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This study found that peroxymonosulfate (PMS) oxidation without activation has the potential to generate a suspected human carcinogen, N-nitrosodimethylamine (NDMA), in water containing N,N-dimethylhydrazine compounds. Considerable amounts of NDMA formed from three compounds by PMS oxidation were observed. 1,1,1',1'-Tetramethyl-4,4'-(methylene-di-p-phenylene) disemicarbazide (TMDS), which is an industrial antiyellowing agent and light stabilizer, was used as a representative to elucidate the kinetics, transformation products, mechanism and NDMA formation pathways of PMS oxidation. TMDS degradation and NDMA formation involved direct PMS oxidation and singlet oxygen (1O2) oxidation. The oxidation by PMS/1O2 was pH-dependent, which was related to the pH-dependent characteristics of the reactive oxygen species and intermediates. The degradation mechanism of TMDS mainly included the side chain cleavage, dealkylation, and O-addition. NDMA was generated from TMDS mainly via O-addition and 1,1-dimethylhydrazine (UDMH) generation. The cleavage of amide nitrogen in O-addition products and primary amine nitrogen in UDMH are likely the key steps in NDMA generation. The results emphasized that the formation of harmful by-products should be taken into account when assessing the feasibility of PMS oxidation.
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Dimetilnitrosamina , Poluentes Químicos da Água , Dimetilidrazinas , Humanos , Cinética , Oxirredução , Peróxidos , Poluentes Químicos da Água/análiseRESUMO
To improve the survival rate and cure rate of patients, it is necessary to find a new treatment scheme according to the molecular composition of (ESCC) in esophageal squamous cell carcinoma. Long non-coding RNAs (lncRNAs) regulate the progression of ESCC by various pathophysiological pathways. We explored the possible function of the lncRNA LINC00261 (LINC00261) on cisplatin (DDP) resistance of ESCC and its relative molecular mechanisms. In the study, we found that LINC00261 was downregulated in ESCC tissues, cell lines, and DDP-resistant ESCC patients. Besides, overexpression of LINC00261 not only inhibited cell proliferation, and DDP resistance but also promotes cell apoptosis. Further mechanistic research showed that LINC00261 sponged miR-545-3p which was negatively correlated with the expression of LINC00261. In addition, functional experiments revealed that upregulation of miR-766-5p promoted proliferation and enhanced DDP resistance. Subsequently, MT1M was testified to be the downstream target gene of miR-545-3p. Rescue experiments revealed that overexpression of MT1M largely restores miR-545-3p mimics-mediated function on ESCC progression. Our results demonstrate that the LINC00261 suppressed the DDP resistance of ESCC through miR-545-3p/MT1M axis.
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BACKGROUND: The tumor volume of high-grade glioma (HGG) after surgery is usually determined by contrast-enhanced MRI (CE-MRI), but the clinical target volume remains controversial. Functional magnetic resonance imaging (multimodality MRI) techniques such as magnetic resonance perfusion-weighted imaging (PWI) and diffusion-tensor imaging (DTI) can make up for CE-MRI. This study explored the survival outcomes and failure patterns of patients with HGG by comparing the combination of multimodality MRI and CE-MRI imaging with CE-MRI alone. METHODS: 102 patients with postoperative HGG between 2012 and 2016 were included. 50 were delineated based on multimodality MRI (PWI, DTI) and CE-MRI (enhanced T1), and the other 52 were delineated based on CE-MRI as control. RESULTS: The median survival benefit was 6 months. The 2-year overall survival, progression-free survival, and local-regional control rates were 48% vs. 25%, 42% vs. 13.46%, and 40% vs. 13.46% for the multimodality MRI and CE-MRI cohorts, respectively. The two cohorts had similar rates of disease progression and recurrence but different proportions of failure patterns. The univariate analysis shows that characteristics of patients such as combined with epilepsy, the dose of radiotherapy, the selection of MRI were significant influence factors for 2-year overall survival. However, in multivariate analyses, only the selection of MRI was an independent significant predictor of overall survival. CONCLUSIONS: This study was the first to explore the clinical value of multimodality MRI in the delineation of radiotherapy target volume for HGG. The conclusions of the study have positive reference significance to the combination of multimodality MRI and CE-MRI in guiding the delineation of the radiotherapy target area for HGG patients.
