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Pelvic Exenteration for Recurrent and Persistent cervical cancer

Chinese Medical Journal 2018年第13期131卷 1541-1548页

作者： Lei Li Shui-Qing Ma Xian-Jie Tan Sen Zhong Ming Wu Department of Obstetrics and Gynecology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100730 China

Background： Pelvic exenteration （PE） for primary and recurrent cervical cancer has resulted in favorable survival outcomes, but there are controversies about specific prognosis factors, and up to now, there have been no published reports from China. This study aimed to share our experiences of PE, which were performed in a single institution. Methods： Frorn January 2009 to January 2016, 38 patients with recurrent or persistent cervical cancer were included in the study, and they were followed up until January 2017. Epidemiological and clinicopathological characteristics of patients were compared for survival outcornes in univariate and Cox hazard regression analysis. Results： There were thirty-one and seven patients with recurrent and persistent cervical cancer, respectively. The median age of patients was 45 years （range 29 65 years）. Total, anterior, and posterior PE consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late complications occurred in 21 （55.3%） patients and 15 （39.5%） patients, respectively. Two （5.3%） patients died due to complications related to surgeries within 3 months after PE. The median overall survival （OS） and disease-free survival （DFS） were 28.5 months （range 9-96 months） and 23 rnonths （range 4.-96 months）, respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox hazard regression analysis showed that, the margin status of the incision and mesorectal lymph node status were independent risk factors liar OS and DFS. Conclusion： In our patients with rect.rrent and persistent cervical cancer, the practice of PE might achieve favorable survival outcomes. Trial Registration： ClinicalTrials.gov, NCT03291275; https：//clinicaltrials.gov/ct2/show/NCT03291275？term-NCT03291275＆rank = 1.

关键词： cervical cancer Pelvic Exenteration Survival

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Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical cancer

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Frontiers of Medicine 2014年第1期8卷 106-112页

作者： Tian Wang Yan Li Abidan Tuerhanjiang Wenwen Wang Zhangying Wu Ming Yuan Shixuan Wang Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan430030 China

cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma （SCC） IA-IIA, and SCC IIB-IIIB （4.3%, 44%, and 88.9%, respectively）. The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated p-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.

关键词： cervical cancer senescence Twist CBX3 lymph node metastasis

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Trends in geographical disparities for cervical cancer mortality in China from 1973 to 2013:a subnational spatio-temporal study

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Chinese Journal of cancer Research 2017年第6期29卷 487-495页

作者： Changfa Xia Chao Ding Rongshou Zheng Siwei Zhang Hongmei Zeng Jinfeng Wang Yilan Liao Ningxu Zhang Zhixun Yang Wanqing Chen National cancer Center/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Resources and Environmental Information System Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of Sciences

Objective： This study was designed to explore the time trends in geographical variations of cervical cancer mortality in China's Mainland over the period 1973 to 2013, to provide subnational spatio-temporal patterns for targeted promotion of human papillomavirus vaccine in China. Methods： Data were extracted from three national retrospective death surveys and cancer registry. The rate ratio （RR） was estimated for the aggregated data for seven geographical regions using generalized linear models to evaluate time trends in geographical disparities of cervical cancer mortality. Results： There was a significant decrease in cervical cancer mortality in China from 1973-1975 to 2004-2005, but leveled off thereafter to 2011-2013. Compared to the period 1973-1975 the RR for the three last time periods were 0.33 [95% confidence interval （95% CI）： 0.30-0.37] for 1990-1992, 0.21 （95% CI： 0.19-0.24） for 2004-2005 and 0.24 （95% CI： 0.22-0.26） for 2011-2013. Females living in the Northwest China and Central China have a high risk of mortality from cervical cancer compared to the nationwide, with the RR being 2.09 （95% CI： 1.83-2.38） and 1.26 （95% CI： t.11-1.44） respectively, while the RRs for South China, Northeast China and Southwest China were below 1.00, indicating the lower death risk. Despite the mortality rate had increased slightly from 2004 to 2013, there was an encouraging sign that the geographical disparities in cervical cancer mortality had gradually narrowed over time across China. Conclusions： Although cervical cancer mortality in China has reduced to very low levels, the high risk of cervical cancer in Northwest China and Central China is still noteworthy. Public health policies including the promotion of vaccine should be targeted to further reduction of geographical disparities in cervical cancer mortality.

