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Continuous estrogen signaling is thought to be the main mechanism causing endometrial cancer (EC). Studies have demonstrated that CD163

Sialyltransferases transfer sialic acid to nascent oligosaccharides and are upregulated in cancer. The inhibition of sialyltransferases is emerging as a potential strategy to prevent metastasis in several cancers, including ovarian cancer. ST3GAL1 is a sialyltransferase that catalyzes the transfer of sialic acid from cytidine monophosphate-sialic acid to galactose-containing substrates and is associated with cancer progression and chemoresistance. However, the function of ST3GAL1 in ovarian cancer is uncertain. Herein, we use qRT-PCR, western blotting, and immunohistochemistry to assess the expression of ST3GAL1 in ovarian cancer tissue and cell lines and investigate whether it influences resistance to paclitaxel in vitro and in a mouse xenograft model. We found that ST3GAL1 is upregulated in ovarian cancer tissues and in the ovarian cancer cell lines SKOV-3 and OVCAR3 but downregulated in A2780 ovarian cancer cells. Overexpression of ST3GAL1 in A2780 cells increases cell growth, migration, and invasion whereas ST3GAL1 knockdown in SKOV-3 cells decreases cell growth, migration, and invasion. Furthermore, overexpression of ST3GAL1 increases resistance to paclitaxel while downregulation of ST3GAL1 decreases resistance to paclitaxel in vitro, and overexpression of ST3GAL1 increases tumorigenicity and resistance to paclitaxel in vivo. Transforming growth factor-β1 can increase ST3GAL1 expression and induce ovarian cell epithelial–mesenchymal transition (EMT). However, knockdown of ST3GAL1 inhibits EMT expression. Taken together, our findings have identified a regulatory mechanism involving ST3GAL1 in ovarian cancer. ST3GAL1 may be a promising target for overcoming paclitaxel resistance in ovarian carcinoma.

BACKGROUND: Decidual γδ T cells are known to regulate the function of trophoblasts at the maternal–fetal interface; however, little is known about the molecular mechanisms of cross talk between trophoblast cells and decidual γδ T cells. METHODS: Expression of chemokine C-X-C motif ligand 6 (CXCL16) and its receptor CXCR6 was evaluated in first-trimester human villus and decidual tissues by immunohistochemistry. γδ T cells were isolated from first-trimester human deciduae and cocultured with JEG3 trophoblast cells. Cell proliferation and apoptosis-related molecules, together with cytotoxicity factor and cytokine production, were measured by flow cytometry analysis. RESULTS: Expression of CXCL16 and CXCR6 was reduced at the maternal–fetal interface in patients who experienced unexplained recurrent spontaneous abortion as compared to healthy pregnancy women. With the administration of pregnancy-related hormones or coculture with JEG3 cells, CXCR6 expression was upregulated on decidual γδ T cells. CXCL16 derived from JEG3 cells caused a decrease in granzyme B production of decidual γδ T cells. In addition, decidual γδ T cells educated by JEG3-derived CXCL16 upregulated the expression of Bcl-xL in JEG3 cells. CONCLUSION: This study suggested that the CXCL16/CXCR6 axis may contribute to maintaining normal pregnancy by reducing the secretion of cytotoxic factor granzyme B of decidual γδ T cells and promoting the expression of antiapoptotic marker Bcl-xL of trophoblasts.

Over the past few years, significant efforts have been made to create new fluorescent probes operating at longer wavelengths, particularly in the second near-infrared (NIR-II) window from 1000 to 1700 nm, offering enhanced tissue penetration compared to light in the visible and first near-infrared window (700-900 nm). However, most of the reported NIR-II fluorophores meet such dilemmas; they are excreted slowly and largely retained within the reticuloendothelial system. Here, we report a rapidly excreted NIR-II lanthanide complex Nd-DOTA (over 50% excreted through the kidneys within 3 h postinjection) with a molecular mass only 0.54 kDa. The NIR-II imaging quality of Nd-DOTA was far superior to that of clinically approved ICG with good photostability and deep tissue penetration (7 mm). Superior tumor-to-normal tissue ratio was successfully achieved to facilitate the abdominal ovarian metastases surgical delineation. Metastases with ≤1 mm can be completely excised under NIR-II bioimaging guidance. Significantly, since the Nd-DOTA structure is same to the clinically approved magnetic resonance imaging (MRI) contrast Gd-DOTA, it will speed up the clinical translation for this novel kind of NIR-II probes in the future.

Krukenberg tumor (KT) is an uncommon ovarian metastatic signet-ring cell adenocarcinoma that mostly metastasizes from gastrointestinal carcinoma. Optimal treatment options for KTs are limited. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have shown remarkable activity in clinical trials for metastatic tumors. Here, we evaluated PD-L1 expression and T cell infiltration in KTs and their corresponding primary tumors. Positive tumor PD-L1 expression was detected in 9 (25.7%) KTs from gastric carcinomas (GCs) and in 20 (66.7%) KTs from colorectal carcinomas (CRCs). Patient survival was assessed according to the PD-L1 status and CD8+ T cell density. Positive tumor PD-L1 expression in KTs from GCs was associated with poor prognosis. In contrast, positive tumor PD-L1 expression in KTs from CRCs was associated with an improved prognosis. We analyzed copy number variations of the PD-L1 gene in KTs. PD-L1 expression was higher in cases with copy number gains. The T cell densities within KTs and their corresponding primary tumors were compared. The densities of CD8+ T cells correlated significantly between the primary tumors and KTs from the same case. Taken together, the research further highlighted targets for immune-based therapy in KTs from GCs and CRCs.

