Publications by authors named "Silvana Gisele Pegorin DE Campos"

8 Publications

  • Page 1 of 1

Gestational and lactational xenoestrogen exposure disrupts morphology and inflammatory aspects in mammary gland of gerbil mothers during involution.

Environ Toxicol Pharmacol 2022 Jan 9;89:103785. Epub 2021 Dec 9.

Department of Biology, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University (Unesp), Rua Cristóvão Colombo, 2265, Jardim Nazareth, 15054-000 São José do Rio Preto, São Paulo, Brazil. Electronic address:

In the mammary gland (MG), the developmental window for gestational/lactational differentiation and growth is highly vulnerable to hormonal disruption. Here we describe that the MG involution process in female gerbil mothers is delayed by bisphenol A (BPA) exposure during gestation and lactation. The process is directly influenced by changes in expression of extracellular matrix proteases MMP-2, MMP-9, and FAP, and the incidence of collagen and elastin is reduced after 7 and 14 days of weaning. A pro-inflammatory environment in the late involution process was confirmed by higher expression of TNF-α, COX-2 and phospho-STAT3 n the MG stroma, allied to increases in the incidence of macrophages and mast cells. These aspects impacted the proliferative pattern of epithelial cells, which decreased on the 14th post-weaning day. These data confirm that the milk production window of susceptibility is vulnerable to the impact of BPA, which promotes a suggestive pro-tumoral microenvironment during mammary involution.
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http://dx.doi.org/10.1016/j.etap.2021.103785DOI Listing
January 2022

Do mineral and corn oil serve as potential endocrine disruptors in the gerbil prostate?

Reprod Toxicol 2019 12 27;90:141-149. Epub 2019 Sep 27.

Department of Biology, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. Electronic address:

Vegetable oils are frequently used as a vehicle in the administration of lipophilic drugs in animal tests. However, the composition of these oils may interfere with the results. One alternative to reduce this potential bias is the use of mineral oil, which is not supposed to interfere in the physiology of experimental models, since this oil is considered to be innocous. The present study shows for the first time the effects of the oral administration of corn and mineral on the prostate, demonstrating their interference in homeostasis and revealing their potential to act as endocrine disruptors. Mineral oil treatment increased the expression of AR and ERα and serum estradiol concentrations, while corn oil increased the expression of positive cells for both types of estrogen receptors. The variation in the expression of these hormone receptors resulted in morphological changes in the prostate.
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http://dx.doi.org/10.1016/j.reprotox.2019.09.004DOI Listing
December 2019

Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats.

Horm Cancer 2018 06 23;9(3):175-187. Epub 2018 Jan 23.

Department of Morphology, Institute of Biosciences, Sao Paulo State University (UNESP), Rua Professor Doutor Antonio Celso Wagner Zanin, 250, Botucatu, SP, 18618-689, Brazil.

Use of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors.
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http://dx.doi.org/10.1007/s12672-018-0323-zDOI Listing
June 2018

Pathological lesions and global DNA methylation in rat prostate under streptozotocin-induced diabetes and melatonin supplementation.

Cell Biol Int 2018 Apr 8;42(4):470-487. Epub 2018 Feb 8.

Department of Biology, Institute of Biosciences, Humanities and Exact Sciences, Univ Estadual Paulista-UNESP, 15054-970, São José do Rio Preto, SP, Brazil.

Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory, and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats. Melatonin was provided in drinking water (10 μg/kg/day) from age 5 weeks until the end of experiment. Diabetes was induced at 13 weeks by administration of streptozotocin (40 mg/kg, ip). Rats were euthanized at 14 or 21 weeks. Histological and stereological analyses were carried out and the incidence and density of malignant and pre-malignant lesions were assessed. Immunohistochemical assays of α-actin, cell proliferation (PCNA), Bcl-2, glutathione S-transferase (GSTPI), and DNA methylation (5-methylcytidine) were performed. Melatonin did not elicit conspicuous changes in the prostate of healthy animals; in diabetic animals there was a higher incidence of atrophy (93%), microinvasive carcinoma (10%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%), and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cell (smc) atrophy, especially at short-term diabetes-and normalized incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at long-term diabetes. MLT was effective in preventing inflammatory disorders and PIN under diabetic condition. Although MLT has antioxidant action, it did not influence DNA methylation and not avoid carcinogenesis at low doses.
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http://dx.doi.org/10.1002/cbin.10920DOI Listing
April 2018

Characterization of p16 and E6 HPV-related proteins in uterine cervix high-grade lesions of patients treated by conization with large loop excision.

Oncol Lett 2013 Jul 20;6(1):63-68. Epub 2013 May 20.

Department of Gynecology, Faculty of Medicine, São Paulo University, Cerqueira César, São Paulo, Brazil ;

Cervical cancer and its precursor lesions represent a significant public health problem for developing and less-developed countries. Cervical carcinogenesis is strongly correlated with persistent high-risk human papillomavirus (HPV) infection, which is mostly associated with expression of the p16 and E6 HPV-related proteins. The aim of this present study was to determine the expression of the p16 and E6 proteins in females with high-grade lesions treated with conization, and to discuss the role of these proteins as prognostic markers following treatment. In total, 114 females were treated for high-grade cervical intraepithelial neoplasia (CIN, grades 2/3) by conization with large loop excision of the transformation zone (LLETZ). Following surgery, the patients returned within 30-45 days for post-operative evaluation. A follow-up was conducted every 6 months for 2 years. At each follow-up appointment, a Pap smear, colposcopy and HPV DNA test were performed. E6 and p16 immunohistochemical tests were conducted on the surgical specimens. The positive expression of p16 was correlated with the presence of lesions with increased severity in the surgical specimens (P= 0.0001). The expression of E6 did not demonstrate the same correlation (P=0.131). The HPV DNA hybrid, collected in the first post-operative consultation as a predictor of the cytological abnormalities identified at the 24-month follow-up assessment, presented a sensitivity of 55.6%, a specificity of 84.8%, a positive predictive value of 33.3% and a negative predictive value of 93.3%. The role of p16INK4A as a marker of CIN was also demonstrated; the expression of p16 and E6, however, did not appear to be of any prognostic value in predicting the clearance of high-risk HPV following conization. A negative hybrid capture test was correlated with a disease-free outcome.
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http://dx.doi.org/10.3892/ol.2013.1356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742822PMC
July 2013

Ki-67 and CD100 immunohistochemical expression is associated with local recurrence and poor prognosis in soft tissue sarcomas, respectively.

