Semen affects the biological behavior of HeLa cells by altering ERK signaling.

INTRODUCTION: The aim of the study was to investigate the effects of human semen on the proliferation, survival, migration and invasion of HeLa cervical cancer cells by analyzing the extracellular regulated protein kinase (ERK) pathway. MATERIAL AND METHODS: HeLa cells were stimulated with different concentrations of human semen. MTT assay was used to analyze the effects on cell proliferation. Apoptosis in the different experimental groups was quantified by Annexin V-FITC/PI staining. The effect of seminal plasma on in vitro invasiveness of cells was evaluated using transwell assay. Western blotting was used to evaluate ERK pathway activation. RESULTS: Human semen promoted HeLa cell proliferation; ERK1/2 phosphorylation and c-myc expression also increased with increasing semen concentration. U0126 inhibited semen-induced ERK1/2 phosphorylation, c-myc upregulation and cell proliferation. Compared with the control group, semen did not significantly affect the apoptotic rate of HeLa cells (p > 0.05). The transwell assays showed that compared with the control group, the number of invading cells increased significantly with increasing semen concentration, and the difference was significant (p < 0.05) when 1 : 50 semen was added, suggesting that semen promotes the invasion of cervical cancer cells. Western blotting indicated that ERK1/2 phosphorylation began to increase when 1 : 100 semen was added; with increasing semen concentration, ERK1/2 phosphorylation was significantly up-regulated, and the expression of its downstream target gene, c-myc, was also up-regulated (p < 0.05). CONCLUSIONS: Semen promoted the proliferation of HeLa cells by activating the ERK pathway and showed increased tumorigenic potential in vivo. Human seminal plasma might be a potential factor contributing to the development of cervical cancer.

Immunoregulatory Effects of Subcutaneous Immunotherapy on Lymphocyte Subgroups and Cytokines in Children with Asthma.

OBJECTIVE: Asthma is a syndrome that incorporates many immune phenotypes. The immunologic effects of subcutaneous immunotherapy (SCIT) exerts on allergic asthma remain still largely unknown. Here, we investigated the effects of SCIT on cytokine production and peripheral blood levels of lymphocyte subtypes in children with mite-induced moderate and severe allergic asthma. METHODS: The study included 60 kids with mite-induced allergic asthma from 5 to 10 years old. All subjects had received antiasthmatic pharmacologic for 3 months at baseline. Half of the children were treated with SCIT combined with pharmacologic treatment named the SCIT group and the other half only with pharmacologic therapy named the no-SCIT group. Total asthma symptom score (TASS) and total medication score (TMS) were recorded. Flow cytometry was used to identify lymphocyte subtypes: type 2 innate lymphocytes (ILC2s), type 1 (Th1) and type 2 (Th2) helper T cells, T helper 17 (Th17) cells, and regulatory T (Treg) cells. ELISA, flow cytometry, and cytometric bead array were used to assess cytokines IL-13, IFN-γ, IL-4, IL-17, and TGF-ß, at baseline and 3 and 6 months after study treatment in both groups of patients. RESULTS: Both groups can significantly improve clinical symptoms in children with asthma. SCIT can significantly reduce asthma medication after 6 months of treatment. SCIT induced a significantly higher and progressive reduction in ILC2 percentage and IL-13 levels after 3 and 6 months of treatment compared with baseline and compared with no-SCIT patients. Significant differences were detected in the Th1/Th2 cell ratio and IFN-γ/IL-4 cytokine ratio between groups after 6 months of treatment. Similarly, the Th17/Treg ratio and IL-17/TGF-ß ratio in the SCIT group were much lower than those in the no-SCIT group after 3-6 months of treatment. CONCLUSION: SCIT is a promising option to reduce the percentage of ILC2 and regulate Th1/Th2 and Th17/Treg immune balance in the peripheral blood of children with asthma.

[Effect of Organic Manure Substitution of Synthetic Nitrogen on Crop Yield and N2O Emission in the Winter Wheat-Summer Maize Rotation System].

