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1.
World Neurosurg ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442642

RESUMO

BACKGROUND: There are no standardized criteria to predict the prognosis of patients with low-grade gliomas. Therefore, novel prognostic biomarkers that can guide follow-up schedules and therapeutic approaches are urgently required in patients with low-grade gliomas. METHODS: One hundred and nineteen patients with World Health Organization (WHO) II gliomas were recruited between January 2010 and December 2016 from Xiangya Hospital for this study. We collected neutrophil and lymphocyte values from the full blood counts measured 24 h before surgery. Neutrophil-to-lymphocyte ratios (NLRs) were then calculated. The significance of the NLR was determined based on a nonparametric test. The Kaplan-Meier method was used to estimate survival rates. The influence of the NLR on progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariate Cox proportional hazards models. RESULTS: Preoperative NLRs were upregulated in patients with WHO II gliomas who relapsed or died. Preoperative NLRs were also significantly correlated with age, preoperative neutrophil values, and preoperative lymphocyte values. Compared with the low preoperative NLR group, patients with WHO II gliomas in the high preoperative NLR group had significantly higher relapse and lower survival rates. Additionally, the preoperative NLR and tumor type were independent prognostic parameters of PFS for WHO II gliomas, while only the preoperative NLR was an independent prognostic parameter of OS for WHO II gliomas. CONCLUSIONS: High preoperative NLRs were significantly associated with greater relapse and poor prognosis in patients with WHO II gliomas.

2.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31092699

RESUMO

Introduction: The treatment strategy for low-grade gliomas (LGGs) is still controversial, and there are no standardized criteria to predict the prognosis of patients with LGGs. Magnetic resonance imaging (MRI) is a routine test for preoperative diagnosis for LGG and can reflect the destructive features for the tumor. In the present study, we aimed to explore the relationship between the MRI features and prognosis in patients with LGG.Methods: Clinical data of 80 patients with pathologically proved LGGs between January 2010 and December 2016 were analyzed retrospectively. MRI features were classified as contrast enhancement pattern (focal enhancement, diffuse enhancement and ring-like enhancement), necrosis and cysts based on the preoperative MR images. Kaplan-Meier method and multivariate analysis were performed on the data by SPSS software to explore the prognostic significance of MRI features.Results: Patients with cystic LGG had a significantly longer 5-year progression-free survival (PFS) than that with no cyst (90.9 ± 8.7 vs 65.7 ± 9.1%, P=0.045). Multivariate analysis further verified cyst as an independent prognosis factor for PFS (P=0.027, hazard ratio [HR] = 0.084). Additionally, patients with ring-like enhancement exhibited significantly longer 5-year PFS time in the Kaplan-Meier survival curves (100 vs 67.2 ± 7.7%, P=0.049). There was no significant difference in PFS and overall survival (OS) between patients with or without necrosis.Conclusion: Our study suggests that cyst formation and ring-like enhancement on preoperative MR images can be useful to predict a favorable prognosis in patients with LGGs.

