Insights into Vincristine-Induced Peripheral Neuropathy in Aged Rats: Wallerian Degeneration, Oxidative Damage, and Alterations in ATPase Enzymes.

This study aimed to elucidate vincristine (VCR)-induced peripheral neuropathy in aged rats, a poorly understood neurotoxicity. Both young and old Wistar rats were administered VCR (0.1 mg/kg, intraperitoneally (i.p.)) and compared to age-matched controls (0.9% saline; 10 mg/mL, i.p.). Mechanical (MN) and thermal nociceptive (TN) responses were assessed on days 0, 6, 11, and 17. Locomotor response, cognitive ability, and anxious-like behavior were evaluated on days 14, 15, and 16. Results showed MN and TN responses in both young and old VCR-exposed rats. In old rats, VCR exacerbated MN (on days 6, 11, and 17) and TN (on days 6 and 17) responses. VCR also induced cognitive impairments and anxiety-like behavior. Histological analysis revealed Wallerian degeneration in the spinal cords of VCR-exposed rats accompanied by macrophage migration. Furthermore, VCR increased Ca2+-ATPase activity while inhibiting Na+, K+-ATPase activity in young and old rats. VCR altered the homeostasis of Mg2+-ATPase activity. Lipid peroxidation and nitrite and nitrate levels increased in young and old rats exposed to VCR. This study provides valuable insights into VCR's mechanistic pathways in aged rats, emphasizing the need for further research in this area.

Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy.

Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07-1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26-100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.

Antitumor Effect of Epigallocatechin Gallate and Vincristine in Mice with L5178Y Lymphoma.

The main objective of research into new therapies is the search for more efficacy and fewer toxic effects in cancer treatments. On one hand, vincristine (VCR) is a chemotherapeutic used in different kinds of tumors. On the other hand, epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in diverse investigations, so the objective of this work is to evaluate the antitumor effects of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG, and their combination allowed tumor growth and survival time recording. After tumor collection, measurements, and immunohistochemistry for p53, Bcl2, and Cyclin D1 were performed. The results showed that the EGCG/vincristine combination had a greater antitumor effect than those effects of vincristine and EGCG. It can be attributed to the fact that the greatest inhibition of Bcl2 was present in gathering of EGCG harvest with vincristine. Therefore, the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival on both substances independently.

Impairments in fine motor skills in children with Acute Lymphoblastic Leukaemia. A cross-sectional study.

AIM: We evaluated fine motor skills; precision, motor integration, manual dexterity, and upper-limb coordination according to sex and risk stratification in children with Acute Lymphoblastic Leukaemia (ALL). METHODS: We evaluated twenty-nine children in the maintenance phase aged 6 to 12 years with the Bruininks-Oseretsky Test of Motor Proficiency-second edition (BOT-2), and sex and age-specific norm values of BOT-2 were used to compare our results. RESULTS: We found lower scores on the upper-limb coordination subtest, p = 0.003 and on the manual coordination composite, p = 0.008, than normative values. Most boys performed "average" on both the subtests and the composites, but girls showed lower scores with a mean difference of 7.69 (95%CI; 2.24 to 3.14), p = 0.009. Girls' scale scores on the upper-limb coordination subtest were lower than normative values, with mean difference 5.08 (95%CI; 2.35 to 7.81), p = 0.006. The mean standard score difference in high-risk patients was lower than normative on the manual coordination composite, 8.18 (95%CI; 2.26 to 14.1), p = 0.015. High-risk children also performed below the BOT-2 normative on manual dexterity 2.82 (95%CI; 0.14 to 5.78), p = 0.035 and upper limb coordination subtest 4.10 (95%CI; 1.13 to 7.05), p = 0.028. We found a decrease in fine motor precision in children with a higher BMI, rho= -0.87, p = 0.056 and a negative correlation between older age and lower manual dexterity, r= -0.41 p = 0.026; however, we did not find any correlation with the weeks in the maintenance phase. CONCLUSIONS: Fine motor impairments are common in children with ALL in the maintenance phase; it is important to identify these impairments to early rehabilitation.

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.

Linfoma de células B de alto grado de malignidad con morfología blastoide durante el embarazo: reporte de un caso / High-grade malignant B-Cell lymphoma with blastoid during pregnancy: a case report

Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.

Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.

In vitro chemosensitivity of a canine tumor venereal transmissible cancer cell line.

The canine transmissible venereal tumor (CTVT) is the most common malignity in dogs. Because there are reports that this tumor is resistant to vincristine sulfate, the chemotherapeutic options are scarce, and the development of new therapeutic approaches is necessary. In this study, we evaluated the cytotoxic activity of vincristine, doxorubicin, temozolomide, panobinostat, toceranib, gemcitabine, cisplatin, fluorouracil, cyclophosphamide, and methotrexate on a CTVT cell line, determining that all drugs decreased the viability in a dose-dependent manner. Furthermore, they inhibit cellular migration in a time- and drug-dependent manner, as evaluated by the wound healing assay. On the other hand, vincristine, panobinostat, gemcitabine, toceranib, cyclophosphamide, and methotrexate increased the percentage of cells in the subG1 phase, and doxorubicin, temozolomide, gemcitabine, toceranib, and methotrexate decreased the percentage of cells in the synthesis phase. To efficientize the use of vincristine, only toceranib increased the cytotoxic effect of vincristine in a synergistic manner. Our results confirm the use of vincristine as the gold standard for CTVT treatment as monotherapy and suggest the use of a combinatorial and sequential treatment with toceranib.

Tumor venéreo transmissível (TVT) nasal em cães / Nasal transmissible venereal tumor (TVT) in dogs

Background: Transmissible venereal tumors (TVT) are naturally occurring neoplasms that can be transmitted throughcopulation or cell transplantation. It is a disease that affects canines, has no preference for sex or breed, and generallynoticed in the external genital apparatus. Extragenital occurrence may eventually be seen; however, nasal involvementhas been described in only a few reports of studies conducted in Brazil. Therefore, the objective of this study is to report3 cases of nasal TVT in dogs who were treated in 2 municipalities in the mountainous region of Santa Catarina, Brazil.Cases: This case report includes 3 male mixed-breed canines of age 3-13. Only 1 of the animals was castrated. As per themedical history, some points, such as an enlarged nasal region, sneezing, nasal discharge, and hoarseness, reported by thedogs’ respective owners were similar among all the dogs. Likewise, nosebleed was observed on physical examination inall the cases. The result of cytological examination was inconclusive only in 1 case. Rhinoscopy, incisional biopsy, andhistopathological examination were then performed for achieving a definitive diagnosis. In the 2 cases wherein cytologygave conclusive results, the cytological smears showed changes suggestive of TVT, such as cells with eccentric nuclei andlittle cytoplasm, which had vacuoles inside them. In 2 cases, radiographic examinations of the skull were also performed.The images showed changes in bone radiopacity, conformation of trabeculae with areas of bone lysis and cell proliferation,and irregularity in the contour of the nasal bone. After TVT diagnosis was confirmed, chemotherapy was initiated usingvincristine at a dose of 0.75 mg/m2 for 2 cases and 0.025 mg/kg for the remaining case...

Tumor venéreo transmissível (TVT) nasal em cães / Nasal transmissible venereal tumor (TVT) in dogs

Background: Transmissible venereal tumors (TVT) are naturally occurring neoplasms that can be transmitted throughcopulation or cell transplantation. It is a disease that affects canines, has no preference for sex or breed, and generallynoticed in the external genital apparatus. Extragenital occurrence may eventually be seen; however, nasal involvementhas been described in only a few reports of studies conducted in Brazil. Therefore, the objective of this study is to report3 cases of nasal TVT in dogs who were treated in 2 municipalities in the mountainous region of Santa Catarina, Brazil.Cases: This case report includes 3 male mixed-breed canines of age 3-13. Only 1 of the animals was castrated. As per themedical history, some points, such as an enlarged nasal region, sneezing, nasal discharge, and hoarseness, reported by thedogs respective owners were similar among all the dogs. Likewise, nosebleed was observed on physical examination inall the cases. The result of cytological examination was inconclusive only in 1 case. Rhinoscopy, incisional biopsy, andhistopathological examination were then performed for achieving a definitive diagnosis. In the 2 cases wherein cytologygave conclusive results, the cytological smears showed changes suggestive of TVT, such as cells with eccentric nuclei andlittle cytoplasm, which had vacuoles inside them. In 2 cases, radiographic examinations of the skull were also performed.The images showed changes in bone radiopacity, conformation of trabeculae with areas of bone lysis and cell proliferation,and irregularity in the contour of the nasal bone. After TVT diagnosis was confirmed, chemotherapy was initiated usingvincristine at a dose of 0.75 mg/m2 for 2 cases and 0.025 mg/kg for the remaining case...(AU)

