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Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.
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Neoplasias da Mama , Ciclo-Oxigenase 2 , Progressão da Doença , Óxido Nítrico Sintase Tipo II , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Ciclo-Oxigenase 2/metabolismo , Feminino , Óxido Nítrico Sintase Tipo II/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Animais , Óxido Nítrico/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Espécies Reativas de Nitrogênio/metabolismoRESUMO
A strong correlation between NOS2 and COX2 tumor expression and poor clinical outcomes in ER breast cancer has been established. However, the mechanisms of tumor induction of these enzymes are unclear. Analysis of The Cancer Genome Atlas (TCGA) revealed correlations between NOS2 and COX2 expression and Th1 cytokines. Herein, single-cell RNAseq analysis of TNBC cells shows potent NOS2 and COX2 induction by IFNγ combined with IL1ß or TNFα. Given that IFNγ is secreted by cytolytic lymphocytes, which improve clinical outcomes, this role of IFNγ presents a dichotomy. To explore this conundrum, tumor NOS2, COX2, and CD8+ T cells were spatially analyzed in aggressive ER-, TNBC, and HER2 + breast tumors. High expression and clustering of NOS2-expressing tumor cells occurred at the tumor/stroma interface in the presence of stroma-restricted CD8+ T cells. High expression and clustering of COX2-expressing tumor cells extended into immune desert regions in the tumor core where CD8+ T cell penetration was limited or absent. Moreover, high NOS2-expressing tumor cells were proximal to areas with increased satellitosis, suggestive of cell clusters with a higher metastatic potential. Further in vitro experiments revealed that IFNγ + IL1ß/TNFα increased the elongation and migration of treated tumor cells. This spatial analysis of the tumor microenvironment provides important insight into distinct neighborhoods where stroma-restricted CD8+ T cells exist proximal to NOS2-expressing tumor niches that could have increased metastatic potential.
Assuntos
Interferon gama , Neoplasias de Mama Triplo Negativas , Microambiente Tumoral , Feminino , Humanos , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A strong correlation between NOS2 and COX2 tumor expression and poor clinical outcomes in ER-breast cancer has been established. However, mechanisms of tumor induction of these enzymes are unclear. Analysis of The Cancer Genome Atlas (TCGA) revealed correlations between NOS2 and COX2 expression and Th1 cytokines. Herein, single cell RNAseq analysis of TNBC cells shows potent NOS2 and COX2 induction by IFNγ combined with IL1ß or TNFα. Given that IFNγ is secreted by cytolytic lymphocytes, which improve clinical outcomes, this role of IFNγpresents a dichotomy. To explore this conundrum, tumor NOS2, COX2, and CD8 + T cells were spatially analyzed in aggressive ER-, TNBC, and HER2+ breast tumors. High expression and clustering of NOS2-expressing tumor cells occurred at the tumor/stroma interface in the presence of stroma-restricted CD8 + T cells. High expression and clustering of COX2-expressing tumor cells extended into immune desert regions in the tumor core where CD8 + T cell penetration was limited or absent. Moreover, high NOS2-expressing tumor cells were proximal to areas with increased satellitosis suggestive of cell clusters with a higher metastatic potential. Further in vitro experiments revealed that IFNγ+IL1ß/TNFα increased elongation and migration of treated tumor cells. This spatial analysis of the tumor microenvironment provides important insight of distinct neighborhoods where stroma-restricted CD8 + T cells exist proximal to NOS2-expressing tumor niches that could have increased metastatic potential.
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Testicular ultrasound enables the evaluation of changes in the testicular parenchyma. This study aimed to report the occurrence of hypoechogenic testicular alterations and their relationship with semen quality in five breeding buffaloes. Two buffaloes presented with hyperechoic points characteristic of fibrosis and anechoic density content between the parietal and visceral tunica. The two bulls without ultrasonographic changes showed higher average trajectory speed, linear velocity, curvilinear velocity, amplitude of lateral displacement of the spermatic head, total motility, progressive motility, fast speed, and acrosomal membrane values within the normal range. The number of spermatozoa with major and total defects was higher in the group of animals without alterations. The three buffaloes that presented with testicular alterations produced semen within established freezing standards.