Oncol Lett 2013 May 5;5(5):1527-1535. Epub 2013 Mar 5.

Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Barretos 14780-000;

Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors of >50 subtypes. However, STSs represent <1% of types of cancer. Despite this low frequency, the disease is aggressive and treatment, when possible, is based on traditional chemotherapies. A number of cases of resistance to adjuvant therapies have been reported. Metastases are commonly identified in STS patients during diagnosis and the development of effective clinical parameters is crucial for correct management of the disease. The use of biological markers in cancer is a useful tool to determine patient prognosis. Ki-67 is a protein marker for proliferation of somatic cells and is widely used in prognostic studies of various types of tumor, including STSs. Cluster of differentiation 100 (CD100) is a member of the semaphorin family. The family was initially described as axon guidance molecules important for angiogenesis, organogenesis, apoptosis and neoplasia. CD100 was previously utilized as a prognostic factor in tumors and also in STSs. In the present study, protein expression of Ki-67 and CD100 was analyzed by immunohistochemistry in samples of STS patients of the Barretos Cancer Hospital (Barretos, Brazil) to establish prognostic criteria of the disease. Results demonstrate a correlation between CD100 expression and poor prognosis, consistent with a previous study. Moreover, the expression of Ki-67 was identified to correlate with presence of local or locoregional recurrence. To the best of our knowledge, no large casuistic study has revealed this correlation between Ki-67 and local recurrence in STSs. The use of Ki-67 and CD100 as markers in clinical pathological analysis may be suitable as a prognostic criterion in disease progression.
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http://dx.doi.org/10.3892/ol.2013.1226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678859PMC
May 2013

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: proliferative and inflammatory disorders and a possible role of androgens.

Toxicology 2009 Aug 21;262(3):215-23. Epub 2009 Jun 21.

Department of Morphology, Institute of Biosciences, UNESP, Botucatu, SP, 18618-000, Brazil.

In the present study we evaluated the toxic effects on the male adult rat prostate of DBP exposure during fetal and lactational periods, because although many studies have addressed the influence of phthalates on the male reproductive system, only a few have discussed their possible effects on prostate development. Pregnant females were distributed into two experimental groups: Control (C) and Treated (T). The females of the T group received DBP (100mg/kg, by gavage) from gestation day 12 to postnatal day 21, while C rats received the vehicle (corn oil). In adulthood (90 days old), the animals were euthanized. The serum and testicular testosterone levels were measured. Ventral prostate was removed and weighed. Distal segment fragments of the ventral prostate were fixed and processed for histochemistry and immunohistochemistry to detect androgen receptor (AR) and Ki67 antigens. Protein extraction from ventral prostate fragments was performed for AR immunoblotting and Gelatin zymography for MMP-2 and MMP-9 (MMP, metalloproteinase). Stereological and histopathological analyses were also performed. Serum and testicular testosterone levels and prostate weight were comparable between groups. In the T group the relative proportions (%) of epithelial (C=32.86; T=42.04*) and stromal (C=21.61; T=27.88*) compartments were increased, while the luminal compartment was decreased (C=45.54; T=30.08*), *p<0.05. InT, disseminated inflammatory infiltrate in the stroma, associated or not with epithelial dysplasia and PIN (Prostatic Intraepithelial Neoplasia), was observed. Increases in AR expression, proliferation index and metalloproteinase 9 (MMP-9) activity were noted in T animals. In some T animals, collagen fibrils accumulated adjacent to the epithelium. As far as we are aware, this is the first report in the literature showing that phthalates could play a role in proliferative and inflammatory disorders of the rat prostate.
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http://dx.doi.org/10.1016/j.tox.2009.06.011DOI Listing
August 2009

Biological behavior of the gerbil ventral prostate in three phases of postnatal development.

Anat Rec A Discov Mol Cell Evol Biol 2006 Jul;288(7):723-33

Department of Cell Biology, Institute of Biology, UNICAMP, São Paulo, Brazil.

In this study, we characterized the gerbil's ventral prostate histology ultrastructurally and quantitatively throughout three phases of postnatal development (young, adult, and old) in order to comprehend its biological behavior and propensity to developing spontaneous lesions with aging. The gerbil prostate is composed of alveoli and ducts immersed in a stroma composed of smooth muscle, fibroblasts, collagen and elastic fibers and vessels. The prostate tissue components present morphological and quantitative aspects that vary according to age. Young animals have an immature gland with modest secretory activity. Synthetic activity remained stable in adult and old gerbil. However, prostatic morphology was altered in the aging, showing an increased epithelium and stromal fibrosis. The nuclei of the secretory cells increased with aging, whereas nucleoli presented few alterations during postnatal development. The epithelial proliferation and stromal remodeling noted in this study indicate that the gerbil prostate may respond to the androgen declines typical of senescence through epithelial proliferation and stromal remodeling.
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http://dx.doi.org/10.1002/ar.a.20347DOI Listing
July 2006
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