The DOI matches its Crossref record; 45 of the 48 references it cites were found in a registry or an index.
The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie’s Disease
Open accessAbstract
Peyronie’s disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These pathways often interact and crosstalk with each other, amplifying fibrotic processes and tissue remodeling in the penile tissue.”
From Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets. (2024) · cites this paper as [79]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Elevated levels of Bcl-2 prevent the release of cytochrome c from mitochondria, a crucial step in initiating apoptosis.”
From Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets. (2024) · cites this paper as [79]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
Oltval, Z. N., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)90509-o · Cited by 6,003
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
Vaux, D., Cory, S., & Adams, J. (1988) · Nature · doi:10.1038/335440a0 · Cited by 3,355
Yin, X.-M., Oltvai, Z., & Korsmeyer, S. (1994) · Nature · doi:10.1038/369321a0 · Cited by 1,383
Bcl-2 initiates a new category of oncogenes: regulators of cell death
Korsmeyer, S. J. (1992) · Blood · doi:10.1182/blood.v80.4.879.bloodjournal804879 · Cited by 1,115
(2005) · doi:10.1016/j.ucl.2005.08.007 · Cited by 759 · cited 1×
“Fibrosis, its major pathological manifestation, arises from fibroblast proliferation and accumulation of extracellular matrix; PD progresses with formation of plaques or even ectopic calcification having the appearance of scar tissue, which prevents TA expansion during erections [6, 7].”
BackgroundCONGENITAL CURVATURE OF THE PHALLUS: REPORT OF THREE CASES WITH DESCRIPTION OF CORRECTIVE OPERATION.
Nesbit, R. M. (1965) · Transactions of the American Association of Genito-Urinary Surgeons · doi:10.1016/s0022-5347(17)63751-0 · Cited by 471 · cited 1×
“Control samples were specimens from 4 patients (mean age 23 ± 3 years; range 21–27) with congenital penile curvature who underwent Nesbit’s corrective procedure [22].”
BackgroundProposal: Trauma as the Cause of the Peyronie's Lesion
Devine, C. J. J., Somers, K. D., Jordan, G. H., & Schlossberg, S. M. (1997) · Journal of Urology · doi:10.1016/s0022-5347(01)65361-8 · Cited by 381
The apoptosis cascade — morphological and immunohistochemical methods for its visualization
Huppertz, B., Frank, H., & Kaufmann, P. (1999) · Anatomy and Embryology · doi:10.1007/s004290050254 · Cited by 325 · cited 1×
“These complex events lead to apoptotic death, with collapse of the nucleus and of the cell itself and DNA fragmentation [31].”
BackgroundInsights into Programmed Cell Death through Structural Biology
Fesik, S. W. (2000) · Cell · doi:10.1016/s0092-8674(00)00119-7 · Cited by 317
Surgery of the Penis and Urethra
Jordan, G., & Mccammon, K. (2012) · doi:10.1016/b978-1-4160-6911-9.00036-0 · Cited by 216
PENILE TRAUMA: AN ETIOLOGIC FACTOR IN PEYRONIE'S DISEASE AND ERECTILE DYSFUNCTION
Jarow, J. P., & Lowe, F. C. (1997) · Journal of Urology · doi:10.1016/s0022-5347(01)64222-8 · Cited by 202
Rowinsky, E. K. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.2889 · Cited by 196 · cited 3×
“In the fully formed organism it mediates the maintenance of tissue homeostasis involved in normal tissue turnover, whereas its dysregulation plays a role in multiple disease processes [14].”
BackgroundFibrin Deposition in Peyronie's Disease Plaque
Somers, K. D., & Dawson, D. M. (1997) · The Journal of Urology · doi:10.1016/s0022-5347(01)65367-9 · Cited by 193
Bcl‐2 family proteins: The sentinels of the mitochondrial apoptosis pathway
Wong, W. W.-L., & Puthalakath, H. (2008) · IUBMB Life · doi:10.1002/iub.51 · Cited by 184
Peyronie's Disease: Etiology, Medical, and Surgical Therapy
HELLSTROM, W. J. G., & BIVALACQUA, T. J. (2000) · Journal of Andrology · doi:10.1002/j.1939-4640.2000.tb03387.x · Cited by 170
Antifibrotic Role of Inducible Nitric Oxide Synthase
Ferrini, M. G., Vernet, D., Magee, T. R., SHAHED, A. R., Qian, A., Rajfer, J., & González-Cadavid, N. F. (2002) · Nitric Oxide · doi:10.1006/niox.2001.0421 · Cited by 168
Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie's disease
Gonzalez-Cadavid, N. F., & Rajfer, J. (2005) · Nature Clinical Practice Urology · doi:10.1038/ncpuro0201 · Cited by 168 · cited 1×
“An external stress, sustained most likely in the erect state (typically during sexual activity), has been suggested to initiate plaque development [8]; the resulting TA injury or tearing then is suggested to heal abnormally [9].”
