150 results on '"Navone N"'
Search Results
2. Hyperactivated FRS2α-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients
- Author
-
Liu, J, You, P, Chen, G, Fu, X, Zeng, X, Wang, C, Huang, Y, An, L, Wan, X, Navone, N, Wu, C-L, McKeehan, W L, Zhang, Z, Zhong, W, and Wang, F
- Published
- 2016
- Full Text
- View/download PDF
3. Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
- Author
-
Cotignola, J, Leonardi, D B, Shahabi, A, Acuña, A D, Stern, M C, Navone, N, Scorticati, C, De Siervi, A, Mazza, O, and Vazquez, E
- Published
- 2013
- Full Text
- View/download PDF
4. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma
- Author
-
Yang, J, He, J, Wang, J, Cao, Y, Ling, J, Qian, J, Lu, Y, Li, H, Zheng, Y, Lan, Y, Hong, S, Matthews, J, Starbuck, M W, Navone, N M, Orlowski, R Z, Lin, P, Kwak, L W, and Yi, Q
- Published
- 2012
- Full Text
- View/download PDF
5. Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer
- Author
-
Ferrando, M., Gueron, G., Elguero, B., Giudice, J., Salles, A., Leskow, F. Coluccio, Jares-Erijman, E. A., Colombo, L., Meiss, R., Navone, N., De Siervi, A., and Vazquez, E.
- Published
- 2011
- Full Text
- View/download PDF
6. A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation
- Author
-
Lin, S-H, Cheng, C-J, Lee, Y-C, Ye, X, Tsai, W-W, Kim, J, Pasqualini, R, Arap, W, Navone, N M, Tu, S-M, Hu, M, Yu-Lee, L-Y, and Logothetis, C J
- Published
- 2008
- Full Text
- View/download PDF
7. Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone
- Author
-
Li, Z G, Yang, J, Vazquez, E S, Rose, D, Vakar-Lopez, F, Mathew, P, Lopez, A, Logothetis, C J, Lin, S-H, and Navone, N M
- Published
- 2008
- Full Text
- View/download PDF
8. Outcomes of men with ductal prostate cancer undergoing definitive therapy for localized disease
- Author
-
Ranasinghe, W., primary, Shapiro, D., additional, Reichard, C.A., additional, Elsheshtawi, M., additional, Nyame, Y., additional, Sundi, D., additional, Tosoian, J., additional, Wilkins, L., additional, Alam, R., additional, Achim, M.F., additional, Bathala, T., additional, Tang, C., additional, Aparicio, A., additional, Tu, S., additional, Navone, N., additional, Pisters, L., additional, Stephenson, A.J., additional, Klein, E.A., additional, Ross, A.E., additional, Allaf, M.E., additional, Davis, J., additional, and Chapin, B.F., additional
- Published
- 2020
- Full Text
- View/download PDF
9. Engineered bone for probing organotypic growth and therapy response of prostate cancer tumoroids in vitro
- Author
-
Paindelli, C., Navone, N., Logothetis, Christopher J., Friedl, P., Dondossola, Eleonora, Paindelli, C., Navone, N., Logothetis, Christopher J., Friedl, P., and Dondossola, Eleonora
- Abstract
Contains fulltext : 201779.pdf (publisher's version ) (Closed access)
- Published
- 2019
10. Supplement II: Abstracts of the international symposium on Skin Carcinogenesis in man and in experimental models. Heidelberg, 29–31 October 1991 (pp S61–S88)
- Author
-
Barrett, J. C., Afshari, C. A., Annab, L. A., Burkhart, B. A., Boyd, J. A., Owen, R. D., Futreal, P. A., Richter, K. H., Moses, H. L., Lavker, R. M., Miller, Stanley, Sun, T. -T., Stingl, G., Bianchi, A. B., Navone, N. M., Conti, C. J., Spencer, James M., Kahn, S., Weinstein, I. B., Silvers, D. S., DeLeo, V. A., Larcher, F., Bauluz, C., Quintanilla, M., Ballestin, C., Jorcano, J. L., Schön, M., Haas, M., Klein, C. E., Weber, L., Cerri, A., Tadini, G., Gitto, R., Berti, E., Cano, A., Caulín, C., Gómez, M., Gandarillas, A., Martín, M., Montes, A., Navarro, P., Bastian, B. C., Van der Piepen, U., Römisch, J., Pâques, E., Hartmann, A. A., Krieg, P., Schnapke, R., Feil, S., Fürstenberger, G., Marks, F., Missero, C., Cajal, S. Ramon y, Filvaroff, E., Dotto, G. P., Sherman, J., Albert, R. E., Baxter, C. S., Bauer, G., Höfler, P., Götschl, M., Viesel, E., Jürgensmeier, J., Schaefer, D., Picht, G., Grande, T., Real, A., Rünqer, T. M., Möller, K., Fuchs, P., Bauer, C., Epe' B., Gruner, S., Diezel, W., Macejewski, J., Weber, H., Eckert, R., Volk, H. D., Sönnichsen, N., Bavinck, Jan N. Bouwes, Vermeer, Bert J., Van Der Woude, Fokko J., Vandenbroucke, Jan P., Claas, Frans H. J., Griffin, E. F., Harris, H., Tilgen, W., Garbe, C., Østerlind, Anne, Weiss, J., Jung, E. G., Ruiter, D. J., Danen, E., Broecker, E. -B., Johnson, J. P., van Muijen, G. N. P., Halaban, R., Krüger-Krasagakes, S., Orfanos, C. E., Newton, J. A., Bataille, V., Cuzick, J., Bishop, T., Schwaaf, A., Azizi, E., Bröcker, E. B., Eberlein, B., Froschermaier, S., Gollhausen, R., Przybilla, B., Krasagakis, K., Abdel-Naser, M. B., Lopez-Bran, E., Robledo, A., Lopez-Bran, E., Heine, H., Hennig, B., Graf, G., Nährig, J., Niedner, R., Schöpf, E., Mailhammer, R., Reisbach, G., Kempkes, B., Hültner, L., Thalmeier, K., Anders, F., Zechel, C., Schleenbecker, U., Leers, J., Smith, A., Wagner, E., Burcin, U., Hug, H., Fiebich, B., Anders, A., Gröger, H., Schlatterer, B., Moll, I., Wollina, U., Leigh IM, Purkis PE, Markey A., Neill S., Proby C., Glover M., Lane EB, Klein-Szanto, A. J. P., Yaar, M., Garmyn, M., Gilani, A., Gilchrest, B. A., Bowden, G. T., Nelson, M., Levy, J., Tanooka, Hiroshi, Ootsuyama, Akira, Urbach, F., van der Leun, J. C., de Gruijl, F. R., Kripke, Margaret L., Yuspa, S. H., Glick, A., Lee, E., Diugosz, A., Balmain, A., Bums, P., Kemp, C. J., Stoler, A. B., Harks, F., Boukamp, P., Pascheberg, U., Breitkreutz, D., Hülsen, A., Altmeier, S., Tomakidi, P., Fusenig, N. E., Lowy, Douglas R., Sedman, Sylvia A., Cohen, Bruce D., Schiller, John T., Kricker, A., Armstrong, B. K., English, D., Heenan, P. J., Randell, P. L., de Gruijl, F. R., Kelfkens, G., van Weelden, H., van der Leun, J. C., Grabbe, S., Bruvers, S., Granstein, R. D., Albert, R., Miller, M., Cody, T., Baxter, C., Shukla, R., Ueda, M., Ichihashi, M., Yamamura, K., Hayashibe, K., Funasaka, Y., Mishima, Y., Fujiwara, Y., Ichihashi, M., Jimbo, T., Mishima, Y., Popanda, O., Thielmann, H. W., Jahrens, D., Edler, L., Ootsuyama, A., Tanooka, H., Sutter, C., Mukhtar, H., Strickland, P. T., Winter, H., Schweizer, J., Schmidt, R., Weber, E., Rippmann, F., Hecker, E., Kopp-Schneider, A., Lehmann, W. D., Stephan, M., Troll, W., Wei, H., Fujiki, H., Garte, S. J., Frenkel, K., Svetek, J., Schara, M., Pečar, S., Hergenhahn, M., Kinzel, V., Richards, J., Plein, P., Schiess, K., Kaszkin, M., Yamamoto, S., Wang, J. C., Kato, R., Kuroki, T., Hashimoto, Y., Osada, S., Ohno, S., Gilles, C., Piette, M., Foidart, J. -M., Ranki, A., Lassus, J., Lehmus, A., Niemi, K. -M., Friesel, H., Schneider, T., Steinbauer, B., Sorg, B., Winter, A., Krauter, G., Krauß, R., Roeser, H., Unger, Sylvia, Janiaud, Paul, Rueß, Doris, Mechler, Bernard M., Stanbridge, Eric J., Gross, Monika M., Buček, M., Klein-Bauernschmitt, P., Schlehofer, J. R., Kosters, R., Stark, H. -J., Okulov, V. B., Elgjo, K., Ushmorov, A. G., Danilov, A. O., Zubova, S. G., Furstenberger, G., and Faissner, A.