Although human papillomavirus (HPV) infection is a major cause leading to the development of cervical intraepithelial neoplasia (CIN), the relationship between genital microbiome and HPV persistence/clearance is not well established. Loop electrosurgical excision procedure (LEEP) is one of standard treatments of CIN 2/3 globally, yet little is known about how the LEEP influence genital microbiota. We conducted a prospective study of 26 patients with CIN2/3 who underwent analysis of cervical microbiome before and after 3 months of LEEP treatment. Cervical swabs were collected, and microbiomes were analyzed by 16S ribosomal RNA gene sequencing. A decrease of cervical microbial diversity was observed after 3 months of LEEP treatment. Notably, a significant shift from community type of a Prevotella-containing and lack of a consistent dominant species to lactobacillus iners dominated microbiome correlated with LEEP. Particularly, Leptotrichia and clostridium were further decreased after LEEP treatment (P = 0.049 and P = 0.002, respectively). Our results suggest that the cervical microbiome is altered after LEEP treatment in patients with CIN2/3. Further studies with larger sample sizes are needed to validate these findings.

In order to elucidate the mechanisms underlying the biobehavioral factors responsible for cervical cancer from the perspective of lncRNAs. Tumor samples were obtained from patients with stage Ib-IIb squamous cervical cancer, which were divided into high- and low-risk groups according to biobehavioral risk factors. A lncRNA + mRNA microarray was performed, and the results were validated using qRT-PCR. Gene ontology (GO), pathway, and lncRNA-mRNA co-expression analysis were performed to predict the potential functions of the differentially expressed transcripts. 1,621 lncRNAs and 1,345 mRNAs were found to be differentially expressed between the high-risk and low-risk groups. The results of the qR-TPCR validation were in 100% agreement with the microarray analysis results. GO analysis revealed that the transcripts showing significantly different expression were mainly associated with various aspects of immune response. Pathway analysis indicated that systemic lupus erythematosus signaling was the most significantly down-regulated pathway in the high-risk group. Co-expression analysis indicated NONHSAT002712, NONHSAT095060, and TCONS_00026535 had significant correlations with ZNF683 and BTLA, which were found to be associated with the GO term "adaptive immune response". The levels of genome-wide lncRNAs are significantly altered in cervical tumors from patients with higher biobehavioral risk factors.

Patients with ovarian cancer frequently develop acquired drug resistance after the long-term chemotherapy, leading to disease progression. Enhanced epithelial-mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian cancer cells; however, the molecular mechanisms involved are largely undefined. Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian cancer in terms of growth and EMT was investigated. PDK1 was upregulated in cisplatin-resistant ovarian cancer cells. PDK1 knockdown in resistant cells led to increased sensitivity to cisplatin-induced cell death and apoptosis. PDK1 downregulation also reversed the EMT and cell motility in cisplatin-resistant cells. In a mouse xenograft model, tumors derived from PDK1-silenced ovarian cancer cells exhibited decreased tumor growth and EMT compared with control after the cisplatin treatment. Mechanistically, PDK1 overexpression led to increased phosphorylation of EGFR, and blocking EGFR kinase activity by erlotinib reversed cisplatin resistance induced by PDK1 overexpression. Furthermore, in patients with ovarian cancer, higher PDK1 and p-EGFR levels were associated with chemoresistance. These results supported that PDK1 contributes to chemoresistance of ovarian cancer by activating EGFR. Therefore, PDK1 may serve as a promising target to combat chemoresistance of ovarian cancer.

Human papillomaviruses (HPVs) including high-risk (HR) and low-risk (LR) subtypes have distinguishable variation on both genotypes and phenotypes. The co-infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accumulating reports have focused on the interaction between virus and host, particularly the role of human microRNAs (miRNAs) in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miRNAs, miR-875 and miR-3144, and is located in E6 oncogene open reading frame (ORF) and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosis in HPV16-positive cervical cancer cells. This study provides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low expressed human miRNAs on tumour suppression.

Human papillomavirus (HPV) infection is associated with several cancers such as cancer in the cervix, vagina, and vulva and oropharyngeal, anal, penile, and cutaneous carcinomas, which is regarded as a great public health concern. The association between HPV is the strongest with cervical cancer because almost all such malignancies contain viral DNA, notably HPV types 16 and 18. The present chapter summarizes recent progresses of the HPV-associated cancers regarding epidemiology, molecular biology, HPV testing, vaccination, and treatment of HPV-related cancers.

Chen Chen,1,* Jie Wu,2,* Pengfei Zhu,3 Congjian Xu,1 Liangqing Yao1 1Obstetrics and Gynecology Hospital and Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, 2Department of Chemistry, Fudan University, Shanghai, 3Department of Obstetrics and Gynecology, Shangyu City Hospital, Shangyu, Zhejiang Province, People’s Republic of China *These authors contributed equally to this work Objective: To discover novel isoquinoline derivatives for inhibition of inhibitor of apoptosis proteins (IAP) for the treatment of ovarian cancer. Methods: We first synthesized 533 isoquinoline derivatives, and screened them using CCK-8 to measure their antiproliferative activity. These compounds were further tested by Hoechst staining and flow cytometric analysis to assess proapoptotic activity. The in vivo antitumor efficacy and safety of the screened compounds were evaluated on the xenograft mouse model. Ki-67 staining and TUNEL assay were used to evaluate proliferation and apoptosis in the resected tumors, respectively. Western blot and polymerase chain reaction (PCR) were conducted to evaluate the levels of proliferating cell nuclear antigen (PCNA), caspase-3, PARP, and IAP in resected tumors. Results: Compound B01002 and C26001 displayed antiproliferative and proapoptotic activity on SKOV3 ovarian cancer with an IC50 of 7.65 and 11.68µg/mL, respectively. Both compounds inhibited tumor growth in a xenografted mouse model with good safety profiles, and tumor growth inhibition (TGI) of B01002 and C26001 was 99.53% and 84.23%, respectively. Resected tumors showed that both compounds inhibited tumor cell proliferation and induced apoptosis in vivo. Caspase-3 and PARP were activated, whereas IAP proteins were downregulated at the protein level. Conclusion: Compound B01002 and C26001 could inhibit ovarian tumor growth and promote tumor apoptosis, partly by downregulating the IAPs, and, thus, might be promising candidates for treatment of ovarian cancer. Keywords: isoquinoline derivatives, target-oriented syntheses, IAP inhibitor, chemotherapy, ovarian cancer