Synthesis and Characterization of a Fe3O4@PNIPAM-Chitosan Nanocomposite and Its Potential Application in Vincristine Delivery.

In this research, we conducted a systematic evaluation of the synthesis parameters of a multi-responsive core-shell nanocomposite (Fe3O4 nanoparticles coated by poly(N-isopropylacrylamide) (PNIPAM) in the presence of chitosan (CS) (Fe3O4@PNIPAM-CS). Scanning electron microscopy (SEM) was used to follow the size and morphology of the nanocomposite. The functionalization and the coating of Fe3O4 nanoparticles (Nps) were evaluated by the ζ-potential evolution and Fourier Transform infrared spectroscopy (FTIR). The nanocomposite exhibited a collapsed structure when the temperature was driven above the lower critical solution temperature (LCST), determined by dynamic light scattering (DLS). The LCST was successfully shifted from 33 to 39 °C, which opens the possibility of using it in physiological systems. A magnetometry test was performed to confirm the superparamagnetic behavior at room temperature. The obtained systems allow the possibility to control specific properties, such as particle size and morphology. Finally, we performed vincristine sulfate loading and release tests. Mathematical analysis reveals a two-stage structural-relaxation release model beyond the LCST. In contrast, a temperature of 25 °C promotes the diffusional release model. As a result, a more in-depth comprehension of the release kinetics was achieved. The synthesis and study of a magnetic core-shell nanoplatform offer a smart material as an alternative targeted release therapy due to its thermomagnetic properties.

LOPH: a novel chemotherapeutic protocol for feline high-grade multicentric or mediastinal lymphoma, developed in an area endemic for feline leukemia virus.

OBJECTIVES: The aim of this study was to establish the safety and efficacy of a novel multidrug lomustine-based chemotherapeutic protocol for cats with high-grade multicentric or mediastinal lymphoma, in an area endemic for feline leukemia virus (FeLV). METHODS: This prospective study included owned cats, diagnosed (cytologically) with multicentric or mediastinal lymphoma and treated with the LOPH (lomustine, vincristine [Oncovin; Antibióticos do Brasil], prednisolone and hydroxydaunorubicin [doxorubicin]) protocol. A complete blood count was performed before every chemotherapy session and any significant abnormalities recorded as possible related toxicities. Median survival time (MST) and disease-free interval were estimated by Kaplan-Meier curves. RESULTS: Twenty-one cats were included in this study. Nineteen (90.5%) tested positive for FeLV and were therefore considered to have persistent viremia. Complete response was reported in 81% (n = 17/21), while three had partial remission and one had no response. Seven cats finished the induction protocol within 20-31 weeks (23.1 ± 4.5; median 20) and all seven received a maintenance protocol. The MST (lymphoma-related survival) for the 21 cats was 214 days. The MST was 214 days for cats with mediastinal lymphoma (n = 13), but it was not reached for multicentric lymphoma (n = 8; P = 0.9). The MST of cats with persistent FeLV antigenemia was 171 days. Grade I anorexia and vomiting occurred in 19% of the cats (n = 4/21). Hematologic toxicity was found in 100% of the cats at some point during their treatment, but it was mostly grade I or II. Neutropenia, thrombocytopenia and anemia occurred in 16/21, 21/21 and 15/21 cats, respectively. CONCLUSIONS AND RELEVANCE: The LOPH protocol was well tolerated by cats with lymphoma and persistent FeLV viremia, and resulted in a better MST than similar studies with other protocols. Novel studies and controlled trials are necessary in order to evaluate the efficacy of different protocols according to the lymphoma subtype, anatomic form and FeLV status.

Morin exhibits leukemic cellular apoptosis through caspase pathway.