- Published
- 1991
- Full Text
- View/download PDF
11. Erratum: Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma
- Author
-
Yang, J, He, J, Wang, J, Cao, Y, Ling, J, Qian, J, Lu, Y, Li, H, Zheng, Y, Lan, Y, Hong, S, Matthews, J, Starbuck, M W, Navone, N M, Orlowski, R Z, Lin, P, Kwak, L W, and Yi, Q
- Published
- 2015
- Full Text
- View/download PDF
12. Intravital microscopy of osteolytic progression and therapy response of cancer lesions in the bone
- Author
-
Dondossola, E., Alexander, S., Holzapfel, B.M., Filippini, S., Starbuck, M.W., Hoffman, R.M., Navone, N., De-Juan-Pardo, E.M., Logothetis, C.J., Hutmacher, D.W., Friedl, P., Dondossola, E., Alexander, S., Holzapfel, B.M., Filippini, S., Starbuck, M.W., Hoffman, R.M., Navone, N., De-Juan-Pardo, E.M., Logothetis, C.J., Hutmacher, D.W., and Friedl, P.
- Abstract
Item does not contain fulltext, Intravital multiphoton microscopy (iMPM) in mice provides access to cellular and molecular mechanisms of metastatic progression of cancers and the underlying interactions with the tumor stroma. Whereas iMPM of malignant disease has been performed for soft tissues, noninvasive iMPM of solid tumor in the bone is lacking. We combined miniaturized tissue-engineered bone constructs in nude mice with a skin window to noninvasively and repetitively monitor prostate cancer lesions by three-dimensional iMPM. In vivo ossicles developed large central cavities containing mature bone marrow surrounded by a thin cortex and enabled tumor implantation and longitudinal iMPM over weeks. Tumors grew inside the bone cavity and along the cortical bone interface and induced niches of osteoclast activation (focal osteolysis). Interventional bisphosphonate therapy reduced osteoclast kinetics and osteolysis without perturbing tumor growth, indicating dissociation of the tumor-stroma axis. The ossicle window, with its high cavity-to-cortex ratio and long-term functionality, thus allows for the mechanistic dissection of reciprocal epithelial tumor-bone interactions and therapy response.
- Published
- 2018
13. P3.11-25 Analysis Indicates Low Incremental Cost-Effectiveness Ratio for Implementation of Lung Cancer Screening in Italy
- Author
-
Veronesi, G., primary, Ghislandi, S., additional, Vanni, E., additional, Dieci, E., additional, Toschi, L., additional, Velutti, L., additional, Solinas, M., additional, Novellis, P., additional, Alloisio, M., additional, Riboli, E., additional, and Navone, N., additional
- Published
- 2018
- Full Text
- View/download PDF
14. PO-259 Identification of a clinically meaningful site-specific steroid roadmap in prostate cancer
- Author
-
Sakellakis, M., primary, Ramachandran, S., additional, Efstathiou, E., additional, Mao, X., additional, Hoang, A., additional, Navone, N., additional, Logothetis, C., additional, and Titus, M., additional
- Published
- 2018
- Full Text
- View/download PDF
15. Introduzione
- Author
-
Curcio, Giovanna, Navone, N., and Villari, S.
- Published
- 2011
16. Hyperactivated FRS2α-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients
- Author
-
Liu, J, primary, You, P, additional, Chen, G, additional, Fu, X, additional, Zeng, X, additional, Wang, C, additional, Huang, Y, additional, An, L, additional, Wan, X, additional, Navone, N, additional, Wu, C-L, additional, McKeehan, W L, additional, Zhang, Z, additional, Zhong, W, additional, and Wang, F, additional
- Published
- 2015
- Full Text
- View/download PDF
17. Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
- Author
-
Cotignola, J, primary, Leonardi, D B, additional, Shahabi, A, additional, Acuña, A D, additional, Stern, M C, additional, Navone, N, additional, Scorticati, C, additional, De Siervi, A, additional, Mazza, O, additional, and Vazquez, E, additional
- Published
- 2012
- Full Text
- View/download PDF
18. Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer
- Author
-
Sacca, P, primary, Meiss, R, additional, Casas, G, additional, Mazza, O, additional, Calvo, J C, additional, Navone, N, additional, and Vazquez, E, additional
- Published
- 2007
- Full Text
- View/download PDF
19. Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone
- Author
-
Li, Z G, primary, Yang, J, additional, Vazquez, E S, additional, Rose, D, additional, Vakar-Lopez, F, additional, Mathew, P, additional, Lopez, A, additional, Logothetis, C J, additional, Lin, S-H, additional, and Navone, N M, additional
- Published
- 2007
- Full Text
- View/download PDF
20. Detection of loss of heterozygosity in formalin-fixed paraffin-embedded tumor specimens by the polymerase chain reaction
- Author
-
Bianchi, A. B., Navone, N. M., and Conti, C. J.
- Subjects
Heterozygote ,Mice ,Skin Neoplasms ,Formaldehyde ,Histological Techniques ,Molecular Sequence Data ,Tumor Cells, Cultured ,Animals ,Chromosome Mapping ,Amino Acid Sequence ,Polymerase Chain Reaction ,Alleles ,Research Article - Abstract
A polymerase chain reaction-based procedure was used for the detection of DNA length polymorphisms generated by naturally occurring genetic deletions or insertions of known sequence. This method consists of a simple one-step assay that does not require any restriction enzyme analysis or Southern blot hybridization, allowing identification in ethidium bromide-stained gels. The procedure described here was used to detect loss of heterozygosity at various loci, including the Hbb beta-globin gene cluster, in chemically induced mouse skin tumors, using a variety of tissue preparations, including microdissection of formalin-fixed, paraffin-embedded specimens, short-term cultures, and fluorescence-activated cell sorting of epithelial populations. This approach may be useful in detecting tumor-specific reduction to homozygosity at polymorphic chromosomal loci, allowing the mapping of putative tumor-suppressor loci involved in carcinogenesis.
