Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors.

BACKGROUND: To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). METHODS: Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan-Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. RESULTS: We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150-2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255-2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057-2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185-1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347-2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761). CONCLUSION: R-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.

Tumor lesion detection in patients with cervical cancer by indocyanine green near-infrared imaging.

PURPOSE: To investigate the feasibility and accuracy of near-infrared fluorescence (NIRF) imaging for detecting the extent of tumor invasion in cervical cancer using indocyanine green (ICG). METHODS: We enrolled 51 patients who were diagnosed with cervical cancer with FIGO stage IB1-IIA2 disease. Patients were administered indocyanine green (ICG) at a dose of 5 mg/kg 24 h prior to surgery. A customized near-infrared fluorescence (NIRF) imaging system was used to identify the extent of tumor invasion when radical hysterectomy specimens were harvested. The relationship between tumor fluorescence intensity and clinicopathological characteristics was analyzed. RESULTS: Of the 51 enrolled patients, 3 patients did not have residual tumors after cervical conization, and tumor lesions were identified by NIRF imaging in all the remaining 48 patients. The results of NIRF imaging were in agreement with the postoperative pathological findings in 95.8% of the patients with stromal invasion, 100% of those with surgical margin invasion, 100% of those with parametrial tumor involvement, and 100% of patients with uterine corpus invasion. The mean signal-to-background ratio (SBR) of the cervical tumors was 2.91 ± 1.64, and the SBR was independent of clinicopathological characteristics. Fluorescence microscopy confirmed that ICG fluorescence was present in the tumor nests. CONCLUSIONS: NIRF imaging enables objective, accurate, and safe identification of tumor invasion during cervical cancer surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04224467.

Intraoperative near-infrared fluorescence imaging can identify pelvic nerves in patients with cervical cancer in real time during radical hysterectomy.

PURPOSE: Radical hysterectomy combined with pelvic lymphadenectomy is the standard treatment for early-stage cervical cancer, but unrecognized pelvic nerves are vulnerable to irreversible damage during surgery. This early clinical trial investigated the feasibility and safety of intraoperative near-infrared (NIR) fluorescence imaging (NIR-FI) with indocyanine green (ICG) for identifying pelvic nerves during radical hysterectomy for cervical cancer. METHODS: Sixty-six adults with cervical cancer were enrolled in this prospective, open-label, single-arm, single-center clinical trial. NIR-FI was performed in vivo to identify genitofemoral (GN), obturator (ON), and hypogastric (HN) nerves intraoperatively. The primary endpoint was the presence of fluorescence in pelvic nerves. Secondary endpoints were the ICG distribution in a nerve specimen and potential underlying causes of fluorescence emission in pelvic nerves. RESULTS: In total, 63 patients were analyzed. The ON was visualized bilaterally in 100% (63/63) of patients, with a mean fluorescence signal-to-background ratio (SBR) of 5.3±2.1. The GN was identified bilaterally in 93.7% (59/63) of patients and unilaterally in the remaining 4 patients, with a mean SBR of 4.1±1.9. The HN was identified bilaterally in 81.0% (51/63) of patients and unilaterally in 7.9% (5/63) of patients, with a mean SBR of 3.5±1.3. ICG fluorescence was detected in frozen sections of a nerve specimen, and was mainly distributed in axons. No ICG-related complications were observed. CONCLUSION: This early clinical trial demonstrated the feasibility and safety of NIR-FI to visualize pelvic nerves intraoperatively. Thus, NIR-FI may help surgeons adjust surgical decision-making, avoid nerve damage, and improve surgical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04224467.

Lewis-Basic EDTA as a Highly Active Molecular Electrocatalyst for CO2 Reduction to CH4.

The most active catalysts so far successful in hydrogenation reduction of CO2 are mainly heterogeneous Cu-based catalysts. The complex coordination environments and multiple active sites in heterogeneous catalysts result in low selectivity of target product, while molecular catalysts with well-defined active sites and tailorable structures allow mechanism-based performance optimization. Herein, we firstly report a single ethylenediaminetetraacetic acid (EDTA) molecular-level immobilized on the surface of carbon nanotube as a catalyst for transferring CO2 to CH4 with an excellent performance. This catalyst exhibits a high Faradaic efficiency of 61.6 % toward CH4 , a partial current density of -16.5 mA cm-2 at a potential of -1.3 V versus reversible hydrogen electrode. Density functional theory calculations reveal that the Lewis basic COO- groups in EDTA molecule are the active sites for CO2 reduction reaction (CO2 RR). The energy barrier for the generation of CO from *CO intermediate is as high as 0.52 eV, while the further protonation of *CO to *CHO follows an energetic downhill path (-1.57 eV), resulting in the high selectivity of CH4 . This work makes it possible to control the product selectivity for CO2 RR according to the relationship between the energy barrier of *CO intermediate and molecular structures in the future.

