Fibrosis in canine transmissible venereal tumor after chemotherapy with vincristine.

The canine transmissible venereal tumor is type of transmissible cancer that occurs naturally through allogenic cellular transplants. Commonly diagnosed in the genital area of sexually active dogs, the tumor typically responds well to vincristine sulfate chemotherapy, although there are cases of resistance to the drug correlated with the tumoral phenotype. We describe herein a case of fibrosis in an area affected by the tumor in a dog after vincristine chemotherapeutic treatment that was associated with an idiosyncratic reaction to the drug.

O tumor venéreo transmissível canino é um tipo de câncer transmissível que ocorre naturalmente através do transplante celular alogênico. Comumente diagnosticado na área genital de cães sexualmente ativos, o tumor normalmente responde bem à quimioterapia com sulfato de vincristina, embora existam casos de resistência à droga correlacionados com o fenótipo tumoral. Descrevemos neste relato de caso um cão com fibrose na área acometida pelo tumor após o tratamento quimioterápico com vincristina associado a uma reação idiossincrática à droga.

Cell-mediated immunity and expression of MHC class I and class II molecules in dogs naturally infected by canine transmissible venereal tumor: Is there complete spontaneous regression outside the experimental CTVT?

The canine transmissible venereal tumor (CTVT) is a transplantable cancer with the ability evade the immune system, despite strict immune surveillance of the host; in this context, the relationship between inflammatory infiltrate and CTVT prognosis is not entirely understood. Natural canine transmissible venereal tumors of 22 dogs were evaluated for tumor/host interaction through clinical and epidemiological data, cyto-histopathological and cytogenetic findings and, mainly, cell-mediated immune response. We performed analysis on dogs with naturally acquired disease to provide information from the study of CTVT biology in its natural course, as the clinical evolution of the natural tumor in the host is not yet as well known as in the laboratory. Populations for T cell labeling (CD3+ CD4+ CD8+), B cells, NK cells, and macrophages were analyzed by flow cytometry in blood and tumor samples and expressions of MHC class I and class II molecules were quantified by immunohistochemistry and compared mainly between the phases of progression and regression in the natural CTVT. Dogs were also treated with vincristine sulfate and evaluated for chemotherapeutic response. Chemotherapy was effective in 88% of cases and there was no recurrence of the disease 12 months after the cure. Tumor cells displayed a numerical chromosomal variation between 54 and 72, not correlating with the host genotype. Although a greater expression of MHC molecules [18.6 ± 5.8% class I (P < 0.004) and 38.5 ± 6.5% class II (P < 0.003)] was observed in the regression phase, no significant effect was observed between the clinical phase of the tumor and cellular immune response in the analysis by flow cytometry (P > 0.05). We also found no correlation between cytological subtype of the tumor (plasmacytoid, lymphocytoid and mixed) and cellular immune response, suggesting that there is no difference in tumor immunogenicity. Here, we found no immunological evidence to support the theory of the immune-induced complete spontaneous regression in CTVT.

Morphological Alterations and Increased Gelatinase Activity in the Superficial Digital Flexor Tendon of Chickens During Growth and Maturation.

The superficial digital flexor tendon (SDFT) connects the superficial digital flexor muscle to the digits and its main function is to participate in digit flexion. The SDFT presents different regions along its length, which adapt to different biomechanical forces. During growth and maturation, the tendon may present changes in the regions subjected to compression and tension, with variations in the composition of the extracellular matrix (ECM), in the arrangement of collagen fibers and cellularity. With the purpose of analyzing the morphological and biochemical alterations of ECM of tendons during the growth and maturation, Gallus domesticus were euthanized at 1, 5, and 8 months of age and their SDFT were divided into regions of tension/compression (Sp) and tension (Sd). From 1 month of age, the Sp region already presented fibrocartilage characteristics with cells similar to chondrocytes. At 5 and 8 months, the Sd region displayed formation of a new structure similar to bone matrix, and intense metachromasia. The animals of 5 and 8 months presented an increase in MMP-2 and -9 activities and a lower number of cells when compared with the animals of 1 month, in both regions. In conclusion, structural and biochemical alterations occur during the maturation process of the SDFT, involving a decrease in the number of cells and changes in the degradation and composition of the ECM. Anat Rec, 302:964-972, 2019. © 2018 Wiley Periodicals, Inc.

Biochemical and morphological alterations of the extracellular matrix of chicken calcaneal tendon during maturation.

