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1.
J Cancer Res Ther ; 18(2): 399-404, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35645106

RESUMO

Purpose: To reveal the survival and safety of percutaneous microwave ablation (MWA) combined with chemoradiotherapy (CRT) in treating small cell lung cancer (SCLC). Materials and Methods: Clinical data of 48 SCLC patients who underwent MWA were retrospectively collected; survival and incidence of major complications were analyzed. Results: Totally, 48 SCLC patients underwent 51 MWA procedures. The median overall survival (OS) for all SCLC was 27.0 months (95% confidence interval 22.4-31.6 months). The OS of limited-stage (LS-SCLC) was longer than the extensive-stage (ES-SCLC) (median 48.0 months vs. 25.0 months, P = 0.022). The OS of SCLC with tumor diameter ≤3.0 cm was longer than that of tumor diameter >3.0 cm (median 48.0 months vs. 27.0 months, P = 0.041). For LS-SCLC, the 1-, 2-, 3-, and 5-year survival rate was 91.67%, 72.22%, 66.67%, and 61.11%, respectively. For ES-SCLC, the 1-, 2-, and 3-year survival rates were 83.33%, 50.0%, and 8.33%. Major complications included pneumothorax needing tube placement (29.4%), rarely arrhythmia (2.0%), empyema (2.0%), pulmonary fungal infection (2.0%), and shingles (2.0%). Conclusion: For SCLC patients, who received MWA combined with CRT, OS of LS-SCLC and tumor diameter ≤3.0 cm was better than that of the ES-SCLC and tumor diameter >3.0 cm. For inoperable SCLC, MWA was safe.


Assuntos
Neoplasias Pulmonares , Ablação por Radiofrequência , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Micro-Ondas/efeitos adversos , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Pequenas Células do Pulmão/cirurgia
2.
Int J Immunopathol Pharmacol ; 35: 2058738420966087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33583218

RESUMO

Long non-coding RNA (lncRNA) X inactive specific transcript (XIST) is reported to play an oncogenic role in non-small cell lung cancer (NSCLC). However, the role of XIST in regulating the radiosensitivity of NSCLC cells remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expressions of XIST and miR-16-5p in NSCLC in tissues and cells, and Western blot was used to assess the expression of WEE1 G2 checkpoint kinase (WEE1). Cell counting kit-8 (CCK-8), colony formation and flow cytometry assays were used to determine cell viability and apoptosis after NSCLC cells were exposed to different doses of X-rays. The interaction between XIST and miR-16-5p was confirmed by StarBase database, qRT-PCR and dual-luciferase reporter gene assays. TargetScan database was used to predict WEE1 as a target of miR-16-5p, and their targeting relationship was further validated by Western blot, qRT-PCR and dual-luciferase reporter gene assays. XIST was highly expressed in both NSCLC tissue and cell lines, and knockdown of XIST repressed NSCLC cell viability and cell survival, and facilitated apoptosis under the irradiation. MiR-16-5p was a target of XIST, and rescue experiments demonstrated that miR-16-5p inhibitors could reverse the role of XIST knockdown on radiosensitivity in NSCLC cells. WEE1 was validated as a target gene of miR-16-5p, and WEE1 could be negatively regulated by XIST. XIST promotes the radioresistance of NSCLC cells by regulating the expressions of miR-16-5p and WEE1, which can be a novel target for NSCLC therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ciclo Celular/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Tirosina Quinases/genética , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Sobrevivência Celular , Humanos , Neoplasias Pulmonares/radioterapia , Proteínas Tirosina Quinases/metabolismo , Radiação Ionizante
3.
Transl Cancer Res ; 10(1): 273-287, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35116259

