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1.
Cancer Radiother ; 25(1): 72-76, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33414058

RESUMO

PURPOSE: This study aimed to compare the absolute numbers of various types of lymphocytes in the peripheral blood before and after chemotherapy following radio-chemotherapy in patients with cervical cancer, so as to explore the correlation between the changes in the absolute numbers of peripheral various types of lymphocytes and the overall survival rate of patients. METHODS: Data of 205 patients with cervical cancer admitted to the hospital from June 2014 to August 2016 were retrospectively analyzed. These patients underwent concurrent radio-chemotherapy, followed by chemotherapy. The absolute numbers of peripheral blood lymphocytes and subtypes were compared before and after re-chemotherapy. RESULTS: For patients with a good prognosis, the number of lymphocytes, T cells, and cytotoxic T cells (Tc) significantly decreased (P<0.05) after re-chemotherapy, while this phenomenon was not observed in patients with poor prognosis. Kaplan-Meier univariate analysis showed that patients with cervical cancer who had an advanced FIGO stage before treatment, presence of lymph node metastasis, and increased numbers of Tc and T helper cells after re-chemotherapy showed a low 30-month survival rate; the overall log-rank analysis showed significant differences (P<0.05). Multivariate Cox proportional hazards regression analysis, presence of lymph node metastasis: HR=9.718, P=0.002, 95% CI=0.183-0.679; Tc grouping: HR=3.239, P=0.0.072, 95% CI=0.950-03.347; Th group: HR=3.197, P=0.074, 95% CI=0.943-3.564. CONCLUSIONS: After radio-chemotherapy, in patients with advanced cervical cancer, the change in the numbers of peripheral blood Tc and Th before and after re-chemotherapy was associated with the 30-month overall survival rate of patients. It can be considered as a predictor of the survival of patients with advanced cervical cancer.


Assuntos
Quimiorradioterapia , Linfócitos T , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalos de Confiança , Feminino , Humanos , Estimativa de Kaplan-Meier , Células Matadoras Naturais , Contagem de Linfócitos , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Taxa de Sobrevida , Linfócitos T Citotóxicos , Linfócitos T Auxiliares-Indutores , Linfócitos T Reguladores , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Adulto Jovem
2.
Life Sci ; 260: 118489, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32976882

RESUMO

AIMS: Cervical cancer (CC) is a common tumor of women worldwide. Here, we conducted a non-targeted lipidomic study to discover novel lipid biomarkers for early-stage CC. MAIN METHODS: The lipidomic analysis of 71 samples in discovery set and 72 samples in validation set were performed by coupling ultra-high-pressure liquid chromatography (UHPLC) with quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS). Lipids with variable importance (VIP) values greater than 1, adj. p < 0.05 (the adjusted p value obtained from false discovery rate correction) and fold change (FC) higher than 1.5 were reserved as potential biomarkers. Subsequently, receiver operating characteristic (ROC) curve and binary logistic regression were implemented to assess the diagnostic potential of these biomarkers and to acquire the best biomarker combination. KEY FINDINGS: A lipid biomarker panel, including phosphatidylcholine (PC, PC 14:0/18:2) and phosphatidylethanolamine (PE, PE 15:1e/22:6 and PE 16:1e/18:2), was established. This panel was effective in distinguishing between CC and non-CC (squamous intraepithelial lesions [SIL] and healthy controls) within the area under the ROC curve (AUC), sensitivity, and specificity reaching 0.966, 0.952, and 0.860 for discovery set and 0.961, 0.920, and 0.915 for external validation set. Furthermore, this panel was also capable of discriminating early-stage CC from SIL with AUC, sensitivity, and specificity reaching 0.946, 0.952, and 0.800 for discovery set and 0.956, 0.960, and 0.815 for external validation set. SIGNIFICANCE: The combination of PC 14:0/18:2, PE 15:1e/22:6, and PE 16:1e/18:2 could serve as a promising serum biomarker for discriminating early-stage CC from SIL and healthy subjects.