关键词： cervical cancer mortality spado-temporal epidemiology China

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Population-based Study of Invasive cervical cancer Patients in Beijing： 1993-2008

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Chinese Medical Journal 2015年第24期128卷 3298-3304页

作者： Tong Wang Ming-Hui Wu Yu-Mei Wu Wei-Yuan Zhang Department of Gynecologic Oncology Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China Department of Women and Child Health Care Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China Beijing Obstetrics and Gynecology Hospital Capital Medical University Beijing 100026 China

Background： In recent years, the incidence of cervical cancer has been rising, particularly in young adults, as the second most common gynecological cancer in China. The aim of this study was to explore the incidence change and the epidemiological characteristics of cervical cancer in Beijing over the past 16 years. Methods： All the cases of the study were limited to Beijing residents diagnosed with cervical cancer and registered in Beij ing from January 1, 1993, to December 31,2008. A total of4100 patients with cervical cancer were obtained from the Statistics Database of Beijing cancer Registry （BJCaR）. According to the registered data, we retrospectively reviewed all original cases which we can acquired in reported hospital. cervical situ cancer, cervical metastatic cancer, non-Beijing residents and repeatedly registered cases were excluded. Totally, 3641 registered cases were verified correctly. Meanwhile, we also collected the following data： Age, occupation, detected methods, histological type, and staging. The trends of incidence and mortality were analyzed by Joinpoint Regression Program 4.***.1.1 produced by National cancer Institute （NCI, USA）. The annual percent change （APC） was calculated using the Joinpoint regression model. Results： The crude rates of incidence and mortality were 10.4 and 1.0 per 100,000 women, respectively during 1993 to 2008. The average WHO age-standardized incidence rates were 11.5 per 100,000 women. There was a decrease in incidence annually by 8.0% （P = 0.3） during 1993-1906 and a rapid increase annually by 18.9% after 1999 （P 〈 0.01）. The median age was 67 years in 1993, but the median age decreased to 45 years in 2008. The peak of the age-specific incidence curve was at 40 years in the most recent period （2005-2008）, which was 25-30 years earlier than that in previous periods （1993-1996）. In the 2224 cases, the numbers of patients with stage Ⅰ,Ⅱ , Ⅲ and IV were 910 （40.9%）, 601 （27%）, 542 （24.4%）, 171 （7.7%）, respectively. The percentage of patients with stage I was 7.6% （ 13/

关键词： cervical cancer Diagnosis Epidemiology Screening

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Upregulation of kazrin F by miR-186 suppresses apoptosis but promotes epithelial-mesenchymal transition to contribute to malignancy in human cervical cancer cells

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Chinese Journal of cancer Research 2017年第1期29卷 45-56页

作者： Chang Liu Jinghua Wang Yang Hu Hong Xie Min Liu Hua Tang Tianjin Life Science Research Center and Department of Pathogen School of Basic Medical Sciences Tianjin Medical University Tianjin 300070China

Objective：Previous studies have identified that kazrin is a constituent of desmosome and influences intercellular adhesion,growing development and morphology.We previously cloned another new isoform,kazrin F and found that it has anti-apoptotic effects on human glioma cell line.To further explore whether kazrin F is involved in tumorigenesis,we investigated its expression and role in cervical cancer（CC） cells.Methods：The role of kazrin F and miR-186 in CC was determined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay,colony formation,transwell,and apoptosis assays.Using enhanced green fluorescent protein（EGFP） reporter assays,reverse transcription-quantitative polymerase chain reaction（RT-qPCR） and western blot analysis,we identified kazrin F post-transcriptional regulation by miR-186.Results：We demonstrate that kazrin F is highly expressed in CC tissues compared with the adjacent noncancerous tissues and promotes cell proliferation,colony formation,migration and invasion in HeLa and C33 A cells by suppressing apoptosis and facilitating epithelial-to-mesenchymal transition（EMT）.Furthermore,miR-186 was confirmed as a regulator of kazrin F dysregulation.An EGFP reporter assay proved that miR-186 directly targets the 3＇-untranslated region（3＇UTR） of kazrin F and downregulates its expression,and miR-186 expression showed an inverse correlation with kazrin F levels in CC tissues.In addition,overexpression of miR-186 suppressed the malignant behaviors of CC cells.The ectopic expression of kazrin F rescued the inhibitory effects of miR-186.Conclusions：Our findings indicate that the upregulation of kazrin F due to downregulated miR-186 levels contributes to malignancy,and highlight the significance of kazrin F in CC tumorigenesis.

