular, competing endogenous RNA network revealed the important role of the gene RASD2, which is regulated by miR-4763-3p. Indeed, analysis of blood samples confirmed that RASD2 is downregulated in schizophrenia patients. Moreover, positron emission tomography data collected for 44 human samples identified the prefrontal and temporal lobes as potential key brain regions in schizophrenia patients. Mechanistic studies indicated that miR-4763-3p inhibits RASD2 by base-pairing with the 3’ untranslated region of RASD2 mRNA. Importantly, RASD2 has been shown to interact with β-arrestin2, which contributes to the regulation of the DRD2-dependent CREB response element-binding protein pathway in the dopamine system. Finally, results obtained with a mouse model of schizophrenia revealed that inhibition of miR)4763-3p function alleviated anxiety symptoms and improved memory. The dopamine transporters in the striatal regions were significantly reduced in schizophrenia model mice as compared with wild-type mice, suggesting that inhibition of miR-4763-3p can lessen the symptoms of schizophrenia. Our findings demonstrate that miR)4763-3p may target RASD2 mRNA and thus may serve as a potential biomarker and therapeutic target for schizophrenia, providing a theoretical foundation for further studies of the molecular basis of this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression.
- Author
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Luo, Qiuhua, Zhang, Qianying, and Wang, Puxiu
- Subjects
HYDROCHLOROTHIAZIDE ,LOSARTAN ,BEAGLE (Dog breed) ,ORAL drug administration ,DRUG solubility ,DOSAGE forms of drugs - Abstract
Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab
® 14SD, 19.53–26.91%), microcrystalline cellulose (MCC PH102, 32.86–43.31%), pre-gelatinized starch (Starch-1500, 10.96–15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150–300 MPa) and tableting speed (1200–2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar® tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar® tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F0.05 ). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
50. The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a Ca 2+ -Independent Manner.
- Author
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Schnipper, Julie, Kouba, Sana, Hague, Frédéric, Girault, Alban, Rybarczyk, Pierre, Telliez, Marie-Sophie, Guénin, Stéphanie, Tebbakha, Riad, Sevestre, Henri, Ahidouch, Ahmed, Pedersen, Stine Falsig, and Ouadid-Ahidouch, Halima
- Subjects
PANCREATIC duct ,CELL proliferation ,ION channels ,CELL cycle ,CELL growth ,ADENOCARCINOMA - Abstract
Dysregulation of the transient receptor canonical ion channel (TRPC1) has been found in several cancer types, yet the underlying molecular mechanisms through which TRPC1 impacts pancreatic ductal adenocarcinoma (PDAC) cell proliferation are incompletely understood. Here, we found that TRPC1 is upregulated in human PDAC tissue compared to adjacent pancreatic tissue and this higher expression correlates with low overall survival. TRPC1 is, as well, upregulated in the aggressive PDAC cell line PANC-1, compared to a duct-like cell line, and its knockdown (KD) reduced cell proliferation along with PANC-1 3D spheroid growth by arresting cells in the G1/S phase whilst decreasing cyclin A, CDK2, CDK6, and increasing p21
CIP1 expression. In addition, the KD of TRPC1 neither affected Ca2+ influx nor store-operated Ca2+ entry (SOCE) and reduced cell proliferation independently of extracellular calcium. Interestingly, TRPC1 interacted with the PI3K-p85α subunit and calmodulin (CaM); both the CaM protein level and AKT phosphorylation were reduced upon TRPC1 KD. In conclusion, our results show that TRPC1 regulates PDAC cell proliferation and cell cycle progression by interacting with PI3K-p85α and CaM through a Ca2+ -independent pathway. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
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