This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuc...This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuclear cell direct cytotoxicity assay(MTT) in vitro.HeLa cells were treated by cisplatin/docetaxel of 10 percent of IC20 alone or combined with LY294002 for 24 h,and then radiated by different doses of X-ray.The cell survival ratio was obtained by means of clone formation.One-hit multi-target model was fitted to the cell survival curve to calculate dose quasithreshold(Dq),mean lethal dose(D0),2Gy survival fraction(SF2) and sensitization enhancement ratio(SER).The pAkt and total Akt expression was detected by Western blotting and DNA damage by neutro-comet electrophoresis.The HeLa cells were randomly divided into 7 groups in terms of different treatments:Control;radiation treatment(RT) group;LY294002+RT group;cisplatin+RT group;docetaxel+RT group;LY294002+cisplatin+RT group;LY294002+docetaxel+RT group.The apoptosis ratio of each group was measured by flow cytometry.The results showed that docetaxel and cisplatin significantly enhanced the phosphorylation of Akt in radiation-treated HeLa cells.The Dq,D0 and SF2 in LY294002-contained groups were lower than those in docetaxel or cisplatin+RT group.The SER in the LY294002+docetaxel+RT group was 1.35 times that of the docetaxel+RT group,and that in the LY294002+cisplatin+RT group 1.26 times that of the cisplatin+RT group.The Comet electrophoresis showed that tail distance in the LY294002+cisplatin+RT group or LY294002+docetaxel+RT group was longer than in the cisplatin+RT group or docetaxel+RT group.The apoptosis ratio in the LY294002+cisplatin+RT group or LY294002+docetaxel +RT group was higher than in the cisplatin+RT group or docetaxel+RT group.It was concluded that inhibiting PI3K/Akt pathway can increase the effect of docetaxel and cisplatin on the radiosensitivity of HeLa cells and DNA damage resulted from radiation.展开更多
Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi pr...Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.展开更多
Objective To study the expression of a novel inhibitor of apptosis and survivin in cervical carcinoma and its relationship to the expression of Bcl-2.Methods Using SP immunohistochemical technique, we examined the exp...Objective To study the expression of a novel inhibitor of apptosis and survivin in cervical carcinoma and its relationship to the expression of Bcl-2.Methods Using SP immunohistochemical technique, we examined the expression of survivin and Bcl 2 in 59 cervical invasive squamous cell carcinomas.Results Survivin was expressed in 41 of 59 cases(69.5%) of cervical carcinomas. In contrast, no expression of survivin in normal cervical tissues was observed. Overexpression of survivin was related to the tumor grade and clinical stage. Survivin positive cases were strongly associated with Bcl 2 expression(80% versus 35.7%; P <0.005).Conclusion Apoptosis inhibition by survivin abnormal expression, alone or in cooperation with Bcl 2, may participate in the onset and progression of cervical carcinoma. Survivin is a new diagnostic/therapeutic target in cervical cancer.展开更多
Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have develop...Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have developed hybridization, washing and autoradiography conditions that minimize thecross-hybridization among different specific types of HPV so as to allow clear - cut type assignmentthrough practical dot blot hybridization technique using nylon membrane and <sup>35</sup>S - labeled HPV - 16DNA probe. Under these conditions seventeen of thirty （56.7%） of squamous cell carcinomas of thecervix uteri obtained from Tianjin women were detected in the presence of HPV - 16 DNA.展开更多
Objective To investigate the significance of overexpression of p5s and bcl-2 protein in carcinogene- sis of cervix. Methods 10 cases of cervical intraepithelial neoplasis(CIN) and 57 cases of invasive cancer were in- ...Objective To investigate the significance of overexpression of p5s and bcl-2 protein in carcinogene- sis of cervix. Methods 10 cases of cervical intraepithelial neoplasis(CIN) and 57 cases of invasive cancer were in- vestigated with immunohistochemistry technique. Results The overexpresion or P53 protein ir CIN and cervical can- cer was significantly higher than that or control, respectively (P<0.01). But there was no significant difference be- tween CIN and cervical cancer(P>0.05). The immunoreactivity of bcl-2 in CIN was much more higher than that of control (P<0.05). The positive rate and immunoreactivity of bcl-2 in cervical carcinoma were both remarkably high- er than those of control (P<0.0l),but there was no significant difference between CIN and cervical carcinoma (P> 0.05). It was also found that there was a remarkably positive correlation between the overexpression of bcl-2 and P53 (P<0.01). Conclusion Because of the loss of wtP53 function,the expression of bcl-2 can not be down-reguated, which is associated with the pathogenesis and development of cervical carcinoma.展开更多
