RESUMEN
Resumo O estudo visa analisar a prevalência de estadiamento avançado ao diagnóstico do câncer do colo do útero e sua associação com indicadores individuais e contextuais socioeconômicos e de oferta de serviços de saúde no Brasil. Estudo transversal, realizado com casos de câncer do colo do útero em mulheres de 18 a 99 anos, no período de 2006 a 2015, extraídos do Integrador de Registros Hospitalares de Câncer. Variáveis contextuais foram coletadas no Atlas do Desenvolvimento Humano, no Cadastro Nacional de Estabelecimentos de Saúde e no Sistema de Informações Ambulatoriais. Usou-se o modelo de regressão de Poisson multinível com intercepto aleatório. A prevalência de diagnóstico em estádio avançado foi de 48,4%, apresentando associação com idades mais avançadas (RP 1,06; IC 1,01-1,10), raça/cor da pele preta, parda e indígena (RP 1,04; IC 1,01-1,07), menores níveis de escolaridade (RP 1,28; IC 1,16-1,40), ausência de parceiro conjugal (RP 1,10; IC 1,07-1,13), encaminhamento do tipo público ao serviço de saúde (RP 1,07; IC 1,03-1,11) e menor taxa de realização de exame citopatológico (RP 1,08; IC 1,01-1,14). Os resultados reforçam a necessidade de melhorias no programa nacional de prevenção do câncer do colo do útero em áreas com baixa cobertura da citologia oncótica.
Abstract The scope of this study is to analyze the prevalence of advanced stage diagnosis of cervical cancer and its association with individual and contextual socioeconomic and healthcare service indicators in Brazil. A cross-sectional study was conducted using cervical cancer cases in women aged 18 to 99 years, from 2006 to 2015, extracted from the Hospital Cancer Registry (HCR) Integrator. Contextual variables were collected from the Atlas of Human Development in Brazil; the National Registry of Health Institutions (NRHI); and the Outpatient Information System. Multilevel Poisson Regression with random intercept was used. The prevalence of advanced stage diagnosis was 48.4%, revealing an association with older age groups (PR 1.06; CI 1.01-1.10), black, brown, and indigenous race/skin color (PR 1.04; CI 1.01-1.07), lower levels of schooling (PR 1.28; CI 1.16-1.40), no marital partner (PR 1.10; CI 1.07-1.13), public referral to the health service (PR 1.07; CI 1.03-1.11), and lower rates of cytological examination (PR 1.08; CI 1.01-1.14). The results reinforce the need for improvements in the national cervical cancer prevention program in areas with low coverage of oncotic cytology.
RESUMEN
Previous studies show that glycogen synthase kinase 3β (GSK3B) plays an important role in tumorigenesis. However, its role in cervical cancer is unclear. The present study silenced GSK3B with siRNAs and/or chemical inhibitors to determine its role in HeLa cervical cancer cell proliferation and migration as well as in xenograft tumor growth. Cell Counting Kit (CCK)-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine cell survival and proliferation. Scratch and Transwell® assays were used to evaluate cell migration. Xenograft tumors were used to evaluate the effect of GSK3B on tumor growth. Transcriptomic sequencing was used to clarify the mechanisms underlying the foregoing processes. Public databases and clinical specimens showed that GSK3B was upregulated in cervical cancer tissues and correlated with poor prognosis. In vitro experiments indicated that GSK3B inhibition reduced cell viability, proliferation, and migration. In vivo experiments demonstrated that GSK3B inhibition slowed xenograft tumor growth. Transcriptomic sequencing revealed that GSK3B inhibition modulated the phosphatidylinositol 3-carboxykinase (PI3K)/protein kinase B (Akt) and extracellular matrix (ECM)-receptor interaction signaling pathways. GSK3B inhibition decreased the protein levels of phosphorylated PI3K and Akt and the levels of mesenchymal markers but increased those of epithelial markers. An activator of the PI3K/Akt signaling pathway counteracted the suppressive effects of GSK3B inhibition on HeLa cell viability and proliferation and on PI3K/Akt signaling. Our data suggested that GSK3B regulated cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition (EMT).