RESUMO

BACKGROUND: Tendency toward extensive regional lymph node metastasis (LNM) is an important clinical characteristic of esophageal squamous cell carcinoma (ESCC) and differs greatly between patients. MicroRNAs (miRNAs) are involved in the invasion and metastasis of ESCC. We performed a microarray analysis of miRNAs based on LNM status to identify tumor-specific miRNAs for the prediction of LNM in ESCC. METHODS: Four pairs of ESCC tumor tissues with or without LNM were selected for microarray analysis to identify differentially expressed miRNAs, then 50 tumor tissue samples were selected to verify the differences of the screened miRNAs with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The relations between candidate miRNAs and clinicopathologic features were analyzed to confirm tumor specificity in the prediction of LNM in ESCC. Target gene prediction using miRWalk2.0 was used to analyze the potential mechanisms of the tumor-specific miRNAs. RESULTS: The present microarray analysis identified significant differential expression in 62 miRNAs in the ESCC samples with LNM, compared to those without LNM. Of these, 19 miRNAs were selected for qRT-PCR verification, and three miRNAs were significantly upregulated in ESCC samples with LNM compared to those without LNM. The three miRNAs were not significantly associated with any other clinicopathologic features except for the TNM stage and could be regarded as tumor-specific miRNAs capable of predicting LNM in ESCC. Finally, 858 mRNAs were significantly associated with tumor-specific miRNAs and possibly involved in the regulation of LNM in ESCC. CONCLUSIONS: The present microarray analysis based on LNM status identified three tumor-specific miRNAs for predicting regional LNM in ESCC, which provides valuable clues for potential mechanism research and guarantees further investigation.

4.
Transl Cancer Res ; 10(6): 2694-2706, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35116581

RESUMO

BACKGROUND: A tendency towards extensive regional lymph node metastasis (LNM) is a typical clinical characteristic of esophageal squamous cell carcinoma (ESCC). Up-regulated microRNA (miR)-19a-3p was verified as a predictor of LNM in ESCC in previous microarray analyses, but the underlying mechanisms remain unclear. Here, in vitro experiments were performed to confirm the effect of miR-19a-3p on promoting LNM and to explore the underlying mechanisms. METHODS: KYSE-150 and TE-1 cell lines were transfected with lentiviral vectors to inhibit miR-19a-3p (LV-miR-19a-3p-inhibition), and cell proliferation, invasion, and migration were assessed. Target genes of miR-19a-3p were identified by sequencing analysis and quantitative reverse transcription PCR (qRT-PCR); Western blotting was performed to confirm targets and explore the potential mechanisms underlying the effect of miR-19a-3p on LNM. RESULTS: miR-19a-3p had no effect on ESCC cell proliferation, whereas miR-19a-3p overexpression promoted the invasion and migration of ESCC cells. qRT-PCR verification and western blot analysis showed that LV-miR-19a-3p-inhibition downregulated cell division cycle 42 (CDC42), Rac family small GTPase 1 (RAC1), and p21 activated kinase 1 (PAK1). CONCLUSIONS: Overexpression of miR-19a-3p increased the invasion and migration of ESCC cells via the RAC1/CDC42-PAK1 pathway, suggesting that this pathway mediates the effect of miR-19a-3p on promoting LNM in ESCC.

5.
Biochem Biophys Res Commun ; 511(3): 685-692, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30827510

RESUMO

The relationship between colorectal cancer (CRC) and cholesterol has been confirmed for many years, but the mechanism was not very clear. miR-33a was important in cholesterol metabolism and was abnormally expressed in many tumors, thus our study hypothesized that cholesterol effect on CRC by regulating miR-33a and its target gene PIM3, and verify it by series of assay. From results of CCK8 and flow cytometry, we confirmed cholesterol can stimulate CRC cell proliferation, promote cell cycle progression and inhibit cell apoptosis. miR-33a and SREBP2 mRNA expression were inhibited by cholesterol, and when cells transfected with miR-33a mimics or inhibitor the effect of cholesterol appeared a significant difference than before. In addition, PIM3 showed up-regulation with cholesterol treatment, and it was proved to be the target gene of miR-33a by dual luciferase reporter assay, it modulated CRC cells proliferation and apoptosis by phosphorylating p27, p21 and Bad protein. Thus, it inferred that cholesterol can regulate CRC development by miR-33a-PIM3 pathway.


