Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Evaluation of the Factors Associated with Delay in Initiation of Treatment of Advanced Stage Cervical Cancer Patients in Bangladesh

Research Background: Cervical cancer is the second most common cancer in women and the third leading cause of female cancer death in Bangladesh. Delay in initiation of treatment in advanced stage cervical cancer patients is an important modifiable risk factor for cancer-related mortality. Identifying elements associated with delay of diagnosis will help reduce barriers to timely treatment of cervical cancer. Research Objectives: The objective of this study was to analyze the factors leading to delay in diagnosis and treatment of women with advanced stage cervical cancer. Methods: A cross-sectional observational study analyzed the factors associated with delay in initiation of treatment for 138 patients with advanced-stage cervical cancer from November 2019 to October 2020 at the National Institute of Cancer Research and Hospital (NICRH) in Dhaka, Bangladesh. Advanced-stage cervical cancer patients between the ages of 30 to 70 years were included in this study. Face-to-face interviews with the participants used a predesigned data collection sheet. In this study, three components of delay were identified: primary delay due to patient factors, healthcare provider delay, and healthcare-system infrastructure delay. Factors associated with delay were the independent variables and durations of delay were the outcome variables. Descriptive statistics were expressed as mean + standard deviation, median, percentage, and frequency. Results: One hundred and thirty-eight patients with advanced stage cervical cancer were included in the study. The mean age of the patients was 48.74 (±9.57) years. Thirty-four percent of patients were illiterate. More than half (57.25%) of the patients were from lower middle-class families. Delays were categorized as patient-related, healthcare provider delay, and healthcare-system infrastructure related. Patient-related factors included low monthly income, residence in a rural area, embarrassment, fear, lack of knowledge regarding cervical cancer, delay in contacting a spouse, family member or friend prior to the first medical encounter. These elements predicted a primary delay of more than 60 days (P value Conclusion: Three broad categories of delay in diagnosis and treatment of cervical cancer: patient-related factors, healthcare provider-related factors, and healthcare-system infrastructure factors were analyzed. Illiteracy, lack of awareness regarding cervical cancer, lack of health-seeking behavior, and poor income status were associated with patient-related primary delay. Nonperformance of speculum examination in the initial consultation, misdiagnosis, inappropriate management, and delay in referral to the cancer treatment center by primary healthcare providers were the contributing factors for healthcare provider delay. Lack of availability and accessibility of health services and limitation of radiotherapy resources led to healthcare-system infrastructure delays. All three categories of delay must be addressed through the education of communities, the gynecologic training of community healthcare providers, the improvement of medical infrastructure, and the increase of medical resources.

Association between Pretreatment Levels of Serum Vascular Endothelial Growth Factor (VEGF) and Survival Outcomes in Locally Advanced Cervical Cancer Patients

Objective: To evaluate the association between pretreatment levels of serum vascular endothelial growth factor (VEGF) and long-term treatment outcomes in patients with locally advanced cervical cancer (LACC). Methods: Thirty-nine patients diagnosed with LACC (stage IIB-IVA) and obtaining blood for serum VEGF were identified. All patients received complete treatment as radical radiotherapy with or without concurrent chemotherapy. Surveillance for all patients was every 3 months during the first 2 years, and every 6 months later. Results: Mean age of 39 patients was 52.3 ± 10.8 years old. Twenty-three patients (59.0%) had stage IIB, and 16 patients (41.0%) had stage IIIB. Histological cell type was mostly squamous cell carcinoma (89.7%). The median and 75th percentile level of serum VEGF were 610.2 pg/ml (0.0 - 4067.2 pg/ml) and 825.6 pg/ml, respectively. At median follow-up of 37.0 months (range, 26.8 - 46.3 months), the 3-year OS rate was 78.6%. Clinical stage (p = 0.04) and 75th percentile of VEGF level (p = 0.04) were impacted on OS in univariable analysis. The 3-year OS of patients in stage IIB with serum VEGF of ≤825.6 pg/ml and of > 825.6 pg/ml was slightly different, 94.4% and 80.0% respectively (p = 0.34), whereas there were many differences in stage IIIB, 71.4% and 25.0% in patients with serum VEGF of ≤825.6 pg/ml and of >825.6 pg/ml respectively (p = 0.05). Conclusion: High pretreatment serum VEGF level has an influence on OS for LACC. It is potentially used as a predictive factor, especially in patients stage IIIB, in order to provide efficient treatment and improve survival outcomes in the future.

