NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer.

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.

Interferon-gamma is quintessential for NOS2 and COX2 expression in ER- breast tumors that lead to poor outcome.

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.

Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER - Breast Tumors that Lead to Poor Outcome.

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.

Follicular Atresia, Cell Proliferation, and Anti-Mullerian Hormone in Two Neotropical Primates (Aotus nancymae and Sapajus macrocephalus).

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.

Sulforaphane: An emergent anti-cancer stem cell agent.

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.

NOS2 and COX2 Provide Key Spatial Targets that Determine Outcome in ER- Breast Cancer.

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.

Spatial analysis of NOS2 and COX2 interaction with T-effector cells reveals immunosuppressive landscapes associated with poor outcome in ER- breast cancer patients.

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.

In vitro anticancer properties of anthocyanins: A systematic review.

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.

Hepatic lesions in captive owl monkeys (Aotus infulatus) with ultrasonographic "starry sky" liver.

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.

miRNA-195 expression in the tumor tissues of female Brazilian breast cancer patients with operable disease.

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.

Prevalence of canine atopic dermatitis at the Veterinary Hospital of the Universidade Federal Rural da Amazônia in Belém/Pará, Brazil

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.

Prevalence of canine atopic dermatitis at the Veterinary Hospital of the "Universidade Federal Rural da Amazônia" in Belém/Pará, Brazil / Prevalência de dermatite atópica canina no Hospital Veterinário da Universidade Federal Rural da Amazônia em Belém/Pará, Brasil

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)

miRNA-195 expression in the tumor tissues of female Brazilian breast cancer patients with operable disease

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.

Mirna21 Expression in the Breast Cancer Tumor Tissue is Independent of Neoadjuvant Chemotherapy.

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.

Can Paraplegia by Disruption of the Spinal Cord Tissue Be Reversed? The Signs of a New Perspective.

Central nervous system (CNS) trauma is often related to tissue loss, leading to partial or complete disruption of spinal cord function due to neuronal death. Although generally irreversible, traditional therapeutic efforts, such as physical therapy exercises, are generally recommended, but with a poor or reduced improvement of the microenvironment, which in turn stimulates neuroplasticity and neuroregeneration. Mesenchymal stem cells (MSCs) have paracrine, immunomodulatory, and anti-inflammatory effects. Here we use stem cells to see if they can promote not only physical but also the functional regeneration of neuronal tissue in dogs with CNS traumas. Two dogs, one with chronic spinal cord injury and one with subacute spinal cord injury, underwent infusion of autologous MSCs in association with physiotherapy. The two treatments in combination were able to partially or completely recover the dog's walking movement again. The treatment of MSCs in association with physical therapy improved the microenvironment, which could be evidence of a paradigm shift that the CNS is not capable of functional regeneration after aggressive traumas. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1812-1820, 2020. © 2019 American Association for Anatomy.

Single-port laparoscopic ovariectomy using a pre-tied loop ligature in Santa Ines ewes / Ovariectomia por um portal laparoscópico com aplicação de ligaduras pré-montadas em ovelhas Santa Inês

ABSTRACT:The aim of the study was to develop and assess the feasibility, postoperative pain and inflammatory response of the single-port laparoscopic ovariectomy in ewes, using a simple pre-tied loop ligature technique. Pre-tied Meltzer's knot was employed for prophylactic hemostasis of the ovarian pedicle. Slipknot was inserted within the abdominal cavity through a 14-gauge needle and tied surrounding the ovarian pedicle. Mean surgical time, manipulation, ligature and resection of each ovary and anesthesia time were 63±20, 20±10 and 91±26 minutes, respectively. No bleeding occurred during the surgeries. Ewes showed low scores pain (0.5±0.5) at all time-points. Postsurgical plasma fibrinogen was within the normal range for sheep specie at all time-points. The ewes showed a significant weight gain in comparison to the basal scaling (one day before the surgery). Single-port laparoscopic ovariectomy using a pre-tied loop ligature is feasible in the ovine specie and provided minimal postoperative distress and quick weight gain.

