The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications.

Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.

An Overview of Heavy Chain Ferritin in Cancer.

As a spherical protein that acts as a repository for intracellular iron, Ferritin is the most important iron storage form and is known to influence tumor immunity. Unbound ferritin is composed of 24 subunits, made up of ferritin light chain (FTL) and ferritin heavy chain (FTH). Ferritin can be automatically put together to form hollow nanocages that measure 12 nm around the outside and 8 nm around the inside. Cancer causes the second-most deaths worldwide, effective elimination of tumor cells while protecting normal cells is the foundation of modern tumor therapy. To this end, the innate tumor-targeting activity of human FTH1, first identified ten years ago, is highly appealing. Unmodified human FTH1 binds to its receptor, transferrin receptor 1 (TfR1), which is frequently overexpressed in cancer cells. FTH1-TfR1 binding permits improved drug efficacy by promoting ferritin-mediated targeted delivery. In addition, FTH is also associated with the prognosis of multiple typies of cancer. The level of FTH1 is significantly and positively correlated with the infiltration of tumor-associated macrophages. FTH1 also plays an important role in regulating the tumor immunity of solid cancer. As such, FTH1 has been extensively applied in the targeted delivery of anticancer drugs, diagnostic molecules (e.g., radioisotopes and fluorophones), and inorganic nanoparticles (NPs) to tumors.This article reviews the role of FTH in cancer and its potential as a therapeutic target.

Etiological relationship between lipid metabolism and endometrial carcinoma.

Endometrial carcinoma (EC) has become one of the most common gynecological malignant neoplasms in developed countries worldwide. Studies have shown that this may be closely related to the abnormal metabolism of blood lipids, which was the most significant metabolic change in the human body in this cancer. In this review, we focus on the correlation between lipid metabolism and EC and discuss the evidence that abnormal lipid metabolism promotes an increase in EC growth and metabolism, as well as the regulatory mechanism and related signaling pathways involved in this relationship. In addition, we also discussed the research progress of targeted therapies and drug treatments for EC that act on lipid metabolism, and statins are expected to become adjuvant drugs for EC in the future. This review will provide a systematic view for a better understanding of the etiological relationship between lipid metabolism and EC and further open up new therapeutic possibilities and effective treatments for EC by targeting lipid metabolism.

Identification of EMP1 as a critical gene for cisplatin resistance in ovarian cancer by using integrated bioinformatics analysis.

BACKGROUND: Cisplatin resistance is among the main reasons for the poor prognosis of ovarian cancer (OC) patients. Until now, effective biomarkers for predicting cisplatin resistance in OC and specific drugs for reversing this resistance are lacking. This study identified the critical gene associated with cisplatin resistance in OC and provided a potential target for overcoming this resistance. METHODS: Differentially expressed genes between cisplatin-resistant and -sensitive OCs were identified by screening public datasets. Survival analysis was conducted to screen prognosis-related DEGs. CIBERSORT, ESTIMATE, and immune checkpoint genes were used to assess the association between EMP1 expression and tumor microenvironment features. CTRP and GDSC databases were employed to analyze the correlation between EMP1 expression and cisplatin resistance. Furthermore, immunohistochemistry, qPCR, Western blotting, siRNA interference, and the CCK8 assay were performed to verify the role of EMP1 in cisplatin resistance in vitro. Finally, xenograft mouse models were generated to further confirm the role of EMP1 in cisplatin resistance in vivo. RESULTS: EMP1 was identified as a critical gene associated with cisplatin resistance in OC. According to bioinformatics analyses, increased EMP1 expression was linked to higher stromal/ESTIMATE scores as well as greater ICG expression levels. The in vitro experiments showed that EMP1 was highly expressed in cisplatin-resistant OC tissues and cells, and silencing this EMP1 expression enhanced OC cell sensitivity to cisplatin. Finally, in vivo experiments confirmed that EMP1 promotes tumor growth and cisplatin resistance. CONCLUSIONS: EMP1 can act as a predictive biomarker for cisplatin resistance in OC and as a potential therapeutic target.

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.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

Evaluation efficacy and safety of epidural analgesia in second-trimester induced labor: A single-center, prospective, non-randomized, controlled study.

