Efficient Tin-Lead Perovskite Solar Cells with a Ultrawide Usage Windows of Precursor Solution Opened by SnF2.

High quality tin-lead perovskite solar cells (Sn─Pb PSCs) can be fabricated via simple solution processing methods. However, the instability of precursor solutions and their narrow usage windows still pose challenges in manufacturing efficient and reproducible Sn─Pb PSCs, hindering the commercialization of PSCs. Fluorine tin (SnF2) is widely used as an antioxidant to improve the crystallinity of perovskite. In this study, another role of SnF2 as a stabilizer is found to restrain the deprotonation of methylammonium iodide (MAI) in the precursor solution, which improves their stability and expands their usage windows. Due to the inhibition of SnF2 on oxidation and deprotonation, stable large-sized colloidal clusters form gradually in perovskite precursor solution during aging, leading to uniform nucleation/crystallization during film growth, significantly reducing the roughness and defect density in the films. Because of the competitive deprotonation and oxidation process of Sn2+, the benefit of larger cluster maximizes after about ten days storage of precursor solution. The champion efficiency of Sn─Pb PSCs prepared with 10 days aged precursor solution is 22.00%. High performance of devices fabricated with precursor solution stored for even ≈40 days discloses the wide usage windows of precursor solution with SnF2 additive.

Differential diagnosis of non-molar gestational trophoblastic neoplasia with ectopic pregnancy by clinical-pathological features.

PURPOSE: This study was presented to investigate the clinical-pathological characteristics of gestational trophoblastic neoplasia (GTN) following non-molar pregnancy and differentiated with ectopic pregnancy (EP). METHODS: The clinical data of 83 patients who were admitted for suspected GTN after non-molar pregnancy at the Women's Hospital School of Medicine Zhejiang University from January 2015 to September 2022 were selected for analysis. RESULTS: In total, 41 cases were confirmed non-molar GTN, including 31 choriocarcinoma, 9 PSTT (placental site trophoblastic tumor), and 1 ETT (epithelioid trophoblastic tumor), while 42 cases were confirmed EP. Compared with ectopic pregnancy, non-molar GTN patients had lower levels of serum progesterone compared with EP (3.81 nmol/L vs 17.70 nmol/L, P = 0.001). Based on the ultrasound, the thickness of the endometrium was thinner in patients with non-molar GTN compared with EP (0.565 cm vs 0.70 cm, P = 0.018). By histopathologic examination, the endothelium of non-molar GTN showed less decidual-like changes compared with EP (64.3% vs 14.6%, P = 0.001). CONCLUSION: A combination of serum progesterone levels, endometrium thickness, and histopathologic features of the endometrium can help to differentiate non-molar GTN and EP. Surgeries including hysteroscopy with curettage and/or laparoscopy are needed.

NDR1 increases NOTCH1 signaling activity by impairing Fbw7 mediated NICD degradation to enhance breast cancer stem cell properties.