Assuntos
Biomarcadores Tumorais/sangue , Lipidômica/métodos , Lipídeos/sangue , Neoplasias do Colo do Útero/sangue , Adulto , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Análise Multivariada , Fosfatidilcolinas/sangue , Fosfatidiletanolaminas/sangue , Reprodutibilidade dos Testes , Lesões Intraepiteliais Escamosas/sangue , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
3.
BMC Womens Health ; 20(1): 126, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552719

RESUMO

BACKGROUND: Nearly all uterine cervical cancer (UCC) cases result from human papillomavirus (HPV) infection. After high-risk HPV infection, most HPV infections are naturally cleared by humoral and cell-mediated immune responses. Thus, cervical lesions of only few patients progress into cervical cancer via cervical intraepithelial neoplasia (CIN) and lead to persistent oncogenic HPV infection. This suggests that immunoregulation plays an instrumental role in the carcinogenesis. However, there was a few studies on the relation between the immunologic dissonance and clinical characteristics of UCC patients. METHOD: We examined the related immune cells (Th1, Th2, Th17, and Treg cells) by flow cytometric analysis and analyzed their relations with UCC stages, tumor size, differentiation, histology type, lymph node metastases, and vasoinvasion. Next, we quantified the Th1, Th2, Th17, and Treg cells before and after the operation both in UCC and CIN patients. RESULTS: When compared with stage I patients, decreased levels of circulating Th1 cells and elevated levels of Th2, Th17, and Treg cells were detected in stage II patients. In addition, the imbalance of Th1/Th2 and Th17/Treg cells was related to the tumor size, lymph node metastases, and vasoinvasion. We found that immunological cell levels normalized after the operations. In general, immunological cell levels in CIN patients normalized sooner than in UCC patients. CONCLUSIONS: Our findings suggested that peripheral immunological cell levels reflect the patient's condition.


Assuntos
Neoplasia Intraepitelial Cervical/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Neoplasias do Colo do Útero/imunologia , Adulto , Neoplasia Intraepitelial Cervical/sangue , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Carga Tumoral , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/metabolismo
4.
Technol Cancer Res Treat ; 19: 1533033820914983, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32356483

RESUMO

OBJECTIVE: This study aimed to investigate the diagnostic values of microRNA-21, microRNA-124, and macrophage colony-stimulating factor in patients with cervical cancer. METHODS: A total of 68 patients with cervical cancer admitted in our hospital (cervical cancer group) and 57 healthy individuals undergoing physical examinations (healthy group, also control group) were enrolled in this study. The expression of serum microRNA-21 and microRNA-124 was detected by quantitative reverse transcription polymerase chain reaction. The expression of serum macrophage colony-stimulating factor was detected by enzyme-linked immunosorbent assay. The diagnostic values of microRNA-21, microRNA-124, and macrophage colony-stimulating factor in cervical cancer were analyzed. The correlations between the expression of microRNA-21 and microRNA-124 with that of macrophage colony-stimulating factor were also analyzed. RESULTS: Compared to those in the healthy group, patients in the cervical cancer group had a higher expression of microRNA-21 and macrophage colony-stimulating factor (P < .05) but lower expression of microRNA-124 (P < .05). The expression of microRNA-21, microRNA-124, and macrophage colony-stimulating factor in the patients correlated with the tumor size, tumor node metastasis (TNM) staging, tumor differentiation, and the presence or absence of lymph node metastasis and human papillomavirus infection (P < .05). According to the receiver operating characteristic curves, the area under the curve of microRNA-21 for diagnosing cervical cancer was 0.723, the specificity was 58.82%, and the sensitivity was 91.23%. The area under the curve of microRNA-124 was 0.766, the specificity was 94.12%, and the sensitivity was 57.89%. The area under the curve of macrophage colony-stimulating factor was 0.754, the specificity was 64.71%, and the sensitivity was 87.72%. Pearson correlation analysis showed that the expression of microRNA-21 positively correlated with that of macrophage colony-stimulating factor (r = 0.6825, P < .001), and the expression of microRNA-124 negatively correlated with that of macrophage colony-stimulating factor (r = -0.6476, P < .001). CONCLUSION: MicroRNA-21, microRNA-124, and macrophage colony-stimulating factor may be involved in the development and progression of cervical cancer. The detection of serum microRNA-21, microRNA-124, and macrophage colony-stimulating factor has good sensitivity and specificity in the diagnosis of cervical cancer.


Assuntos
Fator Estimulador de Colônias de Macrófagos/sangue , MicroRNAs/genética , Neoplasias do Colo do Útero/diagnóstico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Curva ROC , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/genética
5.
J Cancer Res Clin Oncol ; 146(8): 1971-1978, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447484

RESUMO

PURPOSE: Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer. METHODS: Genomic DNA was extracted from patient's peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire. RESULTS: Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI95% 1.02-4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI95% 1.05-4.47). CONCLUSION: Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.


