Comparative study of the expression of proteins involved in the cell cycle in renal secondary hyperparathyroidism

Alcázar, José A. Sánchez; Polo, José R.; Tardío, Juan C.; Anguita, Javier; Martínez-Montero, Juan Carlos; Jofre, R.; García-Criado, Francisco Javier; Menárguez, Javier

doi:10.1046/j.1523-1755.63.s85.8.x

Cited by 3 publications

(5 citation statements)

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“…MDM2 overexpression has been observed in other diseases, including SLE and LN, pSS, FXS, RSH, atherosclerosis, MI, TAD, ARCI, and pterygium . Interestingly, MDM2 could be differentially expressed in different stages of the disease.…”

Section: General Discussion and Future Research Directionsmentioning

confidence: 98%

Section: Roles Of Mdm2 In Kidney Diseases and Diabetesmentioning

confidence: 99%

“…Renal secondary hyperparathyroidism (RSH) is a chronic and multifactorial kidney disease . Alcázar et al have recently examined the expression of G1/S transition‐related proteins, including MDM2, p53, and p21, in the parathyroid glands from 41 patients who underwent parathyroidectomies and seven patients with persistent hyperparathyroidism following renal transplantation. The results have indicated that the expression levels of MDM2, p53, and p21 are significantly increased in the parathyroid glands of patients with RSH, compared with normal glands (Figure ) …”

Section: Roles Of Mdm2 In Kidney Diseases and Diabetesmentioning

confidence: 99%

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Targeting MDM2 for novel molecular therapy: Beyond oncology

Wang

Qin

Rajaei

et al. 2019

Medicinal Research Reviews

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The murine double minute 2 (MDM2) oncogene exerts major oncogenic activities in human cancers; it is not only the bestdocumented negative regulator of the p53 tumor suppressor, but also exerts p53-independent activities. There is an increasing interest in developing MDM2-based targeted therapies. Several classes of MDM2 inhibitors have been evaluated in preclinical models, with a few entering clinical trials, mainly for cancer therapy. However, noncarcinogenic roles for MDM2 have also been identified, demonstrating that MDM2 is involved in many chronic diseases and conditions such as inflammation and autoimmune diseases,

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Section: General Discussion and Future Research Directionsmentioning

confidence: 98%

Section: Roles Of Mdm2 In Kidney Diseases and Diabetesmentioning

confidence: 99%

Section: Roles Of Mdm2 In Kidney Diseases and Diabetesmentioning

confidence: 99%

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Targeting MDM2 for novel molecular therapy: Beyond oncology

Wang

Qin

Rajaei

et al. 2019

Medicinal Research Reviews

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“…Among such diseases were epidermolysis bullosa, primary immunodeficiency, congenital generalized lipodystrophy, classic complement pathway component defects, and immune system diseases. 1 diabetes, and systemic lupus erythematosus (21)(22)(23), but also in the parathyroid glands of patients with renal secondary hyperparathyroidism (24). Therefore, we think that there was a strong association between the up-regulation of p53 and mdm4 and thymoma, as well as autoimmune hepatitis/myocarditis.…”

Section: Discussionmentioning

confidence: 93%

Clinical and Genetic Characteristics of Thymoma Patients With Autoimmune Hepatitis and Myocarditis

Yu¹,

Yu²,

Du³

et al. 2022

Front. Oncol.

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BackgroundOur study investigated a special series of thymoma with autoimmune hepatitis and myocarditis and tried to reveal the gene expression profiles of this series of thymoma.MethodsFrom 2011 to 2019, a total of 13 special thymoma patients presented with autoimmune hepatitis and myocarditis, accounting for about 1.26% of thymoma patients undergoing surgery in Beijing TongRen Hospital. Clinical data were retrospectively collected. All samples were harvested during surgical procedures, and analyzed to identify changes in gene expression using the CapitalBio mRNA microarray analysis, the Whole exome sequencing analysis (WES), qPCR and immunohistochemistry (IHC) tools.ResultsAfter surgery, patient symptoms were relieved gradually. Levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), and alanine amiotransferase (ALT) increased to some extent within 1 to 3 months after surgery, and fluctuated, and then, gradually decreased close to normal within 6 months after surgery. Enrichment analysis of Kyoto Genome and Genome Encyclopedia (KEGG) pathway was performed and enrichment results were visualized. It indicated that gene expression of 5 signaling pathways, including cell cycle and p53 signaling pathway, were generally abnormal. P53 expression was up-regulated in all tumor tissues. However, IHC and qPCR analysis showed that there was no significant difference in p21 expression between normal and tumor tissue. Results of WES showed that only one driver gene-MDM4 amplified 4 fold in 53.2% thymoma cells. Further qPCR and IHC analysis confirmed the up-regulation of the expression of p53 and mdm4 in 13 thymoma patients with autoimmune hepatitis and myocarditis.ConclusionOur study reveals the clinical and genetic characteristics of thymoma patients with autoimmune hepatitis and myocarditis. For this special category of thymoma, the up-regulation of p53 and mdm4 plays an important role in the occurrence of thymoma and autoimmune hepatitis/myocarditis.

