Luciana Boffoni Gentile - Academia.edu (original) (raw)

Papers by Luciana Boffoni Gentile

Brazilian Journal of Veterinary Research and Animal Science, Dec 10, 2015

Melanomas are the most common oral malignancy in dogs. Cell proliferation and connexin expression... more Melanomas are the most common oral malignancy in dogs. Cell proliferation and connexin expression has been shown to differ in canine melanotic and amelanotic oral melanomas. This study aimed to analyze the c-Kit protein expression in melanotic and amelanotic melanomas from canine buccal cavity. A total of 34 canine buccal melanomas (19 melanotic and 15 amelanotic).were collected. The amelanotic melanomas presented faster evolution and higher incidence of metastasis than melanotic tumors. A significantly higher number of c-Kit positive cells were observed in amelanotic neoplasms. In addition, the intensity of c-Kit immunolabeling was predominantly stronger in amelanotic melanomas. These results confirm a potential role for c-Kit in canine oral melanomas with clear differences in expression patterns between the two histological types of tumor, melanotic and amelanotic. This study highlights the importance of a detailed study of c-Kit mutations in canine oral melanomas to better understand the molecular mechanisms implicated in the development of this disease.

Copyright © 2015 Luciana Boffoni Gentile et al.This is an open access article distributed under t... more Copyright © 2015 Luciana Boffoni Gentile et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibitor (indomethacin) on tumor growth of Ehrlich Ascites Tumor (EAT) in mice, using as parameters the tumor growth and cytokine profile. Mice were inoculated with EAT cells and treated with indomethacin. After 1, 3, 6, 10, and 13 days the animals were evaluated for the secretion of TNF

Frontiers in Veterinary Science, 2021

Mammary tumors are the most prevalent neoplasms in non-neutered female dogs, with genetic and epi... more Mammary tumors are the most prevalent neoplasms in non-neutered female dogs, with genetic and epigenetic alterations contributing to canine mammary carcinogenesis. This study quantified global DNA methylation in 5-methylcytosine (5mC)-immunostained canine mammary tumor samples and established histopathological and clinical correlations. A total of 91 formalin-fixed paraffin-embedded mammary tumor samples from female dogs were retrospectively selected and subjected to immunohistochemistry using an anti-5mC mouse monoclonal antibody. We evaluated 5mC+ stained nuclei of neoplastic epithelial cells in canine mammary glands to obtain semiquantitative histoscores based on staining intensity. Survival rates were estimated based on owners' or veterinary records. Histological samples comprised 28 and 63 benign and malignant canine mammary gland tumors, respectively. Results revealed significant differences between global DNA methylation patterns when mammary samples were categorized as b...

Frontiers in Oncology, 2019

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Frontiers in microbiology, 2018

Chagas disease is a neglected disease caused by the protozoan and affects 8 million people worldw... more Chagas disease is a neglected disease caused by the protozoan and affects 8 million people worldwide. The main chemotherapy is based on benznidazole. The efficacy in the treatment depends on factors such as the parasite strain, which may present different sensitivity to treatment. In this context, the expression of ABC transporters has been related to chemotherapy failure. ABC transporters share a well-conserved ABC domain, responsible for ATP binding and hydrolysis, whose the energy released is coupled to transport of molecules through membranes. The most known ABC transporters are ABCB1 and ABCC1, involved in the multidrug resistance phenotype in cancer, given their participation in cellular detoxification. In , 27 ABC genes were identified in the genome. Nonetheless, only four ABC genes were characterized: ABCA3, involved in vesicular trafficking; ABCG1, overexpressed in strains naturally resistant to benznidazole, and P-glycoprotein 1 and 2, whose participation in drug resistanc...

Frontiers in oncology, 2018

The tumor microenvironment (TME) is composed by cellular and non-cellular components. Examples in... more The tumor microenvironment (TME) is composed by cellular and non-cellular components. Examples include the following: (i) bone marrow-derived inflammatory cells, (ii) fibroblasts, (iii) blood vessels, (iv) immune cells, and (v) extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. "Lactagenic" or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10...

International Journal of Environmental and Agriculture Research, 2017

Natural and synthetic estrogens have been detected in rivers, lakes and estuaries in many parts o... more Natural and synthetic estrogens have been detected in rivers, lakes and estuaries in many parts of the world. Primary sources of these compounds are domestic and industrial effluents, which are not deleted after the water treatment. Estrogen has been the endocrine disruptor most researched to be very active biologically and be the etiologic agent of diverse types of cancer and other conditions such as endometriosis, precocious puberty, feminization, masculinization, sterility. In this context, we use water of 36 natural reservoirs or dams, in a bioassay to characterize their estrogenicity in culture of MCF7 cells and obtained high concentration of estrogen in samples taken in Ibiúna and Equestrian Santo Amaro / SP. However, certain concentration in our samples for most water samples from different regions was very close to the limit of quantification by bioassay and estrogen was in fmol. It has been shown that e-screen assay with MCF7 cells is a sensitive and stable tool for quantitative analysis of estrogenicity of water and can easily be developed and implemented for routine for estrogen quantification also in animal food and man, aqueous and plastics etc.

PLOS ONE, 2017

There are many factors which make canine cancer like cancer in humans. The occurrence of spontane... more There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, β and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRβ and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development.