Previously, we have demonstrated that NRF2 plays a key role in mediating cisplatin resistance in ovarian cancer. To further explore the mechanism underlying NRF2-dependent cisplatin resistance, we stably overexpressed or knocked down NRF2 in parental and cisplatin-resistant human ovarian cancer cells, respectively. These two pairs of stable cell lines were then subjected to microarray analysis, where we identified 18 putative NRF2 target genes. Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters, has previously been reported to contribute to chemoresistance in clear cell ovarian cancer. A detailed analysis on ABCF2 revealed a functional antioxidant response element (ARE) in its promoter region, establishing ABCF2 as an NRF2 target gene. Next, we investigated the contribution of ABCF2 in NRF2-mediated cisplatin resistance using our stable ovarian cancer cell lines. The NRF2-overexpressing cell line, containing high levels of ABCF2, was more resistant to cisplatin-induced apoptosis compared to its control cell line; whereas the NRF2 knockdown cell line with low levels of ABCF2, was more sensitive to cisplatin treatment than its control cell line. Furthermore, transient overexpression of ABCF2 in the parental cells decreased apoptosis and increased cell viability following cisplatin treatment. Conversely, knockdown of ABCF2 using specific siRNA notably increased apoptosis and decreased cell viability in cisplatin-resistant cells treated with cisplatin. This data indicates that the novel NRF2 target gene, ABCF2, plays a critical role in cisplatin resistance in ovarian cancer, and that targeting ABCF2 may be a new strategy to improve chemotherapeutic efficiency.

Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis.

Background Ovarian cancer is one of the most lethal gynecological malignancies, in which platinum resistance is a common cause of its relapse and death. Glycosylation has been reported to be involved in drug resistance, and glycomic analyses of ovarian cancer may improve our understanding of the mechanisms underlying cancer cell drug resistance and provide potential biomarkers and therapeutic targets. Methods The serous ovarian cancer cell line A2780 and its platinum-resistant counterpart A2780-cp were used in this study. We performed a lectin array analysis to compare the glycosylation patterns of the two cell lines, a gene expression array was employed to probe the differences in glycogenes. Furthermore, the results were verified by lectin blots. Results A2780-cp cell exhibited stronger intensities of Lens culinaris (LCA) Canavalia ensiformis (ConA), and Lycopersicon esculentum (LEL) and weaker intensities of Sambucus nigra (SNA) lectins. The gene expression array analysis revealed increased expression of Fut8, B3gnt4, B3gnt5, B4galt2 and decreased expression of Fut1 and ST6GalNAc 6 expression were evident in the A2780-cp cells. The lectin blot confirmed the differences in LCA, ConA, SNA and LEL between the A2780 and A2780-cp cells. Conclusions The combination of the lectin and gene expression analyses showed that the levels of core fucosylation and poly-LacNAc were increased in the A2780-cp cells and the levels of Fuc α1-2(gal β1-4) GlcNAc and α2-6-linked sialic structures were decreased in the A2780-cp cells. These glycans represent potential biomarkers and might be involved in the mechanism of drug resistance in ovarian cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12014-017-9155-z) contains supplementary material, which is available to authorized users.

As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.

Chronic inflammation is a well-known epidemiologic factor of ovarian clear cell carcinomas (OCCC), but has an uncertain role in prognosis. We developed a systemic inflammation score (SIS) based on preoperative serum albumin and neutrophil-to-lymphocyte ratio (NLR) for predicting progression-free survival (PFS) and overall survival (OS) in OCCC patients. A retrospective review was performed in 155 patients with OCCC undergoing primary debulking and chemotherapy at a single institute between 1995 and 2010. Cox regression models were fitted to analyze the effect of prognostic factors on PFS and OS. Harrell's concordance index was calculated to assess predictive accuracy. The SIS consisting of serum albumin and NLR was retained as an independent indicator adjusting for traditional clinicopathological features. A high SIS was significantly associated with aggressive tumor behavior, platinum resistance, and served as an independent predictor of reduced PFS (P = 0.006) and OS (P = 0.019). The SIS had a good discrimination ability for the predictive PFS (c-index = 0.712) and OS (c-index = 0.722). We have developed a system inflammation score for predicting prognosis of OCCC patients, which may help stratify patients for postsurgical management.

Human papillomavirus (HPV) infection is associated with several cancers such as cancer in the cervix, vagina, and vulva and oropharyngeal, anal, penile, and cutaneous carcinomas, which is regarded as a great public health concern. The association between HPV is the strongest with cervical cancer because almost all such malignancies contain viral DNA, notably HPV types 16 and 18. The present chapter summarizes recent progresses of the HPV-associated cancers regarding epidemiology, molecular biology, HPV testing, vaccination, and treatment of HPV-related cancers.

Objective Traditional chemotherapy drugs have an obvious drawback of nonspecific biodistribution in treating ovarian cancer. Follicle-stimulating hormone receptor (FSHR), a G-protein coupled receptor which is mainly expressed in reproductive system, is an important drug target in developing novel therapeutics. Methods Using a polypeptide of follicle-stimulating hormone (named as FSHP), a conjugated nanoparticle, FSHP-NP was developed to target FSHR in lymphatic metastasis of ovarian cancer. FSHP-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. A paclitaxel (PTX)-loaded FSHP-NP (FSHP-NP-PTX) was further developed and its anti-tumor effect was determined in vivo and in vitro. Results Taking NuTu-19 cells as an example, FSHP-NP-PTX displayed significantly stronger anti-cell proliferative and anti-tumor effects in a dose- and time-dependent manner when compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) in vitro. In vivo examinations showed that the size and weight of the lymph nodes were reduced in the FSHP-NP-PTX group. Conclusion FSHR as a novel therapeutic target in ovarian cancer and delivery of PTX via conjugated nanoparticle (FSHP-NP) might represent a new therapeutic approach in ovarian cancer.