RESUMEN
Cervical cancer is a common gynecological malignant tumor. Vaccination with human papilloma virus （HPV） vaccine is of great significance to prevent condyloma acuminatum， HPV infection， and cervical cancer. This paper reviews the epidemic situation and risk factors of cervical cancer， the prevention strategies of cervical cancer， HPV types， HPV vaccine types and mechanisms of action， the safety and effectiveness of vaccines， men’s HPV vaccination， vaccination policies in various countries and so on， and further puts forward suggestions on HPV vaccination policies in China.
RESUMEN
Objective To evaluate the predictive value of a dose-surface histogram (DSH) for radiation cystitis (RC) in patients with cervical cancer. Methods We retrospectively included 190 patients with cervical cancer who underwent image-guided radiotherapy (IGRT) from the HIS system of The First Affiliated Hospital of Hebei North University from May 2013 to May 2023. The patients were divided into test group (n = 100) and control group (n = 90). The dose distribution in the bladder was evaluated by using a DSH for the test group and using a dose-volume histogram (DVH) for the control group. Receiver operating characteristic curves were used to evaluate the predictive value of DSH for RC in comparison with DVH. Results There were no significant differences in baseline data and RC incidence between the two groups (all P＞0.05). All evaluation indicators were significantly different between DSH and DVH (all P＜0.05). The predictive value of S45 and V45 for the incidence of grade-I, -II, and -III RC was low (all P＜0.05). The predictive value of S50 and V50 for the incidence of grade-I, -II, and -III RC was moderate (all P＜0.05). S55−S57 and V55−V57 showed high value for predicting the incidence of grade-I, -II, and -III RC (all P＜0.05). Conclusion DSH shows basically the same predictive value for the incidence of RC caused by IGRT in cervical cancer as DVH, which is expected to become a new tool for evaluating radiotherapy plans.
RESUMEN
Objective To explore the mechanism of malignant behavior of cervical cancer(CC)cells based on AMP-activated protein kinase(AMPK)/rapamycin target protein(mTOR)signaling pathway mediated by nucleo-tide-binding oligomerization domain receptor 2(NOD2).Methods Bioinformatics analysis was performed to deter-mine the expression of NOD2 in CC tissue.Plasmids targeting NOD2(shNOD2)and shRNAs negative control(shNC),NOD2 overexpression(NOD2)and vectors(Vec)were transfected into CC cells.The effect of NOD2 on the growth of CC cells was determined by cell counting kit-8 assay,colony formation and Transwell cell invasion as-say.Transcriptome analysis was performed by high throughput RNA sequencing(RNA-Seq).Western blot was used to detect the expression of NOD2,AMPK/mTOR signaling pathway and autophagy protein in the cell line.24 female BALB/c nude mice were randomly divided into four groups,with 6 mice in each group:vector group(Vec group),NOD2 overexpression group(NOD2 group),shNC group and shNOD2 group.The distant metastasis mod-el was established in mice,and the fluorescence intensity of lung metastasis was monitored and the number of lung metastasis nodules was counted.Results On-line database analysis showed that the expression of NOD2 in CC tis-sues was significantly higher than that in normal tissues,and there were significant differences in the mRNA expres-sion of NOD2 in different stages of CC(P＜0.05).In addition,the high expression of NOD2 was associated with poor overall survival and disease-free survival(P＜0.05).NOD2 overexpression promoted the proliferation,colony formation,migration and invasion of CC cells,while NOD2 knock-down was the opposite.Consistent with the re-sults in vitro,the lung colonization and lung metastasis of CC cells in NOD2 group were significantly higher than those in Vec group(P＜0.05),while those in shNOD2 group were significantly lower than those in shNC group(P＜0.05).RNA-Seq results showed that the expression of NOD2 was significantly related to AMPK signal activa-tion,mTOR signal inhibition,autophagy regulation pathway activation and autophagy formation.Compared with shNC group,the expression of phosphorylated AMPK and LC3 protein decreased significantly in shNOD2 group(P＜0.05),and the expression levels of phosphorylated mTOR and p62 protein increased significantly(P＜0.05).Compared with Vec group,the expression levels of LC3 and AMPK protein in NOD2 group increased significantly(P＜0.05),and the expression levels of phosphorylated mTOR and p62 protein decreased significantly(P＜0.05).Compared with shNC group,the point accumulation of GFP-mRFP-LC3 in shNOD2 group decreased signifi-cantly(P＜0.05).Compared with Vec group,the point accumulation of GFP-mRFP-LC3 increased significantly(P＜0.05).Conclusion NOD2 may promote the proliferation,migration and invasion of CC through AMPK/mTOR signal,and its mechanism partly involves autophagy activation.
