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This study explored the synergistic effects of autophagy inhibitors combined with cisplatin against cisplatinresistant nasopharyngeal cancer cells by treating HNE-1 and cisplatin (diamminedichloroplatinum; DDP)-resistant HNE1/DDP nasopharyngeal cancer cell lines with DDP, autophagy inhibitors, or a combination of autophagy inhibitors and DDP. Cell viability was determined via MTT (colorimetric) and colony-forming assays, and the rate of apoptosis was determined using propidium iodide (PI) and annexin V double-staining. The expressions of proteins were determined by Western blotting. For our in-vivo studies, a murine xenograft model was established to evaluate the anti-tumor effects of the combination of autophagy inhibitor and DDP. The results showed that treatment with DDP increased the expressions of ATP-binding cassette sub-family B member 1 (ABCB1), ATP Binding Cassette Subfamily C Member 1 (ABCC1), and P-glycoprotein 1 (P-gp) in the HNE1/DDP cell lines. Treatment with chloroquine decreased the expression levels of ABCB1, ABCC1, and P-gp, and increased the formation of LC3-II and the expression levels of p62 in the HNE1/DDP cells. Additionally, the combination of autophagy inhibitors and DDP produced a synergistic effect on DDP-induced cell death and apoptosis. Furthermore, the combination of the autophagy inhibitor and DDP showed significant anti-tumor effects in the xenograft mouse model. In summary, autophagy inhibitors show synergistic anti-tumor effects with DDP in vitro against DDP-resistant nasopharyngeal cancer cells and in vivo in our xenograft murine model. Key words: nasopharyngeal cancer, autophagy, chloroquine, HNE1/DDP, cisplatin. La présente étude vise à explorer les effets synergiques d'un inhibiteur de l'autophagie combiné au cisplatine sur des cellules cancéreuses du nasopharynx résistantes au cisplatine. Pour les études in vitro, les lignées cellulaires de cancer du nasopharynx HNE-1 et HNE-1/DDP résistante au cisplatine (DDP) ont été traitées avec du DDP, un inhibiteur de l'autophagie ou une combinaison de l'inhibiteur de l'autophagie et de DDP. La viabilité cellulaire a été déterminée par un dosage au MTT et un test de formation de colonies, séparément. L'apoptose a été déterminée par double coloration à l'iodure de propidium (PI) et à l'Annexine V. L'expression des protéines a été déterminée par transfert Western. Pour les études in vivo, un modèle de xénogreffe chez la souris a été établi pour évaluer les effets antitumoraux de la combinaison de l'inhibiteur d'autophagie et du DDP. Ainsi, le traitement au DDP augmentait l'expression d'ABCB1, d'ABCC1 et de la P-glycoprotéine 1 (P-gp) dans les cellules HNE1/DDP. Le traitement à la chloroquine diminuait l'expression d'ABCB1, ABCC1 et de P-gp et augmentait la formation de LC3-II et l'expression de p62 dans les cellules HNE1/DDP. De plus, l'inhibiteur de l'autophagie et le DDP montraient des effets synergiques sur la mort cellulaire et l'apoptose induites par le DDP. Par ailleurs, la combinaison de l'inhibiteur d'autophagie et du DDP présentait des effets antitumoraux significatifs dans le modèle de xénogreffe chez la souris. En résumé, l'inhibiteur de l'autophagie a montré des effets antitumoraux synergiques avec le DDP contre les cellules cancéreuses du nasopharynx résistantes au DDP et dans les modèles animaux de xénogreffes. [Traduit par la Rédaction] Mots-clés: cancer du nasopharynx, autophagie, chloroquine, HNE1/DDP, cisplatine., Introduction Nasopharyngeal carcinoma is a malignant tumor that occurs in the nasopharynx. It is one of the most common malignancies in southeast Asia and southern China (McDermott et al. 2001; [...]

