Efficacy and pregnancy outcomes of hysteroscopic surgery combined with progestin as fertility-sparing therapy in patients with early stage endometrial cancer and atypical hyperplasia.

PURPOSE: This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility. METHODS: This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. RESULTS: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/m2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001). CONCLUSION: The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients.

Centralized surveillance of hydatidiform mole: 7-year experience from a regional hospital in China.

OBJECTIVE: To assess the strategy and value of centralized surveillance of hydatidiform mole at a regional hospital in China and to investigate the necessity of prophylactic chemotherapy for high-risk complete hydatidiform mole. METHODS: Between February 2013 and February 2020, all women with hydatidiform mole in Dalian Women's and Children's Medical Center (Group) were registered for surveillance and treatment when indicated. Women with complete hydatidiform mole were categorized into low-risk and high-risk groups according to the criteria from Song Hongzhao's trophoblastic neoplasia. Outcomes and treatments were analyzed retrospectively. RESULTS: In total, 703 women with hydatidiform mole were registered for surveillance with a follow-up rate of 97.9% (688/703). 680 women were enrolled and 52 (7.6%) developed post-molar gestational trophoblastic neoplasia, all with low-risk International Federation of Gynecology and Obstetrics (FIGO) scores 0-5. Post-molar gestational trophoblastic neoplasia was diagnosed in 12.3% (51/413) of patients with complete hydatidiform moles and 0.4% (1/263) of patients were diagnosed with partial hydatidiform moles (χ2=32.415, p<0.001). Post-molar gestational trophoblastic neoplasia was diagnosed in 27.7% (28/101) of the high-risk complete hydatidiform mole group and in 7.4% (23/312) of the low-risk complete hydatidiform mole group (χ2=29.196, p<0.001). No difference in the pre-treatment assessments of patients with post-molar gestational trophoblastic neoplasia was found between the low-risk and high-risk complete hydatidiform mole groups (all p>0.05). All 52 patients with post-molar gestational trophoblastic neoplasia were cured, with a complete response rate of 61.2% (30/49) with first-line single-agent chemotherapy. CONCLUSIONS: A centralized hydatidiform mole surveillance program is feasible and effective and may improve the prognosis of patients with post-molar gestational trophoblastic neoplasia. Prophylactic chemotherapy is not recommended for women with high-risk complete hydatidiform mole with adequate surveillance.

MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma.

One of the best prognostic predictors for patients with epithelial ovarian cancer is the Federation of Obstetrics and Gynecology (FIGO) stage at diagnosis. Advanced-stage ovarian serous carcinoma (OSC) generally have poor prognosis. The goal of this study is to develop and validate a miRNA expression profile that can differentiate the OSC at early and advanced stages and study its correlation with the prognosis of OSC. To identify a unique microRNA (miRNA) pattern associated with the progression of OSC at early and advanced stages, a miRNA microarray was performed using Chinese tumor bank specimens of patients with OSC stage I or III in a retrospective analysis. The expression of four dysregulated miRNAs was validated using quantitative real-time polymerase chain reaction (qRT-PCR) in an external cohort of 51 cases of OSC samples at stages I and III. Kaplan-Meier analysis was performed to analyze the correlation between the expression of some miRNAs and prognosis. Of the 768 miRNAs analyzed in the microarray, 26 miRNAs were significantly either up- or downregulated, with at least a 2-fold difference, in OSC stage I compared with stage III. The qRT-PCR results showed that miR-510, miR-509-5p, and miR-508-3p were significantly downregulated and that miR-483-5p was upregulated in stage III OSC compared with stage I, which was consistent with the microarray results. Kaplan-Meier analysis showed low miR-510 expression, low miR-509-5p expression, and advanced FIGO stage, and chemotherapy resistance were significantly associated with poorer overall survival (P < 0.05). Our results suggest that miRNAs may play a role in the progression of OSC, and miR-510 and miR-509-5p may be considered novel-candidate clinical biomarkers for predicting OSC outcome.