The region in tendons that surrounds bone extremities adapts to compression forces, developing a fibrocartilaginous structure. During maturation, changes occur in the amount and organization of macromolecules of the extracellular matrix of tendons, changing the tissue morphology. To study the effect of maturation on tendons, Pedrês chickens were sacrificed at 1, 5, and 8 months old and had the calcaneal tendon (CT) divided into proximal region, submitted to tension/compression forces (p), and distal region submitted to tension force (d). Morphological analysis of the p region showed the presence of fibrocartilage in all ages. In the central part of the fibrocartilage, near a diminishment of the metachromasy, there was also a development of a probable fat pad that increased with the maturation. The activity of MMP-2 and MMP-9 was higher at 5 and 8 months old, in both regions, compared with 1-month-old animals. In SDS-PAGE analysis, components with electrophoretic migration similar to decorin and fibromodulin increased with maturation, particularly in the d region. The Western blotting confirmed the increased amount of fibromodulin with maturation. In conclusion, our results show that process of maturation leads to the appearance of a probable fat pad in the center of the fibrocartilage of CT, with a reduced amount of glycosaminoglycans and an increased activity of MMPs.

Do alterations in gene expressions influence tumorigenesis in the transmissible venereal tumor in dogs? / Alterações nas expressões gênicas influenciam na tumorigênese no tumor venéreo transmissível em cães?

Canine transmissible venereal tumor (CTVT) is a transmissible neoplasm, which spreads naturally between dogs through the halogenic transfer of tumor cells, mainly during coitus. It is the oldest known tumoral lineage in nature and reports on gene mutations have been extended. Also, this tumor shares several genetic mutations with some cancers in humans, among them lung carcinomas, melanoma, prostate, breast, among other cancers. Thus, expression of tumor suppressor genes such as TP53, P21, and apoptosis-related genes such as BAX, BCL-2, and BCL-xL, both in vivo and in vitro (primary cell culture) were quantified. In the present study, the comparison of gene expression, the TP53 gene, in most cases, was shown to be high in the majority of tissues (65%) and primary cell culture (100%), while BCL-2, BCL-xL, and BAX presented variation among the animals analyzed. Moreover, in these situations, the results suggested that the apoptotic regulation of these genes did not occur for TP53. The P21 gene was shown to be mostly normal (70%); although, absence (6%) and underexpressions (24%) were also observed. Statistical analysis of the BCL-xL gene demonstrated significant differences between the tissues of the animals when compared to the cell cultures; however, to the other genes, no statistical difference was observed between the groups. Preliminarily, the results suggested the presence of alterations in the gene expressions of the TP53, P21, BAX, BCL-2 and BCL-xL leading to loss of function in these genes, which affect the tumorigenesis of CTVT.(AU)

O tumor venéreo transmissível canino (TVTC) se trata de uma neoplasia transmissível, que se propaga naturalmente entre os cães pela transferência halogênica de células tumorais, principalmente, durante o coito. É a mais antiga linhagem tumoral conhecida na natureza e relatos sobre mutações gênicas vêm sendo ampliadas. Além disso, este tumor compartilha uma série de mutações genéticas com alguns cânceres em seres humanos, dentre eles, carcinomas de pulmão, melanoma, próstata, mama, entre outros tipos de câncer. Assim, quantificou-se a expressão de genes supressores de tumores, como TP53, P21 e genes relacionados à apoptose, como BAX, BCL-2 e BCL-xL, tanto in vivo quanto in vitro (cultura celular primária). No presente estudo, na comparação das expressões gênicas, o gene TP53 se mostrou elevado na maioria dos casos em tecidos (65%) e em cultura celular primária (100%), enquanto BCL-2, BCL-xL e BAX apresentaram-se variáveis entre os animais analisados. Ademais, nessas situações os resultados sugerem que não ocorreu regulação apoptótica desses genes pelo TP53. O gene P21 mostrou-se, em sua maioria, normal (70%), embora a ausência (6%) e subexpressões (24%) também tenham sido observadas. A análise estatística do gene BCL-xL demonstrou diferenças significativas entre os tecidos dos animais, quando comparadas às culturas celulares, entretanto, para os demais genes, não foi observada diferença estatística entre os grupos. Preliminarmente, os resultados sugerem a presença de alterações nas expressões gênicas dos genes TP53, P21, BAX, BCL-2 e BCL-xL, levando a perda de função desses genes, os quais afetam a tumorigênese do CTVT.(AU)

Changes in the connective tissue sheath of Wistar rat nerve with aging.