Controlling agricultural greenhouse gas emissions, such as N2O, is important in mitigating global climate warming. Through monitoring the dynamics of N2O emission fluxes, we investigated the effect of organic nitrogen (N) substitution of synthetic N on N2O emissions and the yield of winter wheat and summer maize in the Guanzhong Plain of Shaanxi Province, China. The study involved six treatments, consisting of no fertilizer (CK), synthetic N, phosphorus (P), and potassium (K) fertilizers alone (NPK), 75% NPK+25% organic N through manure (25%M), 50% NPK+50% organic N (50%M), 25% NPK+75% organic N (75%M), 100% organic N (100%M). The results showed that the peak value of the N2O emission flux appeared after fertilization, rainfall, and irrigation. In the wheat season, the emission flux of N2O varied from -1.33 to 144.2 µg·(m2·h)-1, with the highest peak value in the NPK treatment. In the maize season, the emission flux of N2O varied from 88.2 to 1800.1 µg·(m2·h)-1, and the 50%M treatment showed the highest peak value. The range in the total amount of N2O emissions from the different treatments in the wheat-maize rotation system was 429.8-2632.1 g·hm-2, and the amount for the treatments decreased in order as follows:50%M > 25%M > NPK > 75%M > 100%M > CK. The yields of wheat, maize, or wheat plus maize were significantly higher in the fertilized treatments compared to the CK. Organic substitution treatments significantly increased wheat yield by 26.1% to 50.0% relative to the NPK treatment. While the maize yield in 50%M and 75%M treatments was similar to that in the NPK treatment, the 25%M and 100%M treatments showed significantly lower yields than with the NPK treatment. The total yield of wheat plus maize varied from 9166 to 17496 kg·hm-2, of which total yield was significantly higher with 50%M and 75%M compared to NPK. Overall, the 75%M treatment is the best measure to guarantee crop yield and to reduce N2O emissions in the wheat-maize rotation system based on a one year study in the Guanzhong plain of Shaanxi Province.

Association of rs2075876 polymorphism of AIRE gene with rheumatoid arthritis risk.

BACKGROUND: Autoimmune regulator (AIRE), a protein encoded by AIRE gene, is a transcriptional factor primarily expressed in medullary thymic epithelial cells (mTECs). It has pivotal role in regulation of human immunology. The mutations of AIRE gene or protein level changes would alter the status of body immunity and therefore onset of diseases. Therefore we aimed at investigating the association of AIRE gene with the risk of rheumatoid arthritis (RA). METHODS: We genotyped 9 SNPs of AIRE gene of recruited 691 patients of rheumatoid arthritis and 800 healthy people in Chinese Han population. RESULTS: Our results indicated that a variant rs2075876 with minor allele A increased the risk of rheumatoid arthritis (pa=0.008, OR=1.991, 95%CI 1.214-2.919). Other two SNPs rs933150 and rs760426 were borderline-associated with rheumatoid arthritis risk (pa=0.055; pa=0.074, respectively). Furthermore, in correlation analysis of SNPs in AIRE gene with clinical characteristics of rheumatoid arthritis, we found the SNP rs2075876 had significant correlation with CRP concentration (pa=0.020). CONCLUSION: We might provide a new inside look into the AIRE gene variants in development and progression of rheumatoid arthritis.

Specific siRNA inhibits XIAP expression in human endometrial carcinoma cell apoptosis.

The aim of the study was to investigate the inhibitory effects of RNA interference on XIAP gene expression of human endometrial carcinoma RL95-2 cell and the cell apoptosis. Specific small interference RNA (siRNA) of XIAP was designed and composed. Transfection of siRNA was conducted in endometrial carcinoma cell line RL95-2. The XIAP gene mRNA was assessed by real-time PCR and the change of XIAP protein was assessed with Western Blotting. The cell proliferation and apoptosis was assessed by MTT and flow cytometry methods. After transfection of siRNA specifically targeting XIAP, the relative fold of mRNA transfection in the specific transfection group was (0.04 ± 0.06) and the relative protein expression was (0.590 ± 0.178), which was significantly decreased when compared with the control group (P < 0.05); the cell growth inhibition rate in the transfection group was (47.86 ± 4.46)%, which was significantly increased when compared to the control group (P < 0.05). In vitro experiment showed that synthetic siRNA could effectively inhibit the transfection and expression of XIAP gene of human endometrial carcinoma RL95-2 cell at the mRNA level and protein level, thus significantly promote the apoptosis of endometrial carcinoma cell. The mechanisms involved in the apoptosis still require further investigation.

miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression.

