Presença da mutação do gene BRCA1 em cadelas com tumores mamários malignos / Presence of BRCA1 gene mutation in bitches with malignant mammary tumors

Mammary tumors (MTs) in bitches are similar to breast cancers in women. Thus, they can be used as a model for human breast cancer and findings can be extrapolated for use in human medicine. BRCA1 is a tumor suppressor gene. When the gene has a mutation, it cannot repair damaged DNA, which causes genetic instability and tumorigenesis. Therefore, we aimed to study the frequency of single nucleotide polymorphisms (SNPs) in the BRCA1 gene that are associated with distinct histological types of malignant MT in bitches. The study population consisted of 91 bitches, including a control group of 6 animals with healthy mammary glands and 85 animals with MTs. All animals underwent a presurgery evaluation consisting of a questionnaire administered to the person responsible for the animal, a physical examination, collection of peripheral blood for hematological and serum biochemistry evaluations, an electrocardiogram, and a preanesthesia evaluation. In addition, distant metastasis was studied via chest radiography and abdominal ultrasound. After evaluations were complete, the animals that could undergo surgery were administered general anesthesia and underwent a mastectomy or mammary gland sample collection. Histopathological examination and molecular analysis were performed to identify mutations in the BRCA1 gene. Histopathological examinations found 10 different types of malignant tumors in 36 sick animals. Tumor samples plus samples from the 6 control animals were subjected to DNA extraction, polymerase chain reaction (PCR) analysis, and genetic sequencing. The tumor with the highest incidence (33.33%) was a complex carcinoma, followed by carcinoma in mixed tumor (13.88), tubular carcinoma (13.88) and carcinosarcoma (13.88). Molecular analysis revealed 3 different SNP points in 5 samples (4006G>A, 3619A>G, and 3761C>T). The allelic variant 4006G>A (1/36) resulted in the alteration of the amino acid valine by isoleucine (V1336 I). The mutation 3619A>G (2/36) inserted the amino acid alanine instead of threonine (T1207 A). The mutation 3761C>T (2/36) led to the alteration of the amino acid serine by phenylalanine (S1254 F), a mutation for which there are no published reports. The histological types that showed BRCA1 mutations were complex carcinoma (1/5), carcinoma in mixed tumor (1/5), papillary carcinoma (1/5) and tubular carcinoma (2/5). Software analysis identified the new SNP (nucleotide 3761) in BRCA1 and 2 point mutations in nucleotides 4006 and 3619 and responsible for genetic instability. The development of breast cancer is caused by many endogenous and exogenous factors. The results of our study show that these factors have a greater presence in female, mixed breed, uncastrated, and older dogs, confirming the data in the veterinary literature. In the present study, we found different histological types of malignant breast tumors with mutations in the BRCA1 gene, as other authors have reported. However, we also found the mutation 3761C>T, which, to the best of our knowledge, has not been reported in the literature. This shows the need for studies in veterinary medicine that assess mutations in the BRCA1 gene and the most common histological types. In conclusion, SNPs in the BRCA1 gene cause genetic instability, resulting in additional mutations that lead to the development of breast tumors. They are point mutations that affect transcription, resulting in truncated proteins. These proteins may have a loss of function, leading to carcinogenesis.(AU)

Comparison of the effects of maropitant, lidocaine, and dextroketamine administered by the intratesticular route in dogs undergoing elective orchiectomy

Background: Balanced anesthesia achieved with combinations of inhaled and injectable drugs administered systemicallyor in loco-regional anesthetic blocks, is widely used in veterinary medicine. The use of anesthesia and/or local analgesiahas already demonstrated benefits in the performance of elective orchiectomy in different species, there is no literature thatevaluates the use of the maropitant intratesticular route. The present study evaluated the cardiorespiratory variables andanalgesia produced by intratesticular blockade with maropitant, lidocaine, or dextroketamine during the trans-operativeperiod along with the discharge and anesthetic recovery of dogs that underwent elective orchiectomy.Materials, Methods & Results: Used twenty-four dogs from routine elective orchiectomy, considered healthy based onthe results of clinical and hematological tests. The animals were randomly divided into three groups and was applied intratesticularly 2% lidocaine at a dose of 1 mg/kg (GL), 5% dextrocetamina at a dose of 2.5 mg/kg (GC), or 1% maropitantat a dose of 1 mg/kg (GM). Anesthesia induction was performed with propofol (to effect), and stabilization of inhalationalanesthesia was achieved with 1.7 V% of sevoflurane diluted in 100% oxygen administered through a calibrated vaporizerand appropriate anesthetic system based on the animal’s weight, being kept under spontaneous ventilation, After induction, we waited 10 min for stabilization of exhaled anesthetic concentration and then administered one of the treatmentsintratesticularly. After five min from the local block the surgical procedure was started during up to 15 min. Heart rate(HR), respiratory rate (RR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure(MAP), oxygen saturation of hemoglobin (SatO2), end-tidal carbon dioxide partial pressure (EtCO2), end-tidal sevofluraneconcentration...

