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1. The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology

Author

Loupy, A, Haas, M, Solez, K, Racusen, L, Glotz, D, Seron, D, Nankivell, BJ, Colvin, RB, Afrouzian, M, Akalin, E, Alachkar, N, Bagnasco, S, Becker, JU, Cornell, L, Drachenberg, C, Dragun, D, de Kort, H, Gibson, IW, Kraus, ES, Lefaucheur, C, Legendre, C, Liapis, H, Muthukumar, T, Nickeleit, V, Orandi, B, Park, W, Rabant, M, Randhawa, P, Reed, EF, Roufosse, C, Seshan, SV, Sis, B, Singh, HK, Schinstock, C, Tambur, A, Zeevi, A, and Mengel, M

Subjects
Organ Transplantation, Clinical Research, Transplantation, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Renal and urogenital, Arteritis, Complement C4b, Graft Rejection, Humans, Isoantibodies, Kidney Transplantation, Peptide Fragments, Research Report, clinical research, practice, translational research, science, kidney transplantation, nephrology, pathology, histopathology, organ transplantation in general, rejection, rejection: antibody-mediated, rejection: subclinical, rejection: T cell mediated, clinical research/practice, kidney transplantation/nephrology, pathology/histopathology, translational research/science, Medical and Health Sciences, Surgery
Abstract

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next-generation clinical trials.

Published
2017

3. Banff 2013 Meeting Report: Inclusion of C4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions

Author

Haas, M., Sis, B., Racusen, L.C., Solez, K., Glotz, D., Colvin, R.B., Castro, M.C.R., David, D.S.R., David-Neto, E., Bagnasco, S.M., Cendales, L.C., Cornell, L.D., Demetris, A.J., Drachenberg, C.B., Farver, C.F., Farris, A.B., III, Gibson, I.W., Kraus, E., Liapis, H., Loupy, A., Nickeleit, V., Randhawa, P., Rodriguez, E.R., Rush, D., Smith, R.N., Tan, C.D., Wallace, W.D., and Mengel, M.

Published
2014
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6. Contributors