Objective:To explore correlation between red blood cell distribution width(RDW)and cervical carcinoma.Methods:50 cervical carcinoma patients and 75 healthy controls from the First Affiliated Hospital of Soochow Univer...Objective:To explore correlation between red blood cell distribution width(RDW)and cervical carcinoma.Methods:50 cervical carcinoma patients and 75 healthy controls from the First Affiliated Hospital of Soochow University from June 2020 to December 2020 were involved as the patients group and the control group respectively.Demographic data were collected from routine blood tests and biochemistry examination,the correlation of RDW with hemoglobin(Hb)and c-reactive protein(CRP)was evaluated by Spearman rank correlation,and receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of RDW for cervical carcinoma.Result:The levels of RDW,squamous cell carcinoma antigen(SCCA)and carcinoembryonic antigen(CEA)in patients with cervical carcinoma were higher than those in the controls.The levels of high-density lipoprotein(HDL),Albumin,Prealbumin,Hb,RBC and neuron-specific enolase(NSE)in patients were lower than those in the controls(all P<0.05).There was no statistical significance on the difference in other markers between the two groups(P>0.05).The AUC of RDW in the diagnosis of cervical carcinoma was 0.834.Based on Spearman's rank correlation coefficient analysis,RDW was positively correlated with Hb(r=0.434,P<0.05)and CRP(r=0.366,P<0.05)RDW,and was negatively correlated with hematocrit(r=-0.363,P<0.05),in cervical carcinoma group,cervical carcinoma subgroupⅠ-ⅡandⅢ-Ⅳwere higher than the control group(P<0.05).Conclusions:Elevated RDW is associated with the occurrence of cervical carcinoma,and it may have clinical value in the diagnosis of cervical carcinoma and the course of reaction.展开更多
Exact staging of cervical malignant neoplasms is essential in the selection of the most favorable therapy. MR imaging plays a comprehensive role in primary tumor staging. It monitors response to treatment, detects rec...Exact staging of cervical malignant neoplasms is essential in the selection of the most favorable therapy. MR imaging plays a comprehensive role in primary tumor staging. It monitors response to treatment, detects recurrence and helps in the planning of radiotherapy. Patients with advanced disease usually receive external-beam radiation therapy followed by intracavitary brachytherapy with concurrent chemotherapy. Brachytherapy based on cross-sectional imaging, especially MR imaging, improves local control and overall survival. MRI-based brachytherapy allows accurate positioning of the probe and the depiction of the tumor volume contour, which also permits individualized treatment planning. In order to obtain successful radiation treatment, the radiologist must provide the radiation oncologist with adequate knowledge regarding this technique and its possible complications.展开更多
Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive che...Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive chemoradiotherapy.Methods:Sixty consecutive women diagnosed with uterine cervical cancer FIGO 2009 stage IB1-IVA during 2011-2012 treated with definitive chemoradiotherapy/radiotherapy with curative intent at the Department of Gynaecological Oncology at Karolinska University Hospital were retrospectively included.A review of MRI reports and medical records with focus on follow-up interventions associated to imaging was performed.Results:On follow-up MRI three months post treatment,29/60 women had complete remission(mrCR),24/60 women had partial remission(mrPR)and 7/60 had progressive disease(mrPD).In patients with mrCR,no additional procedures were performed.The group with mrPR had 27 additional MRIs,3 PET/CT examinations and 9 biopsy procedures,none leading to diagnosis of residual tumour.Locoregional control rate was 96%after 6.5 months(median).No patient had cervical relapse only;2/53 had cervical relapse in combination with non-regional lymph nodes and distant relapse.There was no statistically significant difference in overall survival between patients with mrCR and mrPR(HR=2.2,P=0.21).Conclusion:Patients with residual changes on MRI at three months post treatment have a low risk for locoregional recurrence.If this is not recognised,follow-up MRI results in unnecessary additional procedures with low impact on treatment outcome.Further studies are needed regarding the most appropriate imaging modality and timing of post-treatment evaluation.展开更多
BACKGROUND Extramedullary plasmacytoma(EMP),a variant form of myeloma,is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3%of all plasma cell tumors.EMP ...BACKGROUND Extramedullary plasmacytoma(EMP),a variant form of myeloma,is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3%of all plasma cell tumors.EMP can affect various tissues and organs,about 90%of which is found in the head and neck.However,EMP in the reproductive organs is rare,and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings.CASE SUMMARY Herein,we report a case with coexistence of EMP and squamous cell carcinoma in the cervix.The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP.Both ultrasound and pelvic enhanced magnetic resonance imaging(MRI)indicated that there was a tumor in the cervix.Thus,another cervical biopsy and pathological examination were performed,which indicated EMP combined with squamous cell carcinoma.Then,the patient underwent extensive total hysterectomy(type C1)+systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery.During 2-year follow-up,no recurrence was reported.CONCLUSION In conclusion,EMP involving the reproductive system is relatively rare.In this case,MRI,B-ultrasound,and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma.The patient had improved prognosis after appropriate treatments.展开更多