The present study investigated the possibility of apoptosis-inducing activity in human leukemia U-937 and THP-1 cells by the flavonoid morin. The treatments were evaluated by using the MTT and LDH assays; analysis of mitochondrial membrane potential (ΔΨm) was evaluated by flow cytometry, cell death by apoptosis was confirmed by fluorescence microscopy and by assessing the activity of caspases-3 and -6. The data indicated that the flavonoid morin has promoted a decrease in cell viability in a concentration-dependent way for both of the cancerous cell lines. An increase in the percentage of cell death caused by apoptosis was associated to a potential alteration in the mitochondrial membrane (ΔΨm) suggesting the involvement of cell death in intrinsic apoptotic pathways. Activation of caspases-3 and -6 confirmed the presence of apoptotic activity from morin. The results reinforce the antileukemic potential of flavonol morin.

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor / Comparação entre as alterações hematológicas e bioquímicas ocasionadas pela quimioterapia convencional e quimioterapia metronômica no tratamento do tumor venéreo transmissível canino

This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)

Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor

ABSTRACT: This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p 0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.

RESUMO: Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p 0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor / Comparação entre as alterações hematológicas e bioquímicas ocasionadas pela quimioterapia convencional e quimioterapia metronômica no tratamento do tumor venéreo transmissível canino

This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)

Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)

Effect of Arrabidaea chica extract against chemically induced breast cancer in animal model

Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. Conclusion: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.

Tumor venéreo transmissível em região perianal em canino: relato de caso / Transmissible venereal tumor in perianal region in canine: case report / Tumor venéreo transmisible en região perianal en perro: reporte de caso

o tumor venéreo transmissível ou Tumor de Sticker, trata se de uma neoplasia de ocorrência espontânea comum nos órgãos genitais, sem envolvimento de qualquer agente infeccioso em sua etiologia, quando células tumorais ou neoplásicas são implantadas mecanicamente, através de montas naturais e também por lambedura excessiva da área genital, ocasionando lesões em nariz, boca, cavidade oral e até mesmo na pele, porém tem sido descrito em várias localizações extragenitais, como ânus, globo ocular, tecido subcutâneo e pele. Foi atendido numa Clínica Veterinária em Maceió - AL, um cão, macho, raça Poodle, 7 anos, domiciliado, apresentando aumento de volume na região perianal, uma massa com aspecto vegetante irregular e friável há 2 semanas, com presença de secreção serossanguinolenta ininterrupta, foram realizados exames citológicos através de decalque da lesão, onde foi possível observar a presença de células redondas, excêntricas, com nucléolo único proeminente e com múltiplos vacúolos claros individualmente com limites citoplasmáticos bem definidos. Foi instituído tratamento com quimioterápico, através do sulfato de vincristina na dose de 0,1 mg/kg, administrado por via intravenosa com fluidoterapia, uma vez por semana, durante quatro semanas. O animal recebeu alta com remissão completa das lesões.

Transmissible venereal tumor or Sticker tumor is a neoplasm of spontaneous occurrence common in the genital organs, without involvement of any infectious agent in its etiology, when tumor or neoplastic cells are implanted mechanically, through natural mounts and also by excessive licking of the genital area, causing lesions in the nose, mouth, oral cavity and even in the skin, but has been described in several extragenital locations, such as anus, eyeball, subcutaneous tissue and skin. It was attended at a Veterinary Clinic in Maceió - Al, a dog, male, Poodle breed, 7 years old, domiciled with increased volume in the perianal region, a mass with irregular and friable vegetative appearance for 2 weeks, with uninterrupted serosanguinolenta secretion, cytological exams were performed through a lesion decal, where it was possible to observe the presence of round, eccentric cells with prominent single nucleolus and with multiple clear vacuoles individually with well defined cytoplasmic limits. Treatment with chemotherapy with vincristine sulfate at a dose of 0.1 mg/kg was given intravenously with fluid therapy once a week for four weeks. The animal was discharged with complete remission of the lesions.

