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1.
Int J Oncol ; 56(3): 685-696, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922238

RESUMO

Protein regulator of cytokinesis­1 (PRC1) is a microtubule­associated factor involved in cytokinesis. Recent studies have indicated that PRC1 overexpression is involved in tumorigenesis in multiple types of human cancer. However, the expression, biological functions and the prognostic significance of PRC1 in ovarian cancer have not yet been clarified. In this study, it was confirmed that the PRC1 mRNA and protein expression levels were upregulated in high­grade serous ovarian carcinoma (HGSOC) tissues, particularly in patients without breast cancer susceptibility gene (BRCA) pathogenic mutations. PRC1 overexpression contributed to drug resistance, tumor recurrence and a poor prognosis. The findings also indicated that PRC1 knockdown decreased the proliferation, metastasis and multidrug resistance of ovarian cancer cells in vitro. It was also demonstrated that forkhead box protein M1 (FOXM1) regulated the mRNA and protein expression of PRC1. Dual­luciferase reporter assay and rescue assay confirmed that PRC1 was a direct crucial downstream target of FOXM1. On the whole, the findings of this study confirmed that PRC1 was a major prognostic factor of HGSOC and a promising therapeutic biomarker for the treatment of ovarian cancer.

2.
Gynecol Oncol ; 156(3): 676-681, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31882242

RESUMO

OBJECTIVE: To determine the value of the tumor-stroma ratio (TSR) while identifying prognostic factors in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC squamous cell carcinoma of the cervix following primary radical surgery. METHODS: Three hundred eighty-four patients with node-positive squamous cell carcinoma of the cervix (2018 FIGO stage IIIC) who underwent radical surgery between January 2005 and December 2016 were included in this retrospective study. The TSRs were assessed on hematoxylin and eosin-stained tumor slides and classified as stroma-low (<50% stroma) or stroma-high (≥50% stroma). RESULTS: Sixty-seven patients were categorized as stroma-high; they had shorter disease-free survival (DFS) and overall survival (OS) periods than did their stroma-low counterparts. On multivariate analysis, a tumor size ≥4 cm, ≥3 metastatic lymph nodes, and stroma-high status were independent predictors of shorter DFS and OS. These factors were incorporated into a prognostic scoring system in which patients were categorized into low- (score 0), intermediate- (score 1), and high-risk (scores 2-3) groups. The scoring system differentiated DFS and OS well (C-index = 0.65, 95% confidence interval, 0.59-0.72; and C-index = 0.65, 95% confidence interval, 0.59-0.72, respectively). CONCLUSIONS: The TSR is an independent prognostic factor, and our prognostic scoring system that incorporates this parameter exhibits good discriminative ability for both recurrence and survival in patients with 2018 FIGO stage IIIC cervical cancer after radical surgery. The TSR is a potentially novel clinicopathological variable for predicting the prognoses of these patients contingent on the validation of our findings.

3.
Seizure ; 75: 55-62, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874360

RESUMO

PURPOSE: The association between anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) and teratoma is formally recognized. This study compared the clinical features, treatments and outcomes between female patients with or without accompanying teratomas and determined the potential influences of coexisting teratomas. METHOD: Fifty-six female patients diagnosed with anti-NMDAR encephalitis were enrolled in two major tertiary hospitals in East China from January 2013 through March 2018 and were grouped as patients with or without teratoma. The clinical features were reviewed, and follow-up studies were performed. Comparisons were made between the two groups. RESULTS: Patients with teratoma reported fewer viral prodromes (p = 0.0085) and stronger positive intensity of anti-NMDAR antibodies in cerebrospinal fluid (CSF) (p = 0.0368), while nontumor patients tended to demonstrate lymphocytic pleocytosis in CSF (p = 0.0306). Seizure types varied between individuals, with complex partial seizures more common in teratoma patients (p = 0.0105). Nontumor patients frequently required combinations of first-line and second-line immunotherapy (p = 0.0014), which may be attributed to higher mRS scores at admission (p = 0.0300). Also, they had higher mean mRS scores since the 12-month follow-up and greater probability of relapse than did patients with teratomas (p = 0.0286). CONCLUSIONS: Symptomatology and auxiliary findings indicate that ovarian teratoma may be the immunologic trigger for anti-NMDAR encephalitis patients, while viral infection is likely to play a major part in pathogenesis for those without any detectable tumor. Overall, anti-NMDAR encephalitis patients with teratomas present with milder neurological symptoms and have better long-term outcomes after tumor removal.