BACKGROUND In recent years,the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles,posing a serious threat to women's physical and mental health.AIM To...BACKGROUND In recent years,the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles,posing a serious threat to women's physical and mental health.AIM To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma.METHODS A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects.They were equally divided into the test group and the control group(60 patients each)with a random number table.The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy,and the control group was treated with concurrent radiotherapy and chemotherapy.We compared the serum thymidine kinase 1(TK1),human epididymis protein 4(HE4),vascular endothelial growth factor(VEGF),and squamous cell carcinoma-associated antigen(SCC-Ag)levels,the clinical effects and survival before and after radiotherapy and chemotherapy,the quality score,and the 3-year follow-up outcomes between the two groups.RESULTS After chemotherapy,the complete remission+partial remission rate was 85.00%in the test group and 68.33%in the control group;the difference was not statistically significant(P>0.05).Before chemotherapy,the serum TK1,HE4,VEGF,and SCC-Ag levels of the two groups were not significantly different(P>0.05).After chemotherapy,the levels of serum TK1(1.27±0.40 pmol/L),HE4(81.4±24.0 pmol/L),VEGF(235.1±38.0 pg/mL),and SCC-Ag(1.76±0.55 ng/mL)were lower than those in the control group[TK1(1.58±0.51 pmol/L),HE4(98.0±28.6)pmol/L,VEGF(284.2±54.1 pg/mL),and SCC-Ag(2.34±0.78 ng/mL)].The difference was statistically significant(P<0.05).Before chemotherapy,there were no significant differences in the physical,role,mood,cognition,social and symptom scale scores of the two groups(P>0.05).After chemotherapy,the physical,role,mood,cognitive and social scores were higher in the test group than in the control group,and the difference was statistically significant(P<0.05).The symptom scale scores of the test group were all lower than those of the control group,and the difference was statistically significant(P<0.05).The 3-year progression-free survival(PFS)rate was 43.33%in the test group and 26.67%in the control group;the overall survival(OS)rate was 48.33%in the test group and 33.33%in the control group;the differences were not statistically significant(P>0.05).The 3-year PFS time of the test group was 20.0 mo,which was longer than that of the control group(15.0 mo),and the difference was significant(P<0.05).The OS time of the test group was 30.0 mo,which was longer than that of the control group(18.0 mo),and the difference was significant(P<0.05).CONCLUSION Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients,prolonging the PFS and OS times of patients,and improving the quality of life.展开更多
BACKGROUND Cervical squamous cell carcinoma(SCC)is the most common type of cervical carcinoma and is generally derived from a precancerous stage called cervical high-grade squamous intraepithelial lesion(HSIL).Usually...BACKGROUND Cervical squamous cell carcinoma(SCC)is the most common type of cervical carcinoma and is generally derived from a precancerous stage called cervical high-grade squamous intraepithelial lesion(HSIL).Usually,the cancer metastasizes through lymphatic or hematogenous dissemination,but rarely spreads upward into the uterus.Here,we report a case of cervical HSIL extending into the endometrium and finally progressing to SCC in the uterine cavity.CASE SUMMARY A 57-year-old postmenopausal woman visited our department and requested a routine cervical check-up.Four years ago,she had undergone a cervical loop electrosurgical excision procedure because of HSIL found during the gynecological examination,and she had not been checked again since.This time,a relapse of the cervical HSIL was diagnosed along with uterine pyometra and endometrial polyps.After 2 wk of antibiotic treatment,a laparoscopic hysterectomy was performed,and the final pathological examination revealed that the cervical HSIL had spread directly upward into the uterine cavity,gradually developing into cervical SCC in the endometrium.CONCLUSION Cervical HSIL/SCC can directly spread upward into the uterus with the most common symptoms of pyometra and cervical stenosis.More attention should be given to the early detection and prevention of this disease.展开更多
Invasive stratified mucin-producing carcinoma(ISMC)is a recently described histologic variant of high-risk human papillomavirus(HPV)-associated endocervical adenocarcinoma,as the putative invasive counterpart of the s...Invasive stratified mucin-producing carcinoma(ISMC)is a recently described histologic variant of high-risk human papillomavirus(HPV)-associated endocervical adenocarcinoma,as the putative invasive counterpart of the stratified mucin-producing intraepithelial lesion(SMILE).ISMC can display variable architectural patterns and usually coexists with other more conventional types of HPV-associated carcinomas,which makes diagnosis and differential diagnosis of ISMC is difficult for pathologists.Moreover,the prognosis of ISMC is still controversial.We analyzed 6 ISMCs with detailed pathological and clinical information.Intraepithelial lesion,including 1 high-grade squamous intraepithelial lesion and 1 SMILE,was found.Various architectures were observed(including nest,glandular,solid,trabecular,and single cell).Nuclear peripheral palisading,apoptotic bodies and mitoses,and variable cytoplasmic mucin vacuoles were seen in all of our cases.The predominance of neutrophils infiltration was seen in only 1 tumor.All the tumors infiltrated the cervical stroma in Silva pattern C manner.p63 and/or p40 was characteristically expressed in the peripheral cells in only 2 cases.High-risk HPV infection was observed in 3/3 detected cases.All the patients were alive during the follow-up time.Recognition of this infrequent tumor may help pathologists and oncologists for an accurate diagnosis and a better understanding of the clinicopathological behavior.展开更多
