Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma

BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Mechanisms of Sophora flavescens in the treatment of cervical squamous cell carcinoma based on comprehensive biological analysis,network pharmacology,and experimental verification

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.

Bone marrow-sparing intensity-modulated radiotherapy for postoperative treatment of cervical cancer

Objective： The aim of this study was to compare bone marrow-sparing intensity-modulated radiotherapy （IMRT） with IMRT without entering pelvic bone marrow as a planning constraint in the treatment of cervical cancer after hysterectomy. Methods： For a cohort of 10 patients, bone marrow-sparing IMRT and routine IMRT planning were designed. The prescribed dose was 45 Gy/1.8 Gy/25f, 95% of the planning target volume received this dose. Doses were computed with a commercially available treatment planning system （TPS） using convolution/superimposition （CS） algorithm. Plans were compared according to dose-volume histogram （DVH） analysis in terms of planning target volume （PTV） homogeneity and conformity indices （HI and CI） as well as organs at risk （OARs） dose and volume parameters. Results： Bone marrow-sparing IMRT had an vantages over routine IMRT in terms of CI, but inferior to the latter for HI. Compared with routine IMRT, V5, Vl0, V20, V30, V40 of pelvic bone marrow of bone marrow-sparing IMRT reduced by 1.81%, 8.61%, 31.81%, 29.50%, 28.29%, respectively. No statistically significant differences were observed between bone marrow-sparing IMRT and routine IMRT in terms of small bowel, bladder and rectum. Conclusion： For patients with cervical cancer after hysterectomy, bone marrowsparing IMRT reduced the pelvic bone marrow volume irradiated at all dose levels and might be conducive to preventing the occurrence of acute bone marrow toxicity.

Expression of HMGB1 Protein in Human Cervical Squamous Epithelium Carcinoma

OBJECTIVE To investigate the expression of the high mobility group boxl（HMGB1） in human cervical squamous epithelial carcinoma （CSEC） and to explore the relationship of HMGB1 expression to the differentiation degree, size, invasion and metastasis of CSEC. METHODS Immunohistochemical staining of tissue microarrays and Western blot analysis were conducted to detect the expression of HMGB1 in the following tissue samples： 30 carcinoma in situ, 90 invasive CSEC without metastasis, 30 invasive CSEC with metastasis, 30 cases of normal cervical squamous epithelia. RESULTS The positive-expression rate of HMGB1 was 58.7% （88/150） in CSEC, showing a significant difference compared to normal cervical squamous epithelia. The expression of HMGB1 was correlated with tumor size, invasion and metastasis of CSEC （respectively, P〈0.01）, but had no relationship with the degree of differentiation （P〉0.05）. CONCLUSION The over-expression of HMGB1 in CSEC might be a useful parameter as an indication of tumor invasion, metastasis, prognosis and overall biological behavior of human CSEC, as well as a noval target site for gene therapy.

The Expression of Apoptosis-Related Genes Bcl-2 and Bax Protein and Apoptosis Positivity in Cervical Carcinoma during Irradiation

To evaluate the apoptosis positivity, the expression of Bcl-2, bax proteinsin 30 patients with squamous cell cervix carcinoma before and after radiotherapy. Methods: By usingimmuno-histochemical and TDT-dUTP nick end labelling techniques, 30 cases of squamous cell cervicalcarcinoma were analyzed. Results: The apoptosis positivity before and after irradiation was 76.7%and 100% respectively, with the difference being significant (P 【 0.05); The positive rates of Bcl-2protein before and after irradiation were 73.3% and 46.7% respectively, with the difference beingsignificant (P 【 0.05); The positive rates of bax protein before and after irradiation were 86% and100% respectively, with the difference being significant (P 【 0.05). Conclusion: bax and Bcl-2protein play an important role in apoptosis induced by fractionated radiation therapy. Apoptosisinduced by irradiation is contributed to upregulation of bax protein or downregulation of Bcl-2protein.

Relationship between Cell Proliferation and Apoptosis in Cervical Carcinoma

Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed, paraffin-embedded tissue sections of normal cervix, cervical intraepithelial neoplasms (GIN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue. The proliferation index (PI) and apoptosis index (AI) were calculated and their correlation with clinical and pathological data was analyzed.Results PI was gradually increased, but the AI and AI/PI ratio decreased from normal cervical epithelium, GIN to cervical carcinoma. There was no significant relationship among cell proliferation, apoptosis, clinical stages and pathological grades. High AI was always associated with a poor prognosis of the patients.Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium, GIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/m L, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/m L, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.