- Published
- 1991
21. 661 An androgen-receptor (AR)-negative human prostate cancer xenograft induces mouse-derived osteogenesis
- Author
-
Mathew, P., primary, Sikes, C., additional, Multani, A., additional, Bucana, C., additional, Prieto, V.G., additional, Troncoso, P., additional, Raymond, K., additional, Logothetis, C., additional, and Navone, N., additional
- Published
- 2004
- Full Text
- View/download PDF
22. Inhibition of functional osteoblasts with the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate in androgen-independent prostate cancer (PCa)
- Author
-
Mathew, P., primary, Yang, J., additional, Kim, S.-J., additional, Fidler, I., additional, Bucana, C., additional, Troncoso, P., additional, Wang, X., additional, Thall, P., additional, Logothetis, C., additional, and Navone, N., additional
- Published
- 2004
- Full Text
- View/download PDF
23. Modulation of cellular proliferation and production of prostate-specific antigen and matrix adhesion molecules in human prostate carcinoma cells by polypeptide growth factors: comparative analyses of MDA PCa2a with established cell lines.
- Author
-
Rajagopal, S, primary, Navone, N M, additional, Troncoso, P, additional, Fritsche, H A, additional, and Chakrabarty, S, additional
- Published
- 1998
- Full Text
- View/download PDF
24. Overlapping loss of heterozygosity by mitotic recombination on mouse chromosome 7F1-ter in skin carcinogenesis.
- Author
-
Bianchi, A B, primary, Navone, N M, additional, Aldaz, C M, additional, and Conti, C J, additional
- Published
- 1991
- Full Text
- View/download PDF
25. p53 protein accumulation and gene mutation in the progression of human prostate carcinoma.
- Author
-
Navone, Nora M., Troncoso, Patricia, Pisters, Louis L., Goodrow, Tamra L., Palmer, Judy L., Nichols, Warren W., Eschenbach, Andrew C. von, Conti, Claudio J., Navone, N M, Troncoso, P, Pisters, L L, Goodrow, T L, Palmer, J L, Nichols, W W, von Eschenbach, A C, and Conti, C J
- Abstract
Background: Nuclear accumulation of p53 protein has been shown to be strongly associated with missense p53 mutations. Studies of nuclear accumulation of p53 protein in prostate carcinoma cells have to date been confined to material from primary tumors.Purpose: We studied the accumulation of p53 protein in specimens obtained from primary and metastatic sites of prostate carcinoma. By examining the accumulation of this protein as a function of stage, histologic grade, and androgen responsiveness of the tumor, we hoped to determine the role of p53 mutation in the progression of prostate carcinoma.Methods: The accumulation of the p53 protein in the cell nuclei was determined by immunohistochemical methods using polyclonal antibody to human p53 CM-1. The material studied consisted of formalin-fixed, paraffin-embedded tissue obtained from primary tumors and metastases of 92 patients with prostate carcinoma. Twelve samples from 11 patients were analyzed for the presence of mutations within exons 5-8 of the p53 gene (also known as TP53) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) analysis. Sequence analysis was subsequently performed on DNA obtained by polymerase chain reaction amplification of PCR-SSCP reactions produced from six different specimens. The chi-square test, Fisher's exact test, and the Freeman Halton test were used for statistical analyses of the results.Results: All tumors with p53 accumulation were metastatic (stage D), poorly differentiated, and androgen independent. Nuclear accumulation of p53 protein was strongly associated with stage (D2 versus D1 versus A-C, P < .0001), grade (Gleason score 8-10 versus 5-7, P < .003), and androgen sensitivity (androgen independent versus dependent, P < .0001). Logistic regression analysis demonstrated that androgen sensitivity predicted p53 outcome better than did stage (P < .0001) or grade alone (P < .006). There was a perfect concordance between the results obtained by PCR-SSCP analysis and the p53 protein accumulation determined by immunohistochemistry in the 12 samples studied. Mutation of the p53 gene was confirmed by sequencing DNA obtained from six specimens positive in the PCR-SSCP assay.Conclusions: p53 gene mutation is a late event in the progression of prostate cancer and is associated with advanced (metastatic) stage, loss of differentiation, and the transition from androgen-dependent to androgen-independent growth.Implication: Testing of prostate cancer biopsy specimens from metastatic sites for p53 protein accumulation and gene mutation may provide useful prognostic information and could influence the recommended course of treatment. [ABSTRACT FROM AUTHOR]- Published
- 1993
26. Inhibition of in vivo proliferation of MDA-PCa-2b human prostate cancer by a targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207
- Author
-
Plonowski, A., Schally, A. V., Nagy, A., Groot, K., Krupa, M., Navone, N. M., and Logothetis, C.
- Published
- 2002
- Full Text
- View/download PDF
27. Griseofulvin-induced hepatopathy due to abnormalities in heme pathway
- Author
-
Polo, C. F., Buzaleh, A. M., Vazquez, E. S., Afonso, S. G., Navone, N. M., and Batlle, A. M. Del Carmen
- Published
- 1997
- Full Text
- View/download PDF
28. Structural Alterations of Chromosome 5 in Twelve Human Prostate Cancer Cell Lines
- Author
-
Ozen, M., Navone, N. M., Multani, A. S., Troncoso, P., Logothetis, C. J., Chung, L. W. K., Eschenbach, A. C. Van, and Pathak, S.
- Published
- 1998
- Full Text
- View/download PDF
29. Expression of six inflammation-related genes in monocytes and CD4+T lymphocytes from patients with multiple sclerosis
- Author
-
Navone, N. D., Perga, S., Martire, S., Francesca Montarolo, Berchialla, P., and Bertolotto, A.
30. Erratum: Erratum: Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases (Science Translational Medicine (2015) 7 (287er3))
- Author
-
Wan, X., Corn, P. G., Yang, J., Nallasivam Palanisamy, Starbuck, M. W., Efstathiou, E., Tapia, E. M., Zurita, A. J., Aparicio, A., Ravoori, M. K., Vazquez, E. S., Robinson, D. R., Wu, Y. -M, Cao, X., Iyer, M. K., Mckeehan, W., Kundra, V., Wang, F., Troncoso, P., Chinnaiyan, A. M., Logothetis, C. J., and Navone, N. M.
31. Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma.
- Author
-
Yang, J, He, J, Wang, J, Cao, Y, Ling, J, Qian, J, Lu, Y, Li, H, Zheng, Y, Lan, Y, Hong, S, Matthews, J, Starbuck, M W, Navone, N M, Orlowski, R Z, Lin, P, Kwak, L W, and Yi, Q
- Subjects
MITOGEN-activated protein kinases ,MULTIPLE myeloma ,TUMORS - Abstract
A correction to the article "Constitutive activation of p38 MAPK in tumor cells contributes to osteolytic bone lesions in multiple myeloma" published in the volume 26, 2012 issue is presented.