Objective To examine the differentially expressed invasion-related genes in two anchorage-independent uterine cervical carcinoma cell lines derived from the same patient using a cDNA array. Methods Two human uterine c...Objective To examine the differentially expressed invasion-related genes in two anchorage-independent uterine cervical carcinoma cell lines derived from the same patient using a cDNA array. Methods Two human uterine cervical carcinoma subclonal cell lines CS03 and CS07 derived from a single donor line CS1213 were established by limited dilution procedure. The two cDNA samples retro-transcribed from total RNA derived from CS03 and CS07 cells were screened by a cDNA microarray carrying 234 human cell-cycle related genes and 1011 human signal transduction and membrane receptor-associated genes, scanned with a ScanArray 3000 laser scanner. Results The cDNA microarray analysis showed that 12 genes in CS03 were up-regulated compared to CS07, and 24 genes in CS07 were up-regulated. The function of a number of differentially expressed genes was consistently associated with cell-cycle, cell proliferation, migration, apoptosis, signal transduction and tumor metastasis, including p34 cdc2 , TSC22, plasminogen activator inhibitor I (PAI-1)and desmosome associated protein(Pinin). Conclusion Multiple genes are differentially expressed in uterine cervical carcinoma cell lines even came from the same patient. It is suggested that these genes are involved in the different phenotypic characteristics and development of cervical carcinoma.展开更多
Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Metho...Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Methods:Consistently altered genes involved in cervical squamous cell cancerization were analyzed in the GEO database.The chemical ingredients and target genes of Sophora flavescens were explored using the TCMSP database.We obtained the potential therapeutic targets of Sophora flavescens by intersecting the above genesets and validated them in the GEPIA database.The interaction between Sophora flavescens and target genes was predicted by molecular docking.RT-qPCR was used to verify the changes of target genes in HeLa cells treated with Sophora flavescens.Single-gene GSEA functional analysis were performed to determine the molecular mechanisms.Results:Fifteen genes related to the transformation of cervical squamous cell carcinoma were identified,among which AR and ESR1 were confirmed as targets for kaempferol,wighteone,formononetin,and phaseolinon.These compounds are the active ingredients in Sophora flavescens.Low expressions of AR and ESR1 correlate with a poor prognosis,while Sophora flavescens treatment increases the expression of AR and ESR1 in HeLa.GSEA analysis showed that AR and ESR1 mainly participate in the epithelial-mesenchymal transition in cervical squamous cell carcinoma.Conclusion:Sophora flavescens exert anti-tumor effects by targeting AR and ESR1,which may regulate cancer metastasis.展开更多
Objective To observe the expression of RAR-β gene in SiHa, HeLa,C33A and CasKi cell lines of cervical carcinoma and to investigate the role of methylated RAR-β in its expressive defection. Methods Reverse transcript...Objective To observe the expression of RAR-β gene in SiHa, HeLa,C33A and CasKi cell lines of cervical carcinoma and to investigate the role of methylated RAR-β in its expressive defection. Methods Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression of RAR-β gene. Immunohistochemistry and Western Blot were used to analyze the protein expression of RAR-β gene in four cervical cancer cell lines as well as the influence of 5-Aza-cdR on gene expressive defection. Methylation specific PCR (MSP) was used to detect whether there was the methylation in RAR-β gene in four cell lines. The change of RAR-β gene methylation state was also observed by MSP. The cell proliferation rate influenced by the 5-Aza-cdR was observed by MTT assay. Results The expression of RAR-β mRNA and protein in SiHa, HeLa and CasKi cell lines of cervical cancer was silent or decreased, whereas its expression was detected in C33A cell line. By using MSP method, it was found that there was RAR-β gene methylation in those three cell lines, whereas there was no RAR-β gene methylation in C33A cell line. After treated with the 5-Aza-cdR, methylated RAR-β gene was partly demethylated, and RAR-β mRNA and protein were re-expressed in the previous three cell lines in which RAR-β gene expression was silent or decreased. The 5-Aza-cdR treatment could supress cell proliferation as well. Conclusion The RAR-β gene expressive defection plays an important role in the carcinogenesis of cervical cancer. The abnormal RAR-β gene methylation in the the promotor region has an important role in gene expressive defection. The cell proliferation can be supressed by demethylated treatment.展开更多
In this study,40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi’an Jiaotong University,China,were retrospectively assessed using immunohistochemistry for CD4^(+) and CD8...In this study,40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi’an Jiaotong University,China,were retrospectively assessed using immunohistochemistry for CD4^(+) and CD8^(+) tumor-infiltrating lymphocytes(TILs)and were analyzed for the expression of FOXP3,OX40,granzyme B(GrB)and perforin(Prf).The proliferating index of the TILs was determined by assessing Ki67 expression.We determined the prognostic value of low and high numbers of TILs on survival by performing Kaplan–Meier analysis using median values as the cut-off points.Except for the number of CD4^(+)FOXP3^(+) regulatory T cells(Tregs)and the CD4/CD8 ratio,none of the CD4^(+),CD8^(+),OX401,GrB^(+) or Prf^(+) TILs were associated with the overall 5-year survival rate.The 5-year survival rate was significantly lower in patients who had a high percentage of Tregs as compared with the those who had a lower percentage(35.3%versus 88.9%,P50.001),while the 5-year survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared with patients who had a low CD4/CD8 ratio(82.4%versus 44.4%,P50.029).When we considered the deaths and surviving cases as separate groups,we found that both the number of CD4^(+) T cells and the CD4/CD8 ratio were significantly lower in patients who died as compared with those who survived(26.33±11.80 versus 47.79±38.18,P=0.023 and 0.60±0.25 versus 1.17±1.02,P=0.019,respectively).In conclusion,decreased proportions of tumor-infiltrating CD4^(+) T cells with high percentages of Tregs and reversed CD4/CD8 ratios were significantly associated with the clinical outcome of patients with cervical carcinoma.展开更多