4.
World J Clin Cases ; 7(22): 3872-3880, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31799317

RESUMO

BACKGROUND: Primary peritoneal cancer (PPC) patients with BRCA mutations have a good prognosis; however, for patients with BRCA mutations who are diagnosed with PPC after prophylactic salpingo-oophorectomy (PSO), the prognosis is poor, and survival information is scarce. CASE SUMMARY: We treated a 56-year-old woman with PPC after bilateral mastectomy, hysterectomy, and bilateral salpingo-oophorectomy. This patient had primary drug resistance and died 12 mo after the diagnosis of PPC. The genetic test performed on this patient indicated the presence of a germline BRCA1 mutation. We searched the PubMed, Scopus, and Cochrane databases and extracted studies of patients with BRCA mutations who developed PPC after PSO. After a detailed literature search, we found 30 cases, 7 of which had a history of breast cancer, 14 of which had no history of breast cancer, and 9 of which had an unknown history. The average age of PSO patients was 48.86 years old (range, 31-64 years). The average time interval between the diagnosis of PPC and preventive surgery was 61.03 mo (range, 12-292 mo). The 2-year survival rate for this patient population was 78.26% (18/23), the 3-year survival rate was 50.00% (9/18), and the 5-year survival rate was 6.25% (1/16). CONCLUSION: Patients with BRCA mutations who are diagnosed with PPC after preventative surgery have a poor prognosis. Prevention measures and treatments for these patients need more attention.

5.
J Biochem ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782782

RESUMO

Evidence has indicated the associations between thioredoxin interacting protein (TXNIP) and cancers. However, the role of TXNIP in cervical cancer remains unclear. Hence, this study aims to investigate the role of TXNIP in regulating cervical cancer cell proliferation, migration, and invasion. TXNIP expression can be regulated by either MondoA or ChREBP in a cell- or tissue- dependent manner. Thus, we also explored whether TXNIP expression in cervical cancer can be regulated by MondoA or ChREBP. Our results showed that TXNIP expression was decreased in cervical cancer cells (HeLa, SiHa, CaSki, MS751, C-33A). Furthermore, TXNIP overexpression inhibited cell proliferation, migration, and invasion in HeLa cells, whereas TXNIP silencing exerted the opposite effect in C-33A cells. Moreover, TXNIP expression could be induced by MondoA, rather than ChREBP in HeLa cells. Additionally, MondoA overexpression inhibited cell proliferation, migration, and invasion through upregulating TXNIP in HeLa cells. In summary, TXNIP induced by MondoA, rather than ChREBP, suppresses cervical cancer cell proliferation, migration and invasion. Our findings provide new ideas for the prevention and treatment of cervical cancer.