Nano-assembly of ursolic acid with platinum prodrug overcomes multiple deactivation pathways in platinum-resistant ovarian cancer.

As the most common cause of gynecological cancer-related deaths worldwide, ovarian cancer requires novel therapy strategies. Pt(ii)-Based antitumor drugs (e.g. cisplatin) are one of the most successful and frequently used drugs in ovarian cancer chemotherapy at present. However, drug resistance and severe side effects are the major problems in cancer treatment. Herein, the design of a reduction responsive platinum(iv) (Pt(iv))/ursolic acid (UA)/polyethylene glycol (PEG) dual prodrug amphiphile (Pt(iv)-UA-PEG) to treat cisplatin-resistant ovarian cancer is reported for the first time. Pt(iv)-UA-PEG could self-assemble into nanoparticles (Pt(iv)-UA NPs) with a fixed and precise Pt/UA ratio, and a constantly high content of drugs. Pt(iv)-UA NPs could be efficiently taken up by cisplatin-resistant ovarian cancer cells and release the drug in intracellular reductive and acidic environments. In vitro studies show that the released UA and cisplatin have different anticancer mechanisms, and their synergistic effects overcome the detoxification and anti-apoptotic mechanisms of cancer cells. Furthermore, the in vivo results indicate that Pt(iv)-UA NPs have a prolonged blood circulation time, enhanced tumor accumulation, and significantly improved antitumor efficacy in A2780/DDP tumor-bearing mice, without causing any side effects. In summary, our results demonstrate that the development of the stimuli-responsive dual prodrug amphiphile nano-assembly provides a new strategy to overcome drug resistance.

Clinical analysis of five case reports of ovarian teratoma withanti-N-methyl-D-aspartate receptor encephalitis.

We have collected the data of five patients with ovarian teratoma and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis admitted to the Southern Hospital of Southern Medical University from June 2014 to December 2017, we found that all of them started with psychiatric symptoms, four had autonomic nervous system dysfunction, while all of them exposed to abnormal brain and pelvic imaging, four patients required mechanical ventilation to assist breathing during the hospital stay. The serum anti-NMDAR antibodies were positive in five patients. After immunotherapy and surgery, all patients showed favorable prognosis. Pathology: four mature teratomas and one immature teratoma. In conclusion, patients with ovarian teratoma with anti-NMDAR encephalitis often begins with neurological and psychiatric symptoms, it is easy to be misdiagnosed due to the lack of overt symptoms, while the early detection and tumor resection combined with immunotherapy will win favorable prognosis.

Ultrasound Features Improve Diagnostic Performance of Ovarian Cancer Predictors in Distinguishing Benign and Malignant Ovarian Tumors.

To determine whether ultrasound features can improve the diagnostic performance of tumor markers in distinguishing ovarian tumors, we enrolled 719 patients diagnosed as having ovarian tumors at Nanfang Hospital from September 2014 to November 2016. Age, menopausal status, histopathology, the International Federation of Gynecology and Obstetrics (FIGO) stages, tumor biomarker levels, and detailed ultrasound reports of patients were collected. The area under the curve (AUC), sensitivity, and specificity of the bellow-mentioned predictors were analyzed using the receiver operating characteristic curve. Of the 719 patients, 531 had benign lesions, 119 had epithelial ovarian cancers (EOC), 44 had borderline ovarian tumors (BOT), and 25 had non-EOC. AUCs and the sensitivity of cancer antigen 125 (CA125), human epididymis-specific protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA), Risk of Malignancy Index (RMI1), HE4 model, and Rajavithi-Ovarian Cancer Predictive Score (R-OPS) in the overall population were 0.792, 0.854, 0.856, 0.872, 0.893, 0.852, and 70.2%, 56.9%, 69.1%, 60.6%, 77.1%, 71.3%, respectively. For distinguishing EOC from benign tumors, the AUCs and sensitivity of the above mentioned predictors were 0.888, 0.946, 0.947, 0.949, 0.967, 0.966, and 84.0%, 79.8%, 87.4%, 84.9%, 90.8%, 89.1%, respectively. Their specificity in predicting benign diseases was 72.9%, 94.4%, 87.6%, 95.9%, 86.3%, 90.8%, respectively. Therefore, we consider biomarkers in combination with ultrasound features may improve the diagnostic performance in distinguishing malignant from benign ovarian tumors.