Comparison of the effects of maropitant, lidocaine, and dextroketamine administered by the intratesticular route in dogs undergoing elective orchiectomy

Background: Balanced anesthesia achieved with combinations of inhaled and injectable drugs administered systemicallyor in loco-regional anesthetic blocks, is widely used in veterinary medicine. The use of anesthesia and/or local analgesiahas already demonstrated benefits in the performance of elective orchiectomy in different species, there is no literature thatevaluates the use of the maropitant intratesticular route. The present study evaluated the cardiorespiratory variables andanalgesia produced by intratesticular blockade with maropitant, lidocaine, or dextroketamine during the trans-operativeperiod along with the discharge and anesthetic recovery of dogs that underwent elective orchiectomy.Materials, Methods & Results: Used twenty-four dogs from routine elective orchiectomy, considered healthy based onthe results of clinical and hematological tests. The animals were randomly divided into three groups and was applied intratesticularly 2% lidocaine at a dose of 1 mg/kg (GL), 5% dextrocetamina at a dose of 2.5 mg/kg (GC), or 1% maropitantat a dose of 1 mg/kg (GM). Anesthesia induction was performed with propofol (to effect), and stabilization of inhalationalanesthesia was achieved with 1.7 V% of sevoflurane diluted in 100% oxygen administered through a calibrated vaporizerand appropriate anesthetic system based on the animals weight, being kept under spontaneous ventilation, After induction, we waited 10 min for stabilization of exhaled anesthetic concentration and then administered one of the treatmentsintratesticularly. After five min from the local block the surgical procedure was started during up to 15 min. Heart rate(HR), respiratory rate (RR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure(MAP), oxygen saturation of hemoglobin (SatO2), end-tidal carbon dioxide partial pressure (EtCO2), end-tidal sevofluraneconcentration...(AU)

AVALIAÇÃO DE POLIMORFISMO NO GENE BRCA1 EM CADELAS COM TUMORES MAMÁRIOS

Tumores mamários (TM) são altamente incidentes em fêmeas inteiras, adultas e possui padrão multifatorial. O gene BRCA1 é um gene supressor tumoral e, por isso, mutações nele causam defeitos no reparo de danos ao DNA e uma instabilidade genética que favorece a tumorigênese. Está diretamente relacionado ao risco de desenvolvimento do câncer mamário humano familiar. Há poucos estudos na veterinária que associam o desenvolvimento de TM caninos com polimorfismos em nucleotídeo simples (SNP) encontrados no BRCA1. Trinta e seis amostras de TM malignos e seis amostras controle foram submetidas à extração de DNA, PCR e sequenciamento genético. As analises de polimorfismo foram realizadas por meio de um software, Polyphen2. Foram encontrados 10 tipos histológicos distintos de tumores. O carcinoma complexo foi o tumor com maior incidência com 33,33%. Três pontos diferentes de SNP foram identificados em cinco amostras de cadelas com tumores mamários. Dois em 3761C > T, e um em 4006G > A, que causaram alteração do aminoácido, e classificados pelo Software PolyPhen como prejudiciais. E dois SNP em 3619A > G, que também causou substituição do aminoácido, mas foi considerado pelo Software como benigno. Em conclusão, SNPs no gene BRCA1 podem causar perda da estrutura da proteína, causando perda de função, assim favorecendo o processo de carcinogênese.

Breast tumors (TM) are highly incidental in whole adult females and have a multifactorial pattern. The BRCA1 gene is a tumor suppressor gene because mutations in it cause defects in the repair of DNA damage and genetic instability that favors tumorigenesis. It is directly related to the risk of developing familial human breast cancer. There are few veterinary studies that associate the development of canine TM with single nucleotide polymorphisms (SNPs) found in BRCA1. Thirty-six malignant TM samples were submitted to DNA extraction, PCR and genetic sequencing, and six samples that formed a control group. Ten different histological types of tumors were found. Complex carcinoma was the tumor with the highest incidence with 33.33%. Three different SNP sites were identified in five samples. Two at 3761C> T, and one at 4006G> A that caused amino acid change, and classified by the PolyPhen Software as harmful. And two SNPs in 3619A> G, which also caused amino acid substitution, but was considered by the Software as benign. In conclusion, SNPs in the BRCA1 gene can cause loss of protein structure, causing loss of function, thus favoring the process of carcinogenesis.