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2.
Mol Cancer Ther ; 19(3): 906-919, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31879364

RESUMO

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.


Assuntos
Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Peptidilprolil Isomerase de Interação com NIMA/antagonistas & inibidores , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Tretinoína/farmacologia , Adulto , Animais , Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Peptidilprolil Isomerase de Interação com NIMA/genética , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , RNA Interferente Pequeno/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
3.
World J Gastrointest Oncol ; 11(1): 1-8, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30984345

RESUMO

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.

4.
World Neurosurg ; 90: 698.e7-698.e11, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26852708

RESUMO

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.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Testes Genéticos/métodos , Glioblastoma/secundário , Glioblastoma/terapia , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias de Cabeça e Pescoço/terapia , Biomarcadores Tumorais/genética , Feminino , Glioblastoma/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-840197

RESUMO

Objective: To investigate the protective effect of compound Xueshuantong capsule against damage of diabetic nephropathy in rat diabetic model. Methods: Male SD rats were given intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg, and diabetic rat model was deemed successfully induced when the blood glucose level ≥16.7 mmol/L 3 days after injection. Thirty model rats were randomly divided into the following 3 groups equally: diabetic model group (DM), compound Xueshuantong capsule group (XST), and α-lipoic acid treatment group (ALA). Another 10 normal rats served as normal control group (NG). The body weight, blood glucose, blood fat, kidney weight/body weight (KW/BW), 24 h-urinary protein excretion, urea nitrogen, and serum creatinine were observed and compared between different groups after 12 weeks' treatment. The ultrastructure changes of kidney were observed by electron microscopy and light microscope. Results: Compared with NG group, rats in DM group had a higher 24 h-urinary protein excretion (P<0.05), and those in XST group and ALA group had a significantly lower one compared with the DM group (P<0.05). Compared with NG group, rats in the other 3 groups had a higher KW/BW, with significant difference found between DM group and XST group (P<0.05). Electron microscopic results showed uneven glomerular basement membrane thickening, foot process integration, and mesangial cell proliferation in the model group; all the above changes were improved in the XST and ALA groups. Conclusion: Compound Xueshuantong capsule can lower the 24 h-urinary protein secretion, decrease KW/BW, and improve the structure of glomerular basement membrane, thus exerting renal protective effect in diabetic rats.

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