This study was to investigate the effect of miR-200c on regulation of ovarian cancer cell metastasis potential and explore the underlying molecular events. qRT-PCR was used to analyze the level of miR-200c expression in 48 ovarian cancer and 30 normal ovarian tissue samples. pre-miR-200c was used to manipulate miR-200c expression in ovarian cancer cells for detection of changed phenotypes of tumor cells. Bioinformatics analysis was then used to predict target genes of miR-200c and GO and pathway analyses drew the miR-200c-related gene network. Luciferase reporter assay confirmed the target of miR-200c as ZEB2. Western blot was used to detect gene expressions in ovarian cancer cells. Level of miR-200c expression was much higher in ovarian cancer than in normal ovarian tissues, and miR-200c expression was inversely associated with advanced clinical stage and lymph node metastasis of ovarian cancer (p < 0.01). The database search predicted 186 miR-200c-targeting genes, and GO analysis showed that functions of these target genes were enriched in the protein binding and other biological processes. Furthermore, miR-200c expression inhibited ovarian cancer cell ES-2 migration and invasion capacity by suppression of ZEB2 expression (p < 0.01). Overexpression of miR-200c regulated E-cadherin and vimentin expression in ovarian cancer cells. This study demonstrated high miR-200c expression in ovarian cancer tissues and ZEB2 as a targeting gene of miR-200c, which mediated the effects of miR-200c on regulation of ovarian cancer cell migration and invasion capacity and epithelial-to-mesenchymal transition. Thus, targeting of miR-200c or ZEB2 may serve as a potential therapeutic strategy for control of ovarian cancer.

Inhibition potential of UDP-glucuronosyltransferases (Ugts) 1A isoforms by the analogue of resveratrol, bakuchiol.

Bakuchiol is a promising anti-tumor candidate with resveratrol-like structure. The present study aims to evaluate the inhibition potential of bakuchiol towards UDP-glucuronosyltransferases (UGT) 1A isoforms. An in vitro incubation system using 4-methylumbelliferone (4-MU) glucuronidation was used to evaluate the inhibition capability of bakuchiol towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The glucuronidation of trifluoperazine (TFP) was employed as the probe reaction to determine bakuchiol's inhibition towards UGT1A4. At 1 microM and 10 microM of bakuchiol, no or weak inhibition was observed for all the tested UGT1A isoforms. At 100 microM of bakuchiol, the activity of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9 and 1A10 was inhibited by -46.2%, 74.7%, 17.8%, 98.7%, 70.4%, 99.2%, 75.8%, and 93.3%, respectively. Further inhibition kinetic behaviour was determined for UGT1A6, 1A8, and 1A10. Both Dixon plot and Lineweaver-Burk plot showed the noncompetitive inhibition of bakuchiol towards all these three UGT isoforms. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 1.8, and 92.6 microM for UGT1A6, 1A8, and 1A10, respectively. In combination with the in vivo exposure of bakuchiol, the high possibility of in vivo inhibition of UGT1A6 and 1A8 was predicted. However, relatively low possibility of in vivo inhibition towards UGT1A10 was predicted due to lower in vivo concentration of bakuchiol than its inhibition parameter (Ki). All these information will be helpful for the R&D of bakuchiol as a promising anti-tumor drug.

Assessment of retrospective dose estimation, with fluorescence in situ hybridization (FISH), of six victims previously exposed to accidental ionizing radiation.