RESUMEN
Objective To compare paired boxed gene 1(PAX1)methylation and p16/Ki-67 double staining alone and in combination in thinprep cytologic test(TCT)for distinguishing atypical squamous cells of undetermined significance(ASC-US)and low-grade squamous intraepithelial lesion(LSIL)population.Methods A total of 247 patients with TCT results of ASC-US and LSIL admitted in our hospital from January 2021 to December 2022 were enrolled in this study.Detection efficacy of PAX1 methylation and p16/Ki-67 double staining alone and in combination was evaluated with colposcopic pathologic results as the gold standard and the sensitivity,specificity,accuracy and area under the curve(AUC)as evaluation indexes.Results The positive rates of PAX1 methylation and p16/Ki-67 double staining were increased with the severity of pathological findings.Combined detection of PAX1 methylation and p16/Ki-67 assay had a sensitivity of 91.25％,specificity of 97.72％and accuracy of 95.51％in the women with TCT of ASC-US,and these values were statistically better than those of PAX1 methylation and p16/Ki-67 double staining alone(P＜0.01).Conclusion The combination of PAX1 methylation and p16/Ki-67 double-staining assay can further improve the diagnostic efficacy in patients with ASC-US on TCT results.
RESUMEN
Objective To explore the effects of HPV16 E6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.Methods HUCEC models infected with HPV16 E6 were constructed,and transcriptome sequencing was performed to screen for differentially expressed genes(DEGs),which were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis,the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition,RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines,SiHa and CaSki.Results A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes;KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6,and RT-qPCR and Western blotting confirmed that HPV16 E6 down-regulated DHRS2 mRNA(P＜0.01)and protein(P＜0.05)and ETV5 protein expression(P＜0.01).In SiHa and CaSki cells,compared with the control group,the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression(P＜0.05).Conclusion HPV16 E6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating DHRS2 expression.
RESUMEN
Objective To explore the expression of serum long noncoding RNA(lncRNA)CCDC18-AS1 and microRNA-501(miR-501)in patients with human papillomavirus(HPV)-infected cervical cancer,and its correlation with prognosis.Methods A total of 78 patients with HPV-infected cervical cancer who underwent treatment in the hospital from May 2019 to May 2020 were enrolled as study group,meantime,80 patients with simple HPV infection and 81 patients with simple non-HPV infected cervical cancer were set as control group 1 and control group 2.Serum lncRNA CCDC18-AS1 and miR-501 expression levels were detected by re-al-time quantitative PCR.Then the clinical features,postoperative overall survival and progression-free surviv-al were analyzed in the study group.Results The relative expression levels of serum lncRNA CCDC18-AS1 and miR-501 in the study group were higher than those in control group 1 and control group 2(P<0.05),and the relative expression levels of serum lncRNA CCDC18-AS1 and miR-501 in control group 2 were higher than those in control group 1(P<0.05).Pearson correlation analysis showed that serum lncRNA CCDC18-AS1 and miR-501 were positively correlated in the study group(r=0.421,P<0.001).Serum lncRNA CCDC18-AS1 and miR-501 in study group were not related to age,but were related to clinical stage,differentiation de-gree,lymph node metastasis,and squamous epithelial cell antigen(P<0.05).Kaplan Meier analysis showed that the postoperative overall survival and progression-free survival of high lncRNA CCDC18-AS1 and miR-501 expression groups were shorter than those of low expression groups(P<0.05).Conclusion HPV-infec-ted cervical cancer patients have up-regulated expression of serum lncRNA CCDC18-AS1 and miR-501,and the abnormal changes are closely related to patients'clinical characteristics and postoperative survival,so the two indicators could be used as auxiliary indicators for the disease assessment and prognosis evaluation.