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Imagem de Difusão por Ressonância Magnética , Glioma/diagnóstico por imagem , Angiografia por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Glioma/diagnóstico , Glioma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Gradação de Tumores , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Adulto JovemRESUMO
BACKGROUND: This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian® ) plus cisplatin (SP regimen) and 5-fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco-regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. RESULTS: In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow-up period, the estimated 3-year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3-year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3-4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). CONCLUSIONS: These data indicate that SP and FP therapies have similar efficacy in treating LA-NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA-NPC treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/efeitos dos fármacos , Quimiorradioterapia/efeitos adversos , Distribuição de Qui-Quadrado , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Intervalo Livre de Progressão , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Estomatite/induzido quimicamente , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Adulto JovemRESUMO
PURPOSE: To assess the survival, local and distant control, and toxicity in patients with unresectable locally advanced non-small cell lung cancer treated with radical-intent hypofractionated radiation therapy delivering approximately 60 Gy in 4-Gy fractions. METHODS AND MATERIALS: Consecutive patients with unresectable stage III non-small cell lung cancer (n = 42) who received hypofractionated intensity modulated radiation therapy were retrospectively analyzed (2012-2016). Treatments consisted of first-line platinum-based doublet induction chemotherapy followed by an intended dose of 60 Gy in 15 fractions. RESULTS: During a median follow-up period of 46 months (95% confidence interval, 41-59) the median overall survival was 47 months (95% confidence interval, 31 to not reached). The 1-, 2-, 3-, and 5-year overall survival rates were 81%, 69%, 64%, and 32%, respectively. The 1-, 2-, 3-, and 5-year progression-free survival rates were 58%, 35%, 25%, and 25%, respectively. An isolated locoregional recurrence was seen in 12% of the patients (n = 5). The incidence of grade (G) 3 or higher treatment-related lung toxicity was 14% (n = 6), among which G3 toxicity was 9.5% (n = 4) and G5 toxicity was 4.8% (n = 2). Twelve percent of patients (n = 5) experienced G3 radiation esophagitis, and 2% (n = 1) had G4 esophageal toxicity. CONCLUSIONS: Patients with unresectable locally advanced non-small cell lung cancer treated with hypofractionated intensity modulated radiation therapy in doses up to 60 Gy at 4 Gy per fraction had promising survival, although high-grade esophageal and lung toxicities were seen. Our findings deserve further evaluation in prospective studies.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Segurança , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Prospectivos , Planejamento da Radioterapia Assistida por ComputadorRESUMO
It has been demonstrated that microRNAs (miRNAs) serve important roles in various biological processes, such as tumorigenesis. In the present study, the role of miR30a3p in the pathogenesis of esophageal carcinoma (EC) was investigated. Reverse transcriptionquantitative polymerase chain reaction was performed to determine the levels of miR30a3p expression in EC tissues and cell lines. Then, the effects of miR30a3p on the migration, invasion and radiosensitivity of EC cells were investigated using scratchwound, Transwell and radiosensitivity assays, respectively. A dualluciferase reporter assay was performed to determine potential interactions between miR30a3p and the 3'untranslated region (3'UTR) of insulinlike growth factor 1 receptor (IGF1R). The results demonstrated that the levels of miR30a3p expression in EC tissues and cell lines were significantly decreased compared with those in paired healthy tissues and a human esophageal epithelial cell line. Upregulation of miR30a3p expression significantly suppressed migration, invasion and epithelialmesenchymal transition (EMT), and enhanced radiosensitivity in EC cells. Analysis of luciferase activity demonstrated that miR30a3p interacted with the 3'UTR of IGF1R, and knockdown of IGF1R induced similar effects on the migration, invasion, EMT and radiosensitivity of EC cells. The results indicated that miR30a3p suppressed metastasis and enhanced the radiosensitivity of EC cells via downregulation IGF1R, suggesting that miR30a3p may be a potential therapeutic target in the treatment of EC.