- Published
- 2015
- Full Text
- View/download PDF
32. Prioritizing genes associated with prostate cancer development
- Author
-
Troncoso Patricia, Gorlova Olga Y, Navone Nora M, Maity Sankar N, Zhao Hongya, Sircar Kanishka, Gorlov Ivan P, Pettaway Curtis A, Byun Jin, and Logothetis Christopher J
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The genetic control of prostate cancer development is poorly understood. Large numbers of gene-expression datasets on different aspects of prostate tumorigenesis are available. We used these data to identify and prioritize candidate genes associated with the development of prostate cancer and bone metastases. Our working hypothesis was that combining meta-analyses on different but overlapping steps of prostate tumorigenesis will improve identification of genes associated with prostate cancer development. Methods A Z score-based meta-analysis of gene-expression data was used to identify candidate genes associated with prostate cancer development. To put together different datasets, we conducted a meta-analysis on 3 levels that follow the natural history of prostate cancer development. For experimental verification of candidates, we used in silico validation as well as in-house gene-expression data. Results Genes with experimental evidence of an association with prostate cancer development were overrepresented among our top candidates. The meta-analysis also identified a considerable number of novel candidate genes with no published evidence of a role in prostate cancer development. Functional annotation identified cytoskeleton, cell adhesion, extracellular matrix, and cell motility as the top functions associated with prostate cancer development. We identified 10 genes--CDC2, CCNA2, IGF1, EGR1, SRF, CTGF, CCL2, CAV1, SMAD4, and AURKA--that form hubs of the interaction network and therefore are likely to be primary drivers of prostate cancer development. Conclusions By using this large 3-level meta-analysis of the gene-expression data to identify candidate genes associated with prostate cancer development, we have generated a list of candidate genes that may be a useful resource for researchers studying the molecular mechanisms underlying prostate cancer development.
- Published
- 2010
- Full Text
- View/download PDF
33. Frequency and Characterization of p53 Mutations in Clinically Localized Prostate Cancer
- Author
-
Hall, M. C., Navone, N. M., Troncoso, P., and Pollack, A.
- Published
- 1995
- Full Text
- View/download PDF
34. Favorable incremental cost-effectiveness ratio for lung cancer screening in Italy
- Author
-
Marco Alloisio, Pierluigi Novellis, Giulia Veronesi, Elena Vanni, Niccolò Navone, Michela Solinas, Simone Ghislandi, Luca Toschi, Laura Velutti, Elisa Dieci, Veronesi, G, Navone, N, Novellis, P, Dieci, E, Toschi, L, Velutti, L, Solinas, M, Vanni, E, Alloisio, M, and Ghislandi, S.
- Subjects
Quality of life ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,Lung Neoplasms ,Cost effectiveness ,Cost-Benefit Analysis ,Population ,03 medical and health sciences ,0302 clinical medicine ,Lung cancer screening ,COST/EFFECTIVENESS ,medicine ,Humans ,Lung cancer ,education ,Early Detection of Cancer ,health care economics and organizations ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Health Care Costs ,LUNG CANCER ,Cost-effectiveness analysis ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,LUNG CANCER, SCREENING, COST/EFFECTIVENESS ,SCREENING ,Annual Screening ,Survival Rate ,030104 developmental biology ,Italy ,Oncology ,Cost effectiveness analysi ,030220 oncology & carcinogenesis ,Female ,Quality-Adjusted Life Years ,Low dose computed tomography ,business ,Incremental cost-effectiveness ratio ,Follow-Up Studies - Abstract
Objectives: Lung cancer detection by low-dose computed tomographic screening reduces mortality. However, it is essential to assess cost-effectiveness. We present a cost-effectiveness analysis of screening in Italians at high risk of lung cancer, from the point of view of the Italian tax-payer. Materials and methods: We used a decision model to estimate the cost-effectiveness of annual screening for 5 years in smokers (≥30 pack-years) of 55–79 years. Patients diagnosed in the COSMOS study were the screening arm; patients diagnosed and treated for lung cancer in the Lombardy Region, Italy, constituted the usual care arm. Treatment costs were extracted from our hospital database. Lung cancer survival in screened patients was adjusted for 2-year lead-time bias. Life-years and quality-adjusted life-years were estimated by stage at diagnosis, from which incremental cost-effectiveness ratios per life-year and quality-adjusted life-year gained were estimated. Results: Base-case incremental cost-effectiveness ratios were 3297 and 2944 euro per quality-adjusted life-year and life-year gained, respectively. Deterministic sensitivity analysis indicated that these values were particularly sensitive to lung cancer prevalence, screening sensitivity and specificity, screening cost, and treatment costs for stage I and IV disease. From the probabilistic sensitivity analysis incremental cost-effectiveness ratios had a 98 % probability of being
- Published
- 2020
35. Kinesin Facilitates Phenotypic Targeting of Therapeutic Resistance in Advanced Prostate Cancer.
- Author
-
Archer M, Begemann D, Gonzalez-Kozlova E, Nepali PR, Labanca E, Shepherd P, Dogra N, Navone N, and Kyprianou N
- Subjects
- Male, Humans, Animals, Mice, Cell Line, Tumor, Xenograft Model Antitumor Assays, Taxoids pharmacology, Taxoids therapeutic use, Epithelial-Mesenchymal Transition drug effects, Phenotype, Prostatic Neoplasms drug therapy, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Prostatic Neoplasms metabolism, Drug Resistance, Neoplasm, Kinesins genetics, Kinesins metabolism, Prostatic Neoplasms, Castration-Resistant drug therapy, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant pathology, Prostatic Neoplasms, Castration-Resistant metabolism
- Abstract
Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer. Previous work showed that dynamic interconversions between epithelial-mesenchymal transition to mesenchymal-epithelial transition defines the phenotypic landscape of prostate tumors, as a potential driver of the emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa patient-derived xenograft models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between antiandrogen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype. Transcriptomic profiling revealed that resistant and sensitive prostate cancer C4-2B cells have a unique differential gene signature response to cabazitaxel. Gene pathway analysis showed that sensitive cells exhibit an increase in DNA damage, while resistant cells express genes associated with protein regulation in response to cabazitaxel. The patient-derived xenograft model specimens are from patients who have metastatic lethal castration-resistant prostate cancer, treated with androgen deprivation therapy, antiandrogens, and chemotherapy including second-line taxane chemotherapy, cabazitaxel. Immunohistochemistry revealed high expression of E-cadherin and low expression of vimentin resulting in redifferentiation toward an epithelial phenotype. Furthermore, the mitotic kinesin-related protein involved in microtubule binding and the SLCO1B3 transporter (implicated in cabazitaxel intracellular transport) are associated with resistance in these prostate tumors. Combinational targeting of kinesins (ispinesib) with cabazitaxel was more effective than single monotherapies in inducing cell death in resistant prostate tumors. Implications: Our findings are of translational significance in identifying kinesin as a novel target of cross-resistance toward enhancing therapeutic vulnerability and improved clinical outcomes in patients with advanced prostate cancer., (©2024 American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
36. Bone mimetic environments support engineering, propagation, and analysis of therapeutic response of patient-derived cells, ex vivo and in vivo.