[Free posterior interosseous artery perforator flap in the treatment of finger with skin and soft tissue defect].

OBJECTIVE: To explore clinical effects of repairing skin and soft tissue defect of finger with free posterior interosseous artery perforator flap. METHODS: Totally 8 patients with finger skin and soft tissue defect repaired with free posterior interosseous artery perforator flap were treated from May 2021 to November 2022, including 7 males and 1 female aged from 24 to 54 years old, and soft tissue defect area ranged from 3.0 cm×1.5 cm to 5.0 cm×3.0 cm. The time from injury to flap repair ranged from 3 to 83 h. The free posterior interosseous artery perforator flap was applied to repair finger defect, the area of the flap ranged from 3.5 cm×2.0 cm to 5.2 cm×3.5 cm, the donor area of flap was sutured directly. The survival, appearance, texture and donor complications of the flap were observed after operation, and Dargan functional standard was used to evaluate clinical effect of finger function. RESULTS: All flap of 8 patients were survived, and followed up from 3 to 12 months. There was no obvious swelling, soft texture, obvious pigmentation, linear intaglio in donor area only, and without obvious complications were found. Among them, 3 patients'skin flaps were repaired for the defect of palm of the fingers, and sensory recovery was good, two-point discrimination ranged from 5 to 9 mm. According to Dargan functional evaluation, 3 patients excellent, and 5 good. CONCLUSION: Free posterior interosseous artery perforation branch flap could be used to repair the defect of finger. The thickness of flap is moderate, operation is convenient, appearance and texture of the operative flap are good, and the donor site is small without obvious complications, and obtain satisfactory clinical effect.

Value of the combination of a smartphone-compatible infrared camera and a hand-held doppler ultrasound in preoperative localization of perforators in flaps.

This study was conducted to evaluate the effectiveness of the FLIR ONE PRO, a thermal imaging camera for smartphones, combined with handheld Doppler (HHD) in the localization of perforator arteries and to assess the efficacy of the FLIR ONE PRO in distinguishing perforators of the descending branch of the lateral circumflex femoral artery (LCFA) from other perforators of the anterolateral thigh perforator (ALTP) flap. We enrolled 29 free perforator flaps from 22 patients in our study. Before surgery, dynamic infrared thermography was performed using a FLIR ONE PRO to visualize hotspots on the flaps. Subsequently, HHD was used to further determine the perforators under the hotspots, which were ultimately identified and confirmed through intraoperative findings. Additionally, infrared images of the ALTP flap were analyzed using FLIR Tools. The performances of the FLIR ONE PRO and FLIR ONE PRO + HHD groups were evaluated by comparing the intraoperative findings. Using FLIR ONE PRO + HHD, 119 hotspots and 106 perforators were identified during surgery. Using FLIR ONE PRO + HHD, sensitivity and positive predictive value were 97.87% and 88.46%, respectively, in the young (age≤45 years). In the elderly group (age>45 years), these percentages were 93.22% and 82.09%, respectively. In addition, we found that the FLIR ONE PRO could be useful for differentiating perforators in the descending branch of the LCFA from other perforators within 5 min. The results showed a sensitivity of 96.15%, a specificity of 98.9%, a positive predictive value of 96.15%, and a negative predictive value of 98.9%. Compared to using FLIR ONE PRO alone, the combined application of HHD and FLIR ONE PRO had a higher value in perforator localization by increasing the positive predictive value. The FLIR ONE PRO may have significance in the rapid prediction of perforators deriving from the descending branch of the LCFA.

[Microsurgical thinned anterolateral thigh perforator flap to repair soft tissue defects of foot and ankle].