El tumor venéreo transmisible o Tumor de Sticker, se trata de una neoplasia de ocurrencia espontánea común en los órganos genitales, sin implicación de ningún agente infeccioso en sue tiología, cuando células tumorales o neoplásicas son implantadas mecánicamente, a través de montas naturales y también por lamedura excesiva de la zona genital, ocasionando lesiones en nariz, boca, cavidad oral e incluso en la piel, pero ha sido descrito en varias localizaciones extragenitales, como ano, globo ocular, tejido subcutáneo y piel. En el caso de la vacunación, se observó un aumento del volumen en la región perianal, una masa con aspecto vegetativo irregular y friable hace 2 semanas, con presencia de secreción serosanguinolenta ininterrumpida, se realizaron exámenes citológicos a través de la caldera de la lesión, donde fue posible observar la presencia de células redondas, excéntricas, con nucléolo único prominente y con múltiples vacuolos claros individualmente con límites citoplasmáticos bien definidos. Se estableció tratamiento con quimioterápico a través del sulfato de vincristina a una dosis de 0,1 mg/kg, administrada por vía intravenosa con fluidoterapia una vez a la semana durante cuatro semanas. El animal recibió alta con remisión completa de las lesiones.

Tumor venéreo transmissível em região perianal em canino: relato de caso / Transmissible venereal tumor in perianal region in canine: case report / Tumor venéreo transmisible en região perianal en perro: reporte de caso

o tumor venéreo transmissível ou Tumor de Sticker, trata se de uma neoplasia de ocorrência espontânea comum nos órgãos genitais, sem envolvimento de qualquer agente infeccioso em sua etiologia, quando células tumorais ou neoplásicas são implantadas mecanicamente, através de montas naturais e também por lambedura excessiva da área genital, ocasionando lesões em nariz, boca, cavidade oral e até mesmo na pele, porém tem sido descrito em várias localizações extragenitais, como ânus, globo ocular, tecido subcutâneo e pele. Foi atendido numa Clínica Veterinária em Maceió - AL, um cão, macho, raça Poodle, 7 anos, domiciliado, apresentando aumento de volume na região perianal, uma massa com aspecto vegetante irregular e friável há 2 semanas, com presença de secreção serossanguinolenta ininterrupta, foram realizados exames citológicos através de decalque da lesão, onde foi possível observar a presença de células redondas, excêntricas, com nucléolo único proeminente e com múltiplos vacúolos claros individualmente com limites citoplasmáticos bem definidos. Foi instituído tratamento com quimioterápico, através do sulfato de vincristina na dose de 0,1 mg/kg, administrado por via intravenosa com fluidoterapia, uma vez por semana, durante quatro semanas. O animal recebeu alta com remissão completa das lesões.(AU)

Transmissible venereal tumor or Sticker tumor is a neoplasm of spontaneous occurrence common in the genital organs, without involvement of any infectious agent in its etiology, when tumor or neoplastic cells are implanted mechanically, through natural mounts and also by excessive licking of the genital area, causing lesions in the nose, mouth, oral cavity and even in the skin, but has been described in several extragenital locations, such as anus, eyeball, subcutaneous tissue and skin. It was attended at a Veterinary Clinic in Maceió - Al, a dog, male, Poodle breed, 7 years old, domiciled with increased volume in the perianal region, a mass with irregular and friable vegetative appearance for 2 weeks, with uninterrupted serosanguinolenta secretion, cytological exams were performed through a lesion decal, where it was possible to observe the presence of round, eccentric cells with prominent single nucleolus and with multiple clear vacuoles individually with well defined cytoplasmic limits. Treatment with chemotherapy with vincristine sulfate at a dose of 0.1 mg/kg was given intravenously with fluid therapy once a week for four weeks. The animal was discharged with complete remission of the lesions.(AU)

