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Designing DNA cage-based immuno-fluorescence strategy for rapid diagnosis of clinical cervical cancer tissues

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Chinese Chemical Letters 2022年第2期33卷 788-792页

作者： Juanjuan Li Hongjie Luo Xueqiong Zhu Jianfu Zhao Tianfeng Chen Department of Oncology The First Affiliated Hospitaland Department of ChemistryJinan UniversityGuangzhou 510632China Department of Obstetrics and Gynecology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325000China

Exploiting a tissue diagnosis method to abstain the involuted operating and consume valuable reagents while realizing high-speed and inexpensive pathological grading technology to supply a better scheme for cancer therapy is a significant method of cancers detection. A promising immuno-fluorescence strategy was rationally designed and synthesized by loading ruthenium complex into cervical cancer-targeted DNA-cage, which was well used to realize high-speed and inexpensive diagnosis of clinical cervical cancer tumor tissues avoiding the traditional multi-stage process, thus demonstrating high application potential in clinical pathological grading and surgical judgment. Moreover, it has been finding that Apts-DNA@Ru can enrichment in the tumor region, interestingly, no enrichment in normal cervical cancer tissue. It has the potential to realize the integration of in vivo diagnose and further synchronous treatment in the near future. Thence, this study demonstrates a strategy for integration of cancer-targeted DNA-cage and fluorescent Ru POP as alternative IHC reagents for next-generation more rapid convenient cancer detection.

关键词： Rapid diagnostic Pathological grading cervical cancer Immuno-fluorescence cancer-targeted DNA-cage

SMC1A served as a potential therapeutic target to regulate malignant phenotypes of cervical cancer

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BIOCELL 2023年第11期47卷 2471-2484页

作者： WEILAN LIU XIAOYAN DUAN KAIYUN QIN YAN JIANG CAIFU ZHAO CONGWEI DAI Department of Gynecology Hebei General HospitalShijiazhuang050051China

Introduction:Structural maintenance of chromosome 1A(SMC1A)is a crucial compound of the cohesin complex.It has been reported to regulate the epithelial-mesenchymal transition(EMT)process in multiple cancers.Objectives:The present study aims to further clarify the role of SMC1A in cervical cancer.Methods:We analyzed data from four datasets and confirmed that SMC1A showed high expression in cervical cancer samples and was related to poor prognosis of patients with cervical cancer.Cell proliferation of SiHa and C-33A with knockdown of SMC1A was assessed using CCK-8 and colony formation assay.The migration and invasion were estimated by wound healing assay and Transwell assay separately.The effect of SMC1A on the chemosensitivity of cisplatin and paclitaxel in cervical cancer cells was detected by flow cytometry assay.Results:Results of the immunohistochemistry(IHC)assay confirmed that the expression of SMC1A was increased in tumor tissues.The cell viability was remarkably suppressed in SiHa and C-33A by knocking down the expression of SMC1A.The increase of E-cadherin expression and decrease of N-cadherin and Snail expression verified that inhibition of SMC1A suppressed the EMT process of cervical cancer cells.Further,cell migration,and invasion were significantly repressed by the absence of SMC1A.Cisplatin and paclitaxel are effective chemotherapeutic agents used in the treatment of cervical cancer.Silencing of SMC1A remarkably promoted the apoptosis induced by cisplatin and paclitaxel,revealing that the chemotherapy resistance to cisplatin and paclitaxel in cervical cancer could reduce by knocking down SMC1A.Further,metastasis associated with colon cancer 1(MACC1)was identified as the downstream factor of SMC1A.Its upregulation reversed the proliferation and the EMT process induced by SMC1A silencing.Conclusion:Therefore,our study concluded that SMC1A serves as a therapeutic molecular target to regulate the malignant phenotypes of cervical cancer.