OBJECTIVE: To explore method and clinical effect of microsurgical thinned anterolateral thigh perforator flap to repair soft tissue defects of foot and ankle. METHODS: From March 2017 to January 2022, totally 20 patients with soft tissue defects of ankle joint were treated with micro-thinning anterolateral perforator flap for free transplantation, included 13 males and 7 females, aged from 22 to 58 years old with an average of (36.45±12.36) years old. The size of flap ranged from 8.0 cm×5.0 cm to 20.0 cm×12.0 cm. Before operation, perforating vessels on the anterolateral thigh region were detected and marked with a portable Doppler detector. For the defect width less than 8 cm, 11 patients were repaired with a single flap. For the defect width more than 8 cm, the wound could not be sutured directly, and the lobulated flap technique was used in 9 patients, the width was converted to length, and the donor site was closed directly. Under the microscope, all flaps were thinened in a stepwise manner from the center of the pedicle to the periphery. After operation, survival of the flap, the shape, texture, sensory function recovery were observes, and recovery of foot function was evaluated by Maryland foot function evaluation standard. RESULTS: All 20 patients with microsurgical thinned anterolateral thigh perforator flaps were survived. Venous crisis occurred in 1 patient due to subcutaneous hematoma, after removal of the hematoma, the crisis was relieved and the flap survived successfully. The wounds in the donor and recipient sites healed well, and only linear scars left in the donor sites. Twenty patients were followed up for 3 to 26 months after operation, good shape of flaps without bloated, and good texture. The two-point discrimination of free flaps ranged from 9.0 to 16.0 mm, and the protective sensation was restored. The ankle flexion and extension function recovered well and patients could walk normally. According to Maryland foot function evaluation standard, 8 patients got excellent result, 10 patients good and 2 middle. CONCLUSION: Microsurgical thinned anterolateral thigh perforator flap is an ideal method to repair soft tissue defects in functional area of foot and ankle, with good appearance and texture of the flap, no need for re-plastic surgery, reduced hospitalization costs, and less donor site damage.

Predictive value of preoperative serum squamous cell carcinoma antigen level for lymph node metastasis in early-stage cervical squamous cell carcinoma.

ABSTRACT: To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ2 = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ2 = 14.339, P < .001), LVSI (χ2 = 12.866, P  < .001), parametrial involvement (χ2 = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.

Sentinel lymph node mapping in high-risk endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: In the staging of endometrial cancer (EC), the role of sentinel lymph node (SLN) mapping for high-risk EC is still unclear. METHODS: Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. English studies published in PubMed, Embase, and Cochrane Library before 20th SEP, 2019 were retrieved to perform a systematic evaluation and meta-analysis which evaluate the detection rate and diagnostic accuracy of SLN mapping in high-risk EC. Statistical analysis was conducted using stata14.0 software. RESULTS: A total of 12 studies were included, including 758 high-risk EC patients. The detection rate of SLN mapping was 84.8% (95% CI, 79.9-89.6%). The pooled bilateral detection rate was 67.0% (95% CI, 56.8-77.3%). The pooled para-aortic detection rate was 8.4% (95% CI, 1.8-14.9%). The pooled sensitivity was 87% (95% CI, 79-92%), and the pooled specificity was 98% (95% CI, 96-99%). Pooled negative predictive value (NPV) was 97.7% (95% CI, 96.4-99.1%), AUC =0.99 (95% CI, 0.97-0.099). CONCLUSIONS: SLN mapping still has a high detection rate and diagnostic accuracy in high-risk EC. SLN mapping is a reliable alternative to systematic lymph node dissection, but its prognostic effect on high-risk EC is yet to be further studied and verified by large sample studies.

Mixed large and small cell neuroendocrine carcinoma of the endometrium with serous carcinoma: A case report and literature review.

