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1.
Medicine (Baltimore) ; 98(32): e16592, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393358

RESUMO

RATIONALE: Refractory nasopharyngeal carcinoma is challenging to treat and at present there is no standard treatment or any good choice. PATIENT CONCERNS: Although the three patients in our case reports had already underwent multiple treatments before, they still suffered from disease recurrence of nasopharyngeal carcinoma. DIAGNOSIS: They were diagnosed as refractory nasopharyngeal carcinoma. INTERVENTIONS: A continuous infusion of Endostar, an antiangiogenic agent, combined with chemotherapy and radiation therapy was given to treat the patients. OUTCOMES: Patients showed complete or partial response to the combined therapy as evidenced by regression of tumors and decrease in plasma Epstein-Barr virus (EBV) DNA load. LESSONS: Continuous infusions of Endostar in combination with chemotherapy and/or radiation therapy showed promising efficacy and safety. The combination therapy indicates a new approach to treat refractory nasopharyngeal carcinoma.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Endostatinas/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Adulto , Quimiorradioterapia/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia
3.
Cancer Commun (Lond) ; 39(1): 40, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248459

RESUMO

BACKGROUND: Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy (CCRT) were reported in head and neck cancer. In addition, the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma (NPC) was verified. However, CCRT with docetaxel for locoregionally advanced NPC are not well studied. This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC. METHODS: Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel (15 mg/m2) or tri-weekly cisplatin (80-100 mg/m2) were reviewed. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics. Adverse events and survival were compared between the two groups. RESULTS: A total of 962 patients were included as the whole cohort, and 448 patients were matched and were regarded as the matched cohort. The median follow-up duration was 48 months for the whole cohort. The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole (hazard ratio [HR] = 0.37, 95% confidence interval [CI] 0.19-0.72, P = 0.030) and matched cohorts (HR = 0.33, 95% CI 0.14-0.79, P = 0.023). However, no significant differences were observed in overall survival, local recurrence-free survival, and distant metastasis-free survival between the two groups in both cohorts. Significantly higher rates of grade 3 radiodermatitis (6.7% vs. 1.8%, P = 0.001), mucositis (74.5% vs. 37.9%, P < 0.001), and leucopenia (2.2% vs. 11.6%, P < 0.001) were observed in the docetaxel group, but any grade of renal injury (1.8% vs. 15.1%, P < 0.001), vomiting (18.8% vs. 88.3%, P < 0.001), and ALT elevation (19.2% vs. 31.3%, P = 0.027) were more common in the cisplatin group. CONCLUSIONS: CCRT with weekly low-dose docetaxel is an effective and tolerable therapeutic regimen for locally advanced NPC. It provides a survival benefit mainly by improving the control of regional lymph node metastases, especially for patients with low pretreatment EBV DNA levels.

4.
Biol Sex Differ ; 10(1): 13, 2019 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-30909962

RESUMO

BACKGROUND: The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far. METHODS: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716). RESULTS: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10-5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10-5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10-4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10-2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10-4) and Taiwan datasets (P = 2.99 × 10-2). CONCLUSION: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.

5.
J Cancer ; 9(18): 3352-3360, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271496

RESUMO

Purpose: Investigating surrogate endpoints shortening the time of therapeutic evaluation in nasopharyngeal carcinoma (NPC) after radical treatment. Patients and Methods: We retrospectively analyzed 830 patients receiving intensity-modulated radiotherapy (IMRT) from 2008 to 2010 and being stratified by the 8th edition of UICC/AJCC staging system and the plasma Epstein-Barr virus DNA (EBV DNA). The annual rates of overall survival (OS), progression-free survival (PFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were sequentially calculated using the life table and compared by the McNemar method. Results: The time of shortening therapeutic evaluation by surrogate endpoints: OS, PFS, LRFS and DMFS could be shortened to 1-year (100% vs 100%, P=1) in patients with stage I; OS, PFS, LRFS and DMFS could be shortened to 3-year (96.9% vs 96.1%, P = 1; 94.6% vs 92.2%, P = 0.125; 96.9% vs 95.3%, P = 0.5) and 4-year (92.2% vs 91.2%, P = 0.125) in stage II; In the high EBV DNA group , OS and DMFS could be shortened to 1-year (100% vs 100%, P = 1;100% vs 100%, P = 0.25) in stage II; OS and PFS could be shortened to 3-year (94.3% vs 91.4%, P = 1;82.9% vs 74.3%, P = 0.25) in stage III; OS could be shortened to 4-year (75% vs 72.7%, P = 1) in stage IVA. Conclusions: The time of therapeutic evaluation could be shortened to <5-year in stages I-II patients. The year of surrogate endpoints could be ahead in stages II-IVA with high EBV DNA.