Frontiers in microbiology, 2017

Trans-sialidase from Trypanosoma cruzi (Tc-TS) belongs to a superfamily of proteins that may have... more Trans-sialidase from Trypanosoma cruzi (Tc-TS) belongs to a superfamily of proteins that may have enzymatic activity. While enzymatically active members (Tc-aTS) are able to transfer sialic acid from the host cell sialyl-glycoconjugates onto the parasite or to other molecules on the host cell surface, the inactive members (Tc-iTS) are characterized by their lectinic properties. Over the last 10 years, several papers demonstrated that, individually, Tc-aTS or Tc-iTS is able to modulate several biological events. Since the genes encoding Tc-iTS and Tc-aTS are present in the same copy number, and both proteins portray similar substrate-specificities as well, it would be plausible to speculate that such molecules may compete for the same sialyl-glycan structures and govern numerous immunobiological phenomena. However, their combined effect has never been evaluated in the course of an acute infection. In this study, we investigated the ability of both proteins to modulate the production ...

Brazilian Journal of Veterinary Research and Animal Science, 2015

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Jan 27, 2016

Reactive oxygen species (ROS) are produced by both enzymatic and non-enzymatic systems within euk... more Reactive oxygen species (ROS) are produced by both enzymatic and non-enzymatic systems within eukaryotic cells and play important roles in cellular physiology and pathophysiology. Although physiological concentrations are crucial for ensuring cell survival, ROS overproduction is detrimental to cells, and considered key-factors for the development of several diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Cancer cells are usually submitted to higher ROS levels that further stimulate malignant phenotype through stimulus to sustained proliferation, death evasion, angiogenesis, invasiveness, and metastasis. The role of ROS on breast cancer etiology and progression is being progressively elucidated. However, less attention has been given to the development of redox system-targeted strategies for breast cancer therapy. In this review, we address the basic mechanisms of ROS production and scavenging in breast tumor cells, and the emerging possibilities o...

Mediators of Inflammation, 2015

The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibit... more The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibitor (indomethacin) on tumor growth of Ehrlich Ascites Tumor (EAT) in mice, using as parameters the tumor growth and cytokine profile. Mice were inoculated with EAT cells and treated with indomethacin. After 1, 3, 6, 10, and 13 days the animals were evaluated for the secretion of TNFα, IL-1α, IL-2, IL-4, IL-6, IL-10, and IL-13 and PGE2level in peritoneal cavity. The results have shown that EAT induces PGE2production and increases tumor cells number from the 10th day. The cytokine profile showed EAT induces production of IL-6 from 10th day and of IL-2 on 13th day; the other studied cytokines were not affected in a significant way. The indomethacin treatment of EAT-bearing mice inhibited the tumor growth and PGE2synthesis from the 10th day. In addition, the treatment of EAT-bearing mice with indomethacin has stimulated the IL-13 production and has significantly inhibited IL-6 in the 13th day...

BMC Proceedings, 2013

Gentile et al.: Evaluation of different methods to obtain primary mammary epithelial cell culture... more Gentile et al.: Evaluation of different methods to obtain primary mammary epithelial cell cultures from canine spontaneous mammary gland tumors. BMC Proceedings 2013 7(Suppl 2): P41.

Brazilian Journal of Veterinary Research and Animal Science, 2014

Os tumores das glândulas mamárias são as neoplasias mais comuns em cadelas em nosso país; no enta... more Os tumores das glândulas mamárias são as neoplasias mais comuns em cadelas em nosso país; no entanto, são poucos os trabalhos brasileiros dedicados ao estudo clinicopatológico e de sobrevida nesta doença. O presente trabalho teve por objetivo o estudo clínico e patológico dos tumores mamários caninos na Região Metropolitana de Santos, uma área no estado de São Paulo com uma população canina estimada em 120 mil animais. Dados de 14.298 cães foram coletados retrospectivamente dos prontuários médicos do Hospital Veterinário da Universidade Metropolitana de Santos – São Paulo – Brasil. Durante o período do estudo, foram atendidas 317 fêmeas com diagnóstico histopatológico de neoplasia, dos quais, 170 se referiam a lesões mamárias epiteliais distribuídas em 13 tumores benignos, 152 malignos (89,4% dos diagnósticos) e 5 lesões epiteliais não-neoplásicas (hiperplasia ductal). O tumor mais frequente foi o carcinoma tubular (38,2% dos tumores malignos) e tumores de grau I, respondendo por 73...

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2010

Cyclooxygenase (COX)-2-derived prostaglandin (PG)E 2 controls many aspects of colon cancer develo... more Cyclooxygenase (COX)-2-derived prostaglandin (PG)E 2 controls many aspects of colon cancer development, modulating from apoptosis resistance and cell proliferation to angiogenesis, invasion, and metastasis. Here, we investigated the role of different phospholipases (PL)A 2 in supplying arachidonic acid (AA) for COX-2-dependent PGE 2 generation and signaling pathways involved in activation of colon cancer cells by a physiologically relevant stimulus. To emulate the hypertonic environment found physiologically in colon, the human colon cancer cell line Caco-2 was maintained in hypertonic complete DMEM medium. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked AA release, COX-2 induction and PGE 2 generation. Selective secretory (s)PLA 2 and calcium-independent (i)PLA 2 inhibitors did not modify PGE 2 generation, while either COX-2 or cytosolic (c)PLA 2 inhibitors completely inhibited PGE 2 generation. cPLA 2-a was responsible for AA supply for PGE 2 generation, but had no role in COX-2 induction. Mitogen-activated protein (MAP) kinases, ERK 1/2, p38, and JNK, participated in the signaling events that lead to PGE 2 generation by modulating AA release, but only ERK 1/2 was involved in COX-2 upregulation. Our results indicate that hypertonic stress activates PGE 2 generation by Caco-2 cells through a mechanism dependent on MAP kinase-regulated AA mobilization, increased cPLA 2-a activity, and COX-2 induction.

Veterinary Research Communications, 2013

Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently ... more Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.