Objective To analyze the clinical characteristics of ovarian masses in children and adolescents. Materials and Methods We performed a retrospective analysis of patients less than 20 years of age who were treated at the Obstetrics and Gynecology Hospital of Fudan University between March 2003 and January 2012. Medical records were reviewed for age at operation, including presentation of symptoms and signs; the levels of tumor markers; imaging examinations; pathologic findings; the size of masses; treatment; and outcome. Data management and descriptive analyses were performed using SPSS 16.0. Results A total of 521 patients were included in this study. Among them, 92 had non-neoplastic lesions, 382 had benign neoplasms, and 47 had malignant tumors. The mean age of the patients was 16.3 ± 2.2 years. The primary presenting symptoms and signs were abdominal pain (39.5%), menstrual disorder (31.1%), abdominal swelling (5.4%), and an enlarged abdominal perimeter (3.3%). Malignant tumors tended to be larger than benign neoplasms (17.3 ± 8.6 cm vs 9.0 ± 5.7 cm; P = .000). There was no age difference between patients with benign neoplasms (16.3 ± 2.1 y) and those with malignant tumors (15.7 ± 2.5 y). The operations included salpingo-oophorectomy, ovarian cystectomy, and oophorectomy. Two patients with malignant tumors had bilateral salpingo-oophorectomy, and 2 patients who had tumor metastasis underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Forty-one cases of malignant tumors received postoperative chemotherapy. Conclusions Germ cell tumors are the most common malignancy, and mature teratomas are the most common benign neoplasms in children and adolescents. Abdominal pain and menstrual disorder are the main reasons for doctor's visit. Although examination by ultrasound is the preferred auxiliary in the diagnosis of ovarian pathology, it could not distinguish between benign and malignant tumors. However, tumor size and tumor markers are helpful to identify the properties of masses. Surgery is usually better for treatment, and it is preferable to attempt conservative, fertility-sparing surgery in adolescents. Postoperative chemotherapy is necessary for malignant tumors.

Monodispersed mesoporous phenolic polymer nanospheres with uniform diameters were prepared and used as the core for the further growth of core–shell mesoporous nanorattles. The hierarchical mesoporous nanospheres have a uniform diameter of 200 nm and dual-ordered mesopores of 3.1 and 5.8 nm. The hierarchical mesostructure and amphiphilicity of the hydrophobic carbon cores and hydrophilic silica shells lead to distinct benefits in multidrug combination therapy with cisplatin and paclitaxel for the treatment of human ovarian cancer, even drug-resistant strains.

Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced cell viability and invasion and induced growth arrest in vitro and in vivo. Dual-luciferase reporter assays revealed that miR-424 directly targets DCLK1 and downregulates its expression. Transfection of ES-2 cells with miR-424 mimics downregulated DCLK1 and suppressed the effects of DCLK1 overexpression on upregulating matrix metalloprotease-9 and promoting epithelial-mesenchymal transition (EMT). Taken together, these data demonstrate that miR-424 has the capacity to suppress cell invasion and EMT in OCCC by downregulating DCLK1, suggesting potential therapeutic targets and strategies for the treatment of this disease.

Ethnopharmacological relevance Pinellia pedatisecta Schott (PPS)is a traditional Chinese medicine functioning as reducing swelling and drying dampness. Pinellia pedatisecta Schott extract (PE) has been confirmed to suppress cervical tumor growth and modulate the antitumor CD4+T helper immunity towards Th1. Aims To explore the roles of PE in modulating tumor-associated dendritic cell (TADC) activation and function. Methods For in vivo studies, HPV+TC-1 mouse tumor models were conducted and treated with PE for 3 weeks (10 mg/kg/d or 20 mg/kg/day). The immune profiles of spleen, tumor-draining lymph nodes (TDLNs), tumor and serum were analyzed by flow cytometry and multiplexed bead-based immunoassay. For in vitro studies, TADCs were generated by tumor-conditioned medium and treated with PE solution. The maturation and function of TADCs were evaluated by flow cytometry, ELISA, mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) assay. Furthermore, the effect of PE on SOCS1 pathway was examined by western blotting and real time PCR. Results PE upregulated the expression of major histocompatibility complex class II (MHCII) and costimulatory molecules CD80 and CD86 on TADCs and promoted IL-12 secretion from TADCs. In addition, PE-treated TADCs promoted the proliferation of CD4+ and CD8+ T cells and induced the differentiation of IFN-γ+CD4+ and GZMB+CD8+ T cells. PE-treated TADCs also elicited a more powerful antigen-specific cytotoxic T lymphocyte (CTL) response. Furthermore, PE treatment in vivo enhanced the proliferation, activated the functional ability (increased Ki67, CD137, GZMB or IFN-γ, TNF-α expression) and reversed the exhaustion (impaired CD95 or PD-1 expression) of antitumor T cells. Mechanistically, PE inhibited SOCS1-restrained JAK2 activation in TADCs. Conclusions PE efficiently restored the immature status of TADCs and enhanced their function as antigen-presenting cells to further elicit antitumor Th1 and CTL responses, suggesting that PE may be a potential immunomodulatory drug for cancer treatment.

Objective To introduce a model incorporating expected risks for a vaginal procedure based on objective measurements of a patient's characteristics and propose it as a potential tool to assist in the selection of candidates for vaginal surgery. Study design A quantitative model consisting of 13 clinical variables identified as risk factors in a prospective vaginal procedure was developed. Medical records of 315 women undergoing a set of routine gynecological surgeries via the vaginal, laparoscopic, and abdominal routes were obtained during January 2010 and November 2011. These surgeries included hysterectomy, myomectomy, bilateral or unilateral salpingo-oophorectomy and adnexal cystectomy. After that, each patient was scored according to the model. Sensitivity and specificity of the model were analyzed in one data set (cohort I) by receiver operating characteristic (ROC) curve and independently validated in a second data set (cohort II). Results 175 patients were included in cohort I while the other 140 patients formed cohort II. The intra- and post-operative complication rates were 0.6% and 0%, respectively. A vaginal procedure was predicted with good accuracy (AUC = 0.852). The sensitivity was 86.0% and specificity was 72.0% at an optimal cut-off point of score = 3. The predication accuracy of this model was further validated in cohort II and reached as high as 85.7%. Furthermore, the score was significantly associated with the volume of estimated blood loss and the duration of operation time ( P Conclusion Our quantitative risk assessment model predicts safe vaginal surgery with good accuracy. Predictive tools based on such a model could help surgeons to optimize patient selection and thus contribute to reducing costs while enhancing patients’ satisfaction. We invite other researchers to modify and validate the model in other populations.