6.
Radiat Oncol ; 13(1): 130, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30016978

RESUMO

BACKGROUND: To investigate the incidence of radiation esophagitis (RE) and tumor local control using esophagus sparing technique in locally advanced non-small cell lung cancer (LANSCLC) treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) and concurrent chemotherapy. METHODS: Eighty-seven patients with stage IIIA/B NSCLC who received definitive SIB-IMRT and concurrent chemotherapy had been divided into two groups: 1.with esophagus sparing technique; 2.without esophagus sparing technique. Chi-square test was performed to compare sex, clinical stage, histology, concurrent chemotherapy, RE and nutrition status between two groups. T-test was used to compare the dosimetric parameters. Overall survival (OS) and loco-regional failure free survival (LRFS) were calculated by the Kaplan-Meier method and compared by a log-rank test. RESULTS: There were 44 patients in the esophagus sparing group and 43 in the non-sparing group. The incidence of severe RE (Grade 3) was significantly lower in patients with esophagus sparing technique (p = 0.002). Patients in esophagus sparing group had better nutrition status (p = 0.045). With a median follow-up of 18 months (range 1-51 months), the 1-year, 2-year and 3-year OS of all the patients was 86.6, 65.4 and 43.7%. The 1-year, 2-year LRFS was 78.4, 65.9%. OS time (p = 0.301) and LRFS (p = 0.871) was comparable between two groups. CONCLUSIONS: Esophagus-sparing technique is an effective and essential method to limit RE in LANSCLC treated by SIB-IMRT and concurrent chemotherapy without compromising local control.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Esofagite/prevenção & controle , Neoplasias Pulmonares/terapia , Tratamentos com Preservação do Órgão/métodos , Lesões por Radiação/prevenção & controle , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/efeitos adversos , Distribuição de Qui-Quadrado , Esofagite/etiologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Qualidade de Vida , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos
7.
J Control Release ; 281: 178-188, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29777796

RESUMO

The sodium pump Na+/K+ ATPase a1 subunit(NKA a1), an attractive cancer-related biomarker and therapeutic target, is closely related to the development and progression of several cancers including breast cancer. Currently, a NKA a1 inhibitor, UNBS1450, has already evidenced its great therapeutic potential in personalized cancer treatment. The ability of non-invasive imaging of NKA a1 expression would be useful for selecting cancer patients who may benefit from this drug. Here, we identified an S3 peptide that is specifically homed to breast cancer by phage display. All data of in vitro and in vivo experiments suggested the excellent targeting character of the S3 peptide. As the binding activity of the S3 phage was positively correlated to the level of NKA α1 expression in various breast cancer cells, NKA α1 was validated as the primary target of the S3 peptide. Based on immunohistochemistry staining result of 107 breast cancer patients, NKA α1 was verified to be a novel tracking marker and a prognostic predictor for breast cancer. Importantly, we proposed and validated an S3 peptide-based radiotracer 18F-ALF-NOTA-S3 for PET (Positron Emission Tomography) imaging of breast cancer and other NKA α1-overexpressing cancers, including hepatocellular carcinoma and non-small cell lung cancer, in mouse models. Our findings demonstrated the potential application of 18F-ALF-NOTA-S3 for visualization of NKA α1-positive lesions, which provide a new approach to character tumor phenotypic imaging.