BACKGROUND: Second-trimester induced labor in pregnant women was often more likely to suffer from psychological and physiological double pain. However, the analgesic management received less attention, and the optimal analgesic mode for second-trimester induced labor had not been determined. Our objective was to evaluate the feasible of epidural analgesia (EA) in second-trimester induced labor. METHODS: From January 2020 to December 2021, Primipara who planned to undergo second-trimester induced labor in the First Affiliated Hospital of Yangtze University were collected. The method of labor induction was oral mifepristone + amniotic cavity injection of Ethacridine Lactate. Based on whether or not patients received epidural analgesia, which were divided into EA group (30 cases) and non-EA (NEA) group (30 cases). The primary outcome were visual analog scale (VAS) score of pain and result of follow-up, the secondary outcomes included relative clinical parameter and labor duration. RESULTS: Vaginal induction of labor was successful in both groups. There was no statistically significant difference in VAS of pain between the two groups before analgesia (P > .05), but the VAS of pain in the EA group was significantly lower than the NEA group (P < .05) after analgesia or at delivery. The following outcomes showed no statistical difference between two groups: labor duration, postpartum hemorrhage, hemorrhage ≥ 500 mL, intrapartum injury, second days hemoglobin, C-reactive protein, antibiotic therapy days, hospitalizations days, and placenta residue (P > .05). The median hospitalization costs of EA group was 4697.5 yuan, and NEA group was 3673 yuan, the difference was statistically significant (P < .001). No adverse events related to EA occurred during hospitalization, only 3 patients showed mild lumbago and back pain after follow-up to three months postpartum, which was significantly relieved after proper rest. CONCLUSION: EA can significantly reduce the pain of parturients, which may be effective and safe in the second-trimester induced labor.

Risk factors predicting residual lesion in subsequent hysterectomy following cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL).

OBJECTIVE: To determine risk factors predicting residual lesion in a subsequent hysterectomy follow a cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL). METHOD: Between January 2010 and December 2021, a total of 740 patients who underwent a hysterectomy within 3 months after CKC for HSIL were included in this study. We analyzed their demographic features and pathological parameters. A logistic regression model was used to analyze the relationship between parameters and residual lesion in subsequent hysterectomy specimens. RESULTS: 104 (14.1%) had residual lesion in the hysterectomy specimen, 3 patients with microinvasive carcinoma. The rate of residual lesion in patients with positive endocervical margin was 31.3%, with positive ectocervical margin was 15.3%, with positive combine margin was 38.6%. In multivariate analysis, positive margin (OR 4.015; 95% CI 2.526-6.381; P < 0.001), glandular involvement (OR 3.484; 95% CI 1.457-8.330; P = 0.005), HPV16/18 infection (OR 2.804; 95% CI 1.705-4.611; P < 0.001) and multiple HR-HPV infection (OR 1.813; 95% CI 1.130-2.909; P < 0.014) were independent risk factors for residual lesion. The AUC calculated by logistic regression model was 0.78. CONCLUSION: Positive margin, positive glandular involvement, HPV16/18 and multiple HR-HPV infection were independent high risk factors of residual lesion in a subsequent hysterectomy following CKC for HSIL.

Diabetes mellitus and endometrial carcinoma: Risk factors and etiological links.

The presence of diabetes mellitus (DM) has a critical influence on the occurrence and development of endometrial cancer (EC) and is associated with a poor prognosis. Patients with DM are twice as likely to progress to EC, probably because a high-glucose environment contributes to the growth and invasiveness of EC cells. In this review, we focus on the etiological links between DM and EC and provide an overview of potential biological mechanisms that may account for this relationship, including hyperglycemia, insulin resistance, hyperinsulinemia, glycolysis, chronic inflammation, obesity, and activation of signaling pathways involved in EC. Furthermore, we discuss the pharmacological management of EC associated with DM. Early treatment with metformin is expected to be an effective adjuvant alternative for EC in the future. This knowledge is important for further opening up preventive and therapeutic strategies for EC by targeting glucose metabolism.

Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study.

BACKGROUND: Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods. METHODS: In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard. FINDINGS: For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886-0·936) in the internal dataset, 0·870 (95% CI 0·822-0·918) in external validation dataset 1, and 0·831 (95% CI 0·793-0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% [85·0-90·2] vs 78·3% [72·1-84·5], p<0·0001; 82·7% [78·5-86·9] vs 70·4% [59·1-81·7], p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05). INTERPRETATION: The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists' accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials. FUNDING: National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.