6.
Technol Cancer Res Treat ; 18: 1533033819871306, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31530094

RESUMO

Cancer cells undergo metabolic changes that support their malignant growth. These changes are often associated with increased expression of the rate-limiting glycolytic enzyme hexokinase 2. Hexokinase 2 is an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate. In this study, we utilized Gene Expression Profiling Interactive Analysis (GEPIA) database analysis and clinical sample analysis to find that hexokinase 2 was highly expressed in cervical cancer. Furthermore, we found that high hexokinase 2 expression in cervical cancer demonstrated a positive correlation with tumor size (P = .009696), pathological grade (P = .028551), and prognosis (P = .00069) but not with age (P = .956201) or lymph node metastasis (P = .131379). At the cellular level, we knocked down the expression of hexokinase 2 in the human cervical cancer cell line SiHa. The results demonstrated that knockdown of hexokinase 2 inhibited the proliferation and migration of SiHa cells and promoted cell apoptosis. During this process, knockdown of hexokinase 2 inhibited phosphorylation of AKT and mammalian target of rapamycin and promoted p53 expression. At the same time, overexpression of human papillomavirus 18 oncogenes E6 and E7 significantly promoted the expression of hexokinase 2. Most importantly, we discovered a novel upstream regulatory microRNA for hexokinase 2: miR-9-5p. Luciferase reporter assays and Western blot assays demonstrated that hexokinase 2 expression was inhibited by miR-9-5p by directly binding its 3'-untranslated region in SiHa cells. Next, we determined that miR-9-5p could suppress the proliferation and migration of SiHa cells and induce apoptosis. In conclusion, we found that hexokinase 2 serves a carcinogenic role in cervical cancer through the miR-9-5p/hexokinase 2/AKT pathway, which serves as the basis for potential therapeutic targets and prognostic indicators.


Assuntos
Carcinogênese/genética , Hexoquinase/genética , Neoplasias do Colo do Útero/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Transdução de Sinais , Neoplasias do Colo do Útero/patologia
7.
Cancer Manag Res ; 11: 8081-8093, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507330

RESUMO

Background: It is unclear whether low density lipoprotein receptor-related protein 11 (LRP11), a newly found lipoprotein receptor regulatory protein, has the carcinogenic effects in cervical cancer. Methods: Bioinformatics analysis, immunohistochemical (IHC) staining and evaluation, cell proliferation assay, flow cytometry, transwell migration and invasion assays, Western blotting, growth of LRP11-silenced cells in athymic nude mice were performed in this research. Results: We found that LRP11 expression was higher in high-grade squamous intraepithelial lesions (HSIL) and cervical cancer tissue than in normal cervix, and high expression of LRP11 was associated with differentiation degree (P=0.0266), indicating poor prognosis (P=0.0210). The silencing of LRP11 in SiHa and CaSki cell lines inhibited cell proliferation, reduced migration and invasion and suppressed cell growth in nude mice, which possibly related to cell cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF. Furthermore, LRP11 showed substantial positive correlation with P16 in vivo and in vitro. Conclusion: LRP11 plays important roles in proliferation, migration and invasion, with the potential to be a useful prognostic marker and therapeutic target for patients with HSIL and cervical cancer.

8.
J Obstet Gynaecol Res ; 45(11): 2267-2274, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31411802

RESUMO

AIM: Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing breast cancer and ovarian cancer. At present, knowledge of BRCA1/2 mutation frequency in Chinese patients with ovarian cancer is still insufficient, and the detailed clinical information of these patients is poorly understood. METHODS: A total of 547 unselected ovarian cancer patients were enrolled, and their gBRCAm status was detected. Clinical characteristics including age, personal and family history, histopathologic diagnosis, carbohydrate antigen 125 (CA-125) level, ascites, Federation International of Gynecology and Obstetrics (FIGO) stage, residual lesions, platinum sensitivity, recurrence interval and survival information were collected. Accurate assessments of disease response were based on the RECIST standard or CA-125 level. RESULTS: In 547 patients with ovarian cancer, we detected 129 (23.6%) patients with pathogenic mutations, 84 patients with BRCA1 mutations (15.4%) and 45 patients with BRCA2 mutations (8.2%). Twenty-five novel mutations were identified, and the mutation of BRCA1, c.5470_5477del8, was the most common mutation in this study. BRCA1/2 mutations were significantly associated with age; personal and family history; FIGO stage; secondary recurrence interval; sensitivity to platinum in 1st, 2nd and 3rd line treatment; and response to doxorubicin liposomes. Patients with BRCA1/2 mutations showed significant advantages in 3- and 5-year survival rates but no advantage in long-term survival. CONCLUSION: BRCA1/2 mutation prevalence in Chinese ovarian cancer patients is higher than the international rate. We recommend BRCA1/2 testing for patients with family histories and personal histories of malignancy and genetic counseling for cancer in healthy people with high-risk family histories.