Assuntos
Interleucina-10/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Feminino , Genótipo , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia
6.
Medicine (Baltimore) ; 99(9): e19273, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118737

RESUMO

A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV), progress rapidly to cervical disease. We characterized HPV genotypes within cervical tumor biopsies, assessed the relationships of cervical disease stage with age, HIV-1 status, absolute CD4 count, and CD4 percentage, and identified the predictive power of these variables for cervical disease stage in a cohort of South African women.We recruited 181 women who were histologically diagnosed with cervical disease; 87 were HIV-1-positive and 94 were HIV-1-seronegative. Colposcopy-directed tumor biopsies were confirmed by histology and used for genomic DNA extraction. The Roche Linear Array HPV genotyping test was used for HPV genotyping. Peripheral whole blood was used for HIV-1 rapid testing. Fully automated FC500MPL/CellMek with PanLeucogate (PLG) was used to determine absolute CD4 count, CD4 percentage, and CD45 count. Chi-squared test, a logistic regression model, parametric Pearson correlation, and ROC curves were used for statistical analyses. We used the Benjamini-Horchberg test to control for false discovery rate (FDR, q-value). All tests were significant when both P and q were <.05.Age was a significant predictor for invasive cervical cancer (ICC) in both HIV-1-seronegative (P < .0001, q < 0.0001) and HIV-1-positive women (P = .0003, q = 0.0003). Sixty eight percent (59/87) of HIV-1-positive women with different stages of cervical disease presented with a CD4 percentage equal or less than 28%, and a median absolute CD4 count of 400 cells/µl (IQR 300-500 cells/µl). Of the HIV-1-positive women, 75% (30/40) with ICC, possessed ≤28% CD4 cells vs 25% (10/40) who possessed >28% CD4 cells (both P < .001, q < 0.001). Furthermore, 70% (28/40) of women with ICC possessed CD4 count >350 compared to 30% (12/40) who possessed CD4 count ≤ 350 (both P < .001, q < 0.001).Age is an independent predictor for ICC. In turn, development of ICC in HIV-1-positive women is independent of the host CD4 cells and associates with low CD4 percentage regardless of absolute CD4 count that falls within the normal range. Thus, using CD4 percentage may add a better prognostic indicator of cervical disease stage than absolute CD4 count alone.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Infecções por HIV , HIV-1 , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Neoplasia Intraepitelial Cervical/sangue , Neoplasia Intraepitelial Cervical/virologia , Estudos de Coortes , Feminino , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/virologia , Fatores de Risco , África do Sul/epidemiologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/virologia
7.
BMC Cancer ; 20(1): 138, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085736

RESUMO

BACKGROUND: To study the kinetic profile and clinicopathological implications of squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients who underwent surgery by a self-developed SCC-Ag single molecule assay (Simoa) prototype immunoassay. METHODS: Participants were prospectively enrolled between 04/2016 and 06/2017. Consecutive serum samples were collected at five points: day 0 (the day before surgery), postoperative day 4, weeks 2-4, months 2-4 and months 5-7. In total, 92 patients and 352 samples were included. The kinetic change in SCC-Ag levels and their associations with clinicopathological characteristics were studied. RESULTS: Simoa SCC-Ag was validated by comparison with the Architect assay. SCC-Ag levels measured by the Simoa assay were highly correlated with the Architect assay's levels (Pearson's correlation coefficient = 0.979, Passing-Bablok regression slope 0.894 (0.847 to 0.949), intercept - 0.009 (- 0.047 to 0.027)). The median values for each time-point detected by the Simoa assay were 2.49, 0.66, 0.61, 0.72, and 0.71 ng/mL, respectively. The SCC-Ag levels decreased dramatically after surgery and then stabilized and fluctuated to some extent within 6 months. Patients with certain risk factors had significantly higher SCC-Ag values than their negative counterparts before surgery and at earlier time points after surgery, while no difference existed at the end of observation. Furthermore, although patients with positive lymph nodes had sustained higher SCC-Ag levels compared to those with negative lymph nodes, similar kinetic patterns of SCC-Ag levels were observed after surgery. Patients who received postoperative treatment had significantly higher SCC-Ag values than those with surgery only at diagnosis, while no difference existed after treatment. CONCLUSIONS: The Simoa SCC-Ag prototype was established for clinical settings. The SCC-Ag levels were higher in patients with risk factors, whereas the kinetic trend of SCC-Ag might be mainly affected by postoperative adjuvant therapy. These data indicate that the SCC-Ag level might be a good predictor for the status of cervical cancer, including disease aggressiveness and treatment response.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Histerectomia/métodos , Serpinas/sangue , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Estudos Longitudinais , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/cirurgia
8.
Gynecol Oncol ; 157(1): 181-187, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31955861