Neoadjuvant intra-arterial infusion chemotherapy followed by surgery in patients with locally advanced cervical cancer

Objective： The aim of this study was to investigate the role of preoperative neoadjuvant intra-arterial infusion chemotherapy （NAIC） in treating locally advanced cervical caner. Methods： Nineteen locally advanced cervical cancer （LACC） patients from November 2003 to November 2005 were analyzed retrospectively. NAIC was administrated 2 courses every 2 weeks using a combination of 30 mg/m^2 bleomycin and 50 mg/m^2 cisplatin via bilateral femur artedes. The response to NAIC was assessed by pelvic examination and imaging diagnostics and histological analysis. Two weeks after NAIC radical hysterectomy with pelvic lymphadenectomy was performed. Results： Radical hysterectomy with pelvic lymphadenectomy were performed in 18 patients successfully. The mean tumor reduction rate was 73.04%. The overall clinical response rate of NAIC was 84.2% with 2 complete responses and 16 partial responses. Only 1 nonresponder. Six of 7 cases who had parametrial infiltration had a absence after chemotherapy, no significant change was observed in 1 case who followed by radiotherapy. Multivariate logistic regression analysis indicated that tumor volume prior to treatment was determining factor affecting the efficacy of NAIC in LACC. Conclusion： pre-operative NAIC inhibited the growth of LACC, minimized the size, eliminate effectively the pathologic dsk factors in the pelvic cavity, to improve the operability in cervical cancer patients with stage lib or above, considered inoperable.

Effect of preoperative hyperselective uterine arterial chemoembolization on the infiltrative growth of cancer cells in locally advanced cervical cancer

Objective:To study the effect of preoperative hyperselective uterine arterial chemoembolization on the infiltrative growth of cancer cells in locally advanced cervical cancer.Methods: Patients with locally advanced cervical cancer who underwent surgical resection in Ankang Municipality Maternity and Child Care between February 2015 and October 2017 were selected and randomly divided into the observation group who received preoperative hyperselective uterine arterial chemoembolization and the control group who received routine preoperative preparation. The contents of tumor markers in serum were determined at diagnosis and 1 day before undergoing surgery;the expression levels of tumor suppressor genes and invasion genes were determined after surgical resection.Results: 1 day before undergoing surgery, serum CA125, TSGF, SCC and HE4 levels of observation group were lower than those at diagnosis whereas serum CA125, TSGF, SCC and HE4 levels of control group were not significant different from those at diagnosis;after surgical resection, RASSF2A, FHIT, eIF4E3, RIZ1, DAPK and Syk protein expression in cervical cancer lesions of observation group were significantly higher than those of control group;whereas RbAp48, Vimentin, N-cadherin, Sox2,β-catenin and MMP9 protein expression were significantly lower than those of control group.Conclusion: Preoperative hyperselective uterine arterial chemoembolization can inhibit the infiltrative growth of cancer cells in locally advanced cervical cancer.

Effect of cisplatin-based concurrent radiochemotherapy on malignant degree of advanced cervical cancer and expression of proto-oncogene and tumor suppressor genes

Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.

