Objectives: Cervical cancer remains a significant global health burden for women. While neoadjuvant chemotherapy (NACT) has emerged as a potential treatment option, the prognostic implications of early non-response to NACT remain inadequately characterized. This systematic review aims to elucidate the association between early non-response to NACT and long-term disease-free survival (DFS) in cervical cancer patients. Methods: A comprehensive systematic review was conducted following PRISMA guidelines. PubMed, Embase, Elsevier, Springer, EBSCO, and Cochrane Library were systematically searched to identify eligible studies. Pooled hazard ratios (HRs) for DFS with 95% confidence intervals (CIs) were calculated using R software (version 4.5.1). Heterogeneity was assessed via Cochran’s Q test and I2 statistics. Publication bias was evaluated using funnel plots, Begg’s test, Egger’s test, and trim-and-fill methods. Sensitivity analyses further validated result robustness. Results: Eleven studies (n = 2064 patients; 1546 responders, 518 non-responders) met inclusion criteria. The pooled early non-response rate ranged from 13% to 39%. Early non-response significantly correlated with poorer DFS (HR = 3.29, 95% CI 2.35–4.62). Subgroup analyses by response criteria showed HRs of 2.94 (95% CI 1.72–5.03) for WHO criteria and 4.00 (95% CI 2.52–6.34) for RECIST criteria. No significant publication bias was detected (Begg’s p = 0.35; Egger’s p = 0.28). Sensitivity analyses and trim-and-fill adjustments confirmed result stability. Conclusions: Early non-response to NACT predicts worse DFS in women with cervical cancer. These findings proposed the need for large-scale or prospective studies to validate the prognostic value of early non-response and optimize treatment strategies for non-responders. Future prospective trials with standardized protocols are essential to validate these findings and establish criteria for optimizing patient selection for NACT-based therapeutic strategies.
Endometriosis-associated adenocarcinoma of the rectum is rare and is usually misdiagnosed as colorectal carcinoma or other gynecological tumors. In the current report, the clinicopathological features of endometriosis-associated adenocarcinoma of the rectum in 2 patients were retrospectively analyzed and a literature review regarding this rare malignancy is presented. Case 1, a 49-year-old postmenopausal female patient, was admitted to Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China) due to a pelvic mass. Pelvic MRI revealed a 4.5×3.7-cm mass in the rectal wall, which severely adhered to the uterine wall. Microscopically, moderately differentiated glandular adenocarcinoma diffusely extended throughout all intestinal wall layers. Adenomyosis was found in the uterine body adherent to the rectum. Case 2, a 38-year-old reproductive female patient, presented with hematochezia. Histopathology of the resected tumor demonstrated benign endometriosis foci and atypical hyperplasia glands contiguous with endometrioid carcinoma invading the intestinal wall, and no other primary tumor sites were found, which satisfied the criteria for the diagnosis of malignant transformation of endometriosis of the rectum. Immunohistochemical (IHC) staining of both tumors revealed a Müllerian origin but not an intestinal origin. Furthermore, next-generation sequencing detected mutations of the BRCA1 (c.329dup), KRAS (c.35G>T), PIK3CA (c.3140A>G) and PTEN (c.750_751del) genes, and that microsatellite instability was high in case 1. In conclusion, endometriosis-associated adenocarcinoma of the rectum is a rare malignant tumor that should be distinguished from colorectal carcinoma for optimal treatment. Surgery and pathologic examination with IHC staining, even with molecular analysis, are essential for the final diagnosis. Primary cytoreductive surgery with resection of all macroscopic detectable lesions should be performed whenever possible. More prospective, multicenter, large-scale trials are required to examine the regimens and therapeutic value of adjuvant chemotherapy or radiology.