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Carcinoma/radioterapia , Neoplasias Esofágicas/radioterapia , Tolerância a Radiação/genética , Receptor IGF Tipo 1/genética , Idoso , Carcinogênese/genética , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase NeoplásicaRESUMO
Aberrant microRNAs (miRNAs) expressions could contribute to the progression of numerous cancers, including esophageal squamous cell carcinoma, while miR-10a participates in multiple biological processes on cancers. However, the molecular mechanism of miR-10a in esophageal squamous cell carcinoma (ESCC) has not been investigated. Herein, miR-10a was significantly reduced in ESCC clinical tissues and ESCC cell lines (EC109 and TE-3). In addition, immunohistochemistry indicated that the expressions of α-SMA, Ki-67, and PCNA in tumor tissues were higher than that of controls. In vitro, overexpression of miR-10a dramatically suppressed cell proliferation and enhanced cell apoptosis, while the decrease of miR-10a expressed the opposite outcome. Specially, overexpression of miR-10a caused a G0/G1 peak accumulation. Moreover, miR-10a also negatively regulated ESCC cell migration and invasion. Furthermore, targetscan bioinformatics predictions and the dual-luciferase assay confirmed that Tiam1 was a direct target gene of miR-10a. The statistical analysis showed Tiam1 was negatively in correlation with miR-10a in ESCC patient samples. And silencing Tiam1 could lead to a decline on cell growth, invasion, and migration in ESCC cell lines, while it could enhance cell apoptosis and cause a G0/G1 peak accumulation. In vivo, it revealed that miR-10a notably decreased the tumor growth and metastasis in xenograft model and pulmonary metastasis model. And it showed a lower expressions of Tiam1 in the miR-10a mimics group by immunohistochemistry. Taken together the results, they indicated that miR-10a might function as a novel tumor suppressor in vitro and in vivo via targeting Tiam1, suggesting miR-10a to be a candidate biomarker for the ESCC therapy.
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BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor characterized by highly malignant local invasion and distant metastasis. Recently, increasing attention has been paid to long noncoding RNAs (lncRNAs), which play significant roles in tumorigenesis and progression. However, little is known about the potential role of the lncRNA urothelial carcinoma-associated 1 (UCA1) in NPC cell invasion and migration. METHODS: Real-time quantitative PCR was used to analyze the expression of lncRNA UCA1 in NPC cell lines and NP69. lncRNA UCA1 knock-down nasopharyngeal carcinoma cell line models were established through siRNA. Cell viability was evaluated by Cell counting kit-8 and Colony forming assay. The migration and invasion capacities were evaluated by wound healing and transwell migration and invasion assays. Western blot analysis were used to examine protein changes followed by UCA1 knock-down. RESULTS: Our study confirmed that UCA1 was upregulated in NPC cell lines and involved in NPC tumorigenesis according to our established UCA1-associated competing endogenous RNA network. Moreover, functional analyses indicated that the downregulation of UCA1 exerted inhibitory effects on cell proliferation, invasion, and migration. Mechanistic analyses revealed that UCA1 was the target of miR-145 and functioned as a sponge to repress miR-145 expression. Rescue experiments suggested that lncRNA UCA1 reversed the miR-145-mediated inhibition on oncogene ADAM17 expression, thus promoting the proliferation, invasion, and migration of NPC cells. CONCLUSION: LncRNA UCA1 functions as a tumor promoter in NPC. UCA1 promotes the proliferation and invasion of NPC cells by sponging miR-145, functionally altering ADAM17 expression targeted by miR-145. Our exploration of the underlying mechanism of UCA1 in NPC may provide novel therapeutic targets for NPC.
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Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation. Dose-dependent increase of antioxidant genes by HupA were associated with up-regulated Nrf2 and down-regulated Keap-1 expression, which was confirmed by increasing nuclear accumulation, and inhibiting of degradation of Nrf2. Notably, augmented luciferase activity of ARE may explained Nrf2/ARE-mediated signaling pathways behind HupA protective properties. Moreover, expression of Nrf2 HupA-mediated was significant attenuated by AKT inhibitor (LY294002), p38 MAPK inhibitor (SB202190) and ERK inhibitor (PD98059). Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells.