8.
J Cancer ; 9(5): 797-806, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29581758

RESUMO

Background: To establish a prognostic score based on clinical routine factors to stratify nasopharyngeal carcinoma patients with bone metastasis into risk groups with different survival rates. Materials and Methods: Total 276 patients from multicenter were retrospectively analyzed. Kaplan-Meier method and Cox regression were used to confirm independent risk factors, which were checked for internal validity by bootstrapping method. The prognostic score, deriving from the corresponding regression coefficients in Cox model, classified patients into low and high risk groups. Finally, two independent cohorts were used for external validation. Results: In development cohort, six risk factors were identified: age>46 year-old (point=1), N>0 stage (point=2), anemia (point=2), bone metastasis free interval≤12 months (point=1), without radiotherapy to primary sites (point=1), and without radiotherapy to first metastasis sites (point=1). The derived prognostic score divided patients into low (score, 0-4) and high (score, 5-8) risk groups, with highly significant differences of 5-year overall survival rates (high vs. low risk: 24.6% vs. 58.2%, HR 3.47, P<0.001). Two external validations presented congruent results. Conclusion: A feasible and applicative prognostic score was successfully established and validated to discriminate bone metastatic nasopharyngeal carcinoma into low/high risk groups, which will be useful for individual treatment.

9.
Clin Cancer Res ; 24(3): 659-673, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29133573

RESUMO

Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC.Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC.Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1-positive HNC samples than in negative samples.Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659-73. ©2017 AACR.

10.
Cancer Res Treat ; 50(4): 1203-1213, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29268566

RESUMO

PURPOSE: This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). Materials and Methods: RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. RESULTS: The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. CONCLUSION: CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

11.
Cell Death Dis ; 8(7): e2912, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28682313

RESUMO

Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release. The inhibition of autophagy effectively suppressed the neuroprotective effect of SPK2. SPK2 overexpression reduced the co-immunoprecipitation of Beclin-1 and Bcl-2, while Beclin-1 knockdown inhibited SPK2-induced autophagy. Both co-immunoprecipitation and GST pull-down analysis suggest that SPK2 directly interacts with Bcl-2. SPK2 might interact to Bcl-2 in the cytoplasm. Notably, an SPK2 mutant with L219A substitution in its putative BH3 domain was not able to activate autophagy. A Tat peptide fused to an 18-amino acid peptide encompassing the native, but not the L219A mutated BH3 domain of SPK2 activated autophagy in neural cells. The Tat-SPK2 peptide also protected neurons against OGD injury through autophagy activation. These results suggest that SPK2 interacts with Bcl-2 via its BH3 domain, thereby dissociating it from Beclin-1 and activating autophagy. The observation that Tat-SPK2 peptide designed from the BH3 domain of SPK2 activates autophagy and protects neural cells against OGD injury suggest that this structure may provide the basis for a novel class of therapeutic agents against ischemic stroke.


Assuntos
Isquemia Encefálica/genética , Neurônios/metabolismo , Fragmentos de Peptídeos/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Recombinantes de Fusão/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Sequência de Aminoácidos , Animais , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Regulação da Expressão Gênica , Glucose/deficiência , Hipocampo/metabolismo , Hipocampo/patologia , Precondicionamento Isquêmico/métodos , Isoflurano/administração & dosagem , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fragmentos de Peptídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Cultura Primária de Células , Ligação Proteica , Domínios Proteicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
12.
J Cancer ; 8(6): 1030-1037, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28529616

RESUMO

Objective: Great heterogeneity exists in clinical behavior and survival outcome in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). In this study, we proposed lymphocyte/monocyte ratio (LMR) as a new prognostic factor for these early stage ENKTL. Methods: We retrospectively examined the LMR as a prognostic variable in a cohort of 379 patients with newly diagnosed stage IE/IIE ENKTL. The relationship between the LMR and clinicopathologic variables were analyzed in Kaplan-Meier log-rank survival analysis, and the Cox proportional hazards model was used to determine the survival significance of the LMR for both progression-free survival (PFS) and overall survival (OS). Results: Patients were categorized into two different groups based on the LMR using cut-off value of 2.0. The 5-year PFS rates in the low and high LMR group were 43.9% and 62.7%, respectively, and the 5-year OS rates in the two groups were 59.1% and 77.7%, respectively. In multivariate analysis, low LMR at diagnosis was associated with worse PFS (hazard ratio 1.611, 95% confidence interval: 1.027-2.525, P =0.038) independent of age (P=0.033) and treatment stratagem (P<0.001), and indicated worse OS (hazard ratio 2.003, 95% confidence interval: 1.124-3.569, P =0.018) independent of age (P=0.007), LDH level (P=0.042), local tumor invasiveness (P=0.008), and treatment stratagem (P<0.001). Conclusion: The LMR is an independent prognostic factor for both DFS and OS in patients with stage IE/IIE ENKTL, and provides additional prognostic value beyond standard clinicopathological parameters.

