RESUMEN
Twenty-five cats at a private animal sanctuary received multiple nonimmunosuppressive doses of parenteral methylprednisolone acetate for at least 3 yr. Complete blood count, chemistry, and T4 results from these cats were examined to look for statistically significant changes. Results found significant changes in triglycerides, amylase, and monocytes. However, these changes remained within the reference interval. All other values showed no significant changes. These results suggest that after 3 yr of chronic parenteral administration of nonimmunosuppressive doses of methylprednisolone acetate, the complete blood count, chemistry, and T4 values in 25 cats were not significantly affected and did not result in abnormal laboratory values.
Asunto(s)
Recuento de Células Sanguíneas/veterinaria , Gatos/sangre , Acetato de Metilprednisolona/uso terapéutico , Animales , Análisis Químico de la Sangre/veterinaria , Esquema de Medicación , Acetato de Metilprednisolona/administración & dosificación , Acetato de Metilprednisolona/efectos adversos , Faringitis/tratamiento farmacológico , Faringitis/veterinaria , Valores de Referencia , Estudios Retrospectivos , Estomatitis/tratamiento farmacológico , Estomatitis/veterinariaRESUMEN
Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although once used in clinical medicine as skin adhesives, these products caused tissue toxicity and thus their use in live tissue was discontinued. SCCA were replaced by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St Paul, Minnesota), which were found to be less toxic than the short-chain formulations. Some researchers prefer to use SCCA due to the belief that they create a stronger bond than do the longer-chain counterparts. In survival surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation, and bone regeneration in the calvaria of control (naïve), surgery-only, SCCA-treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery, all mice except those treated with SCCA showed statistically similar bone measurements to those of the naive control group. The SCCA group had significantly less bone regeneration than did all other groups. These results suggest that the application of SCCA causes bone damage resulting in the loss of bone regeneration. This finding may assist investigators in choosing a tissue glue for their studies and may support the IACUC in advocating the use of pharmaceutical-grade tissue glues.
Asunto(s)
Cianoacrilatos/toxicidad , Enbucrilato/toxicidad , Cráneo/efectos de los fármacos , Adhesivos Tisulares/toxicidad , Animales , Regeneración Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Cianoacrilatos/administración & dosificación , Enbucrilato/administración & dosificación , Femenino , Ratones , Cráneo/citología , Adhesivos Tisulares/administración & dosificaciónRESUMEN
The insulin-like growth factor binding protein IGFBP-3 is a proapoptotic and antiangiogenic protein in prostate cancer (CaP). Epidemiologic studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IGFBP-3KO mice) failed to undergo apoptosis after castration. Spontaneous prostate tumors did not develop in IGFBP-3KO mice, but splenic lymphomas occurred in 23% of female IGFBP-3KO mice by 80 weeks of age. To assess the effects of IGFBP-3 deficiency on prostate cancer development, we crossed IGFBP-3KO mice with a c-Myc-driven model of CaP that develops slow-growing, nonmetastatic tumors. By 24 weeks of age, well-differentiated prostate cancers were observed in all mice regardless of IGFBP-3 status. However, by 80 weeks of age IGFBP-3KO mice tended to exhibit larger prostate tumors than control mice. More strikingly, lung metastases were observed at this time in 55% of the IGFBP-3KO mice but none in the control animals. Cell lines established from IGFBP-3KO:Myc tumors displayed more aggressive phenotypes in proliferation, invasion, and colony formation assays, relative to control Myc tumor cell lines. In addition, Myc:IGFBP-3KO cells exhibited evidence of epithelial-mesenchymal transition. Our findings established a function for IGFBP-3 in suppressing metastasis in prostate cancer, and they also offered the first reported transgenic model of spontaneous metastatic prostate cancer for studies of this advanced stage of disease.
Asunto(s)
Adenocarcinoma/secundario , Andrógenos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/fisiología , Invasividad Neoplásica/genética , Proteínas de Neoplasias/fisiología , Neoplasias Hormono-Dependientes/secundario , Neoplasias de la Próstata/patología , Adenocarcinoma/genética , Animales , Apoptosis , Línea Celular Tumoral/citología , Cruzamientos Genéticos , Transición Epitelial-Mesenquimal/genética , Femenino , Perfilación de la Expresión Génica , Genes myc , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/deficiencia , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neoplasias Pulmonares/secundario , Linfoma no Hodgkin/genética , Masculino , Ratones , Ratones Noqueados , Neoplasias Hormono-Dependientes/genética , Orquiectomía , Fenotipo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias del Bazo/genética , Carga Tumoral , Ensayo de Tumor de Célula MadreRESUMEN
UNLABELLED: Better intraprostatic cancer imaging techniques are needed to guide clinicians in prostate cancer treatment decisions. Because many genes are specifically overexpressed in cancer cells, one strategy to improve prostate cancer detection is to image intraprostatic cancer-specific transcriptional activity. Because of the obstacles of weak cancer- or tissue-specific promoter activity and bladder clearance of many PET tracers, intraprostatic PET of gene transcriptional activity has not been previously reported. METHODS: The two-step transcriptional amplification (TSTA) system that amplifies the prostate-specific antigen promoter activity was used for PET imaging of the reporter gene herpes simplex virus type-1 sr39 thymidine kinase (HSV1-sr39tk). The TSTA-sr39tk system was injected directly into prostates or prostatic tumors as a replication-incompetent adenovirus (AdTSTA-sr39tk) and imaged using PET. RESULTS: AdTSTA-sr39tk was able to image prostate-specific antigen promoter transcriptional activity by 9-(4-(18)F-fluoro-3-[hydroxymethyl]butyl)guanine PET, in both mouse and canine prostates in vivo. Ex vivo small-animal PET images, scintigraphic counts, and sr39tk expression analysis confirmed the specificity of the observed signal. CONCLUSION: Here, by combining the TSTA-amplified signal with a protocol for tracer administration, we show that in vivo PET detection of transcriptional activity is possible in both mouse and immunocompetent canine prostates. These results suggest that imaging applications using transcription-based tumor-specific promoters should be pursued to better visualize cancer foci that escape detection by conventional biopsies.