Author

Abbasi, S., primary, Adolphi, N.L., additional, Aikawa, E., additional, Akbar, H., additional, Akilesh, S., additional, Aladjem, M.I., additional, Allocca, M., additional, Alpini, G., additional, Alroy, J., additional, Altman, B.J., additional, Andujar, P., additional, Antonello, Z.A., additional, Antsiferova, M., additional, Apica, B.S., additional, Ariel, I., additional, Aronow, B.J., additional, Ashley, J.W., additional, Badell, I.R., additional, Bagg, A., additional, Bajaj, M., additional, Banerjee, S., additional, Barbieri, J.S., additional, Bardes, E.E., additional, Barisoni, L., additional, Barletta, J.A., additional, Baskin, D.G., additional, Bastarrachea, R.A., additional, Bayat, A., additional, Bayrak-Toydemir, P., additional, Beck, A.H., additional, Beebe, D.C., additional, Beltran, H., additional, Benichou, G., additional, Bergman, M., additional, Bernard, S.A., additional, Bernardi, P., additional, Best, D.H., additional, Blair, H.C., additional, Bonaldo, P., additional, Bondy, J., additional, Bosman, F.T., additional, Bouma, B.E., additional, Brandi, M.L., additional, Bresler, S.C., additional, Brewer, M.T., additional, Britto, C.J., additional, Brock, J.E., additional, Brosens, L.A.A., additional, Budge, H., additional, Burd, E.M., additional, Burness, M.L., additional, Bushnell, T., additional, Byrd, J., additional, Calderone, A., additional, Campbell, M.J., additional, Cao, D., additional, Capell, W., additional, Cardigan, R., additional, Carey, P.M., additional, Carneiro, F., additional, Carp, S.A., additional, Carter, A.M., additional, Cascio, M.J., additional, Castellani, R.J., additional, Castellanos, J., additional, Caviglia, J.M., additional, Cecconi, F., additional, Chamarthy, S., additional, Chamma, E., additional, Chang, A., additional, Chang, A.Y., additional, Chang, N.C., additional, Chapman, D.G., additional, Charles, A.K., additional, Chen, D., additional, Chen, D.F., additional, Chen, P., additional, Cheng, J., additional, Chernock, R.D., additional, Cheruvu, S., additional, Chiang, J., additional, Childs, G.V., additional, Cho, Y.-B., additional, Choi, A.M.K., additional, Choi, J.K., additional, Cipriani, N.A., additional, Cleary, J.O.S.H., additional, Clementi, E., additional, Clines, G.A., additional, Cohen, M.L., additional, Coleman, W.B., additional, Coletta, D.K., additional, Collie, A.M.B., additional, Cooling, L., additional, Coron, E., additional, Côté, D., additional, Coussens, L.M., additional, Crielaard, B.J., additional, Cron, R.Q., additional, Crum, C.P., additional, Cruz, N.M., additional, Dairkee, S.H., additional, Daly, C.A., additional, Dang, C.V., additional, Danila, M.I., additional, Daradich, A., additional, Darnell, C.M., additional, Dartt, D.A., additional, Das, A., additional, D’Asta, F., additional, DeFronzo, R., additional, De Hertogh, G., additional, Dela Cruz, C.S., additional, de la Cruz-Merino, L., additional, De Palma, C., additional, Demetris, A.J., additional, DeMorrow, S., additional, Denechaud, P.-D., additional, Di Carli, M.F., additional, DiCarlo, E.F., additional, Dikic, I., additional, Dimberg, A., additional, Dowell, M.L., additional, Doyle, L.A., additional, Drachenberg, C.B., additional, Driskell, E., additional, Duda, D.G., additional, Duker, J., additional, Dyck, J.R.B., additional, Ecker, C., additional, Elifritz, J.M., additional, Elsheikh, T.M., additional, Ensari, A., additional, Ernst, L.M., additional, Esch, K.J., additional, Fajas-Coll, L., additional, Fang, Q., additional, Farhat, N.A., additional, Farshid, G., additional, Faye-Petersen, O.M., additional, Fehlings, M.G., additional, Fend, F., additional, Feng, X., additional, Fernandes, H., additional, Fernandez-Checa, J.C., additional, Ferreira, B.P., additional, Fidler, I.J., additional, Finn, J.A., additional, Fischer, A., additional, Fishbein, M.C., additional, Fleit, H.B., additional, Flomenbaum, M., additional, Folkins, A., additional, Francis, H., additional, Frank, K.M., additional, Frevert, C.W., additional, Frias, A.E., additional, Friedman, J.R., additional, Fukumura, D., additional, Furie, M.B., additional, Gaffo, A.L., additional, Galateau-Sallé, F., additional, Gallegos-Cabriales, E.C., additional, Gandhi, C.R., additional, Gannon, M., additional, García-Moliner, M.L., additional, Gardner, J.M., additional, Gasper, C.A., additional, Gaulard, P., additional, Gaut, J.P., additional, Gavia-García, G., additional, Gerrard, C., additional, Ghosh, A.P., additional, Giersch, A.B.S, additional, Gilbert, S.R., additional, Gill, J.R., additional, Giusti, F., additional, Glorioso, J.M., additional, González-Torres, M.C., additional, Goolsby, C.L., additional, Gora, M.J., additional, Gordon, I.O., additional, Gotlieb, A.I., additional, Gouw, A.M., additional, Goyal, A., additional, Grégoire, M., additional, Graham, B.B., additional, Granger, D.N., additional, Greene, A.