- Author
-
Paindelli C, Parietti V, Barrios S, Shepherd P, Pan T, Wang WL, Satcher RL, Logothetis CJ, Navone N, Campbell MT, Mikos AG, and Dondossola E
- Subjects
- Male, Humans, Xenograft Model Antitumor Assays, Bone and Bones pathology, Osteoblasts pathology, Bone Neoplasms therapy, Bone Neoplasms secondary, Prostatic Neoplasms pathology
- Abstract
Bone metastases are the most common milestone in the lethal progression of prostate cancer and prominent in a substantial portion of renal malignancies. Interactions between cancer and bone host cells have emerged as drivers of both disease progression and therapeutic resistance. To best understand these central host-epithelial cell interactions, biologically relevant preclinical models are required. To achieve this goal, we here established and characterized tissue-engineered bone mimetic environments (BME) capable of supporting the growth of patient-derived xenograft (PDX) cells, ex vivo and in vivo. The BME consisted of a polycaprolactone (PCL) scaffold colonized by human mesenchymal stem cells (hMSCs) differentiated into osteoblasts. PDX-derived cells were isolated from bone metastatic prostate or renal tumors, engineered to express GFP or luciferase and seeded onto the BMEs. BMEs supported the growth and therapy response of PDX-derived cells, ex vivo. Additionally, BMEs survived after in vivo implantation and further sustained the growth of PDX-derived cells, their serial transplant, and their application to study the response to treatment. Taken together, this demonstrates the utility of BMEs in combination with patient-derived cells, both ex vivo and in vivo. STATEMENT OF SIGNIFICANCE: Our tissue-engineered BME supported the growth of patient-derived cells and proved useful to monitor the therapy response, both ex vivo and in vivo. This approach has the potential to enable co-clinical strategies to monitor bone metastatic tumor progression and therapy response, including identification and prioritization of new targets for patient treatment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eleonora Dondossola reports financial support was provided by The Prostate Cancer SPORE (P50 CA140388–07). Eleonora Dondossola reports financial support and equipment, drugs, or supplies were provided by Bayer HealthCare Pharmaceuticals (57440)., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
37. Role of adenosine deaminase in prostate cancer progression.
- Author
-
Charles C, Lloyd SM, Piyarathna DWB, Gohlke J, Rasaily U, Putluri V, Simons BW, Zaslavsky A, Nallandhighal S, Michailidis G, Palanisamy N, Navone N, Jones JA, Ittmann MM, Putluri N, Rowley DR, Salami SS, Palapattu GS, and Sreekumar A
- Abstract
Prostate cancer (PCa) is the second most common cancer and constitutes about 14.7% of total cancer cases. PCa is highly prevalent and more aggressive in African-American (AA) men than in European-American (EA) men. PCa tends to be highly heterogeneous, and its complex biology is not fully understood. We use metabolomics to better understand the mechanisms behind PCa progression and disparities in its clinical outcome. Adenosine deaminase (ADA) is a key enzyme in the purine metabolic pathway; it was found to be upregulated in PCa and is associated with higher-grade PCa and poor disease-free survival. The inosine-to-adenosine ratio, which is a surrogate for ADA activity was high in PCa patient urine and higher in AA PCa compared to EA PCa. To understand the significance of high ADA in PCa, we established ADA overexpression models and performed various in vitro and in vivo studies. Our studies have revealed that an acute increase in ADA expression during later stages of tumor development enhances in vivo growth in multiple pre-clinical models. Further analysis revealed that mTOR signaling activation could be associated with this tumor growth. Chronic ADA overexpression shows alterations in the cells' adhesion machinery and a decrease in cells' ability to adhere to the extracellular matrix in vitro . Losing cell-matrix interaction is critical for metastatic dissemination which suggests that ADA could potentially be involved in promoting metastasis. This is supported by the association of higher ADA expression with higher-grade tumors and poor patient survival. Overall, our findings suggest that increased ADA expression may promote PCa progression, specifically tumor growth and metastatic dissemination., Competing Interests: None., (AJCEU Copyright © 2023.)
- Published
- 2023
38. Characterization of prostate cancer adrenal metastases: dependence upon androgen receptor signaling and steroid hormones.
- Author
-
Sakellakis MJ, Hahn AW, Ramachandran S, Zhang M, Hoang A, Song JH, Liu J, Wang F, Basu HS, Sheperd P, Wang X, Frigo DE, Lin SH, Panaretakis T, Zhang J, Navone N, Troncoso P, Logothetis CJ, and Titus MA
- Subjects
- Male, Humans, Animals, Mice, Receptors, Androgen genetics, Receptors, Androgen metabolism, Retrospective Studies, Steroids metabolism, Testosterone metabolism, DNA, Cell Line, Tumor, Tumor Microenvironment, Androgens metabolism, Prostatic Neoplasms pathology
- Abstract
Background: Prostate cancer (PCa) typically spreads to the bone, and this distribution is attributed to the central role of the microenvironment in progression. However, metastasis to the adrenal glands, while not as common, does occur. The biology that accounts for adrenal metastases may be attributed to the unique local steroid metabolome and co-clinical characterization may elucidate the role steroid biosynthesis plays in PCa progression., Methods: Three patients with metastatic PCa who had archived tumor tissue from an adrenalectomy were retrospectively identified, and one adrenal metastasis was developed into a xenograft (MDA-PCa-250). The adrenal metastases were characterized by performing somatic DNA whole exome sequencing (WES), RNA-Seq, immunohistochemistry (IHC), and steroid metabolite quantitation. The influence of steroid metabolites on adrenal metastasis cells and tumor growth was tested in vitro and in vivo., Results: Clinically, adrenalectomy was performed during castration-resistant oligometastatic disease, and two men experienced resensitization to leuprolide. Somatic DNA WES revealed heterogeneous alterations in tumor suppressor and DNA damage repair pathway genes. Adrenal metastases had active androgen receptor (AR) signaling by IHC, and RNA-Seq supported a potential role for adrenal androgen precursor metabolism in activating the AR. Steroid quantitation suggested the adrenal androgen precursors were converted into testosterone in these metastases, and stable isotope tracing of an organoid from MDA-PCa-250 confirmed the capability of adrenal metastases to biosynthesize testosterone from adrenal precursors. In vitro testing of a cell line derived from MDA-PCa-250 showed that testosterone and cortisol stimulated tumor cell growth. In vivo experiments demonstrated that MDA-PCa-250 grew in intact mice with circulating testosterone, but not in castrated mice., Conclusions: PCa adrenal metastases depend upon AR signaling driven by androgen precursors, androstenedione and dehydroepiandrosterone, available in the microenvironment, despite the presence of heterogeneous somatic DNA alterations. Moreover, MDA-PCa-250 provides a preclinical model that can recapitulate the unique androgen-dependence of adrenal metastases., Clinical Trial Registration: This study does not report the clinical results of a clinical trial, but it does use samples from a completed clinical trial that is registered with clinicaltrials.gov (NCT01254864)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
- Full Text
- View/download PDF
39. Bone Progenitors Pull the Strings on the Early Metabolic Rewiring Occurring in Prostate Cancer Cells.
- Author
-
Sanchis P, Anselmino N, Lage-Vickers S, Sabater A, Lavignolle R, Labanca E, Shepherd PDA, Bizzotto J, Toro A, Mitrofanova A, Valacco MP, Navone N, Vazquez E, Cotignola J, and Gueron G
- Abstract
Metastatic prostate cancer (PCa) cells soiling in the bone require a metabolic adaptation. Here, we identified the metabolic genes fueling the seeding of PCa in the bone niche. Using a transwell co-culture system of PCa (PC3) and bone progenitor cells (MC3T3 or Raw264.7), we assessed the transcriptome of PC3 cells modulated by soluble factors released from bone precursors. In a Principal Component Analysis using transcriptomic data from human PCa samples (GSE74685), the altered metabolic genes found in vitro were able to stratify PCa patients in two defined groups: primary PCa and bone metastasis, confirmed by an unsupervised clustering analysis. Thus, the early transcriptional metabolic profile triggered in the in vitro model has a clinical correlate in human bone metastatic samples. Further, the expression levels of five metabolic genes ( VDR, PPARA, SLC16A1, GPX1 and PAPSS2 ) were independent risk-predictors of death in the SU2C-PCF dataset and a risk score model built using this lipid-associated signature was able to discriminate a subgroup of bone metastatic PCa patients with a 23-fold higher risk of death. This signature was validated in a PDX pre-clinical model when comparing MDA-PCa-183 growing intrafemorally vs. subcutaneously, and appears to be under the regulatory control of the Protein Kinase A (PKA) signaling pathway. Secretome analyses of conditioned media showcased fibronectin and type-1 collagen as critical bone-secreted factors that could regulate tumoral PKA. Overall, we identified a novel lipid gene signature, driving PCa aggressive metastatic disease pointing to PKA as a potential hub to halt progression.