RESUMEN
Objective To investigate the value of human papillomavirus(HPV)DNA and HPV E6/E7 mRNA detection in screening for cervical lesions.Methods A total of 619 patients who were screened for cer-vical lesions in West China Second University Hospital from September 2021 to August 2022 were selected as the study objects.The value of HPV DNA and HPV E6/E7 mRNA detection in cervical lesion screening was evaluated based on their pathological results.Results The positive rate of HPV DNA detection was 64.78％(401/619)and that of HPV E6/E7 mRNA detection was 60.74％(376/619)in 619 patients.Cervical lesion screening was mainly conducted in sexually active people aged 30-＜40 years and 40-＜50 years.The posi-tive rates of HPV DNA and HPV E6/E7 mRNA increased with the increase of cervical lesion grade.The sen-sitivity,positive predictive value and negative predictive value of the two methods were higher than those of HPV DNA or HPV E6/E7 mRNA detection.Conclusion The combined detection of the two methods can be used for screening cervical lesions at various pathological stages,which can provide greater guidance value in clinical diagnosis and treatment.
RESUMEN
Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.
RESUMEN
Objective To investigate the effect of transmembrane protein CD147 expression on AIM2 inflammasome-mediated pyroptosis and proliferation of cervical cancer cells.Methods Western Blot was used to detect the expression of CD147 in cervical cancer cell lines SiHa(HPV+)and C33a(HPV-)and normal cervical epithelial cells H8(HPV+)and HCer Epic(HPV-).SiHa cells were transfected with lentivirus to down-regulate the expression of CD147.According to the different treatments,SiHa cells were divided into SiHa group,negative control group(shCD147-NON),knockdown group 1(shCD147-1)and knockdown group 2(shCD147-2).The transfection effect was verified by Western Blot,RT-qPCR and green fluorescence expression.The protein and mRNA expressions of AIM2,Caspase-1,IL-18 and GSDMD were detected by Western Blot and RT-qPCR.The lactate dehydrogenase(LDH)release was measured in the cell culture supernatant,and the cell morphology was observed under the fluorescence inverted microscope;the proliferation ability of cells was measured by CCK-8 and the colony formation ability was measured by cell cloning experiments.Results Western Blot results showed that CD147 protein expression in SiHa cells was the highest compared with that in HCerEpic cells.CD147 low expression lentivirus effectively down-regulated the expression of CD147 in SiHa cells.The results of Western Blot and RT-qPCR experiments showed that the expression of AIM 2,Caspase-1,IL-18,GSDMD protein and mRNA increased in shCD147-1 and shCD147-2 group(P<0.05).Lactate dehydrogenase(LDH)release assay showed that compared with the SiHa group,the shCD147 group had a significant increase in LDH release(P<0.05).Fluorescence inverted microscope showed that the shCD147 group had swelling and vacuolization,showing typical pyroptosis.Compared with the SiHa group,the shCD147-1 and shCD147-2 groups had significantly reduced the cell proliferation and colony formation ability(P<0.05).Conclusion Low expression of CD147 effectively up-regulates the expression of AIM2 inflammation-related factors in cervical cancer SiHa cells,induces the pyroptosis,and inhibits the cell proliferation and cloning.