BACKGROUND: The existence of breast cancer stem cells (BCSCs) causes tumor relapses, metastasis and resistance to conventional therapy in breast cancer. NDR1 kinase, a component of the Hippo pathway, plays important roles in multiple biological processes. However, its role in cancer stem cells has not been explored. The purpose of this study was to investigate the roles of NDR1 in modulating BCSCs. METHODS: The apoptosis was detected by Annexin V/Propidium Iodide staining and analyzed by flow cytometry. BCSCs were detected by CD24/44 or ALDEFLUOR staining and analyzed by flow cytometry. The proliferation ability of BCSCs was evaluated by sphere formation assay. The expression of interested proteins was detected by western blot analysis. The expression of HES-1 and c-MYC was detected by real-time PCR. Notch1 signaling activation was detected by luciferase reporter assay. Protein interaction was evaluated by immunoprecipitation. Protein degradation was evaluated by ubiquitination analysis. The clinical relevance of NDR1 was analyzed by Kaplan-Meier Plotter. RESULTS: NDR1 regulates apoptosis and drug resistance in breast cancer cells. The upregulation of NDR1 increases CD24low/CD44high or ALDEFLUORhigh population and sphere-forming ability in SUM149 and MCF-7 cells, while downregulation of NDR1 induces opposite effects. NDR1 increased the expression of the Notch1 intracellular domain (NICD) and activated the transcription of its downstream target (HES-1 and c-MYC). Critically, both suppression of Notch pathway activation by DAPT treatment or downregulation of Notch1 expression by shRNA reverses NDR1 enhanced BCSC properties. Mechanically, NDR1 interactes with both NICD or Fbw7 in a kinase activity-independent manner. NDR1 reduces the proteolytic turnover of NICD by competing with Fbw7 for NICD binding, thereby leading to Notch pathway activation. Furthermore, NDR1 might function as a hub to modulate IL-6, TNF-α or Wnt3a induced activation of Notch1 signaling pathway and enrichment of breast cancer stem cells. Moreover, we find that the elevation of NDR1 expression predictes poor survival (OS, RFS, DMFS and PPS) in breast cancer. CONCLUSION: Our study revealed a novel function of NDR1 in regulating BCSC properties by activating the Notch pathway. These data might provide a potential strategy for eradicating BCSC to overcome tumor relapses, metastasis and drug resistance.

Clinicopathological features and outcomes in gastric-type of HPV-independent endocervical adenocarcinomas.

BACKGROUND: We aimed to analyze the clinicopathological features and outcomes of patients with gastric-type of HPV-independent endocervical adenocarcinoma (GAS HPVI ECA), and compare them with non-GAS HPVI ECA cases. METHODS: Thirty-eight GASs [including 17 minimal deviation adenocarcinoma (MDA), 21 non-MDA GAS] and 17 non-GAS HPVI ECAs were studied. Data of clinical features, pathological characteristics, treatment, and outcomes were evaluated. RESULTS: The median age of patients with GAS and non-GAS HPVI ECA was 46 and 48 years, respectively (p = 0.93). Compared with non-GAS HPVI ECAs, GAS had more common complains of vaginal watery discharge (p = 0.04). GAS cases were also associated with higher clinical stage (p = 0.036), more common in deeper cervical stromal invasion (p = 0.002) and lymphoavascular invasion (p = 0.044). GAS was associated with worse median progression-free survival (PFS) (p = 0.02) and median overall survival (OS) (p = 0.03) over patients with non-GAS HPVI ECAs. MDA had similar clinical and pathological features and prognosis compared with non-MDA GAS. Of note, serum CA19-9 levels were significantly higher in GAS than that in non-GAS HPVI ECA cases. CONCLUSIONS: GAS cases were more likely to have high risk pathological factors and poorer PFS and OS compared with non-GAS HPVI ECAs. Serum CA19-9 may be helpful for diagnosis and screening in patients with GAS.

Notch1 Affects Chemo-resistance Through Regulating Epithelial-Mesenchymal Transition (EMT) in Epithelial Ovarian cancer cells.

Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, chemo-resistance is the main cause for treatment failure. Our previous studies have found that SKOV3 could promote immune escape and tumor progression via Notch1 pathway. Therefore, Notch1 is suspected to be involved in chemo-resistance. The current study is to investigate the possible mechanisms of platinum-resistance in epithelial ovarian cancer mediated by Notch1. Methods: The expressions of Notch1, Snail, MMP-2, N-cadherin, Vimentin and E-cadherin were detected by Western-blot. A stable high expression or low expression of Notch1 in ovarian cancer cells was established by using lentiviral gene engineering. The cell migration and invasion ability were observed by scratch test and transwell test. Cell apoptosis rate and cell cycle were analyzed by flow cytometry. Results: The expression levels of Notch1, Snail, MMP-2, N-cadherin and Vimentin in ovarian cancer were high, while the expression levels of E-cadherin were low.Notch1 promoted the expression of Snail, vimentin, N-cadherin and MMP2 protein, but inhibiting the expression of E-cadherin, promoting cell migration and invasion. Notch1 affected apoptosis of cells through Epithelial-Mesenchymal Transition (EMT), increasing the proportion of cells in S phase and G2 phase, thus affecting drug resistance. Conclusion: Notch1 affects EOC cells chemo-resistance by regulating EMT. This may provide a new target for the treatment of ovarian cancer.

