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BACKGROUND: Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. METHODS: This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. RESULTS: The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. CONCLUSIONS: The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.
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Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias Colorretais/terapia , Curcumina/administração & dosagem , Terapia por Estimulação Elétrica/métodos , Hipertermia Induzida/métodos , Resveratrol/administração & dosagem , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Disponibilidade Biológica , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Linhagem Celular Tumoral/transplante , Neoplasias Colorretais/patologia , Terapia Combinada/métodos , Curcumina/efeitos adversos , Curcumina/farmacocinética , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Nanopartículas/administração & dosagem , Ratos , Resveratrol/efeitos adversos , Resveratrol/farmacocinética , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
Plasmacytoid and rhabdoid variants of urothelial carcinomas (UCs) of the urinary bladder have been described in humans with plasma cell-like or rhabdoid cellular appearance and aggressive clinical outcome. Canine UC of the bladder is generally classified as papillary/nonpapillary and infiltrating/noninfiltrating with limited information regarding other histological patterns. We report 3 cases of UC of the urinary bladder showing a unique discohesive cellular morphology with malignant behavior resembling the human plasmacytoid and rhabdoid variants of UC, which may raise some difficulties in diagnosis. Epithelial-mesenchymal transition and reduced E-cadherin expression were revealed by immunohistochemistry in 2 cases, possibly explaining the discohesive and invasive behavior of the tumor cells. The findings broaden the morphological spectrum as well as the distinct clinical features of canine UC of the urinary bladder.
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Carcinoma/veterinária , Doenças do Cão/patologia , Transição Epitelial-Mesenquimal , Neoplasias da Bexiga Urinária/veterinária , Animais , Caderinas/metabolismo , Carcinoma/diagnóstico , Carcinoma/patologia , Doenças do Cão/diagnóstico , Cães , Feminino , Masculino , Bexiga Urinária/citologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologiaRESUMO
Forty-four dogs with multicentric lymphoma were treated using a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) induction protocol or treated using a cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CMOP) induction protocol. There was no statistical difference in signalment and the presence of historical negative prognostic factors between the groups. The median progression-free survival (PFS) in the CHOP and CMOP groups were 222 d and 162 d, respectively (P = 0.75). The median survival time (MST) of dogs in CHOP and CMOP groups were 318 d and 242 d, respectively (P = 0.63). Anorexia and diarrhea episodes were significantly higher in the CHOP group than in the CMOP group (P = 0.02 and P = 0.01, respectively). These results suggest that the CMOP protocol provides similar PFS, MST and causes fewer side effects compared to the CHOP protocol. Therefore, the CMOP protocol may be another treatment choice for canine multicentric lymphoma.
Comparaison de l'efficacité et de la toxicité de la doxorubicine et du mitoxantrone dans la chimiothérapie combinée pour le lymphome canin. Quarante-quatre chiens atteints d'un lymphome multicentrique ont été traités à l'aide d'un protocole d'induction au cyclophosphamide, à la doxorubicine, à la vincristine et à la prednisolone (CHOP) ou traités en utilisant un protocole d'induction à la cyclophosphamide, au mitoxantrone, à la vincristine et à la prednisolone (CMOP). Il n'y a eu aucune différence statistique dans le signalement et la présence des facteurs de pronostic négatifs historiques entre les groupes. La survie sans progression (SSP) médiane des groupes CHOP et CMOP était de 222 jours et de 162 jours, respectivement (P = 0,75). La durée de survie moyenne (DSM) des chiens des groupes CHOP et CMOP a été de 318 jours et de 242 jours, respectivement (P = 0,63). Les épisodes d'anorexie et de diarrhée ont été significativement plus élevés dans le groupe CHOP comparativement au groupe CMOP (P = 0,02 et P = 0,01, respectivement). Ces résultats suggèrent que le protocole CMOP offre une SSP et une DSM semblables tout en causant moins d'effets secondaires comparativement au protocole CHOP. Par conséquent, le protocole CMOP peut représenter un autre choix de traitement pour les lymphomes multicentriques canins.(Traduit par Isabelle Vallières).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doxorrubicina/uso terapêutico , Linfoma/veterinária , Mitoxantrona/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Cães , Doxorrubicina/efeitos adversos , Feminino , Linfoma/tratamento farmacológico , Masculino , Mitoxantrona/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Vincristina/uso terapêuticoRESUMO
Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumor-bearing dogs. Ten dogs were enrolled; three dogs did not report any adverse events; three had a mildly altered appetite; one had a mildly increased liver index, while the other three developed suspected anaphylaxis at different levels. The median progression-free interval was 49 days. Dogs with progressive disease during treatment had a shorter survival. This pilot study indicates limited efficacy with potential adverse events of this ACT. Most recruited patients were in a later stage and had macroscopic disease, which might affect the treatment efficacy. Further exploration of this cell therapy in an adjuvant setting, with adequate protocol modification and standardization, could still be considered.