13.
J Cancer ; 8(5): 832-838, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28382146

RESUMO

Background: Weight loss during radiotherapy has been known as a negative prognostic factor for nasopharyngeal carcinoma (NPC) patients, but the factors related to weight loss during radiotherapy were not fully understood. Methods: A total of 322 newly diagnosed NPC patients receiving intensity modulated radiotherapy (IMRT) in Sun Yat-sen University Cancer Center between June 2002 and August 2006 were enrolled. Kaplan-Meier methods and log-rank test were applied for survival analysis; a multiple regression was used to identify the factors related to weight loss during radiotherapy. Results: The mean and median values of weight loss (%) during radiotherapy were 6.85% and 6.70%. NPC patients with critical weight loss (> 5.4%) have poorer overall survival (OS) and distant metastasis-free survival (DMFS) than the patients without critical weight loss (p = 0.002 and 0.021, respectively). Pre-radiotherapy weight, acute mucosal toxicity, acute pharynx and esophagus toxicity, and acute upper gastrointestinal toxicity were related to the weight loss during radiotherapy independently (p = 0.01, p < 0.001, p < 0.001, and p = 0.009, respectively). Conclusions: Acute radiation toxicities had significant and independent impact on weight loss during radiotherapy. The vicious circle of acute radiation toxicities and weight loss had bad effect on prognosis of NPC patients.

14.
Oncotarget ; 8(7): 11480-11488, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28002792

RESUMO

This study retrospectively investigated asparaginase-based chemotherapy treatment outcomes with or without radiotherapy in 143 patients with stage IE-IIE extranodal natural killer/T cell lymphoma (ENKTCL). All patients received a median of three cycles of asparaginase-based chemotherapy, while 121 patients received radiotherapy following the chemotherapy. The complete remission (CR) rate for all patients post-chemotherapy was 58.7%, and rose to 73.4% by the end of treatment. Patients who received radiotherapy achieved better survival outcomes than those who did not (89.7% vs. 49.0% for 2-year overall survival (OS), P<0.001; 86.8% vs. 37.4% for 2-year progression-free survival (PFS), P<0.001). Additionally, even patients who achieved CR post-chemotherapy exhibited differential survival rates with or without radiotherapy (90.8% vs. 60% for 2-year OS, P=0.006; 86.1% vs. 60% for 2-year PFS, P=0.044). Multivariate analysis revealed that radiotherapy was an independent factor favoring OS (HR=0.098, 95%CI=0.031-0.314, P=0.001) and PFS (HR=0.156, 95%CI=0.062-0.396, P=0.001). Thus, radiotherapy is recommended for stage IE-IIE ENKTCL patients treated with asparaginase-based chemotherapy, even in cases of CR following chemotherapy.


Assuntos
Quimiorradioterapia/métodos , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
15.
Cancer Med ; 6(1): 310-319, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27860387