The present study aims to evaluate the use of the fluorescence in situ hybridization (FISH) translocation assay for retrospective dose estimation of acute accidental exposure to radiation in the past. Reciprocal translocation analysis by FISH with three whole-chromosome probes was performed on normal peripheral blood samples. Samples were irradiated with 0-5Gy (60)Co γ-rays in vitro, and dose-effect curves were established. FISH-based translocation analyses for six accident victims were then performed, and biological doses were estimated retrospectively by comparison with the dose-effect curves. Reconstructed doses by FISH were compared with estimated doses obtained by analysis of di-centrics performed soon after exposure, or with dose estimates from tooth-enamel electron paramagnetic resonance (EPR) data obtained at the same time as the FISH analysis. Follow-up FISH analyses for an adolescent victim were performed. Results showed that dose-effect curves established in the present study follow a linear-quadratic model, regardless of the background translocation frequency. Estimated doses according to two dose-effect curves for all six victims were similar. FISH dose estimations of three adult victims exposed to accidental radiation less than a decade prior to analysis (3, 6, or 7 years ago) were consistent with those estimated with tooth-enamel EPR measurements or analyses of di-centrics. Estimated doses of two other adult victims exposed to radiation over a decade prior to analysis (16 or 33 years ago) were underestimated and two to three times lower than the values obtained from analysis of di-centrics or tooth-enamel EPR. Follow-up analyses of the adolescent victim showed that doses estimated by FISH analysis decrease rapidly over time. Therefore, the accuracy of dose estimates by FISH is acceptable only when analysis is performed less than 7 years after exposure. Measurements carried out more than a decade after exposure through FISH analysis resulted in underestimation of the biological doses compared with values obtained through analysis of di-centrics and tooth-enamel EPR.

[Multicenter randomized controlled clinical study for the operative treatment of malignant ovarian germ cell tumors].

OBJECTIVE: To investigate the operative treatment for first-treated patients with malignant ovarian germ cell tumors who need preservation of fertility. METHODS: The clinical data of 105 patients who were treated with fertility-sparing surgery in 11 hospitals from 1992 to 2010 were collected to evaluate the outcomes of different primary surgical operative procedures. All 105 cases were performed the surgeries that preserved fertility and divided into three groups according to the surgical approaches, comprehensive staging surgery group: 47 cases (44.8%) received comprehensive staging surgeries that including the ipsilateral oophorectomy + omentectomy + retropertoneal lymph node dissection ± appendectomy + multiple biopsies;oophorectomy group:45 cases (42.9%)received ipsilateral oophorectomy ± biopsy of contralateral ovary ± omentectomy;tumor resection group:13 cases (12.4%) received enucleation of the mass with preservation of the ovary. Differences were compared among the three groups of patients in the surgery-related indicators, complications, fertility and prognosis. RESULTS: (1) Surgery-related indicators:the average blood loss of the comprehensive staging surgery group, the oophorectomy group and the tumor resection group were 496, 104 and 253 ml, the mean operation time were 176, 114 and 122 minutes, respectively, and there were significant differences among three groups (P = 0.011, P = 0.000). (2) Complication:the surgical complication rates of the three groups were 17% (8/47), 0 and 1/13, with significant differences (P = 0.015). (3) Reproductive function status: the pregnancy rate and birth rate of the three groups were no significant differences (9/19 vs. 7/19 vs. 2/3, P = 0.515; 8/19 vs. 5/19 vs. 2/3, P = 0.636). (4) PROGNOSIS: the recurrence rate of the three groups were significant differences [13% (6/47) vs. 0 vs. 2/13, P = 0.013], but the death rate with no significant differences [6% (3/47) vs. 0 vs. 0, P = 0.129]; The five-year survival rate of three different groups were 89%, 100% and 100% (P > 0.05), while disease free survival rate were 85%, 100% and 83% (P < 0.05), respectively. CONCLUSIONS: Compared with comprehensive staging surgery, oophorectomy group have higher surgical security and satisfactory prognosis, considerable pregnancy rates and birth rate. The tumor resection security may be reliable, but the prognosis is poor.

Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy.