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“…A previous step of heat-induced antigen retrieval was used for all antibodies (Abs) except for p16/INK4a. [11][12][13] Briefly, slides were heated in a pressure cooker for 10 minutes in 0.01 M solution of sodium citrate buffer before incubation with the primary Ab. After overnight incubation at 4 8C with primary Abs, immunodetection was performed manually with biotinylated antimouse immunoglobulins.…”

Section: Ihcmentioning

confidence: 99%

Retinoblastoma (Rb) tumor‐suppressor pathway alterations in meningeal hemangiopericytomas: High E2F transcription factor 1 expression and loss of Rb expression

Martínez

Palomino

Samaniego

et al. 2008

Cancer

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BACKGROUND.The authors analyzed the retinoblastoma (Rb) tumor‐suppressor pathway in meningeal hemangiopericytomas (MHPCs).METHODS.Immunohistochemical detection of the Rb pathway proteins (Rb; E2F transcription factor 1 [E2F1]; cyclins D1, D3, and E; cyclin‐dependent kinase 4 [CDK4]; and the CDK4 inhibitor p16/INKa) was followed by double immunofluorescence (DIF) staining and laser‐scanning confocal microscopy (LSCM) in 11 MHPC specimens and from 4 specimens of recurrent disease from 1, 2, and 4 recurrences (total, 18 specimens).RESULTS.All specimens displayed Rb pathway alterations, including low or negative Rb protein expression (17 specimens), high Rb protein expression (1 specimen), and loss of p16/INK4a expression (17 specimens). High levels of positive cell‐cycle regulators were observed for E2F1 (10 specimens), cyclin E (7 specimens), CDK4 (5 specimens), cyclin D3 (1 specimen), and cyclin D1 (1 specimen). DIF and LSCM revealed no or very weak Rb and E2F1 colocalization, indicating that Rb does not act as a growth suppressor. High levels of human mouse double‐minute 2 (HDM2) expression were observed in a previous study of these tumors, and they displayed colocalization with E2F1 and Rb in the current study, which supports the argument that HDM2 activates E2F1 and inactivates Rb.CONCLUSIONS.The current findings demonstrated that loss of Rb and p16/INKa expression and high E2F1 expression indicate impairment of the Rb suppressor pathway. HDM2 colocalization with E2F1 and Rb also indicates that Rb suppressor pathway inactivation and transactivation of DNA synthesis genes may play pathogenic roles in MHPCs. High expression levels of cyclin E, cyclin D1, cyclin D3, and CDK4 were associated with Rb suppressor pathway neutralization. Cancer 2008. © 2008 American Cancer Society.

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Comparative study of the expression of proteins involved in the cell cycle in renal secondary hyperparathyroidism

Abstract: In both groups IHC profiles of proteins involved in G1/S transition regulation significantly differed from normal PT glands. The results support partial reversion to normal IHC profile in post-transplantation HPT.

Cited by 3 publications

References 25 publications

Targeting MDM2 for novel molecular therapy: Beyond oncology

Targeting MDM2 for novel molecular therapy: Beyond oncology

Clinical and Genetic Characteristics of Thymoma Patients With Autoimmune Hepatitis and Myocarditis

Retinoblastoma (Rb) tumor‐suppressor pathway alterations in meningeal hemangiopericytomas: High E2F transcription factor 1 expression and loss of Rb expression

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