The alterations due to aging in the peripheral nerves can affect the physiology of these structures. Thus, the purpose of the present study was to describe the activity of the MMP-2 and MMP-9, as well as the structure and composition of the extracellular matrix of the rat sciatic nerve during maturation and aging. Our results have shown that the extracellular matrix of the sciatic nerve of 30-, 180- and 730-day-old Wistar rats present ultrastructural, morphometrical and biochemical changes during aging. The perineurium was the structure most affected by age, as evidenced by a decrease in thickness and in collagen fibril content. Cytochemical analysis detected proteoglycans in the basal membrane of Schwann cells and around perineural cells, as well as on the collagen fibrils of the perineurium and endoneurium at all ages. Biochemical analyses showed that the quantity of non-collagenous proteins was higher in 730-day-old animals compared to other ages, while the uronic acid content was higher in 30-day-old animals. Morphometrical analysis detected greater numbers of myelinated fibers and increased myelin thickness in 180-day-old animals. Zymography analysis detected greater amounts and activity of MMP-2 and MMP-9 in 180- and 730-day-old animals compared to younger rats. In conclusion, our results showed changes in the structural organization and composition of extracellular matrix of the sciatic nerve during aging, such as increase in the non-collagenous protein content and higher MMP-2 and MMP-9 activity, decrease in uronic acid concentration and in collagen fibril content in the perineurium, as well as degeneration of nerve fibers.

Synchronization of estrus in paca (Cuniculus paca L. ): possible impacts on reproductive and productive parameters / Sincronização do estro em pacas (Cuniculus paca L. ): possíveis impactos sobre parâmetros reprodutivos e produtivos

Estrus synchronization is a reproductive biotechnology used to improve artificial insemination or pairing through the manipulation of the estrous cycle at a desirable time. Employing this technique in captive pacas (Cuniculus paca L.) is important because it creates expectation of meeting the demand for paca meat and, consequently, reduces poaching. Thus, this research aims to verify the effect of a progestogen implant associated with two doses of eCG on the synchronization and induction of fertile estrus. Twenty-seven adult pacas were used, 18 non-pregnant females and nine males, divided into three groups. G1 and G2 females groups (treatments) received 1.5 mg Norgestomet and were injected intramuscularly, seven days later, with 0.13 mg of prostaglandin. After 24 hours the implants were removed and the animals immediately received 25 IU and 50 IU of ECG intramuscularly, respectively. The mating of the three groups took place on the same days. G3 females' group (control) showed estrus on different days after D0. Females under treatment displayed estrus only after removing the implant (D8). G1, G2, and G3 pregnancy rates were 100%, 66%, and 50%, respectively. Regarding births per parturition, 100% of G1 and G3 produced one offspring, while 50% of G2 produced two. Progestogen in the form of subcutaneous implants was effective in mimicking the luteal phase of the estrous cycle. After removal, implants favored the occurrence of a fertile estrus. As a conclusion, further studies must be conducted in order to establish in-depth possible association between 50 IU of eCG, and the occurrence of twin pregnancies.(AU)

A sincronização é uma biotécnica reprodutiva que melhora a porcentagem de cobertura por meio da manipulação do ciclo estral. Empregar esta biotécnica em pacas de cativeiro (Cuniculus paca L.) é importante, pois cria-se a expectativa de que a demanda pela carne seja atendida e a caça ilegal diminua. O objetivo da pesquisa foi verificar o efeito de implantes de progestágenos associados a duas doses de gonadotrofina coriônica equina (eCG) na sincronização e indução de cios férteis de pacas. Foram utilizadas 18 fêmeas não prenhas e nove machos, divididos em três grupos. Fêmeas do G1 e G2 receberam implantes com 1,5mg de Norgestomet e, sete dias depois, 0,13mg de prostaglandina via intramuscular (IM). No dia 8 (D8), foram retirados os implantes e G1 e G2 receberam 25 UI e 50 UI de eCG, IM, respectivamente; G3 foi o controle. O pareamento nos três grupos aconteceu nos mesmos dias. As fêmeas do G3 apresentaram cio alguns dias após o dia zero (D0). Fêmeas que receberam tratamento apresentaram cio só após a retirada do implante no dia 8 (D8). As taxas de prenhez de G1, G2 e G3 atingiram 100%, 66% e 50%, respectivamente. Em relação a filhotes por parto, 100% do G1 e G3 produziram uma cria, enquanto 50% do G2 produziram duas crias. O progestágeno do implante foi eficaz em mimetizar a fase lútea do ciclo estral. Após a remoção, o tratamento hormonal favoreceu a ocorrência de cio fértil. Outros estudos devem ser realizados a fim de estabelecer uma possível associação entre 50 UI de eCG e a ocorrência de gestações gemelares.(AU)