Assessment of the serum tumor markers and lesion cancer cell proliferation after Nimotuzumab combined with cisplatin and radiotherapy treatment of middle-advanced cervical cancer

Objective:To study the change of serum tumor markers and lesion cancer cell proliferation gene expression after Nimotuzumab combined with cisplatin and radiotherapy treatment of middle-advanced cervical cancer.Methods:A total of 78 patients with middle-advanced cervical cancer who were treated in our hospital between August 2013 and February 2016 were collected and divided into the control group (n=39) who received routine radiotherapy and chemotherapy and the observation group (n=39) who received Nimotuzumab combined with cisplatin and radiotherapy according to the single-blind randomized control method, and both groups were treated for 6 weeks. Before treatment and after 6 weeks of treatment, enzyme-linked immunosorbent assay (ELISA) was used to detect serum tumor marker levels, and fluorescence quantitative PCR method was used to detect the lesion proliferation gene mRNA expression.Results: Before treatment, the differences in serum tumor marker levels and lesion proliferation gene mRNA expression were not statistically significant between two groups of group. After 6 weeks of treatment, serum tumor markers SCC, CA125 and CA19-9 levels of observation group were lower than those of control group, lesion pro-proliferation genes B7-H4, HIF-1α, Sp2 and PCNA mRNA expression were lower than those of control group, and lesion anti-proliferation genes PTEN, FHIT and STC1 mRNA expression were higher than those of control group.Conclusion: Nimotuzumab combined with cisplatin and radiotherapy can effectively reduce the serum tumor marker levels, and also inhibit the lesion cancer cell proliferation in patients with middle-advanced cervical cancer.

Specific Immunotherapy in Advanced Cervical-Uterine Cancer Using Humanized Monoclonal Antibody Nimotuzumab and CIMAvax-EGF^®Therapeutic Vaccine

Cervical uterine cancer represents the fourth most common malignant neoplasm worldwide in the female sex in terms of incidence, principally from epithelial origen. The high expression of EGFR in this tumor leads to the search for therapeutic alternatives. An Expanded Access Clinical Program was carried out in parallel groups, randomized, multicenter and prospective study, to evaluate the survival of patients with advanced cervical carcinoma, without therapeutic alternative, who would be treated with the therapeutic vaccine CIMAvax-EGF®, the humanized mAb nimotuzumab or the combination of both products, which targeted EGF and EGFR respectively. The patients were included between 2008 and 2010 with a more than five years follow-up. The results show that the serious adverse events related to the experimental treatments were 0.9%;1.1% and 2.6% and a median ITT survival of 9.1, 23.5, and 16.3 months for CIMAvax-EGF®, nimotuzumab and the combination of both, respectively. Thus fulfilling the hypothesis of safety and efficacy proposed in the investigation was achieved. The three therapeutic regimens achieved overall survival rates greater than 35% at 60 months, encouraging results for advanced uterine cervical cancer. A phase III clinical trial is proposed to consolidate these results in a greater number of patients with nimotuzumab as study drug.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Effects of high-intensity focused ultrasound combined with interventional chemoembolization on the advanced cervical cancer lesion growth and cell invasion

Objective:To study the effects of high-intensity focused ultrasound (HIFU) combined with interventional chemoembolization on the advanced cervical cancer lesion growth and cell invasion.Methods:Patients with stage IIB-IVA cervical cancer treated in Suining Hospital of TCM between May 2014 and October 2016 were selected and randomly divided into two groups, HIFU group received HIFU combined with interventional chemoembolization, and the control group accepted interventional chemoembolization. The levels of tumor markers in serum as well as the expression of tumor suppressor genes and invasion genes in tumor lesions were determined before and after treatment.Results: 2 weeks, 3 weeks and 4 weeks after treatment, serum TK-1, SCC and CA125 levels of both groups were lower than those before treatment, serum TK-1, SCC and CA125 levels of HIFU group 2 weeks after treatment were not different from those of control group, and serum TK-1, SCC and CA125 levels of HIFU group 3 weeks and 4 weeks after treatment were significantly lower than those of control group;4 weeks after treatment, AIF, NDRG4, SARI and eIF4E3 mRNA expression in tumor lesions of both groups were higher than those before treatment while FAK, KGFR and MMP9 mRNA expression were lower than those before treatment, and AIF, NDRG4, SARI and eIF4E3 mRNA expression in tumor lesions of HIFU group were higher than those of control group while FAK, KGFR and MMP9 mRNA expression were lower than those of control group.Conclusion: HIFU combined with interventional chemoembolization can be more effective in suppressing the advanced cervical cancer lesion growth and cell invasion than interventional chemoembolization alone.