关键词： SMC1A cervical cancer MACC1 Proliferation Epithelial-mesenchymal transition(EMT)

Knockdown Annexin A8 inhibits the proliferation and invasion of cervical cancer cells

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BIOCELL 2023年第12期47卷 2697-2708页

作者： WEILING ZHANG YONG LI CAN ZHANG QING HAN YU ZHANG AIQIN HE WEIPEI ZHU Department of Gynecology and Obstetrics The Second Affiliated Hospital of Soochow UniversitySuzhou215004China Department of Gynecology Oncology Affiliated Tumor Hospital of Nantong UniversityNantong226300China

This study aimed to explore the expression,function,and molecular mechanism of ANXA8,the gene for annexin 8,in cervical cancer.Methods:The gene expression of the ANX family members in cervical cancer tissues was classified via The cancer Genome Atlas(TCGA)database.The expression of ANXA8 in paracancerous tissues,cervical cancer tissues,and cell lines was identified by fluorescence quantitative polymerase chain reaction(PCR)and immunohistochemistry.The effects of ANXA8 knockdown on the cellular growth and cell invasion of cervical cancer were examined by MTT,clone-formation assay,scratch test,and Transwell assay.The effect of ANXA8 knockdown on the proliferative potency of cervical cancer cells was assessed through an in vivo nude-mouse tumor-formation test.The gene expression levels of Ki-67 and ANXA8 in tumor-bearing tissues were measured through Immunohistochemical analysis.Results:TCGA data analysis and fluorescence quantitative PCR exhibited significantly increased expression of ANXA8 in cervical cancer tissues.Further examination exhibited that ANXA8 was expressed exceedingly in cervical cancer tissue,and it was associated with lymph node metastasis,FIGO stage,degree of differentiation,and infiltration depth of cancer patients.Cell-function assays revealed that knocking down ANXA8 may substantially suppress the propagation,colony formation,invasion,and migration of cervical cancer cells.In vivo experiments demonstrated that ANXA8 knockdown had a substantial inhibitory effect on the propagation of cervical cancer cells in nude mice and inhibited the expression of Ki-67.Conclusion:ANXA8 is specifically and significantly upregulated within cervical cancer tissues.The knockdown of this gene showed remarkable outcomes,as evidenced by the substantial inhibition of cervical cancer cell proliferation in in vitro and in vivo experimentations.Therefore,ANXA8 is a potential target or a marker that can serve as a therapeutic or diagnostic tool for cervical cancer.

关键词： cervical cancer Marker Molecular mechanisms

RASAL2 acts as a tumor suppressor in cervical cancer cells

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BIOCELL 2023年第7期47卷 1549-1560页

作者： LI CHEN FANGFANG LI SHOUYAN CAO XIA LI CHAO ZHOU SAI HAN YOUZHONG ZHANG Department of Obstetrics and Gynecology Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012China Department of Obstetrics and Gynecology Binzhou Medical University HospitalBinzhou256603China

This study was designed to investigate the roles of RASAL2 in cervical cancer(CC).Methods:Fifty-four CC tissues and 33 adjacent tissues were obtained from CC patients admitted to our hospital between March 2012 and June 2014.Real-time polymerase chain reaction and western blotting were performed to analyze the expression of RASAL2 mRNA and protein in these tissues,CC cell lines,and normal cervical cells.Over-expression and silencing of RASAL2 were induced after transfection,and the migration,invasion,and proliferation of the CC cell lines were examined.Results:RASAL2 mRNA and protein expressions were significantly down-regulated in CC tissues and cell lines than in adjacent tissues and normal cervical cells,respectively.While low RASAL2 expression correlated with advanced stage and metastasis of CC,its over-expression significantly inhibited proliferation and metastasis of CC cells and induced apoptosis.Under in vitro conditions,silencing of RASAL2 expression could significantly increase the proliferation,invasion,and migration of CC cells.Conclusion:RASAL2 functioned as a tumor suppressor in CC,and was down-regulated in CC tissue samples and cell lines.

关键词： RASAL2 cervical cancer Knockdown Silencing Tumor suppressor

Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3^(+) dendritic cells with CD4^(+) regulatory T cells and CD8^(+) exhausted T cells:synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications

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cancer Communications 2023年第11期43卷 1207-1228页

作者： Xinyu Qu Yumeng Wang Qian Jiang Tingting Ren Chenyan Guo Keqin Hua Junjun Qiu Department of Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghaiP. R. China Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases ShanghaiP. R. China