9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(6): 666-670, 2019 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-31197990

RESUMO

Objective: To explore the effectiveness of proximal femoral nail antirotation (PFNA) assisted by mesh locator in treatment of intertrochanteric fracture in the elderly. Methods: Ninety-four elderly patients with intertrochanteric fractures admitted between August 2014 and July 2017 were selected as the study subjects. They were randomly divided into trial group (48 cases) and control group (46 cases). In trial group, PFNA was implanted assisted by mesh locator after closed reduction; while in control group, PFNA was implanted by conventional method. There was no significant difference between the two groups in terms of gender, age, cause of injury, time from injury to admission, fracture side and classification, and medical complications ( P>0.05). The operation time, intraoperative blood loss, fluoroscopy times, hospital stay, incision length, and complications were recorded. Visual analogue scale (VAS) was used to evaluate the degree of pain at 3 days after operation, and Harris score was used to evaluate hip function before operation and at 3, 6, and 9 months after operation. Results: Compared with control group, the operation time and incision length of trial group shortened, the blood loss and fluoroscopy times reduced, the pain after operation alleviated obviously; the differences between the two groups were significant ( P<0.05). There was no significant difference in hospital stay between the two groups ( P>0.05). The patients in both groups were followed up 9-12 months, with an average of 10.6 months. X-ray films showed that the fractures healed in both groups, and the healing time in control group was (11.2±3.2) weeks, while that in trial group was (11.6±2.9) weeks, showing no significant difference between the two groups ( t=1.262, P=0.120). There was no significant difference in Harris score between the two groups before operation and at 3, 6, and 9 months after operation ( P>0.05). There was 1 case of incision infection, 2 cases of coxa vara, and 1 case of pressure ulcer in trial group, and the incidence of complications was 8.3%. There was 1 case of coxa vara, 2 cases of pressure ulcer, and 1 case of internal fixation loss in control group, and the incidence of complications was 8.7%. There was no significant difference in the incidence of complications between the two groups (χ 2=0.783, P=0.112). Conclusion: It is feasible to implant PFNA assisted by mesh locator in treatment of intertrochanteric fracture in the elderly. Compared with the traditional operation, it can shorten the operation time, shorten the incision, and relieve the pain after operation.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Idoso , Pinos Ortopédicos , Fêmur , Fraturas do Quadril/cirurgia , Humanos , Telas Cirúrgicas , Resultado do Tratamento
10.
Open Med (Wars) ; 14: 362-368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31157301

RESUMO

High-grade squamous intraepithelial lesions (HSILs) are regarded as precancerous lesions that can progress to cervical carcinoma; however, it is very difficult to effectively differentiate these precancerous cells from cancerous cells based on morphology alone. Additionally, the difference between precancerous cells and cancerous cells in regard to biological behaviour remains unclear. We previously cultured primary normal uterine cervical keratinocytes from human normal cervical tissue and cervical precancerous cells that were naturally infected with human papillomavirus from small-sized neoplastic cervical tissues. Here, we extended our study to further observe the in vitro proliferative characteristics of cervical precancerous cells at the cellular and molecular levels. In this study, we found that the growth rate of precancerous cells was significantly faster than that of normal cervical cells and slower than that of Caski cells. However, the proliferative capacity of such precancerous cells was similar to that of cancerous cells of the cervix at the molecular level. These results suggest that the surrounding environment of the cells may play an important role in the development of cervical cancer, which provides an important basis for the further study of precancerous and cancerous lesions of the cervix.