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Alcaloides/farmacologia , Elementos de Resposta Antioxidante , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Fator 2 Relacionado a NF-E2/genética , Protetores contra Radiação/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Catalase/genética , Catalase/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Cromonas/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Imidazóis/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Peróxidos Lipídicos/antagonistas & inibidores , Peróxidos Lipídicos/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Morfolinas/farmacologia , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/metabolismo , Células NIH 3T3 , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Raios X , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
MicroRNAs (miRNAs) have been reported to regulate the expression of genes by suppressing translation or facilitating mRNA decay. Their expression regulates a wide variety of cellular processes, including the development and progression of cancer. Esophageal squamous cell carcinoma (ESCC) is a malignant cancer with high morbidity and recurrence in Asia. In the present study, the biological function of miR-125b and its underlying mechanism in ESCC were explored. The results revealed that miR-125b expression was significantly decreased in ESCC tissues and cell lines. A decrease in miR-125b was markedly related to lymphatic metastasis in patients. Functional analysis revealed that the overexpression of miR-125b using miR-125b mimics significantly inhibited cell growth and induced cell apoptosis, and increased the G1 phase of the cell cycle in EC109 and EC9706 cells. Notably, the miR-125b inhibitors revealed the opposite effect. Additionally, overexpression of miR-125b significantly inhibited tumor growth in vivo. Furthermore, BCL-2-modifying factor (BMF) was considered to be a potential candidate target of miR-125b based on miRNA target databases. miR-125b negatively regulated BMF expression by directly binding to its 3'-untranslated region. BMF was a functional target of miR-125b in the regulation of cell proliferation, cell apoptosis and the cell cycle in EC109 and EC9706 cells. In clinical ESCC specimens, BMF expression was upregulated, and negatively correlated with that of miR-125b. In conclusion, miR-125b had an antitumor role in ESCC cells mediated by targeting BMF, which can be potentially useful for tumorigenesis in ESCC.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologiaRESUMO
Lung cancer is notorious for high morbidity and mortality around the world. Interleukin (IL)-8, a proinflammatory chemokine with tumorigenic and proangiogenic effects, promotes lung cancer cells growth and migration and contributes to cell aggressive phenotypes. Integrin αvß6 is a receptor of transmembrane heterodimeric cell surface adhesion, and its overexpression correlates with poor survival from non-small cell lung cancer. However, the cross talk between αvß6 and IL-8 in lung cancer has not been characterized so far. Herein, human lung cancer samples were analyzed, and it revealed that the immunohistochemical and mRNA expression of integrin αvß6 was significantly correlated with the expression of IL-8. Furthermore, in vitro, integrin αvß6 increased cell proliferation, migration, and invasion by impairing the expressions of MMP-2 and MMP-9 and inhibited cell apoptosis in human lung cancer cells A549 and H460. In addition, integrin αvß6 upregulated IL-8 expression through activating MAPK/ERK signaling. The in vivo experiment showed that integrin αvß6 promoted tumor growth in xenograft model mice by accelerating tumor volume and reducing apoptosis. Meanwhile, lung metastasis model experiment suggested that integrin αvß6 stimulated tumor metastasis with the increase of lung/total weight and tumor nodules. Simultaneously, integrin αvß6 upregulated IL-8 expression detected by both Western blots and immunohistochemistry, along with the activation of MAPK/ERK signaling. Overall, these data suggested that, in vitro and in vivo, integrin αvß6 promoted lung cancer proliferation and metastasis, at least in part, through upregulation of IL-8-mediated MAPK/ERK signaling. Thus, the inhibition of integrin αvß6 and IL-8 may be the key for the treatment of lung cancer.
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Iron silicate was synthesized and characterized as an efficient ozonation catalyst. Results indicated that iron silicate is a microporous material with poor crystallinity. Fe-O-Si and Fe-O bonds were observed on its surface. The Fe-O bonds belonged to α-Fe2O3. Heterogeneous catalytic ozonation test was performed in batch reaction mode, and 4-chloronitrobenzene was used as model organic compounds. Amorphous iron silicate exhibited high catalytic activity, ozone utilization efficiency, and stability in catalytic ozonation. Hydroxyl radical was the dominant oxide species in this process. The reaction mechanism at the solid-water interface indicates that Fe-Si binary oxides on iron silicate surface inhibited ozone futile decomposition. This behavior resulted in enhanced probability of the reaction between ozone and α-Fe2O3 on the iron silicate surface to generate hydroxyl radicals, which promoted 4-chloronitrobenzene removal in aqueous solution.