Peroxiredoxins (Prxs) are a ubiquitously expressed family of antioxidant enzymes that either facilitate or inhibit tumorigenesis, depending on the cancer type and Prx isoform. Prx2 is a typical Prx that has a dual role in tumorigenesis and tumor progression. However, the expression of Prx2 and its precise role in cervical cancer remains to be elucidated. Therefore, the present study aimed to investigate the expression of Prx2 and its association with the progression and prognosis of cervical squamous cell cancer (CSCC). In the present study, the clinicopathological data of 105 patients diagnosed with CSCC were collected from the medical record system at Jingzhou Central Hospital, Tongji Medical College of Huazhong University of Science and Technology (Jingzhou, China). Prx2 protein was also detected in 105 CSCC tissues and 40 adjacent peri-tumoral tissues by immunohistochemical staining. The relationships between Prx2 expression and clinicopathological features, vascular endothelial growth factor A (VEGF-A) expression and micro-vessel density (MVD) in CSCC were then analyzed. Progression-free survival (PFS) was also assessed using both univariate and multivariate analyses. The results of the present study demonstrated that the expression of Prx2 was upregulated in CSCC tissues compared with the adjacent peri-tumoral tissues (P<0.001). In addition, higher Prx2 expression was associated with greater depth of stromal invasion (P=0.023) and positive lymph vascular space invasion (P=0.044), while the Prx2 expression level was not associated with age, tumor size, histological grade, lymph node (LN) metastasis or International Federation of Gynecology and Obstetrics (FIGO) stage (all P>0.05). Furthermore, increased Prx2 expression was associated with high MVD (P=0.016), while expression of VEGF-A was not associated with Prx2 expression (P>0.05). Kaplan-Meier analysis showed that patients with high Prx2 expression (log-rank test, P=0.039), high MVD (log-rank test, P=0.015), a higher FIGO stage (log-rank test, P=0.021) and LN metastasis (log-rank test, P=0.022) had a shorter PFS time than patients with low Prx2 expression, low MVD, a lower FIGO stage and without LN metastasis, respectively. Cox proportional hazard regression analysis revealed that expression of Prx2 [hazard ratio (HR), 2.551; 95% confidence interval (CI), 1.056-6.162; P=0.037], MVD (HR, 2.436; CI, 1.034-5.735; P=0.042) and FIGO stage (HR, 1.543; CI, 1.027-2.319; P=0.037) were independent factors for PFS time. In conclusion, the results of the present study suggested that Prx2 could act as a potential biomarker for predicting CSCC progression and prognosis and could be a novel target for antiangiogenic therapy of CSCC.
The objective of this study was to investigate whether Hsa_circ_0009910 regulates cisplatin sensitivity of ovarian cancer cells by regulating the expression of miR-455-5p /PAX2. The expressions of circ_0009910, miR-455-5p and PAX2 mRNA in HOSEPiCs and ovarian cancer cells SKOV3 and SKOV3/DDP were detected by qRT-PCR. SKOV3/DDP cells were grouped according to the transfection of different genes. The sensitivity of SKOV3/DDP cells to cisplatin was detected by CCK8 assay, and the apoptosis of SKOV3/DDP cells induced by cisplatin was detected by flow cytometry.Western blot was used to detect the expressions of apoptotic proteins Bax, Bcl-2, cleaved caspase and PAX2 in SKOV3/DDP cells, and the targeted relationship between circ_0009910, miR-455-5p and PAX2 was verified by double luciferase. Our results showed that circ_0009910 and PAX2 genes were significantly up-regulated in SKOV3/DDP cells, and miR-455-5p was significantly down-regulated in SKOV3/DDP cells. circ_0009910 could enhance cisplatin sensitivity of SKOV3/DDP cells. circ_0009910 targeted miR-455-5p, and knockdown of circ_0009910 up-regulated the expression of miR-455-5p in SKOV3/DDP cells. Overexpression of miR-455-5p can enhanced cisplatin sensitivity of SKOV3/DDP cells. miR-455-5p targeted PAX2 and overexpressed miR-455-5p down-regulated the expression of PAX2 gene in SKOV3/DDP cells. Inhibition of miR-455-5p or overexpression of PAX2 reversed the enhanced cisplatin sensitivity of knockdown circ_0009910 on SKOV3/DDP cells. It is concluded that circ_0009910 enhanced cisplatin sensitivity of ovarian cancer cells SKOV3/DDP by regulating miR-455-5p /PAX2 axis.