11.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 47(4): 357-361, 2018 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-30511521

RESUMO

OBJECTIVE: To analyze the clinical features and prognosis of cervical adenocarcinoma (AC) and adenosquamous carcinoma of cervix (ASC). METHODS: The clinical data of 237 patients, including 201 cases of AC and 36 cases of ASC (FIGO stage ⅠB1-ⅡA), who underwent surgery in Qilu Hospital between September 2007 and September 2016 were reviewed. Clinical features of two groups were compared, and Kaplan-Meier survival analysis was performed to evaluate the prognosis. RESULTS: A larger proportion of ASC patients had lymphovascular space invasion compared with AC patients (P<0.01), but no significant differences were observed in the age, FIGO stage, size of tumor, depth of stromal invasion, parametrial invasion, lymphatic metastasis and risk grade between two groups (all P>0.05). The 5-year overall survival rates of AC and ASC groups were 79.4% and 78.3%, and the 5-year recurrence-free survival rates were 77.4% and 73.0%. Among patients received concurrent chemoradiotherapy, the 5-year overall survival rates were 71.0% and 61.4%, and the 5-year recurrence-free survival rates were 68.8% abd 61.1%, respectively. No significant differences were observed in 5-year overall survival rates and recurrence-free survival rates between AC and ASC patients (all P>0.05). CONCLUSIONS: Lymphovascular space invasion was more likely to occur in patients with ASC, but there was no significant difference in the prognosis between AC and ASC patients.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Neoplasias do Colo do Útero , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/mortalidade , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade
12.
Front Microbiol ; 9: 2896, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30546351

RESUMO

Human papillomaviruses (HPV) are the first viruses to have been acknowledged to prompt carcinogenesis, and they are linked with cancers of the uterine cervix, anogenital tumors, and head and neck malignancies. This paper examines the structure and primary genomic attributes of HPV and highlights the clinical participation of the primary HPV serotypes, focusing on the roles that HPV-16 and 18 play in carcinogenesis. The mechanisms that take place in the progression of cervical neoplasia are described. The oncogenic proteins E6 and E7 disrupt control of the cell cycle by their communication with p53 and retinoblastoma protein. Epidemiological factors, diagnostic tools, and management of the disease are examined in this manuscript, as are the vaccines currently marketed to protect against viral infection. We offer insights into ongoing research on the roles that oxidative stress and microRNAs play in cervical carcinogenesis since such studies may lead to novel methods of diagnosis and treatment. Several of these topics are surfacing as being critical for future study. One particular area of importance is the study of the mechanisms involved in the modulation of infection and cancer development at cervical sites. HPV-induced cancers may be vulnerable to immune therapy, offering the chance to treat advanced cervical disease. We propose that oxidative stress, mRNA, and the mechanisms of HPV infection will be critical points for HPV cancer research over the next decade.

13.
Biomed Res Int ; 2018: 2897937, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402468

RESUMO

Cervical cancer is one of the leading causes of cancer-related deaths among women and it is caused by the human papillomavirus (HPV). High variation has been reported in the attribution of specific HPV genotypes to cervical neoplasia among various geographic regions. For effective control of cervical cancer through HPV vaccination, it is essential to estimate the cost-effectiveness of vaccination, to monitor the potential transition into other HPV genotypes, and to understand the distribution of specific HPV genotypes across a specific geographic region. In this study, the distribution of HPV genotypes was investigated in southeast China, from 2011 to 2016. The 12,816 cervical swabs collected from women (age 18-78 years, median 43.6 years) outpatients were analyzed. HPV prevalence among 12,816 cervical swabs analyzed was 22.3% (2,856/12,816). Among these positive cases, 2,216 had only one HPV genotype while 640 had multiple HPV genotypes. The cases with multiple types revealed 23 different HPV genotypes with the five most prevalent being HPV18 (18.2%), HPV52 (14.1%), HPV16 (11.9%), HPV58 (10.6%), and HPV33 (5.5%). The rates of HPV infection in patients with cervical inflammation, CIN-1, CIN-2, CIN-3, squamous carcinoma, and adenocarcinoma were 38.4%, 80.5%, 82.6%, 92.3%, 97.5%, and 93.4%, respectively. Four HPV genotypes, HPV18, HPV16, HPV52, and HPV58, were more prevalent in patients with CIN-2-CIN-3 and invasive cervical cancer. A comparison of HPV genotypes attribution to cervical cancer between southeast China and global incidences revealed distinct differences. Due to this unique prevalence, it is essential to streamline the vaccination development protocol prior to administering vaccines based on global data.