关键词： Kazrin F miR-186 apoptosis EMT cervical cancer

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Evolution of radical hysterectomy for cervical cancer along the last two decades: single institution experience

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Chinese Journal of cancer Research 2016年第2期28卷 215-220页

作者： Claudia Arispe Ana Isabel Pomares Javier De Santiago Ignacio Zapardiel Gynecologic Oncology Department La Paz University Hospital

Background： The radical hysterectomy （RH） surgical technique has improved along the years. It is used for the treatment of cervical cancer, endometrial cancer when affecting the cervix, and upper vaginal carcinomas. Our aim was to describe the historical evolution of the technique after the introduction of laparoseopy at our institution. Methods： We performed a retrospective review of medical records of patients who underwent RH, grouped in three periods according to the year of surgery： 1990-1999, 2000-2009 and 2010-2013. Patients＇ characteristics, pathologic details, intraoperative and postoperative complications were analyzed and comoared throughout the time periods. Results： A total of 102 cases of RH were performed at our center during the study period. Among all data collected, the presence of necrosis, age, number of lymph nodes, surgery route, operating time, hospital stay, blood loss and transfusion requirement were statistically significant different among groups. Conversion to laparotomy rate was 19% for the second period compared to the absence of cases in the last one. No significant differences （P=0.124） were observed in the adjuvant treatment received among the three different groups. At the time of the last contact the patients free of disease were 12 （85.7%）, 53 （91.3%） and 26 （86.6%） respectively （P=0.406）. Regarding the disease-free interval, we found significant better outcomes in the group of laparotomy compared to laparoscopy （P=0.015）.Conclusions： Laparoscopic RH is an acceptable surgery with advantages like magnified vision of the operation＇s field, lower surgical complications, shorter hospital stay and earlier resumption to daily activities.

关键词： Gynaecological cancer radical hysterectomy （RH） laparoscopy cervical cancer

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Adjuvant chemotherapy for early-stage cervical cancer

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Chinese Journal of cancer Research 2016年第2期28卷 228-234页

作者： Hiroshi Asano Yukiharu Todo Hidemichi Watari Department of Obstetrics and Gynecology Hokkaido University School of Medicine Division of Gynecologic Oncology National Hospital OrganizationHokkaido Cancer Center

The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery （RS） has not yet been established, and radiation therapy （RT） or concurrent chemoradiotherapy （CCRT） is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life （QOL） or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival （OS） with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin （TP） regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group （GOG）, had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial （RCT） of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable condition, it is necessary that the therapeutic s

关键词： Adjuvant chemotherapy cervical cancer quality of life （QOL） survival intermediate-risk disease

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Neoadjuvant chemotherapy for locally advanced cervical cancer

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Chinese Journal of cancer Research 2016年第2期28卷 235-240页

作者： Takashi Iwata Azumi Miyauchi Yukako Suga Hiroshi Nishio Masaru Nakamura Akiko Ohno Nobumaru Hirao Tohru Morisada Kyoko Tanaka Hiroki Ueyama Hidemichi Watari Daisuke Aoki Department of Obstetrics and Gynecology Keio University School of Medicine Department of Obstetrics and Gynecology Hokkaido University Graduate School of Medicine

Neoadjuvant chemotherapy followed by surgery （NCS） has not been fully evaluated clinically. Currently, the main regimen of neoadjuvant chemotherapy （NAC） used in NCS includes cisplatin. The antitumor effects of NAC reduce lymph node metastasis and the tumor diameter in patients prior to surgery, and this can reduce the number of high risk patients who require postoperative radiation therapy. Many randomized controlled trials （RCTs） have examined the long-term prognosis of NCS compared to primary surgery, but the utility of NCS remains uncertain. The advent of concurrent chemoradiotherapy （CCRT） has markedly improved the outcome of radiotherapy （RT）, and CCRT is now used as a standard method in many cases of advanced bulky cervical cancer. NCS gives a better treatment outcome than radiation therapy alone, but it is important to verify that NCS gives a similar or better outcome compared to CCRT.