RESUMEN
Objective To detecte the differential metabolites and related pathways in Siha cells of cervical cancer by screening the inhibition of HPV16 E6/E7 expression based on 1H NMR metabolomics so as to identify the key metabolic markers involved in the development of high-risk HPV16 cervical cancer.Methods Siha cells were transfected with RNAi fragments to down-regulate the expression of E6/E7,which were divided into the normal control group(Siha cells),no-load group(si-NON),si-E6 group and si-E7 group,and their transfection efficiency was verified.1H NMR metabolomics was used to reveal the differential metabolites involved in interfering E6/E7 expression in Siha cells.Combined with MetaboAnalyst 5.0 online software,differential metabolites and related metabolic pathways were obtained.Results Fluorescence was observed by inverted fluorescence microscope.Western blotting results showed that compared with Siha group,the expression of E6/E7 in si-E6 group and si-E7 group was decreased(F=145.8,P<0.001).After down-regulating the expression of E6/E7,13 common differential metabolites,including Isoleucine,Leucine and valine,were detected.The results of MetaboAnalyst 5.0 online software analysis suggested that the above metabolites were mainly involved in the biochemical synthesis pathway of aminoacyl-trNA,biochemical synthesis pathway of isoleucine,Leucine and valine;There were 10 metabolic pathways of tyrosine,phenylalanine and tryptophan biochemical synthesis.Conclusion After HPV16 infection,changes of glucose and amino acid metabolism can promote the progression of cervical cancer,which provide a theoretical basis for the prevention and treatment of cervical cancer.
RESUMEN
Objective To investigate the correlation between rs712 and rs7973450 located at the 3'UTR region of the KRAS gene and the risk of cervical cancer(CC)and cervical intraepithelial neoplasia(CIN)in Chinese Han population in Yunnan province.Methods A total of 2405 individuals(461 subjects with CIN,961 subjects with CC and 983 healthy controls)were enrolled.The SNPs were genotyped used TaqMan assay and the correlation of these SNPs with CIN and CC was analyzed.Results The A allele of rs7973450 might be a protective factor for the occurrence of CIN(P = 0.004,OR= 0.651,95%CI 0.487～0.871)and CC(P = 7.00×10-4,OR= 0.667,95%CI 0.529～0.844).There was no significant difference in allelic and genotypic distribution of rs712 among CIN,CC and Control groups(P>0.017).The haplotype assay showed thatrs712A-rs7973450G was associated with increased risk of CIN(P = 4.00×10-4;OR= 1.714,95%CI 1.269～2.314)and CC(P = 3.84×10-5,OR= 1.667,95%CI 1.305～2.131).While haplotype rs712A-rs7973450A was associated with a lower risk of CC(P = 0.012,OR= 0.790,95%CI 0.658～0.950).Conclusion The A allele of rs7973450 in 3'UTR of KRAS gene might be the protective factor for the occurrence of CIN and CC in a Chinese Han population in Yunnan province.
RESUMEN
Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.