Assuntos
Búfalos , Análise do Sêmen , Testículo , Animais , Bovinos , Masculino , Cruzamento , Criopreservação/normas , Criopreservação/veterinária , Análise do Sêmen/veterinária , Preservação do Sêmen/normas , Preservação do Sêmen/veterinária , Motilidade dos Espermatozoides , Espermatozoides/patologia , Testículo/diagnóstico por imagem , Testículo/patologia , Ultrassonografia/veterináriaRESUMO
This study evaluated the follicular atresia, cell proliferation, and anti-Mullerian hormone action in Aotus nancymae and Sapajus macrocephalus during three sexual phases (follicular, luteal, and gestational). Follicular quantification and immunolocalization of Caspase-3 protein, B-cell lymphoma 2 (BCL-2), proliferating cell nuclear antigen (PCNA), and anti-Mullerian hormone (AMH) were performed. A significant difference in the quantification between preantral and antral follicles, with a progressive decrease in the antrals, was identified. Protein and hormonal markers varied significantly between follicle cell types (A. nancymae p = 0.001; S. macrocephalus, p = 0.002). Immunostaining in the preantral and antral follicles was present in all sexual phases; for Caspase-3, in granulosa cells, oocytes, and stroma; for BCL-2, in granulosa cells, oocytes, and theca; and for PCNA and AMH, in oocytes and granulosa cells. The immunostaining for Caspase-3 was more expressive in the preantral follicles (follicular phase, p < 0.05), while that for BCL-2 and PCNA was more expressive in the antral follicles of the follicular phase. The AMH was more expressive in the primary and antral follicles of nonpregnant females, in both the follicular and luteal phases. Our results contribute to understanding the ovarian follicular selection, recruitment, and degeneration of these species.
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During the Zika virus (ZIKV) outbreak and after evidence of its sexual transmission was obtained, concerns arose about the impact of the adverse effects of ZIKV infection on human fertility. In this study, we evaluated the clinical-laboratory aspects and testicular histopathological patterns of pubertal squirrel monkeys (Saimiri collinsi) infected with ZIKV, analyzing the effects at different stages of infection. The susceptibility of S. collinsi to ZIKV infection was confirmed by laboratory tests, which detected viremia (mean 1.63 × 106 RNA copies/µL) and IgM antibody induction. Reduced fecal testosterone levels, severe testicular atrophy and prolonged orchitis were observed throughout the experiment by ultrasound. At 21 dpi, testicular damage associated with ZIKV was confirmed by histopathological and immunohistochemical (IHC) analyses. Tubular retraction, the degeneration and necrosis of somatic and germ cells in the seminiferous tubules, the proliferation of interstitial cells and an inflammatory infiltrate were observed. ZIKV antigen was identified in the same cells where tissue injuries were observed. In conclusion, squirrel monkeys were found to be susceptible to the Asian variant of ZIKV, and this model enabled the identification of multifocal lesions in the seminiferous tubules of the infected group evaluated. These findings may suggest an impact of ZIKV infection on male fertility.
Assuntos
Infecção por Zika virus , Zika virus , Animais , Masculino , Humanos , Zika virus/genética , Testículo , SaimiriRESUMO
Cancer is a major public health concern worldwide responsible for high morbidity and mortality rates. Alternative therapies have been extensively investigated, and plant-derived compounds have caught the attention of the scientific community due to their chemopreventive and anticancer effects. Sulforaphane (SFN) is one of these naturally occurring agents, and studies have shown that it is able to target a specific cancer cell population displaying stem-like properties, known as cancer stem cells (CSCs). These cells can self-renewal and differentiate to form highly heterogeneous tumor masses. Notably, most of the conventional chemotherapeutic agents cannot target CSCs once they usually exist in a quiescent state and overall, the available cytotoxic drugs focus on highly dividing cells. This is, at least in part, one of the reasons why some oncologic patients relapse after standard therapy. In this review we bring together studies supporting not only the chemopreventive and anticancer properties of SFN, but especially the emerging anti-CSCs effects of this natural product and its potential to be used with conventional antineoplastic drugs in the clinical setting.