RESUMO

OBJECTIVE: To measure anti-glycan antibodies (AGA) in cervical cancer (CC) patient sera and assess their effect on therapeutic outcome. PATIENTS AND METHODS: Serum AGA was measured in 276 stage II and 292 stage III Peruvian CC patients using a high content and throughput Luminex multiplex glycan array (LMGA) containing 177 glycans. Association with disease-specific survival (DSS) and progression free survival (PFS) were analyzed using Cox regression. RESULTS: AGAs were detected against 50 (28.3%) of the 177 glycans assayed. Of the 568 patients, 84.5% received external beam radiation therapy (EBRT) plus brachytherapy (BT), while 15.5% only received EBRT. For stage-matched patients (Stage III), receiving EBRT alone was significantly associated with worse survival (HR 6.4, p < 0.001). Stage III patients have significantly worse survival than Stage II patients after matching for treatment (HR = 2.8 in EBRT+BT treatment group). Furthermore, better PFS and DSS were observed in patients positive for AGA against multiple glycans belonging to the blood group H, Lewis, Ganglio, Isoglobo, lacto and sialylated tetrarose antigens (best HR = 0.49, best p = 0.0008). CONCLUSIONS: Better PFS and DSS are observed in cervical cancer patients that are positive for specific antiglycan antibodies and received brachytherapy.


Assuntos
Anticorpos/sangue , Glucanos/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Fatores Etários , Idoso , Anticorpos/imunologia , Braquiterapia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Taxa de Sobrevida , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/mortalidade
9.
Anticancer Res ; 40(1): 451-458, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892600

RESUMO

BACKGROUND/AIM: We evaluated the clinical implications of pre- and post-treatment hematological parameters as prognostic factors in patients with locally advanced cervical cancer (LACC) who received definitive concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: We retrospectively analyzed 125 patients with LACC (FIGO stage IIB to IIIB) who received definitive CCRT. Clinical factors and hematological parameters, including neutrophil-to-lymphocyte ratio (NLR) were assessed pre- and post-CCRT. Univariate and multivariate analysis for disease-free survival (DFS) and overall survival (OS) were performed using clinicopathological and hematological parameters. RESULTS: Disease recurred in 46 (36.8%) patients, and 24 patients (19.2%) died. On multivariate analysis, post-treatment NLR, ΔNLR (pre-treatment NLR/post-treatment NLR) and ΔPLR (platelet-to-lymphocyte ratio) (pretreatment PLR/post-treatment PLR) were significant prognostic factors for DFS, and only post-treatment NLR was a significant prognostic factor for OS (p<0.001). However, pre-treatment hematological parameters were not associated with prognosis. CONCLUSION: Post-treatment hematological parameters, particularly NLR, may serve as a prognostic indicator in patients with LACC who received definitive CCRT.


Assuntos
Quimiorradioterapia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/terapia , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neutrófilos/patologia , Prognóstico , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia
10.
Eur J Surg Oncol ; 46(1): 131-138, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31481274

RESUMO

OBJECTIVE: We seek to explore the clinical significance of serum squamous cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting tumor recurrence and survival in operable cervical squamous cell carcinoma patients. METHODS: A total of 3471 patients with cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The cut-off value of serum SCC-Ag for tumor recurrence was calculated using the receiver operating characteristic (ROC) curve. The progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed. RESULTS: The optimal cut-off value of serum SCC-Ag level for predicting tumor recurrence was calculated and set at 2.75 ng/mL. Compared to the value of 1.5 ng/mL used in clinical practice, our results showed that serum SCC-Ag level >2.75 ng/mL was closely related to extrapelvic metastases in relapsed patients (P = 0.035). Multivariate analysis showed that neither serum SCC-Ag level >1.5 ng/mL nor serum SCC-Ag level >2.75 ng/mL was independent risk factors for PFS and OS in all patients. However, among 964 patients with at least one high-risk factor (parametrial invasion, vaginal margin invasion and lymph node metastasis), serum SCC-Ag level > 2.75 ng/mL, instead of serum SCC-Ag level > 1.5 ng/mL, could be used as an independent factor affecting PFS (P = 0.018). CONCLUSION: Preoperative serum SCC-Ag level > 2.75 ng/mL is closely related to extrapelvic recurrence, and is an independent factor for tumor recurrence and survival in cervical squamous cell carcinoma patients with high-risk factors.