3.
Biomed Res Int ; 2018: 2653497, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967769

RESUMO

Purpose: To compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in treating early T-stage nasopharyngeal carcinoma (NPC). Method: Ten patients with early T-stage NPC who received tomotherapy using simultaneously integrated boost (SIB) strategies were replanned with VMAT (RapidArc of Varian, dual-arc). Dosimetric comparisons between the RapidArc plan and the HT plan included the following: (1) D98, homogeneity, and conformity of PTVs; (2) sparing of organs at risk (OARs); (3) delivery time and monitor units (MUs). Results: (1) Compared with RapidArc, HT achieved better dose conformity (CI of PGTVnx + nd: 0.861 versus 0.818, P = 0.004). (2) In terms of OAR protection, RapidArc exhibited significant superiority in sparing ipsilateral optic nerve (Dmax: 27.5Gy versus 49.1Gy, P < 0.001; D2: 23.5Gy versus 48.2Gy, P < 0.001), contralateral optic nerve (Dmax: 30.4Gy versus 49.2Gy, P < 0.001; D2: 26.2Gy versus 48.1Gy, P < 0.001), and optic chiasm (Dmax: 32.8Gy versus 48.3Gy, P < 0.001; D2: 30Gy versus 47.6Gy, P < 0.001). HT demonstrated a superior ability to protect the brain stem (D1cc: 43.0Gy versus 45.2Gy, P = 0.012), ipsilateral temporal lobe (Dmax 64.5Gy versus 66.4 Gy, P = 0.015), contralateral temporal lobe (Dmax: 62.8Gy versus 65.1Gy, P = 0.001), ipsilateral lens (Dmax: 4.27Gy versus 5.24Gy, P = 0.009; D2: 4.00Gy versus 5.05Gy, P = 0.002; Dmean: 2.99Gy versus 4.31Gy, P < 0.001), contralateral lens (Dmax: 4.25Gy versus 5.09Gy, P = 0.047; D2: 3.91Gy versus 4.92Gy, P = 0.005; Dmean: 2.91Gy versus 4.18Gy, P < 0.001), ipsilateral parotid (Dmean: 36.4Gy versus 41.1Gy, P = 0.002; V30Gy: 54.8% versus 70.4%, P = 0.009), and contralateral parotid (Dmean: 33.4Gy versus 39.1Gy, P < 0.001; V30Gy: 48.2% versus 67.3%, P = 0.005). There were no statistically significant differences in spinal cord or pituitary protection between the RapidArc plan and the HT plan. (3) RapidArc achieved a much shorter delivery time (3.8 min versus 7.5 min, P < 0.001) and a lower MU (618MUs versus 5646MUs, P < 0.001). Conclusion: Our results show that RapidArc and HT are comparable in D98, dose homogeneity, and protection of the spinal cord and pituitary gland. RapidArc performs better in shortening delivery time, lowering MUs, and sparing the optic nerve and optic chiasm. HT is superior in dose conformity and protection of the brain stem, temporal lobe, lens, and parotid.

4.
Oncol Lett ; 15(4): 4445-4450, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29552107

RESUMO

The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively. Multivariate Cox regression analysis identified that targeted treatment [hazard ratio (95% confidence interval), 2.642 (1.001, 6.972); P=0.0497] served as an independent negative prognostic factor in locally advanced NPC. The results of immunostaining revealed that the staining intensity of the radiation-resistant group was increased compared with that of the radiation-sensitive group. These results demonstrate that a high expression of EGFR may be associated with radiation resistance, and targeted treatment may not be effective in patients with locally advanced nasopharyngeal carcinoma with low expression of EGFR.

5.
Onco Targets Ther ; 10: 5445-5458, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29180878

RESUMO

Background: The potential benefits and possible risks associated with combined nimotuzumab and concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma (NPC) have yet to be determined. Methods: The databases PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang were systematically searched through February 2017 for studies comparing combined nimotuzumab and chemoradiotherapy versus chemoradiotherapy alone in the treatment of NPC. Primary outcomes were complete and partial responses, and the secondary outcome was adverse reactions. The random-effect model was used to pool relative risks (RRs) and 95% confidence intervals (CIs). Results: Nine randomized control trials and six cohort studies were included in the final analysis (n=1,015 patients). Compared with chemoradiotherapy alone, chemoradiotherapy combined with nimotuzumab was associated with an increased response rate (RR =1.11, 95% CI: 1.01-1.22). Combined treatment further reduced the occurrence rate of erythropenia (RR =0.11, 95% CI: 0.05-0.28) and neutropenia (RR =0.12, 95% CI: 0.05-0.27). The differences in the rates of other complications were not significant. Conclusion: Nimotuzumab combined with concurrent chemoradiotherapy is more effective in patients with advanced NPC than chemoradiotherapy alone. Patients receiving combination therapy did not have a higher rate of adverse reactions. Nimotuzumab can thus be recommended as an adjunct therapy in patients with advanced NPC.