Effects of Interferometric Radar Altimeter Errors on Marine Gravity Field Inversion.

The traditional altimetry satellite, which is based on pulse-limited radar altimeter, only measures ocean surface heights along tracks; hence, leads to poorer accuracy in the east component of the vertical deflections compared to the north component, which in turn limits the final accuracy of the marine gravity field inversion. Wide-swath altimetry using radar interferometry can measure ocean surface heights in two dimensions and, thus, can be used to compute vertical deflections in an arbitrary direction with the same accuracy. This paper aims to investigate the impact of Interferometric Radar Altimeter (InRA) errors on gravity field inversion. The error propagation between gravity anomalies and InRA measurements is analyzed, and formulas of their relationship are given. By giving a group of possible InRA parameters, numerical simulations are conducted to analyze the accuracy of gravity anomaly inversion. The results show that the accuracy of the gravity anomalies is mainly influenced by the phase errors of InRA; and the errors of gravity anomalies have a linear approximation relationship with the phase errors. The results also show that the east component of the vertical deflections has almost the same accuracy as the north component.

Clinical Predictors of Recurrence and Prognostic Value of Lymph Node Involvement in the Serous Borderline Ovarian Tumor.

AIM: This study was aimed to evaluate the risk factors of recurrence and the value of nodal involvement in patients with serous borderline ovarian tumors (SBOT). METHODS: Two hundred twenty-five patients who underwent surgery and were diagnosed with SBOT were retrospectively studied. Univariate and multivariate analyses were used to assess the risk factors for recurrence. Patients' clinical pathologic characteristics were compared between the patients who presented lymph node involvement and those who did not. The significant values of lymph condition influencing 5-year disease-free survival were also evaluated by statistical analysis. RESULTS: Both univariate and multivariate analyses showed that risk factors for recurrence were micropapillary (P = 0.021), fertility-preserving surgery (P = 0.014), and laparoscopic approach (P = 0.009). Of these 112 patients on whom lymphadenectomy was performed, 17 cases showed lymph node positive, whereas the remaining 95 patients did not. Significant differences in terms of lymph node numbers (P < 0.0001), invasive implant (P = 0.022), and International Federation of Gynecology and Obstetrics staging (P < 0.0001) were observed between the 2 groups of lymphatic node involved or not. Kaplan-Meier curves of 5-year disease-free survival revealed that there were no significant differences either between groups of lymphatic node involved or not (P = 0.778) and groups of removed nodes whether more than 10 or not (P = 0.549). CONCLUSIONS: Micropapillary, fertility-preserving, and laparoscopic approach were factors significantly affecting the recurrence of SBOT by both univariate and multivariate analysis. Lymph node metastasis did not seem to be correlated to a worse prognosis of SBOT.

A metastatic invasive mole arising from iatrogenic uterus perforation.

BACKGROUND: Invasive mole derives from hydatidiform mole, but its pathogenesis remains unknown. Invasive mole arising from iatrogenic uterine perforation has not been reported yet. CASE PRESENTATION: A reproductive woman was admitted because she suffered form severe abdominal pain and acute intra-abdominal hemorrhage after suction evacuation due to misdiagnosis as inevitable abortion. The patient underwent hysteroscopy and laparoscopy, by which an iatrogenic uterine perforation and omentum and pelvic peritoneum metastases were confirmed. All lesions were removed and the final pathological diagnosis was metastatic invasive mole. The patient underwent post-operative chemotherapy with methotrexate and presented a good prognosis. CONCLUSION: Invasive mole arising form iatrogenic uterine perforation displays an unusual metastatic manner other than general invasive moles. The prevention of uterine perforation should be emphasized during suction evacuation for mole pregnancy.

