RESUMEN
Gastric cancer is the third leading cause of cancer-related death worldwide. Diffuse type gastric cancer has the worst prognosis due to notorious resistance to chemotherapy and enrichment of cancer stem-like cells (CSC) associated with the epithelial-to-mesenchymal transition (EMT). The unique proline isomerase PIN1 is a common regulator of oncogenic signaling networks and is important for gastric cancer development. However, little is known about its roles in CSCs and drug resistance in gastric cancer. In this article, we demonstrate that PIN1 overexpression is closely correlated with advanced tumor stages, poor chemo-response and shorter recurrence-free survival in diffuse type gastric cancer in human patients. Furthermore, shRNA-mediated genetic or all-trans retinoic acid-mediated pharmaceutical inhibition of PIN1 in multiple human gastric cancer cells potently suppresses the EMT, cell migration and invasion, and lung metastasis. Moreover, PIN1 genetic or pharmaceutical inhibition potently eliminates gastric CSCs and suppresses their self-renewal and tumorigenicity in vitro and in vivo Consistent with these phenotypes, are that PIN1 biochemically targets multiple signaling molecules and biomarkers in EMT and CSCs and that genetic and pharmaceutical PIN1 inhibition functionally and drastically enhances the sensitivity of gastric cancer to multiple chemotherapy drugs in vitro and in vivo These results demonstrate that PIN1 inhibition sensitizes chemotherapy in gastric cancer cells by targeting CSCs, and suggest that PIN1 inhibitors may be used to overcome drug resistance in gastric cancer.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos , Neoplasias Pulmonares/tratamiento farmacológico , Peptidilprolil Isomerasa de Interacción con NIMA/antagonistas & inhibidores , Células Madre Neoplásicas/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Tretinoina/farmacología , Adulto , Animales , Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Pronóstico , ARN Interferente Pequeño/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed. AIM: To investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor. METHODS: In this study, a rabbit liver VX2 tumor model was established. After laparotomy, under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis. RESULTS: The spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue. CONCLUSION: Hyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.
RESUMEN
BACKGROUND: The diagnosis of extraneural metastasis from glioblastoma is usually based on the histopathology and immunohistochemical staining of a tumor specimen. Information regarding the molecular features of glioblastoma and optimal treatment strategies for extraneural metastasis is limited. CASE DESCRIPTION: A 58-year-old woman with a glioblastoma located in the left temporal lobe underwent resection followed by radiotherapy plus concomitant and adjuvant temozolomide. Ipsilateral cervical lymph node tumors were treated 29 months later with supraomohyoid neck dissection and temozolomide. The diagnosis of lymph node metastases from glioblastoma was confirmed with an OncoScan assay and pathologic analysis. The brain and lymph node tumors had identical genotypes: C228T-mutated TERT promoter, wild-type IDH1, wild-type IDH2, wild-type TP53, EGFR amplification, and unmethylated MGMT promoter. Subsequently, multiple bone metastases were detected and treated with CyberKnife radiosurgery. Widespread extraneural metastases were detected 49 months after the initial diagnosis, and the patient underwent chemotherapy with cisplatin and semustine. There was no evidence of intracranial relapse until death, which occurred 5 months after chemotherapy. CONCLUSIONS: Similar to carcinomas, glioblastomas can spread via the lymphatic route. Extensive therapies for extraneural metastases from glioblastoma can alleviate discomfort and prolong survival, especially in patients without intracranial relapse.