RESUMEN
Objective:To investigate the influences of lupinol on the proliferation,apoptosis and invasion of cer-vical cancer cells by regulating autophagy mediated by phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway.Methods:The proliferation rate of human cervical cancer cell line HeLa cells treated with 0,10,25,50,70,90 μmol/L lupinol was determined,and the appropriate concentration of lupinol was screened out.HeLa cells cultured in vitro were randomly grouped into control group,low-dose lupinol group,high-dose lupinol group,740 Y-P group(PI3K activator),and high-dose lupinol+740 Y-P group.After group intervention with lupinol and 740 Y-P,MDC fluorescence staining was used to detect the forma-tion of autophagic vacuolation of HeLa cells in each group;western blot was used to detect the expression of au-tophagy and PI3K/AKT/mTOR pathway-related proteins in HeLa cells in each group.HeLa cells cultured in vitro were randomly grouped into control group,low-dose lupinol group,high-dose lupinol group,high-dose lupinol+rapamycin(Rapa),and high-dose lupinol+3-methyladenine(3-MA)group.After the intervention of high dose of lupinol,Rapa and 3-MA,the proliferation of HeLa cells in each group was detected by MTT assay and plate colony formation assay;flow cytometry was used to detect the apoptosis of HeLa cells in each group;transwell assay was used to detect the invasion of HeLa cells in each group;western blot was used to detect the expressions of proliferation,apoptosis and epithelial-mesenchymal transition-related proteins in HeLa cells in each group.Re-sults:Compared with the control group,the relative content of autophagic vacuoles,the protein expressions of Mi-crotubule-associated protein 1A/1 B-light chain 3(LC3)Ⅱ/LC3Ⅰ,and Beclin-1 in the low and high dose lupinol groups were all increased(P＜0.05),the phosphorylated PI3K(p-PI3K)/PI3K,phosphorylated AKT(p-AKT)/AKT,and phosphorylated mTOR(p-mTOR)/mTOR decreased(P＜0.05);the relative content of autophagic vac-uoles,the protein expressions of LC3Ⅱ/LC3Ⅰ,and Beclin-1 in the high-dose lupinol group were further increased compared with the low-dose lupinol group(P＜0.05),the p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR were further decreased(P＜0.05);the relative content of autophagic vacuoles,the protein expressions of LC3Ⅱ/LC3Ⅰ,and Beclin-1 in 740 Y-P group decreased compared with the control group(P＜0.05),the p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR increased(P＜0.05).Compared with the high-dose lupinol group,the relative content of autophagic vacuoles,the protein expressions of LC3Ⅱ/LC3Ⅰ,and Beclin-1 in the high-dose lupinol+740 Y-P group decreased(P＜0.05),the p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR increased(P＜0.05).Com-pared with the control group,the cell proliferation rate,colony formation rate,invasion number,and the protein ex-pressions of proliferating cell nuclear antigen(PCNA),B cell lymphoma 2(Bcl-2)and Vimentin in the low and high dose groups of lupinol were all decreased(P＜0.05),the apoptosis rate,and the protein expressions of Bcl-2 as-sociated x protein(Bax)and zonula occludens protein 1(ZO-1)were all increased(P＜0.05);compared with the low-dose lupinol group,the cell proliferation rate,colony formation rate,invasion number,and the protein expres-sions of PCNA,Bcl-2 and Vimentin in the high-dose lupinol group were further decreased(P＜0.05),the apopto-sis rate,and the protein expressions of Bax and ZO-1 were further increased(P＜0.05).Compared with the high-dose lupinol group,the cell proliferation rate,colony formation rate,invasion number,and the protein expres-sions of PCNA,Bcl-2 and Vimentin in the high-dose lupinol+Rapa group were increased(P＜0.05),the apopto-sis rate,and the protein expressions of Bax and ZO-1 were decreased(P＜0.05);the cell proliferation rate,colo-ny formation rate,invasion number,and the protein expressions of PCNA,Bcl-2 and Vimentin in the high-dose lu-pinol+3-MA group were decreased(P＜0.05),the apoptosis rate,and the protein expressions of Bax and ZO-1 were increased(P＜0.05).Conclusions:Lupinol induces protective autophagy by inhibiting the PI3K/AKT/mTOR pathway,thereby promoting the apoptosis of cervical cancer cells and inhibiting their proliferation and inva-sion.Activation of autophagy attenuates the effects of lupinol on the proliferation,apoptosis and invasion of cervi-cal cancer cells.