Effect of Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy on the cellular malignant biological processes in advanced cervical cancer lesion

Objective:To study the effect of Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy on the cellular malignant biological processes in advanced cervical cancer lesion.Methods: Patients who were diagnosed with advanced cervical cancer in the Second People Hospital of Banan District Chongqing between April 2015 and March 2017 were selected and divided into two groups, group A received Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy, and group B received cisplatin + intensity-modulated radiation therapy. Serum contents of tumor markers, tumor invasion molecules and tumor proliferation molecules of two groups of patients were detected before treatment as well as 2 weeks and 4 weeks after treatment.Results: Serum E-cad, STMN1, Fas and p53 levels of both groups of patients 2 weeks and 4 weeks after treatment were significantly higher than those before treatment while TSGF, TK1, SCC-Ag, CA125, OPN, MMP9, NGAL, CyclinE, CyclinD1 and PCNA levels were significantly lower than those before treatment, and serum E-cad, STMN1, Fas and p53 levels of group A 2 weeks and 4 weeks after treatment were significantly higher than those of group B while TSGF, TK1, SCC-Ag, CA125, OPN, MMP9, NGAL, CyclinE, CyclinD1 and PCNA levels were significantly lower than those of group B.Conclusion: Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy for advanced cervical cancer can induce cancer cell apoptosis and inhibit cancer cell proliferation and invasion.

HSP70 inhibitor combined with cisplatin suppresses the cervical cancer proliferation in vitro and transplanted tumor growth:An experimental study

Objective:To study the regulating effect of HSP70 inhibitor(PES) combined with cisplatin on cervical cancer proliferation in vitro and transplanted tumor growth.Methods:Cervical cancer Hela cell lines were cultured and divided into control group,cisplatin group,PES group and cisplatin+PES group that were treated with serum-free DMEM,cisplatin with final concentration of 10 μmol/L,PES 20 μmol/L and cisplatin 10 μmol/L combined with PES with 20 μmol/L,respectively;animal models with cervical cancer xenografts were established and divided into control group,cisplatin group,PES group and cisplatin+PES group who received intra-tumor injection of normal saline,10 μmol/L cisplatin,20 μmol/L PES as well as 10 μmol/L cisplatin+20 μmol/L PES,respectively.Cell proliferation activity,transplanted tumor volume and mitochondria apoptosis molecule expression were detected.Results:Cell viability value and Bcl-2 mRNA expression in cells of cisplatin group,PES group and cisplatin+PES group were significantly lower than those of control group while Bax,Caspase-3 and Caspase-9 mRNA expression in cells were significantly higher than those of control group;transplanted tumor volume and the Bcl-2 mRNA expression in transplanted tumor tissue of cisplatin group,PES group and cisplatin+PES group were significantly lower than those of control group while Bax,Caspase-3 and Caspase-9 m RNA expression in transplanted tumor tissue were significantly higher than those of control group.Conclusions:HSP70 inhibitor combined with cislatin can inhibit cervical cancer cell proliferation in vitro and transplanted tumor growth through mitochondrial apoptosis pathway.

Anti-tumor effect of matrine combined with cisplatin on rat models of cervical cancer

Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.

Retrospective research of neoadjuvant therapy on tumordownstaging,post-operative complications,and prognosis in locally advanced rectal cancer

BACKGROUND Neoadjuvant therapy(NAT)is becoming increasingly important in locally advanced rectal cancer.Hence,such research has become a problem.AIM To evaluate the downstaging effect of NAT,its impact on postoperative complications and its prognosis with different medical regimens.METHODS Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy(NRCT)group and the neoadjuvant chemotherapy(NCT)group.The differences between the two groups in tumor regression,postoperative complications,rectal function,disease-free survival,and overall survival were compared using theχ2 test and Kaplan-Meier analysis.RESULTS Baseline data showed no statistical differences between the two groups,whereas the NRCT group had a higher rate of T4(30/55 vs 5/22,P<0.05)than the NCT groups.Twelve cases were evaluated as complete responders,and 15 cases were evaluated as tumor regression grade 0.Except for the reduction rate of T stage(NRCT 37/55 vs NCT 9/22,P<0.05),there was no difference in effectiveness between the two groups.Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage.No significant difference in postoperative complications and disease-free survival between the two groups was observed,although the NRCT group might have better long-term overall survival.CONCLUSION NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor.Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.