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Fibrinogen-fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.
Assuntos
Biomarcadores Tumorais , Doenças do Cão , Produtos de Degradação da Fibrina e do Fibrinogênio , Neoplasias , Cães , Animais , Doenças do Cão/sangue , Doenças do Cão/mortalidade , Doenças do Cão/diagnóstico , Neoplasias/veterinária , Neoplasias/sangue , Neoplasias/mortalidade , Neoplasias/diagnóstico , Prognóstico , Estudos Retrospectivos , Masculino , Feminino , Biomarcadores Tumorais/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Análise de Sobrevida , Fibrinogênio/análiseRESUMO
Medical disputes in veterinary practices are widespread; yet, a limited amount of research has been conducted to investigate the factors contributing to medical disputes. This study examined veterinarians' and clients' perceptions regarding risk factors and possible solutions to medical disputes. A total of 245 respondents from Taiwan, including 125 veterinarians and 120 clients, completed an electronic self-administered, semi-structured questionnaire in 2022. The questionnaire covered six dimensions: medical skills, complaint management, the attitudes of stakeholders during interactions, medical expenses, clients' perspectives, and communication modes. The results highlighted significant differences in the perceptions of risk factors for inducing medical disputes and possible solutions between clients and veterinarians in veterinary practice. First, young veterinarians and clients perceived medical skills as the highest risk factor for inducing medical disputes, while experienced veterinarians disagreed (p < 0.001). In addition, veterinarians with medical dispute experience identified stakeholders' attitudes during interactions as the top contributing factor. Second, regarding possible solutions, all veterinarians preferred offering clients cost estimates and cultivating empathy and compassion towards them. On the other hand, clients underscored the importance of obtaining informed consent for treatments and expenses and suggested that veterinarians should supply comprehensive written information to facilitate this process. This study underlies the importance of understanding stakeholders' perceptions to mitigate medical disputes and advocates for improved communication education and training for young veterinarians. These findings provide valuable insights for veterinarians and clients, contributing to preventing and managing medical disputes in veterinary practices.
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This study compared the risk perceptions of medical disputes among veterinarians and veterinary students in Taiwan between 2014 and 2022. Online validity-tested questionnaires were used to collect data, with 106 (73 veterinarians and 33 students) and 157 (126 veterinarians and 31 students) surveys collected in 2014 and 2022, respectively. Respondents would be asked to rate their perceptions on how likely each risk factor constitutes a medical dispute according to their past experiences on a five-point Likert scale from 1 to 5: "Very unlikely, unlikely, neutral, likely, very likely." The results showed that overall risk perceptions increased significantly in 2022 compared to 2014, with the top risk factors being attitudes during interactions and complaint management among experienced veterinarians. In contrast, students considered medical skills and clients' perspectives as the top two risk factors, with complaints management ranking as the least significant factor. The findings suggest that effective communication and complaint management are crucial in preventing medical disputes, highlighting the importance of developing these skills in young veterinarians and veterinary students to reduce medical disputes. The study also recommends increasing practical experiences of medical disputes and complaint management in veterinary education to bridge the gap between the perceptions of experienced veterinarians and students.