K., additional, Greenlee, J.J., additional, Griffiths, R., additional, Guimarães, A.R., additional, Gulati, M., additional, Gullet, A., additional, Gupta, S., additional, Haider, N.B., additional, Halushka, M.K., additional, Hambuch, T.M., additional, Hamza, S.M., additional, Han, Y., additional, Hansen, W.P., additional, Hard, R., additional, Harris, B.T., additional, Harris, J.E., additional, Hartnett, M.E., additional, Hasserjian, R.P., additional, Hatch, G.M., additional, Hefti, M.M., additional, Heller, D.S., additional, Hemminger, J.A., additional, Hendrickson, J.E., additional, Henley, K.D., additional, Herzog, E., additional, Hess, J.R., additional, Hill, C.E., additional, Hipp, J., additional, Hobbs, R., additional, Höller, D., additional, Hodges, R.R., additional, Homer, R.J., additional, Horowitz, N., additional, Hsi, E.D., additional, Hsieh, A.L., additional, Hunt, J.M., additional, Hure, S., additional, Husain, A.N., additional, Hussey, S., additional, Hutcheson, J.D., additional, Hutson, R.M., additional, Illescas-Vacas, A., additional, Irvin, C.G., additional, Jaffer, F.A., additional, Jäger, R., additional, Jain, R.K., additional, Jain, S., additional, James, J., additional, Jansen, M., additional, Jarzembowski, J.A., additional, Jaurand, M.-C., additional, Jean, D., additional, Jegga, A.G., additional, Jellinger, K.A., additional, Jen, K.-Y., additional, Jo, V.Y., additional, Johnson, B., additional, Jones, R.L., additional, Kalfa, T.A., additional, Kamionek, M., additional, Kang, D., additional, Kantari, C., additional, Kantor, P.F., additional, Kanzaki, G., additional, Karns, R., additional, Katzman, P.J., additional, Kawai, T., additional, Kelley, T.W., additional, Kent, J.W., additional, Kerr, E.H., additional, Kew, R.R., additional, Khalighi, M., additional, Khanh Vu, T.H., additional, Khong, T.Y., additional, Kim, B.S., additional, Kim, J., additional, Klein, M.J., additional, Knechtle, S.J., additional, Konkle, B.A., additional, Kowalewska, J., additional, Kricka, L.J., additional, Krishnan, B., additional, Kumar, A., additional, Kumar, S., additional, Kvietys, P., additional, Kwong, R.Y., additional, Lafont, E., additional, Laga, A.C., additional, Lagarrigue, S., additional, Lakin, A., additional, Laszik, Z.G., additional, Lauwers, G.Y., additional, Laver, N.V., additional, Lawlor, M.W., additional, Lederer, J.A., additional, Lee, R.E., additional, Lee, W.M., additional, LeGallo, R., additional, Leich, E., additional, Lemmens, B., additional, Le Pimpec-Barthes, F., additional, Leval, L., additional, Levy, B.D., additional, Lewis, J.S., additional, Lewis, T.L., additional, Leyva-Illades, D., additional, Li, L., additional, Li, Y.-P., additional, Lianidou, E.S., additional, Liao, L., additional, Liapis, H., additional, Lin, J.B., additional, Lin, A.-L., additional, Lindsay, M.E., additional, Liu, E., additional, Longacre, T., additional, Lopez-Alvarenga, J.C., additional, Lopez-Mejía, I., additional, Lozanski, G., additional, Lucia, M.S., additional, Luk, E., additional, Lutty, G.A., additional, Maclellan, R.A., additional, Madabhushi, A., additional, Mahindra, A., additional, Malek, E., additional, Mammucari, C., additional, Mani, H., additional, Mao, S.A., additional, Marboe, C.C., additional, Marí, M., additional, Marini, F., additional, Markou, A., additional, Marshall, A.H., additional, Martin, S.J., additional, Marzioni, M., additional, Masli, S., additional, Matsukuma, K.E., additional, Matulonis, U.A., additional, Mayfield, J., additional, McCoy, J.P., additional, McDougle, C.J., additional, McGinnis, M.R., additional, McGuire, A., additional, McKinstry, K.K., additional, McManus, B.M., additional, Means, A.L., additional, Meny, G.M., additional, Merchant, N., additional, Meserve, E.E.K, additional, Mess, A.M., additional, Minervini, M.I., additional, Mitchell, R.N., additional, Monaco, S.E., additional, Monga, S.P., additional, Monica Way, H.-Y., additional, Montecucco, C., additional, Montone, K.T., additional, Morgan, E.A., additional, Morgan, T.K., additional, Morrissey, K., additional, Mortensen, R.M., additional, Moser, S.A., additional, Mosquera, J.M., additional, Mossman, B.T., additional, Motta, A.C.F., additional, Mullins, E., additional, Murphy, G.F., additional, Murray, L., additional, Mysorekar, I.U., additional, Nadel, B., additional, Nadon, A.S., additional, Nagathihalli, N., additional, Nájera-Medina, O., additional, Nalesnik, M.A., additional, Nast, C.C., additional, Natkunam, Y., additional, Nault, J.C., additional, Nava-González, E.J., additional, Nayar, R., additional, Nerenz, R.D., additional, Neumann, H., additional, Ni, H., additional, Nolte, K.B., additional, Norton, L., additional, Nowak, J., additional, Nucera, C., additional, Nyberg, S.L., additional, Oakes, S.A., additional, Offerhaus, G.J.A., additional, Ojha, S., additional, Okabe, H., additional, Oliveira, A.M., additional, Osborn, E.A., additional, O'Tierney-Ginn, P., additional, Ott, G., additional, Ozcan, A., additional, Padera, R.F., additional, Pagano, M.B., additional, Page, E.K., additional, Paintal, A.S., additional, Pairon, J.