- Published
- 2022
- Full Text
- View/download PDF
40. Exploiting Interdata Relationships in Prostate Cancer Proteomes: Clinical Significance of HO-1 Interactors.
- Author
-
Lage-Vickers S, Sanchis P, Bizzotto J, Toro A, Sabater A, Lavignolle R, Anselmino N, Labanca E, Paez A, Navone N, Valacco MP, Cotignola J, Vazquez E, and Gueron G
- Abstract
Prostate cancer (PCa) cells display abnormal expression of proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown the anti-tumoral role of heme oxygenase 1 (HO-1) in this disease. In this work, we undertook a mass spectrometry-based proteomics study to identify HO-1 molecular interactors that might collaborate with its modulatory function in PCa. Among the HO-1 interactors, we identified proteins with nuclear localization. Correlation analyses, using the PCa GSE70770 dataset, showed a significant and positive correlation between HMOX1 and 6 of those genes. Alternatively, HMOX1 and YWHAZ showed a negative correlation. Univariable analyses evidenced that high expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with increased relapse-free survival (RFS) in PCa patients. Further, PCa patients with high HSPB1/HMOX1 , DDB1/HMOX1 , and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, a decrease in RFS for patients with higher scores of this signature was observed using a prognostic risk score model. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ . Multivariable analyses confirmed HSPB1 , DDB1 , and YWHAZ independence from PCa clinic-pathological parameters. In parallel, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (protein encoded by YWHAZ ) interaction. Herein, we describe a novel protein interaction between HO-1 and 14-3-3ζ/δ in PCa and highlight these factors as potential therapeutic targets.
- Published
- 2022
- Full Text
- View/download PDF
41. Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel.
- Author
-
Labanca E, Bizzotto J, Sanchis P, Anselmino N, Yang J, Shepherd PDA, Paez A, Antico-Arciuch V, Lage-Vickers S, Hoang AG, Tang X, Raso MG, Titus M, Efstathiou E, Cotignola J, Araujo J, Logothetis C, Vazquez E, Navone N, and Gueron G
- Subjects
- Animals, Cell Line, Tumor, Disease Progression, Fatty Acids metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Male, Mice, Neoplasm Transplantation, Prostatic Neoplasms, Castration-Resistant metabolism, Signal Transduction drug effects, Androgen Antagonists pharmacology, Ketone Bodies metabolism, Prostatic Neoplasms, Castration-Resistant pathology, Receptors, Androgen metabolism
- Abstract
Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The underlying mechanisms that account for the ultimate emergence of resistance to ADT, progressing to castrate-resistant prostate cancer (CRPC), include those that reactivate androgen receptor (AR), or those that are entirely independent or cooperate with androgen signaling to underlie PCa progression. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis to assess the metabolic shift occurring in PCa that progresses with low AR expression. We used PCa patient-derived xenografts (PDXs) to assess the metabolic changes after castration of tumor-bearing mice and subsequently confirmed main findings in human donor tumor that progressed after ADT. We found that relapsed tumors had a significant increase in fatty acids and ketone body (KB) content compared with baseline. We confirmed that critical ketolytic enzymes (ACAT1, OXCT1, BDH1) were dysregulated after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. In an in silico approach, increased ACAT1, OXCT1, BDH1 expression was also observed for a subset of PCa patients that relapsed with low AR and ERG (ETS-related gene) expression. Further, expression of these factors was also associated with decreased time to biochemical relapse and decreased progression-free survival. Our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
42. HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells.
- Author
-
Cascardo F, Anselmino N, Páez A, Labanca E, Sanchis P, Antico-Arciuch V, Navone N, Gueron G, Vázquez E, and Cotignola J
- Abstract
Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of LDHA , LDHB and HMOX1 in PCa, identifying that high LDHA or low LDHB expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low HMOX1 and high LDHA, while an improved prognosis was observed for those with high HMOX1 and LDHB . Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.
- Published
- 2021
- Full Text
- View/download PDF
43. Optimizing the diagnosis and management of ductal prostate cancer.
- Author
-
Ranasinghe W, Shapiro DD, Zhang M, Bathala T, Navone N, Thompson TC, Broom B, Aparicio A, Tu SM, Tang C, Davis JW, Pisters L, and Chapin BF
- Subjects
- Humans, Male, Carcinoma, Ductal diagnosis, Carcinoma, Ductal therapy, Prostatic Neoplasms diagnosis, Prostatic Neoplasms therapy
- Abstract
Ductal adenocarcinoma (DAC) is the most common variant histological subtype of prostate carcinoma and has an aggressive clinical course. DAC is usually characterized and treated as high-risk prostatic acinar adenocarcinoma (PAC). However, DAC has a different biology to that of acinar disease, which often poses a challenge for both diagnosis and management. DAC can be difficult to identify using conventional diagnostic modalities such as serum PSA levels and multiparametric MRI, and the optimal management for localized DAC is unknown owing to the rarity of the disease. Following definitive therapy for localized disease with radical prostatectomy or radiotherapy, the majority of DACs recur with visceral metastases at low PSA levels. Various systemic therapies that have been shown to be effective in high-risk PAC have limited use in treating DAC. Although current understanding of the biology of DAC is limited, genomic analyses have provided insights into the pathology behind its aggressive behaviour and potential future therapeutic targets.
- Published
- 2021
- Full Text
- View/download PDF
44. Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles from the Metastatic Prostate Cancer Bone Microenvironment.