BackgroundVernet, D., Ferrini, M., Valente, E. G. A., Magee, T., Bou-Gharios, G., Rajfer, J., & Gonzalez-Cadavid, N. (2002) · Nitric oxide · doi:10.1016/s1089-8603(02)00124-6 · Cited by 141
Davila, H., Ferrini, M., Rajfer, J., & Gonzalez-Cadavid, N. (2003) · BJU International · doi:10.1046/j.1464-410x.2003.04224.x · Cited by 119
Bivalacqua, T. J., Diner, E. K., Novak, T. E., Vohra, Y., Sikka, S. C., Champion, H. C., Kadowitz, P. J., & Hellstrom, W. J. G. (2000) · The Journal of Urology · doi:10.1016/s0022-5347(05)67616-1 · Cited by 116
Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: pathogenetic implications.
Pardo, A., Barrios, R. J., Maldonado, V., Meléndez, J., Perez, J., Ruíz, V., Segura-Valdez, L., Sznajder, J., & Selman, M. (1998) · American Journal of Pathology · doi:10.1016/s0002-9440(10)65625-8 · Cited by 115
Treatment of Peyronie's disease with PDE5 inhibitors: an antifibrotic strategy
González-Cadavid, N. F., & Rajfer, J. (2010) · Nature Reviews Urology · doi:10.1038/nrurol.2010.24 · Cited by 86 · cited 4×
“Increased expression of TGF-β1, plasminogen activator inhibitor 1, reactive oxygen species (ROS), and other profibrotic factors as well as of inducible nitric oxide synthase (iNOS) leads to fibroblast/myofibroblast proliferation and collagen buildup [40, 41] as a defense mechanism against oxidative stress.”
BackgroundInfluentialThe microscopic pathology of Peyronie's disease.
Davis, C. (1997) · Journal of Urology · doi:10.1016/s0022-5347(01)65360-6 · Cited by 85
Gene expression in Peyronie's disease
Gonzalez-Cadavid, N. F., Magee, T. R., Ferrini, M., Qian, A., Vernet, D., & Rajfer, J. (2002) · International Journal of Impotence Research · doi:10.1038/sj.ijir.3900873 · Cited by 84 · cited 3×
“the mechanism entails their persistence inducing fibrosis, collagen buildup, and tissue contraction [7].”
BackgroundShindel, A., Lin, G., Ning, H., Banie, L., Huang, Y.-C., Liu, G., Lin, C.-S., & Lue, T. (2010) · Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.01790.x · Cited by 78
The management of Peyronie's disease
Ralph, D., & Minhas, S. (2004) · BJU International · doi:10.1111/j.1464-410x.2004.04587.x · Cited by 78 · cited 1×
“Even though PD has been described in the 18th century, its pathogenic mechanism and molecular basis are poorly understood and its therapeutic approach is still empirical [25].”
BackgroundSelf-citationMusumeci, G., Castrogiovanni, P., Loreto, C., Castorina, S., Pichler, K., & Weinberg, A. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140815767 · Cited by 71 · cited 1×
“2 for 10min as previously described [23].”
Self-citationFerrini, M., Magee, T., Vernet, D., Rajfer, J., & Gonzalez-Cadavid, N. (2002) · International journal of impotence research · doi:10.1038/sj.ijir.3900851 · Cited by 70
Ganabathi, K., Dmochowski, R. R., Zimmern, P. E., & Leach, G. (2003) · International journal of impotence research · doi:10.1097/00005392-199503000-00031 · Cited by 70
Induction of p53 and Bax during TGF-beta 1 initiated apoptosis in rat liver epithelial cells.
Teramoto, T., Kiss, A., & Thorgeirsson, S. (1998) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.1998.9411 · Cited by 68
Scar contracture: cellular and connective tissue aspects in Peyronie's disease.
Ehrlich, H. (1997) · Journal of Urology · doi:10.1016/s0022-5347(01)65368-0 · Cited by 52 · cited 1×
“An external stress, sustained most likely in the erect state (typically during sexual activity), has been suggested to initiate plaque development [8]; the resulting TA injury or tearing then is suggested to heal abnormally [9].”
BackgroundSalgado, C., Chim, H., Tang, J. C., Monstrey, S., & Mardini, S. (2011) · Seminars in Plastic Surgery · doi:10.1055/s-0031-1281492 · Cited by 51 · cited 1×
“The TA was incised and grafted at the level of the maximum penile curvature, where plaque formation was most prominent [21].”
