RESUMO
Histone deacetylation is an important mechanism involved in human breast cancer tumorigenesis and recent veterinary oncology studies also demonstrate a similar relationship in some canine neoplasms. The use of HDAC inhibitors in vitro and in vivo has demonstrated antitumor action on several strains of human and animal cancers. The present study aims to correlate the expression of H3K9Ac, H4K12Ac, HDAC1, HDAC2 and HDAC6 in simple mammary carcinomas in dogs with clinicopathological parameters and overall survival time. To this end, 61 samples of simple breast carcinomas were analyzed by the immunohistochemistry technique with subsequent validation of the antibodies by the Western Blot technique. The expressions obtained via a semi-quantitative way were categorized by assigning scores and classified into high or low expressions according to the given score, except for HDAC6, when the marking percentage was considered and subdivided into high and low expressions using the median value. For statistical analysis, the chi-square test or Fisher exact test were used as univariate analysis and correspondence analysis as a multivariate test, in addition to the Kaplan-Meier survival analysis. In the studied samples, the highest frequencies were determined for the high expression proteins H4K12Ac (88.5%), HDAC2 (65.6%) and HDAC6 (56.7%) and the low expression proteins H3K9Ac (73.8%) and HDAC1 (54.1%). An association between the low expression of HDAC1 and the presence of lymph node metastasis (p = 0.035) was indicated by univariate analysis while the high expression of HDAC1 was associated with favorable prognostic factors, such as the absence of lymph node metastasis and low mitotic index by multivariate analysis. Also, by multivariate analysis, the low expression of HDAC6 was correlated with the low expression of Ki67, smaller tumors, and better prognosis factors as well. Protein expression was not correlated with patients' overall survival time (p > 0.05). The high expressions of HDAC2 and HDAC6 in mammary carcinomas in female dogs may be useful information for research involving therapeutic targets with iHDACs since their inhibition favors hyperacetylation and transcription of tumor suppressor genes.
RESUMO
Electroporation is a technique that increases the uptake of chemotherapeutic drugs by tumors. Electrochemotherapy (ECT) has been successfully used to treat solid tumors. Recently, novel applications have been explored in the treatment of visceral tumors. This report aimed to describe the ECT as an approach to vesical carcinoma in three dogs. The patients received ECT with bleomycin as an intravenous bolus and intra-lesional cisplatin (cases 2 and 3). The ECT was performed by electroporator (Onkodisruptor®) using a plate and/or a single pair needle array electrode. Case 1 was a 7-year-old female Pitbull dog with a history of hematuria and stranguria. The ECT was performed during cystotomy using a single pair array electrode. However, the patient developed uroabdomen two days post-ECT and died 5 days later. Case 2 was a 12-year-old female Poodle dog with hematuria, dysuria, and pollakiuria. Cystotomy and ECT were performed using plate array electrodes. Complete remission of the intra-luminal mass was observed 11 days post-ECT. However, 21 days after the procedure, an acute unilateral renal failure occurred possibly due to a neoplastic embolus into the right ureter leading to kidney hydronephrosis, and the patient was euthanized. Case 3 was a 10-year-old female Cocker dog with hematuria and pollakiuria. The patient was fully competent after ECT without clinical signs of pollakiuria and recovered from hematuria 7 days post-ECT. The bladder returned to normal status 28 days post-ECT. The ECT was not able to increase the overall survival of the patients evaluated and should be indicated carefully.