Inhibition of Notch 1 receptor influenced the differentiation of Lin-CD45RA-dendritic cell precursors within ovarian carcinoma microenvironment.

BACKGROUND: Previous evidence suggested that the differentiation of Lin-CD45RA-DC precursors were prior to plasmcytoid dendritic cells (pDCs) than myeloid dendritic cells (mDCs) within ovarian cancer microenvironment. However, the mechanism is still unclear. Therefore, we investigated the function of Notch 1 signal pathway in the differentiation of Lin-CD45RA-DC precursors. METHODS: The CD34+ hematopoietic stem cells were extracted from umbilical cord blood in term parturition, and Lin-CD45RA-DC precusors were separated and induced mature. Expression of Notch1 receptor and ligands in Lin-CD45RA-DC precusors was detected by Real-time PCR and was down-regulated by shRNA or γ-secretase inhibitor (GSI). Flow cytometry was used to analyze the subset of DCs with or without SKOV3 culture supernatants. IL-12 level was detected by ELISA. RESULTS: Expression of Notch1 receptors and ligands were detected in Lin-CD45RA-DC precursor cells. The Notch1 mRNA in Lin-CD45RA-DC precursors can be down-regulated by shRNA-Notch1 lentivirus transfection and GSI. ShRNA mediated Notch 1 knock-down significantly differentiated less plasmcytoid dendritic cells (pDCs), but generated more myeloid dendritic cells (mDCs), and this would not be influenced by the supernatant of the ovarian carcinoma cell line. GSI had the same effect in the differentiation of pDC. The secretion of IL-12 significantly increased after Notch1 knock-down with or without SKOV3 culture supernatants. CONCLUSIONS: Notch1 is an important signaling pathway in the differentiation of Lin-CD45RA-DC precursor cells to plasmcytoid dendritic cells (pDCs). And this would not be affected by the supernatant of the ovarian carcinoma cell line.

Long-term outcome of patients with persistent low-level elevation of human chorionic gonadotrophin.

AIM: The aim of this study was to investigate a series of patients with sustained low-level elevated human chorionic gonadotrophin (hCG) and explore the management of these patients. METHODS: A total of 47 patients with persistent low levels of hCG were selected for analysis between January 2002 and January 2014 at the Women's Hospital of Zhejiang University, Hangzhou, China. Data were retrospectively reviewed for patient characteristics, therapeutic strategies, and follow-ups. We compared the characteristics of patients who were and were not eventually considered to have malignancies. RESULTS: Among the 47 patients, 17 with persistent low-level elevated hCG and no detectable lesions were considered to have no active malignancy. Fifteen of the 17 patients had hCG levels that returned to normal range by the end of follow-up, while the remaining two did not. The other 30 patients were eventually diagnosed as having active malignancies due to detected lesions or increasing elevation of hCG. A large proportion of these patients were diagnosed with placental site trophoblastic tumor or epithelioid trophoblastic tumor. CONCLUSION: For patients with persistent low-level elevated hCG, frequent follow-up rather than any therapy is recommended. Treatment was considered effective and safe once diagnosis of active malignancy was confirmed.

Analysis of Clinical Characteristics and Outcomes in 7 Patients with Re-recurrent Gestational Trophoblastic Neoplasia.