Background cervical cancer(CC)is the fourth most common cancer in women worldwide.Although immunotherapy has been applied in clinical practice,its therapeutic efficacy remains far from satisfactory,necessitating further investigation of the mechanism of CC immune remodeling and exploration of novel treatment targets.This study aimed to investigate the mechanism of CC immune remodeling and explore potential therapeutic targets.Methods We conducted single-cell RNA sequencing on a total of 17 clinical specimens,including normal cervical tissues,high-grade squamous intraepithelial lesions,and CC tissues.To validate our findings,we conducted multicolor immunohistochemical staining of CC tissues and constructed a subcutaneous tumorigenesis model in C57BL/6 mice using murine CC cell lines(TC1)to evaluate the effectiveness of combination therapy involving indoleamine 2,3-dioxygenase 1(IDO1)inhibition and immune checkpoint blockade(ICB).We used the unpaired two-tailed Student's t-test,Mann-Whitney test,or Kruskal-Wallis test to compare continuous data between two groups and one-way ANOVA with Tukey's post hoc test to compare data between multiple groups.Results Malignant cervical epithelial cells did not manifest noticeable signs of tumor escape,whereas lysosomal-associated membrane protein 3-positive(LAMP3^(+))dendritic cells(DCs)in a mature state with immunoregulatory roles were found to express IDO1 and affect tryptophan metabolism.These cells interacted with both tumor-reactive exhausted CD8^(+)T cells and CD4^(+) regulatory T cells,synergistically forming a vicious immunosuppressive cycle and mediating CC immune escape.Further validation through multicolor immunohistochemical staining showed co-localization of neoantigen-reactive T cells(CD3^(+),CD4^(+)/CD8^(+),and PD-1^(+))and LAMP3+DCs(CD80^(+) and PD-L1^(+)).Additionally,a combination of the IDO1 inhibitor with an ICB agent significantly reduced tumor volume in the mouse model of CC compared with an ICB agent alone.Conclusions Our study suggested that a combinatio

关键词： cervical cancer dendritic cell immune checkpoint blockade immune escape indoleamine 2,3-dioxygenase 1 single-cell analysis T cell

Pre Screening of cervical cancer Through Gradient Boosting Ensemble Learning Method

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Intelligent Automation & Soft Computing 2023年第3期35卷 2673-2685页

作者： S.Priya N.K.Karthikeyan D.Palanikkumar Coimbatore Institute of Technology CoimbatoreIndia Dr.NGP Institute of Technology CoimbatoreIndia

In recent years,cervical cancer is one of the most common diseases which occur in any woman regardless of any age.This is the deadliest disease since there were no symptoms shown till it is diagnosed to be the last stage.For women at a certain age,it is better to have a proper screening for cervical can-cer.In most underdeveloped nations,it is very difﬁcult to have frequent scanning for cervical cancer.Data Mining and machine learning methodologies help widely inﬁnding the important causes for cervical cancer.The proposed work describes a multi-class classiﬁcation approach is implemented for the dataset using Support Vector Machine(SVM)and the perception learning method.It is known that most classiﬁcation algorithms are designed for solving binary classiﬁcation problems.From a heuristic approach,the problem is addressed as a multiclass classiﬁcation problem.A Gradient Boosting Machine(GBM)is also used in implementation in order to increase the classiﬁer accuracy.The proposed model is evaluated in terms of accuracy,sensitivity and found that this model works well in identifying the risk factors of cervical cancer.

关键词： cervical cancer SVM GBM ensemble learning

Association between IDEAL-IQ MRI fat fraction quantification and pelvic bone marrow reserve function in concurrent chemoradiotherapy for cervical cancer

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Radiation Medicine and Protection 2023年第3期4卷 136-144页

作者： Xiaomin Wen Qinghua Qin Yanling Wu Zhouyu Li Xinglong Yang Jinquan Liu Ling Lin Mingyi Li The 5th Ward of Radiotherapy Department Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China Department of Oncology Liuzhou Worker's HospitalLiuzhou 545005China Radiotherapy Center Department Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China

Objective:To analyze the association between iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification sequence(IDEAL-IQ)magnetic resonance imaging(MRI)of bone marrow fat fraction and bone marrow reserve function during concurrent chemoradiotherapy for cervical cancer.Methods:The study retrospectively analyzed twenty-six patients with stage IB1 to IVA cervical cancer treated between February 2020 and November 2020.All patients received concurrent chemoradiotherapy that included platinum alone or combined paclitaxel and platinum.Pelvic IDEAL-IQ MRI(plain and enhanced)was performed before and after treatment.Regions of interest,including the fifth lumbar vertebra,sacrum,ilium,ischium,and femoral neck,were manually delineated,and the bone marrow fat fraction was measured.Peripheral blood cell counts were recorded during treatment,and the relationship between the fat fraction values and changes in the blood cell counts was explored.Results:IDEAL-IQ MRI bone marrow fat fraction was associated with platelet nadir and platelet decline during treatment.The average pelvic bone marrow fat fraction before chemoradiotherapy was moderately negatively correlated with platelet count nadir during concurrent chemoradiotherapy(r=-0.450,P?0.021).The change in average pelvic bone marrow fat fraction through chemoradiotherapy was moderately positively correlated with the degree of thrombocytopenia(r=0.399,P=0.044).Conclusion:Bone marrow fat content quantified by IDEAL-IQ was associated with platelet count nadir and the degree of thrombocytopenia in patients with cervical cancer undergoing concurrent chemoradiotherapy.