Assuntos
Alphapapillomavirus/genética , Genótipo , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/virologia
14.
J Cancer ; 9(16): 2817-2824, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123350

RESUMO

Objective: First, to evaluate the sensitivity and positive predictive value (PPV) of intra-operative frozen section (FS) diagnosis in borderline ovarian tumors (BOTs), and to explore the factors affecting the diagnostic accuracy. Second, to assess the clinical outcomes of misdiagnosed BOT patients. Methods: We performed a retrospective study of all patients diagnosed as BOT through FS or paraffin section (PS) at Qilu Hospital between January 2005 and December 2015. Clinical and pathologic data were extracted. Univariate analysis was performed using standard two-sided statistical tests. We also performed a meta-analysis to further validate the findings. Results: In our retrospective study, 155 patients were included. Agreement between FS and PS diagnosis was observed in 127/155 (81.9%) patients, yielding a sensitivity of 92.7% and a PPV of 87.6%. Under-diagnosis and over-diagnosis occurred in 22 cases (14.2%) and 6 cases (3.9%), respectively. In our univariate analysis of our retrospective study, tumor size (p=0.048) and surgery approach (p=0.024) were significantly associated with misdiagnosis. The pooled analysis of 13 studies including 1,577 patients indicated that the accuracy (69.2%), sensitivity (82.5%), and PPV (81.1%) were low; also under-diagnosis (20.2%) and over-diagnosis (10.5%) were frequent. The meta-analysis results showed that mucinous histology (p < 0.0001, OR=2.03 [1.47-2.81]) and unilateral tumors (p=0.001, OR=2.39 [1.41-4.06]) were associated with the misdiagnosis of BOT. In our retrospective study, there was no statistical significance of clinical outcome such as extent of surgery (p=0.838), recurrence (p=0.586), fertility (p=0.560), death (p=0.362) between misdiagnosed and accurately diagnosed BOT patients. Conclusions: FS analysis of BOTs has low accuracy, sensitivity, and PPV. Under-diagnosis and over-diagnosis are frequent. Meta-analysis results verify that mucinous histology and unilateral tumors are associated with misdiagnosis of FS. Nevertheless, misdiagnosed patients have a good clinical outcome despite the high frequency of misdiagnosis through FS.

15.
Exp Cell Res ; 371(1): 222-230, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30099052

RESUMO

Although persistent human papilloma virus (HPV) infection exerts a crucial influence on cervical carcinogenesis, other factors are also involved in its development, such as intraepithelial lesions and cervical cancer. B7-H3 and B7-H4, which have been reported to be co-regulatory ligands in the B7 family, had been found to be overexpressed in cervical cancer and correlated with adverse clinicopathological features and poor prognosis in our previous studies. In this study, we sought to explore the effects of B7-H3 and B7-H4 on the cervical microenvironment. Among several immune cytokines, interleukin-10 (IL-10) and transforming growth factor (TGF) ß1 stand out as important immunosuppressive factors. Our studies found that IL-10 expression increased with pathological change levels and significantly correlated with cervical cancer differentiation (P < 0.05). TGF-ß1 correlated with lymph node metastasis (LNM) (P < 0.01). Expression of B7-H3 and B7-H4 positively correlated with the expression of IL-10 and TGF-ß1. After co-culture, we found that overexpression of B7-H3 and B7-H4 in cervical cancer cell lines resulted in activation of the cell cycle and decreased apoptosis of U-937 cells. In addition, the contents of IL-10 and TGF-ß1, as well as their protein expression levels, increased in co-culture supernatants in U-937 cells, suggesting regulation by the p-JAK2/STAT3 pathway. The in vivo results demonstrated that with the increasing expression of B7-H3/B7-H4, the expression of IL-10 and TGF-ß1 also increased significantly. Overall, the expression of B7-H3 and B7-H4 favored an immunosuppressive microenvironment by promoting the production of IL-10 and TGF-ß1, thereby resulting in progression of cervical carcinogenesis.