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Estrogen receptor-negative (ER-) breast cancer is an aggressive breast cancer subtype with limited therapeutic options. Upregulated expression of both inducible nitric oxide synthase (NOS2) and cyclo-oxygenase (COX2) in breast tumors predicts poor clinical outcomes. Signaling molecules released by these enzymes activate oncogenic pathways, driving cancer stemness, metastasis, and immune suppression. The influence of tumor NOS2/COX2 expression on the landscape of immune markers using multiplex fluorescence imaging of 21 ER- breast tumors were stratified for survival. A powerful relationship between tumor NOS2/COX2 expression and distinct CD8+ T cell phenotypes was observed at 5 years post-diagnosis. These results were confirmed in a validation cohort using gene expression data showing that ratios of NOS2 to CD8 and COX2 to CD8 are strongly associated with poor outcomes in high NOS2/COX2-expressing tumors. Importantly, multiplex imaging identified distinct CD8+ T cell phenotypes relative to tumor NOS2/COX2 expression in Deceased vs Alive patient tumors at 5-year survival. CD8+NOS2-COX2- phenotypes defined fully inflamed tumors with significantly elevated CD8+ T cell infiltration in Alive tumors expressing low NOS2/COX2. In contrast, two distinct phenotypes including inflamed CD8+NOS2+COX2+ regions with stroma-restricted CD8+ T cells and CD8-NOS2-COX2+ immune desert regions with abated CD8+ T cell penetration, were significantly elevated in Deceased tumors with high NOS2/COX2 expression. These results were supported by applying an unsupervised nonlinear dimensionality-reduction technique, UMAP, correlating specific spatial CD8/NOS2/COX2 expression patterns with patient survival. Moreover, spatial analysis of the CD44v6 and EpCAM cancer stem cell (CSC) markers within the CD8/NOS2/COX2 expression landscape revealed positive correlations between EpCAM and inflamed stroma-restricted CD8+NOS2+COX2+ phenotypes at the tumor/stroma interface in deceased patients. Also, positive correlations between CD44v6 and COX2 were identified in immune desert regions in deceased patients. Furthermore, migrating tumor cells were shown to occur only in the CD8-NOS2+COX2+ regions, identifying a metastatic hot spot. Taken together, this study shows the strength of spatial localization analyses of the CD8/NOS2/COX2 landscape, how it shapes the tumor immune microenvironment and the selection of aggressive tumor phenotypes in distinct regions that lead to poor clinical outcomes. This technique could be beneficial for describing tumor niches with increased aggressiveness that may respond to clinically available NOS2/COX2 inhibitors or immune-modulatory agents.
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Multiple immunosuppressive mechanisms exist in the tumor microenvironment that drive poor outcomes and decrease treatment efficacy. The co-expression of NOS2 and COX2 is a strong predictor of poor prognosis in ER- breast cancer and other malignancies. Together, they generate pro-oncogenic signals that drive metastasis, drug resistance, cancer stemness, and immune suppression. Using an ER- breast cancer patient cohort, we found that the spatial expression patterns of NOS2 and COX2 with CD3+CD8+PD1- T effector (Teff) cells formed a tumor immune landscape that correlated with poor outcome. NOS2 was primarily associated with the tumor-immune interface, whereas COX2 was associated with immune desert regions of the tumor lacking Teff cells. A higher ratio of NOS2 or COX2 to Teff was highly correlated with poor outcomes. Spatial analysis revealed that regional clustering of NOS2 and COX2 was associated with stromal-restricted Teff, while only COX2 was predominant in immune deserts. Examination of other immunosuppressive elements, such as PDL1/PD1, Treg, B7H4, and IDO1, revealed that PDL1/PD1, Treg, and IDO1 were primarily associated with restricted Teff, whereas B7H4 and COX2 were found in tumor immune deserts. Regardless of the survival outcome, other leukocytes, such as CD4 T cells and macrophages, were primarily in stromal lymphoid aggregates. Finally, in a 4T1 model, COX2 inhibition led to a massive cell infiltration, thus validating the hypothesis that COX2 is an essential component of the Teff exclusion process and, thus, tumor evasion. Our study indicates that NOS2/COX2 expression plays a central role in tumor immunosuppression. Our findings indicate that new strategies combining clinically available NOS2/COX2 inhibitors with various forms of immune therapy may open a new avenue for the treatment of aggressive ER-breast cancers.