AIM OF THE STUDY: This study aims to analyze the clinical manifestations and sequelae of peripheral nerve radiation damage of two cases of cancer patients after radiotherapy at the corresponding sites in clinical practice and to summarize experiences and lesions in order to provide a reference for future tumor radiotherapy. MATERIAL AND METHODS: Some data of two cases of patients, such as doses of radiotherapy, clinical manifestations and damage occurrence time, were collected and examinations were conducted to define diagnosis. Afterwards, therapies and follow-up were conducted. RESULTS: Case 1 (rectal cancer) was diagnosed as mild left lower extremity nerve damage. After the symptomatic treatment, the disease condition was improved, and there was no tumor recurrence sign. Case 2 (breast cancer) was diagnosed as left brachial plexus damage, and left upper extremity movement function was lost completely. While the analgesic treatment was conducted, anti-tumor relevant treatments were being carried out. CONCLUSIONS: Radiotherapy can cause different extents of radioactive nerve damage. In practice, it is necessary to constantly improve the radiotherapy technology level and actively prevent the occurrence of complications. Once symptoms appear, the diagnosis and treatment should be conducted as early as possible in order to avoid aggravating damage to cause dysfunction and cause lifetime pain to patients.

Cytogenetic analysis in 16-year follow-up study of a mother and fetus exposed in a radiation accident in Xinzhou, China.

In November 1992, a radiation accident occurred in Xinzhou, due to the collection by a farmer of an unused (60)Co source; 37 individuals were exposed to ionizing radiation. Three individuals died and the farmer's 19-weeks-pregnant wife suffered acute radiation symptoms. Conventional chromosome analysis, cytokinesis-block micronuclei (CBMN) assay and fluorescence in situ hybridization (FISH) painting with three pairs of whole chromosome probes were used to analyze chromosomal aberrations for the pregnant female and her baby during the 16 years following the accident. The yields of dicentrics and rings (dic+r) continually declined between 41 days and 16 years after the accident. The frequency of binucleated MN also decreased over time for both mother and daughter. Sixteen years after exposure, the yields of dic+r and binucleated MN decreased to normal levels, but the reciprocal translocation frequencies remained elevated, for both mother and daughter. FISH results showed a decreasing yield of translocations with time. Based on the changes in maternal translocation frequency, the daughter's dose at the time of exposure was estimated as 1.82 (1.35-2.54)Gy. This was consistent with the clinical manifestations of severe mental retardation and low IQ score. FISH-based translocation analysis can be used for follow-up studies on accidental exposure and, after correction, for retrospective dose estimation for individuals prenatally exposed to radiation.

Suppression of HER-2 via siRNA interference promotes apoptosis and decreases metastatic potential of SKOV­3 human ovarian carcinoma cells.

The aberrant expression of human epidermal growth factor receptor-2 (HER-2) has been detected in ovarian cancer. However, the role of HER-2 in the development of ovarian cancer has not been sufficiently elucidated. The objective of this study was to determine the role of HER-2 in the apoptosis and metastasis of SKOV-3 ovarian cancer cells. SKOV-3 cells were transfected with three double­stranded small interfering RNA (siRNA) molecules that target HER-2. Various sequences were synthesized by T7 transcription in vitro to select the most effective HER-2­silencing siRNA. SKOV-3 cells were examined for growth inhibition using the MTT proliferation assay and apoptosis was assessed using flow cytometry and TUNEL assay. The Matrigel basement memebrane matrix was used to assess invasion and chemotactic mobility, as a model of tumor cell metastasis. Western blot analysis was used to detect the expression of matrix metallopeptidase-9 (MMP-9), E-cadherin, N-cadherin and vimentin. siRNA interference in HER-2 resulted in decreased cell proliferation and invasion and increased apoptosis. Western blot analysis demonstrated a marked increase in E-cadherin and MMP-9 and a reduction in N-cadherin and vimentin protein levels in the SKOV-3 cells. The suppression of HER-2 expression resulted in apoptosis and the inhibition of metastasis of SKOV-3 cells. Therefore, the overexpression of the HER-2 gene can enhance the metastatic potential of SKOV-3 cells by increasing the protein levels of MMP-9. Epithelial-mesenchymal transition may be involved in the HER-2 siRNA-induced invasion and migration of SKOV-3 cells. Taken together, these results suggest that HER-2 functions as an oncogene and may thus be an attractive therapeutic target in SKOV-3 ovarian cancer cells.

[Different methods for the diagnosis of endometrial histological comparative study].