Assuntos
Proliferação de Células , Colesterol/metabolismo , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética
6.
Eur J Pharmacol ; 834: 45-53, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30017802

RESUMO

The epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression, metastasis and drug resistance. The transcription factor(TF) and microRNA (miR) chimeric [SNAIL/miR-34]:[ZEB/miR-200] unit is the core regulatory system for the EMT process. Here, we proposed to assess the anti-EMT abilities and explore the inherent pharmacological mechanisms of the classic hypoglycaemic agent metformin for colorectal cancer(CRC). For the EMT model, the TGF-ß-induced CRC cell lines SW480 and HCT116 were treated with metformin. The viability, migration and invasion abilities of the cells were evaluated with the Cell Counting Kit-8, wound-healing and trans-well assay. The alterations of the [SNAIL/miR-34]:[ZEB/miR-200] system and the EMT markers E-cadherin and vimentin were detected by western blot, qPCR and immunofluorescent staining. Metformin exhibited inhibitory effects on the proliferation, migration and invasion of the CRC SW480 cells. The up-regulation of E-cadherin and the down-regulation of vimentin for both SW480 and HCT116 cells revealed the anti-EMT abilities of metformin. For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-ß-induced EMT. From immunofluorescence, we observed increased E-cadherin and ZEB1 co-expression in metformin-treated cells. Metformin may perform bidirectional regulations of the [SNAIL/miR-34]:[ZEB/miR-200] system in the EMT process for colorectal cancer. Such regulation is expressed as the inhibition of EMT in general as well as an increased higher proportion of E/M hybrid cells in the total population.


Assuntos
Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Metformina/farmacologia , MicroRNAs/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Humanos , Invasividade Neoplásica , Fator de Crescimento Transformador beta/farmacologia
7.
Kaohsiung J Med Sci ; 33(11): 543-549, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29050671

RESUMO

Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce apoptosis, and enhance reactive oxygen species accumulation. However, whether GA could improve multidrug resistance through modulating autophagy has never been explored. We demonstrated that the combination of GA and cisplatin (CDDP) resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using the MTT assay. Furthermore, treatment with GA significantly increased autophagy in these cells. More importantly, GA-induced cell death could be largely abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting that GA-induced cell death was dependent on autophagy. Western blot analysis showed that GA treatment suppressed the activation of Akt, mTOR, and S6. In addition, using a GA and rapamycin combination induced more cell death compared to either GA or rapamycin alone. In summary, GA may have utility as an adjunct therapy for non-small cell lung cancer (NSCLC) patients through autophagy-dependent cell death, even when cancer cells have developed resistance to apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Garcinia/química , Regulação Neoplásica da Expressão Gênica , Xantonas/farmacologia , Células A549 , Adenina/análogos & derivados , Adenina/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Autofagia/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Cisplatino/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína S6 Ribossômica/antagonistas & inibidores , Proteína S6 Ribossômica/genética , Proteína S6 Ribossômica/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Xantonas/isolamento & purificação
8.
Gastroenterol Res Pract ; 2017: 2520581, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28744307

RESUMO

OBJECTIVES: We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. METHODS: We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. RESULTS: In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P = 0.014) and less vimentin (P = 0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P = 0.048, P = 0.009), tumor invasive depth (T) (P < 0.001, P = 0.045), and lymph invasion (N) (P = 0.013, P = 0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P = 0.038) and metformin use (P = 0.015P = 0.044) and lymph invasion (P = 0.016P = 0.023) were considered as the prognostic factors for both DFS and overall survival (OS). CONCLUSION: Our study suggested that metformin may impede the EMT process and improve survival for stage I-III CRC patients with DM II.