Assuntos
Antígenos de Neoplasias/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/sangue , Serpinas/sangue , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
11.
Oncol Res Treat ; 43(1-2): 10-18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31747660

RESUMO

BACKGROUND: The impact of preoperative glycemic control on the survival outcomes of patients undergoing a radical hysterectomy (RH) for cervical cancer has not been investigated. PATIENTS AND METHODS: We reviewed patients who underwent a type III RH for cervical cancer between January 2004 and June 2011 in our institution. RESULTS: A total of 431 patients were included and 83 (19.3%) were diagnosed with diabetes mellitus (DM). Poorly controlled DM (preoperative hemoglobin A1c [HbA1c] ≥7.0%) was observed in 49 (59.0%) diabetic patients. Compared to patients without DM and diabetic patients with good glycemic control (preoperative HbA1c <7.0%), diabetic patients with poor glycemic control had significantly higher risks of tumor recurrence, cervical cancer-specific death, and overall death. In multivariate analysis, DM with poor glycemic control independently predicted recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). We excluded patients without DM and performed a sensitivity analysis. When HbA1c levels were treated as a dichotomous variable, preoperative HbA1c ≥7.0% was independently associated with RFS, CSS, and OS. When HbA1c level was treated as a continuous variable, it remained an independent predictor of RFS, CSS, and OS. CONCLUSION: DM with poor glycemic control prior to RH was significantly associated with an increased risk of recurrence and mortality in cervical cancer patients. These results underscore the importance of intensive glycemic control and close follow-up for diabetic patients.


Assuntos
Glicemia , Cuidados Pré-Operatórios , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Hemoglobina A Glicada/metabolismo , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
12.
J Trace Elem Med Biol ; 57: 68-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568922

RESUMO

BACKGROUND AND AIM: Major and trace elements play an important role in human body, and it has been reported that ionomic distribution differ greatly in tumor patients. The aim of the present study was to investigate the effects of cisplatin-based neoadjuvant chemoradiotherapy on the ionomic profile in human plasma as a potential biomarker for the therapeutic effects of cervical cancer. METHOD: Thirty-seven patients with cervical cancer receiving neoadjuvant chemoradiotherapy were included in this study, pretherapy and post-treatment blood samples were collected and concentrations of 24 ions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The results showed that after cisplatin chemotherapy and radiotherapy, patients' plasma Pt level significantly increased, Na, Mg, P, K, Ca, Se, Cu, Zn, Se, Sr, Ba levels significantly decreased (P < 0.01), and Al, Cu ions were significantly correlated with the treatment effect (P < 0.05). In addition, the pattern of elemental correlations changed dramatically after the neoadjuvant chemoradiotherapy. CONCLUSION: The results indicated that the plasma ionomic profile may serve as a quick and convenient tool to reflect the therapeutic effect of cisplatin-based chemoradiotherapy in cervical cancer patients, and supplement of certain essential elements may be of great importance for the maintenance of ion homeostasis in human body and for the reduction of adverse effect of chemotherapy and radiotherapy.


Assuntos
Íons/sangue , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/diagnóstico , Quimiorradioterapia , Feminino , Humanos , Espectrometria de Massas , Terapia Neoadjuvante , Oligoelementos/sangue , Neoplasias do Colo do Útero/tratamento farmacológico
13.
Anticancer Res ; 39(11): 6403-6412, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704874

RESUMO

BACKGROUND: Cytokines, metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) take part in many processes involved in tumor progression and invasion such as degradation of the extracellular matrix, influence on immune cells associated with tumor tissue, and angiogenesis. Thus, the aim of this study was to compare the concentration of plasma levels and tissue expression of macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2 and MMP9, and their tissue inhibitors TIMP1 and TIMP2 in patients with cervical cancer, patients with high-grade cervical intraepithelial dysplasia (CIN3) and patients with ectropion. PATIENTS AND METHODS: Concentration and expression of all tested parameters was measured in serum with enzyme-linked immunosorbent assay (ELISA) and in tissue with immunohistochemistry method. RESULTS: The epithelial expression of M-CSF and TIMP1 in cancer tissue was much stronger as compared to that in ectropion and CIN3. In the case of MMP2, lack of or weak expression in epithelial cells was observed in all tested groups. Our studies showed statistical differences of tested parameters in tissue expression and in plasma concentrations in patients with cervical cancer, patients with CIN3 and patients with ectropion. Moreover, data revealed positive correlation between plasma level and cervical cancer cell expression of VEGF. CONCLUSION: Our findings indicate a potential role of all the proteins tested here in cervical cancer diagnosis, especially VEGF. However, further studies will show whether they play a role in the progression of cancerous changes in epithelial tissue of the cervix.