Serum Spondin-2 expression,tumor invasion,and antitumor immune response in patients with cervical cancer

BACKGROUND Cervical cancer is a gynecological malignancy common in middle-aged and older patients,with a high mortality rate.Spondin-2 is an extracellular matrix protein that involved in innate and acquired immune responses.Herein,we investigated the relationship between serum Spondin-2 expression,tumor invasion and infiltration,and immune response in patients with cervical cancer and provided a theoretical basis for clinical practice.AIM To investigate the relationship between serum Spondin-2 expression and cervical cancer-related indicators.METHODS Overall,147 patients with cervical cancer who were admitted to our institution between January 2019 and August 2019 were assigned to the cervical cancer group,and 92 patients with benign uterine lesions and 86 healthy individuals were assigned to the benign and control groups,respectively.In each group,serum Spondin-2 expression was measured,and the receiver operating characteristic(ROC)curve was determined.Patients with cervical cancer were classified into high or low Spondin-2 groups depending on the Spondin-2 threshold value used for diagnosing cervical cancer.Patient’s clinical data were collected to compare the clinicopathologic characteristics,immune cytokine levels,and prognosis of patients with varying Spondin-2 expression levels.RESULTS The expression level of serum Spondin-2 was significantly higher in the cervical cancer group than in the benign and control groups(P<0.05).According to the ROC curve,the cutoff value of Spondin-2 used in the diagnosis of cervical carcinoma was 25.68±7.11μg/L.The proportion of patients with Federation of Gynecology and Obstetrics stage III,nerve invasion,vascular invasion,and lymph node metastasis was higher in the high Spondin-2 group than in the low Spondin-2 group(P<0.05).Interleukin-5(IL-5)and IL-4 Levels were higher in the high Spondin-2 group than in the low Spondin-2 group.In contrast,IL-2 and tumor necrosis factor-αlevels were lower in the high Spondin-2 group than in the low Spondin-2 group(P<0.05).After 3 years of follow-up,progression-free survival and overall survival were significantly shorter in the high Spondin-2 group than in the low Spondin-2 group(P<0.05).CONCLUSION The expression of serum Spondin-2 is upregulated in patients with cervical carcinoma and is related to tumor invasion and infiltration,antitumor immune response,and prognosis.

MR IMAGING ASSESSMENT OF IRREGULAR SHRINKAGE OF TUMOR MORPHOLOGY AND VOLUME IN CERVICAL CANCER DURING RADIATION THERAPY

To study the clinical significance of the morphological and volume changes in cervical cancer during an ongoing course of radiation therapy (RT) using MR imaging. Methods: Serial MR imaging examinations were performed in 60 advanced cervical cancer patients. MR imaging was obtained at the start of RT, at 20-25 Gy (2-2.5 weeks of RT), at 45-50 Gy (4-5 weeks of RT), and 1-2 month post-RT. Tumor morphology was classified qualitatively as well-defined (round/oval with a well-demarcated smooth margin) vs. lobulated vs. irregular and tumor volume was assessed in each serial MR examination independently by ROI volumetry and diameter volumetry. ROI volumetry was traced on the computer workstation with a trackball in each sagittal T2-weighted image and calculated by the summation of all tumor areas in each slice and multiplication by the slice profile. Diameter volumetry was to measure the largest three orthogonal tumor diameters in each orthogonal measurement plane and calculate as an ellipsoid formula (V=d1 x d2 x d3 x p/6). Serial tumor volume was compared between the two measurement methods. Results: The proportion of lobulated and irregular tumors increased early during RT and declined lately post-RT (68% pre-RT, 80% at 2-2.5 weeks of RT, 72% at 4-5 weeks of RT, 33% post-RT). Accordingly, ROI volumetry and diameter volumetry correlated well pre-RT (r1=0.89) and post-RT (r4=0.80), but poorly during RT (r2 = 0.17 at 2-2.5 weeks of RT, r3 = 0.69 at 4-5 weeks of RT). Conclusions: Cervical cancers regress in a non-uniform fashion during RT and undergo increasingly irregular shrinkage. Measurement with ROI volumetry techniques, which can optimally measure irregular volumes, provides better assessment of radiation response during treatment than diameter volumetry.