RATIONALE: Endometrial neuroendocrine carcinoma is a rare histological subtype of endometrial cancer, divided into low-grade neuroendocrine carcinoma (carcinoid) and high-grade neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma). It is characterized by high invasiveness and poor prognosis. L/SCNEC is an extremely rare pathological type of endometrial carcinoma, and the number of reports on this condition is few globally. PATIENT CONCERNS: A 54-year-old Chinese female presented with vaginal bleeding. DIAGNOSES: Outpatient hysteroscopy and endometrial biopsy were performed, and the pathological examination revealed that cervix was invaded by endometrial malignancy. The patient underwent a laparoscopic radical hysterectomy was diagnosed with the mixed large and small cell neuroendocrine carcinoma (L/SCNEC) of the endometrium combined with serous carcinoma III C2 (FIGO2009). INTERVENTIONS: Chemotherapy-radiotherapy-chemotherapy "sandwich" treatment was performed as postoperative therapy. OUTCOMES: After three chemotherapy circles, the patient showed no evidence of further disease progression. LESSONS: L/SCNEC is a rare and invasive disease. Once diagnosed, comprehensive treatments including surgery, radiotherapy, and chemotherapy can prolong the survival of patients and improve the prognosis.

Prediction of a miRNA-mRNA functional synergistic network for cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CSCC) accounts for a significant proportion of cervical cancer; thus, there is a need for novel and noninvasive diagnostic biomarkers for this malignancy. In this study, we performed integrated analysis of a dataset from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) between CSCC, cervical intraepithelial neoplasia (CIN) and healthy control subjects. We further established protein-protein interaction and DEmiRNA-target gene interaction networks, and performed functional annotation of the target genes of DEmiRNAs. In total, we identified 1375 DEGs and 19 DEmiRNAs in CIN versus normal control, and 2235 DEGs and 33 DEmiRNAs in CSCC versus CIN by integrated analysis. Our protein-protein interaction network indicates that the common DEGs, Cyclin B/cyclin-dependent kinase 1 (CDK1), CCND1, ESR1 and Aurora kinase A (AURKA), are the top four hub genes. P53 and prostate cancer were identified as significantly enriched signaling pathways of common DEGs and DEmiRNA targets, respectively. We validated that expression levels of three DEGs (TYMS, SASH1 and CDK1) and one DEmiRNA of hsa-miR-99a were altered in blood samples of patients with CSCC. In conclusion, a total of four DEGs (TYMS, SASH1, CDK1 and AURKA) and two DEmiRNAs (hsa-miR-21 and hsa-miR-99a) may be involved in the pathogenesis of CIN and the progression of CIN into CSCC. Of these, TYMS is predicted to be regulated by hsa-miR-99a and SASH1 to be regulated by hsa-miR-21.

MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2.

In this study, we examined the role of the miRNA miR-770-5p in cisplatin chemotherapy resistance in ovarian cancer (OVC) patients. miR-770-5p expression was reduced in platinum-resistant patients. Using a 6.128-fold in expression as the cutoff value, miR-770-5p expression served as a prognostic biomarker and predicted the response to cisplatin treatment and survival among OVC patients. Overexpression of miR-770-5p in vitro reduced survival in chemoresistant cell lines after cisplatin treatment. ERCC2, a target gene of miR-770-5p that participates in the NER system, was negatively regulated by miR-770-5p. siRNA-mediated silencing of ERCC2 reversed the inhibition of apoptosis resulting from miR-770-5p downreglation in A2780S cells. A comet assay confirmed that this restoration of cisplatin chemosensitivity was due to the inhibition of DNA repair. These findings suggest that endogenous miR-770-5p may function as an anti-oncogene and promote chemosensitivity in OVC, at least in part by downregulating ERCC2. miR-770-5p may therefore be a useful biomarker for predicting chemosensitivity to cisplatin in OVC patients and improve the selection of effective, more personalized, treatment strategies.

[Dipeptidyl peptidase IV gene expression in ovarian carcinoma cell lines with various maligant behaviour].

