Combined oral contraceptives promote androgen receptor and oestrogen receptor alpha upregulation in the female prostate (Skene’s paraurethral glands) of adult gerbils (Meriones unguiculatus)

2018 ◽  
Vol 30 (10) ◽  
pp. 1286
Author(s):  
Eliana G. Pinto ◽  
Mônica S. Campos ◽  
Luiz R. Falleiros-Júnior ◽  
Mara R. Marques ◽  
Sebastião R. Taboga ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hormonal Regulation ◽  
Oestrogen Receptor ◽  
Combined Treatment ◽  
Secretory Activity ◽  
Intraepithelial Neoplasia ◽  
Meriones Unguiculatus ◽  
Proliferation Index ◽  
Cell Degeneration ◽  
Female Prostate

The aim of this study was to evaluate the effects of cyproterone acetate (CPA) and ethinyloestradiol (EE) alone or in combination on the female prostate of adult gerbils. Adult females were exposed for 21 days to daily oral doses of CPA (1 mg kg−1), EE (10 µg kg−1) or a combination of CPA and EE. Female prostatic complexes were removed, weighed and subjected to morphological, stereological, immunohistochemical and ultrastructural analyses. CPA treatment caused epithelial atrophy and decreased prostate secretory activity. The EE treatment group showed glandular hyperplasia, a high cell-proliferation index and an increase in androgen and oestrogen receptor α (AR and ERα) immunoreactivity. Combined treatment (CPA+EE) caused adverse effects, such as an increase in cell proliferation, higher AR and ERα immunoreactivity, prostatic intraepithelial neoplasia, cell degeneration and aging. In conclusion, the CPA-only treatment promoted antiandrogenic effects on the female gerbil prostate, whereas EE-only had a potent oestrogenic activity. However, when combined, EE overlapped the effects of CPA, changing the pattern of glandular hormonal regulation and stimulating the development of prostatic lesions in female gerbils.

Prenatal exposure to finasteride promotes sex-specific changes in gerbil prostate development

2019 ◽  
Vol 31 (11) ◽  
pp. 1719 ◽  
Author(s):  
Juliana S. Maldarine ◽  
Bruno D. A. Sanches ◽  
Ágata S. Cabral ◽  
Maria L. D. Lima ◽  
Luiz H. A. Guerra ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Prenatal Exposure ◽  
Oestrogen Receptor ◽  
Chemotherapeutic Agent ◽  
Three Dimensional ◽  
Prostatic Hyperplasia ◽  
Serological Analysis ◽  
Prostate Development ◽  
Female Prostate ◽  
Dimensional Reconstruction

Finasteride is a drug that is widely used in the treatment of benign prostatic hyperplasia, hair loss and even as a chemotherapeutic agent in the treatment of prostatic adenocarcinoma. However, its use is known to cause several side effects in adults and it can also cause changes in the embryonic development of the male prostate, which is a cause for concern given the possibility of the accumulation of finasteride in the environment. Nevertheless, no studies have investigated the effects of finasteride on the development of the prostate in females, which occurs in several species of mammals. To evaluate the effects of intrauterine exposure to finasteride (500μgkg−1 day−1) on postnatal prostate development in the Mongolian gerbil in the present study, we used immunohistochemistry, immunofluorescence, serological analysis and three-dimensional reconstruction techniques. Differences were observed in the effects of finasteride on periductal smooth muscle and cell proliferation between the sexes, as well as intersex differences in the presence of the androgen receptor, which was elevated in males, and the oestrogen receptor ERα, which was increased in females. Together, the data indicate that the female prostate has its own hormone dynamics and that there are sex-specific differences in the way in which the female prostate reacts to prenatal exposure to finasteride.

scholarly journals Testosterone Stimulates Growth and Secretory Activity of the Female Prostate in the Adult Gerbil (Meriones unguiculatus)1