Background: To analyze the clinicopathologic characteristics and prognosis in malignant transformation of mature cystic teratoma (MT-MCT). Methods: We retrospectively reviewed 23 patients (cohort 3) diagnosed with MT-MCT from the medical center (Tongji Hospital and Hubei cancer hospital), between January 1990 to June 2020. Cohort 2 was obtained from the PubMed, CNKI, Web of Science, and MEDLINE database, between January 1990 to June 2020. Cohort 3 was based on the surveillance, epidemiology, and results registry (SEER) database, between January 1975 and December 2016. Results: Among 3865 cases diagnosed with mature cystic teratoma, the incidence of MT-MCT is 23 (0.59%). The mean age of 23 patients was 50.6 years (median 49.0, range 24 to71 years). Patients mainly had abdominal pain (21.7%) or complained about an abdominal mass (30.4%). The mean tumor size was 11.6 cm (median 11.9, range 5.2 to 14.8 cm). According to the FIGO stage, eight patients were in stage I (34.8%), two cases were in stage II (8.6%), III (47.8%), and IV (8.7%), respectively. Most patients were diagnosed with squamous cell carcinoma (91.3%). Most patients received total hysterectomy, salpingo-oophorectomy, and omentectomy. Five patients (21.7%) received lymphadenectomy. Platinum-based chemotherapy and radiotherapy were selectively used for patients after surgical resection. The mean of disease-free survival was 27.3 months (median 22.0, range 3.0 to 67.0 months). According to the published data analysis of 342 cases, the 1-, 3-, and 5-year overall survival rates were 53.2%, 33.1%, and 23.2%, respectively. The young patients (<55 years) showed better prognosis. Conclusion: MT-MCT has an aggressive clinical course, with poor long-term prognosis. The high incidence in postmenopausal women should not be ignored. The effectiveness of adjuvant chemotherapy or radiotherapy after surgery is needed to elucidate in the future.
It is still controversial whether cervical cancer patients with clinical responses after neoadjuvant chemotherapy (NACT) have a better long-term survival or not. This study was designed to investigate the effect of the clinical response on the disease-free survival (DFS) of cervical cancer patients undergoing NACT. A total of 853 patients from a retrospective study were used to evaluate whether the clinical response was an indicator for the long-term response, and 493 patients from a prospective cohort study were used for further evaluation. The survival difference was detected by log-rank test, univariate and multivariate Cox regression and a pooled analysis. The log-rank test revealed that compared with non-responders, the DFS of responders was significantly higher in the retrospective data (P = 0.007). Univariate Cox regression showed that the clinical response was an indicator of long-term survival in the retrospective study (HR 1.83, 95% CI 1.18-2.85, P = 0.007). In a multivariate Cox model, the clinical response was still retained as an independent significant prognostic factor in the retrospective study (HR 1.59, 95% CI 1.01-2.50, P = 0.046). The result was also validated in the prospective data with similar results. These findings implied that the clinical response can be regarded as an independent predictor of DFS.
This study was designed to develop a risk model for disease recurrence among cervical cancer patients who underwent neoadjuvant chemotherapy and radical surgery. Data for 853 patients were obtained from a retrospective study and used to train the model and then data for 447 patients from a prospective cohort study were employed to validate the model. The Cox regression model was used for calculating the coefficients of the risk factors. According to risk scores, patients were classified into high-, intermediate- and low-risk groups. There were 49 (49/144, 34%) recurrences observed in the high-risk group (with a risk score ≥ 2.65), compared with 3 (3/142, 2%) recurrences in the low-risk group (with a risk score < 0.90). Disease-free survival (DFS) was significantly different (log-rank p < 0.001) among the three risk groups; the risk model also revealed a significant increase in the accuracy of predicting 5-year DFS with the area under the ROC curve (AUC = 0.754 for risk model vs 0.679 for FIGO stage system); the risk model was also validated with data from the prospective study (log-rank p < 0.001, AUC = 0.766). Both high-risk and intermediate-risk patients can be more effectively identified by this risk model.