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The study of fetal development allows for evaluating the different strategies adopted by mammal species to maximize neonatal survival. Autonomous locomotion is fundamental for newborns to perform foraging activities and increases newborn survival from predation. In this study, we assess the gestational bone development of 53 collared (CP, Pecari tajacu) and 61 white-lipped (WLP, Tayassu pecari) peccaries, collected through the collaboration of subsistence hunters in the Amazon. The bone mineralization and biometry of the axial and appendicular skeleton were assessed by ultrasound examinations, and the timing of the main bone developmental events was calculated in relation to the total dorsal length (TDL) and the percentage of the total gestational period (GP). The first US signs of mineralization of the axial skeleton in CP and WLP were observed in fetuses with 3.4 cm (42 gestation days, 30% GPCP ) and 5.1 cm (51 gestation days, 32% GPWLP ). The early development of the appendicular skeleton was observed by the synchronic appearance of the mineralized scapula, humerus, radius, ulna, ilium, ischium, femur, tibia, and fibula at 36% GPCP (50 gestation days), and 35% GPWLP (56 gestation days). The pubis was mineralized in fetuses at 55% GPCP (75 gestation days) and 59% GPWLP (94 gestation days). The mineralization was observed in all autopod bones at 79% GPCP (109 gestation days) and 67% GPWLP (106 gestation days). All primary ossification centers in long bones of thoracic and pelvic limbs were mineralized in advanced fetuses (GPCP and GPWLP ≥75%). The mineralized patella was not observed in advanced fetuses in either species. Secondary ossification centers first appeared at the distal epiphysis of the femur in the CP (99 gestation days, 72% GPCP ) and the distal epiphysis of the radius, femur, and tibia in the WLP (106 gestation days, 67% GPWLP ). Advanced fetuses of CP and WLP presented 60% (15/25) and 68% (17/25) of the total secondary ossification centers observed present in the adult domestic pig, while newborns from the domestic pig presented 52% (13/25). The early intrauterine development of the skeletal system in both peccary species suggests a precocial development strategy, which likely correlates with neonatal ability to escape predators and reduces the dependence on parental care.
Assuntos
Artiodáctilos , Animais , Desenvolvimento Ósseo , Desenvolvimento Fetal , Feto/diagnóstico por imagem , Sus scrofa , SuínosRESUMO
Anthocyanins have been associated with beneficial effects on human health. Cancer has been one of the main public health issues due to its aggressiveness and high mortality rate. This systematic review aimed to address recent research (from January 2000 to September 2021) on the anticancer activity of anthocyanins assessed by in vitro assays. The selected studies revealed that anthocyanins have anticancer potential by inhibiting cancer cell viability and proliferation, controlling cell cycle, and promoting apoptosis.
Assuntos
Antocianinas , Extratos Vegetais , Antocianinas/metabolismo , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Apoptose , Proliferação de Células , Sobrevivência Celular , Humanos , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Comparative studies of kidney morphophysiology in nonhuman primates can help us investigate interspecies differences in growth and aging patterns. METHODS: We tested the effect of age and sex in renal morphophysiology in 21 Alouatta caraya and 21 Sapajus apella (age range = 0.5-26 years) by ultrasound, red blood cell (RBC) count, and kidney function tests. RESULTS: A. caraya had greater growth rate and absolute renal volume than S. apella, but the latter showed a greater relative renal volume and RBC count. There was a negative relationship between RBC and age, a positive relationship between creatinine and body mass, and an apparent negative relationship between creatinine and age only in S. apella. CONCLUSIONS: Our results indicate that A. caraya has a faster aging mechanism than S. apella, and the higher relative kidney volume in S. apella is suggestive of high metabolic demands in this species.