基金supported by grants from the Hubei Province Natural Sciences Foundation (No.2008cdb133)Science Foundation for The Youth Scholars of Ministry of Education of China (No.200804871034)
文摘This study examined the role of PI3K/Akt pathway in radiosensitization of DNA damage of cervical carcinoma cells.The 50% inhibition concentration(IC50) of cisplatin and docetaxel in HeLa cells was detected by Mono-nuclear cell direct cytotoxicity assay(MTT) in vitro.HeLa cells were treated by cisplatin/docetaxel of 10 percent of IC20 alone or combined with LY294002 for 24 h,and then radiated by different doses of X-ray.The cell survival ratio was obtained by means of clone formation.One-hit multi-target model was fitted to the cell survival curve to calculate dose quasithreshold(Dq),mean lethal dose(D0),2Gy survival fraction(SF2) and sensitization enhancement ratio(SER).The pAkt and total Akt expression was detected by Western blotting and DNA damage by neutro-comet electrophoresis.The HeLa cells were randomly divided into 7 groups in terms of different treatments:Control;radiation treatment(RT) group;LY294002+RT group;cisplatin+RT group;docetaxel+RT group;LY294002+cisplatin+RT group;LY294002+docetaxel+RT group.The apoptosis ratio of each group was measured by flow cytometry.The results showed that docetaxel and cisplatin significantly enhanced the phosphorylation of Akt in radiation-treated HeLa cells.The Dq,D0 and SF2 in LY294002-contained groups were lower than those in docetaxel or cisplatin+RT group.The SER in the LY294002+docetaxel+RT group was 1.35 times that of the docetaxel+RT group,and that in the LY294002+cisplatin+RT group 1.26 times that of the cisplatin+RT group.The Comet electrophoresis showed that tail distance in the LY294002+cisplatin+RT group or LY294002+docetaxel+RT group was longer than in the cisplatin+RT group or docetaxel+RT group.The apoptosis ratio in the LY294002+cisplatin+RT group or LY294002+docetaxel +RT group was higher than in the cisplatin+RT group or docetaxel+RT group.It was concluded that inhibiting PI3K/Akt pathway can increase the effect of docetaxel and cisplatin on the radiosensitivity of HeLa cells and DNA damage resulted from radiation.
基金The study was supported by National Natural Science Foundation of China (No.39970035) .
文摘Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.
文摘Objective To study the expression of a novel inhibitor of apptosis and survivin in cervical carcinoma and its relationship to the expression of Bcl-2.Methods Using SP immunohistochemical technique, we examined the expression of survivin and Bcl 2 in 59 cervical invasive squamous cell carcinomas.Results Survivin was expressed in 41 of 59 cases(69.5%) of cervical carcinomas. In contrast, no expression of survivin in normal cervical tissues was observed. Overexpression of survivin was related to the tumor grade and clinical stage. Survivin positive cases were strongly associated with Bcl 2 expression(80% versus 35.7%; P <0.005).Conclusion Apoptosis inhibition by survivin abnormal expression, alone or in cooperation with Bcl 2, may participate in the onset and progression of cervical carcinoma. Survivin is a new diagnostic/therapeutic target in cervical cancer.
文摘Accurate typing of the different human papillomavirus types is csscntial in view of the differ-ent pathological potential of the common virus types of human papillomavirus （HPV） present in thecervix. We have developed hybridization, washing and autoradiography conditions that minimize thecross-hybridization among different specific types of HPV so as to allow clear - cut type assignmentthrough practical dot blot hybridization technique using nylon membrane and <sup>35</sup>S - labeled HPV - 16DNA probe. Under these conditions seventeen of thirty （56.7%） of squamous cell carcinomas of thecervix uteri obtained from Tianjin women were detected in the presence of HPV - 16 DNA.
文摘Objective To investigate the significance of overexpression of p5s and bcl-2 protein in carcinogene- sis of cervix. Methods 10 cases of cervical intraepithelial neoplasis(CIN) and 57 cases of invasive cancer were in- vestigated with immunohistochemistry technique. Results The overexpresion or P53 protein ir CIN and cervical can- cer was significantly higher than that or control, respectively (P<0.01). But there was no significant difference be- tween CIN and cervical cancer(P>0.05). The immunoreactivity of bcl-2 in CIN was much more higher than that of control (P<0.05). The positive rate and immunoreactivity of bcl-2 in cervical carcinoma were both remarkably high- er than those of control (P<0.0l),but there was no significant difference between CIN and cervical carcinoma (P> 0.05). It was also found that there was a remarkably positive correlation between the overexpression of bcl-2 and P53 (P<0.01). Conclusion Because of the loss of wtP53 function,the expression of bcl-2 can not be down-reguated, which is associated with the pathogenesis and development of cervical carcinoma.