In response to tumor development, cells initially undergo invasion and metastasis followed by epithelial-mesenchymal transition (EMT, a process by which cells acquire motility) and overriding senescence (an endogenous defense mechanism against tumor progression). Oncogenic activation of Twist1 and Twist2 is essential for EMT and senescence; however, little is known about the specific contributions of Twist1 versus Twist2 to prognosis, metastasis, and the mechanism underlying cervical carcinoma. Here, we investigated the similarities and differences between Twist1 and Twist2 in assessing prognosis and promoting invasion and metastasis of cervical carcinoma as well as their roles in the underlying molecular mechanisms. By monitoring the survival of 144 clinical cervical cancer patients, we demonstrated that Twist2 shows more effective predictive performance compared with Twist1 and is more closely correlated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Compared with Twist1, Twist2 more strongly promotes invasivity and motility by inducing EMT and overriding senescence. Differences between Twist1 and Twist2 in regulating senescence and the cell cycle might be due to their individual roles in regulating the cyclin D1/cyclin dependent kinase 4 (Cdk4) pathway. Overall, our data indicate that Twist2 is the key Twist isoform coupling aberrant signals from EMT to senescence and is an important candidate biomarker for cervical cancer prognosis.
Endometriosis is a steroid-dependent complex disease. The oestrogen receptor plays an important role by mediating oestrogen action and eutopic or ectopic endometrium development. This study investigated whether single-nucleotide polymorphisms in the genes for oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) are associated with endometriosis and endometriosis-related infertility. The participants included 157 infertile and 155 fertile endometriosis women as well as 92 women with primary infertility and 265 fertile women as controls. The iPLEX Gold system (MassARRAY system, Sequenom) was used for genotyping of ESR1 and ESR2. Statistical analysis showed that ESR1 (rs3798573 A/G) was significantly associated with endometriosis and endometriosis-related infertility (P = 0.011, P = 0.009). No association was found with ESR1 (rs1159327 A/G, rs3020348 A/C) and ESR2 (rs17179740 A/G) either for endometriosis or endometriosis-related infertility. According to the revised American Fertility Society classification, all of the detected single-nucleotide polymorphisms had no association with endometriosis in stage I-II or in stage III-IV. The results suggest that the ESR1 polymorphism rs3798573 A/G is associated with increased risk of endometriosis and endometriosis-related infertility in Han women from central China. RBMOnline (C) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Cast-in-place flat hollow slab is a new kind of floor system,which can decrease the floor thickness and allow flexible space arrangement.To investigate in-depth the technical indexes of cast-inplace flat slabs,a comparison was made between flat slab system and traditional primary and secondary beam floor system.Based on computer simulations,the technical performance of flat slabs were analyzed,specifically,cast-in-place flat slab floor system and primary and secondary beam floor system were compared with respect to their plane stiffness and self weight.This work gives a guidance to the design of flat hollow slabs in engineering projects.
The water tank used to be prefabricated and lifted to inverted cone water tower in Angola,which lead to the bad integrity and water leakage.In order to improve the inadequate,this paper works out cantilevered oblique truss platform which can lift overall and pour concrete of water tank at high altitude by calculation of different working load conditions according to tank lifting technology.Then the paper particularly introduce design,hoisting preparation,entire hoisting,fixing,casting at high altitude and dismantling of the truss system.By practical application of cast-in-situ water tank of some inverted cone water tower with truss support system,the goals of improving security,controlling quality and improving maneuverability are reached.