Aim Although much is known about the structure and biological functions of follicle-stimulating hormone (FSH) receptor (FSHR), the interaction of FSHR and FSH has been challenging to characterize due to the limited quantity of active FSHR protein produced by simple methods. The goal of this study was to express and purify the extracellular domain (ECD) of human FSHR (hFSHR). Methods Total RNA was isolated from normal human ovary tissue. cDNA for hFSHR ECD were amplified and subsequently ligated into the pET32a(+) vector. The plasmid vector construct was confirmed by polymerase chain reaction and sequencing. Expression in Escherichia coli Rosetta (DE3) pLysS strain was induced by isopropyl-thio-β-D-thiogalactoside, and the recombinant products were purified by immuno-affinity chromatography using an Ni-NTA and High-Q column. The recombinant protein was confirmed by western blotting. Results Following induction, E. coli expressed a recombinant protein of approximately 65 kDa in size, whereas the non-induced E. coli did not express the recombinant protein. The recombinant fragments purified using a High-Q column demonstrated a single band and an abundant yield. The recombinant protein was soluble and specifically recognized by an antibody for hFSHR. Additionally, four mutation sites were detected that resulted in amino acid shifts at position 112 Asn/Thr, 197 Glu/Ala, 198 Leu/Val and 307 Ala/Thr. Conclusion The recombinant hFSHR ECD protein was expressed and purified. This method could be easily scaled for increased production and may facilitate additional applications utilizing FSHR in assisted reproductive technology, a contraceptive FSH vaccine and FSHR-targeted therapeutic agents used to treat ovarian cancer.

CA-125, the most frequently used biomarker for ovarian cancer detection, cannot provide accurate diagnosis due to its poor specificity as it may also increase in many benign gynecological conditions. Thus, reducing the false-positive outcomes is urgently needed. Decrease in terminal galactosylated N-glycans of serum IgG has been found in various malignancies compared to healthy controls. Here, this alteration of IgG galactosylation was extended to be investigated between ovarian cancer and benign conditions with similar elevated CA-125 levels, in an attempt to effectively distinguish between false-positive subjects and ovarian cancer patients. In the study of 58 patients with elevated CA-125 levels (>35 U/mL), the degree of IgG galactosylation was measured from the relative intensities of IgG digalactosyl (G2), monogalactosyl (G1), and agalactosylated (G0) N-glycans according to the formula G0/(G1+G2·2). This ratio was found significantly higher in the malignant group than in the benign group (0.74 vs 0.34; p

To establish a model of ovarian cancer with highly lymphatic metastasis in immunocompetent rats. Thirty-two female Fischer 344 rats were divided randomly and equally into two groups: footpad group and intraperitoneal (i.p.) group. At 8 weeks after injection with NuTu-19 ovarian cancer cells, lymphatic metastasis were analyzed by pathohistology; body weight was monitored per week, Survival curves were determined by Kaplan–Meier analysis. Footpad injection could efficiently generate the lymphatic metastasis; specifically, the incidences of metastasis in the ipsilateral popliteal, inguinal and para-iliac lymph nodes were 100 % (8/8), 75 % (6/8), and 37.5 % (3/8), respectively. The mean volume and weight of the ipsilateral popliteal lymph nodes were 0.405 ± 0.096 cm3 and 0.418 ± 0.118 g in footpad group. However, no lymphatic metastasis lesions were found in i.p. group. Moreover, Kaplan–Meier analysis showed that the average survival time of the footpad group was significantly longer than that of the i.p. group (18.429 ± 1.112 vs. 10.286 ± 0.505 weeks). Our experiments suggest that footpad injection is a very efficient method to generate ovarian cancer with lymphatic metastasis in an immune-competent animal, and we believe that this model will be very helpful for shedding light on the mechanism of lymphogenous metastasis and developing novel therapeutic targets for ovarian cancer patients.

microRNAs (miRNAs) are important regulators of gene expression during tumorigenesis. The downregulation of microRNA-9 (miR-9) has been reported in ovarian serous carcinoma (OSC), indicating a role for miR-9 in this type of cancer. In this study, we investigated the biological significance of miR-9 in OSC in vitro. Using 3 OSC cell lines, SKOV3, CAOV3 and OVCAR3, which underexpresss miR-9, we demonstrate that the exogenous miR-9 transfection inhibits OSC cell proliferation, migration and invasion. In addition, we demonstrate that the focal adhesion protein, talin 1 (TLN1), whose expression has been associated with OSC development and progression to metastasis, is a direct target of miR-9. TLN1 knockdown mimicked the effects of miR-9 overexpression. Moreover, the activation of the TLN1-modulated FAK/AKT pathway was inhibited by the increased miR-9 levels. These results suggest that miR-9 plays a role as a tumor suppressor in OSC by suppressing TLN1 expression.