Assuntos
Fator Estimulador de Colônias de Macrófagos/análise , Metaloproteases/análise , Inibidores Teciduais de Metaloproteinases/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Fator A de Crescimento do Endotélio Vascular/análise , Adenocarcinoma/sangue , Adenocarcinoma/química , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/química , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/sangue , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteases/sangue , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/sangue , Inibidores Teciduais de Metaloproteinases/sangue , Displasia do Colo do Útero/sangue , Neoplasias do Colo do Útero/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
14.
Future Oncol ; 15(30): 3467-3481, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31580723

RESUMO

Aim: Cervical cancer is one of the leading causes of cancer mortality in women. Peripheral white blood cell parameters such as neutrophil (NE), eosinophil (EO), basophil (BA), as well as lymphocyte (LY) and monocyte (MO), are correlated with tumor outcomes. Methods: In total, 110 cervical squamous cell carcinoma patients were recruited in this study. The potential prognostic factors were evaluated by univariate and multivariate survival analysis. Results: Cox regression analysis model indicated that higher pretreatment EO level and increased post-/preradiotherapy EO ratio were independently associated with worse progression-free survival. Lower pretreatment LY or higher EO levels and increased post-/preradiotherapy EO ratio were independently associated with worse overall survival. Conclusion: LY and EO are correlated with outcomes of cervical squamous cell cancer.


Assuntos
Carcinoma de Células Escamosas/sangue , Eosinófilos/patologia , Linfócitos/patologia , Neoplasias do Colo do Útero/sangue , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Contagem de Linfócitos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
15.
BMC Cancer ; 19(1): 986, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646977

RESUMO

BACKGROUND: To examine differences in the plasma levels of miRNA-21, - 214, -34a, and -200a in patients with persistent high-risk human papillomavirus (hr-HPV) infection or with cervical lesions of different grades. METHODS: Venous blood was collected from 232 individuals to measure the plasma expression levels of miRNA-21, - 214, -34a, and -200a. The subjects included normal controls and patients with persistent hr-HPV infection, CIN1, CIN2, CIN3, or cervical cancer (n = 42, 31, 19, 54, 71, and 15 patients, respectively). Cervical conization specimens were collected from all the women. To ensure the accuracy of histopathology, three consecutive tissue sections with an identical diagnosis were selected, and dissection samples were taken from them for miRNA detection. Eligible cases met the inclusion criteria based on sample observation using the middle slice of sandwich tissue sections from the pathological tissue in accordance with the diagnosis of CIN1, CIN2 and CIN3 in 8, 29, and 26 cases, respectively. The miRNA-21, - 214, -34a, and -200a expression levels in the paraffin-embedded tissue samples were determined. The percentage of patients with a CIN2+ diagnosis at 30-49 years old was significantly different from that of those diagnosed with CIN1. The incidence of CIN2+ patients exposed to passive smoking was significantly different from that of CIN1- patients. The percentage of CIN2+ patients with three pregnancies was significantly different from that of those with CIN1, and the percentage of CIN2+ subjects with ≥4 pregnancies was significantly different from that of CIN1- patients. The number of CIN2+ patients with two or more induced abortions was significantly different from that of patients with CIN1. The percentage of CIN2+ patients who underwent a caesarean section was significantly different from that of patients with CIN. The percentage of CIN2+ patients with first-degree relatives with cancer was significantly different from that of those with CIN1. Among CIN2+ patients, the percentage with a first sexual encounter at ≤20 years old was significantly different from that of those with CIN1. The percentage of CIN2+ patients with ≥2 sexual partners was significantly different from that of CIN1- patients. RESULTS: The plasma miRNA-214, -34a, and -200a expression levels were decreased in patients with more severe cervical lesions. Plasma miRNA levels in CIN1- patients were significantly different from those in CIN2+ patients. The kappa values for miRNA-21, - 214, -34a and -200a in tissue versus plasma were 0.7122, 0.9998, 0.8986 and 0.7458, respectively. The sensitivity of each biomarker for detecting CIN2 was calculated, and ROC curves of the four miRNA biomarkers were drawn. The AUC of the four plasma miRNAs was greater than 0.5, with the AUC of miRNA-21 being the largest at 0.703. The plasma miRNA expression levels exhibited at least one tie between CIN1 and CIN2. The AUCs for miRNA-21, -34a, -200a and - 214 were 0.613, 0.508, 0.615 and 0.505, respectively. CONCLUSIONS: Changes in plasma miRNA-21, - 214, -34a and -200a levels were associated with cervical lesion severity. The plasma miRNA levels in CIN1- subjects were significantly different from those in CIN2+ subjects. This analysis may help in detection of high-grade cervical lesions.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/sangue , MicroRNAs/genética , Infecções por Papillomavirus/sangue , Doenças do Colo do Útero/sangue , Adulto , Área Sob a Curva , Neoplasia Intraepitelial Cervical/sangue , Neoplasia Intraepitelial Cervical/patologia , Colo do Útero/metabolismo , Colo do Útero/patologia , Colo do Útero/virologia , Feminino , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Infecções por Papillomavirus/patologia , Curva ROC , Fatores de Risco , Doenças do Colo do Útero/patologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia
16.
Cancer Biomark ; 26(4): 491-500, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31658043