Assuntos
Alouatta caraya , Alouatta , Alouatta/fisiologia , Animais , Creatinina , Rim/diagnóstico por imagem , Rim/fisiologia , Primatas , Sapajus apellaRESUMO
BACKGROUND: The "starry sky" (SK) liver is ultrasonographic pattern characterized by multiple hyperechogenic foci in hepatic parenchyma. The study aimed to characterize the microscopic hepatic lesions in captive owl monkeys with SK liver. METHODS: Thirty-seven clinically healthy owl monkeys had their liver scanned and 18 of them had liver biopsy. Animals with SK and peliosis hepatis (PH) were subjected to immunohistochemical and molecular screening for Bartonella spp. RESULTS: SK liver occurred in 59.4% (22/37) of the owl monkeys. Biopsied animals showed steatosis, hydropic degeneration, hemosiderosis, PH, and multifocal granulomatous hepatitis. Two monkeys had SK, granulomatous hepatitis, and PH which were negative for Bartonella spp. CONCLUSIONS: PH and granulomatous hepatitis associated with hepatocellular degenerative lesions may present as hyperechoic nodular liver lesions consisted of SK liver; therefore, concomitant occurrence of two lesions or more contributed to the hepatic SK pattern among owl monkeys and such cases might be clinically monitored.
Assuntos
Aotidae , Hepatopatias , Animais , Granuloma , Fígado/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Hepatopatias/veterináriaRESUMO
OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient's response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.
Assuntos
Neoplasias da Mama , MicroRNAs , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/genética , Brasil , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , MicroRNAs/genética , Terapia Neoadjuvante , Estadiamento de Neoplasias , PrognósticoRESUMO
During the Zika virus (ZIKV) outbreak in Brazil (2015-2016), the clinical manifestations associated with its infection were complex and included miscarriage and congenital malformations, not previously described. In this study, we evaluated the prenatal conditions of pregnant female squirrel monkeys (Saimiri collinsi) infected during different gestational thirds (GTs) and assessed all clinical aspects, diagnostic imaging, viremia and the immune response. In our study, 75% of the infected animals in the 1st GT group had significant clinical manifestations, such as miscarriage and prolonged viremia associated with a late immune response. Consequently, their neonates showed fetal neuropathology, such as cerebral hemorrhage, lissencephaly or malformations of the brain grooves, ventriculomegaly, and craniofacial malformations. Thus, our study demonstrated the relevance of pregnant squirrel monkeys as a model for the study of ZIKV infection in neonates due to the broad clinical manifestations presented, including the typical congenital Zika syndrome manifestations described in humans.
Assuntos
Doenças Fetais , Microcefalia , Doenças dos Macacos , Saimiri/virologia , Infecção por Zika virus , Zika virus/metabolismo , Animais , Brasil/epidemiologia , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/metabolismo , Doenças Fetais/veterinária , Doenças Fetais/virologia , Microcefalia/embriologia , Microcefalia/metabolismo , Microcefalia/virologia , Doenças dos Macacos/epidemiologia , Doenças dos Macacos/metabolismo , Doenças dos Macacos/virologia , Gravidez , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/veterináriaRESUMO
The study evaluated an echo-guided oocyte recovery technique in owl monkeys. Twelve females were selected for the transabdominal ovum retrieval technique. This procedure collected twenty-six follicles, of which nine oocytes were recovered, without harm to the animals. The technique is feasible and is a minimally invasive protocol for neotropical primates.
Assuntos
Aotidae/fisiologia , Oócitos/fisiologia , Ultrassonografia/métodos , Animais , FemininoRESUMO
OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient's response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.
Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , MicroRNAs/genética , Prognóstico , Brasil , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/genética , Terapia Neoadjuvante , Estadiamento de NeoplasiasRESUMO
ABSTRACT: Canine atopic dermatitis (CAD) is a pruritic, chronic inflammatory disease, recurrent and genetically predisposed, which is the second most frequent allergic skin disorder, and ranks second among all the causes of pruritus in dogs worldwide. Given the absence of data on the occurrence of CAD in the northern region of Brazil, the aim of the current study was to conduct a survey to define the prevalence of canine atopic dermatitis attended at the Dermatology Department of the Mário Dias Teixeira Veterinary Hospital of the Universidade Federal Rural da Amazônia (HOVET-UFRA). To determine the prevalence of CAD, a retrospective survey was carried out of clinical records and results of dermatological examinations conducted at the Dermatology Department of HOVET-UFRA Belém, Pará from October 2018 to October 2019. During this period, 456 dogs were examined, of which 25.65% (117) were diagnosed with atopic dermatitis. Among the animals diagnosed, 62.4% (73) were females and 51.7% (29) were of the Shih-tzu breed. This level of atopic dermatitis is considered high. There are still no exact data on the incidence and prevalence of this dermatopathy, with described occurrence ranging from 3 to 15% of the canine population, a geographical relationship may be present. Although a sex-related predisposition has not been proven, a higher incidence of atopy in females is described, which indicated this may be the case. The most commonly diagnosed dogs in this study were the Shih-tzu breed. It is suspected that the regional popularity of some breeds, or the different genetic backgrounds in different geographical areas, may affect the predominance of CAD in some breeds. The results of the present study demonstrate the need for more research on the prevalence of canine atopic dermatitis, and better means of characterizing the population of atopic dogs in the region, so that it is possible to obtain a reliable epidemiological profile.