OBJECTIVE: To evaluate the feasibility of endometrial sampler Pipelle for endometrial histologic diagnosis. METHODS: Using prospective and self-control methods, 200 patients with endometrial biopsy firstly used Pipelle endometrial sampler for endometrial tissue, then followed by diagnostic curettage, the same pathologist evaluated the specimen quality and made the histologic diagnosis. RESULTS: Totally 200 patients completed the observation, the specimen satisfaction of Pipelle was 93.0% (in this 200 cases, 186 cases were satisfactory), its pathological accuracy was 85.0% (in this 200 cases, 170 cases' pathological results are highly consistent with diagnostic curettage). There was no significant difference between two kinds of endometrial sampling (P > 0.05). There was no pain for patients during the Pipelle using process. CONCLUSION: Pipelle could obtain satisfactory samples used for histological diagnosis in normal endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and endometrial cancer disease, because its pathological accuracy is so close to the diagnostic curettage, which may be used as a routine screening tool of endometrial diseases.

[Correlation study of HPV-16 existential status with Th17/Treg cytokines].

OBJECTIVE: To explore the relationship between the presence of HPV-16 DNA and the expression Treg surface marker Foxp3(+), peripheral blood levels of Th17/Treg cell-associated cytokines and explore their roles and significance in cervical cancer progression. METHODS: Between January 2012 and October 2012 at Shengjing Hospital of China Medical University, a total of 142 HPV16 positive patients were divided into cervical cancer (CC, n = 60), cervical intraepithelial neoplasia (CIN, n = 65) and control group (n = 17). Cervical liquid-based cytological (LBC) samples were collected to detect E2 and E6 genes of HPV type 16 using multiple real-time polymerase chain reaction (PCR). E2/E6 ratio was used to evaluate the physical status of HPV-16 DNA in host cell genome. The SP immunohistochemical method was used to detect the expressions of FOXP3 in cervical lesions. The concentrations of Th17/Treg cell-associated cytokines were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Under the same status of HPV16 DNA in vivo, the levels of Foxp3(+), transforming growth factor-ß (TGF-ß) and interleukin-10 (IL-10) were significantly higher than those of the control group (P < 0.01) while the levels of interleukin-17 (IL-17) and interleukin-21 (IL-21)were significantly lower than those of the control group (P < 0.05) . In the same disease, HPV16 DNA integration rate grew with the increases of Foxp3(+), TGF-ß and IL-10 while IL-17 and IL-21 were opposite. In the different status of HPV16 type DNA, the expression of Foxp3(+) was closely correlated with Federation International of Gynecology and Obstetrics (FIGO) stage, histological grade and lymphnode metastasis (P < 0.05) except for age (P > 0.05). CONCLUSION: Treg cytokines, HPV16 integration rate and severity of cervical lesions are positively correlated while Th17 cytokines show opposite effects. Th17/Treg cell-associated cytokines may play an important role in the occurrence and development of cervical cancer.

Association between p53 codon 72 polymorphism and cervical cancer risk among Asians: a HuGE review and meta-analysis.

OBJECTIVE: The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the association between p53 codon 72 polymorphism (Arg72Pro, rs1042522 G>C) and cervical cancer risk among Asians. METHODS: A literature search of Pubmed, Embase, Web of Science and CBM databases from inception through June 2012 was conducted. The meta-analysis was performed using STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. Twenty-eight case-control studies were included with a total of 3,580 cervical cancer cases and 3,827 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that the Pro/Pro genotype was associated with increased risk of cervical cancer under the heterozygous model (Pro/ Pro vs. Arg/Pro: OR = 1.25, 95%CI: 1.02-1.53, P= 0.005). However, no statistically significant associations were found under four other genetic models (Pro vs. Arg: OR = 0.97, 95%CI: 0.85-1.10, P= 0.624; Pro/Pro + Arg/ Pro vs. Arg/Arg: OR = 0.84, 95%CI: 0.70-1.01, P= 0.058; Pro/Pro vs. Arg/Arg + Arg/Pro: OR = 1.13, 95%CI: 0.92-1.39, P= 0.242; Pro/Pro vs. Arg/Arg: OR = 0.97, 95%CI: 0.76-1.22, P= 0.765; respectively). In the subgroup analysis based on country, the Pro/Pro genotype and Pro carrier showed significant associations with increased risk of cervical cancer among Indian populations, but not among Chinese, Japanese and Korean populations. CONCLUSION: Results from the current meta-analysis suggests that p53 codon 72 polymorphism might be associated with increased risk of cervical cancer, especially among Indians.