OBJECTIVE:To assess the association between single nucleotide polymorphisms (SNPs) of forkhead box P3 gene (FOXP3) and endometriosis in Chinese Han women from central China.METHODS:MassARRAY IPLEX and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technique was used to determine the genotypes of FOXP3 gene in 314 patients with endometriosis and 358 healthy controls.RESULTS:Genotypes of C/T polymorphism for the rs2280883 locus, A/C for the rs3761548 locus, and C/T for the rs3761549 locus were determined. No significant difference was detected in distribution of genotypes CC, CT and TT (P=0.770, OR=0.960; P=0.923, OR=1.013) and frequencies of C and T alleles (P=0.772, OR=0.960; P=0.925, OR=1.013) for rs2280883 and rs3761549 between the two groups. And no significant difference was detected in distribution of genotypes AA, AC and CC (P=0.762, OR=0.958) and frequencies of A and C alleles (P=0.715, OR=0.950) for rs3761548 was detected between the two groups. Based on r-AFS classification, the patients were divided into two groups (respectively with I-II stage and III-IV stage endometriosis). Again, no significant difference was detected in distribution of genotypes CC, CT and TT (P=0.454, OR=1.198, P=0.526, OR=0.909; P=0.220, OR=0.750, P=0.548, OR=1.094) and frequencies of C and T alleles (P=0.473, OR=1.215, P=0.532, OR=0.912; P=0.204, OR=0.737, P=0.558, OR=1.089) for rs22080883 and rs3761549 loci between the two patient groups. No association was found between distribution of genotypes AA, AC and CC (P=0.431, OR=1.211; P=0.508, OR=0.905) and frequencies of A and C alleles (P=0.417, OR=1.226; P=0.516, OR=0.908) for rs3761548 locus between the two patient groups.CONCLUSION:Our study has failed to found any association between FOXP3 gene polymorphisms rs2280883, rs3761548 and rs3761549 with endometriosis in Chinese Han patients.
Objective To systematically assess the correlation between smoking and the risk of endometriosis,so as to offer scientific basis to health education and preventing decision.Methods A literature search was performed in The Cochrane Library,Pubmed,Embase,CBM,CNKI and Wanfang database to collect the case control studies on the correlation between smoking and endometriosis.Two reviewers independently screened the literatures according to the inclusion and exclusion criteria,extracted the data,assessed the quality,and then conducted Meta-analyses on the 13 included RCTs by using RevMan 5.0 software,with calculation of the OR value and 95%CI.Results A total of 13 case control studies involving 14260 cases were included,of which 1900 ones were endometriosis.The quality assessment indicated that 2 studies were in quality of Level A,4 were Level B,7 were Level C,totally meant low quality.Meta-analyses showed that compared with non-smokers,there was no increasing possibility of endometriosis in smokers(OR= 0.91,95%CI 0.82 to 1.02).The geographical subgroup analyses showed there was no significant difference in the incidence of endometriosis between the non-smokers and smokers in North America(OR=0.96,95%CI 0.84 to 1.08),but a significant difference was found between non-smokers and smokers in Europe(OR=0.72,95%CI 0.54 to 0.97).Conclusion There is no causative relationship between smoking and incidence of endometriosis.However,more high-quality trials are expected for further study because of the heterogeneity and poor quality of the current included studies.
OBJECTIVE:To investigate the relationship of TWIST induced epithelial-mesenchymal transitions and cervical cancer progression.METHODS:Immunohistochemistry was used to examine the distribution and expression of TWIST and E-cadherin in 128specimens inclnding normal cervial tissue,cervical intraepithelial neoplasia(CIN) and squamous cell carcinoma of cervix(SCC).To construct eukaryotic expression vector of human TWIST pcDNA3.1(+)/ TWIST and establish its stable transfected SiHa cell line.The morphology of the cell line was observed and alteration of the EMT markers was tested by western blot.RESULTS:In specimens of normal cervial tissues,CINⅠ-Ⅱ,CINⅢ,SCC(ⅠA-ⅡA),and SCC(ⅡB-ⅢB),the positive expression of TWIST in cytoplasm were 14.2%,63.4%,64.3%,100.0%,100.0%,and in cell nucleus were 21.4%,56.6%,57.1%,88.0%,100.0%.In the same specimens,the positive expression of E-cadherin in cellular membrane were 71.4%,36.7%,35.7%,12.0%,11.1%,and in cytoplasm were 18.6%,63.3%,64.3%,88.0%,88.9%.The inverse correlation was obtained between the expression of TWIST and E-cadherin.The expression of TWIST in the SCC groups with lymph node metastasis were higher than that in the groups without lymph node metastasis(P=0.012,P=0.033).The morphology of pcDNA3.1(+)/ TWIST / SiHa cell line obviously transformed and expression of EMT markers had also changed(P0.05).CONCLUSIONS:The expression of TWIST escalats during the tumorigenesis and progression of cervical cancer.Additionally,EMT induced by TWIST plays an important role in this process.