Background Ovarian cancer is the most lethal gynecological malignancy due to its frequent recurrence and drug resistance even after successful initial treatment. Accumulating scientific evidence indicates that subpopulations of cancer cells with stem cell-like properties, such as so-called side population (SP) cells, are primarily responsible for these recurrences. A better understanding of SP cells may provide new clues for detecting and targeting these cancer-initiating cells and ultimately help to eradicate cancer. Changes in glycosylation patterns are remarkable features of SP cells. Here, we isolated SP cells from ovarian cancer cell lines and analyzed their glycosylation patterns using multiple glycomic strategies. Methods Six high-grade serous ovarian cancer cell lines were used for SP cell isolation. Among them, HO8910 pm, which contained the highest proportion of SP cells, was used for glycomic analysis of SP cells. Cell lysate of SP cells and main population cells was applied to lectin microarray and mass spectrometry for glycan profiling. Differently expressed glycan structures were further verified by lectin blot, flow cytometry, and real-time PCR analysis of their relevant enzymes. Results Expression of core fucosylated N-glycan and tumor-associated Tn, T and sT antigens were increased in SP cells. By contrast, SP cells exhibited decreased hybrid glycan, α2,3-linked sialic glycan and multivalent sialyl-glycan. Conclusions Glycan structures, such as Tn, T, sT antigens, and core fucosylation may serve as biomarkers of ovarian cancer stem cells. Electronic supplementary material The online version of this article (doi:10.1186/s12014-016-9131-z) contains supplementary material, which is available to authorized users.

Lysyl oxidase (LOX) is the key enzyme involved in the crosslinking of collagen and elastin that is essential for the formation of extracellular matrix (ECM). LOX-mediated ECM remodeling plays a critical role in follicle development, oocyte maturation and corpus luteum formation. To date, the regulation of LOX in human ovary has never been elucidated. Activin A and its functional receptors are highly expressed in ovarian follicles from an early developmental stage. They locally regulate follicle progression. The aim of this study was to investigate the effects of activin A on the expression of LOX and its extracellular enzyme activity in primary and immortalized human granulosa–lutein cells obtained from patients undergoing anin vitrofertilization procedure. We demonstrated that activin A significantly upregulated the expression of connective tissue growth factor (CTGF) and LOX via an activin/TGF-β type I receptor mediated-signaling pathway. Using a target depletion small interfering RNA knockdown approach, we further confirmed that the upregulation of CTGF expression resulted in an activin-A-induced increases in LOX expression and activity. These findings may provide insight into the mechanisms by which intrafollicular growth factors regulate the expression of LOX for ECM formation and tissue remodeling in the human ovary.

Recently an explosion in the discovery of long noncoding RNAs (lncRNAs) was obtained by high throughput sequencing. Genome-wide transcriptome analyses, in conjugation with research for epigenetic modifications of chromatins, identified a novel type of non-protein-coding transcripts longer than 200 nucleotides named lncRNAs. They are gradually emerging as functional and critical participants in many physiological processes. Here we give an overview of the characteristics, biological functions, and working mechanism for this new class of noncoding factors.

Recently an explosion in the discovery of long noncoding RNAs (lncRNAs) was obtained by high throughput sequencing. Genome-wide transcriptome analyses, in conjugation with research for epigenetic modifications of chromatins, identified a novel type of non-protein-coding transcripts longer than 200 nucleotides named lncRNAs. They are gradually emerging as functional and critical participants in many physiological processes. Here we give an overview of the characteristics, biological functions, and working mechanism for this new class of noncoding factors.

Additional file 1. SP cells sorted from ES-2 cells exhibited higher intensity of ABA and VVA. The intensity of ABA (left) and VVA (right) for SP sphere cells after culturing for 1weeks without serum was detected by flow cytometry.

Discovery of novel metabolite biomarker(s) for improved ovarian cancer diagnosis is of great importance. In this paper, the differences of urinary hydrophilic and hydrophobic metabolic profiling between healthy women, benign ovarian tumor, and ovarian cancer patients were studied by metabolomics strategy. Metabolites in urine were analyzed on hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) coupled to MS. Data from HILIC or RPLC, positive or negative ion detection mode were found to be complementary. Data were filtered by orthogonal signal correction (OSC) method, and the three groups were discriminated by partial least squares discrimination analysis (PLS-DA) models. By combining the four datasets, maximum information can be collected, and a PLS-DA model was built after OSC filtering. The model based on combined dataset is superior to the ones based on the separate dataset, and important metabolites were screened based on the combined dataset model. Five metabolites were found to be specific to ovarian cancer and ten metabolites were considered commonly related to ovarian cancer and benign ovarian tumor. Combination of RPLC and HILIC separation, as well as positive and negative ion detection in metabolomic studies show advantages in collecting various metabolites information that helps us better understand the metabolic event.

Ginkgolide B (GB), the primary active component of Ginkgo biloba extracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine cell viability. The apoptosis rates of cells were measured by flow cytometric analysis. The expression of apoptosis-associated and proliferation-associated proteins was detected by Western blot. The cytotoxicity of GB was analyzed using a lactate dehydrogenase assay. Treatment with 100 µM GB for 3 days significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells, respectively, as determined by MTT assay. Similarly, the apoptotic cell population was increased when treated with GB in a dose-dependent manner both in SKOV3 and CAOV3 cells. These effects were characterized by the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1. In addition, a combined treatment of low concentrations of GB and CDDP showed an additive effect on the inhibition of SKOV3 cell proliferation. Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.

To evaluate the feasibility and safety of transabdominal ultrasound-guided suction curettage to treat cesarean scar pregnancy (CSP) and investigate factors affecting prognosis of CSP.This was a retrospective case study of 43 cases who were diagnosed as CSP and treated by suction curettage under transabdominal ultrasound guidance as an initial treatment of CSP in Obstetrics and Gynecology Hospital of Fudan University over past 7 years (from 2007 to 2013); factors affecting prognosis of CSP were investigated.39 of the 43 cases (91%) were successfully treated. There were no statistically significant differences in maternal age, gravidity, abortion frequency, and the time interval between current CSP and last cesarean delivery, the myometrium thickness between the gestational sac and the bladder wall between the success group and the failure group (all P0.05). Statistically significant difference was found in crown-rump length (CRL) between the two group (median of the two group was 18.5, 2.0 mm) by rank sum test (P = 0.047). Univariate logistic regression analysis demonstrated that CRL was strongly associated with the prognosis and the OR for no complications was 18.50, comparing CRL ≤ 6 mm versus CRL6 mm (P = 0.020).Transabdominal ultrasound-guided suction curettage is effective and safe in the treatment of CSP with CRL ≤ 6 mm.