Assuntos
Antígenos B7/genética , Regulação Neoplásica da Expressão Gênica , Interleucina-10/genética , Fator de Crescimento Transformador beta1/genética , Microambiente Tumoral/genética , Neoplasias do Colo do Útero/genética , Inibidor 1 da Ativação de Células T com Domínio V-Set/genética , Adulto , Animais , Apoptose/genética , Antígenos B7/imunologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Células HeLa , Xenoenxertos , Humanos , Interleucina-10/imunologia , Metástase Linfática , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Transdução de Sinais , Análise de Sobrevida , Fator de Crescimento Transformador beta1/imunologia , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/imunologia
16.
J Cancer ; 9(15): 2612-2624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087701

RESUMO

B7-H3, which has been reported to be a co-regulatory ligand of the B7 family, can suppress T cell-mediated immunity and has also been reported to be expressed in many malignancies. In this study, we found that B7-H3 was primarily expressed in the cytoplasm of cervical cancer cells and was associated with deep stromal invasion (P=0.0013). The disease-free survival data showed that cervical cancer patients whose tumours were positive for B7-H3 expression had higher mortality rates compared with patients whose tumours lacked B7-H3 expression (P=0.0317), representing an advantage over P16 (P=0.3486). In contrast, the level of serum B7-H3 was low in cases of cervical intraepithelial neoplasia and cervical cancer. The silencing of B7-H3 in the SiHa, CaSki and H8 cell lines inhibited cell proliferation and enhanced apoptosis, while the over-expression of B7-H3 in HeLa cells showed inverse changes. These changes were partially due to the regulation of cell cycle- and apoptosis-related proteins, such as E2F, P21, P16, PARP-1, Caspase-8, Bax, Bcl-2 and Bcl-xl. The results of in vivo experiments revealed that the knockdown of B7-H3 in tumour cells suppressed SiHa cell growth in nude mice. Overall, B7-H3 is involved in the development and progression of cervical intraepithelial neoplasia and cervical cancer through its effects on the cell cycle and apoptosis, which are mediated via the E7/Rb pathway. B7-H3 also has the potential to be a useful prognostic marker for patients with cervical cancer.

17.
Mol Med Rep ; 17(5): 6319-6326, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29488616

RESUMO

Cervical cancer is the second most common type of cancer among women worldwide and a leading cause of mortality in women. Metastases reduce the overall survival rate in patients with cervical cancer. Thus, it is clinically urgent to investigate the molecular mechanism of cervical cancer metastasis. The aim of the present study was to investigate the mechanism of microRNA (miR)­378 in the metastasis of cervical cancer. In the present study, miR­378 expression levels were significantly upregulated in cervical cancer tissues and cervical intraepithelial neoplasia III tissues when compared with normal cervix tissues. Re­expression of miR­378 significantly promoted tumor migration and invasion in vitro, and metastasis in vivo, while downregulation of miR­378 suppressed the effect in vitro. Luciferase reporter assay revealed that autophagy­related protein 12 (ATG12) was a direct target of miR­378 and its expression was downregulated by miR­378. In cervical cancer tissues with lymph node metastasis, miR­378 was upregulated while ATG12 was downregulated when compared with lymph node negative cases. To the best of our knowledge, the present study is the first to provide evidence that miR­378 may be associated with ATG12. Collectively, the data of the present study suggested that miR­378 may function as an oncogene by promoting metastasis in cervical cancer. The finding that miR­378 targets ATG12 indicated that miR­378 may have a potential role in autophagy. These findings may provide novel insights into the mechanism of metastasis in cervical cancer and a novel therapeutic target for the treatment of cervical cancer.