RESUMO:Objetivou-se com este trabalho desenvolver e descrever uma técnica de ovariectomia por videolaparoscopia utilizando um portal laparoscópico e um sistema de ligadura pré-montada, avaliando a sua viabilidade, o desconforto doloroso e o processo inflamatório provocado em ovelhas. O nó de Meltzer pré-montado foi utilizado para hemostasia profilática do pedículo ovariano. O nó corrediço foi inserido na cavidade abdominal através de uma agulha 14G e atado em torno do pedículo ovariano. O tempo médio de cirurgia foi de 63±20min, o de manipulação, ligadura e ressecção para cada ovário foi de 20±10min, e o de anestesia 91±26min. Não houve hemorragia durante as cirurgias. As ovelhas apresentaram escores de dor considerados baixos (0,5±0,5). Todos os valores do fibrinogênio plasmático estiveram dentro do padrão de normalidade, não havendo diferença estatística entre os momentos avaliados. Houve aumento significativo nas médias de peso das fêmeas, quando comparados ao momento controle (um dia anterior ao experimento). A ovariectomia por um portal laparoscópico com aplicação de ligaduras pré-montadas é factível para a espécie ovina, provocando mínimo estresse, desconforto doloroso e rápido ganho de peso nos animais.

Functional morphology of the tubular genital organs in the female owl monkey (Aotus spp.).

BACKGROUND: Studies on reproductive morphology are important to understand the reproductive cycle of non-human primates. METHODS: This study describes the functional morphology of the adult female tubular genital organs in 41 Aotus (12.8 ± 6.8 years old, ranging from 3 to 25 years), with respect to reproductive status and number of parturitions. RESULTS: In females with developing embryos, endometrial glands showed a higher secretion than other females, and the embryo implantation occupied this secretive endometrium. Changes in the thickening, number of layers, and keratinization in the vaginal epithelium suggest that vaginal cytology may be an indicator of the estrous cycle. Non-pregnant multiparous females had a larger uterine body than nulliparous females. Number of parturitions and reproductive state had an impact on tubular genital organs in female owl monkeys. CONCLUSIONS: These results can be useful for the development of biotechnologies of reproduction and for improvement of the management of this species.

Endoscopic approach for a laryngeal neoplasm in a dog / Abordagem endoscópica de neoplasia em laringe em um cão

Laryngeal and tracheal tumors are rare in pets; some piece of information on their disease behavior, therapy and evolution are limited. Neoplasms in this area are a diagnostic challenge. In many cases, they can be biopsied and excised using endoscopic instruments, but there is no report of this in canines. The goal of this study is to report a successful case of a laryngeal neoplasm removal through endoscopy. A head and neck radiogram revealed a mass in the laryngeal lumen protruding into the trachea. The patient then underwent an endoscopy to confirm the radiographic diagnosis and to surgically remove the tumor. The histopathological diagnosis was poorly differentiated carcinoma. The most appropriate treatment for laryngeal tumors is the resection of the submucosa or a partial laryngectomy however, partial and total laryngectomies are associated with many postoperative complications. In contrast, the endoscopic approach allows for highly magnified visualization of the lesion in situ, which facilitates the surgical removal of the mass through videosurgery. With little manipulation of the affected area, the chances of postoperative complications are reduced, leading to a more rapid recovery. .

Tumores de laringe e traqueia são raros em animais de estimação e as informações sobre o comportamento, terapia e evolução destas neoplasias são limitadas. Neoplasias nesta área são desafios diagnósticos. Em muitos casos, pode ser feita a biópsia e excisão da massa utilizando instrumentos endoscópicos, mas não existe relato deste tipo de procedimento em caninos. O objetivo deste estudo foi relatar um caso de sucesso da remoção endoscópica de um tumor de laringe. A radiografia da região cervical revelou uma massa na luz da laringe invadindo a traqueia. O paciente foi então submetido a uma endoscopia para confirmar o diagnóstico radiográfico e remover cirurgicamente o tumor. O diagnóstico histopatológico foi de carcinoma pouco diferenciado. O tratamento mais adequado para os tumores da laringe é a ressecção da submucosa ou uma laringectomia parcial, no entanto, estas estão associadas a muitas complicações pós-operatórias. Em contraste, a abordagem endoscópica permite a visualização da lesão in situ, o que facilita a remoção cirúrgica da massa através de videocirurgia. Com pouca manipulação da área afetada, as chances de complicações pós-operatórias são reduzidas, levando a uma recuperação mais rápida. .