OBJECTIVE: To study the relationship between the expression of dipeptidyl peptidase IV (DPP IV) gene and malignant behavior of cells of ovarian carcinoma. METHODS: The differences of the malignant behavior of A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were examined by drawing cell proliferative curves, adhesive test, assay of incursion and chemotaxis. The expression of DPP IV among the cell lines and its relationship with the malignant behavior of ovarian carcinoma cell were detected by techniques of DPP IV activity assay, cytometry and reverse transcription polymerase chain reaction. RESULTS: Among all cell lines, the ability of proliferation, adhesion, incursion and chemotaxis of HO-8910PM were the highest, while those of A2780 were the lowest. The transcription of mRNA in A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were 0.7512 +/- 0.0012, 0.5596 +/- 0.0015, 0.3369 +/- 0.0009, and 0.2777 +/- 0.0006, respectively. The activity of DPP IV were 0.79 +/- 0.02, 0.64 +/- 0.03, 0.21 +/- 0.02, and 0.18 +/- 0.01, respectively; and the protein expression of DPP IV gene were 657.83 +/- 1.14, 538.53 +/- 5.29, 130.50 +/- 1.46, and 33.14 +/- 0.47, respectively, as assayed by cytometry. The correlation coefficients of the transcription of DPP IV gene and the adhesive, incursive and migratory ability of ovarian carcinoma cells were -0.987, -0.983, and -0.991, respectively; the correlation coefficients of the expression of DPP IV and those ability of cells were -0.959, -0.988, and -0.968; the correlation coefficients of the activity of DPP IV and those ability of cells were -0.952, -0.868, and -0.983. CONCLUSION: There is a negative correlation between the expression of DPP IV gene and the adhesive and incursive capability of cells of ovarian carcinoma.

Expression of miR-136 is associated with the primary cisplatin resistance of human epithelial ovarian cancer.

MicroRNAs (miRNAs) are involved in regulating the response of cancer cells to various therapeutic interventions, yet their involvement in the chemoresistance of human epithelial ovarian cancer is not fully understood. We found that miR-136 was significantly downregulated in specimens from patients with chemoresistant epithelial ovarian cancer. In the present study, we aimed to clarify the role of miR-136 in regulating the chemoresistance of ovarian cancer. Thirty-four tumor bank specimens and 2 well-established human ovarian cancer cell lines, C13 and OV2008, were used. We found that miR-136 expression was significantly reduced in primary platinum-resistant patients and the ovarian cancer OVC cell line. Enforced expression of miR-136 decreased the chemoresistance to cisplatin in OVC cells through inhibition of cell survival. In addition, we found no association between miR-136 and migration or invasion potential in the ovarian cancer cell lines. However, in the platinum-resistant C13 cell line, the overexpression of miR-136 markedly promoted an apoptotic response to cisplatin. Furthermore, the levels of adducts corrected with their extent of DNA damage/repair, in terms of the percentage of DNA in comet tails, tail length, tail moment (TM), and olive tail moment (OTM), revealed that miR-136 is essential for the repair of cisplatin-induced DNA damage. Our findings suggest that miR-136 may function as an anti-oncogene and deficiency of miR-136 expression in ovarian cancer can induce chemoresistance at least in part by downregulating apoptosis and promoting the repair of cisplatin-induced DNA damage. Thus, miR-136 may provide a biomarker for predicting the chemosensitivity to cisplatin in patients with epithelial ovarian cancer.

Expression of miR-224-5p is associated with the original cisplatin resistance of ovarian papillary serous carcinoma.