9.
Int Immunopharmacol ; 46: 75-79, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28268208

RESUMO

OBJECTIVE: The predictive value of HALP in esophageal cancer is currently unclear. We aimed to evaluate the value of HALP in predicting platinum-based definitive chemoradiotherapy response in male patients with esophageal squamous cell carcinoma. METHODS: Data from all newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) were collected from January 1, 2010 to December 31, 2014 in Qilu Hospital. The treatment protocol was definitive chemoradiotherapy consisting of docetaxel plus cisplatin or carboplatin. The response assessment of the definitive chemoradiotherapy was based on computed tomography (CT) and barium meal test results. RESULTS: A total of 39 patients were included in the present study. The median value of HALP was 48.34. The chemoradiotherapy response rate of patients in the low HALP value group was 35%, compared with 78.95% of patients in the high HALP group (P=0.010). Additionally, the median progression-free survival in the 2 patient groups was significantly different (10.7 vs. 24.7m, P=0.041). In the multivariate analysis, patients with HALP higher than 48.34 had longer progression-free survival than patients with HALP of 48.34 or less (HR 2.745; 95% CI, 1.176-6.408; P=0.020). However, there was no significant difference for overall survival between the high HALP group and low HALP group. CONCLUSION: Our data suggested that pretreatment HALP could predict the platinum-based chemoradiotherapy response of tumors and progression free survival in male patients with ESCC. Therefore, HALP could be used in routine clinical practice to guide the therapeutic strategies for individual treatment in patients with ESCC.


Assuntos
Plaquetas/patologia , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Linfócitos/patologia , Adulto , Idoso , Albuminas/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/uso terapêutico , Valor Preditivo dos Testes , Prognóstico , Resultado do Tratamento
10.
Oncol Lett ; 13(1): 196-200, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28123541

RESUMO

In the present study, we evaluated the effects of recombinant human (rh-)endostatin treatment on differentiated and undifferentiated tumor vasculature in Lewis lung cancer for the first time. Lewis lung carcinoma models were established. The animals were treated daily with varying doses of rh-endostatin or physiological saline for 14 days. Intravital microscopy was performed following treatment. The expression of CD31 and CD34 was determined by immunohistochemical staining, and microvessel density (MVD) was determined. Rh-endostatin treatment significantly decreased the tumor volume compared with the control group. Rh-endostatin treatment normalized the architecture of the vascular network. CD31+ cells decreased following rh-endostatin treatment, whereas CD34+ cells were unaffected by the treatment. Accordingly, the MVD value of CD31+ cells in rh-endostatin treatment groups significantly decreased (P<0.01), and the MVD value of CD34+ cells in the rh-endostatin treatment groups did not decrease. Undifferentiated tumor blood vessels were significantly inhibited by rh-endostatin treatment. In conclusion, the normalization of the tumor vasculature by endostatin may be related to the differential effects of endostatin on differentiated and undifferentiated blood vessels.

11.
Jpn J Clin Oncol ; 46(12): 1118-1126, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27702836

RESUMO

OBJECTIVE: We want to review the value of 18-fluoro-deoxy-glucose positron emission tomography for response prediction of primary tumor in patients with esophageal cancer during or after neoadjuvant chemoradiotherapy. METHODS: Studies were searched in Pubmed, Embase and Cochrane Library with specific search strategy. The published articles were included according to the criteria established in advance. The included studies were divided into two groups according to the time of the repeat positron emission tomography: during (Group A) or after neoadjuvant chemoradiotherapy (Group B). The studies that performed the repeat positron emission tomography after neoadjuvant chemoradiotherapy were graded Quality Assessment of Diagnostic Accuracy Studies. The pooled sensitivity, specificity and diagnostic odds ratio were obtained for both groups on the basis of no-existing of threshold effect. RESULTS: Fifteen studies were included in the present study. The threshold effect did not exist in both groups. The pooled sensitivity, specificity and diagnostic odds ratio were 85%, 59%, 6.82 with 95% confidence interval 76-91%, 48-69%, 2.25-20.72 in Group A. The equivalent values were 67%, 69%, 6.34 with 95% confidence interval 60-73%, 63-74%, 2.08-19.34 in Group B. The pooled sensitivity was 90% in four studies that enrolled patients with esophageal squamous cell carcinoma merely in Group B. CONCLUSIONS: According to the present data, positron emission tomography should not be used routinely to guide treatment strategy in esophageal cancer patients. We speculated that positron emission tomography could be used as a tool to predict treatment response after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Fluordesoxiglucose F18/química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Bases de Dados Factuais , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Humanos , Terapia Neoadjuvante , Razão de Chances , Sensibilidade e Especificidade , Resultado do Tratamento
12.
J BUON ; 21(1): 161-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27061544