[Clinical significance of serum squamous cell carcinoma antigen in the diagnosis, treatment and prognosis of cervical squamous cell carcinoma].

OBJECTIVE: To explore the clinical significance of squamous cell carcinoma antigen (SCC-Ag) in the diagnosis, treatment and prognosis of cervical squamous cell carcinoma. METHODS: The serum SCC-Ag concentrations were measured for 1195 patients with cervical squamous cell carcinoma, 54 patients with non-squamous cell type cervical cancer, 325 patients with cervical intraepithelial neoplasm and 69 healthy women treated at Gynecology Ward of Shengjing Hospital, China Medical University from August 2008 to October 2010. And the correlations with their clinical pathological features of squamous cell carcinoma were analyzed and the changes in the diagnosis, treatment and prognosis monitored. RESULTS: Serum SCC-Ag in patients with cervical squamous cell carcinoma showed a sensitivity of 62.32% and a specificity of 90.10% with the optimal cutoff point of diagnosis at 1.45 µg/L. The differences of pretreatment serum SCC-Ag levels were statistically significant in clinical stage, histological differentiation, depth of invasion and lymph node metastasis (P < 0.01). The posttreatment serum SCC-Ag levels of 106 patients undergoing radical surgery and 264 patients on chemotherapy significantly decreased and were significant different with their pretreatment levels (P < 0.05). There was no relationship of serum SCC-Ag levels and human papillomavirus (HPV) opportunistic infection (all P > 0.05). The best threshold values of pretreatment serum SCC-Ag concentration for predicting early postoperative cervical lymph node metastasis and prognosis of cervical cancer were 2.15 and 12.1 µg/L respectively. CONCLUSION: As a relatively specific tumor maker for cervical squamous cell carcinoma, squamous cell carcinoma antigen is correlated with clinicopathological features of cervical squamous cell carcinoma. And it has important clinical reference values in the diagnosis, prognosis, follow-up evaluation and treatment monitoring of cervical squamous cell carcinoma.

[Association of interferon-γ gene polymorphism and risk of cervical HPV infection].

OBJECTIVE: To investigate the association of interferon (IFN) γ gene polymorphisms and risk and prognosis of HPV cervical infection. METHODS: PCR-ASP was used for detecting IFN-γ rs2430561 polymorphism in 179 HPV positive patients and 328 HPV negative normal controls. RESULTS: The frequency of A allele of 63.7% (228/358) was significantly higher than the frequency of T allele of 36.3% (130/358) in HPV positive group (P = 0.045). The frequencies were 41.3% (74/179) in AA genotype and 14.0% (25/179) in TT genotype, women carrying AA genotype increased the risk of HPV infection compare with those with TT genotype (OR = 1.784, 95% CI: 1.031 - 3.088, P = 0.039). During follow-up, the rate of HPV positive again in AA genotype was 83.8% (62/74), while TT genotype was 20.0% (5/25). In the analysis of Kaplan-Meier, the cumulative HPV negative rates of AA, TA and TT genotype exhibited significantly different (P = 0.008). The cumulative HPV negative rate of AA genotype was the lowest (1.1% - 5.9%). CONCLUSIONS: IFN-γ rs2430561 polymorphisms confer the susceptibility to HPV infection. Women with AA genotype exhibited higher risk of infection and inclined to be continuous status and recurrence after HPV infection.

Expression and correlation of Lewis y antigen and TGF-ß1 in ovarian epithelial carcinoma.