Synchronization of estrus in paca (Cuniculus paca L. ): possible impacts on reproductive and productive parameters / Sincronização do estro em pacas (Cuniculus paca L. ): possíveis impactos sobre parâmetros reprodutivos e produtivos

Estrus synchronization is a reproductive biotechnology used to improve artificial insemination or pairing through the manipulation of the estrous cycle at a desirable time. Employing this technique in captive pacas (Cuniculus paca L.) is important because it creates expectation of meeting the demand for paca meat and, consequently, reduces poaching. Thus, this research aims to verify the effect of a progestogen implant associated with two doses of eCG on the synchronization and induction of fertile estrus. Twenty-seven adult pacas were used, 18 non-pregnant females and nine males, divided into three groups. G1 and G2 females groups (treatments) received 1.5 mg Norgestomet and were injected intramuscularly, seven days later, with 0.13 mg of prostaglandin. After 24 hours the implants were removed and the animals immediately received 25 IU and 50 IU of ECG intramuscularly, respectively. The mating of the three groups took place on the same days. G3 females' group (control) showed estrus on different days after D0. Females under treatment displayed estrus only after removing the implant (D8). G1, G2, and G3 pregnancy rates were 100%, 66%, and 50%, respectively. Regarding births per parturition, 100% of G1 and G3 produced one offspring, while 50% of G2 produced two. Progestogen in the form of subcutaneous implants was effective in mimicking the luteal phase of the estrous cycle. After removal, implants favored the occurrence of a fertile estrus. As a conclusion, further studies must be conducted in order to establish in-depth possible association between 50 IU of eCG, and the occurrence of twin pregnancies.(AU)

A sincronização é uma biotécnica reprodutiva que melhora a porcentagem de cobertura por meio da manipulação do ciclo estral. Empregar esta biotécnica em pacas de cativeiro (Cuniculus paca L.) é importante, pois cria-se a expectativa de que a demanda pela carne seja atendida e a caça ilegal diminua. O objetivo da pesquisa foi verificar o efeito de implantes de progestágenos associados a duas doses de gonadotrofina coriônica equina (eCG) na sincronização e indução de cios férteis de pacas. Foram utilizadas 18 fêmeas não prenhas e nove machos, divididos em três grupos. Fêmeas do G1 e G2 receberam implantes com 1,5mg de Norgestomet e, sete dias depois, 0,13mg de prostaglandina via intramuscular (IM). No dia 8 (D8), foram retirados os implantes e G1 e G2 receberam 25 UI e 50 UI de eCG, IM, respectivamente; G3 foi o controle. O pareamento nos três grupos aconteceu nos mesmos dias. As fêmeas do G3 apresentaram cio alguns dias após o dia zero (D0). Fêmeas que receberam tratamento apresentaram cio só após a retirada do implante no dia 8 (D8). As taxas de prenhez de G1, G2 e G3 atingiram 100%, 66% e 50%, respectivamente. Em relação a filhotes por parto, 100% do G1 e G3 produziram uma cria, enquanto 50% do G2 produziram duas crias. O progestágeno do implante foi eficaz em mimetizar a fase lútea do ciclo estral. Após a remoção, o tratamento hormonal favoreceu a ocorrência de cio fértil. Outros estudos devem ser realizados a fim de estabelecer uma possível associação entre 50 UI de eCG e a ocorrência de gestações gemelares.(AU)

Tumor venéreo transmisible canino: análisis de casos de 2008- 2014 en el Hospital Veterinario de Botucatu / Canine transmissible venereal tumor: casuistic analisis of 2008- 2014 at the Veterinary Hospital of Botucatu / Tumor venéreo transmissível canino: análise da casuística 2008- 2014 no Hospital Veterinário de Botucatu

El Tumor Venéreo Transmisible (TVT) es un tumor de células redondas de origen incierta, su diseminación ocurre principalmente por el contacto sexual o por el trasplante directo de células neoplásicas. Con el objetivo de establecer parámetros según la predisposición sexual, racial, etaria y la localización extragenital de mayor incidencia de ese tumor en perros atendidos en el Hospital Veterinario de Botucatu, fue realizado un estudio retrospectivo con 260 casos de ocurrencia natural de TVT durante el periodo de 6 años. Los machos, sin raza definida (SRD) y con edad superior a 7 años fueron los más afectados. La región más afectada fue la genital, seguida por la región nasal, este último aspecto, lleva al TVT a un nuevo nivel en la lista de diagnósticos diferenciales cuando consideramos los signos clínicos de epistaxis uni y/o bilaterar, dispnea compensatoria, secreción mucopurulenta a serosanguinolenta y obstrucción nasal.