Circular RNAs in stem cells: from basic research to clinical implications.

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, microRNA (miRNA) sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNA-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.

Identification and construction of lncRNA-associated ceRNA network in diabetic kidney disease.

ABSTRACT: Diabetic kidney disease (DKD) has become the major contributor to end-stage renal disease with high incidence and mortality. The functional roles and exact mechanisms of long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in DKD are still largely unknown. This study sought to discover novel potential biomarkers and ceRNA network for DKD.The candidate differentially expressed genes (DEGs), lncRNAs and microRNAs (miRNAs) in human glomerular and tubular tissues derived from Gene Expression Omnibus database were systematically selected and analyzed. Functional enrichment analysis and protein-protein interaction network analysis were conducted to identify hub genes and reveal their regulatory mechanisms involved in DKD. Following this, the integrated ceRNA network was constructed by bioinformatics methods.A total of 164 DEGs, 6 lncRNAs and 18 miRNAs correlated with DKD were finally filtered and identified. It is noteworthy that the global lncRNA-associated ceRNA network related to DKD was constructed, among which lnc-HIST2H2AA4-1, VCAN-AS1 and MAGI2-AS1 were identified as the 3 key lncRNAs, and VCAN, FN1, CCL2, and KNG1 were identified as the predominant genes. Consistent with that observed in the training set, 3 of the key genes also showed significant differences in the 2 validation datasets. Integrating with functional enrichment analysis results, these key genes in the ceRNA network were mainly enriched in the immune and inflammation-related pathways.This study first identified key lncRNAs, miRNAs and their targets, and further revealed a global view of lncRNA-associated ceRNA network involved in DKD by using whole gene transcripts analysis.

Clinical characteristics of 9 cancer patients with SARS-CoV-2 infection.

In December 2019, a cluster of pneumonia cases was caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. Cancer patients are a special group, the immunity of them will be suppressed because of various anti-tumor treatments, and the risk of infection will be greatly increased, so we will report clinical features of 9 cancer patients with SARS-CoV-2 infection. 5 (56%) patients were ordinary type, 3 (33%) were severe type, and 1 (11%) was critical type. A total of 8 patients received combined therapy of traditional Chinese medicines and western medicines. From the clinical outcomes of these 8 patients, western combined therapy of traditional Chinese medicine was indeed an effective treatment method. D-dimmer rise, infection index rise, and chest CT(computed tomography) progression may be clinical warning indicators for severe patients, in our study, more 50% of patients had elevated levels of these indicators, but only 44% (including the dead) of patients had received treatment in the intensive care unit. 5 (56%) ordinary type patients had been discharged, while the 1 (11%) critical type patient died 3 days after admission. Cancer comorbidity seems to have no direct relationship with severe events, and the combination of traditional Chinese medicine and western medicine may be effective in the prevention and treatment of novel coronavirus-infected pneumonia (NICP).

High Glucose Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in A20 Murine Diffuse Large B-Cell Lymphoma Cells Through Increased Expression of High Mobility Group AT-Hook 2 (HMGA2).

BACKGROUND Patients with type 2 diabetes mellitus have been reported to be at increased risk of developing non-Hodgkin's lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common type of high-grade NHL. This study aimed to investigate the effects of high glucose on cell migration, invasion and epithelial-mesenchymal transition (EMT), and the expression of high mobility group AT-hook 2 (HMGA2) in A20 murine DLBCL cells. MATERIAL AND METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expression of HMGA2 at the gene and protein level and EMT markers in the A20 murine DLBCL cell line. A transwell assay evaluated cell migration and invasion of A20 cells. Short-interfering RNA (siRNA) was used to knockdown HMGA2 expression. RESULTS High glucose levels upregulated the expression of HMGA2, induced phenotypic changes of EMT, and increased cell migration and invasion in A20 cells. Knockdown of HMGA2 by siRNA effectively inhibited EMT induced by high glucose in A20 cells by directly regulating the Wnt/ß-catenin signaling pathway. CONCLUSIONS In the A20 murine DLBCL cell line, high glucose upregulated the expression of HMGA2 to induce EMT and promote cell migration and invasion through the Wnt/ß-catenin signaling pathway.

Overexpression of erythropoietin-producing hepatocyte receptor B4 and ephrin-B2 is associated with estrogen receptor expression in endometrial adenocarcinoma.