Chemoresistance is a major challenge to successful chemotherapy of ovarian cancer, which represents the leading cause of mortality from gynecologic malignancies. We demonstrated that overexpression of miR-224-5p in ovarian cancer patients is associated with platinum-based chemoresistance using miRNA microarray analysis and quantitative real-time polymerase chain reaction (qRT-PCR) validation in vivo, as well as in 4 human ovarian cancer cell lines (C13/OV2008; A2780CP/A2780S) in vitro. In the present study, we aimed to clarify the role of miR-224-5p in regulating the chemoresistance of ovarian cancer. By using the sensitive miRNA transient transfection, we demonstrated expression and bioactivity of miR-224-5p in ovarian cancer cell lines. It is of note that enforced expression of miR-224-5p enhanced chemoresistance to cisplatin in ovarian cancer cells through apoptosis reversion. We predicted and identified the PRKCD gene as one of the targets of miR-224-5p in mediating the primary chemoresistance of ovarian cancer patients. We showed reciprocal expression of miR-224-5p and PRKCD by quantitative analysis in complete response and incomplete response patients in vivo, and 2 pairs of cisplatin resistance and sensitive cell lines in vitro, after either miR-224-5p overexpression or knockdown transfection. Additionally, miR-224-5p and PRKCD can serve as novel predictors and prognostic biomarkers for ovarian papillary serous carcinoma (OPSC) patient response to overall disease-specific survival. Our findings suggest that miR-224-5p may function as an oncogene and induce platinum resistance in OPSC at least in part by downregulating PRKCD, thereby providing a biomarker for predicting chemosensitivity to cisplatin in patients with ovarian cancer.

The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma.

Histological grade has already been recognized as a very important prognostic factor for ovarian papillary serous carcinoma (OPSC). On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC consisting of types I (low-grade) and II (high-grade) cancers. High-grade OPSC is responsible for most ovarian cancer deaths. The goal of our investigation was to identify the differences in key miRNAs and possible regulators through miRNA microarray chip analysis, as well as functional target prediction and clinical outcome between the low and high-grade OPSC patients. The pathogenic basis in differentiation of ovarian cancer subtypes was studied to provide insight into diagnosis and therapy for high-grade cases. Through microarray analysis, we found that miR-30a* and miR-30e* were the top 2 significantly different miRNAs between type I and type II OPSC patients, and both were remarkably downregulated in the latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a* and miR-30e*, and showed a significant upregulation in type II patients. As ATF3 and MYC are often associated with aggressive behavior and poor differentiation, especially in human cancers, these results are in good agreement with our findings and point toward a regulating differentiation function of the miR-30a* and miR-30e* genes. Further analysis using leave­one-out cross predictions and Kaplan-Meier survival analysis strongly suggested that miR-30a* and miR-30e* can be used as biomarkers to tailor histological grade before starting the regimen, and they showed important roles in ovarian cancer differentiation resulting in poorer prognosis. In general, miR-30a* and miR-30e* coupled with expression data that reveal pathogenic regulation to predict histological differentiation, may operate to direct the formation of early detection and therapeutic approaches to individual OPSC patients, especially differentiation therapy to high-grade cases.

miRNA expression pattern associated with prognosis in elderly patients with advanced OPSC and OCC.

The long-term survival for elderly patients with advanced ovarian papillary serous carcinoma (OPSC) does not exceed 30%, and the incidence and prognosis rise continuously after menopause. The aim of this study was to identify the differences in key miRNAs and their potential regulators through miRNA microarray analysis, functional target prediction, and clinical outcome between the elderly patients with advanced OPSC and ovarian clear cell carcinoma (OCC) who all suffered poor prognosis, to identify the pathogenetic basis, and to improve the understanding of the molecular basis of advanced OPCS in elderly patients. Through microarray analysis, we found 52 unique miRNAs with significant fold­change in expression levels, of which 9 were upregulated, whereas 43 were downregulated in OCC patients compared to elderly OPSC patients with advanced stage. Among these prediction miRNAs, miR-30a, miR-30e and miR-505 were found to have some common cancer-related targets. Lower expression of these three miRNAs of advanced OPSC in elderly patients, all associated with significantly poorer survival rate, strongly suggesting that they could be critical oncogenes and take important roles in OPSC etiology in elderly patients with advantaged stage. Functional analyses support the above hypothesis. Their targets, ATF3, STMN1 and MYC suggest that OPSC also has aggressive biological behavior when presented with advanced stage, and support the epidemiology results that incidence and mortality of advanced OPSC increases continuously. miR-30a, miR-30e and miR-505 may be important pathogenetic factors for OPSC in elderly patients with advanced stage. Age could be regarded as a continuous covariate in this process. This may improve the understanding of molecular underpinnings of advanced OPSC in elderly patients, and provide improved diagnostic, prognostic and therapeutic approaches.