Loreto, C., Almeida, L., Trevilatto, P., & Leonardi, R. (2011) · Journal of Oral Pathology & Medicine · doi:10.1111/j.1600-0714.2010.00920.x · Cited by 46 · cited 1×
“The initiator caspase 9 then cleaves and activates the executioner caspases 3, 6, and 7, resulting in cell apoptosis [14, 17].”
BackgroundSelf-citationCaltabiano, R., Leonardi, R., Musumeci, G., Bartoloni, G., Rusu, M., Almeida, L., & Loreto, C. (2013) · Acta Odontologica Scandinavica · doi:10.3109/00016357.2012.700060 · Cited by 35 · cited 1×
“The intrinsic pathway is influenced by members of the bcl family bound to the mitochondrial membrane, including bax and bcl-2, which act as pro- or antiapoptotic regulatory proteins, respectively [16].”
BackgroundSelf-citationLucattelli, M., Lunghi, B., Fineschi, S., Mirone, V., Bianca, R. D. D. V., Longo, N., Imbimbo, C., Palma, R. D., Sorrentino, R., Lungarella, G., et al. (2008) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2008.05.012 · Cited by 33 · cited 1×
“[47] demonstrated in a new mouse model of PD that mice aged 12 months develop osseous metaplasia, probably as a consequence of upregulation of hypoxia-inducible factor-1 (HIF-1): this seems to determine an increased expression of HIF-1 target genes such as TGF-β and iNOS which, as noted above, are partly responsible f…”
BackgroundPeyronie's Reconstruction for Maximum Length and Girth Gain: Geometrical Principles
Egydio, P., & Sansalone, S. (2008) · Advances in Urology · doi:10.1155/2008/205739 · Cited by 32 · cited 2×
“Carla Loreto,1 Giampiero La Rocca,2 Rita Anzalone,2 Rosario Caltabiano,3 Giuseppe Vespasiani,4 Sergio Castorina,1 David J. Ralph,5 Selim Cellek,6 Giuseppe Musumeci,1 Salvatore Giunta,1 Rados Djinovic,7 Dragoslav Basic,8 and Salvatore Sansalone4 1 Department of Bio-Medical Sciences, Anatomy and Histology Section, Unive…”
MethodSelf-citationLoreto, C., Almeida, L. E., Migliore, M. R., Caltabiano, M., & Leonardi, R. (2010) · European Journal of Histochemistry · doi:10.4081/ejh.2010.e40 · Cited by 31 · cited 1×
“The former pathway involves activation of death signaling ligands like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) through its death receptors DR4 and DR5 and has a role in immune and homeostasis processes [13, 15]; these events in turn activate the initiator caspase 8, which cleaves and activates…”
BackgroundSelf-citationThe genetics and immunology of Peyronie's disease
Noss, M. B., Day, N., Christ, G., & Melman, A. (2000) · International journal of impotence research · doi:10.1038/sj.ijir.3900591 · Cited by 30
Protein Biomarker Analysis of Primary Peyronie’s Disease Cells
Young, L. X. D., Bella, A. J., O’Gorman, D. B., Gan, B. S., Lim, K. B., & Brock, G. B. (2009) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2009.01556.x · Cited by 28
Loreto, C., Barbagli, G., Djinovic, R., Vespasiani, G., Carnazza, M., Miano, R., Musumeci, G., & Sansalone, S. (2011) · Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.02003.x · Cited by 26 · cited 1×
“We have previously described apoptotic cell death in TA plaques from patients with PD and demonstrated its activation via the extrinsic pathway by assessing an overexpression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor, DR5, in fibroblast and myofibroblast cells [19].”
BackgroundSelf-citationGelbard, M. K. (2008) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2008.01011.x · Cited by 19
Loreto, C., Galanti, C., Leonardi, R., Musumeci, G., Pannone, G., Palazzo, G., & Rusu, M. (2013) · International Endodontic Journal · doi:10.1111/iej.12040 · Cited by 16 · cited 1×
“Apoptosis can therefore be regarded as an injury-limiting mode of cell disposal [32].”
BackgroundSelf-citationA novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie’s plaques
Jung, K. H., Ryu, Y.-L., LEE, H.-S., Lee, H., Son, M. K., YAN, H. H., Hong, S., Ryu, J., Hong, S., Suh, J. ‐., et al. (2013) · International Journal of Oncology · doi:10.3892/ijo.2013.1905 · Cited by 11 · cited 2×
“Recent studies have shown that phosphoinositide 3kinase (PI3K)/Akt signaling regulates fibrotic responses including collagen synthesis and cell proliferation [48].”