-C., additional, Papadimitriou, J.C., additional, Park, H.-J., additional, Park, J.Y., additional, Parsons, L.N., additional, Patra, D., additional, Peclovits, A., additional, Peeters, P.M., additional, Perkins, T.N., additional, Perry, G., additional, Perumbeti, A., additional, Petersen, C.A., additional, Petrache, I., additional, Petroff, M.G., additional, Pettus, J.R., additional, Picken, M.M., additional, Pierson, C.R., additional, Pittman, M.E., additional, Pogoriler, J., additional, Politi, K., additional, Pollack, S.M., additional, Quintanilla-Martínez, L., additional, Rai, M.F., additional, Ramkissoon, S., additional, Randhawa, P.S., additional, Rangel, J.R., additional, Rasola, A., additional, Reeves, B., additional, Reheman, A., additional, Remick, D.G., additional, Reynaert, N.L., additional, Richmond, J.M., additional, Rivella, S., additional, Rivenbark, A.G., additional, Rizzuto, R., additional, Roberts, K.A., additional, Robin, D.A., additional, Robinson, L.J., additional, Rockey, D.C., additional, Rosenwald, A., additional, Rossetto, O., additional, Roth, K.A., additional, Roy-Chowdhury, J., additional, Roy-Chowdhury, N., additional, Rubin, M.A., additional, Rudnicki, M.A., additional, Russell, D.S., additional, Ryter, S.W., additional, Saban, D.R., additional, Sacher, R.A., additional, Sacks, D.B., additional, Sagaert, X., additional, Sagdeo, A., additional, Sahay, B., additional, Sahin, A., additional, Samali, A., additional, Sampson, B., additional, Sánchez-Escribano, R., additional, Sandri, M., additional, Sanyal, A., additional, Sasatomi, E., additional, Sauer, V., additional, Scherpereel, A., additional, Schmidt, E.P., additional, Schwabe, R.F., additional, Scorrano, L., additional, Scott, M.G., additional, Scull, J.C., additional, Seidman, M.A., additional, Seki, A., additional, Sellati, T.J., additional, Serban, K., additional, Serhan, C.N., additional, Seshan, S.V., additional, Seth, A., additional, Seykora, J.T., additional, Sharma, N., additional, Shi, C., additional, Shi, S.-R., additional, Shimada, M., additional, Shimizu, A., additional, Singer, D.B., additional, Sitko, K., additional, Smallwood, R.F., additional, Smiraglia, D.J., additional, Smith, B.R., additional, Smola, H., additional, Soubeyrand, M., additional, Stahl, W.L., additional, Stajić, M., additional, Stanworth, S.J., additional, Stathatos, N., additional, Stemler, K.M., additional, Stevens, T.M., additional, Stine, Z.E., additional, Stoll, M.L., additional, Strati, A., additional, Strutt, T.M., additional, Sund, M., additional, Sung, M.M., additional, Symonds, M.E., additional, Tabar, S., additional, Takahashi, N., additional, Talmadge, J.E., additional, Tang, V., additional, Tangrea, M., additional, Tarango, C., additional, Tario, J.D., additional, Taylor, C.R., additional, Taylor, R., additional, Tearney, G.J., additional, Tefera, K., additional, Thomas, S., additional, Thornburg, K.L., additional, Tirado, C.A., additional, Tobian, A.A.R., additional, Tomaszewski, J.E., additional, Tormey, C.A., additional, Torres, R., additional, Tran, M.-H., additional, Tredget, E.E., additional, Treister, N.S., additional, Trotter, J., additional, Troyer, D., additional, Truong, L., additional, Tubbs, R.R., additional, Turakhia, S., additional, Unglert, C.I., additional, Utheim, T., additional, Vahabzadeh, A., additional, van Bokhoven, A., additional, Vanden Berghe, T., additional, Vandenabeele, P., additional, van der Klei, I.J., additional, Vanguri, V.K., additional, Van Noorden, C.J.F, additional, Van Poznak, C., additional, Vassallo, R.R., additional, Vawda, R., additional, Vieth, M., additional, Visscher, D.W., additional, Volk, S.W., additional, Vyas, G.N., additional, Waggoner, S.N., additional, Walczak, H., additional, Walker, D.H., additional, Wallace, P.K., additional, Wanat, K.A., additional, Wang, J., additional, Wang, Y., additional, Wang, Y.X., additional, Warger, W.C., additional, Wei, S., additional, Weinman, S.A., additional, Wenig, B.M., additional, Wentz, S.C., additional, Werner, S., additional, Wertheim, G., additional, Whitley, E.M., additional, Wooderchak-Donahue, W., additional, Woods, K., additional, Wouters, E.F.M., additional, Wu, Y., additional, Xing, W., additional, Yachimski, P., additional, Yan, P., additional, Yang, J., additional, Yang, L., additional, Yoshizawa, S., additional, Yuan, J., additional, Yun, S.-H., additional, Yvon, A., additional, Zhang, H., additional, Zhang, P., additional, Zhao, Z., additional, Zhu, G., additional, Zhu, R., additional, Zordoky, B.N., additional, Zou, J., additional, Zuccato, J.A., additional, and Zucman-Rossi, J., additional