- Author
-
Vardaki I, Corn P, Gentile E, Song JH, Madan N, Hoang A, Parikh N, Guerra L, Lee YC, Lin SC, Yu G, Santos E, Melancon MP, Troncoso P, Navone N, Gallick GE, Efstathiou E, Subudhi SK, Lin SH, Logothetis CJ, and Panaretakis T
- Subjects
- Animals, Bone Neoplasms mortality, Bone Neoplasms pathology, Cell Line, Tumor, Exosomes genetics, Gene Expression Profiling, Humans, Male, Mice, Prostatic Neoplasms mortality, RNA genetics, Survival Rate, Bone Neoplasms secondary, Extracellular Vesicles metabolism, Gene Expression drug effects, Gene Expression genetics, Immune Checkpoint Proteins genetics, Immune Checkpoint Proteins metabolism, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Radiopharmaceuticals pharmacology, Radiopharmaceuticals therapeutic use, Radium pharmacology, Radium therapeutic use, Tumor Microenvironment drug effects, Tumor Microenvironment genetics
- Abstract
Purpose: Radium-223 prolongs survival in a fraction of men with bone metastatic prostate cancer (PCa). However, there are no markers for monitoring response and resistance to Radium-223 treatment. Exosomes are mediators of intercellular communication and may reflect response of the bone microenvironment to Radium-223 treatment. We performed molecular profiling of exosomes and compared the molecular profile in patients with favorable and unfavorable overall survival., Experimental Design: We performed exosomal transcriptome analysis in plasma derived from our preclinical models (MDA-PCa 118b tumors, TRAMP-C2/BMP4 PCa) and from the plasma of 25 patients (paired baseline and end of treatment) treated with Radium-223. All samples were run in duplicate, and array data analyzed with fold changes +2 to -2 and P < 0.05., Results: We utilized the preclinical models to establish that genes derived from the tumor and the tumor-associated bone microenvironment (bTME) are differentially enriched in plasma exosomes upon Radium-223 treatment. The mouse transcriptome analysis revealed changes in bone-related and DNA damage repair-related pathways. Similar findings were observed in plasma-derived exosomes from patients treated with Radium-223 detected changes. In addition, exosomal transcripts detected immune-suppressors (e.g., PD-L1) that were associated with shorter survival to Radium-223. Treatment of the Myc-CaP mouse model with a combination of Radium-223 and immune checkpoint therapy (ICT) resulted in greater efficacy than monotherapy., Conclusions: These clinical and coclinical analyses showed that RNA profiling of plasma exosomes may be used for monitoring the bTME in response to treatment and that ICT may be used to increase the efficacy of Radium-223., (©2021 American Association for Cancer Research.)
- Published
- 2021
- Full Text
- View/download PDF
45. Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies.
- Author
-
Ranasinghe W, Shapiro DD, Hwang H, Wang X, Reichard CA, Elsheshtawi M, Achim MF, Bathala T, Tang C, Aparicio A, Tu SM, Navone N, Thompson TC, Pisters L, Troncoso P, Davis JW, and Chapin BF
- Subjects
- Aged, Humans, Male, Middle Aged, Retrospective Studies, Risk Assessment, Treatment Outcome, Adenocarcinoma therapy, Prostatic Neoplasms therapy
- Abstract
Background: Ductal prostate adenocarcinoma (DAC) is a rare, aggressive, histologic variant of prostate cancer that is treated with conventional therapies, similar to high-risk prostate adenocarcinoma (PAC)., Objective: To assess the outcomes of men undergoing definitive therapy for DAC or high-risk PAC and to explore the effects of androgen deprivation therapy (ADT) in improving the outcomes of DAC., Design, Setting, and Participants: A single-center retrospective review of all patients with cT1-4/N0-1 DAC from 2005 to 2018 was performed. Those undergoing radical prostatectomy (RP) or radiotherapy (RTx) for DAC were compared with cohorts of high-risk PAC patients., Outcome Measurements and Statistical Analysis: Metastasis-free survival (MFS) and overall survival (OS) rates were analyzed using Kaplan-Meier and Cox regression models., Results and Limitations: A total of 228 men with DAC were identified; 163 underwent RP, 34 underwent RTx, and 31 had neoadjuvant therapy prior to RP. In this study, 163 DAC patients and 155 PAC patients undergoing RP were compared. Similarly, 34 DAC patients and 74 PAC patients undergoing RTx were compared. DAC patients undergoing RP or RTx had worse 5-yr MFS (75% vs 95% and 62% vs 93%, respectively, p < 0.001) and 5-yr OS (88% vs 97% and 82% vs 100%, respectively, p < 0.05) compared with PAC patients. In the 76 men who received adjuvant/salvage ADT after RP, DAC also had worse MFS and OS than PAC (p < 0.01). A genomic analysis revealed that 10/11 (91%) DACs treated with ADT had intrinsic upregulation of androgen-resistant pathways. Further, none of the DAC patients (0/15) who received only neoadjuvant ADT prior to RP had any pathologic downgrading. The retrospective nature was a limitation., Conclusions: Men undergoing RP or RTx for DAC had worse outcomes than PAC patients, regardless of the treatment modality. Upregulation of several intrinsic resistance pathways in DAC rendered ADT less effective. Further evaluation of the underlying biology of DAC with clinical trials is needed., Patient Summary: This study demonstrated worse outcomes among patients with ductal adenocarcinoma of the prostate than among high-grade prostate adenocarcinoma patients, regardless of the treatment modality., (Copyright © 2020. Published by Elsevier B.V.)
- Published
- 2021
- Full Text
- View/download PDF
46. The expression of YWHAZ and NDRG1 predicts aggressive outcome in human prostate cancer.
- Author
-
Lage-Vickers S, Bizzotto J, Valacco MP, Sanchis P, Nemirovsky S, Labanca E, Scorticati C, Mazza O, Mitrofanova A, Navone N, Vazquez E, Cotignola J, and Gueron G
- Subjects
- Adenocarcinoma mortality, Adult, Aged, Biomarkers, Tumor metabolism, Humans, Male, Mass Spectrometry, Middle Aged, Prostatic Neoplasms mortality, Proteome, Risk Assessment, 14-3-3 Proteins metabolism, Adenocarcinoma metabolism, Cell Cycle Proteins metabolism, Intracellular Signaling Peptides and Proteins metabolism, Prostatic Hyperplasia metabolism, Prostatic Neoplasms metabolism
- Abstract
Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction in PCa. LC ESI-MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues and peptide data was integrated with omic analyses. We identified high YWHAZ and NDRG1 expression to be associated with poor PCa prognosis considering all Gleason scores (GS). YWHAZ and NDRG1 defined two subpopulations of PCa patients with high and intermediate risk of death. Multivariable analyses confirmed their independence from GS. ROC analysis unveiled that YWHAZ outperformed GS beyond 60 months post-diagnosis. The genomic analysis of PCa patients with YWHAZ amplification, or increased mRNA or protein levels, revealed significant alterations in key DNA repair genes. We hereby state the relevance of YWHAZ in PCa, showcasing its role as an independent strong predictor of aggressiveness.
- Published
- 2021
- Full Text
- View/download PDF
47. Enhanced Viability for Ex vivo 3D Hydrogel Cultures of Patient-Derived Xenografts in a Perfused Microfluidic Platform.
- Author
-
Sablatura LK, Bircsak KM, Shepherd P, Queiroz K, Farach-Carson MC, Constantinou PE, Saleh A, Navone N, and Harrington DA
- Subjects
- Animals, Cell Survival, Centrifugation, Density Gradient, Disease Models, Animal, Humans, Image Processing, Computer-Assisted, Mice, Staining and Labeling, Cell Culture Techniques, Heterografts, Hydrogels chemistry, Microfluidics
- Abstract
Patient-derived xenografts (PDX), generated when resected patient tumor tissue is engrafted directly into immunocompromised mice, remain biologically stable, thereby preserving molecular, genetic, and histological features, as well as heterogeneity of the original tumor. However, using these models to perform a multitude of experiments, including drug screening, is prohibitive both in terms of cost and time. Three-dimensional (3D) culture systems are widely viewed as platforms in which cancer cells retain their biological integrity through biochemical interactions, morphology, and architecture. Our team has extensive experience culturing PDX cells in vitro using 3D matrices composed of hyaluronic acid (HA). In order to separate mouse fibroblast stromal cells associated with PDXs, we use rotation culture, where stromal cells adhere to the surface of tissue culture-treated plates while dissociated PDX tumor cells float and self-associate into multicellular clusters. Also floating in the supernatant are single, often dead cells, which present a challenge in collecting viable PDX clusters for downstream encapsulation into hydrogels for 3D cell culture. In order to separate these single cells from live cell clusters, we have employed density step gradient centrifugation. The protocol described here allows for the depletion of non-viable single cells from the healthy population of cell clusters that will be used for further in vitro experimentation. In our studies, we incorporate the 3D cultures in microfluidic plates which allow for media perfusion during culture. After assessing the resultant cultures using a fluorescent image-based viability assay of purified versus non-purified cells, our results show that this additional separation step substantially reduced the number of non-viable cells from our cultures.