RESUMO: A dermatite atópica canina (DAC) é uma doença inflamatória crônica e pruriginosa recorrente e geneticamente predisposta, que se destaca como o segundo transtorno cutâneo alérgico mais frequente e ocupa o segundo lugar entre todas as causas de prurido em cães. Diante da ausência de dados da ocorrência de DAC na região Norte do Brasil, objetivou-se realizar um levantamento de dados para definir a prevalência de dermatite atópica canina atendida no Serviço de Dermatologia do Hospital Veterinário Mário Dias Teixeira da Universidade Federal Rural da Amazônia (HOVET-UFRA). Foi realizado um levantamento retrospectivo através dos registros clínicos e dos resultados de exames dermatológicos com base nos atendimentos dermatológicos no setor de Dermatologia do HOVET-UFRA Belém/Pará, de outubro de 2018 a outubro de 2019 para determinar a prevalência de DAC. Nesse período, foram atendidos 456 cães e destes, 25,65% (117) foram diagnosticados com dermatite atópica. Dentre os animais diagnosticados, 62,4% (73) eram fêmeas e 51,7% (29) eram da raça Shih-tzu. Neste estudo houve uma alta prevalência de cães com Dermatite atópica. Ainda não existem dados exatos sobre a incidência e a prevalência desta dermatopatia, com ocorrência descrita variando de 3 a 15% da população canina, podendo ter relação geográfica. Embora a predisposição sexual não tenha sido comprovada, descreve-se maior incidência de atopia em fêmeas, concordando com esta pesquisa. Os cães mais acometidos neste estudo foram da raça Shih-tzu. Suspeita-se que a popularidade regional de algumas raças ou os diferentes antecedentes genéticos em diferentes áreas geográficas afetam a predominância de algumas raças. Estes resultados mostraram que a prevalência de DAC em cães é a mais frequentemente diagnosticada no setor de Dermatologia do HOVET-UFRA, sendo mais prevalente em fêmeas e na raça Shih-tzu, podendo refletir um aspecto regional desta dermatopatia. Os resultados do presente estudo contribuíram para demonstrar a importância de mais pesquisas sobre a prevalência da Dermatite atópica canina e melhor caracterizar a população de cães atópicos na região, para que seja possível obter um perfil epidemiológico confiável.