RESUMEN
Objective:To explore the clinical value of modified laparoscopic radical surgery without uterine ma-nipulator in the treatment of early cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 105 patients with early cervical cancer(stages ⅠB1,ⅠB2,ⅡA1)who underwent radical resection of cer-vical cancer in West China Second University Hospital,Sichuan University from January 2019 to January 2020.According to the operation methods,the patients were divided into uterine lifter-free group(35 cases),uterine lifter group(35 cases)and laparotomy group(35 cases).The operation duration,intraoperative blood loss,number of resected lymph nodes,postoperative anal exhaust time,drainage tube placement time,hospitalization time,inci-dence of surgical complications,recurrence rate and mortality rate were compared among the three groups.Re-sults:There was no statistically significant difference in the number of lymph node resection,the postoperative anal exhaust time,drainage tube placement time and hospitalization time among the three groups(P>0.05).Comparison between two groups showed that the operation time of the group without uterine lifting was longer than that of the laparotomy group,and the intraoperative bleeding volume and the Postoperative anal exhaust time of the laparotomy group were more than those of the other two groups,and the differences were statistically signif-icant(P<0.05).There were 18 cases of surgical complications in the three groups.The incidence rate of uterine lifter-free group,laparotomy group and uterine lifter group was 11.4%,20.0%and 20.0%,respectively,with no statistically significant difference(P>0.05).There were 8 patients with recurrence 2 years after operation,the re-currence rates of the uterine lifter-free group,the laparotomy group and the uterine lifter group were 0,5.7%and 17.1%,respectively,the difference was statistically significant(P<0.05).The recurrence rate of the group with-out uterine lifting was significantly lower than that of the uterine lifting group(P<0.05).There were0 death in the non-lifting group,0 in the laparotomy group,and 1 case in the uterine lifting device group within 2 years after oper-ation,the difference was no statistically significant(P>0.05).Conclusions:The modified laparoscopic radical re-section without uterine lifter can reduce the risk of tumor recurrence in laparoscopic radical resection with uterine lifter,which is equivalent to the treatment effect of open surgery,and does not increase the risk of surgical compli-cations.It has clinical application value.
RESUMEN
Objective To investigate the value of short diameter of lymph nodes combined with neutrophil to lymphocyte ratio(NLR)in evaluating lymph node metastasis of cervical cancer by enhanced CT.Methods A total of 82 patients with cervical cancer were selected and divided into metastatic group(n=13)and non-metastatic group(n=69)according to whether lymph node metas-tasis occurred.The clinicopathological features of the two groups were compared,and the relationship between NLR and clinicopath-ology was analyzed.Logistic regression was used to analyze the influencing factors of lymph node metastasis of cervical cancer.The short diameter of lymph nodes and serum NLR were compared between the two groups.Receiver operating characteristic(ROC)curve,DeLong test and compare the area under the curve(AUC)analysis was used to evaluate the value of lymph node metastasis in cervical cancer.The diagnostic efficacy of the above indexes were compared between the two groups.Results The short diameter of lymph nodes and NLR in the metastatic group were(0.686±0.120)cm and 2.23±0.41 respectively,while thosein the non-metastatic group were(0.602±0.106)cm and 1.76±0.30 respectively.The difference between the two groups was statistically signifi-cant(P＜0.05);There was no significant difference in age,growth pattern and vascular infiltration between the metastatic group and the non-metastatic group(P＞0.05).There were significant differences in clinical stage,maximum diameter of tumor,NLR and short diameter of enhanced CT lymph nodes(P＜0.05);The NLR was related to clinical stage,pelvic lymph node metastasis,and the short diameter of lymph nodes on enhanced CT scan(P＜0.05);Clinical stage Ⅲ,maximum diameter of tumor≥4 cm,NLR＞1.80 and short diameter of enhanced CT lymph nodes≥0.632 cm were independent risk factors for cervical cancer lymph node metastasis(P＜0.05);The ROC curve analysis showed that the AUC of the combined detection of cervical cancer was 0.871,higher than that of the enhanced CT lymph nodes short diameter and serum NLR(0.645,0.795),and its specificity was better than that of the independent detection.The best cutoff values of the enhanced CT lymph nodes short diameter and serum NLR were 0.630 cm and 1.91,respectively.Conclusion The short diameter of lymph nodes and the serum NLR can predict lymph node metastasis of cervical cancer,and the combined detection can improve the evaluation efficiency.