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Ozônio , Poluentes Químicos da Água , Catálise , Ferro , Nitrobenzenos , SilicatosRESUMO
Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, can regulate gene expression in mammals. CircRNAs have recently been identified as microRNA sponges and involved in the development of some human diseases. However, the role of circRNAs in the process of tumorigenesis and development of lung cancer remains vague. The purpose of this study is to investigate the role of circRNAs in the lung cancer. In this study, we chose hsa_circ_0000064 as a targeted circRNA to investigate its clinical significances in lung cancer patients. The result indicated that hsa_circ_0000064 was up-regulated in lung cancer tissues and lung cancer cell lines (A549 and H1229). Moreover, its aberrant expression was correlated with several clinical characteristics, including T stage, lymphatic metastasis, and TNM stage. Fluorescence in situ hybridization detected that hsa_circ_0000064 was mostly located in the cytoplasm in A549 and H1229 cells. In addition, knockdown of hsa_circ_0000064 with siRNA dramatically attenuated the proliferation, blocked cell cycle progression, and promoted cell apoptosis. Western blot analysis showed that the protein levels of caspase-3, caspase-9, bax, p21, CDK6 and cyclin D1 significantly restrained by si-hsa_circ_0000064, while the expression of bcl-2 notably increased in A549 and H1229 cells. Further, si-hsa_circ_0000064 also abated migration and invasion activities of A549 and H1229 cells, which may be associated with reduced expressions of MMP-2 and MMP-9. In general, our data suggest that hsa_circ_0000064 represents a novel potential biomarker and therapeutic target of lung cancer.
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Proliferação de Células/genética , Neoplasias Pulmonares/genética , Metástase Linfática/genética , RNA/genética , Células A549 , Apoptose/genética , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/patologia , Caspase 3/genética , Caspase 9/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Ciclina D1/genética , Quinase 6 Dependente de Ciclina/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Circular , Regulação para Cima/genética , Proteína X Associada a bcl-2/genética , Quinases Ativadas por p21/genéticaRESUMO
PURPOSE: The objective of this study is to evaluate the contribution of induction (IC) or adjuvant (AC) chemotherapy additional to concurrent chemoradiotherapy (CCRT) for patients with T3-4N0-1 nasopharyngeal carcinoma (NPC) in the era of intensity-modulate radiotherapy (IMRT). METHOD AND MATERIALS: We retrospectively reviewed the data on 685 patients with newly diagnosed T3-4N0-1 NPC. Propensity score matching (PSM) method was used to match patients. Survival outcomes between different groups were calculated by Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was adopted to establish independent prognostic factors. RESULTS: In total, 236 pairs were selected from the primary cohort. Univariate analysis revealed 3-year overall survival (OS) (90.8% vs. 90.3%, P = 0.820), distant failure-free survival (DFFS) (87.3% vs. 89.4%, P = 0.896) and locoregional failure-free survival (LRFFS) (95.4% vs. 93.0%, P = 0.311) rates were comparable between CCRT plus IC/AC and CCRT alone groups. Multivariate analysis found that treatment group was not an independent prognostic factors for OS (HR, 0.964; 95% CI, 0.620-1.499; P = 0.869), DFFS (HR, 1.036; 95% CI, 0.626-1.714; P = 0.890) and LRFFS (HR, 0.670; 95% CI, 0.338-1.327; P = 0.250). Further subgroup analysis according to overall stage also obtained similar results. CONCLUSION: Patients with T3-4N0-1 NPC receiving CCRT could not benefit from additional induction or adjuvant chemotherapy in the era of IMRT.