Published
2014
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8. Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells

Author

Antonelli, G, Angelotti, Ml, Allinovi, M, Guzzi, F, Sisti, A, Semeraro, R, Conte, C, Mazzinghi, B, Nardi, S, Melica, Me, De Chiara, L, Lazzeri, E, Lasagni, L, Lottini, T, Landini, S, Giglio, S, Mari, A, Di Maida, F, Antonelli, A, Porpiglia, F, Schiavina, R, Ficarra, V, Facchiano, D, Gacci, M, Serni, S, Carini, M, Netto, Gj, Roperto, Rm, Magi, A, Christiansen, Cf, Rotondi, M, Liapis, H, Anders, Hj, Minervini, A, Raspollini, Mr, and Romagnani, P.

Subjects
Acute kidney injury, renal cell carcinoma, renal progenitors
Published
2020

9. Banff ʼ09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups

Author

Sis, B., Mengel, M., Haas, M., Colvin, R. B., Halloran, P. F., Racusen, L. C., Solez, K., Baldwin, W. M., III, Bracamonte, E. R., Broecker, V., Cosio, F., Demetris, A. J., Drachenberg, C., Einecke, G., Gloor, J., Glotz, D., Kraus, E., Legendre, C., Liapis, H., Mannon, R. B., Nankivell, B. J., Nickeleit, V., Papadimitriou, J. C., Randhawa, P., Regele, H., Renaudin, K., Rodriguez, E. R., Seron, D., Seshan, S., Suthanthiran, M., Wasowska, B. A., Zachary, A., and Zeevi, A.

Published
2010
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10. Banff ʼ05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy (‘CAN’)

Author

Solez, K., Colvin, R. B., Racusen, L. C., Sis, B., Halloran, P. F., Birk, P. E., Campbell, P. M., Cascalho, M., Collins, A. B., Demetris, A. J., Drachenberg, C. B., Gibson, I. W., Grimm, P. C., Haas, M., Lerut, E., Liapis, H., Mannon, R. B., Marcus, P. B., Mengel, M., Mihatsch, M. J., Nankivell, B. J., Nickeleit, V., Papadimitriou, J. C., Platt, J. L., Randhawa, P., Roberts, I., Salinas-Madriga, L., Salomon, D. R., Seron, D., Sheaff, M., and Weening, J. J.

Published
2007

20. Banff ’09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups

Author

Sis, B., Mengel, M., Haas, M., Colvin, R.B., Halloran, P.F., Racusen, L.C., Solez, K., Baldwin, W.M., III, Bracamonte, E.R., Broecker, V., Cosio, F., Demetris, A.J., Drachenberg, C., Einecke, G., Gloor, J., Glotz, D., Kraus, E., Legendre, C., Liapis, H., Mannon, R.B., Nankivell, B.J., Nickeleit, V., Papadimitriou, J.C., Randhawa, P., Regele, H., Renaudin, K., Rodriguez, E.R., Seron, D., Seshan, S., Suthanthiran, M., Wasowska, B.A., Zachary, A., and Zeevi, A.

Published
2010
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23. MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: a comparison with clinicopathologic features and survival

Author

Nakopoulou, L. Gakiopoulou, H. Zervas, A. Giannopoulou, I. Constantinides, C. Lazaris, A.C. Liapis, H. Kyriakou, G. Dimopoulos, C.

Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients’ disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients’ disease-free and overall survival. In conclusion, the authors’ results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.

Published
2001

24. Matrix metalloproteinase-1 and -3 in breast cancer: Correlation with progesterone receptors and other clinicopathologic features

Author

Nakopoulou, L Giannopoulou, I Gakiopoulou, H Liapis, H and Tzonou, A Davaris, PS

Abstract

Although matrix metalloproteinases (MMPs) are implicated in breast cancer progression, the contribution of MMP-1 and MMP-3 to this process, has not been thoroughly investigated. Matrix metalloproteinases (MMPs) are important at several points during multistage neoplastic progression. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1, MMM-3 proteins, and MMP-3 mRNA, respectively, in 77 infiltrative breast carcinomas. MMP-1, MMP-3 protein, and MMP-3 mRNA detection were analyzed in parallel with clinicopathologic features (menopausal status, histological type, nuclear and histological grade, stage) and the immunohistochemical reactivity of estrogen (ER), progesterone (PR) receptors, and c-erbB-2 oncoprotein in breast carcinomas. Statistical analysis was performed using the multiple linear regression test.. Immunoreactivity for MMP-1 and MMP-3 was observed in 59 of 77 (77%) and 22 of 77 (28.5%) breast carcinomas and was evaluated separately in cancer cells and in stromal fibroblasts. MMP-3 mRNA was detected in 72 of 77 (93.5%) carcinomas exclusively in stromal cells within the tumors or in the marginal portion, of tumors. MMP-1 protein immunoreactivity in stromal fibroblasts but not in cancer cells showed a statistically significant correlation with tumor stage (P = .04). MMP-1 reactivity either in stromal or in cancer cells showed a statistically significant inverse correlation with PR expression (P = .04 and P = .04, respectively). MMP-3 protein immunoreactivity in cancer or stromal cells and MMP-3 mRNA expression was not associated with the clinicopathologic features studied. MMP-3 mRNA was detected more often in ductal carcinomas. These results indicate that MMP-1 may contribute to breast cancer invasiveness. Furthermore, they suggest differential functions for MMP-1 and MMP-3 in breast cancer progression. Copyright (C) 1999 by W.B. Saunders Company.

