RESUMO
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is essential for apoptosis, proliferation, differentiation, and immune responses, and is a candidate marker for residual feed intake (RFI) in pig. We cloned the full-length cDNA sequence of porcine MAP3K5 by rapid-amplification of cDNA ends. The 5451-bp gene contains a 5'-untranslated region (UTR) (718 bp), a coding region (3738 bp), and a 3'-UTR (995 bp), and encodes a peptide of 1245 amino acids, which shares 97, 99, 97, 93, 91, and 84% sequence identity with cattle, sheep, human, mouse, chicken, and zebrafish MAP3K5, respectively. The deduced MAP3K5 protein sequence contains two conserved domains: a DUF4071 domain and a protein kinase domain. Phylogenetic analysis showed that porcine MAP3K5 forms a separate branch to vicugna and camel MAP3K5. Tissue expression analysis using real-time quantitative polymerase chain reaction (qRT-PCR) revealed that MAP3K5 was expressed in the heart, liver, spleen, lung, kidney, muscle, fat, pancrea, ileum, and stomach tissues. Copy number variation was detected for porcine MAP3K5 and validated by qRT-PCR. Furthermore, a significant increase in average copy number was detected in the low RFI group when compared to the high RFI group in a Duroc pig population. These results provide useful information regarding the influence of MAP3K5 on RFI in pigs.
Assuntos
MAP Quinase Quinase Quinase 5/genética , Sus scrofa/genética , Sequência de Aminoácidos , Animais , Domínio Catalítico , Clonagem Molecular , Variações do Número de Cópias de DNA , Dosagem de Genes , Expressão Gênica , Interações Hidrofóbicas e Hidrofílicas , MAP Quinase Quinase Quinase 5/química , MAP Quinase Quinase Quinase 5/metabolismo , Modelos Moleculares , Especificidade de Órgãos , Filogenia , Conformação Proteica em alfa-Hélice , Sus scrofa/metabolismoRESUMO
BACKGROUNDS: The present study aimed to evaluate benefit of hepatic arterial infusion chemotherapy (HAI) combined with systemic chemotherapy (SCT) for patients with colorectal liver metastases (CLMs) in a palliative setting. METHODS: This was a retrospective single-center study including 43 consecutive patients with CLM after failure of standard SCT. Among them, 20 (47 %) patients underwent HAI combined with SCT (Group A) and 23 historical control patients who had received SCT with or without targeted agent treatment (Group B). RESULTS: The two groups had similar characteristics. Compared with SCT alone, HAI combined with SCT prolonged survival (median 19.8 vs. 9.0 months; P = 0.045). Median hepatic progression-free survival was significantly longer for HAI combined with SCT vs. SCT alone (median 8.1 vs. 4.7 months; P = 0.027), as were response rates (25 and 0 %; P = 0.038) and progression-free survival (median 5.7 vs. 3.0 months; P = 0.02). Three patients (15 %) achieved conversion to potentially curative surgery. Grade 3/4 toxicities for Group A and Group B were neutropenia (5 and 8.7 %, respectively), anemia (5 and 0 %, respectively), and hyperbilirubinemia (0 and 4.3 %, respectively). Other complications were mostly grade 1 or 2. CONCLUSIONS: HAI combined with SCT treatment can improve overall survival compared with SCT alone in highly advanced CLM refractory to intravenous chemotherapy.