关键词： Neoadjuvant chemotherapy （NAC） cervical cancer

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Self-perceived burden and influencing factors in patients with cervical cancer administered with radiotherapy

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World Journal of Clinical Cases 2021年第17期9卷 4188-4198页

作者： Ting Luo Rong-Zhi Xie Yan-Xia Huang Xiao-Hua Gong Hui-Ying Qin Yi-Xiao Wu cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000Guangdong ProvinceChina Cardiovascular Disease Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000Guangdong ProvinceChina Nursing Department Sun Yat-Sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Power Operation Department The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000Guangdong ProvinceChina

BACKGROUND cervical cancer is the fourth commonest malignancy in women around the world.It represents the second most commonly diagnosed cancer in South East Asian women,and an important cancer death cause in women of developing nations.Data collected in 2018 revealed 5690000 cervical cancer cases worldwide,85%of which occurred in developing countries.AIM To assess self-perceived burden(SPB)and related influencing factors in cervical cancer patients undergoing radiotherapy.METHODS Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University,China between March 2018 and March 2019.The survey was completed using a self-designed general information questionnaire,the SPB scale for cancer patients,and the self-care self-efficacy scale,Strategies Used by People to Promote Health,which were delivered to patients with cervical cancer undergoing radiotherapy.Measurement data are expressed as the mean±SD.Enumeration data are expressed as frequencies or percentages.Caregivers were the spouse,offspring,and other in 46.4,40.9,and 12.7%,respectively,and the majority were male(59.1%).As for pathological type,90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas,respectively.Stage IV disease was found in 12(10.9%)patients.RESULTS A total of 115 questionnaires were released,and five patients were excluded for too long evaluation time(n=2)and the inability to confirm the questionnaire contents(n=3).Finally,a total of 110 questionnaires were collected.They were aged 31-79 years,with the 40-59 age group being most represented(65.4%of all cases).Most patients were married(91.8%)and an overwhelming number had no religion(92.7%).Total SPB score was 43.13±16.65.SPB was associated with the place of residence,monthly family income,payment method,transfer status,the presence of radiotherapy complications,and the presence of pain(P<0.05).The SPB and self-care self-efficacy were negatively correlated(P<0.01).In multivariate analysis,self-care self-efficacy,place of

关键词： cervical cancer Radiotherapy Self-perceived burden Influencing factors Self-perceived burden Prospective research

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LncRNA AFAP1-AS1/miR-27b-3p/VEGF-C axis modulates stemness characteristics in cervical cancer cells

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Chinese Medical Journal 2021年第17期134卷 2091-2101页

作者： Meng Xia Li-Jun Duan Bi-Nan Lu Yu-Zhou Pang Zong-Ran Pang School of Pharmacy Minzu University of ChinaBeijing 100081China Department of Orthopedics Bayannaoer City HospitalBayannaoerInner Mongolia 015000China Guangxi Zhuang Yao Medicine Center of Engineering and Technology Guangxi University of Chinese MedicineNanningGuangxi 530200China Key Laboratory of Ethnomedicine of Ministry of Education Minzu University of ChinaBeijing 100081China

Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer-promoting roles in cancer stem cells.However,the regulatory mechanism of AFAP1-AS1 in cervical cancer(CC)stem cells is unknown.The present study aimed to provide a new therapeutic target for the clinical treatment of CC.Methods:Hyaluronic acid receptor cluster of differentiation 44 variant exon 6(CD44v6)(+)CC cells were isolated by flow cytometry(FCM).Small interfering RNAs of AFAP1-AS1(siAFAP1-AS1)were transfected into the(CD44v6)(+)cells.The levels of AFAP1-AS1 were measured by quantitative real-time PCR(qRT-PCR).Sphere formation assay,cell cycle analysis,and Western blotting were used to detect the effect of siAFAP1-AS1.RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor(VEGF)-C.Results:CD44v6(+)CCcells had remarkable stemness and a high level ofAFAP1-AS1.However,AFAP1-AS1knockdownwithsiAFAP1-AS1suppressed the cell cycle transitionofG(1)/S phase and inhibited self-renewal ofCD44v6(+)CCcells,the levels of the stemnessmarkers octamer-binding transcription factor 4(OCT4),osteopontin(OPN),and cluster of differentiation 133(CD133),and the epithelialmesenchymal transition(EMT)-related proteins Twist1,matrix metalloprotease(MMP)-9,and VEGF-C.In the mechanism study,miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+)CC cells.Conclusions:LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.

关键词： Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 Cell stemness cervical cancer Long non-coding RNA actin filament-associated protein 1 antisense RNA 1 MicroRNA-27b-3p

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