6.
Biochem Biophys Res Commun ; 494(1-2): 390-396, 2017 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-28947213

RESUMO

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in Southern China and Southeast Asia compared with Western countries. The standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to satisfactory treatment, it can cause local recurrence and distant metastases in some patients after treatment by radiation. We retrospectively reviewed 108 NPC patients (7th AJCC Ⅲ-Ⅳa) who have received intensity modulated radiation therapy (IMRT) between August 2008 and January 2012 at Xiangya Hospital of Central South University. Ninety-eight patients with >60% reduction of tumor size after radiation treatment were regarded as radiation sensitive, Ten patients with <40% reduction of tumor size after radiation treatment were regarded as radiation resistant. Using immunohistochemistry, we found that the high expression rate of Ki-67 in radiation resistant and radiation sensitive patients was 80.0% and 42.6%, respectively, and the difference was statistically significant (p = 0.025). The 5-year progress free survival rates in patients with low and high expression of Ki-67 was 70.7% and 48.0%, respectively, and the difference was statistically significant (p = 0.0008). Multivariate Cox regression analysis identified that high expression of Ki-67 was an independent negative prognostic factor in nasopharyngeal carcinoma patients [Hazard ratio (95% CI), 2.098(1.101, 3.996); p = 0.024]. These results demonstrate that high expression of Ki-67 contributes to radiation resistance and acts a poor prognosis indicator in patients with locally advanced nasopharyngeal carcinoma.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/diagnóstico , Carcinoma/genética , Antígeno Ki-67/genética , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma/mortalidade , Carcinoma/terapia , Cetuximab/uso terapêutico , Feminino , Raios gama/uso terapêutico , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
7.
Oncotarget ; 8(9): 15642-15650, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28152505

RESUMO

We conducted a meta-analysis to evaluate the diagnostic values of mean cerebral blood volume for recurrent and radiation injury in glioma patients. We performed systematic electronic searches for eligible study up to August 8, 2016. Bivariate mixed effects models were used to estimate the combined sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and their 95% confidence intervals (CIs). Fifteen studies with a total number of 576 participants were enrolled. The pooled sensitivity and specificity of diagnostic were 0.88 (95%CI: 0.82-0.92) and 0.85 (95%CI: 0.68-0.93). The pooled positive likelihood ratio is 5.73 (95%CI: 2.56-12.81), negative likelihood ratio is 0.15 (95%CI: 0.10-0.22), and the diagnostic odds ratio is 39.34 (95%CI:13.96-110.84). The summary receiver operator characteristic is 0.91 (95%CI: 0.88-0.93). However, the Deek's plot suggested publication bias may exist (t=2.30, P=0.039). Mean cerebral blood volume measurement methods seems to be very sensitive and highly specific to differentiate recurrent and radiation injury in glioma patients. The results should be interpreted with caution because of the potential bias.


Assuntos
Volume Sanguíneo Cerebral , Quimiorradioterapia/métodos , Glioma/terapia , Lesões por Radiação/diagnóstico , Radioterapia/métodos , Quimiorradioterapia/efeitos adversos , Feminino , Glioma/irrigação sanguínea , Glioma/patologia , Humanos , Masculino , Recidiva Local de Neoplasia , Curva ROC , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Dosagem Radioterapêutica
8.
Chin J Cancer ; 35(1): 96, 2016 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-27852284

RESUMO

BACKGROUND: Gross target volume of primary tumor (GTV-P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity-modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to find a suitable cut-off value of GTV-P for prognosis prediction. METHODS: Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver operating characteristic (ROC) curves were used to identify the cut-off values of GTV-P for the prediction of different endpoints [overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS)] and to test the prognostic value of GTV-P when compared with that of the American Joint Committee on Cancer T staging system. RESULTS: The 358 patients with locally advanced NPC were divided into two groups by the cut-off value of GTV-P as determined using ROC curves: 219 (61.2%) patients with GTV-P ≤46.4 mL and 139 (38.8%) with GTV-P >46.4 mL. The 3-year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV-P ≤46.4 mL than in those with GTV-P > 46.4 mL (all P < 0.05). Multivariate analysis indicated that GTV-P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve verified that the predictive ability of GTV-P was superior to that of T category (P < 0.001). The cut-off values of GTV-P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively. CONCLUSION: In patients with locally advanced NPC, GTV-P >46.4 mL is an independent unfavorable prognostic indicator for survival after IMRT, with a prognostic value superior to that of T category.


Assuntos
Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/radioterapia , Invasividade Neoplásica , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
9.
Oncotarget ; 7(49): 81862-81869, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27835910

RESUMO

The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency.