[Effect of hepatocyte growth factor on invasion of ovarian cancer cell line SKOV3 and its signal transduction pathway].

BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF) specifically binds to its receptor c-met, activates a complex set of intracellular pathways, and plays important roles in regulating tumor invasion, metastasis, and angiogenesis. HGF and c-met are overexpressed in ovarian cancer. This study was designed to investigate the role of HGF in ovarian cancer invasion and its signal transduction pathway. METHODS: HGF-induced invasion of ovarian cancer cell line SKOV3 was analyzed with Boyden chamber invasion assay. The expression changes of c-met and matrix metalloproteinase-9 (MMP-9) in SKOV3 cells before and after treatment with HGF and nuclear factor kappaB (NF-kappaB) inhibitor pyrrolidine dithiocarbamate (PDTC) were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and flow cytometry. The expression of NF-kappaB in SKOV3 cells was evaluated by immunocytochemistry and Western blot. RESULTS: The invasive cells were significantly more in HGF group than in control group and PDTC plus HGF group (343+/-13 vs. 167+/-11 and 241+/-10, P<0.01). HGF promoted the expression of MMP-9 mRNA by 5.66+/-0.10 folds, but had no effect on c-met mRNA expression; PDTC suppressed the HGF-driven expression of MMP-9 mRNA by 2.75+/-0.80 folds. The positive rates of c-met and MMP-9 were significantly higher in HGF-treated cells than in control cells [(96.6+/-2.0)% vs. (73.3+/-2.4)%, P<0.01; (74.6+/-4.4)% vs. (16.0+/-2.9)%, P<0.01]. The protein levels of c-met and MMP-9 were significantly higher in HGF-treated cells than in control cells (2.84+/-0.18 vs. 1.65+/-0.19, P<0.01; 2.94+/-0.13 vs. 0.54+/-0.18, P<0.01). PDTC significantly suppressed the HGF-driven expression of MMP-9 protein: the positive rate and protein level of MMP-9 were (25.8+/-3.7)% and 0.87+/-0.14 (P<0.05). HGF promoted the expression of NF-kappaB protein in a time-dependent manner. The expression peak appeared 1 h after treatment with HGF (from 0.42+/-0.11 to 1.16+/-0.21, P<0.01). PDTC significantly inhibited the HGF-driven expression of NF-kappaB protein (0.38+/-0.12, P<0.01). CONCLUSION: HGF might stimulate the invasion of SKOV3 cells by up-regulating the expression of MMP-9 via NF-kappaB pathway.

[Effect of environmental supplementation of iodine on infant mortality and growth in children in Xinjiang, China].

OBJECTIVE: To study the effect of iodine supplementation on infant mortality and growth in Xinjiang. METHODS: Urine iodine, height and head circumference (HC) of children aged 5 years in two townships was measured before and yearly after iodine supplementation of irrigation water. Height and HC were expressed as Z scores (United States children used as the reference group). Neonatal and infant mortality rates were obtained from official records in three counties from 1988 to 1999, and analyzed by a logistic regression model. RESULTS: The odds ratio of infant mortality decreased 56.49% and neonatal mortality 65.71% respectively after iodination; there was no significant difference in the odds ratio of infant or neonatal mortality between experimental and control areas without iodination. In Langru township, the mean height of 5 year-old children increased from 95 cm in 1992 to 106.9 cm in 1998 - 1999, and HC from 48.4 cm to 50.5 cm. Median urine iodine increased from <10 to 176 micro g/L. In Bakechi township, mean height increased from 91 cm in 1993 to 106.5 cm in 1998 - 1999, HC from 48.7 to 49.6 cm, and median urine iodine from 39 to 138 micro g/L. CONCLUSION: In Xinjiang, adequate iodine treatment markedly decreased infant and neonatal mortality, and largely preventing stunting of height and HC in children.