OBJECTIVE: To analyze the clinical characteristics and outcomes of patients with re-recurrent gestational trophoblastic neoplasia (GTN). STUDY DESIGN: A total of 547 patients with typical GTN at our institution from 2000-2012 were enrolled in this retrospective study. Of 547 cases, 29 relapsed after initial remission, and 7 of 29 patients with recurrent GTN had repeat relapses. The detailed clinical charac- teristics of patients with re-recurrent GTN were eval- uated. RESULTS: The recurrence and re-recurrence rates in 547 patients with GTN were 5.3% and 24%, respective- ly. In 7 patients with re-recurrent GTN the mean age was 43 years. The mean level of serum [-hCG before each treatment was 11,405 IU/L. The mean time interval from last treatment to recurrence was 38 months. All 7 patients received first- and second-line chemotherapy, and 4 of them required salvage chemotherapy. The total number of chemotherapy courses administered was 137 (mean= 6). In conjunction with chemotherapy, surgery was performed in all 7 patients. After final treatment 7 patients had a median follow-up of 20 months. Although 1 died secondary to disease progression, the remaining 6 achieved serologic complete remission. CONCLUSION: Our anal- ysis suggests that surgical intervention and intensive chemotherapy could be equally important for the treatment of . the patients with re-recurrent GTN. Be- cause the patients have a favorable prognosis, the principles of treatment for re-recurrent GTN should strive to cure.disease rather than simply relieve the symptoms of disease or delay the time of relapse.

Methylation-associated Has-miR-9 deregulation in paclitaxel- resistant epithelial ovarian carcinoma.

BACKGROUND: Drug resistance is still one of the key causes of death in epithelial ovarian carcinoma (EOC) patients, however there are very few strategies to reverse chemoresistance. Here we try to clarify whether and how miR-9 takes part in the regulation of paclitaxel sensitivity. METHODS: miR-9 expressions in EOC cells and tissues were detected by Realtime PCR. The target of miR-9 was validated through dual luciferase reporter assay and Western Blot. Methylation study, RNAi technique and cytotoxicity assay were used to determine the intrinsic mechanism of miR-9 in paclitaxel sensitivity regulation. RESULTS: miR-9 is down-regulated in paclitaxel resistant EOC. The patients with lower miR-9, Grade 3, Stage III -IV and suboptimal surgery present shorter survival time. miR-9 and suboptimal surgery are independent prognostic factors of EOC. Modulating miR-9 expression could change paclitaxel sensitivity of EOC cells. CCNG1, validated as a direct target of miR-9, mediates paclitaxel resistance. miR-9-1 and 3 gene hypermethylation would decrease miR-9 expression, while demethylation of miR-9 gene could restore miR-9 expression and improve paclitaxel sensitivity in chemoresistance EOC cells. Furthermore, methylation-associated miR-9 deregulation in EOC cells could be induced by paclitaxel exposure. CONCLUSIONS: Methylation-associated miR-9 down-regulation is probably one of the key mechanisms for paclitaxel resistance in EOC cells, via targeting CCNG1. Our findings may also provide a new potential therapeutic target to reverse paclitaxel resistance in EOC patients.

[Reliability and Validity of the Jefferson Scale of Physician Empathy in Chinese Medical Students].

OBJECTIVE: To access the reliability and validity of the student version of Jefferson Scale of Physician Empathy (JSPE-S). METHODS: The JSPE-S was translated into Chinese using back-translation procedures and administered to 358 Chinese medical students at Sichuan University. The reliability was evaluated with Split-half reliability and internal consistency. The validity was analyzed using discriminate validity, convergent validity and structure validity. RESULTS: The JSPE-S had a split-half reliability coefficient of 0.853 and Cronbach alpha of 0.861. The convergent test achieved 95.0% success rate. The discriminant test achieved 95.0% success rate. Three factors were extracted, with a cumulative variance contribution of 50.87%. The estimated factor loading ranged from 0.485 to 0.834, with factor variance ranging from 1.736 to 4.625. CONCLUSION: The Chinese JSPE-S has satisfactory reliability and validity in medical students.

Chelating Dual Interface for Efficient and Stable Crystal Growth and Iodine Defect Management in Sn-Pb Perovskite Solar Cells.