Endometrial adenocarcinoma (EC) is one of the most frequently diagnosed types of endometrial cancer and is typically a consequence of continuous estrogen receptor stimulation. Erythropoietin-producing hepatocyte receptor B4 (EphB4) and its ligand ephrin-B2 have been reported to be overexpressed in EC cells; however, the function in EC remains unclear. The present study aimed to elucidate the role of EphB4 and ephrin-B2 in EC. The protein expression pattern of EphB4 and ephrin-B2 was analyzed through immunohistochemistry and western blot analysis in endometrium with adenomyosis or simple endometrial hyperplasia, atypical endometrial hyperplasia, double-positive estrogen receptor (ER)/progesterone receptor (PR) EC and double-negative ER/PR EC. The expression of EphB4 and ephrin-B2 was demonstrated to be increased in atypical EH and ER/PR-positive EC, but not ER/PR-negative EC. Furthermore, EphB4 and ephrin-B2 expression was positively associated with ER expression in EC tissue. The results of the present study suggest that the overexpression of EphB4 and ephrin-B2 in the endometrium serves a role in the pathogenesis of EC, in addition to being associated with ER expression.

Abnormal Expression of TRAIL Receptors in Decidual Tissue of Chlamydia trachomatis-Infected Rats During Early Pregnancy Loss.

Chlamydia trachomatis is the scientific name of pathogenic bacteria causing infection that has been linked to spontaneous abortion. In this study, the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; a cytokine related to cell apoptosis) and its receptors was monitored in the decidua of C trachomatis-infected pregnant rats during early gestation to investigate the potential role of this molecular system in C trachomatis-induced spontaneous abortion. The data showed that C trachomatis infection significantly altered the messenger RNA (mRNA) expression of the receptors; death receptor (DR) 4 and DR5 increased, but decoy receptor (DcR) 1 and DcR2 decreased. Consistent with mRNA data, immunohistochemical staining of TRAIL and its receptors indicated that both DR4 and DR5 protein levels were elevated in infected tissues, primarily, decidual cells, decidual vessel wall, and uterine glands, whereas DcR1 and DcR2 showed lower levels compared to the noninfected group. Although receptor expression was altered, there was no difference detected in TRAIL expression. The observed altered expression of TRAIL receptors in C trachomatis-infected rats compared to noninfected rats during the embryo implantation phase suggests a possible mechanism for spontaneous abortion due to apoptosis and therefore failed embryo implantation. In addition, the observed increase in caspase-3 levels in infected cells further supports this finding. Taken together, the data presented in this study suggests C trachomatis infection altered the expression of TRAIL receptors, thus representing a general mechanism for C trachomatis-induced spontaneous abortion in C trachomatis-infected rats during early pregnancy loss.

Mild oxidative stress induced by a low dose of cisplatin contributes to the escape of TRAIL-mediated apoptosis in the ovarian cancer SKOV3 cell line.

Tumor necrosis factor (TNF)-related apoptosis­inducing ligand (TRAIL) is expressed in ovarian tissue and is widely thought to exhibit strong antitumor activity in a variety of tumor cell types. Therefore, we hypothesized that the cisplatin resistance of ovarian cancer is linked to the ability to escape from TRAIL-mediated apoptosis. We demonstrated that cisplatin-resistant ovarian cancer cell line SKOV3/DDP tolerated treatment with TRAIL, in contrast to the cisplatin­sensitive ovarian cancer cell line SKOV3. SKOV3/DDP cells exhibited a much higher cell viability and a lower apoptosis rate than SKOV3 cells after treatment with TRAIL. To determine whether cisplatin induced the tolerance of TRAIL, we pretreated the SKOV3 cells with cisplatin in the presence of TRAIL. This revealed that a low dose of cisplatin (1 µM) increased the TRAIL tolerance of SKOV3 cells. Furthermore, cisplatin induced oxidative stress in both the SKOV3/DDP and SKOV3 cells, although the oxidative stress level of the SKOV3/DDP cells was generally much higher than that noted in the SKOV3 cells. Similarly, a low dose of hydrogen peroxide increased the TRAIL tolerance in SKOV3 cells. Notably, the TRAIL tolerance in the SKOV3 and SKOV3/DDP cells could be abrogated by the oxidative stress scavenger N-acetyl-cysteine. These results suggest that a low dose of cisplatin induces the tolerance of TRAIL in SKOV3 cells at least partly, depending on the oxidative stress signaling pathway.