RESUMO

Chronic inflammation plays an important role in tumor progression. The aim of this analysis was to evaluate whether inflammatory biomarkers such as the Glasgow prognostic score (GPS), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), and the lymphocyte-monocyte ratio (LMR) could predict the prognosis of nasopharyngeal carcinoma (NPC). In this analysis, pretreatment GPS, NLR, PLR, LMR of 388 patients who were diagnosed as nonmetastatic NPC and recruited prospectively in the 863 Program No. 2006AA02Z4B4 were assessed. Of those, the 249 cases enrolled between December 27th 2006 and July 31st 2011 were defined as the development set. The rest 139 cases enrolled between August 1st 2011 and July 31st 2013 were defined as the validation set. The variables above were analyzed in the development set, together with age, gender, Karnofsky performance score, T stage, and N stage, with respect to their impact on the disease-specific survival (DSS) through a univariate analysis. The candidate prognostic factors then underwent a multivariate analysis. A nomogram was established to predict the DSS, by involving the independent prognostic factors. Its predction capacity was evaluated through calculating Harrell's concordance index (C-index) in the validation set. After multivariate analysis for the development set, age (≤50 vs. >50 years old), T stage (T1-2 vs. T3-4), N stage (N0-1 vs. N2-3) and pretreatment GPS (0 vs. 1-2), NLR (≤2.5 vs. >2.5), LMR (≤2.35 vs. >2.35) were independent prognostic factors of DSS (P values were 0.002, 0.008, <0.001, 0.004, 0.018, and 0.004, respectively). A nomogram was established by involving all the factors above. Its C-index for predicting the DSS of the validation set was 0.734 (standard error 0.056). Pretreatment GPS, NLR, and LMR were independent prognostic factors of NPC. The nomogram based on them could be used to predict the DSS of NPC patients.


Assuntos
Carcinoma/imunologia , Carcinoma/patologia , Monócitos/citologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Neutrófilos/citologia , Contagem de Células Sanguíneas , Feminino , Humanos , Contagem de Linfócitos , Masculino , Carcinoma Nasofaríngeo , Gradação de Tumores , Estadiamento de Neoplasias , Nomogramas , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos
16.
ACS Omega ; 2(6): 2459-2468, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30023665

RESUMO

Extradomain-B fibronectin (EDB-FN), an oncofetal isoform of FN, is a promising diagnostic and therapeutic target of tumors, including breast cancer. Many EDB-FN-targeted drugs have been developed and have shown therapeutic effects in clinical trials. Molecular imaging to visualize EDB-FN-positive cancers may help select the right patients who will be benefit from EDB-FN-targeted therapy. Although a few EDB-FN-targeted imaging probes have been developed, the complicated manufacturing procedure and expensive material and equipment required limit their application for large-scale screening of EDB-FN-positive cancer patients. Thus, more simple and economic EDB-FN-targeted imaging probes are still urgently needed. Previously, we have identified a breast cancer-targeted peptide, CTVRTSADC. Coincidently, it was later identified as an EDB-FN-targeted peptide and named ZD2. In this study, we found a positive correlation between the binding activity of the ZD2 phage and the expression level of EDB-FN in breast cancer cells. Moreover, we observed the colocalization of the ZD2 peptide with EDB-FN in breast cancer cells. Furthermore, in vivo tumor targeting of the ZD2 phage, near-infrared fluorescence imaging, and flow cytometry showed tumor-specific homing of the ZD2 peptide in mice bearing EDB-FN-positive breast cancers. Importantly, on the basis of this EDB-FN-targeted ZD2 peptide, we developed a kit-formulated probe, 99mTc-HYNIC-ZD2, for single-photon-emission computed tomography (SPECT) imaging of breast cancer. The high tumor uptake of 99mTc-HYNIC-ZD2 demonstrated its feasibility for use in visualizing EDB-FN-positive breast cancers in vivo. This kit-formulated EDB-FN-targeted SPECT probe has potential clinical applications for precision screening of EDB-FN-positive cancer patients who may benefit from EDB-FN-targeted therapy.

17.
Onco Targets Ther ; 9: 7011-7017, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27895493

RESUMO

Bone metastasis is the most frequent type of distant metastasis in nasopharyngeal carcinoma (NPC). In this study, we investigated the correlation between the skull base bone destruction and the distant bone metastasis in patients with NPC. A total of 449 cases with NPC who were diagnosed and had definitive radiotherapy from 2001 to 2006 were enrolled in this study. The skull base bone destruction was diagnosed by computed tomography (CT) in all cases, and 191 patients also underwent magnetic resonance imaging scan. Kaplan-Meier method was adopted to perform the univariate analysis; Cox regression model was used to perform multivariate analysis to determine whether the skull base bone destruction when diagnosed by CT was an independent impact factor of the distant bone metastases. The group with skull base bone destruction had a distant bone metastases rate of 9.0% (14/155), whereas the group without skull base bone destruction had rate of 4.1% (12/294). The multivariate analysis showed that the skull base bone destruction, when diagnosed by CT, was an independent impact factor of the distant bone metastases-free survival in the early N-staging cases, but was not an independent impact factor when diagnosed by MRI. The skull base bone destruction diagnosed by CT in patients with NPC had predictive value for the distant bone metastases, especially for the early N-staging cases.