RESUMO

OBJECTIVE: To determine the utility of plasma microRNAs (miRNAs) as biomarkers in cervical cancer (CC). METHODS: Some studies were conducted about the specific expression of plasma miRNAs in the diagnosis of CC. Plasma samples of 97 CC patients and 87 normal controls (NCs) were used to identify dysregulation of miRNAs in the training, testing, and external validation phases. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the sensitivity and specificity of identified individual miRNAs and miRNA panels for the diagnosis of CC. Expression levels of specific miRNAs were also examined in plasma exosomes and tissue samples of CC patients. RESULTS: Four plasma miRNAs (miR-146a-5p, miR-151a-3p, miR-2110 and miR-21-5p) which showed up-regulation were identified and validated in CC patients. A panel of the four miRNAs were constructed as potential diagnostic markers for CC. The AUCs of the panel of these four-miRNAs for the training, testing, and external validation phases were 0.911, 0.774, and 0.786, respectively. miR-146a-5p and miR-21-5p levels were all up-regulated in CC tissue specimens, whereas miR-146a-5p, miR-151a-3p, and miR-2110 levels were up-regulated in plasma exosomes. CONCLUSION: The signature of the four-miRNAs identified in peripheral plasma is a promising novel biomarker for the diagnosis of CC.


Assuntos
MicroRNA Circulante/sangue , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , MicroRNA Circulante/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/sangue
17.
J Gene Med ; 21(11): e3126, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31498525

RESUMO

BACKGROUND: The early diagnosis of cervical cancer is difficult, resulting in an unsatisfactory prognosis. The present study aimed to explore the expression of HPV16-related microRNAs (miRNAs) in the serum of Uygur cervical cancer in Sinkiang and analyze the miRNAs showing different expression. METHODS: The serum of 30 HPV16 positive (HPV16Pos) and 30 negative patients (HPV16Neg) was collected and then the differentially expressed miRNAs were screened out by function and pathway enrichment analyses. Next, the cervical cancer cells were cultured. miR-5701-mimic and inhibitor were transfected into cells. The level of miR-5701 was detected by a quantitative reverse transcriptase-polymerase chain reaction. The proliferation of cells was detected using a Cell Counting Kit-8 assay. Western blotting was used to measure the expression of THBS4. RESULTS: We identified three up-regulated miRNAs (hsa-miR-1291, hsa-miR-144-5p and hsa-miR-5701) and seven down-regulated known-miRNAs (hsa-miR-21-5p, hsa-miR-101-3p, hsa-miR-370-3p, hsa-miR-151a-3p, hsa-miR-144-3p, hsa-miR-199a-3p and hsa-miR-199b-3p) relative to HPV16Neg. The mitogen-activated protein kinase signal pathway is predicted to be a key mechanism of HPV16-related cervical cancer. Furthermore, miR-5701 inhibits the proliferation of cervical cancer cells and suppresses the expression of THBS4 (P < 0.05), which was confirmed as a target gene of miR-5701. CONCLUSIONS: In the present study, we confirm 10 differentially expressed miRNAs that could be potential markers or therapeutic targets of cervical cancer. miR-5701 inhibits the proliferation of cervical cancer cells and the expression of its target gene THBS4.