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BACKGROUND: Tumor biomarkers have used widely in clinical oncology in human medicine. Only a few studies have evaluated the clinical utility of tumor biomarkers for veterinary medicine. A test for fibrinogen and fibrin degradation products (DR-70) has been proposed as an ideal biomarker for tumors in humans. The clinical value of DR-70 for veterinary medicine however has yet to be determined. OBJECTIVES: Investigate the diagnostic value of DR-70 concentrations by comparing them between healthy dogs and dogs with tumors. ANIMALS: Two hundred sixty-three dogs with different types of tumors were included. Sixty healthy dogs also were recruited for comparison. METHODS: The DR-70 concentrations were measured in all recruited individuals by ELISA. Clinical conditions were categorized based on histopathology, cytology, ultrasound examination, radiology, clinical findings, and a combination of these tests. RESULTS: The median concentration of DR-70 was 2.130 ± 0.868 µg/mL in dogs with tumors, which was significantly higher than in healthy dogs (1.202 ± 0.610 µg/mL; P < .0001). With a cut-off of 1.514 µg/mL, the sensitivity and specificity of DR-70 were 84.03% and 78.33%, respectively. The area under curve was 0.883. The DR-70 concentration can be an effective tumor biomarker in veterinary medicine. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased DR-70 concentrations were not affected by tumor type, sex, age, or body weight. However, in dogs with metastatic mast cell tumors and oral malignant melanoma, DR-70 concentrations were significantly increased. Additional studies, including more dogs with nonneoplastic diseases, are needed to further evaluate the usefulness of DR-70 as a tumor biomarker.
Assuntos
Biomarcadores Tumorais , Doenças do Cão , Produtos de Degradação da Fibrina e do Fibrinogênio , Neoplasias , Animais , Cães , Humanos , Biomarcadores Tumorais/sangue , Doenças do Cão/sangue , Doenças do Cão/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/metabolismo , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/veterinária , Sensibilidade e EspecificidadeRESUMO
Research of veterinary communication education is a relatively rare but important field, and its importance has been increasingly noticed recently. This study aims to describe the existing veterinary education research literature by adopting the systematic bibliometric approach. We conducted a comprehensive literature exploration on worldwide veterinary education and veterinary communication education publications in the Web of Science Core Collection database from 1 January 2000 to 31 December 2021. VOSviewer and EXCEL were used to identify trends and patterns in characteristics of the publications, including author affiliations and countries, and the publishing journals. Based on our search criteria, in the past 22 years, there have been 6006 veterinary education publications with 101 publications in 2000, 684 publications in 2021 (577% increase), and 677 communication-related publications with 9 publications in 2000, 107 publications in 2021 (1189% increase). The VOSviewer results indicate that both the United States and England were the most vigorous countries with close collaboration. Our results show the publication quantity has been increasing at a sharp slope rate over the past twenty years, which indicates the importance and growth of veterinary education and the veterinary communication education research field, and identifies the international collaborations among countries and institutions.
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Cyclophosphamide exhibits the weakest therapeutic effect compared with vincristine and doxorubicin in the CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisolone) chemotherapeutic protocol for the treatment of canine lymphoma. Twenty dogs with multicentric lymphoma were treated using the LHOP protocol, which used l-asparaginase in place of cyclophosphamide, and the outcomes were historically compared with those of dogs that received CHOP chemotherapy in the same institution. No significant differences were found in age (p = 0.107), body weight (p = 0.051), sex (p = 0.453), clinical stage V (p = 1), substage b (p = 0.573), T-cell phenotype (p = 0.340), overall response (p = 1), and hypercalcaemia status (p = 1) between the LHOP and CHOP groups. The adverse effects of l-asparaginase were well tolerated and self-limiting. The median PFS (progression-free survival) and median ST (survival time) in the LHOP group were 344 days (range: 28-940 days) and 344 days (range: 70-940 days), respectively. The median PFS and median ST in the CHOP group were 234 days (range: 49-1822 days) and 314 days (range: 50-1822 days), respectively. The dogs that received LHOP chemotherapy had a significantly longer PFS than the dogs that received CHOP chemotherapy (p = 0.001). No significant difference was observed in ST between the LHOP and CHOP groups (p = 0.131). Our study findings thus indicate that the LHOP protocol can be used as a first-line chemotherapeutic protocol in canine multicentric lymphoma.
