cyclin-d1 and Paget-Disease--Extramammary

cyclin-d1 has been researched along with Paget-Disease--Extramammary* in 5 studies

Other Studies

5 other study(ies) available for cyclin-d1 and Paget-Disease--Extramammary

ArticleYear
Cyclin-dependent kinase 4/6 inhibitors suppress tumor growth in extramammary Paget's disease.
    Cancer science, 2022, Volume: 113, Issue:2

    Extramammary Paget's disease (EMPD) is a rare adnexal neoplasm commonly seen in the genital areas among the senior population. The prognosis of advanced EMPD is not favorable; thus, the development of potential treatments has long been sought. Cyclin-dependent kinase (CDK) 4/6 inhibitors such as abemaciclib and palbociclib have been proven effective against metastatic breast cancer; however, no studies have addressed CDK4/6 inhibitors as an EMPD treatment. We herein examine the efficacy of CDK4/6 inhibitors against an EMPD patient-derived xenograft (PDX) model. Abemaciclib (50 mg/kg/day) or palbociclib (120 mg/kg/day) was given orally to tumor-bearing NOD/Scid mice over a 3-week period. We also investigated the protein expression levels of CDK4/6 and cyclin D1 through immunohistochemical staining using EMPD clinical samples. Treatment with abemaciclib or palbociclib as a single agent was found to significantly suppress tumor growth in EMPD-PDX. The Ki-67-positive ratio of the treated EMPD-PDX tumors was significantly lower than that of the nontreated tumors. Clinically, the expression levels of CDK4 and cyclin D1 were significantly higher in the EMPD tumor cells than in the normal epidermis. Our results suggest that CDK4/6 inhibitors could be novel and potent therapeutics for the treatment of EMPD.

    Topics: Aged; Aged, 80 and over; Animals; Cyclin D1; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Female; Humans; Male; Mice; Middle Aged; Paget Disease, Extramammary; Protein Kinase Inhibitors; Skin; Tumor Burden; Xenograft Model Antitumor Assays

2022
Overexpression of cyclin-dependent kinase 4 protein in extramammary Paget's disease.
    The Journal of dermatology, 2019, Volume: 46, Issue:5

    Topics: Aged; Aged, 80 and over; Cyclin D1; Cyclin-Dependent Kinase 4; Disease Progression; Female; Humans; Male; Middle Aged; Paget Disease, Extramammary; Skin; Skin Neoplasms

2019
Androgen receptor, androgen-producing enzymes and their transcription factors in extramammary Paget disease.
    Human pathology, 2015, Volume: 46, Issue:11

    Extramammary Paget disease (EMPD) has been known to frequently express androgen receptor (AR). Therefore, androgens could play roles in the biological behavior of Paget cells. 5α-Reductase (5α-red) types 1 and 2 and 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5) are pivotal in situ regulators of androgen production in androgen-responsive tissues including androgen-dependent neoplasms. Therefore, in this study, we immunolocalized AR, androgen-producing enzymes, and their transcription factors to assess the state of in situ androgen production and actions and its correlation of invasiveness in EMPD. We studied 51 cases of EMPD with known clinicopathological status. AR, 5α-red1, 17β-HSD5, and β-catenin immunoreactivity was evaluated by using the modified H-score method while cyclin D1, p53, forkhead box protein P1, and a proliferation marker, Ki-67, were quantified using labeling index. The mean scores of AR, 5α-red1, and 17β-HSD5 in invasive EMPD were all significantly higher than noninvasive EMPD (P < .0001). Ki-67 labeling index as well as the cyclin D1 score was also significantly higher in invasive than noninvasive lesions of EMPD. These results demonstrated that androgen receptor and androgen-producing enzymes were both associated with cell cycle regulation and subsequently the invasiveness of EMPD lesions and could also indicate those above as potential markers of invasive potentials in EMPD.

    Topics: 17-Hydroxysteroid Dehydrogenases; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Aged; Aged, 80 and over; beta Catenin; Cyclin D1; Female; Forkhead Transcription Factors; Humans; Immunohistochemistry; Male; Middle Aged; Paget Disease, Extramammary; Receptors, Androgen; Repressor Proteins; Skin; Skin Neoplasms

2015
Expression of cyclin D1 and retinoblastoma protein in Paget's disease of the vulva and breast: an immunohistochemical study of 108 cases.
    Histopathology, 2009, Volume: 55, Issue:6

    Loss of retinoblastoma protein expression and overexpression of cyclin D1 have been implicated in the development and progression of some cancers. Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon conditions and the pathogenesis of these diseases is still unclear. The aim was to examine the expression of the retinoblastoma and cyclin D1 proteins in PDV and PDB and to correlate any differences between PDV and PDB, and in the presence or absence of an underlying carcinoma.. Seventy-two archival cases of PDV including 10 with invasive disease and 36 cases of PDB were evaluated immunohistochemically for the expression of cyclin D1 and retinoblastoma protein. Forty-four percent (32/72) of cases of PDV showed loss of expression of the retinoblastoma protein, compared with 67% (24/36) of PDB cases. Fifty-nine percent (41/69) of PDV overexpressed cyclin D1. In PDB, 8% (3/34) overexpressed cyclin D1. There were no significant differences in the expression of retinoblastoma and cyclin D1 in PDV cases with or without underlying invasive disease. There were significant differences between the expression of retinoblastoma (P = 0.03) and cyclin D1 (P < 0.001) in PDV compared with PDB.. The differences in the expression of cyclin D1 and retinoblastoma may indicate the differences in the pathogenesis of PDV and PDB.

    Topics: Breast Neoplasms; Chi-Square Distribution; Cyclin D1; Female; Humans; Immunohistochemistry; Paget Disease, Extramammary; Paget's Disease, Mammary; Retinoblastoma Protein; Vulvar Neoplasms

2009
Expression of phosphorylated Stat3, cyclin D1 and Bcl-xL in extramammary Paget disease.
    The British journal of dermatology, 2006, Volume: 154, Issue:5

    Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin D1 protein has not been investigated in extramammary Paget disease (EMPD).. To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D1 protein in EMPD and to evaluate the relationships among them.. Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL.. Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1 expression and between p-Stat3 and Bcl-xL expression.. Our study shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.

    Topics: Adult; Aged; Aged, 80 and over; bcl-X Protein; Cyclin D1; Female; Humans; Immunoenzyme Techniques; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Paget Disease, Extramammary; Phosphorylation; Skin; STAT3 Transcription Factor

2006
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