目的 构建人grp78基因真核表达载体,并建立稳定高表达grp78的人宫颈癌HeLa细胞系.方法 用RT-PCR方法从人宫颈癌HeLa细胞中扩增grp78基因编码区,将PCR产物克隆到pcDNA3.1(+)真核表达载体,构建重组质粒pcDNA3.1(+)/grp78并测序鉴定.用构建成功的pcDNA3.1(+)/grp78真核表达载体转染入人宫颈癌HeLa细胞,经G418筛选获得grp78稳定高表达的HeLa细胞系,并用RT-PCR及Western 印迹方法鉴定.结果 成功构建pcDNA3.1(+)/grp78真核表达载体,筛选获得稳定高表达人grp78的HeLa细胞系.结论 grp78真核表达载体的成功构建和稳定高表达grp78的HeLa细胞系的建立为进一步研究grp78的功能奠定了基础.
LIGHT is a tumor necrosis factor superfamily ligand that is considered as a promising candidate for cancer therapy. It has a potent antitumor activity through establishing lymphoid-like tissues inside tumor sites and recruiting naive T cells into the tumor. In this study, we examined the possibility of antitumor activity by expressing LIGHT in cervical cancer (CC) model. A recombinant adeno-associated virus (AAV) vector was chosen for the transfer, based on its transfection efficiency and lack of detectable pathology. In vitro transfer of recombinant AAV vector expressing LIGHT (AAV-LIGHT) stimulated T-lymphocyte proliferation and activation. AAV-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against preexisting TC-1 cell CC in C57BL/6 mice. This study confirmed that AAV-LIGHT regressed tumor growth by activating cytotoxic T lymphocyte, enhancing infiltration of inflammatory cells in tumor and increasing stimulatory cytokine expression in tumor microenvironment. Therefore, AAV-LIGHT therapy might have potential utility for the treatment of CC.
Objective. Globally, cervical cancer is the second most common cancer among women, and determining potential targets involved in tumor progression is necessary. This study investigated the clinic-pathological significance of twist homolog 2 (IWIST2), a basic helix-loop-helix transcription factor, and correlated TWIST2 and E-cadherin expression in cervical cancer.Methods. A series of 142 samples, including 14 cases of normal cervical tissues, 58 cases of cervical intraepithelial neoplasia (CIN) and 70 cases of sguamous cell carcinoma (SCC), were examined TWIST2 and E-cadherin immunohistochemical staining and statistical analysis.Results. Increased cytoplasmic and nuclear expression levels of TWIST2 were associated with the malignant transformation of cervical epithelium and the histological progression of cervical cancer. A logistic test showed that TWIST2 was a relatively independent predictor of lymph node metastasis of SCC. Further, increased levels of TWIST2 were also associated with aberrant expression of E-cadherin, an important EMT indicator.Conclusions. The present data suggest that TWIST2 overexpression was significantly linked to cervical cancer progression, which makes it a promising marker for determining the metastatic potential of cervical cancer, and up-regulation of TWIST2, in combination with aberrant E-cadherin expression in primary cervical cancer tissues, may predict the malignant transformation and distal metastasis of carcinomas. (C) 2011 Elsevier Inc. All rights reserved.