2006 ◽  
Vol 75 (3) ◽  
pp. 370-379 ◽  
Author(s):  
Fernanda C.A. Santos ◽  
Rodrigo P. Leite ◽  
Ana M.G. Custódio ◽  
Karina P. Carvalho ◽  
Luiz H. Monteiro-Leal ◽  
...  
Keyword(s):  
Secretory Activity ◽  
Meriones Unguiculatus ◽  
Female Prostate

Anabolic effects of chrysin on the ventral male prostate and female prostate of adult gerbils (Meriones unguiculatus)

2018 ◽  
Vol 30 (9) ◽  
pp. 1180 ◽  
Author(s):  
Mônica S. Campos ◽  
Naiara C. S. Ribeiro ◽  
Rodrigo F. de Lima ◽  
Mariana B. Santos ◽  
Patrícia S. L. Vilamaior ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Intraepithelial Neoplasia ◽  
Meriones Unguiculatus ◽  
Epithelial Hyperplasia ◽  
Female Adult ◽  
Experimental Conditions ◽  
Cellular Toxicity ◽  
Male And Female ◽  
Female Prostate ◽  
Testicular Morphology

Chrysin is a bioflavonoid found in fruits, flowers, tea, honey and wine, which has antioxidant, anti-inflammatory, antiallergic and anticarcinogenic properties. This flavone has also been considered as beneficial for reproduction due its testosterone-boosting potential. Thus, the aim of this study was to evaluate the effects of chrysin on the prostate and gonads of male and female adult gerbils. In addition, a comparative analysis of the effects of testosterone on these same organs was conducted. Ninety-day-old male and female gerbils were treated with chrysin (50 mg kg−1 day−1) or testosterone cypionate (1 mg kg−1 week−1) for 21 days. The ventral male prostate and female prostate were dissected out for morphological, morphometric–stereological and ultrastructural assays. Testes and ovaries were submitted to morphological and morphometric­­–stereological analyses. Chrysin treatment caused epithelial hyperplasia and stromal remodelling of the ventral male and female prostate. Ultrastructurally, male and female prostatic epithelial cells in the chrysin group presented marked development of the organelles involved in the biosynthetic–secretory pathway, whereas cellular toxicity was observed only in female glands. Chrysin preserved normal testicular morphology and increased the number of growing ovarian follicles. Comparatively, testosterone treatment was detrimental to the prostate and gonads, since foci of prostatic intraepithelial neoplasia and gonadal degeneration were observed in both sexes. Thus, under the experimental conditions of this study, chrysin was better tolerated than testosterone in the prostate and gonads.

Effects of Papaya Leaf Extract (Carica papaya L.) on Cellular Proliferation and Apoptosis in Cervical Cancer Mice Model

2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Hela Cells ◽  
Leaf Extract ◽  
Caspase 3 ◽  
Methanol Extract ◽  
Negative Control ◽  
Proliferation Index ◽  
Control Group ◽  
P53 Expression

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.

Expression of β-Catenin in Hepatocellular Carcinoma

2001 ◽  
Vol 71 (3) ◽  
pp. 116-125
Author(s):  
Norina Basa ◽  
Daniela Lazar ◽  
Remus Cornea ◽  
Sorina Taban ◽  
Melania Ardelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Mitotic Index ◽  
Histological Grade ◽  
Proliferation Index ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
B Virus ◽  
Development And Evolution

Alteration of β-catenin expression is involved in the development and evolution of hepatocellular carcinoma (HCC); β-catenin is able to influence tumor cell proliferation. We analyzed the immunohistochemical (IHC) expression of β-catenin on a group of 32 patients diagnosed with HCC using the anti-β-catenin monoclonal antibody (clone E247). We correlated the expression of β-catenin with the proliferation index of Ki-67 (PI Ki-67), the mitotic index (MI) and other clinical and pathological features. We observed an altered β-catenin expression in 58.38% of all HCC cases. This expression was insignificantly correlated with tumor size (]5 cm) (p = 0.683), histological grade G1-G2 (p = 0.307), vascular invasion (p = 0.299) and advanced pT stage (p = 0.453); we obtained a significantly higher MI in HCC with altered β-catenin expression (p = 0.018), as compared to HCC without overexpression (1.66 � 1.37) (p = 0.038) and a PI Ki-67 of 22.49 � 20.1 and 28.24 � 18.2, respectively in tumors with altered β-catenin expression with insignificant differences compared to HCC without overexpression (25.95 � 15.2) (p = 0.682 and p = 0.731, respectively). According to the results we obtained, aberrant β-catenin expression in HCC was correlated with a high mitotic index, therefore playing an important role in tumor progression by stimulating tumor cell proliferation; non-nuclear β-catenin overexpression can have a pathological significance in HCC, especially in cases of HCC associated with hepatitis B virus (HBV) infection.