BackgroundLoreto, C., Orlandi, A., Ferlosio, A., Djinovic, R., Bašić, D., Bettocchi, C., Rutigliano, M., Barbagli, G., Vespasiani, G., Caltabiano, R., et al. (2012) · Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2012.02789.x · Cited by 7 · cited 1×
“In situ detection of apoptosis at the single cell level was performed by terminal deoxynucleotidyl transferase(TdT-) mediated dUTP-biotin nick end labeling, TUNEL (In Situ Cell Death Detection Kit, POD, Roche) as previously described [24].”
MethodSelf-citationSurgical Techniques: Intralesional Injection Therapy for Peyronie's Disease
Hellstrom, W., & Cockerham, Y. (2009) · doi:10.1111/j.1743-6109.2009.01341.x · Cited by 6
Flagged first, then by citations
3 of the 48 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
- 10.1016/S0094-0143(05)70146-4 · DOI
- 2012, Advances in Clinical and Experimental Medicine, 21, 607
- 2012, Sinaling pathway that regulate life and cell death: evolution of apoptosis in the contex of self-defence, 124
- 10.1038/aja.2012.9 · DOI
- 1992, Blood, 80, 879, 10.1182/blood.V80.4.879.879 · DOI
- 10.1016/S0022-5347(01)65360-6 · DOI
- 10.1095/biolreprod64.3.974 · DOI
Cited by
Sorted by citations
Wearable and flexible electronics for continuous molecular monitoring
Yang, Y., & Gao, W. (2019) · Chemical Society Reviews · doi:10.1039/c7cs00730b · Cited by 1,315
Loh, C.-Y., Chai, J., Tang, T. F., Wong, W. F., Sethi, G., Shanmugam, M. K., Chong, P. P., & Looi, C. Y. (2019) · Cells · doi:10.3390/cells8101118 · Cited by 1,360
“Several stimuli such as DNA damage, ischemia and oxidative stress lead to perturbation of mitochondrial membrane and release of cytochrome C into cytosol, where it initiates intrinsic apoptosis by inducing caspase activation [72,74].”
BackgroundWearable sensors for monitoring the physiological and biochemical profile of the athlete
Seshadri, D. R., Li, R. T., Voos, J. E., Rowbottom, J. R., Alfes, C. M., Zorman, C. A., & Drummond, C. K. (2019) · npj Digital Medicine · doi:10.1038/s41746-019-0150-9 · Cited by 537
Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles
Salatin, S., & Khosroushahi, A. Y. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13110 · Cited by 270
Pinheiro, H. T., Rocha, L. A., Macieira, R. M., Carvalho‐Filho, A., Anderson, A. B., Bender, M. G., Dario, F. D., Ferreira, C. E. L., Figueiredo-Filho, J. M., Francini-Filho, R. B., et al. (2018) · Diversity and Distributions · doi:10.1111/ddi.12729 · Cited by 252
Metadata
- Authors
- Loreto, C., La Rocca, G., Anzalone, R., Caltabiano, R., Vespasiani, G., Castorina, S., Ralph, D. J., Cellek, S., Musumeci, G., Giunta, S., Djinovic, R., Basic, D., & Sansalone, S.
- Affiliations
- University of Catania (IT)
- Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, 90100 Palermo, Italy
- University of Palermo (IT)
- University of Rome Tor Vergata (IT)
- University College Hospital (GB)
- Cranfield University (GB)
- Sava Perovic Foundation, Center for Genito-Urinary Reconstructive Surgery, 11000 Belgrade, Serbia
- Clinic of Urology, Clinical Center Nis, 18000 Nis, Serbia
- Corresponding author
- Loreto, Carla
- ORCID
- Venue
- BioMed Research International
- Publisher
- Wiley
- Published
- 2014
- Volume
- 2014
- Pages
- 1-10
- ISSN
- 1110-7243 (ISSN-L)
- 2314-6133
- 2314-6141
- PMC
- PMC4147380
- OpenAlex
- W1973666710
- Cited by
- 108
- References
- 48
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 14 · 2022: 20 · 2021: 22 · 2020: 15 · 2019: 12 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Keywords
- Peyronie's disease, mitochondrial apoptosis, apoptosis, tunica albuginea, fibrous plaque, Bax, Bcl-2, caspase-3, caspase-9, myofibroblasts, fibroblasts, ossification centers, penile deformity
- MeSH terms
- Adult, Aged, Humans, Male, Middle Aged, Penile Induration, Staining and Labeling, Signal Transduction, Apoptosis, Disease Progression, In Situ Nick-End Labeling, bcl-2-Associated X Protein, Caspase 3, Caspase 9, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review