Lewis y is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of Lewis y is frequently observed in epithelial-derived cancers. This study aimed to detect the expression and clinical significance of the Lewis y antigen and TGF-ß1 (transforming growth factor ß1) in ovarian epithelial tumors, and to evaluate the correlation between them. Immunohistochemical staining was used to detect the expression of Lewis y antigen and TGF-ß1 in 60 cases of ovarian epithelial malignant tumors, 20 cases of borderline ovary tumors, 20 cases of benign ovary tumors and 10 cases of normal ovarian tissues. An immunofluorescence double labeling method was also used to detect the correlation between Lewis y antigen and TGF-ß1. The positive rates of Lewis y antigen in ovarian epithelial cancer tissues was 88.33%, significantly higher compared to those of borderline ovarian tumors (60.00%) (P<0.05), benign ovarian tumors (35.00%) (P<0.01) and normal ovarian tissues (0%) (P<0.01). Its expression was not associated with clinical parameters; the positive rates of TGF-ß1 in ovarian epithelial cancers were 78.33%, significantly higher compared to those of benign ovarian tumors (65.00%) (P<0.05) and normal ovarian tissues (40.00%) (P<0.05); the positive rates of the TGF-ß1 and Lewis y were not associated with metastasis of lymph nodes and histological types, differentiation degree and clinical stage (P>0.05). Expression of Lewis y antigen and TGF-ß1 was significantly positively associated with epithelial carcinoma. Close correlation between Lewis y, TGF-ß1 and ovarian cancer was observed. Altered expression of Lewis y antigen may cause changes in TGF-ß1 expression. Lewis y can increase the growth of ovarian cancer cells and the invasion ability by promoting TGF-ß1 abnormal expression and by promoting angiogenesis and a change in its signal transduction pathway. This study provides theoretical evidence for the development of ovarian cancer biological treatments.

Lewis Y regulates signaling molecules of the transforming growth factor ß pathway in ovarian carcinoma-derived RMG-I cells.

LeY (Lewis Y) is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of LeY is frequently observed in epithelial-derived cancers and is correlated to pathological staging and prognosis. To study the role of LeY on cancer cells, a stably LeY-overexpressing cell line, RMG-I-H, was developed previously by transfection of the α1,2-fucosyltransferase gene, a key enzyme that catalyzes the synthesis of LeY, into ovarian carcinoma-derived RMG-I cells. Our studies have shown that LeY is involved in the changes in biological behavior of RMG-I-H cells. However, the mechanism is still largely unknown. In this study, we determined the structural relationship and co-localization between LeY and TßRI/TßRII, respectively, and the potential cellular signaling mechanism was also investigated. We found that both TßRI and TßRII contain the LeY structure, and the level of LeY in TßRI and TßRII in RMG-I-H cells was significantly increased. Overexpression of LeY up-regulates the phosphorylation of ERK, Akt and down-regulates the phosphorylation of Smad2/3. In addition, the phosphorylation intensity was attenuated significantly by LeY monoantibody. These findings suggest that LeY is involved in the changes in biological behavior through TGF­ß receptors via Smad, ERK/MAPK and PI3K/Akt signaling pathways. We suggest that LeY may be an important composition of growth factor receptors and could be an attractive candidate for cancer diagnosis and treatment.

Follow-up study of a pregnant woman 16 years after exposure in the Xinzhou radiation accident.

To investigate the late effects of radiation on child-bearing women, a follow-up study was performed on a 39-year-old survivor 16 years after a (60)Co radiation accident. The woman, Fang, was 19 weeks pregnant at the time of exposure. Physical examinations, a full range of clinical laboratory and imaging tests, as well as cytogenetic analyses were conducted to evaluate Fang's current health conditions. Fang shows the appearance of premature ageing and has a decreased menstrual period. Laboratory studies and imaging tests suggest nodular goitre disease and osteoporosis. Otherwise, no apparent abnormalities were found in the major organs. No malignant tumours were detected by either tumour markers or imaging tests. However, the existence of chromosome aberrations warrants long-term follow-up for tumour incidence in the future. Fang became pregnant 8 years after the accident, but suffered a miscarriage due to the death of the foetus at 6 months into the pregnancy. In conclusion, our findings suggest that the intrauterine death of the foetus might be associated with the previous exposure. There is no evidence of malignant tumours as of the date of the follow-up study. Non-cancerous diseases, i.e. thyroid disease and osteoporosis, which may be related to radiation exposure, are the major manifestations of the long-term effects of the accident.