RESUMEN
Objective To explore the correlation between exponential apparent diffusion coefficient(eADC)value before radical hysterectomy and postoperative clinical results in patients with International Federation of Gynecology and Obstetrics(FIGO)stageⅠ/Ⅱ cervical cancer,and to find MR quantitative indicators for predicting the prognosis of patients with early stage cervical cancer.Methods Patients with FIGO stage Ⅰ/Ⅱ cervical cancer who underwent surgical treatment were retrospectively collected.All patients underwent MRI plain scan and diffusion weighted imaging(DWI)scan before surgery.Baseline parameters included age,menopause,stage,tumor size,pathological differentiation and type,lymph node involvement,and postoperative adjuvant therapy.MR parameters included mean apparent diffusion coefficient(ADCmean),normalized apparent diffusion coefficient(nADC),eADC,SIDWI,and SIT2.Baseline and MRI parameters associated with recurrence were determined by Cox regression analysis.Results The progression-free survival(PFS)in the low eADC group was longer than that in the high eADC group(P=0.010).Univariate analysis showed that ADC,nADC and eADC were associated with recurrence(P<0.05).In multivariate analysis,only eADC[hazard ratio(HR)3.610;95%confidence interval(CI)1.467-8.886;P=0.005]was associated with recurrence.Conclusion Preoperative eADC is associated with PFS in patients with surgically treated FIGO stage Ⅰ/Ⅱ cervical cancer and is helpful in evaluating the prognosis of patients with cervical cancer.
RESUMEN
Objective To evaluate MRI and clinicopathological prognostic factors in predicting disease-free survival(DFS)of stage ⅢC1p cervical cancer patients.Methods A total of 102 stage ⅢC1p cervical cancer patients who underwent surgical treatment were selected.Based on survival status,stage ⅢC1p cases were divided into two subgroups:progression group and no progression group.The influencing factors of clinicopathological indexes and MRI features on prognosis in the two groups were analyzed.Results The results of the univariate analysis showed that squamous cell carcinoma antigen(SCC-Ag)level,T stage and location of lymph node metastasis(LNM)were correlated with the prognosis of stage ⅢC1p cervical cancer patients(P<0.05).Multivariate analysis results showed that late T stage,SCC-Ag>13 ng/mL,and LNM location≥3 were the high risk factors affecting the 3-year DFS decline in stage ⅢC1p cervical cancer patients.Conclusion SCC-Ag,T stage,and LNM location are independent risk factors for 3-year DFS in stage ⅢC1p cervical cancer patients.
RESUMEN
Objective To investigate the correlation between intra-and peri-tumoral radiomics features and the response to con-current chemoradiotherapy(CCRT)in cervical squamous cell carcinoma,and to explore the difference of predictive performance between 2D and 3D radiomics models.Methods The imaging data of 132 patients were analyzed retrospectively and randomly divided into training set(n=92)and validation set(n=40).Radiomics features were extracted based on the dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),the correlation analysis and least absolute shrinkage and selection operator(LASSO)algorithm were used for dimensionality reduction and screening,then the radiomics score was calculated and the logistic model was constructed.The receiver operating characteristic(ROC)curve,internal validation of Bootstrap and Brier score were used to evaluate the discrimina-tion and calibration of the model,and the improvement in predictive performance of 3D model compared with 2D model was evaluated by the integrated discrimination improvement(IDI).Results In the training set,the ROC curve showed that the area under the curve(AUC)of the models(2D-intratumoral,3D-intratumoral,3D-peritumoral,3D-combined)ranged from 0.774 to 0.893.The internal validation of Bootstrap showed the AUC were 0.772,0.860,0.847 and 0.888,respectively,while in the validation set,the AUC were 0.757,0.849,0.824 and 0.887,respectively.The Brier scores indicated that the models were well calibrated.In the training set and the validation set,the IDI values were 0.155 and 0.179,respectively,and the differences were statistically significant(P<0.05).Conclusion The radiomics analysis based on the tumor volume can fully explore the tumor heterogeneity.The intra-and peri-tumoral radiomics combined model shows the best predictive performance,which is important to assist clinicians in developing individualized therapies.