基金National Natural Science Foundation of China(No.81873431)。
文摘Objective:To explore correlation between red blood cell distribution width(RDW)and cervical carcinoma.Methods:50 cervical carcinoma patients and 75 healthy controls from the First Affiliated Hospital of Soochow University from June 2020 to December 2020 were involved as the patients group and the control group respectively.Demographic data were collected from routine blood tests and biochemistry examination,the correlation of RDW with hemoglobin(Hb)and c-reactive protein(CRP)was evaluated by Spearman rank correlation,and receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of RDW for cervical carcinoma.Result:The levels of RDW,squamous cell carcinoma antigen(SCCA)and carcinoembryonic antigen(CEA)in patients with cervical carcinoma were higher than those in the controls.The levels of high-density lipoprotein(HDL),Albumin,Prealbumin,Hb,RBC and neuron-specific enolase(NSE)in patients were lower than those in the controls(all P<0.05).There was no statistical significance on the difference in other markers between the two groups(P>0.05).The AUC of RDW in the diagnosis of cervical carcinoma was 0.834.Based on Spearman's rank correlation coefficient analysis,RDW was positively correlated with Hb(r=0.434,P<0.05)and CRP(r=0.366,P<0.05)RDW,and was negatively correlated with hematocrit(r=-0.363,P<0.05),in cervical carcinoma group,cervical carcinoma subgroupⅠ-ⅡandⅢ-Ⅳwere higher than the control group(P<0.05).Conclusions:Elevated RDW is associated with the occurrence of cervical carcinoma,and it may have clinical value in the diagnosis of cervical carcinoma and the course of reaction.
文摘Exact staging of cervical malignant neoplasms is essential in the selection of the most favorable therapy. MR imaging plays a comprehensive role in primary tumor staging. It monitors response to treatment, detects recurrence and helps in the planning of radiotherapy. Patients with advanced disease usually receive external-beam radiation therapy followed by intracavitary brachytherapy with concurrent chemotherapy. Brachytherapy based on cross-sectional imaging, especially MR imaging, improves local control and overall survival. MRI-based brachytherapy allows accurate positioning of the probe and the depiction of the tumor volume contour, which also permits individualized treatment planning. In order to obtain successful radiation treatment, the radiologist must provide the radiation oncologist with adequate knowledge regarding this technique and its possible complications.
文摘Aim:The aim of this study was to evaluate the impact of MRI performed three months after treatment on further follow-up interventions and outcome in patients with uterine cervical carcinoma treated with definitive chemoradiotherapy.Methods:Sixty consecutive women diagnosed with uterine cervical cancer FIGO 2009 stage IB1-IVA during 2011-2012 treated with definitive chemoradiotherapy/radiotherapy with curative intent at the Department of Gynaecological Oncology at Karolinska University Hospital were retrospectively included.A review of MRI reports and medical records with focus on follow-up interventions associated to imaging was performed.Results:On follow-up MRI three months post treatment,29/60 women had complete remission(mrCR),24/60 women had partial remission(mrPR)and 7/60 had progressive disease(mrPD).In patients with mrCR,no additional procedures were performed.The group with mrPR had 27 additional MRIs,3 PET/CT examinations and 9 biopsy procedures,none leading to diagnosis of residual tumour.Locoregional control rate was 96%after 6.5 months(median).No patient had cervical relapse only;2/53 had cervical relapse in combination with non-regional lymph nodes and distant relapse.There was no statistically significant difference in overall survival between patients with mrCR and mrPR(HR=2.2,P=0.21).Conclusion:Patients with residual changes on MRI at three months post treatment have a low risk for locoregional recurrence.If this is not recognised,follow-up MRI results in unnecessary additional procedures with low impact on treatment outcome.Further studies are needed regarding the most appropriate imaging modality and timing of post-treatment evaluation.
基金Science and Technology Project of Zunyi City and The First People's Hospital of Zunyi,No.187,2018.
文摘BACKGROUND Extramedullary plasmacytoma(EMP),a variant form of myeloma,is a rare solid plasma cell tumor that originates from the bone marrow hematopoietic tissue and accounts for about 3%of all plasma cell tumors.EMP can affect various tissues and organs,about 90%of which is found in the head and neck.However,EMP in the reproductive organs is rare,and is difficult to be distinguished from other primary or metastatic genital tumors according to clinical symptoms and imaging findings.CASE SUMMARY Herein,we report a case with coexistence of EMP and squamous cell carcinoma in the cervix.The first histopathological report of neoplasms on the surface of the cervix and vagina showed an EMP.Both ultrasound and pelvic enhanced magnetic resonance imaging(MRI)indicated that there was a tumor in the cervix.Thus,another cervical biopsy and pathological examination were performed,which indicated EMP combined with squamous cell carcinoma.Then,the patient underwent extensive total hysterectomy(type C1)+systemic lymph node dissection and received 25 external pelvic irradiations with a dose of 50 Gy following surgery.During 2-year follow-up,no recurrence was reported.CONCLUSION In conclusion,EMP involving the reproductive system is relatively rare.In this case,MRI,B-ultrasound,and cervical canal scraping were used to further determine the diagnosis of EMP combined with squamous cell carcinoma.The patient had improved prognosis after appropriate treatments.