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The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased- or decreased-weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained-weight group. The median progression-free survival (PFS) in the increased-weight group, maintained-weight group and decreased-weight group was 226, 256 and 129 days, respectively. The decreased-weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased-weight group, maintained-weight group and decreased-weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox-regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Animais , Antineoplásicos/efeitos adversos , Ciclofosfamida/uso terapêutico , Doenças do Cão/patologia , Cães , Doxorrubicina/uso terapêutico , Feminino , Linfoma , Masculino , Prednisona/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Aumento de Peso , Redução de PesoRESUMO
DNA methylation is a comprehensively studied epigenetic modification and plays crucial roles in cancer development. In the present study, MethylCap-seq was used to characterize the genome-wide DNA methylation patterns in canine high-grade B-cell lymphoma (cHGBL). Canine methylated DNA fragments were captured and the MEDIUM-HIGH and LOW fraction of methylated DNA was obtained based on variation in CpG methylation density. In the MEDIUM-HIGH and LOW fraction, 2144 and 1987 cHGBL-specific hypermethylated genes, respectively, were identified. Functional analysis highlighted pathways strongly related to oncogenesis. The relevant signaling pathways associated with neuronal system were also revealed, echoing recent novel findings that neurogenesis plays key roles in tumor establishment. In addition, 14 genes were hypermethylated in all the cHGBL cases but not in the healthy dogs. These genes might be potential signatures for tracing cHGBL, and some of them have been reported to play roles in various types of cancers. Further, the distinct methylation pattern of cHGBL showed a concordance with the clinical outcome, suggesting that aberrant epigenetic changes may influence tumor behavior. In summary, our study characterized genome-wide DNA methylation patterns using MethylCap-seq in cHGBL; the findings suggest that specific DNA hypermethylation holds promise for dissecting tumorigenesis and uncovering biomarkers for monitoring the progression of cHGBL.
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Metilação de DNA , Doenças do Cão/genética , Doenças do Cão/patologia , Epigênese Genética , Epigenômica , Estudo de Associação Genômica Ampla , Linfoma de Células B/veterinária , Animais , Transformação Celular Neoplásica/genética , Ilhas de CpG , Cães , Epigenômica/métodos , Estudo de Associação Genômica Ampla/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Gradação de Tumores , Análise de Sequência de DNARESUMO
Cyclophosphamide is commonly used in combination chemotherapy to treat dogs with lymphoma. The metabolite of cyclophosphamide, acrolein, can irritate urinary bladder and cause sterile hemorrhagic cystitis. Dividing the administration of cyclophosphamide across multiple days may reduce the concentration of this metabolite in urinary bladder and reduce the possibility of cystitis. However, the impact of the therapeutic effect of this modification is not evaluated and compared to traditional single maximum-tolerated dose regimen. Seventy-two dogs with multicentric lymphoma received either bolus doses or divided doses of cyclophosphamide were included in this study. The incidence of hemorrhagic cystitis between 2 cyclophosphamide treatment groups was not significantly different (Pâ¯=â¯.357). There was no statistical difference in progression-free survival and survival time between 2 groups (Pâ¯=â¯.267 and Pâ¯=â¯.346). This modification of cyclophosphamide administration did not reduce the side effect of cystitis or affect remission and survival times in lymphoma dogs.