High-grade serous ovarian cancer (HGS-OvCa) is characterized by widespread CCNE1 amplification. Current treatments lack specificity to target Cyclin E-driven OvCa.By in silico analysis of the TCGA OvCa dataset we searched association between genes involved in glucose metabolism and cell cycle control. Metabolic shift was studied in Cyclin E-driven OvCa cells treated with CDK inhibition (CDKi). Genetic and pharmaceutical inhibition of succinate dehydrogenase (SDH) was tested in combination with CDKi.OvCa patients with CCNE1 amplification could be divided by concomitant SDHA amplification. A2780 OvCa cells were similar to the Cyclin E-driven and SDHA neutral genotype. CDKi in A2780 cells using Dinaciclib resulted in compensatory enhancement of tricarboxylicacid cycle (TCA) cycle activity. Combined blockade of CDK and SDH, both genetically and pharmaceutically, showed synergy and resulted in inhibited proliferation, migration, invasion and migration in A2780 cells. The combined inhibition did not further alter cell cycle population, but induced apoptosis of A2780 cells.Cyclin E-driven OvCa cells appeared addicted to glucose metabolism via TCA. Combined CDKi with modalities targeting TCA, like SDHA inhibition showed promising effects for this genotype.

Viral integration plays an important role in the development of malignant diseases. Viruses differ in preferred integration site and flanking sequence. Viral integration sites (VIS) have been found next to oncogenes and common fragile sites. Understanding the typical DNA features near VIS is useful for the identification of potential oncogenes, prediction of malignant disease development and assessing the probability of malignant transformation in gene therapy. Therefore, we have built a database of human disease-related VIS (Dr.VIS, http://www.scbit.org/dbmi/drvis) to collect and maintain human disease-related VIS data, including characteristics of the malignant disease, chromosome region, genomic position and viral–host junction sequence. The current build of Dr.VIS covers about 600 natural VIS of 5 oncogenic viruses representing 11 diseases. Among them, about 200 VIS have viral–host junction sequence.

The extreme complexity of protein samples is becoming a great challenge for proteomic analysis, especially for those having large dynamic range of protein abundance. To solve this problem, and to overcome the limitation of the current proteomic technologies, a new method using hydrazide-functionalized magnetic microspheres was established in this study. With this method, tryptophan (Trp)-containing peptides can be selectively and sensitively enriched from complex and low-volume samples. Furthermore, combined with 1D-LC–MS/MS analysis, the strategy was successfully applied to the proteomic study of mouse serum. The proportion of Trp-containing peptides was increased from 19.4% to 80.2% through enrichment, and the complexity of the sample was reduced more than two times. An additional 113 Trp-containing peptides and 48 novel proteins were detected compared to the conventional method. This enrichment method provides a means for identifying more proteins as potential biomarkers in serum and other complex samples.

The aim of this study was to use a two steps strategy metabolomics to screen/identify and validate novel metabolic biomarker(s) for epithelial ovarian cancer (EOC). In the screening step, serum samples from 27 healthy women, 28 benign ovarian tumors, and 29 EOCs were analyzed by using LC-MS based nontargeted metabolomics. The three groups were separated with OSC filtered PLS-DA model, and six metabolites (27-nor-5β-cholestane-3,7,12,24,25 pentol glucuronide (CPG), phenylalanine, glycocholic acid, propionylcarnitine, Phe-Phe and Lyso PC (18:2)) were considered as potential biomarker candidates. In the validation step, the six metabolites were analyzed in targeted metabolomics by LC-selective ion monitoring mass spectrometry in another 685 serum samples with various clinical backgrounds. As a result, CPG was evaluated to be a potential biomarker and its content was elevated in EOC tissues compared with benign ovarian tumor tissues (p = 0.0005). Besides, CPG levels were found to be up-regulated in early stage EOC and in the three types of EOC histological types. Other variables such as nonovarian diseases, medicine consumption, gynecological inflammations, and menopausal state did not interfere in using CPG as diagnosis marker. CPG was found to be complementary to CA125. Our findings suggest that CPG can be considered a statistical relevant biomarker of EOC, ready for early stage detection.

Solution capacity limited estimation of distribution algorithm (L-EDA) is proposed and applied to ovarian cancer prognosis biomarker discovery to expatiate on its potential in metabonomics studies. Sera from healthy women, epithelial ovarian cancer (EOC), recurrent EOC and non-recurrent EOC patients were analyzed by liquid chromatography-mass spectrometry. The metabolite data were processed by L-EDA to discover potential EOC prognosis biomarkers. After L-EDA filtration, 78 out of 714 variables were selected, and the relationships among four groups were visualized by principle component analysis, it was observed that with the L-EDA filtered variables, non-recurrent EOC and recurrent EOC groups could be separated, which was not possible with the initial data. Five metabolites (six variables) with P < 0.05 in Wilcoxon test were discovered as potential EOC prognosis biomarkers, and their classification accuracy rates were 86.9% for recurrent EOC and non-recurrent EOC, and 88.7% for healthy + non-recurrent EOC and EOC + recurrent EOC. The results show that L-EDA is a powerful tool for potential biomarker discovery in metabonomics study.

Rare-earth upconversion nanophosphors (UCNPs) have become one of the most promising classes of luminescent materials for bioimaging. However, there remain numerous unresolved issues with respect to the understanding of how these nanophosphors interact with biological systems and the environment. Herein, we report polyacrylic acid (PAA)-coated near-infrared to near-infrared (NIR-to-NIR) upconversion nanophosphors NaYF(4):Yb,Tm (PAA-UCNPs) as luminescence probes for long-term in vivo distribution and toxicity studies. Biodistribution results determined that PAA-UCNPs uptake and retention took place primarily in the liver and the spleen and that most of the PAA-UCNPs were excreted from the body of mice in a very slow manner. Body weight data of the mice indicated that mice intravenously injected with 15 mg/kg of PAA-UCNPs survived for 115 days without any apparent adverse effects to their health. In addition, histological, hematological and biochemical analysis were used to further quantify the potential toxicity of PAA-UCNPs, and results indicated that there was no overt toxicity of PAA-UCNPs in mice at long exposure times (up to 115 days). The study suggests that PAA-UNCPs can potentially be used for long-term targeted imaging and therapy studies in vivo.