文摘BACKGROUND In recent years,the incidence of cervical cancer has increased with increasing life pressures and changes in women's social roles,posing a serious threat to women's physical and mental health.AIM To explore the clinical effect of Endo combined with concurrent radiotherapy and chemotherapy in the treatment of advanced cervical squamous cell carcinoma.METHODS A total of 120 patients admitted to the oncology department of our hospital were selected as the research subjects.They were equally divided into the test group and the control group(60 patients each)with a random number table.The test group was treated with Endo combined with concurrent radiotherapy and chemotherapy,and the control group was treated with concurrent radiotherapy and chemotherapy.We compared the serum thymidine kinase 1(TK1),human epididymis protein 4(HE4),vascular endothelial growth factor(VEGF),and squamous cell carcinoma-associated antigen(SCC-Ag)levels,the clinical effects and survival before and after radiotherapy and chemotherapy,the quality score,and the 3-year follow-up outcomes between the two groups.RESULTS After chemotherapy,the complete remission+partial remission rate was 85.00%in the test group and 68.33%in the control group;the difference was not statistically significant(P>0.05).Before chemotherapy,the serum TK1,HE4,VEGF,and SCC-Ag levels of the two groups were not significantly different(P>0.05).After chemotherapy,the levels of serum TK1(1.27±0.40 pmol/L),HE4(81.4±24.0 pmol/L),VEGF(235.1±38.0 pg/mL),and SCC-Ag(1.76±0.55 ng/mL)were lower than those in the control group[TK1(1.58±0.51 pmol/L),HE4(98.0±28.6)pmol/L,VEGF(284.2±54.1 pg/mL),and SCC-Ag(2.34±0.78 ng/mL)].The difference was statistically significant(P<0.05).Before chemotherapy,there were no significant differences in the physical,role,mood,cognition,social and symptom scale scores of the two groups(P>0.05).After chemotherapy,the physical,role,mood,cognitive and social scores were higher in the test group than in the control group,and the difference was statistically significant(P<0.05).The symptom scale scores of the test group were all lower than those of the control group,and the difference was statistically significant(P<0.05).The 3-year progression-free survival(PFS)rate was 43.33%in the test group and 26.67%in the control group;the overall survival(OS)rate was 48.33%in the test group and 33.33%in the control group;the differences were not statistically significant(P>0.05).The 3-year PFS time of the test group was 20.0 mo,which was longer than that of the control group(15.0 mo),and the difference was significant(P<0.05).The OS time of the test group was 30.0 mo,which was longer than that of the control group(18.0 mo),and the difference was significant(P<0.05).CONCLUSION Endo combined with concurrent radiotherapy and chemotherapy for the treatment of advanced cervical squamous cell carcinoma has a positive effect on reducing the level of tumor markers in patients,prolonging the PFS and OS times of patients,and improving the quality of life.
文摘BACKGROUND Cervical squamous cell carcinoma(SCC)is the most common type of cervical carcinoma and is generally derived from a precancerous stage called cervical high-grade squamous intraepithelial lesion(HSIL).Usually,the cancer metastasizes through lymphatic or hematogenous dissemination,but rarely spreads upward into the uterus.Here,we report a case of cervical HSIL extending into the endometrium and finally progressing to SCC in the uterine cavity.CASE SUMMARY A 57-year-old postmenopausal woman visited our department and requested a routine cervical check-up.Four years ago,she had undergone a cervical loop electrosurgical excision procedure because of HSIL found during the gynecological examination,and she had not been checked again since.This time,a relapse of the cervical HSIL was diagnosed along with uterine pyometra and endometrial polyps.After 2 wk of antibiotic treatment,a laparoscopic hysterectomy was performed,and the final pathological examination revealed that the cervical HSIL had spread directly upward into the uterine cavity,gradually developing into cervical SCC in the endometrium.CONCLUSION Cervical HSIL/SCC can directly spread upward into the uterus with the most common symptoms of pyometra and cervical stenosis.More attention should be given to the early detection and prevention of this disease.
基金the Scientific Research Funds Project of the Science and Technology Department of Sichuan Province(Grant No.21YYJC1616 to Liu Y).
文摘Invasive stratified mucin-producing carcinoma(ISMC)is a recently described histologic variant of high-risk human papillomavirus(HPV)-associated endocervical adenocarcinoma,as the putative invasive counterpart of the stratified mucin-producing intraepithelial lesion(SMILE).ISMC can display variable architectural patterns and usually coexists with other more conventional types of HPV-associated carcinomas,which makes diagnosis and differential diagnosis of ISMC is difficult for pathologists.Moreover,the prognosis of ISMC is still controversial.We analyzed 6 ISMCs with detailed pathological and clinical information.Intraepithelial lesion,including 1 high-grade squamous intraepithelial lesion and 1 SMILE,was found.Various architectures were observed(including nest,glandular,solid,trabecular,and single cell).Nuclear peripheral palisading,apoptotic bodies and mitoses,and variable cytoplasmic mucin vacuoles were seen in all of our cases.The predominance of neutrophils infiltration was seen in only 1 tumor.All the tumors infiltrated the cervical stroma in Silva pattern C manner.p63 and/or p40 was characteristically expressed in the peripheral cells in only 2 cases.High-risk HPV infection was observed in 3/3 detected cases.All the patients were alive during the follow-up time.Recognition of this infrequent tumor may help pathologists and oncologists for an accurate diagnosis and a better understanding of the clinicopathological behavior.