scholarly journals Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1816
Author(s):  
Jessica Amarù ◽  
Federica Barbieri ◽  
Marica Arvigo ◽  
Agnese Solari ◽  
Adriana Bajetto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Intracellular Signaling ◽  
Somatostatin Receptor ◽  
Combined Treatment ◽  
Primary Cultures ◽  
Receptor Subtype ◽  
Camp Accumulation ◽  
Gh Secretion ◽  
Somatostatin Receptor Ligands

First-generation somatostatin receptor ligands (fg-SRLs), such as octreotide (OCT), represent the first-line medical therapy in acromegaly. Fg-SRLs show a preferential binding affinity for somatostatin receptor subtype-2 (SST2), while the second-generation ligand, pasireotide (PAS), has high affinity for multiple SSTs (SST5 > SST2 > SST3 > SST1). Whether PAS acts via SST2 in somatotroph tumors, or through other SSTs (e.g., SST5), is a matter of debate. In this light, the combined treatment OCT+PAS could result in additive/synergistic effects. We evaluated the efficacy of OCT and PAS (alone and in combination) on growth hormone (GH) secretion in primary cultures from human somatotroph tumors, as well as on cell proliferation, intracellular signaling and receptor trafficking in the rat GH4C1 cell line. The results confirmed the superimposable efficacy of OCT and PAS in reducing GH secretion (primary cultures), cell proliferation, cAMP accumulation and intracellular [Ca2+] increase (GH4C1 cells), without any additive effect observed for OCT+PAS. In GH4C1 cells, co-incubation with a SST2-selective antagonist reversed the inhibitory effect of OCT and PAS on cell proliferation and cAMP accumulation, while both compounds resulted in a robust internalization of SST2 (but not SST5). In conclusion, OCT and PAS seem to act mainly through SST2 in somatotroph tumor cells in vitro, without inducing any additive/synergistic effect when tested in combination.

Noninvasive Carcinoma of the Breast: Angiogenesis and Cell Proliferation

2004 ◽  
Vol 128 (8) ◽  
pp. 893-896 ◽  
Author(s):  
Ying Cao ◽  
Gladell P. Paner ◽  
Leonard B. Kahn ◽  
Prabha B. Rajan
Keyword(s):  
Cell Proliferation ◽  
Microvessel Density ◽  
Carcinoma In Situ ◽  
Nuclear Grade ◽  
Proliferation Index ◽  
Carcinoma Of The Breast ◽  
Cell Proliferation Index ◽  
Noninvasive Carcinoma ◽  
Mib 1

Abstract Context.—Angiogenesis and the cell proliferation index can predict the prognosis of invasive breast carcinoma; however, little is known of their roles in noninvasive tumor. Objective.—To investigate the correlation of microvessel density and cell proliferation index with other histologic parameters (histologic type, nuclear grade, and mitotic count) in 65 cases of noninvasive carcinoma of the breast. Design.—Formalin-fixed, paraffin-embedded tissues from 65 cases of carcinoma in situ of the breast were immunostained with antibody against factor VIII antigen and proliferation-associated nuclear antigen MIB-1. The microvessel density was measured by counting the total number of microvessels around the carcinoma in situ per 10 low-power microscopic fields. The cell proliferation index was calculated by counting MIB-1–positive nuclei in 100 tumor cells. A χ2 test and Spearman rank correlation test were used for statistical analysis. Results.—The microvessel density and cell proliferation index of comedo-type, high-nuclear-grade ductal carcinomas in situ are significantly higher than those of either noncomedo type ductal carcinomas in situ or lobular carcinoma in situ (P < .001). Conclusions.—Angiogenesis and the cell proliferation index are active biological processes and may be considered as markers to separate low- and high-risk patients with noninvasive breast carcinomas.