Suppressing Sn2+ oxidation and rationally controlling the crystallization process of tin-lead perovskite (Sn-Pb PVK) films by suitable bonding methods have emerged as key approaches to achieving efficient and stable Sn-Pb perovskite solar cells (PSCs). Herein, the chelating coordination is performed at the top and bottom interfaces of Sn-Pb PVK films. The chelation strength is stronger toward Sn2+ than Pb2+ by introducing oligomeric proanthocyanidins (OPC) at the bottom interface. This difference in chelation strength resulted in a spontaneous gradient distribution of Sn/Pb within the perovskite layer during crystallization, particularly enhancing the enrichment of Sn2+ at the bottom interface and facilitating the extraction and separation of photogenerated charge carriers in PSCs. Simultaneously, this top-down distribution of gradually increasing Sn content slowed down the crystallization rate of Sn-Pb PVK films, forming higher-quality films. On the top interface of the PVK, trifluoroacetamidine (TFA) was used to inhibit the generation of iodine vacancies (VI) through chelating with surface-uncoordinated Pb2+/Sn2+, further passivating defects while suppressing the oxidation of Sn2+. Ultimately, the PSCs with simultaneous chelation at both top and bottom interfaces achieved a power conversion efficiency (PCE) of 23.31% and an open-circuit voltage (VOC) exceeding 0.90 V. The stability of unencapsulated target devices in different environments also improved.

Case report: Squamous cell carcinoma and spindle cell sarcoma (SCS) arising in a mature cystic teratoma of the ovary.

Objective: Malignant transformation of mature ovarian teratoma is a rare phenomenon, mainly occurring in postmenopausal period. Squamous cell carcinoma accounts for 80% of all malignant transformations. Sarcoma transformation is much less common and tends to imply a poorer prognosis and aggressiveness. Case report: We report a case of undifferentiated sarcoma with squamous cell carcinoma in a mature cystic teratoma of the ovary in a 36-year-old woman. The tumor shows epithelial and stromal components. This is a unique report of a benign teratoma of the ovary with malignant transformation, showing epithelial and sarcomatous components. This young woman presented with abdominal distension and a rapidly enlarging ovario-derived pelvic mass with a slightly elevated CA199 tumor marker of 115.9 U/ml. The woman underwent transabdominal excision of the left ovarian cyst on October 20, 2020. During the operation, rapid freezing pathological examination did not indicate malignancy. The postoperative paraffin pathology revealed undifferentiated sarcoma with squamous cell carcinoma (from mature cystic teratoma malignancy), and she finally received comprehensive staging surgery. Postoperative paraffin pathology showed no residual cancer in uterus and other tissues, and all lymph nodes were negative. The patient was finally diagnosed with ovarian malignant tumor IC1 stage (high-grade spindle cell sarcoma complicated with squamous cell carcinoma). Chemotherapy was completed three times after surgery, and no signs of recurrence were found after follow-up. Conclusion: The preoperative diagnosis and intraoperative rapid freezing examination of malignant transformation of mature teratoma of ovary are challenging.

Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ.

OBJECTIVE: To compare the safety between cervical conization (CC) alone and hysterectomy for patients with adenocarcinoma in situ (AIS) of the cervix. METHODS: Patients diagnosed with AIS after CC during 2007-2021 were identified by computerized databases at Women's Hospital of Zhejiang University School of Medicine. A total of 453 AIS patients were divided into 2 groups according to uterus preservation: hysterectomy group (n=300) and CC(s) alone group (n=153). The prevalence of residual disease and disease recurrence was compared between patients treated by CC(s) alone and hysterectomy. The prevalence of residual disease in specimens from women who had a hysterectomy and repeat CC were compared between positive and negative margins of CC. The factors influencing residual disease and disease recurrence were assessed. RESULTS: Among 310 specimens from women who had a hysterectomy or repeat CC, the prevalence of residual disease was 50.6% (45/89) for a positive margin and 2.3% (5/221) for a negative margin (p=0.000). Four patients had recurrence of vaginal intraepithelial neoplasia in those treated by hysterectomy and one had recurrence of cervical squamous intraepithelial neoplasia in those treated by CC(s) alone. The prevalence of recurrence was 0.7% (1/153) for CC(s) alone and 1.3% (4/300) for hysterectomy (p=0.431). Hysterectomy did not influence residual disease or disease recurrence. CONCLUSION: CC is an efficacious and safe option for patients with AIS of the cervix provided the margin is negative.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1.