文摘Objective To examine the differentially expressed invasion-related genes in two anchorage-independent uterine cervical carcinoma cell lines derived from the same patient using a cDNA array. Methods Two human uterine cervical carcinoma subclonal cell lines CS03 and CS07 derived from a single donor line CS1213 were established by limited dilution procedure. The two cDNA samples retro-transcribed from total RNA derived from CS03 and CS07 cells were screened by a cDNA microarray carrying 234 human cell-cycle related genes and 1011 human signal transduction and membrane receptor-associated genes, scanned with a ScanArray 3000 laser scanner. Results The cDNA microarray analysis showed that 12 genes in CS03 were up-regulated compared to CS07, and 24 genes in CS07 were up-regulated. The function of a number of differentially expressed genes was consistently associated with cell-cycle, cell proliferation, migration, apoptosis, signal transduction and tumor metastasis, including p34 cdc2 , TSC22, plasminogen activator inhibitor I (PAI-1)and desmosome associated protein(Pinin). Conclusion Multiple genes are differentially expressed in uterine cervical carcinoma cell lines even came from the same patient. It is suggested that these genes are involved in the different phenotypic characteristics and development of cervical carcinoma.
基金In 2021,Wuxi Medical Innovation Team CXTD2021023,Jiangsu Province maternal and Child Health research key funding project F201915.
文摘Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Methods:Consistently altered genes involved in cervical squamous cell cancerization were analyzed in the GEO database.The chemical ingredients and target genes of Sophora flavescens were explored using the TCMSP database.We obtained the potential therapeutic targets of Sophora flavescens by intersecting the above genesets and validated them in the GEPIA database.The interaction between Sophora flavescens and target genes was predicted by molecular docking.RT-qPCR was used to verify the changes of target genes in HeLa cells treated with Sophora flavescens.Single-gene GSEA functional analysis were performed to determine the molecular mechanisms.Results:Fifteen genes related to the transformation of cervical squamous cell carcinoma were identified,among which AR and ESR1 were confirmed as targets for kaempferol,wighteone,formononetin,and phaseolinon.These compounds are the active ingredients in Sophora flavescens.Low expressions of AR and ESR1 correlate with a poor prognosis,while Sophora flavescens treatment increases the expression of AR and ESR1 in HeLa.GSEA analysis showed that AR and ESR1 mainly participate in the epithelial-mesenchymal transition in cervical squamous cell carcinoma.Conclusion:Sophora flavescens exert anti-tumor effects by targeting AR and ESR1,which may regulate cancer metastasis.
文摘Objective To observe the expression of RAR-β gene in SiHa, HeLa,C33A and CasKi cell lines of cervical carcinoma and to investigate the role of methylated RAR-β in its expressive defection. Methods Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression of RAR-β gene. Immunohistochemistry and Western Blot were used to analyze the protein expression of RAR-β gene in four cervical cancer cell lines as well as the influence of 5-Aza-cdR on gene expressive defection. Methylation specific PCR (MSP) was used to detect whether there was the methylation in RAR-β gene in four cell lines. The change of RAR-β gene methylation state was also observed by MSP. The cell proliferation rate influenced by the 5-Aza-cdR was observed by MTT assay. Results The expression of RAR-β mRNA and protein in SiHa, HeLa and CasKi cell lines of cervical cancer was silent or decreased, whereas its expression was detected in C33A cell line. By using MSP method, it was found that there was RAR-β gene methylation in those three cell lines, whereas there was no RAR-β gene methylation in C33A cell line. After treated with the 5-Aza-cdR, methylated RAR-β gene was partly demethylated, and RAR-β mRNA and protein were re-expressed in the previous three cell lines in which RAR-β gene expression was silent or decreased. The 5-Aza-cdR treatment could supress cell proliferation as well. Conclusion The RAR-β gene expressive defection plays an important role in the carcinogenesis of cervical cancer. The abnormal RAR-β gene methylation in the the promotor region has an important role in gene expressive defection. The cell proliferation can be supressed by demethylated treatment.
基金This study was supported by the Higher Education Commission of Pakistan and the Foundation of Bureau of Health(Grant No.04D13)of Shaanxi Province,China.
文摘In this study,40 biopsy samples collected from cervical cancer patients at the First Affiliated Hospital of Xi’an Jiaotong University,China,were retrospectively assessed using immunohistochemistry for CD4^(+) and CD8^(+) tumor-infiltrating lymphocytes(TILs)and were analyzed for the expression of FOXP3,OX40,granzyme B(GrB)and perforin(Prf).The proliferating index of the TILs was determined by assessing Ki67 expression.We determined the prognostic value of low and high numbers of TILs on survival by performing Kaplan–Meier analysis using median values as the cut-off points.Except for the number of CD4^(+)FOXP3^(+) regulatory T cells(Tregs)and the CD4/CD8 ratio,none of the CD4^(+),CD8^(+),OX401,GrB^(+) or Prf^(+) TILs were associated with the overall 5-year survival rate.The 5-year survival rate was significantly lower in patients who had a high percentage of Tregs as compared with the those who had a lower percentage(35.3%versus 88.9%,P50.001),while the 5-year survival rate was significantly higher in patients with a high CD4/CD8 ratio as compared with patients who had a low CD4/CD8 ratio(82.4%versus 44.4%,P50.029).When we considered the deaths and surviving cases as separate groups,we found that both the number of CD4^(+) T cells and the CD4/CD8 ratio were significantly lower in patients who died as compared with those who survived(26.33±11.80 versus 47.79±38.18,P=0.023 and 0.60±0.25 versus 1.17±1.02,P=0.019,respectively).In conclusion,decreased proportions of tumor-infiltrating CD4^(+) T cells with high percentages of Tregs and reversed CD4/CD8 ratios were significantly associated with the clinical outcome of patients with cervical carcinoma.