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Ciclofosfamida/efeitos adversos , Cistite/veterinária , Doenças do Cão/induzido quimicamente , Linfoma/veterinária , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Cistite/induzido quimicamente , Cães , Esquema de Medicação , Feminino , Hemorragia/induzido quimicamente , Hemorragia/veterinária , Linfoma/tratamento farmacológico , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.
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Hidratação/instrumentação , Solução de Ringer/uso terapêutico , Choque Hemorrágico/terapia , Trometamina/uso terapêutico , Animais , Soluções Tampão , Soluções Cristaloides/uso terapêutico , Modelos Animais de Doenças , Masculino , Distribuição Aleatória , Ratos , Solução Salina/uso terapêuticoRESUMO
Feline coronavirus (FCoV) varies greatly from causing subclinical or mild enteric infections to fatal feline infectious peritonitis (FIP). The open reading frame (ORF) 7b of FCoV has been speculated to play a determining role in virulence as deletions were found to be associated with avirulent viruses. To further clarify the correlation between this gene and FIP, clinical samples from 20 cats that had succumbed to wet-type FIP and 20 clinically healthy FCoV-infected cats were analysed. The ORF7b from the peritoneal/pleural effusions of FIP cats and from the rectal swabs of healthy cats was amplified. Of the 40 FCoVs analysed, 32 were found to have an intact 7b gene whereas eight showed deletions of either three or 12 nucleotides. Surprisingly, among the eight viruses with deletions, three were from FIP diseased cats. These results show that deletions in the ORF7b gene are not constrained to low pathogenicity/enteric biotypes but also associated with pathogenicity/FIP biotypes of FCoV.
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Coronavirus Felino/genética , Peritonite Infecciosa Felina/virologia , Variação Genética , Genoma Viral , RNA Viral/genética , Animais , Gatos , Coronavirus Felino/patogenicidade , Feminino , Masculino , Dados de Sequência Molecular , RNA Polimerase Dependente de RNA/genéticaRESUMO
Canine MDR1 gene mutations produce translated P-glycoprotein, an active drug efflux transporter, resulting in dysfunction or over-expression. The 4-base deletion at exon 4 of MDR1 at nucleotide position 230 (nt230[del4]) in exon 4 makes P-glycoprotein lose function, leading to drug accumulation and toxicity. The G allele of the c.-6-180Tï¼G variation in intron 1 of MDR1 (single nucleotide polymorphism [SNP] 180) causes P-glycoprotein over-expression, making epileptic dogs resistant to phenobarbital treatment. Both of these mutations are reported to be common in collies. This study develops a more efficient method to detect these two mutations simultaneously, and clarifies the genotype association with the side effects of chemotherapy. Genotype distribution in Taiwan was also investigated. An oligonucleotide microarray was successfully developed for the detection of both genotypes and was applied to clinical samples. No 4-base deletion mutant allele was detected in dogs in Taiwan. However, the G allele variation of SNP 180 was spread across all dog breeds, not only in collies. The chemotherapy adverse effect percentages of the SNP 180 T/T, T/G, and G/G genotypes were 16.7%, 6.3%, and 0%, respectively. This study describes an efficient way for MDR1 gene mutation detection, clarifying genotype distribution, and the association with chemotherapy.
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Cães/fisiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/veterinária , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Polimorfismo de Nucleotídeo Único , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Cães/genética , Mutação/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , TaiwanRESUMO
YKL-40, a secreted glycoprotein, may serve as an autoantigen, which mediates multiple inflammatory diseases and cancers. A high YKL-40 serum level is correlated with metastasis and poor survival in a variety of human cancers. However, the role of YKL-40 in dogs is still under evaluation. Herein, we examined the associations between plasma YKL-40 level and YKL-40 autoantibody (YAA) titers with malignancy and prognosis in canine cancer. Plasma levels of YKL-40 in healthy dogs (n = 20) and in dogs (n = 82) with cancer were evaluated using enzyme-linked immunosorbent assay. Our results indicated that plasma YKL-40 levels were significantly higher (p < 0.01) in dogs with cancer than in healthy dogs. A significant decrease in the YAA titers was detected in the dogs with cancer when compared with those of the healthy dogs (p < 0.05), although the change was not correlated with the YKL-40 levels. Among the dogs with cancer, plasma YKL-40 levels in the dogs that later relapsed or had metastasis were significantly higher than in the dogs with no signs of relapse (p < 0.01) or metastasis (p < 0.05). The relapse and metastasis rates were significantly higher in the high YKL-40 group (> 180 pg/mL) than in the low YKL-40 group (< 180 pg/mL). The results imply that plasma YKL-40 levels might have the potential to be developed as a marker of malignancy progression and prognosis in canine cancers.