Significant value of 18F-FDG-PET/CT in diagnosing small cervical lymph node metastases in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

Background: Little is known about the nature of metaistasis to small cervical lymph nodes(SCLNS) in the patients with nasopharyngeal carcinoma(NPC)examined by using 18-fluoro-2-deoxy-glucose(^(18)F-FDG) positron emission tomography/computed tomography(PET/CT).The present study aimed to evaluate the diagnostic values of PET/CT in identifying metastasis in SCLNs in NPC patients.Methods: Magnetic resonance images(MRI) and PET/CT scans for 470 patients with newly diagnosed, non-distant metastatic NPC were analyzed. Metastatic rates of SCLNs were defined by the positive number of SCLNs on PET/CT scans and total number of SCLNs on MRI scans. Receiver operating characteristic curve was applied to compare PET/CT-determined stage with MRI-determined stage.Results: In total, 2082 SCLNs were identified, with 808(38.8%) ≥ 5 and < 6 mm in diameter(group A), 526(25.3%)≥ 6 and < 7 mm in diameter(group B),374(18.0%)≥ 7 and < 8 mm in diameter(group C), 237(11.4%) ≥8 and<9 mm in diameter(group D),and 137(6.5%) ≥ 9 and <10 mm in diameter(group E).The overall metastatic rates examined by using PET/CT for groups A, B,C,D, and E were 3.5%, 8.0%, 31.3%, 60.0%, and 83.9%, respectively(P< 0.001). In level IV/Vb, the metastatic rate for nodes ≥ 8 mm was 84.6%. PET/CT examination resulted in modification of N category and overall stage for 135(28.7%) and 46(9.8%) patients, respectively. The areas under curve of MRIdetermined and PET/CT-determined overall stage were 0.659 and 0.704 for predicting overall survival, 0.661 and 0.711 for predicting distant metastasis-free survival, and 0.636 and 0.663 for predicting disease-free survival.Conclusions: PET/CT was more effective than MRI in identifying metastatic SCLNs, and the radiologic diagnostic criteria for metastatic lymph nodes in level IV/Vb should be re-defined.

Clinical and Sonographic Assessment of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma

The purpose of this study was to assess the differences in clinical and sonographic features of papillary thyroid carcinoma（PTC） between cervical lymph node metastatic（CLNM） and nonmetastatic groups.Clinical data of PTC patients（414 patients with 624 malignant nodules） who underwent a preoperative ultrasonography and surgery between June 2010 and March 2015 at Renmin Hospital of Wuhan University were retrospectively analyzed.Clinical factors,preoperative ultrasound features and the final pathological findings were obtained.The differences in the sonographic features of PTC between the CLNM group and the non-CLNM group were analyzed.There were 187 CLNM and 227 non-CLNM patients.The median age at the diagnosis of this cohort was 45.4 years old（ranging from 18 to 77 years）.Ultrasonographic parameters that were significantly associated with CLNM [OR=2.569（1.502,4.393）,P〈0.001）] were as follows：the mulifocality of the nodules,size over 2 cm,the presence of microcalcifications,the distance ratio（DR） pattern showing the contact of the nodules with the thyroid capsule,and the extracapsular spread of the nodules.No significant differences in age,gender,thyroid stimulating hormone（TSH） levels and other ultrasonography parameters were found between the CLNM and the non-CLNM groups.Therefore,our results suggest that a larger size,microcalcifications,mulifocality,and the DR pattern showing the contact of the nodules with the thyroid capsule and extracapsular spread are significantly more indicative of CLNM in PTC.

Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a longterm follow-up

Objective: To investigate the prognostic value of pretreatment human papillomavirus(HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.Methods: We conducted a prospective study on cervical squamous cell carcinoma(SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II(HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy(RH) treatment group and concurrent chemoradiotherapy(CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.Results: A total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics(FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography(LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen(SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival(PFS) were constructed [concordance index(C-index): 0.756, 0.749].Conclusions: A low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.

Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma

BACKGROUND Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC).However,the prognostic and predictive factors remain unclear.AIM To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC.METHODS Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS.In order to assess the predictive factors of PA-TACE benefit,the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model.RESULTS A total of 378 patients (PA-TACE vs surgery alone,189:189) from three centerswere included after a propensity-score 1:1 matching analysis.Compared to the group receiving surgery alone,PA-TACE prolonged the OS rate in patients with resected HCC (P <0.001).The Barcelona Clinic Liver Cancer system and ferritinto-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups.Age (P=0.023) and microscopic vascular invasion (MVI)(P=0.002) were also identified in the PA-TACE group,while gender (P=0.027),hepatitis B virus(P=0.034) and albumin-bilirubin grade (P=0.027) were also selected in the surgery alone group.In addition,PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone)<1].Notably,a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P=0.038) and without MVI (P=0.048).CONCLUSION FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS.Moreover,high FHR and the absence of MVI were important predictive factors,which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

Inhibiting PI3K/Akt Pathway Increases DNA Damage of Cervical Carcinoma HeLa Cells by Drug Radiosensitization

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.

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

EFFECTS OF CURCUMIN ON PROLIFERATION AND APOPTOSIS OF HUMAN CERVICAL CARCINOMA HeLa CELLS IN VITRO

Objective: To investigate the regulatory effect of curcumin on proliferation and apoptosis in human cervical carcinoma cell line HeLa in vitro. Methods: Human cervical carcinoma cell line Hela was cultured in vitro. HeLa cells were treated with 10~50 mmol/L curcumin for 24~72 h and the growth inhibition rates of HeLa cells were measured by MTT method. Cell apoptosis was inspected by electron microscopy. In addition, the expression of bcl-2, bcl-xl and caspase-3 protein in HeLa cell were observed by SP immunohistochemistry. Results: Curcumin inhibited the proliferation of HeLa cells on a dose-depending manner. Peak of subG1 appeared on DNA histogram in FCM. A portion of the cells presented the characteristic morphological changes of apoptosis under the electron microscope. The bcl-2, bcl-xl expression was decreased while Caspase-3 expression was increased. Conclusion: Curcumin could significantly inhibit the growth of HeLa cells; inducing apoptosis through up-regulating Caspase-3 and down-regulating expression of bcl-2 and bcl-xl was probably one of its molecular mechanisms.

Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell

Objective:To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism.Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay.The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively.The activation of Akt/mTOR signaling pathway and expression level of MMP2,MMP9 were assayed by western blot.Results:MTT assay indicated bortezomib(2.5 μM.5 μM,10 μM)could inhibit HeLa cell viability,and the inhibitory rate was highest at 48 h.Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion.Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR.and down-regulate the expression of MMP2 and MMP9.Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell,which might be related to Akt/mTOR signal pathway.

RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia （CIN） and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus （HPV） infection. Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18 infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ （HC-Ⅱ） in normal group （25 cases）, CIN Ⅰ （48 cases）, CIN Ⅱ （56 cases）, CIN Ⅲ（54 cases）, and invasive cervical squamous-cell carcinoma （SCC, 31 cases）. Results The positive rates of cyclin G1 expression in CIN（77.85% ）and SCC cervical tissues （87. 10% ） were significantly higher than normal （ 8.00%, P 〈 0. 01 ）, and the intensities of cyclin G1 expression in CIN（40. 60% ） and SCC cervical tissues （61.51%） were significantly higher than normal （2. 72%, P 〈0.05）. The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups （P 〈 0.05 ）. There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ （Kendall＇s tau-b =0. 316, 0. 269, 0. 352, and 0. 474 in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ, and SCC, respectively, P 〈 0. 05 ）. Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.

Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics

Objective： The high expression of cell division cycle 42 protein （CDC42） may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. Methods： The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues （P〈0.05）. Fttrthermore, the tissues of stage Ⅱ-Ⅳ carcinoma patients showed higher CDC42 expression levels compared to stage I patients （P=0.05）. In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis （P〉0.05）. Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. Conclusions： CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.

Expression of Bmi-1,P16,and CD44v6 in Uterine Cervical Carcinoma and Its Clinical Significance

Objective Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. Tlle present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma （UCC）. Methods A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used ill the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed. Results The expression of Bmi-l, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in tlle cervical neoplasia and normal colorectal mucosa （P〈0.05）. The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis （P〈0.01） and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization （P〈0.05）. Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features （P〉0.05）. The Kaplan-Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients （P〈0.05）. A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC （r=0.419, P=0.001）. Conclusions The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-I and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the expression of CD44v6 in UCC patients. The positive expression of p16 protein is possibly associated with the tumorigenesis, but not with the metastasis or prognosis of UCC.