Short hairpin ribonucleic acid constructs targeting insulin-like growth factor binding protein-3 rehabilitated decreased testosterone concentrations in diabetic rats.

BACKGROUND: The aim of this study was to determine if shRNA constructs targeting insulin-like growth factor binding protein-3 can rehabilitate decreased serum testosterone concentrations in streptozotocin-induced diabetic rats. MATERIAL/METHODS: After 12 weeks of intracavernous administration of IGFBP-3 shRNA, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 at mRNA and protein levels was detected by quantitative real-time PCR analysis and Western blot, respectively. The concentrations of serum testosterone and cavernous cyclic guanosine monophosphate were detected by enzyme-linked immunosorbent assay. RESULTS: After 12 weeks of intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic control group (p<0.01). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. Both serum testosterone and cavernous cyclic guanosine monophosphate concentrations were significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic control group (p<0.01). CONCLUSIONS: These results suggest that IGFBP-3 shRNA may rehabilitate erectile function via increases of concentrations of serum testosterone and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats.

Establishment of an orthotopic transplantation tumor model in nude mice using a drug-resistant human ovarian cancer cell line with a high expression of c-Kit.

The resistance of ovarian cancer to platinum-based chemotherapy is a critical issue in the clinical setting. The present study aimed to establish animal models to replicate this clinical condition, as well as to investigate the resistance mechanisms of ovarian cancer. A cisplatin (DDP)-resistant human ovarian cancer cell line, SKOV3/DDP, was screened, validated and injected subcutaneously into the neck of female nude mice. Following tumor establishment, the tumor was collected and cut into small sections, which were subsequently implanted into the ovaries of other nude mice. The growth of the orthotopic tumors was observed and the tumor-bearing mice were sacrificed and dissected. The orthotopic and metastatic tumor tissues were collected, sectioned, stained with hematoxylin and eosin and analyzed. In the present study, 16 nude mice underwent orthotopic transplantation surgery and a tumor model was successfully established in 14/16 of the mice, with an in situ tumor formation rate of 87.5%. Following euthanasia, a laparotomy demonstrated the tumor formation at the site of transplantation, as well as varying degrees of metastasis to additional organs and tissues. Therefore, the present study successfully established an orthotopic tumor transplantation model in nude mice using a c-Kit-positive DDP-resistant human ovarian cancer cell line. This model may represent a useful tool for investigating the resistance mechanism of ovarian cancer, as well as evaluating the efficacy of therapeutic strategies.

Expression and significance of transforming growth factor-ß1 in epithelial ovarian cancer and its extracellular matrix.

The aim of the present study was to investigate the expression and significance of transforming growth factor-ß1 (TGF-ß1) in the cytoplasm and extracellular matrix (ECM) of epithelial ovarian cancer cells. The expression of TGF-ß1 protein was detected in paraffin-embedded sections of 25 normal ovarian epithelial tissues, 10 benign epithelial cysts and 72 epithelial ovarian cancer specimens, using the Strept Avidin Biotin Peroxidase Complex immunohistochemistry method. In addition, the expression of TGF-ß1 mRNA in normal fibroblasts (NFs) and ovarian cancer-associated fibroblasts (CAFs) was assessed using semi-quantitative polymerase chain reaction (PCR). TGF-ß1 protein was expressed in the cytoplasm and ECM, and no significant difference was identified between normal and benign ovarian tissues (P>0.05). However, the cytosolic expression of TGF-ß1 declined gradually between the benign ovarian tumor and epithelial ovarian cancer, while its expression in the ECM significantly increased (P<0.05). The expression of TGF-ß1 in the cytoplasm and ECM in epithelial ovarian cancer was found to negatively correlate with tumor differentiation, however, it was positively associated with the clinical stages. The positive rates of TGF-ß1 in the cytoplasm and ECM between ovarian cancers in clinical stages I-II and III-IV were significantly different (P<0.05). Furthermore, the PCR data indicated that the relative expression of TGF-ß1 mRNA in ovarian CAFs (1.0270±0.0539) was significantly higher than that in NFs (0.7131±0.0186). Therefore, the expression of TGF-ß1 was identified to be associated with the development and progression of epithelial ovarian cancer, and the high expression of TGF-ß1 in the ECM may be associated with the invasion and metastasis of ovarian cancer.