Assuntos
Proteína 12 Relacionada à Autofagia/biossíntese , Movimento Celular , MicroRNAs/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/metabolismo , Neoplasias do Colo do Útero/metabolismo , Adulto , Proteína 12 Relacionada à Autofagia/genética , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
18.
Oncol Lett ; 15(3): 3646-3652, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29467885

RESUMO

The multi-center, randomized, open-label, phase III trial discussed in the present study was performed to compare the clinical outcomes of nedaplatin (NDP) plus paclitaxel, and carboplatin (CBP) plus paclitaxel for the treatment of epithelial ovarian cancer (EOC). In the current study, 182 patients with International Federation of Gynecology and Obstetrics (FIGO) stage II-IV EOC were randomly assigned to receive NDP plus paclitaxel or CBP plus paclitaxel at 3-week intervals for a total of six courses. The primary endpoints were progression-free survival rate (PFS) and overall survival rate (OS). The secondary endpoints were toxicity profiles. The median follow-up was 44.63 months [95% confidence interval (CI) 33.67-46.47 months] for the NDP group and 47.63 months (95% CI 45.13-49.07 months) for the CBP group. Overall, there was no significant difference in PFS or OS between the two groups (P=0.09 for PFS, and P=0.65 for OS). For the patients with FIGO stage III-IV EOC, the NDP plus paclitaxel regimen significantly prolonged PFS (P=0.02) but did not result in improved OS (P=0.53) when compared with the CBP group. The patients in the NDP plus paclitaxel group also exhibited a lower incidence rate of grade 3 or 4 leucopenia (P=0.03). Other hematological and non-hematological toxicity profiles were similar between the two groups. Compared with CBP plus paclitaxel regimens, NDP plus paclitaxel regimens achieved comparable survival outcomes and similar toxicity profiles. However, patients of FIGO stage III-IV EOC may experience more clinical benefits from NDP plus paclitaxel treatment, including a prolonged PFS and a lower incidence rate of leucopenia. Therefore, an NDP-based regimen may be an alternative choice when using platinum-based agents to treat EOC.

19.
Oncol Lett ; 15(1): 588-591, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29285202

RESUMO

The present case report describes a patient with stage IV ovarian cancer who survived for 9 years without achieving a complete remission since the first relapse. The patient's long-term survival may be ascribed to the slow growth of the cancer cells, limited metastasis and favorable responses to the treatments received. The patient manifested initially with malignant pleural effusion and was not able to tolerate surgical treatment. However, the disease was well-controlled using various treatments, including neoadjuvant chemotherapy, interval cytoreductive surgery and post-operative long-term chemotherapy. Management of ovarian cancer is most effective when tailored to the individual needs of the patient, maximizing its efficacy and prolonging the patient's survival rate. The present case may offer useful insight into the clinical management of stage IV ovarian cancer.

20.
Medicine (Baltimore) ; 96(42): e7935, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29049188

RESUMO

This study aims to analyze the risk of venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC).A retrospective audit was conducted examining 147 patients treated for EOC. Surgical treatment with curative intent, with or without NACT and adjuvant chemotherapy, is the treatment approach, which was modified according to the patient's condition. The incidence of VTE with the most commonly used chemotherapy regimen, carboplatin, cisplatin, paclitaxel, docetaxel, and others were evaluated.This study found a 13.6% incidence of VTE in patients undergoing therapy with curative intent for EOC. No association was seen between NACT and VTE compared to VTE after standard treatment: 2/16 (12.5%) vs 5/131 (3.8%) (P = .16). Univariate and multivariate analyses also demonstrated that NACT has no risk for VTE with odds ratio (OR) = 0.89 (95% CI = 0.18-4.28) and P = 1. Results did not vary significantly with the type of chemotherapy used. Furthermore, increased incidence of VTE as an incidental finding supports the well-established role of malignancy in VTE occurrence. Univariate and multivariate analyses demonstrated that VTE occurred more frequently in menopausal women than nonmenopausal women (17.9% vs 5.8%) with OR = 3.55 (95% CI = 0.99-12.78) and P = .04 in patients aged ≥60 (19.3% vs 10%) with OR = 2.15 (95% CI = 0.83-5.57) and P = .13 but is not statistically significant.We conclude that NACT has no association with VTE and the currently used common chemotherapeutic drug combinations for ovarian cancer carry the minimal risk of thromboembolic events.


Assuntos
Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Resultado do Tratamento , Tromboembolia Venosa/induzido quimicamente
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