Diagnostic value of DWI combined with dynamic contrast-enhanced scan of cervical cancer staging弥散加权成像结合动态增强扫描在宫颈癌分期中的诊断价值

目的探讨磁共振弥散加权成像（DWI）结合动态增强扫描在子宫颈癌分期中的诊断价值。方法回顾性分析2013年11月-2014年8月广州医科大学附属第四医院56例经病理证实的宫颈癌患者的DWI及动态增强扫描结果。测量病灶表观扩散系数（ADC）值判断浸润范围，并与手术病理结果进行比较。结果宫颈癌在DWI图像上表现为高信号，ADC值降低，平均ADC值为（0．92±0．16）×10^-3mm^2／s。动态增强扫描早期病灶明显快速强化，延迟期病灶中心呈低信号，病灶边缘呈稍高信号，与邻近正常宫颈组织信号明显不同，形成对比。DWI结合动态增强扫描对宫颈癌FIGO分期（2009）总准确性为93．75％，高于常规MRI分期总准确性（81．25％），对宫旁浸润评估的准确性为100．00％。结论，DWI结合动态增强扫描磁共振检查能提高宫颈癌侵犯程度评价的准确性，对宫颈癌的诊断、临床分期及制订正确的治疗方案具有重要意义。

Preliminary evaluation of pelvic vascular bed isolation chemotherapy in the treatment of advanced cervical carcinoma

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RASAL2 acts as a tumor suppressor in cervical cancer cells

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

Effects of Yiqi Gu Ben Decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer

Objective: To investigate the effects of Yiqi Gu decoction combined with DC chemotherapy on serum tumor markers, inflammatory factors and immune function in patients with locally advanced non-small cell lung cancer. Methods: A total of 95 patients with locally advanced non-small cell lung cancer were selected as the research objects, according to the random data table they were divided into control group (n=48) and observation group (n=47), patients in the control group were given DC chemotherapy, On the basis of this treatment, the patients in the observation group were given Yiqi Gu decoction treatment, Comparison of the levels of serum tumor markers [antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)], inflammatory factor [C reactive protein (CRP) and tumor necrosis factor-α (TNF-α)] and immune function (CD3+, CD4+, CD8+, CD4+/CD8+)Results: Before treatment, there were no significant difference in the levels of CEA, CA19-9, CRP, TNF-α, CD3+, CD4+, CD8+, CD4+/CD8+ between the two groups;After treatment, the CEA, CA19-9, CRP, TNF-α, CD8+ levels of two groups were significantly lower than those in the same group before treatment, and the decreased range in observation group was significantly higher than the control group, moreover the levels after treatment were obviously lower than control group;After treatment, the levels of CD3+, CD4+, CD4+/CD8+ in the observation group were (64.72±5.25)% , (39.51±5.14)% and (1.35±0.27), which were significantly higher than the same group before treatment, and significantly higher than the control group [(58.57±5.09)%, (31.34±5.06)%, (1.14±0.33)], differences were statistically significant. Conclusion: DC chemotherapy combined with Yiqi Guben Decoction in the treatment of locally advanced non-small cell lung cancer, can effectively reduce the serum tumor marker levels, decrease inflammatory stress, improve immune function, has an important clinical value.