18.
Tumour Biol ; 37(11): 14825-14830, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27639382

RESUMO

The X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism (rs861539, C > T) has drawn wide attentions as its association with cancer risk and its involvement in DNA repair. Several studies have attempted to link rs861539 to nasopharyngeal cancer (NPC) risk; however, the sample sizes of these studies are small and the results are controversial. To investigate the relationship of rs861539 and NPC susceptibility, we conducted a large-scale case-control study involving 4001 NPC cases and 2967 controls of southern Chinese. Logistic regression analysis revealed significant association for rs861539 and NPC risk under the recessive model (TT vs. CT + CC) with adjustment of age and gender (odds ratio, OR = 2.72; 95 % CI 1.10-6.72; P = 0.03). Further, meta-analysis involving 4457 NPC cases and 4132 controls from four studies showed consistent association of TT carriers and NPC risk (OR = 3.12; 95 % CI 1.58-6.13; P = 0.001). Taken together, our findings based on large-scale sample size suggested rs861539 at XRCC3 to be associated with NPC risk through recessive model.


Assuntos
Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias Nasofaríngeas/genética , Polimorfismo de Nucleotídeo Único/genética , Carcinoma , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/patologia , Fatores de Risco
19.
Cell Death Dis ; 7(9): e2352, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27584791

RESUMO

Abnormal interaction between non-coding RNAs has been demonstrated to be a common molecular event in various human cancers, but its significance and underlying mechanisms have not been well documented. RNA-binding proteins (RBPs) are key regulators of RNA transcription and post-transcriptional processing. In this study, we found that RNA-binding protein 24 (RBM24) was frequently downregulated in nasopharyngeal carcinoma (NPC). The restoration of RBM24 expression suppressed NPC cellular proliferation, migration and invasion and impeded metastatic colonization in mouse models. Microarray analyses revealed that miR-25 expression was upregulated by RBM24 expression in NPC cells. Similarly, ectopic miR-25 expression suppressed NPC cellular growth and motility by targeting the pro-oncogenic lncRNA MALAT1, and the knockdown of MALAT1 expression exhibited similar effects as RBM24 restoration in NPC cells. Overall, these findings suggest a novel role of RBM24 as a tumor suppressor. Mechanistically, RBM24 acts at least in part through upregulating the expression of miR-25, which in turn targets MALAT1 for degradation.


Assuntos
Carcinoma/genética , Carcinoma/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Regulação para Cima/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Carcinoma Nasofaríngeo , Invasividade Neoplásica , Metástase Neoplásica
20.
Oncotarget ; 7(40): 65946-65956, 2016 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-27602752

RESUMO

c-Fos is a major component of activator protein (AP)-1 complex. It has been implicated in cell differentiation, proliferation, angiogenesis, invasion, and metastasis. To investigate the role of c-Fos in glioma radiosensitivity and to understand the underlying molecular mechanisms, we downregulated c-Fos gene expression by lentivirus-mediated shRNA in glioma cell lines and subsequently analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution. Finally, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that silencing c-Fos sensitized glioma cells to radiation by increasing radiation-induced DNA double strand breaks (DSBs), disturbing the DNA damage repair process, promoting G2/M cell cycle arrest, and enhancing apoptosis. c-Fos protein overexpression correlated with poor prognosis in malignant glioma patients treated with standard therapy. Our findings provide new insights into the mechanism of radioresistance in malignant glioma and identify c-Fos as a potentially novel therapeutic target for malignant glioma patients.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Glioma/patologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Tolerância a Radiação , Adolescente , Adulto , Idoso , Apoptose/efeitos da radiação , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Criança , Feminino , Seguimentos , Glioma/metabolismo , Glioma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Adulto Jovem
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