Published
1999

25. Experimental models of CKD

Author

Kanlaya, R., primary, Sintiprungrat, K., additional, Thongboonkerd, V., additional, Torremade, N., additional, Bindels, R., additional, Hoenderop, J., additional, Fernandez, E., additional, Dusso, A., additional, Valdivielso, J. M., additional, Krueger, T., additional, Boor, P., additional, Schafer, C., additional, Westenfeld, R., additional, Brandenburg, V., additional, Schlieper, G., additional, Jahnen-Dechent, W., additional, Ketteler, M., additional, Jee, W., additional, Li, X., additional, Richards, B., additional, Floege, J., additional, Goncalves, J. G., additional, Canale, D., additional, de Braganca, A. C., additional, Shimizu, M. H. M., additional, Moyses, R. M. A., additional, Andrade, L., additional, Seguro, A. C., additional, Volpini, R. A., additional, Romoli, S., additional, Migliorini, A., additional, Anders, H.-J., additional, Eskova, O., additional, Neprintseva, N., additional, Tchebotareva, N., additional, Bobkova, I., additional, Kozlovskaya, L., additional, Simic, I., additional, Tabatabaeifar, M., additional, Wlodkowski, T., additional, Denc, H., additional, Mollet, G., additional, Antignac, C., additional, Schaefer, F., additional, Ekaterina, I. A., additional, Giardino, L., additional, Rastaldi, M. P., additional, Van den Heuvel, L., additional, Levtchenko, E., additional, Okina, C., additional, Okamoto, T., additional, Kamata, M., additional, Murano, J., additional, Kobayashi, K., additional, Takeuchi, K., additional, Kamata, F., additional, Sakai, T., additional, Naito, S., additional, Aoyama, T., additional, Sano, T., additional, Takeuchi, Y., additional, Kamata, K., additional, Thomasova, D., additional, Bruns, H. A., additional, Liapis, H., additional, Iwashita, T., additional, Hasegawa, H., additional, Takayanagi, K., additional, Shimizu, T., additional, Asakura, J., additional, Okazaki, S., additional, Kogure, Y., additional, Hatano, M., additional, Hara, H., additional, Inamura, M., additional, Iwanaga, M., additional, Mitani, T., additional, Mitarai, T., additional, Savin, V. J., additional, Sharma, M., additional, Wei, C., additional, Reiser, J., additional, McCarthy, E. T., additional, Sharma, R., additional, Gauchat, J.-F., additional, Eneman, B., additional, Freson, K., additional, Van Geet, C., additional, Choi, D. E., additional, Jeong, J. Y., additional, Chang, Y. K., additional, Na, K.-R., additional, Lee, K. W., additional, Shin, Y. T., additional, Ni, H.-F., additional, Chen, J.-F., additional, Zhang, M.-H., additional, Pan, M.-M., additional, Liu, B.-C., additional, Kim, S. S., additional, Suzuki, T., additional, Iyoda, M., additional, Matsumoto, K., additional, Shindo-Hirai, Y., additional, Kuno, Y., additional, Wada, Y., additional, Yamamoto, Y., additional, Shibata, T., additional, Akizawa, T., additional, Munoz-Felix, J. M., additional, Lopez-Novoa, J. M., additional, Martinez-Salgado, C., additional, Ehling, J., additional, Babickova, J., additional, Gremse, F., additional, Kiessling, F., additional, Lammers, T., additional, Lech, M., additional, Gunthner, R., additional, Lorenz, G., additional, Ryu, M., additional, Grobmayr, R., additional, Susanti, H., additional, Kobayashi, K. S., additional, Flavell, R. A., additional, Rayego-Mateos, S., additional, Morgado, J., additional, Sanz, A. B., additional, Eguchi, S., additional, Pato, J., additional, Keri, G., additional, Egido, J., additional, Ortiz, A., additional, Ruiz-Ortega, M., additional, Leduc, M., additional, Geerts, L., additional, Grouix, B., additional, Sarra-Bournet, F., additional, Felton, A., additional, Gervais, L., additional, Abbott, S., additional, Duceppe, J.-S., additional, Zacharie, B., additional, Penney, C., additional, Laurin, P., additional, Gagnon, L., additional, Detsika, M. G., additional, Duann, P., additional, Lianos, E. A., additional, Leong, K. I., additional, Chiang, C.-K., additional, Yang, C.-C., additional, Wu, C.-T., additional, Chen, L.-P., additional, Hung, K.-Y., additional, Liu, S.-H., additional, Carvalho, F. F., additional, Teixeira, V. P., additional, Almeida, W. S., additional, Schor, N., additional, Small, D. M., additional, Bennett, N. C., additional, Coombes, J., additional, Johnson, D. W., additional, Gobe, G. C., additional, Montero, N., additional, Prada, A., additional, Riera, M., additional, Orfila, M., additional, Pascual, J., additional, Rodriguez, E., additional, Barrios, C., additional, Kokeny, G., additional, Fazekas, K., additional, Rosivall, L., additional, Mozes, M. M., additional, Hornigold, N., additional, Hughes, J., additional, Mooney, A., additional, Benardeau, A., additional, Riboulet, W., additional, Vandjour, A., additional, Jacobsen, B., additional, Apfel, C., additional, Conde-Knape, K., additional, Bienvenu, J.-F., additional, Tanaka, T., additional, Yamaguchi, J., additional, Nangaku, M., additional, Niwa, T., additional, Bolati, D., additional, Shimizu, H., additional, Yisireyili, M., additional, Nishijima, F., additional, Brocca, A., additional, Virzi, G., additional, de Cal, M., additional, Ronco, C., additional, Priante, G., additional, Musacchio, E., additional, Valvason, C., additional, Sartori, L., additional, Piccoli, A., additional, Baggio, B., additional, Perkuhn, M., additional, Weibrecht, M., additional, Zok, S., additional, Martin, I. V., additional, Schoth, F., additional, Ostendorf, T., additional, Kuhl, C., additional, Karabaeva, A., additional, Essaian, A., additional, Beresneva, O., additional, Parastaeva, M., additional, Kayukov, I., additional, Smirnov, A., additional, Audzeyenka, I., additional, Kasztan, M., additional, Piwkowska, A., additional, Rogacka, D., additional, Angielski, S., additional, Jankowski, M., additional, Bockmeyer, C. L., additional, Kokowicz, K., additional, Agustian, P. A., additional, Zell, S., additional, Wittig, J., additional, Becker, J. U., additional, Nishizono, R., additional, Venkatareddy, M. P., additional, Chowdhury, M. A., additional, Wang, S. Q., additional, Fukuda, A., additional, Wickman, L. T., additional, Yang, Y., additional, Wiggins, R. C., additional, Fazio, M. R., additional, Donato, V., additional, Lucisano, S., additional, Cernaro, V., additional, Lupica, R., additional, Trimboli, D., additional, Montalto, G., additional, Aloisi, C., additional, Mazzeo, A. T., additional, Buemi, M., additional, Gawrys, O., additional, Olszynski, K. H., additional, Kuczeriszka, M., additional, Gawarecka, K., additional, Swiezewska, E., additional, Chmielewski, M., additional, Masnyk, M., additional, Rafalowska, J., additional, Kompanowska-Jezierska, E., additional, Lee, W.-C., additional, Chau, Y.-Y., additional, Lee, L.-C., additional, Chiu, C.-H., additional, Lee, C.-T., additional, Chen, J.-B., additional, Kim, W.-K., additional, and Shin, S. J., additional