RESUMO

PURPOSE: To evaluate the efficacy and safety of lobaplatin combined with docetaxel as neoadjuvant chemotherapy followed by concurrent lobaplatin with intensity-modulated radiotherapy (IMRT) for high-risk positive lymph node (N+) nasopharyngeal carcinoma (NPC). METHODS: This study enrolled 37 primary high-risk N+ NPC patients. The neoadjuvant chemotherapy program consisted of lobaplatin (30 mg/m(2), day 1) plus docetaxel (75 mg/m(2), day 1) for two cycles, 3 weeks apart. Concurrently with IMRT, patients received a chemotherapy program of lobaplatin 50mg/m(2). Cycle repetition was every 21 days. The IMRT doses were planning target volume (PTV) 68-72 Gy for gross disease in the nasopharynx, and 66-70 Gy for positive lymph nodes in 33 FRACTIONS. The doses for high risk and low risk region PTV were 59.4 Gy in 33 fractions and 50.4 Gy in 28 fractions. RESULTS: The median follow-up duration was 31 months (range 4-52). The 3-year overall survival (OS) was 74.3%. The 3-year distant metastasis-free survival (DMFS) was 67.4%. The 3-year locoregional relapse-free survival (LRFS) was 91.5%, and the 3-year progression-free survival (PFS) was 61.2%. The efficiency of short-term effects of neoadjuvant chemotherapy and chemoradiotherapy were 83.8% and 100.0%, respectively. Serious acute toxicities observed were neutropenia (97.3%), thrombocytopenia (83.8%) and anemia (81.1%). CONCLUSIONS: In patients with high-risk N+ NPC, lobaplatin combined with docetaxel neoadjuvant chemotherapy followed by concurrent lobaplatin with IMRT yielded excellent short-term results with mild and tolerable toxicities.


Assuntos
Quimiorradioterapia , Neoplasias Nasofaríngeas/terapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma , Ciclobutanos/administração & dosagem , Docetaxel , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Taxoides/administração & dosagem
13.
Oncotarget ; 7(18): 26436-43, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27050379

RESUMO

Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two gene clusters encoding nAChR subunits, have been associated with lung cancer risk. In this study, we investigated whether variants in the two gene clusters were associated with prognosis of advanced non-small cell lung cancer (NSCLC). A total of 165 stage IIIB-IV NSCLC patients were enrolled in this study. Three polymorphisms (rs667282 and rs3743073 in CHRNA5-A3 and rs13280604 in CHRNB3-A6) were genotyped using the TaqMan method. Overall survival (OS) was estimated using the log-rank test and the Cox models. Our results showed that patients with CHRNA5-A3 rs667282 TT or TC genotypes had a significantly shorter OS than those carrying the CC genotype (Log-rank, P = 0.043). Furthermore, multivariate Cox regression analysis showed that rs667282 TT/TC genotypes are significantly associated with increased risk of overall deaths (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.7). However, the similar results were not observed for other two polymorphisms. Furthermore, no evident association was found between these variants and clinicopathologic features of advanced NSCLC. Our present study suggested that rs667282 in CHRNA5-A3 may modify the prognosis of patients with advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteínas do Tecido Nervoso/genética , Receptores Nicotínicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais
14.
Biotechnol Lett ; 37(12): 2365-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26264242