scholarly journals The Involvement of Angiotensin Type 1 and Type 2 Receptors in Estrogen-Induced Cell Proliferation and Vascular Endothelial Growth Factor Expression in the Rat Anterior Pituitary

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hanna Lawnicka ◽  
Dorota Ptasinska-Wnuk ◽  
Slawomir Mucha ◽  
Jolanta Kunert-Radek ◽  
Marek Pawlikowski ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Blood Vessels ◽  
Proliferation Index ◽  
Pituitary Cells ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Rat Pituitary ◽  
Endothelial Growth Factor

The aim of our study was to examine the involvement of renin-angiotensin system (RAS) in estrogen-induced lactotropes proliferation and vascular endothelial growth factor (VEGF) expression in rat pituitary. The study was performed on Fisher 344 rats underwent 8-day treatment with diethylstilboestrol (DES). The proliferation index (PCNA) and VEGF expression in pituitary sections were estimated using immunohistochemical methods. Treatment with DES increased the number of PCNA-positive cells, VEGF-positive cells, and VEGF-positive blood vessels in pituitary. Stimulatory effect of estrogen on cell proliferation and VEGF expression in blood vessels was attenuated by losartan, PD123319, and captopril. VEGF immunoreactivity in pituitary cells of DES-treated rats was decreased by AT1 antagonist and not changed by AT2 blocker and ACE inhibitor. Our findings suggest the involvement of RAS in DES-induced cell proliferation and VEGF expression in pituitary. Both the AT1 and AT2 receptors appear to mediate the estrogen-dependent mitogenic and proangiogenic effects in rat pituitary.

scholarly journals Current Paradigm of Treatment for Pancreatic Neuroendocrine Tumor

2021 ◽  
Vol 26 (1) ◽  
pp. 24-32
Author(s):  
Min Je Sung ◽  
Moon Jae Chung
Keyword(s):  
Cell Proliferation ◽  
Medical Treatment ◽  
Neuroendocrine Tumor ◽  
Standard Treatment ◽  
Pancreatic Neuroendocrine Tumor ◽  
Somatostatin Analogues ◽  
Proliferation Index ◽  
Ki 67 ◽  
Grade 3 ◽  
Cell Proliferation Index

Pancreatic neuroendocrine tumor (PNET) refer to tumors originating from the islet of Langerhans and shows various prognosis based on the presence or absence of symptoms due to hormone secretion, the Ki-67 cell proliferation index, and the histologic grade, and according to the degree of disease progression defined by the tumor-node-metastasis (TNM) stage classification. The purpose of medical treatment for PNET is to control symptoms or inhibit tumor growth. Somatostatin analogues can be administered for the purpose of controlling symptoms caused by the secretion of specific hormones, and are accepted as effective drugs for inhibiting the progression of G1/G2 tumors based on World Health Organization (WHO) classification with a Ki-67 cell proliferation index less than 20%. Among the molecularly targeted agents, everolimus and sunitinib can be considered in patients with WHO G1/G2 PNET showing progression after somatostatin analog therapy. Cytotoxic chemotherapy is generally administered to patients with large tumor volume and rapidly progressing metastatic NET, and etoposide/cisplatin combination therapy has been considered as a standard treatment. For the patient group of Grade 3 PNET (well differentiated) newly classified by the WHO 2017 classification, guidelines for standard treatment have not yet been established. As it has been reported, studies are needed to evaluate the treatment response rate of somatostatin analogues or molecularly targeted therapies for the patient with Grade 3 PNET. It is important to consider a multidisciplinary approach with all possible treatment options including medical treatment, radical resection of primary or metastatic lesions, liver-directed therapies, and peptide receptor radionuclide therapy for the patients with PNET.

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