Despite the recent development of treatment strategies for nasopharyngeal carcinoma, the effective management of this disease remains a challenging clinical problem. A better understanding of the regulatory roles of miR‐194 and mitogen‐activated protein kinase kinase kinase 3 (MAP3K3) in the nasopharyngeal‐carcinoma‐related gene network is required to address this issue. Here, we measured relative expression of miR‐194 in human nasopharyngeal carcinoma tissues and normal epithelial tissues by quantitative real time PCR. We transfected cultured CNE‐1 and C666‐1 cells with miR‐194 mimics, and then examined the effects on cell proliferation, cell migration and invasion. Luciferase reporter assay was used to validate the putative binding between miR‐194 and MAP3K3. We then examined the effect of knockdown and overexpression of MAP3K3 on cell tumorigenesis. Expression of miR‐194 is significantly down‐regulated in nasopharyngeal carcinoma specimens and tumor cell lines when compared with normal controls. In addition, miR‐194 suppressed tumor cell proliferation and viability, as well as migration and invasion of carcinoma cells. We found that miR‐194 binds the 3′ untranslated region of MAP3K3, and knockdown of miR‐194 inhibited nasopharyngeal carcinoma cell proliferation, migration and invasion. In accordance, overexpression of MAP3K3 reversed the inhibitory effects of miR‐194 in carcinoma cells. This study suggests that expression of miR‐194 is down‐regulated in nasopharyngeal carcinoma, and that miR‐194 can directly target MAP3K3 to regulate tumor progression. Given the pivotal involvement of MAP3K3 in nasopharyngeal carcinoma development, targeting miR‐194 may be a novel strategy for the treatment of nasopharyngeal carcinoma. miR‐194 was down‐regulated in nasopharyngeal carcinoma. miR‐194 can directly target MAP3K3 for regulating tumor progression. Given the pivotal involvement of MAP3K3 in nasopharyngeal carcinoma development, targeting miR‐194 could provide a novel strategy for the treatment of nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Despite the recent development of treatment strategies for nasopharyngeal carcinoma, the effective management of this disease remains a challenging clinical problem. A better understanding of the regulatory roles of miR-194 and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) in the nasopharyngeal-carcinoma-related gene network is required to address this issue. Here, we measured relative expression of miR-194 in human nasopharyngeal carcinoma tissues and normal epithelial tissues by quantitative real time PCR. We transfected cultured CNE-1 and C666-1 cells with miR-194 mimics, and then examined the effects on cell proliferation, cell migration and invasion. Luciferase reporter assay was used to validate the putative binding between miR-194 and MAP3K3. We then examined the effect of knockdown and overexpression of MAP3K3 on cell tumorigenesis. Expression of miR-194 is significantly down-regulated in nasopharyngeal carcinoma specimens and tumor cell lines when compared with normal controls. In addition, miR-194 suppressed tumor cell proliferation and viability, as well as migration and invasion of carcinoma cells. We found that miR-194 binds the 3' untranslated region of MAP3K3, and knockdown of miR-194 inhibited nasopharyngeal carcinoma cell proliferation, migration and invasion. In accordance, overexpression of MAP3K3 reversed the inhibitory effects of miR-194 in carcinoma cells. This study suggests that expression of miR-194 is down-regulated in nasopharyngeal carcinoma, and that miR-194 can directly target MAP3K3 to regulate tumor progression. Given the pivotal involvement of MAP3K3 in nasopharyngeal carcinoma development, targeting miR-194 may be a novel strategy for the treatment of nasopharyngeal carcinoma.

Purpose: To investigate the impact of chemotherapy and/or radiotherapy on disease-free survival (DFS) and overall survival (OS) rates of patients with thymic carcinoma after complete resection., Methods: Between 2001 and 2013, 54 patients with complete resection of thymic carcinoma in Hangzhou Cancer Hospital were retrospectively reviewed. The Kaplan-Meier method was used to evaluate the survival rates. The Cox proportional hazard model was used for multivariate analysis., Results: Among the 54 patients, Masaoka stage I was observed in seven patients, II in 22 patients, and III in 25 patients. Sixteen patients received adjuvant chemotherapy (six with chemotherapy alone and ten with radiotherapy and chemotherapy), 25 patients received adjuvant radiotherapy, and 13 patients did not receive radiotherapy and/or chemotherapy. The 5-year DFS and OS rates for all patients were 63.0% and 73.4%, respectively. Univariate analysis revealed that radiotherapy was significantly associated with DFS and OS (P=0.014 and P=0.029, respectively), while adjuvant chemotherapy was not (P=0.122 and P=0.373, respectively). Multivariate analysis showed that adjuvant radiotherapy increased DFS (P=0.041), but not OS (P=0.051)., Conclusion: Complete resection followed by adjuvant radiotherapy increased disease-free rates of thymic carcinoma patients.

Objective: To study the etiology, diagnosis and therapeutic strategies of acute low-tone sensorineural hearing loss (ALHL)., Method: Fifty-five patients (58 ears) with ALHL were selected for this study. With detailed history collection, otological examination and pure tone audiometry,acoustic immittance and auditory brainstem response (ABR), all cases were divided into two groups, the prednisone group and the control group, randomly with six months follow-up., Result: ALHL mainly affected young people. The symptoms included the sensation of ear fullness, low-tone tinnitus, and hearing impairment. Otological examinations showed normal results. Mild to moderate sensorineural hearing loss at low frequencies and type "A" tympanograms were found in all cases. Acoustic stapedial reflexes were elicited in 49 out of 58 affected ears and 40 of them had positive results on the Metz test. ABR responses were normal in all 45 tested ears. with comparison of the two groups, the effect of prednisone group was superior to that of the control group., Conclusion: ALHL patients are clinically characterized by low-tone tinnitus, aural fullness and hearing loss, which mainly involve unilateral ear. Audiological findings indicate cochlear impairment, which only invades low frequency region. This study suggest that the corticosteroid therapy probably have some effect.