The Transmissible Venereal Tumor (TVT) is a round cell tumor with uncertain origin, which is spread by sexual contact or by direct transplantation of neoplastic cells. In order to establish parameters according to sexual, racial, age predisposition and mainly to the extragenital location with the highest incidence of this tumor in dogs, a retrospective study of 260 cases of naturally occurring TVT was performed during the period of 6 years. The most affected dogs were male, with mixed breed and over the age of 7 years. The most frequent involvement region is the genitalia, followed by the nasal region, a fact that leads the TVT to a new level in differential diagnosis considering the clinical signs of uni and/or bilateral epistaxis, compensatory dyspnea, sanguinopurulent or mucopurulent discharge and nasal obstruction.

O Tumor Venéreo Transmissível (TVT) é um tumor de células redondas de origem incerta, cuja disseminação ocorre principalmente por contato sexual ou por transplante direto de célula neoplásica. Com o objetivo de estabelecerem-se parâmetros segundo a predisposição sexual, racial, etária e principalmente quanto à localização extragenital de maior incidência desse tumor em cães, foi realizado um estudo retrospectivo de 260 casos de ocorrência natural de TVT no período de 6 anos. Os cães mais acometidos foram os machos, sem raça definida (SRD) e com idade acima de 7 anos. A região de acometimento mais frequente é a genitália, seguida pela região nasal, fato esse que leva o TVT a um novo patamar na lista de diagnósticos diferenciais quando consideramos os sinais clínicos de epistaxe uni e/ou bilateral, dispneia compensatória, secreção mucopurulenta a serosanguinolenta e obstrução nasal.

Tumor venéreo transmisible canino: análisis de casos de 2008- 2014 en el Hospital Veterinario de Botucatu / Canine transmissible venereal tumor: casuistic analisis of 2008- 2014 at the Veterinary Hospital of Botucatu / Tumor venéreo transmissível canino: análise da casuística 2008- 2014 no Hospital Veterinário de Botucatu

El Tumor Venéreo Transmisible (TVT) es un tumor de células redondas de origen incierta, su diseminación ocurre principalmente por el contacto sexual o por el trasplante directo de células neoplásicas. Con el objetivo de establecer parámetros según la predisposición sexual, racial, etaria y la localización extragenital de mayor incidencia de ese tumor en perros atendidos en el Hospital Veterinario de Botucatu, fue realizado un estudio retrospectivo con 260 casos de ocurrencia natural de TVT durante el periodo de 6 años. Los machos, sin raza definida (SRD) y con edad superior a 7 años fueron los más afectados. La región más afectada fue la genital, seguida por la región nasal, este último aspecto, lleva al TVT a un nuevo nivel en la lista de diagnósticos diferenciales cuando consideramos los signos clínicos de epistaxis uni y/o bilaterar, dispnea compensatoria, secreción mucopurulenta a serosanguinolenta y obstrucción nasal.(AU)

The Transmissible Venereal Tumor (TVT) is a round cell tumor with uncertain origin, which is spread by sexual contact or by direct transplantation of neoplastic cells. In order to establish parameters according to sexual, racial, age predisposition and mainly to the extragenital location with the highest incidence of this tumor in dogs, a retrospective study of 260 cases of naturally occurring TVT was performed during the period of 6 years. The most affected dogs were male, with mixed breed and over the age of 7 years. The most frequent involvement region is the genitalia, followed by the nasal region, a fact that leads the TVT to a new level in differential diagnosis considering the clinical signs of uni and/or bilateral epistaxis, compensatory dyspnea, sanguinopurulent or mucopurulent discharge and nasal obstruction.(AU)

O Tumor Venéreo Transmissível (TVT) é um tumor de células redondas de origem incerta, cuja disseminação ocorre principalmente por contato sexual ou por transplante direto de célula neoplásica. Com o objetivo de estabelecerem-se parâmetros segundo a predisposição sexual, racial, etária e principalmente quanto à localização extragenital de maior incidência desse tumor em cães, foi realizado um estudo retrospectivo de 260 casos de ocorrência natural de TVT no período de 6 anos. Os cães mais acometidos foram os machos, sem raça definida (SRD) e com idade acima de 7 anos. A região de acometimento mais frequente é a genitália, seguida pela região nasal, fato esse que leva o TVT a um novo patamar na lista de diagnósticos diferenciais quando consideramos os sinais clínicos de epistaxe uni e/ou bilateral, dispneia compensatória, secreção mucopurulenta a serosanguinolenta e obstrução nasal.(AU)