- Published
- 2020
- Full Text
- View/download PDF
48. Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer.
- Author
-
Ortiz E, Sanchis P, Bizzotto J, Lage-Vickers S, Labanca E, Navone N, Cotignola J, Vazquez E, and Gueron G
- Subjects
- Case-Control Studies, Cell Proliferation, Data Mining, Databases, Genetic, Endoplasmic Reticulum Stress, Gene Expression Regulation, Neoplastic, Heme Oxygenase-1 genetics, Humans, Male, Myxovirus Resistance Proteins genetics, PC-3 Cells, Prostatic Neoplasms genetics, Survival Analysis, Tumor Microenvironment, Computational Biology methods, Heme Oxygenase-1 metabolism, Myxovirus Resistance Proteins metabolism, Prostatic Neoplasms metabolism
- Abstract
The inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological significance of HO-1 interactors. Open-access PCa datasets were mined to address the clinical significance of the HO-1 interactome in human samples. HO-1 interactors were clustered into groups according to their expression profile in PCa patients. We focused on the myxovirus resistance gene ( MX1 ) as: (1) it was significantly upregulated under HO-1 induction; (2) it was the most consistently downregulated gene in PCa vs. normal prostate; (3) its loss was associated with decreased relapse-free survival in PCa; and (4) there was a significant positive correlation between MX1 and HMOX1 in PCa patients. Further, MX1 was upregulated in response to endoplasmic reticulum stress (ERS), and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Altogether, we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and having a high impact in the clinical setting.
- Published
- 2020
- Full Text
- View/download PDF
49. Heme Oxygenase-1 Is a Pivotal Modulator of Bone Turnover and Remodeling: Molecular Implications for Prostate Cancer Bone Metastasis.
- Author
-
Anselmino N, Starbuck M, Labanca E, Cotignola J, Navone N, Gueron G, Zenclussen AC, and Vazquez E
- Subjects
- Animals, Bone Neoplasms secondary, Bone Regeneration, Bone Remodeling, Heme Oxygenase-1 deficiency, Male, Membrane Proteins deficiency, Mice, Mice, Inbred BALB C, Mice, Knockout, Bone Neoplasms metabolism, Heme Oxygenase-1 metabolism, Membrane Proteins metabolism, Prostatic Neoplasms metabolism
- Abstract
Aims: Bone is the most frequent site of prostate cancer (PCa) metastasis. Tumor cells interact with the bone microenvironment interrupting tissue balance. Heme oxygenase-1 (HO-1; encoded by Hmox1 ) appears as a potential target in PCa maintaining the cellular homeostasis. Our hypothesis is that HO-1 is implicated in bone physiology and modulates the communication with PCa cells. Here we aimed at (i) assessing the physiological impact of Hmox1 gene knockout (KO) on bone metabolism in vivo and (ii) determining the alterations of the transcriptional landscape associated with tumorigenesis and bone remodeling in cells growing in coculture (PCa cells with primary mouse osteoblasts [PMOs] from BALB/c Hmox1
+/+ , Hmox1+/- , and Hmox1-/- mice). Results: Histomorphometric analysis of Hmox1-/- mice bones exhibited significantly decreased bone density with reduced remodeling parameters. A positive correlation between Hmox1 expression and Runx2 , Col1a1 , Csf1 , and Opg genes was observed in PMOs. Flow cytometry studies revealed two populations of PMOs with different reactive oxygen species (ROS) levels. The high ROS population was increased in PMOs Hmox1+/- compared with Hmox1+/+ , but was significantly reduced in PMOs Hmox1-/- , suggesting restrained ROS tolerance in KO cells. Gene expression was altered in PMOs upon coculture with PCa cells, showing a pro-osteoclastic profile. Moreover, HO-1 induction in PCa cells growing in coculture with PMOs resulted in a significant modulation of key bone markers such as PTHrP and OPG . Innovation and Conclusion: We here demonstrate the direct implications of HO-1 expression in bone remodeling and how it participates in the alterations in the communication between bone and prostate tumor cells.- Published
- 2020
- Full Text
- View/download PDF
50. Favorable incremental cost-effectiveness ratio for lung cancer screening in Italy.
- Author
-
Veronesi G, Navone N, Novellis P, Dieci E, Toschi L, Velutti L, Solinas M, Vanni E, Alloisio M, and Ghislandi S
- Subjects
- Aged, Aged, 80 and over, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Italy epidemiology, Lung Neoplasms diagnosis, Lung Neoplasms epidemiology, Lung Neoplasms therapy, Male, Middle Aged, Prognosis, Survival Rate, Cost-Benefit Analysis, Early Detection of Cancer economics, Health Care Costs statistics & numerical data, Lung Neoplasms economics, Quality-Adjusted Life Years
- Abstract
Objectives: Lung cancer detection by low-dose computed tomographic screening reduces mortality. However, it is essential to assess cost-effectiveness. We present a cost-effectiveness analysis of screening in Italians at high risk of lung cancer, from the point of view of the Italian tax-payer., Materials and Methods: We used a decision model to estimate the cost-effectiveness of annual screening for 5 years in smokers (≥30 pack-years) of 55-79 years. Patients diagnosed in the COSMOS study were the screening arm; patients diagnosed and treated for lung cancer in the Lombardy Region, Italy, constituted the usual care arm. Treatment costs were extracted from our hospital database. Lung cancer survival in screened patients was adjusted for 2-year lead-time bias. Life-years and quality-adjusted life-years were estimated by stage at diagnosis, from which incremental cost-effectiveness ratios per life-year and quality-adjusted life-year gained were estimated., Results: Base-case incremental cost-effectiveness ratios were 3297 and 2944 euro per quality-adjusted life-year and life-year gained, respectively. Deterministic sensitivity analysis indicated that these values were particularly sensitive to lung cancer prevalence, screening sensitivity and specificity, screening cost, and treatment costs for stage I and IV disease. From the probabilistic sensitivity analysis incremental cost-effectiveness ratios had a 98 % probability of being <25,000 euro (widely-accepted threshold) and a 55 % probability of being <5000 euro., Conclusions: Low-dose computed tomographic screening is associated with an incremental cost of 2944 euro per life-year gained in high risk population, implying that screening can be introduced in Italy at contained cost, saving the lives of many lung cancer patients., Competing Interests: Declaration of Competing Interest GV has financial relationships with AB Medica SpA, Johnson & Johnson Medical SpA, and Medtronic Italia SpA, unrelated to the content of this study. NN received a research grant from the Italian National Insurance Institute for Workplace Injuries (INAIL). None of the other authors has any conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.