Assuntos
Papillomavirus Humano 16 , MicroRNAs/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/etiologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , MicroRNA Circulante , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/virologia , Interferência de RNA , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/patologia
18.
World J Surg Oncol ; 17(1): 132, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375109

RESUMO

BACKGROUND: This meta-analysis summarized the prognostic role of an elevated platelet count before treatment on survival outcomes in patients with cervical cancer. METHODS: The PubMed, Embase, and Cochrane library electronic databases were systematically searched for studies reporting the effect estimates with 95% confidence intervals (CIs) of pretreatment thrombocytosis on survival from the database inceptions to December 2018. The pooled hazard ratios (HRs) with 95% CIs for overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were calculated using random-effects models. RESULTS: Nineteen retrospective studies that recruited 6521 patients with cervical cancer were eligible for this study. The summary results indicated that an elevated platelet count was significantly associated with a poor OS (HR 1.50; 95% CI 1.19-1.88; P = 0.001), PFS (HR 1.33; 95% CI 1.07-1.64; P = 0.010), and RFS (HR 1.66; 95% CI 1.20-2.28; P = 0.002). Sensitivity analysis indicated that the pooled PFS was variable after sequential exclusion of individual studies. The predictive value of pretreatment thrombocytosis on OS differed according to the publication year (P = 0.039), country (P = 0.013), and sample size (P = 0.029), and the role of pretreatment thrombocytosis on PFS could be affected by the study quality (P = 0.046). CONCLUSION: The findings of this study indicated that an elevated platelet count before treatment was associated with poor OS, PFS, and RFS. These results require further verification in large-scale prospective studies.


Assuntos
Trombocitose/complicações , Neoplasias do Colo do Útero/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/sangue
19.
Proc Natl Acad Sci U S A ; 116(37): 18584-18589, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31462499

RESUMO

Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.


Assuntos
Quimiorradioterapia , Neutrófilos/imunologia , Tolerância a Radiação/imunologia , Sarcoma/terapia , Neoplasias do Colo do Útero/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Tolerância a Radiação/genética , Estudos Retrospectivos , Sarcoma/sangue , Sarcoma/imunologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/mortalidade , Irradiação Corporal Total , Adulto Jovem
20.
Gynecol Oncol ; 155(1): 135-143, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31434614

RESUMO

OBJECTIVE: The altered miRNAs expression in cervical cancer tissue can be a critical player during tumorigenesis, may contribute to tumor cell heterogeneity and may determine distinct phenotypes within the tumor. Recent studies have highlighted the role of circulating miRNAs as a minimally-invasive biomarker and its potential as biosignature to complement routine tissue-based procedures. METHODS: In order to determine whether miRNAs in serum can indicate changes in cervical tissue specimens, we performed small RNA sequencing and selected miRNAs were validated using qRT-PCR in serum and tissue specimens (n = 115). Further, luciferase assay were performed to investigate the interactions between hsa-miR-409-3p and hsa-miR-454-3p binding sites on 3'UTR region of MTF2 and ST18 respectively. RESULTS: We have identified a total of 14 differentially expressed miRNAs common in serum and tissue specimens. Among them, hsa-miR-17-5p, hsa-miR-32-5p and hsa-miR-454-3p were upregulated while, hsa-miR-409-3p was downregulated in serum and tissue of cervical cancer subjects. Our in-silico small RNA sequencing data analysis identified isomiRs and classified miRNA into clusters and subtypes (exonic, intronic and intergenic) with respect to the expression status in serum and tissue specimens. Expression level of hsa-miR-409-3p and hsa-miR-454-3p were inversely correlated with their target genes MTF2 and ST18 levels respectively in human cervical cancer specimens. Luciferase assay demonstrated that hsa-miR-409-3p and hsa-miR-454-3p functionally interacts with 3'-UTR of MTF2 and ST18 respectively to decrease their activity. CONCLUSION: Our results support the significant role of circulating miRNAs in disease dissemination and their potential utility as biosignatures of clinical relevance.


Assuntos
MicroRNAs/biossíntese , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , MicroRNAs/sangue , MicroRNAs/genética , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/metabolismo
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