Assuntos
Adenoma/prevenção & controle , Estatura/efeitos dos fármacos , Craniofaringioma/prevenção & controle , Transtornos do Crescimento/tratamento farmacológico , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Neoplasias Hipofisárias/prevenção & controle , Adenoma/epidemiologia , Adolescente , Adulto , Idoso , Craniofaringioma/epidemiologia , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Hipofisárias/epidemiologia , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Int J Clin Exp Pathol ; 8(4): 4054-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26097593

RESUMO

The mechanism by which overexpression of hexokinase 2 (HK2) indicates locally advanced cervical squamous cell carcinoma (LACSCC) with radio-resistance is still unknown despite being an independent biomarker of poor prognosis. Here, we retrospectively analyzed 132 female patients receiving radiotherapy for cervical squamous cell carcinoma including 85 radiation-sensitive cases and 47 radiation-resistant cases. The expression of HK2 was examined by immunohistochemistry. The percentage of high HK2 expression in the radiation-resistant group differed from the radiation-sensitive group with statistical significance (P < 0.001) even if divided into three subgroups including a lower 5-year progression free survival group (PFS) for comparison (P < 0.001). The Kaplan Meier curve analysis showed that there were differences between the two groups (P < 0.001). Therefore, this study proves a close relationship between HK2 expression and radio-resistance. Multivariate Cox regression analysis implied that HK2 was an independent prognostic indicator of cervical squamous carcinoma (HR (95% CI), 2.940 (1.609, 1.609); P = 0.002).


Assuntos
Biomarcadores Tumorais/análise , Braquiterapia , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/radioterapia , Hexoquinase/análise , Tolerância a Radiação , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/mortalidade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Distribuição de Qui-Quadrado , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
11.
Histol Histopathol ; 30(11): 1313-20, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25936600

RESUMO

Our study aimed to investigate the association of Pyruvate Kinase isozyme type M2 (PKM2) with radiation resistance in locally advanced cervical squamous cell carcinoma (LACSCC). We retrospectively reviewed 132 female patients who received primary radiation therapy to treat LACSCC at Federation Internationale of Gynecologie and Obstetrigue (FIGO) stages IB-IVA. Forty-seven patients with progression free survival (PFS) of less than 36 months were regarded to have radiation resistance. Eighty-five patients with PFS no less than 36 months were regarded as radiation sensitive. Using immunohistochemistry, we found that the overexpression rate of PKM2 in radiation resistant and radiation sensitive patients was 87.2% and 57.6%, respectively, and the difference was statistically significant (p<0.001). The 5-year progress free survival rates in patients with low and high expression of PKM2 was 80.4% and 60.5%, respectively, and the difference was statistically significant (p=0.008). Multivariate Cox regression analysis identified that high expression of PKM2 is an independent negative prognostic factor in cervical cancer patients [Hazard ratio (95% CI), 2.888 (1.347, 6.194) p=0.006]. These results demonstrate that overexpression of PKM2 contributes to radiation resistance and acts a poor prognosis indicator in patients with LACSCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/radioterapia , Proteínas de Transporte/análise , Proteínas de Membrana/análise , Tolerância a Radiação , Hormônios Tireóideos/análise , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Neoplasias do Colo do Útero/patologia , Adulto Jovem
12.
J Histochem Cytochem ; 63(2): 88-98, 2015 02.
Artigo em Inglês | MEDLINE | ID: mdl-25380749

RESUMO

Radiotherapy is the first-line treatment for all stages of cervical cancer, whether it is used for radical or palliative therapy. However, radioresistance of cervical cancer remains a major therapeutic problem. Consequently, we explored if E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients divided into two groups (radiation-resistant and radiation-sensitive groups) according to progression-free survival (PFS). In pretreated paraffin-embedded tissues, we evaluated E-cadherin and osteopontin expression using immunohistochemical staining. The percentage of patients with high osteopontin but low E-cadherin expression in the radiation-resistant group was significantly higher than those in the radiation-sensitive group (p<0.001). These patients also had a lower 5-year PFS rate (p<0.001). Our research suggests that high osteopontin but low E-cadherin expression can be considered as a negative, independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI) 6.766 (2.940, 15.572)], p<0.001).


Assuntos
Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica , Osteopontina/metabolismo , Tolerância a Radiação , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
13.
Int J Clin Exp Pathol ; 7(4): 1651-66, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24817962

RESUMO

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.