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Biomarcadores Tumorais/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Doenças do Cão/metabolismo , Neoplasias/veterinária , Animais , Doenças do Cão/diagnóstico , Cães , Neoplasias/diagnóstico , Neoplasias/metabolismo , PrognósticoRESUMO
OBJECTIVE: To investigate the antitumor effect of the chicken anemia virus (CAV) VP3 gene in canine mammary tumor (CMT) cells. SAMPLE POPULATIONS: Established primary canine cell lines that originated from epithelial cells of resected CMTs and nonneoplastic mammary gland epithelial (MGE) cells. PROCEDURES: Expression vectors and lentiviral vectors encoding the VP3 gene from a Taiwan-Ilan isolate of CAV were used to deliver the VP3 gene into CMT cells and nonneoplastic MGE cells. Ectopic gene expression and the pro-apoptotic effect of the VP3 gene on CMT and nonneoplastic MGE cells by either transfection or viral infection were evaluated via immunofluorescence microscopy, western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis. RESULTS: Overexpression of the enhanced green fluorescent protein-VP3 fusion protein was detected predominantly in the nuclei of CMT cells. In contrast, the VP3 protein was localized to the cytoplasm of nonneoplastic MGE cells. Among the fusion protein-expressing CMT cells, most underwent characteristic changes of apoptosis, whereas apoptosis was not detected in fusion protein-expressing, nonneoplastic MGE cells. Induction of apoptosis by VP3 gene overexpression in CMT cells was associated with the caspase-9-, but not the caspase-8-, mediated apoptosis pathway. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate that the VP3 gene of the CAV induces apoptosis in malignant CMT cells, but not in nonneoplastic canine MGE cells. On the basis of such tumor cell-specific killing, the VP3 gene may be a promising agent for the treatment of malignant mammary gland tumors in dogs.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas do Capsídeo/uso terapêutico , Vírus da Anemia da Galinha/genética , Doenças do Cão/terapia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Terapia Genética/métodos , Neoplasias Mamárias Animais/terapia , Animais , Western Blotting/veterinária , Proteínas do Capsídeo/farmacologia , Linhagem Celular Tumoral , Cães , Vetores Genéticos , Marcação In Situ das Extremidades Cortadas/veterinária , Lentivirus , Microscopia de Fluorescência/veterináriaRESUMO
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ (NSG) mice after sublethally irradiation. We examined the GNLY expression and its effects on tumor growth using this system. Our HIS mice expressed human CD45+, CD4+, CD8+ and CD56+ cells in the peripheral blood and spleen. A high expression level of human Th1/Th2 and NK cytokines was detected, indicating the activation of both T and NK cells. Importantly, we found an elevated level of GNLY in the serum and it was produced by human CTLs and NK cells obtained from the peripheral blood mononuclear cells and spleen cells in the HIS mice. The serum level of GNLY was negatively correlated with the proliferation of transplanted tumor cells in HIS mice. Collectively, our findings strongly supported that HIS mouse as a valuable model for studying human cancer under an intact immune system and the role of GNLY in tumorigenesis.
RESUMO
Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P < 0.01), compared with vincristine (n = 9) or doxorubicin (n = 5). Therefore, the therapeutic outcome of traditional CHOP-based chemotherapy might be improved by replacing cyclophosphamide with other cytotoxic drugs.