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OBJECTIVE: To evaluate the influence of multi-drug resistance 1 (MDR1) gene codon 3435 polymorphisms on response to platinum-based chemotherapeutic regimens for advanced non small cell lung cancer (NSCLC). METHODS: Responses and overall survival were evaluated in a series of patients presenting between March 1, 2005 and December 31, 2010. MDR1 gene C3435T polymorphisms were genotyped using peripheral blood with real time polymerase chain reaction (RT-PCR) and relationships between the MDR1 C3435T genetic polymorphism and response rate of chemotherapy were analyzed by SPSS 13.0. RESULTS: Overall response to chemotherapy in the eligible 103 patients was 21.4%. Patients with C/C genotype in MDR1 codon 3435 had a significantly higher response rate (24.5%) than those for C/T(19.0%) and T/T(12.5%) (P<0.05). The overall median survival time (MST) of patients was 19 months, values with C/C, C/T and T/T genotype were 21, 15.5 and 17 months, respectively (P=0.487). CONCLUSION: Our research suggested that patents with the C/C genotype in MDR1 codon 3435 could be more sensitive to platinum-based chemotherapy than patients with C/T and T/T; however, no significant difference was found between overall survival and MDR1 codon 3435 genetic polymorphisms.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Códon , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Compostos Organoplatínicos/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. METHODS: From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. RESULTS: The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio (HR) = 2.01, 95% confidence intervals (CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P = 0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. CONCLUSION: Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Resistência a Múltiplos Medicamentos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polimorfismo Genético , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To validate the clinical value of a computer assisted program (CAP), (visit website; http://xinenhuang.blog.sohu.com for details) for breast cancer patients who receive postoperative adjuvant chemotherapy. METHODS: Patients with histologically confirmed breast cancer after mastectomy who received postoperative chemotherapy in Jiangsu Cancer Hospital and Research Institute were recruited in this study. All eligible patients are divided into three groups: group A, regimen of practical chemotherapy consistent with CAP prediction; group B, partly consistent with CAP prediction; group C, inconsistent with CAP prediction. Overall survival (OS) was compared among groups A, B and C to determine the efficacy of CAP. RESULTS: From November 1992 to July 2007, 310 female breast cancer patients were recruited into this study, with 112, 106 and 89, respectively, in groups A, B, and C. Prognosis of group A was better than both group B and C, with significantly different survival curves between group A and B (p=0.0004) and group A and C (p=0.0046). CONCLUSION: Validation showed our CAP to provide clinically valuable information on adjuvant chemotherapy for postoperative breast cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Assistida por Computador , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Análise de Sobrevida , Taxoides/administração & dosagemRESUMO
OBJECTIVE: To compare the safety and efficacy of a combination of vinorelbine and epirubicin (NE) with fluorouracil/epirubicin/cyclophosphamide (FEC) as a postoperative adjuvant chemotherapy for breast cancer. METHODS: Breast cancer patients were treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1997 to 2006 with either the NE regimen (vinorelbine 40 mg/m2 iv on day 1 and day 8, epirubicin 50 mg/m2 iv on day 1 and day 2, and a cycle repeated every 21-28 days for totally 4-6 cycles) or the FEC regimen (5-Fu 500 mg/m2 iv gtt on day 1, epirubicin 50 mg/m2 iv on day 1 and day 2, CTX 500 mg/m2 iv on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy. RESULTS: Main side effects in both NE and FEC groups were neutropenia and gastrointestinal syndrome, with a 5 year survival rate of 87.9% in the NE and 85.2% in the FEC group. CONCLUSIONS: NE regimen is safe with good long-term survival rate, and thus could be recommended as a postoperative chemotherapy regimen for breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
PURPOSE: Endostar is a proteolytic fragment of collagen XVIII that has been shown to have antitumor activity, with a favorable toxicological profile. We conducted this study to investigate its efficacy and safety when combined with chemotherapy in patients with advanced solid tumors. METHODS: From July 2006 to September 2008, 45 patients with histologically or cytologically confirmed solid tumors were enrolled into this study. All received Endostar at a dose of 7.5 mg/m2 /day as an intravenous infusion for more than 7 days, in combination with chemotherapy. Patients were treated until tumor progression or unacceptable toxicity. RESULTS: No treatment related death occurred in this study. Main reported toxicities included: myelosuppression (82.2%), hepatic impairment (42.2%), anorexia (20.0%), nausea (24.4%), vomiting (22.2%), diarrhea (20.0%), febrile (20.0%) and fatigue (24.4%). No complete response was observed. Two patients (2/42) had partial response, twenty-one (21/42) remained stable, and nineteen (19/42) had progressive disease. Median time to tumor progression was 3.0 months (range, 0.5-12.0). Median overall survival was 30.0 months (95% confidence interval: 20.0-40.0) and 1 year survival rate was 81.0%. CONCLUSION: Our study revealed that toxicity of Endostar combined with chemotherapy in the treatment of solid tumors was tolerable with moderate efficacy.