Pelvic lymph node metastases are regarded as the most important risk factor and a predictor of poor prognosis for patients with cervical cancer. Exploration of metastasis-related molecules is helpful toward improving the prognosis in cervical cancer. To identify the role of miR-375 in metastasis and progression of cervical cancer, we examined the expression of miR-375 in 170 cervical cancer tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and found that the expression of miR-375 in cervical cancer tissues was significantly decreased by 4.45-fold, compared with 68 normal tissues. A significant correlation existed between miR-375 expression and clinicopathologic parameters, including lymph node metastasis of cervical cancer. Overexpressed miR-375 suppressed cell proliferation, blocked G1-to-S cell-cycle transition, and inhibited cell migration and invasion in human cervical SiHa and CaSki cells. SP1, a potential target gene of miR-375, was inversely correlated with miR-375 expression in cervical cancer tissues. Moreover, SP1 was negatively regulated by miR-375, and knockdown of SP1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that down-regulated miR-375 promotes cell malignant behaviors via the target gene SP1 and may consequently contribute to the progression of cervical cancer.

Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29.

miRNAs have the potential to act on diverse downstream genes, and miRNA signatures of HPV-infected tissues may provide insight into HPV-related carcinogenesis. We set out to profile miRNA expression in HPV-infected samples and relate this to histological and grade-specific alterations in the spectrum of cervical carcinogenesis in vivo. A total of 31 miRNAs showed significant and continuous expression along with the progression from normal cervical tissue to cancer, and six of them were validated in 133 samples. By bioinformatics analyses, we established a putative HPV-associated miRNA-mRNA regulatory network, showing that miR-29 is the most highly enriched. We also found that YY1 and CDK6 were both positively correlated with E6/E7 RNA expression and targeted by tumour-suppressive miR-29. Evidence of miR-29 involvement in HPV infection was further verified in patient samples and by various experimental approaches. Taken together, our results suggest that HPVs have oncogenic properties at least in part by reshaping the milieu of cellular miRNAs. miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way.

[Expression and clinical significance of GRIM-19 in epithelial ovarian carcinoma].

OBJECTIVE: To investigate the expression and clinicopathological features of gene associated with retinoid-interferon mortality-19 (GRIM-19) in epithelial ovarian carcinoma. METHODS: The expression of GRIM-19 gene in tissues from 138 cases of epithelial ovarian carcinoma, 102 cases of benign ovarian epithelial tumor and 46 cases of normal ovarian tissues were detected by Immunohistochemistry and Western blot methods. Assembled clinical survival data were analyzed with Kaplan-Meier and Cox regression models. RESULTS: The expression level of GRIM-19 in epithelial ovarian carcinoma (3.4 ± 2.0) was lower than that in benign ovarian tumor tissues (4.7 ± 2.9) and that in normal ovarian tissues (7.5 ± 2.2; P < 0.01). The level of GRIM-19 expression was related to the survival time of epithelial ovarian carcinoma patients by Kaplan-Meier analysis (P = 0.002). The shorter survival time of epithelial ovarian carcinoma patients was significantly associated with the level of GRIM-19 expression (P = 0.001), clinical stage (P = 0.001), volume of ascites (P = 0.023) and the largest diameter of the primary tumor lesion (P = 0.044) by Cox regression models. CONCLUSIONS: The low expression of GRIM-19 in the epithelial ovarian carcinoma suggests that GRIM-19 may be a key gene involved in its carcinogenesis. The expression level of GRIM-19 may be also an independent prognostic factor for epithelial ovarian carcinoma patients.