Published
2013
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26. AKI - Experimental

Author

Kaynar, K., primary, Kaynar, K., additional, Ersoz, S., additional, Aliyazioglu, R., additional, Uzun, A., additional, Ulusoy, S., additional, Al, S., additional, Ozkan, G., additional, Cansiz, M., additional, Bertocchio, J.-P., additional, Lancon, J., additional, El Moghrabi, S., additional, Galmiche, G., additional, Duong Van Huyen, J.-P., additional, Rieu, P., additional, Jaisser, F., additional, Albertoni, G., additional, Andrade, S., additional, Barreto, J. A., additional, Borges, F., additional, Schor, N., additional, Ho, W.-Y., additional, Chen, S.-H., additional, Tseng, C.-J., additional, Bienholz, A., additional, Feldkamp, T., additional, Weinberg, J. M., additional, Suller Garcia, J., additional, Naves, M., additional, Aparecida Reis, L., additional, Simoes, M. d. J., additional, S Almeida, W., additional, Moreau Longo, V., additional, Segreto, H. R. C., additional, Ghoneim, A., additional, Elkholy, A., additional, Medhat Abbas, T., additional, El Hadeedy, M., additional, Elhusseini, F., additional, Elessawey, B., additional, Eltanaihy, E., additional, Lotfy, A., additional, Eldesoky, S., additional, Sheashaa, H., additional, Sobh, M., additional, Minning, D. M., additional, Warnock, D., additional, Mohamed, A. S., additional, Wirthlin, J. B., additional, Chintalacharuvu, S. R., additional, Boone, L., additional, Brenner, R. M., additional, Santina Christo, J., additional, Dos Santos Passos, C., additional, Rene de Alencar, D., additional, De Braganca, A. C., additional, Canale, D., additional, Goncalves, J. G., additional, Brandao, T. P. B., additional, Shimizu, M. H. M., additional, Volpini, R. A., additional, Seguro, A. C., additional, Andrade, L., additional, Lee, J.-W., additional, Kim, H. K., additional, Cho, W. Y., additional, Jo, S.-K., additional, Cho, E., additional, Hocherl, K., additional, Schmidt, C., additional, Mulay, S. R., additional, Kulkarni, O. P., additional, Rupanagudi, K. V., additional, Migliorini, A., additional, Liapis, H., additional, Anders, H.-J., additional, Pevzner, I., additional, Chupyrkina, A., additional, Plotnikov, E., additional, Zorov, D., additional, Lopez-Novoa, J.-M., additional, Eleno, N., additional, Perez-Barriocanal, F., additional, Arevalo, M., additional, Docherty, N., additional, Castellano, G., additional, Divella, C., additional, Loverre, A., additional, Stasi, A., additional, Curci, C., additional, Rossini, M., additional, Ditonno, P., additional, Battaglia, M., additional, Daha, M. R., additional, Van Kooten, C., additional, Gesualdo, L., additional, Schena, F. P., additional, Grandaliano, G., additional, Tsuda, H., additional, Kawada, N., additional, Iwatani, H., additional, Moriyama, T., additional, Takahara, S., additional, Rakugi, H., additional, Isaka, Y., additional, Schley, G., additional, Kalucka, J., additional, Klanke, B., additional, Jantsch, J., additional, Olbrich, S., additional, Baumgartl, J., additional, Amann, K., additional, Eckardt, K.-U., additional, Weidemann, A., additional, Dolgolikova, A., additional, Pilotovich, V., additional, Ivanchik, G., additional, Shved, I., additional, Banki, N. F., additional, Antal, Z., additional, Hosszu, A., additional, Koszegi, S., additional, Vannay, A., additional, Wagner, L., additional, Prokai, A., additional, Muller, V., additional, Szabo, A. J., additional, Fekete, A., additional, Farrag, S., additional, Abulasrar, S., additional, Salama, , M., additional, Amin, M., additional, Ali, A., additional, Rubera, I., additional, Duranton, C., additional, Cougnon, M., additional, Melis, N., additional, Tauc, M., additional, Jankauskas, S., additional, Morosanova, M., additional, Pulkina, N., additional, Zorova, L., additional, Shin, Y. T., additional, Kim, S. S., additional, Chang, Y. K., additional, Choi, D. E., additional, Na, K.-R., additional, Lee, K. W., additional, Choi, J.-Y., additional, Jin, D.-C., additional, Cha, J.-H., additional, Schneider, R., additional, Betz, B., additional, Meusel, M., additional, Held, C., additional, Wanner, C., additional, Gekle, M., additional, Sauvant, C., additional, Pisani, A., additional, Rossano, R., additional, Mancini, A., additional, Arfian, N., additional, Yagi, K., additional, Nakayama, K., additional, Ali, H., additional, Mayasari, D. S., additional, Purnomo, E., additional, Emoto, N., additional, Efrati, S., additional, Berman, S., additional, Abu Hamad, R., additional, Weissgarten, J., additional, Scherbaum, C. R., additional, Allam, R., additional, Lichtnekert, J., additional, Darisipudi, M. N., additional, Hagele, H., additional, Hohenstein, B., additional, Hugo, C., additional, Schaefer, L., additional, Corsi, C., additional, Ferramosca, E., additional, Grandi, E., additional, Pisoni, L., additional, Rivolta, I., additional, Dalpozzo, B., additional, Hoxha, E., additional, Severi, S., additional, Santoro, A., additional, Laurent, M., additional, Cedric, R., additional, Dominique, C., additional, Sophie, V., additional, Nochy, D., additional, Loic, G., additional, Patrice, C., additional, Chantal, J., additional, Marie-Christine, V., additional, Alexandre, H., additional, Eric, R., additional, Cantaluppi, V., additional, Medica, D., additional, Quercia, A. D., additional, Figliolini, F., additional, Dellepiane, S., additional, Randone, O., additional, Segoloni, G. P., additional, Camussi, G., additional, Ahn, B.-H., additional, Kim, S. H., additional, Yasue Saito Miyagi, M., additional, Camara, N., additional, Cerqueira Leite Seelaender, M., additional, Maceratesi Enjiu, L., additional, Estler Rocha Guilherme, P., additional, Pisciottano, M., additional, Hiyane, M., additional, Yuri Hayashida, C., additional, De Andrade Oliveira, V., additional, Olsen Saraiva Camara, N., additional, Tami Amano, M., additional, Sancho-Martinez, S. M., additional, Sanchez-Juanes, F., additional, Vicente, L., additional, Gonzalez-Buitrago, J. M., additional, Morales, A. I., additional, Lopez-Novoa, J. M., additional, Lopez-Hernandez, F. J., additional, Chen, J.-S., additional, Chang, L.-C., additional, Chen, C.-C., additional, Park, M. Y., additional, Choi, S. J., additional, Kim, J. G., additional, Hwang, S. D., additional, Vicente-Vicente, L., additional, Ferreira, L., additional, Prieto, M., additional, Garcia-Sanchez, O., additional, Sevilla, M. A., additional, Lopez-Novoa, F. J., additional, Christoph, K., additional, Kuper, C., additional, Maria-Luisa, F., additional, Franz-Xaver, B., additional, Neuhofer, W., additional, Vervaet, B., additional, Le Clef, N., additional, Verhulst, A., additional, D'haese, P., additional, Tanaka, T., additional, Yamaguchi, J., additional, Eto, N., additional, Kojima, I., additional, Fujita, T., additional, Nangaku, M., additional, Wystrychowski, A., additional, Wystrychowski, G., additional, Obuchowicz, E., additional, Grzeszczak, W., additional, Wiecek, A., additional, Esposito, C., additional, Torreggiani, M., additional, Castoldi, F., additional, Migotto, C., additional, Serpieri, N., additional, Grosjean, F., additional, Manini, A., additional, Pertile, E., additional, and Dal Canton, A., additional

Published
2012
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27. 28 SELECTIVE VERSUS NON-SELECTIVE ARTERIAL CLAMPING FOR LAPAROSCOPIC PARTIAL NEPHRECTOMY: IMPACT UPON RENAL FUNCTION OF A SOLITARY KIDNEY IN A PORCINE MODEL

Author

Benway, B.M., primary, Baca, G., additional, Bhayani, S.B., additional, Das, N.A., additional, Katz, M.D., additional, Diaz, D.L., additional, Maxwell, K.L., additional, Badwan, K.H., additional, Talcott, M.R., additional, Liapis, H., additional, Cabello, J.M., additional, Venkatesh, R., additional, and Figenshau, R.S., additional

Published
2009
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30. Banff ’05 Meeting Report: Differential Diagnosis of Chronic Allograft Injury and Elimination of Chronic Allograft Nephropathy (’CAN’)

Author

Solez, K, primary, Colvin, RB, additional, Racusen, LC, additional, Sis, B, additional, Halloran, PF, additional, Birk, PE, additional, Campbell, PM, additional, Cascalho, M., additional, Collins, AB, additional, Demetris, AJ, additional, Drachenberg, CB, additional, Gibson, IW, additional, Grimm, PC, additional, Haas, M, additional, Lerut, E, additional, Liapis, H, additional, Mannon, RB, additional, Marcus, PB, additional, Mengel, M, additional, Mihatsch, MJ, additional, Nankivell, BJ, additional, Nickeleit, V, additional, Papadimitriou, JC, additional, Platt, JL, additional, Randhawa, P, additional, Roberts, I, additional, Salinas-Madriga, L, additional, Salomon, DR, additional, Seron, D, additional, Sheaff, M, additional, and Weening, JJ, additional