RESUMO

OBJECTIVES: To investigate the effect of retinoblastoma-binding protein 2 (RBP2) on epithelial-mesenchymal transition (EMT) in esophageal squamous cancer cells and to compare the effect of RBP2 in lung squamous cancer cells and esophageal squamous cancer cells. RESULTS: When transfected with RBP2 siRNA, the migrated cells were 36.3 ± 6.03 by transwell migration assay, compared to 107 ± 6.7 cells in the control group. The mRNA level of epithelial cadherin (E-cadherin) was 1.54 ± 0.14 times higher than in the control group, and that of neural cadherin (N-cadherin) fell to 0.76 ± 0.03 times. The relative luciferase activity of E-cadherin promoter rose to 3.84 ± 0.23 times. Correspondingly, the expression of E-cadherin protein increased and that of N-cadherin protein decreased. When SK-MES-1 cells were transfected with RBP2 siRNA, their relative mRNA level of E-cadherin was 8.6 ± 0.37 times as high as that in control group, which was higher than that in Eca-109 cells. The E-cadherin protein was also greater in SK-MES-1 cells. CONCLUSION: RBP2 could induce EMT in esophageal cancer cells and exert a greater effect on the expression of E-cadherin in lung squamous cells than in esophageal squamous cells.


Assuntos
Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal , Neoplasias Esofágicas/patologia , Neoplasias Pulmonares/patologia , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Caderinas/análise , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Modelos Biológicos , Proteína 2 de Ligação ao Retinoblastoma/genética
15.
Carcinogenesis ; 36(5): 538-42, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25823894

RESUMO

Nicotinic acetylcholine receptors are important regulators of smoking behavior and tobacco carcinogenesis. We studied the association of the CHRNB3-A6 variant rs13280604 in relation to esophageal squamous cell carcinoma (ESCC) in Chinese populations. Two independent case-control studies were conducted. The first case-control study, consisted of 866 ESCC patients and 1621 healthy controls from Northern China, and the second case-control study consisted of 853 ESCC patients and 860 unrelated controls from Southern China. A logistic regression model was used to evaluate the associations of rs13280604 with cancer risk. We found that Rs13280604 GG/AG genotypes were significantly associated with increased risk for ESCC in both case-control studies from Northern [odds ratio (OR), 1.42, 95% confidence interval (CI), 1.19-1.70, P = 1.1×10(-4)], Southern China (OR, 1.56, 95% CI, 1.26-1.93, P = 5.2×10(-5)), and the combined population of both studies (OR, 1.44, 95% CI, 1.26-1.65, P = 8.7×10(-8)), respectively. Our results suggest that this CHRNB3-A6 variant confers susceptibility to ESCC risk. However, future larger studies are needed to validate our finding.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores Nicotínicos/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Fatores de Risco
16.
Med Oncol ; 32(1): 325, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25481673

RESUMO

Bevacizumab is an anti-VEGF human monoclonal antibody suitable for chemotherapy for patients with metastatic colorectal cancer (mCRC). This study investigated the efficacy and safety of using bevacizumab plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as second-line chemotherapy option for patients with mCRC in China. Patients with mCRC, who had been previously treated with oxaliplatin-based chemotherapy, but not bevacizumab, were randomly assigned to two groups to receive bevacizumab plus FOLFIRI (FOLFIRI-B) or FOLFIRI alone. In FOLFIRI-B group, patients were given 10 mg/kg bevacizumab plus FOLFIRI every 2 weeks. The primary endpoints were response rates and survival rates. Between June 2010 and May 2014, 65 patients were assigned to FOLFIRI-B group and 77 to FOLFIRI alone group. The median progression-free survivals were 8.5 months (95 % CI 5.8-10.5 months) for FOLFIRI-B and 5.1 months (95 % CI 2.7-9.8 months) for FOLFIRI alone; median overall survivals were 15.2 months (95 % CI 11.8-19.4 months) for FOLFIRI-B and 11.3 months (95 % CI 6.7-16.5 months) for FOLFIRI alone. Incidence rates of grade 3 and 4 adverse events were observed and comparable between FOLFIRI-B and FOLFIRI alone groups. Chinese patients with mCRC treated with second-line chemotherapy of FOLFIRI-B had better survivals than those patients treated with FOLFIRI alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Bevacizumab/efeitos adversos , Camptotecina/análogos & derivados , China , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila , Humanos , Estimativa de Kaplan-Meier , Leucovorina , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Breast Cancer ; 22(4): 413-20, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24114595

