RESUMO
The present study investigated the expression profiles of the epidermal growth factor receptor (EGFR) family, which consists of four transmembrane tyrosine kinase receptors and their eight ligands, in 122 patients with colorectal cancer (CRC) using reverse transcription-quantitative polymerase chain reaction analysis. On comparison of the CRC primary tumor and matched adjacent normal mucosa (ANM) tissue samples, the mRNA expression levels of ErbB3, but not ErbB1, were significantly increased in CRC tissue samples, compared with those in the ANM tissues. The expression levels of the ligands exhibited opposing trends to their corresponding receptors, including EGF, BTC, AREG, EREG and HBEGF, which were increased in the CRC tissues, whereas NRG1 and NGR2 were decreased in thee CRC tissues, compared with those in the AMN tissues. Subsequently, the present study investigated the frequency of K-ras mutations in the patients with CRC. The Kras mutations were found to be present in 36.8% (45/122) of the cases, however, no correlation was observed between Kras mutations and clinicopathological characteristics. In the CRC tissues, the expression levels of the EGFR family receptors and their ligands were determined in wild-type and mutant K-ras CRC cases. The expression levels of ErbB1, ErbB2, ErbB3, BTC, AREG, EREG, NRG1 and NRG2 were significantly decreased in the mutant Kras cases, compared with those in the wildtype Kras cases. These results suggested that the tumorigenesis of CRC with wildtype Kras was mediated through, not only ErbB1, but also through the ErbB2 and ErbB3 pathways. Notably, although ErbB2 does not bind any ErbB ligands, ErbB2 may activate tumorigenesis via a heterodimer, rather than a homodimer. Therefore, the results of the present study suggest that the most effective strategy to target not only ErbB1, but also ErbB2 and ErbB3, is the use of monoclonal antibody treatment.
Assuntos
Neoplasias Colorretais/patologia , Receptores ErbB/genética , Ligantes , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Demografia , Regulação para Baixo , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Feminino , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Neurregulinas/genética , Neurregulinas/metabolismo , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , TranscriptomaRESUMO
BACKGROUND: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and novel effective treatments and diagnostic tools are urgently required. OBJECTIVE: The selection of appropriate targeting tumor-associated antigens (TAAs) is critical for immunotherapy. Therefore, we analyzed TAA expression levels and investigated their relationship with clinical factors in adjacent normal mucosa (ANM) and CRC tissue. METHODS: We obtained specimens of CRC primary tumors and matched ANM from 137 patients with CRC who underwent surgical resection. The mRNA levels of seven TAAs, Wilms' tumor gene (WT1), kinetochore associated-2 (KNTC2), cell division cycle associated-1 (CDCA1), M phase phosphoprotein-1 (MPHOSPH1), DEP domain-containing 1 (DEPDC1), 34-kDa translocase of the outer mitochondrial membrane (TOMM34) and ring finger protein-43 (RNF43), were analyzed using quantitative real-time reverse transcription-polymerase chain reaction, and their relationships with clinicopathological factors and the cell cycle were analyzed. RESULTS: The expression levels of all seven TAAs were significantly higher in CRC tissues than in ANM. Expression levels of WT1 in CRC tissues did not correlate with the cell cycle. Furthermore, WT1 expression in CRC tissues was significantly related to tumor progression, lymph node metastasis, distant metastasis and clinical stage. CONCLUSIONS: WT1 is a potential marker for prognosis and tumor progression in CRC.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Neoplasias Colorretais/patologia , Proteínas WT1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We report a patient with partial oculomotor paresis due to midbrain infarction. A 69-year-old man noticed diplopia suddenly. Ptosis, and impaired adduction and supraduction were found in the right eye. The pupillary size and light reflexes were normal on both sides. Magnetic resonance imaging disclosed an acute lesion in the right inferolateral oculomotor fascicle. These clinicoradiological findings suggested that the inferolateral fascicular damage could cause palsy of the levator palpebrae, medial rectus, superior rectus and inferior oblique muscles. Physicians should pay more attention to oculomotor fascicular infarction in patients with incomplete oculomotor paresis, and spared pupil sphincter and inferior rectus muscles.