Published
2007
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40. The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology

Author

Loupy, A., Haas, M., Solez, K., Racusen, L., Glotz, D., Seron, D., Nankivell, B. J., Colvin, R. B., Afrouzian, M., Akalin, E., Alachkar, N., Bagnasco, S., Becker, J. U., Cornell, L., Drachenberg, C., Dragun, D., de Kort, H., Gibson, I. W., Kraus, E. S., Lefaucheur, C., Legendre, C., Liapis, H., Muthukumar, T., Nickeleit, V., Orandi, B., Park, W., Rabant, M., Randhawa, P., Reed, E. F., Roufosse, C., Seshan, S. V., Sis, B., Singh, H. K., Schinstock, C., Tambur, A., Zeevi, A., and Mengel, M.

Subjects
Meeting Report, clinical research/practice, translational research/science, kidney transplantation/nephrology, pathology/histopathology, organ transplantation in general, rejection, rejection: antibody‐mediated (, rejection: subclinical, rejection: T cell mediated (
Abstract

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d‐negative antibody‐mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor‐specific antibody tests (anti‐HLA and non‐HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i‐IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell–mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus‐based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next‐generation clinical trials.

Published
2016
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48. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion.

Author

Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, Muruve D, Shi Y, Munro F, Liapis H, Anders HJ, Mulay, Shrikant R, Kulkarni, Onkar P, Rupanagudi, Khader V, Migliorini, Adriana, Darisipudi, Murthy N, Vilaysane, Akosua, Muruve, Daniel, Shi, Yan, and Munro, Fay

Abstract

Nephrocalcinosis, acute calcium oxalate (CaOx) nephropathy, and renal stone disease can lead to inflammation and subsequent renal failure, but the underlying pathological mechanisms remain elusive. Other crystallopathies, such as gout, atherosclerosis, and asbestosis, trigger inflammation and tissue remodeling by inducing IL-1β secretion, leading us to hypothesize that CaOx crystals may induce inflammation in a similar manner. In mice, intrarenal CaOx deposition induced tubular damage, cytokine expression, neutrophil recruitment, and renal failure. We found that CaOx crystals activated murine renal DCs to secrete IL-1β through a pathway that included NLRP3, ASC, and caspase-1. Despite a similar amount of crystal deposits, intrarenal inflammation, tubular damage, and renal dysfunction were abrogated in mice deficient in MyD88; NLRP3, ASC, and caspase-1; IL-1R; or IL-18. Nephropathy was attenuated by DC depletion, ATP depletion, or therapeutic IL-1 antagonism. These data demonstrated that CaOx crystals trigger IL-1β-dependent innate immunity via the NLRP3/ASC/caspase-1 axis in intrarenal mononuclear phagocytes and directly damage tubular cells, leading to the release of the NLRP3 agonist ATP. Furthermore, these results suggest that IL-1β blockade may prevent renal damage in nephrocalcinosis. [ABSTRACT FROM AUTHOR]

Published
2013
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50. Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells

Author

Hans-Joachim Anders, Alessandro Antonelli, Tiziano Lottini, Andrea Minervini, Marco Carini, Francesco Guzzi, Paola Romagnani, Mauro Gacci, Alessandro Sisti, Carolina Conte, Fabrizio Di Maida, Mario Rotondi, Samuela Landini, Marco Allinovi, Maria Elena Melica, Rosa Maria Roperto, Francesco Porpiglia, Vincenzo Ficarra, Benedetta Mazzinghi, Sergio Serni, Sabrina Giglio, George J. Netto, Maria Rosaria Raspollini, Maria Lucia Angelotti, Letizia De Chiara, Sara Nardi, Giulia Antonelli, Davide Facchiano, Alberto Magi, Riccardo Schiavina, Elena Lazzeri, Helen Liapis, Andrea Mari, Roberto Semeraro, Christian Fynbo Christiansen, Laura Lasagni, Anna Julie Peired, Peired A.J., Antonelli G., Angelotti M.L., Allinovi M., Guzzi F., Sisti A., Semeraro R., Conte C., Mazzinghi B., Nardi S., Melica M.E., De Chiara L., Lazzeri E., Lasagni L., Lottini T., Landini S., Giglio S., Mari A., Di Maida F., Antonelli A., Porpiglia F., Schiavina R., Ficarra V., Facchiano D., Gacci M., Serni S., Carini M., Netto G.J., Roperto R.M., Magi A., Christiansen C.F., Rotondi M., Liapis H., Anders H.-J., Minervini A., Raspollini M.R., and Romagnani P.

Subjects
Adenoma, 0301 basic medicine, papillary renal cell carcinoma, medicine.disease_cause, urologic and male genital diseases, DISEASE, PATHWAY, PROTECTS, Mice, 03 medical and health sciences, 0302 clinical medicine, AKI, NOTCH1, REGENERATION, Renal cell carcinoma, Biomarkers, Tumor, ABLATION, medicine, Carcinoma, Animals, Progenitor cell, RECURRENCE, Carcinoma, Renal Cell, RECEPTOR, Papillary renal cell carcinomas, business.industry, Stem Cells, Papillary Adenoma, Acute kidney injury, renal carcinoma, General Medicine, Acute Kidney Injury, medicine.disease, TUMORS, Kidney Neoplasms, 3. Good health, NOTCH, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, GROWTH, Neoplasm Recurrence, Local, Stem cell, Carcinogenesis, business
Abstract

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.

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