Assuntos
Basigina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/radioterapia , Transportador de Glucose Tipo 1/metabolismo , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Basigina/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/genética , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Falha de Tratamento , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade
14.
J Histochem Cytochem ; 62(7): 499-509, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24710660

RESUMO

Radiotherapy (RT) as a preoperative or postoperative adjuvant or primary treatment is the most common management modality for locally advanced cervical cancer. Radioresistance of tumor cells remains a major therapeutic problem. Consequently, we aimed to explore if the stem cell biomarkers SOX2 and OCT4 protein could be used to predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). These 132 patients were divided into two groups (radiation-resistant and radiation-sensitive groups) according to progress-free survival (PFS). Using pretreatment paraffin-embedded tissues, we evaluated SOX2 and OCT4 expression using immunohistochemical staining. The percentage of overexpression of SOX2 and OCT4 in the radiation-resistant group was much higher than that in the radiation-sensitive group (p<0.001 and p <0.001, respectively). The patients with high expression of SOX2 and OCT4 showed a shorter PFS than those with low expression. Our study suggests that the expression of SOX2 and OCT4 in tumor cells indicates resistance to radiotherapy and that these two factors were important predictors of poor survival in patients with LACSCC (hazard ratio [95% CI], 2.294 [1.013, 5.195] and 2.300 [1.050, 5.037], respectively; p=0.046 and p=0.037, respectively).


Assuntos
Carcinoma de Células Escamosas/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Neoplasias do Colo do Útero/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Tolerância a Radiação , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
15.
Biochem Biophys Res Commun ; 346(3): 621-8, 2006 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-16793018

RESUMO

Transcription factors play an essential role in altering gene expression. A great progress about transcription factors has been made towards the understanding of normal physiological processes, embryonic development, and human diseases. Here we report the identification and characterization of a novel KRAB-containing zinc-finger protein, ZNF569, which is isolated from a human embryonic heart cDNA library. ZNF569 encodes a putative protein of 686 amino acids. The protein is conserved across different species during evolution. Expression of ZNF569 was found in most of the examined human adult and embryonic tissues with a higher level in heart and skeletal muscles. The KRAB and ZNF motifs of ZNF569 represent potent repression domains. When ZNF569 is fused to Gal-4 DNA-binding domain and co-transfected with VP-16, ZNF569 protein suppresses transcriptional activity. Overexpression of ZNF569 in COS-7 cells inhibited the transcriptional activities of SRE and AP-1, which may be silenced by siRNA. The results suggest that ZNF569 protein may act as a transcriptional repressor that suppresses MAPK signaling pathway to mediate cellular functions.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo , Dedos de Zinco , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Sequência de Bases , Células COS , Cercopithecus aethiops , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Supressores , Genoma Humano/genética , Humanos , Dados de Sequência Molecular , Especificidade de Órgãos , Ligação Proteica , RNA Mensageiro/genética , Proteínas Repressoras/genética , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional/genética
16.
Biochem Biophys Res Commun ; 320(2): 409-15, 2004 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-15219843

RESUMO

The zinc-finger motif found in many transcription factors is thought to be important for human heart development and diseases. In this study, we have identified and characterized a novel zinc-finger gene named ZNF480 using degenerate primers from an early human embryo heart cDNA library. ZNF480 contains a KRAB-A box and 12 C2H2 zinc fingers. The cDNA sequence contains an open reading frame of 1551 bp, encoding a putative protein of 516 amino acid residues with a predicted molecular mass of 57 kDa. Northern blot analysis indicates that a 4.7kb transcript specific for ZNF480 is expressed only in embryonic heart. In the adult tissues, the expression of ZNF480 is restricted largely to heart, skeletal muscle, pancreas, and placenta. Overexpression of ZNF480 in cells activates the transcriptional activities of AP-1 and SRE. Therefore, our data suggest that ZNF480 may act as a positive regulator in MAPK-mediated signaling pathways that lead to the activation of AP-1 and SRE.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Miocárdio/metabolismo , Fator de Transcrição AP-1/fisiologia , Fatores de Transcrição/fisiologia , Transcrição Genética/fisiologia , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , DNA Complementar , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Humanos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/química , Fatores de Transcrição/genética
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