LIN28 is a highly conserved RNA-binding proteins, have been implicated in key biological functions such as development, glucose metabolism and pluripotency. LIN28 overexpression induces the reprogramming of pluripotent stem cells (iPSCs) and supports the proliferative and metabolic capacities of iPSCs. Therefore LIN28 is crucial for the regulation of the cell fate and human embryonic development. In addition, LIN28B is frequently up-regulated in a variety of cancers and correlates with poor prognosis and cancer recurrence, indicating the crucial role of LIN28B in tumorigenesis. Aberrantly expression of LIN28B is responsible for the decrease in the let-7 microRNA family observed in many cancers and Let-7 is frequently down-regulated in numerous different tumors and lower levels of let-7 correlates with poor prognosis. Therefore, LIN28/Let7 may be crucial for the regulation of cell cycle and cell proliferation. In our present study, We first detected the expression of LIN28B in normal placental villi and choriocarcinoma tissue. Our data showed LIN28B was highly expressed in human choriocarcinoma tissues and most LIN28B staining was localized in the nucleus. Comparatively, LIN28B staining was faint in normal placental villi. Our data then demonstrated that LIN28B was highly expressed in human choriocarcinoma cell lines JEG-3 and JAR. However, LIN28B expression was undetectable in HTR-8/Svneo normal trophoblast cells. Our data then demonstrated that LIN28B knockdown by small interfering RNA (siRNA) caused an increase in Let-7a expression. Further, silencing of LIN28 inhibited IGF2BP1 expression and suppressed cell proliferation capacity, which can be markedly restored by Le7a siRNA. These findings reveal that LIN28 may promote IGF2BP1 expression and cell proliferation by Let-7a repression. Moreover, β-catenin knockdown resulted in reduced LIN28 expression and Let-7a up-regulation. β-catenin is the major mediator of canonical Wnt signaling pathway, and activation of canonical Wnt signaling has been reported to play a critical role in the proliferation, invasion, and differentiation of various tumors. Collectively, our present data indicated that β-catenin/LIN28B/Let7a pathway may be crucial for cell proliferation regulation in human choriocarcinoma cells. Citation Format: Jing Wu, Baoxin Luan, Huandi Yu, Yinhua Yu, Congjian Xu, Hongbo Zhao. β-Catenin/LIN28B promotes cell proliferation of human trophoblast cells via let7a repression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 540.

Human papillomavirus 58 (HPV58) is one type of HPV with high risk of causing cervical cancer. Unusually high prevalence of HPV58 has been reported in Asia, Africa and some other areas. However, due to the scattered distribution of global data, in addition to the lack of data of some HPV58 high-incidence nations and regions, like Mainland China, a comprehensive analysis of the global geographical distribution of HPV58 remains blank so far. In this study, HPV58 from the human cervical cancer tissue was detected in Mainland China, and 14 new HPV58-E6/L1 gene sequences were obtained. Moreover, phylogeographic analysis has been conducted combining the HPV58 sequences that have been deposited in GenBank since 1985. The study result shows that the sequences detected from the Shanghai, Jiangsu and Sichuan areas are homologous with those found in the past from Hong Kong and Xi'an, China, as well as Japan and other Southeast Asian areas. Furthermore, Western Africa is considered to be the "root" source of the HPV58 variant, while Mainland China and Southeast Asia are "transit points" and the new sources of HPV58 after receiving the isolates from the "root" source; like HPV16 and HPV18, the HPV58 might also be one of the major HPV types associated with the development and spread of cervical cancer.

Fluorescence targeted imaging in vivo has proven useful in tumor recognition and drug delivery. In the process of in vivo imaging, however, a high autofluorescence background could mask the signals from the fluorescent probes. Herein, a high contrast upconversion luminescence (UCL) imaging protocol was developed for targeted imaging of tumors based on RGD-labeled upconversion nanophosphors (UCNPs) as luminescent labels. Confocal Z-scan imaging of tissue slices revealed that UCL imaging showed no autofluorescence signal even at high penetration depth (approximately 600 microm). More importantly, region of interest (ROI) analysis of the UCL signal in vivo showed that UCL imaging achieved a high signal-to-noise ratio (approximately 24) between the tumor and the background. These results demonstrate that the UCL imaging technique appears particularly suited for applications in tracking and labeling components of complex biological systems.

Chemotherapy is an important treatment for ovarian cancer. However, conventional chemotherapy has inevitable drawbacks due to side effects from nonspecific biodistribution of the chemotherapeutic drugs. To solve such problem, targeted delivery approaches were developed. The targeted delivery approaches combine drug carriers with the targeting system and can preferentially bring drugs to the targeted sites. Follicle-stimulating hormone receptor (FSHR) is an ovarian cancer–specific receptor. By using a peptide derived from FSH (amino acids 33–53 of the FSH β chain, named as FSH33), we developed a conjugated nanoparticle, FSH33-NP, to target FSHR in ovarian cancer. FSH33-NP was tested for recognition specificity and uptake efficiency on FSHR-expressing cells. Then, the antitumor efficiency of paclitaxel (PTX)-loaded FSH33-NP (FSH33-NP-PTX) was determined. FSH33-NP-PTX displayed stronger antiproliferation and antitumor effects compared with free PTX or naked PTX-loaded nanoparticles (NP-PTX) both in vitro and in vivo. In summary, this novel FSH33-NP delivery system showed very high selectivity and efficacy for FSHR-expressing tumor tissues. Therefore, it has good potential to become a new therapeutic approach for patients with ovarian cancer. [Cancer Res 2009;69(16):6506–14]

Objective To compare the transferring efficiency and killing effects of one time and continuous mediation with GE7, a non-viral targeted delivery system, in transfection of thymidine kinase gene of herpes simplex virus (HSV-tk) into ovarian cancer cells.