关键词： IDEAL-IQ cervical cancer Concurrent chemoradiotherapy Bone marrow reserve function

Effect of Endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical cancer

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Radiation Medicine and Protection 2023年第2期4卷 104-108页

作者： Hengzhao Zhuang Yang Jiao Xin Li Jingping Yu Juying Zhou Lili Wang Deparment of Radiation Oncology First Affiliated Hospital of Soochow UniversitySuzhou 215000China School of Radiation Medicine and Protection Medical College of Soochow UniversitySuzhou 215000China Deparment of Radiation Oncology Changzhou No.2 People's HospitalAffiliated Hospital of Nanjing Medical UniversityChangzhou 213000China

ObjectiveTo explore the value of Endostar in the clinical application of locally advanced cervical cancer.MethodsA total of 107 patients with locally advanced cervical cancer who received concurrent chemoradiotherapy(CCRT)in the Department of Radiotherapy,the First Affiliated Hospital of Soochow University and Changzhou No.2 People's Hospital between January 2018 and December 2020 were enrolled in this retrospective study.There were 30 cases in the Endostar combined with CCRT(E-CCRT)group and 77 in the CCRT group.Propensity score matching(PSM)was used to reduce confounding factors.The short-term efficacy and long-term survival rate were compared between the E-CCRT group and the CCRT group.ResultsAfter matching,the objective response rates in the E-CCRT group and CCRT group were 86.7%and 63.3%,respectively,with statistically significant difference(χ^(2)=4.356,P=0.037).But there were no statistically significant differences in the disease control rates(96.7%vs.86.7%,χ^(2)=0.873,P=0.350),3-year overall survival(OS)rates(86.7%vs.83.3%,P=0.681),and 3-year disease-free survival(DFS)rates(both 76.7%and 76.7%,P=0.869).There was no statistically significant difference in the incidence of adverse reactions between the two groups.ConclusionsE-CCRT can improve the response of locally advanced cervical cancer patients without increasing the occurrence of adverse reactions,and has the potential to become a new treatment regimen for cervical cancer.

关键词： cervical cancer Recombinant human Endostatin Concurrent chemoradiotherapy Propensity score matching

cervical cancer: Epidemiology, risk factors and screening

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Chinese Journal of cancer Research 2020年第6期32卷 720-728页

作者： Shaokai Zhang Huifeng Xu Luyao Zhang Youlin Qiao Department of cancer Epidemiology Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Epidemiology National Cancer CenterChinese Academy of Medical SciencesSchool of Population Medicine and Public HealthPeking Union Medical CollegeBeijing 100021China

cervical cancer is one of the leading causes of cancer death among females worldwide and its behavior epidemiologically likes a venereal disease of low infectiousness. Early age at first intercourse and multiple sexual partners have been shown to exert strong effects on risk. The wide differences in the incidence among different countries also influenced by the introduction of screening. Although the general picture remains one of decreasing incidence and mortality, there are signs of an increasing cervical cancer risk probably due to changes in sexual behavior. Smoking and human papillomavirus(HPV) 16/18 are currently important issues in a concept of multifactorial, stepwise carcinogenesis at the cervix uteri. Therefore, society-based preventive and control measures, screening activities and HPV vaccination are recommended. cervical cancer screening methods have evolved from cell morphology observation to molecular testing. High-risk HPV genotyping and liquid-based cytology are common methods which have been widely recommended and used worldwide. In future, accurate,cheap, fast and easy-to-use methods would be more popular. Artificial intelligence also shows to be promising in cervical cancer screening by integrating image recognition with big data technology. Meanwhile, China has achieved numerous breakthroughs in cervical cancer prevention and control which could be a great demonstration for other developing and resource-limited areas. In conclusion, although cervical cancer threatens female health, it could be the first cancer that would be eliminated by human beings with comprehensive preventive and control strategy.

关键词： cervical cancer epidemiology risk factors screening