El tumor venéreo transmisible o Tumor de Sticker, se trata de una neoplasia de ocurrencia espontánea común en los órganos genitales, sin implicación de ningún agente infeccioso en sue tiología, cuando células tumorales o neoplásicas son implantadas mecánicamente, a través de montas naturales y también por lamedura excesiva de la zona genital, ocasionando lesiones en nariz, boca, cavidad oral e incluso en la piel, pero ha sido descrito en varias localizaciones extragenitales, como ano, globo ocular, tejido subcutáneo y piel. En el caso de la vacunación, se observó un aumento del volumen en la región perianal, una masa con aspecto vegetativo irregular y friable hace 2 semanas, con presencia de secreción serosanguinolenta ininterrumpida, se realizaron exámenes citológicos a través de la caldera de la lesión, donde fue posible observar la presencia de células redondas, excéntricas, con nucléolo único prominente y con múltiples vacuolos claros individualmente con límites citoplasmáticos bien definidos. Se estableció tratamiento con quimioterápico a través del sulfato de vincristina a una dosis de 0,1 mg/kg, administrada por vía intravenosa con fluidoterapia una vez a la semana durante cuatro semanas. El animal recibió alta con remisión completa de las lesiones.(AU)

Effect of Arrabidaea chica extract against chemically induced breast cancer in animal model

Purpose:To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats.Methods:We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments.Results:All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups.Conclusion:These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.(AU)

Sub-chronic administration of vincristine sulfate induces renal damage and apoptosis in rats via induction of oxidative stress and activation of Raf1-MEK1/2-Erk1/2 signal transduction / La administración subcrónica de sulfato de vincristina induce daño renal y apoptosis en ratas por inducción de estrés oxidativo y activación de la transducción de señales Raf1-MEK1/2-Erk1/2

SUMMARY: In spite of being one of the most powerful anti-cancer drug, the nephrotoxicity of Vincristine (VCR) is not well established in either animals or humans. Hence, this study evaluates the nephrotoxic effect of VCR in rats after sub-chronic long-term administration. Rats were divided into 2 groups (n=10/group) of either control and VCR treated rats (50 mg/kg). Treatments were carried out for 30 consecutive days, after which a series of biochemical and molecular experiments related to kidney function were evaluated. VCR administration significantly decreased the survival rate (69.8 %) and impaired renal function as evidenced by lowered creatinine (Cr) clearance (Ccr), high serum levels of urea and Cr, increased urinary protein levels and resulted in sever cortex pathological alterations, including glomerulus congestion and damage as well as vascular degenerations up to necrosis of both proximal and distal convoluted tubules. Mechanistically, VCR lowered renal antioxidant potential and ATP levels, enhanced lipid peroxidation and induced inflammation. In addition, VCR induced activation of Raf-1-MEK1/2-ERK1/2 signaling pathway leading to downregulation of Bcl2 and upregulation of P53, Bax, and cleaved caspase-3. In conclusion, these findings show a nephrotoxic effect of VCR sulfate in rats after sub-chronic administration and such effect was mediated by activation of ERK1/2 induced apoptosis.

RESUMEN: A pesar de ser uno de los medicamentos de mayor eficacia contra el cáncer, aún no se ha establecido la nefrotoxicidad de la vincristina (VCR) en animales y humanos. Por lo tanto, este estudio evalúa el efecto nefrotóxico de la VCR en ratas después de la administración subcrónica a largo plazo. Las ratas se dividieron en 2 grupos (n = 10 / grupo) de control y ratas tratadas con VCR (50 mg / kg). Los tratamientos se llevaron a cabo durante 30 días consecutivos, después de los cuales se evaluaron una serie de experimentos bioquímicos y moleculares relacionados con la función renal. La administración de VCR disminuyó significativamente la tasa de supervivencia (69,8 %), dificultó la función renal, lo que se observó además en los bajos niveles de creatinina (Cr) (Ccr), los niveles séricos elevados de urea y Cr, un nivel más alto de proteína urinaria, los que dieron lugar a alteraciones patológicas severas de la corteza, incluido el glomérulo congestión y daño, como también degeneraciones vasculares, incluyendo la necrosis de los túbulos contorneados proximales y distales. Mecánicamente, el VCR redujo el potencial antioxidante renal y los niveles de ATP, mejoró la peroxidación lipídica y la inflamación inducida. Además, la VCR indujo la activación de la vía de señalización Raf-1-MEK1 / 2-ERK1 / 2 que conduce a la regulación negativa de Bcl-2 y la regulación positiva de P53, Bax y la caspasa-3. En conclusión, estos hallazgos muestran un efecto nefrotóxico del sulfato de VCR en ratas después de la administración subcrónica. Dicho efecto fue mediado por la activación de la apoptosis inducida por ERK1 / 2.