RESUMO
Canine atopic dermatitis (CAD) is a pruritic, chronic inflammatory disease, recurrent and genetically predisposed, which is the second most frequent allergic skin disorder, and ranks second among all the causes of pruritus in dogs worldwide. Given the absence of data on the occurrence of CAD in the northern region of Brazil, the aim of the current study was to conduct a survey to define the prevalence of canine atopic dermatitis attended at the Dermatology Department of the Mário Dias Teixeira Veterinary Hospital of the "Universidade Federal Rural da Amazônia" (HOVET-UFRA). To determine the prevalence of CAD, a retrospective survey was carried out of clinical records and results of dermatological examinations conducted at the Dermatology Department of HOVET-UFRA Belém, Pará from October 2018 to October 2019. During this period, 456 dogs were examined, of which 25.65% (117) were diagnosed with atopic dermatitis. Among the animals diagnosed, 62.4% (73) were females and 51.7% (29) were of the Shih-tzu breed. This level of atopic dermatitis is considered high. There are still no exact data on the incidence and prevalence of this dermatopathy, with described occurrence ranging from 3 to 15% of the canine population, a geographical relationship may be present. Although a sex-related predisposition has not been proven, a higher incidence of atopy in females is described, which indicated this may be the case. The most commonly diagnosed dogs in this study were the Shih-tzu breed. It is suspected that the regional popularity of some breeds, or the different genetic backgrounds in different geographical areas, may affect the predominance of CAD in some breeds. The results of the present study demonstrate the need for more research on the prevalence of canine atopic dermatitis, and better means of characterizing the population of atopic dogs in the region, so that it is possible to obtain a reliable epidemiological profile.(AU)
A dermatite atópica canina (DAC) é uma doença inflamatória crônica e pruriginosa recorrente e geneticamente predisposta, que se destaca como o segundo transtorno cutâneo alérgico mais frequente e ocupa o segundo lugar entre todas as causas de prurido em cães. Diante da ausência de dados da ocorrência de DAC na região Norte do Brasil, objetivou-se realizar um levantamento de dados para definir a prevalência de dermatite atópica canina atendida no Serviço de Dermatologia do Hospital Veterinário Mário Dias Teixeira da Universidade Federal Rural da Amazônia (HOVET-UFRA). Foi realizado um levantamento retrospectivo através dos registros clínicos e dos resultados de exames dermatológicos com base nos atendimentos dermatológicos no setor de Dermatologia do HOVET-UFRA Belém/Pará, de outubro de 2018 a outubro de 2019 para determinar a prevalência de DAC. Nesse período, foram atendidos 456 cães e destes, 25,65% (117) foram diagnosticados com dermatite atópica. Dentre os animais diagnosticados, 62,4% (73) eram fêmeas e 51,7% (29) eram da raça Shih-tzu. Neste estudo houve uma alta prevalência de cães com Dermatite atópica. Ainda não existem dados exatos sobre a incidência e a prevalência desta dermatopatia, com ocorrência descrita variando de 3 a 15% da população canina, podendo ter relação geográfica. Embora a predisposição sexual não tenha sido comprovada, descreve-se maior incidência de atopia em fêmeas, concordando com esta pesquisa. Os cães mais acometidos neste estudo foram da raça Shih-tzu. Suspeita-se que a popularidade regional de algumas raças ou os diferentes antecedentes genéticos em diferentes áreas geográficas afetam a predominância de algumas raças. Estes resultados mostraram que a prevalência de DAC em cães é a mais frequentemente diagnosticada no setor de Dermatologia do HOVET-UFRA, sendo mais prevalente em fêmeas e na raça Shih-tzu, podendo refletir um aspecto regional desta dermatopatia. Os resultados do presente estudo contribuíram para demonstrar a importância de mais pesquisas sobre a prevalência da Dermatite atópica canina e melhor caracterizar a população de cães atópicos na região, para que seja possível obter um perfil epidemiológico confiável.(AU)
Assuntos
Animais , Cães , Inquéritos e Questionários , Dermatite Atópica/diagnóstico , Cães/lesões , Hospitais Veterinários , DermatopatiasRESUMO
INTRODUCTION: MicroRNA-21 (miRNA-21) has been described as one of the most significantly upregulated miRNAs in human breast cancer. However, limited knowledge exists on miRNA-21 expression in breast cancer tissue after neoadjuvant chemotherapy (NAC). PURPOSE: The aim of this study was to assess miRNA-21 expression in the tumor tissues of Brazilian patients with breast cancer who underwent NAC and its correlation with clinicopathological variables. PATIENTS AND METHODS: Utilizing qRT-PCR, miRNA-21 expression in tumor tissue was measured in a cohort of female patients with breast cancer who underwent NAC. The correlation of miRNA-21 expression with breast cancer molecular subtypes and other clinicopathological variables was also assessed. RESULTS: A total of 55 patients were included in the study, and 28 (50.9%) underwent NAC. miRNA-21 was upregulated in patients with breast cancer, regardless of previous exposure to chemotherapy, molecular subtypes, tumor-node-metastasis (TNM) staging and lymph node status of the axilla. miRNA-21 expression did not differ between patients with breast cancer who achieved a pathologic complete response after NAC and healthy controls. CONCLUSION: miRNA-21 was upregulated in the tumor tissue of Brazilian patients with breast cancer regardless of NAC treatment, which reinforces its role as an "oncomiR" and a potential biomarker.