RESUMO

BACKGROUND: Gold nanoparticles (GNPs) have been conceived to cause increased cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by cells may induce increased radiation effects. Here we report the radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes (16 nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays. METHODS: Transmission electron microscopy (TEM) was used to observe the distribution of Glu-GNPs in cells. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used to measure the quantities of Glu-GNPs absorbed by cells. After treatment of Glu-GNPs with a series of concentrations, we used the MTT and clonogenic assays to confirm the radiation enhancement effect of Glu-GNPs on MDA-MB-231 cells. The cell cycle distribution was analyzed by flow cytometry to further explore the mechanisms of enhanced radiosensitivity of Glu-GNPs. RESULTS: TEM showed that Glu-GNPs are mainly distributed in the cytoplasm of cells, including endosomes and lysosomes. ICP-AES indicates that MDA-MB-231 cells absorb more 49-nm Glu-GNPs than 16-nm Glu-GNPs in number (P < 0.05). Glu-GNPs have little cytotoxicity toward MDA-MB-231 cells with a concentration below 20 nM. In the clonogenic assay, the combination of Glu-GNPs with radiation induced a significant growth inhibition, compared with radiation alone (P < 0.05). Moreover 49-nm Glu-GNPs induced much greater radiation effects than 16-nm Glu-GNPs (P < 0.05). Flow cytometry shows that Glu-GNPs can help radiation arrest more cells in the G2/M phase, with greater effect with 49-nm Glu-GNPs than 16-nm Glu-GNPs. CONCLUSIONS: Glu-GNPs can increase the cytotoxicity of radiation toward MDA-MB-231 cells, probably by regulating the distribution of the cell cycle, with more cells in the G2/M phase. The effect of radiation enhancement may be related to the quantities of Glu-GNPs in the cells.


Assuntos
Aurotioglucose/farmacologia , Nanopartículas/química , Radiossensibilizantes/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Aurotioglucose/química , Aurotioglucose/farmacocinética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos da radiação , Feminino , Citometria de Fluxo , Humanos , Microscopia Eletrônica de Transmissão , Neoplasias de Mama Triplo Negativas/patologia
18.
Oncol Lett ; 8(6): 2601-2606, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25364434

RESUMO

Radiotherapy is the main locoregional control modality for a number of types of malignant tumors, including glioblastoma. However, radiotherapy fails to prevent recurrence in numerous patients due to the intrinsic radioresistance of cancer cells. Cell senescence is significant in tumor suppressor mechanisms and is closely associated with the radioresistance of cancer cells. Bmi-1 has been proposed to be an oncogene that can induce anti-senescence in tumor cells. The present study investigated the response of U87 glioma cells to radiation exposure and the role of Bmi-1 in the response following radiotherapy. Cell apoptosis and cell cycle distribution were assessed using flow cytometry, and a SA-ß-Gal stain was used to observe the senescence ratio of U87 cells following radiation. The expression of Bmi-1 in U87 cells exposed to different doses of radiation was evaluated by western blot analysis. X-ray radiation was found to inhibit U87 cell proliferation through the induction of senescence rather than apoptosis. Following exposure to radiation, the cell cycle distribution was dysregulated, with an increased number of cells in the G2/M phase, and the expression of Bmi-1 was upregulated, particularly when a dose of ≥6 Gy was administered. The results indicated that senescence is the main mechanism by which U87 cell growth is inhibited following radiation. In addition, Bmi-1 may be significant in increasing the radioresistance of glioma cells by enabling cell senescence.

19.
Tumour Biol ; 35(11): 11455-60, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25123261

RESUMO

The large errors of routine localization for eyeball tumors restricted X-ray radiosurgery application, just for the eyeball to turn around. To localize the accuracy site, the micro-vacuo-certo-contacting ophthalmophanto (MVCCOP) method was used. Also, the outcome of patients with tumors in the eyeball was evaluated. In this study, computed tomography (CT) localization accuracy was measured by repeating CT scan using MVCCOP to fix the eyeball in radiosurgery. This study evaluated the outcome of the tumors and the survival of the patients by follow-up. The results indicated that the accuracy of CT localization of Brown-Roberts-Wells (BRW) head ring was 0.65 mm and maximum error was 1.09 mm. The accuracy of target localization of tumors in the eyeball using MVCCOP was 0.87 mm averagely, and the maximum error was 1.19 mm. The errors of fixation of the eyeball were 0.84 mm averagely and 1.17 mm maximally. The total accuracy was 1.34 mm, and 95% confidence accuracy was 2.09 mm. The clinical application of this method in 14 tumor patients showed satisfactory results, and all of the tumors showed the clear rims. The site of ten retinoblastomas was decreased significantly. The local control interval of tumors were 6 ∼ 24 months, median of 10.5 months. The survival of ten patients was 7 ∼ 30 months, median of 16.5 months. Also, the tumors were kept stable or shrank in the other four patients with angioma and melanoma. In conclusion, the MVCCOP is suitable and dependable for X-ray radiosurgery for eyeball tumors. The tumor control and survival of patients are satisfactory, and this method can effectively postpone or avoid extirpation of eyeball.


Assuntos
Neoplasias Oculares/cirurgia , Melanoma/cirurgia , Radiocirurgia , Retinoblastoma/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Neoplasias Oculares/mortalidade , Neoplasias Oculares/patologia , Feminino , Seguimentos , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Estadiamento de Neoplasias , Prognóstico , Retinoblastoma/mortalidade , Retinoblastoma/patologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Raios X , Adulto Jovem
20.
PLoS One ; 9(8): e106032, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25162518

RESUMO

BACKGROUND: Pathological angiogenesis plays an essential role in tumor aggressiveness and leads to unfavorable prognosis. The aim of this study is to detect the potential role of Retinoblastoma binding protein 2 (RBP2) in the tumor angiogenesis of non-small cell lung cancer (NSCLC). METHODS: Immunohistochemical staining was used to detect the expression of RBP2, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD34. Two pairs of siRNA sequences and pcDNA3-HA-RBP2 were used to down-regulate and up-regulate RBP2 expression in H1975 and SK-MES-1 cells. An endothelial cell tube formation assay, VEGF enzyme-linked immunosorbent assay, real-time PCR and western blotting were performed to detect the potential mechanisms mediated by RBP2 in tumor angiogenesis. RESULTS: Of the 102 stage I NSCLC specimens analyzed, high RBP2 protein expression is closely associated with tumor size (P = 0.030), high HIF-1α expression (P = 0.028), high VEGF expression (P = 0.048), increased tumor angiogenesis (P = 0.033) and poor prognosis (P = 0.037); high MVD was associated with high HIF-1α expression (P = 0.034), high VEGF expression (P = 0.001) and poor prognosis (P = 0.040). Multivariate analysis indicated that RBP2 had an independent influence on the survival of patients with stage I NSCLC (P = 0.044). By modulating the expression of RBP2, our findings suggested that RBP2 protein depletion decreased HUVECs tube formation by down-regulating VEGF in a conditioned medium. RBP2 stimulated the up-regulation of VEGF, which was dependent on HIF-1α, and activated the HIF-1α via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, VEGF increased the activation of Akt regulated by RBP2. CONCLUSIONS: The RBP2 protein may stimulate HIF-1α expression via the activation of the PI3K/Akt signaling pathway under normoxia and then stimulate VEGF expression. These findings indicate that RBP2 may play a critical role in tumor angiogenesis and serve as an attractive therapeutic target against tumor aggressiveness for early-stage NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/genética , Neovascularização Patológica , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Celulares de Ligação ao Retinol/genética , Fator A de Crescimento do Endotélio Vascular/genética , Antígenos CD34/genética , Antígenos CD34/metabolismo , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas Celulares de Ligação ao Retinol/antagonistas & inibidores , Proteínas Celulares de Ligação ao Retinol/metabolismo , Transdução de Sinais , Análise de Sobrevida , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo
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