Reconstruction of three-dimensional vascular models for lymphadenectomy before surgery.

Introduction: A three-dimensional (3D) model of the pelvic vessels was reconstructed before surgery to aid in the understanding of the individual anatomy and help guide lymphadenectomy performance.Material and methods: Thirty patients with early-stage cervical cancer who were scheduled for lymphadenectomy at Nanfang Hospital, Southern Medical University from January 2017 to June 2017 were included. Three-dimensional models of the pelvic vessels were obtained.Results: All 3D models of the 30 patients were reconstructed successfully and were consistent with the operative findings.The most common structural types posterior to the common iliac artery (CIA) and CIA bifurcation (CIAB) were non-vessel structures (23/30 patients) and the common iliac vein (CIV) (27/30); these were observed separately on the left pelvic vein. The confluence of common iliac vein (CCIV) (29/30) and CIV (20/30) were most commonly observed posterior to the CIA and CIAB; these were observed separately on the right pelvic vein. Venous abnormalities were identified in 15 patients. There were variants in venous confluence shown to be homolateral to the CIV (2/15) and contralateral to the CIV (2/15) and CCIV (4/15).Conclusions: Three-dimensional models of the pelvic vessels can provide information on individual anatomy features that can help guide lymphadenectomy performance.

Enhancing the Capacitance of Battery-Type Hybrid Capacitors by Encapsulating MgO Nanoparticles in Porous Carbon as Reservoirs for OH- Ions from Electrolytes.

A novel design of no-loading and bifunctional positive electrode, serving as an active material and current collector simultaneously, has been constructed by grass-like nickel foam which shows a battery-type performance and excellent areal specific capacity at 0.540 mA h·cm-2 (over 4500 mF·cm-2). To obtain a high-performance hybrid capacitor, layered porous carbonaceous composites C/MgO negative electrodes were fabricated, in which MgO nanoparticles serve as "reservoirs" for OH- ions from the electrolyte. Compared with other carbon materials, such as carbon fibers, hollow nanospheres, and nanotubes, the three-dimensional (3D) hierarchical heterostructures of the C/MgO electrode exhibit a higher storage performance of 424.1 mF·cm-2. Assembled by these two working electrodes, a hybrid capacitor with uncommon galvanostatic charge/discharge cycling curve has been well-investigated in an alkaline aqueous electrolyte system. This as-coupled hybrid capacitor exhibits an engaging activation process during multiple cycling tests and leads to a drastically improved energy density of 60% (from 80.4 to 128.8 µW h·cm-2), which can be attributed to a "match behavior" between its positive and negative electrodes.

Discrepancies between clinical staging and surgicopathologic findings in early-stage cervical cancer and prognostic significance.

OBJECTIVE: To investigate discrepancies between clinical staging and surgicopathologic findings in early-stage cervical cancer and explore the prognostic significance of these discrepancies. METHODS: A retrospective review of the clinical records of individuals with early-stage cervical cancer who underwent primary radical surgery in Nanfang Hospital of Southern Medical University, Guangzhou, China, between 2007 and 2013. Discrepancies in clinical staging were investigated by using surgicopathologic findings as the reference. Individuals were classified according to the type of discrepancy. Kaplan-Meier plots were generated to explore the prognostic significance of stage discrepancies. RESULTS: Among 266 individuals included in the study, 182 (68.4%) were accurately staged, 58 (21.8%) were clinically over-staged, and 26 (9.8%) were clinically under-staged. More relapses (19.2% vs 4.9% vs 6.8%, P=0.027) and deaths (11.5% vs 2.2% vs 3.4%, P=0.048) were observed among those who were clinically under-staged than among those who were accurately or clinically over-staged. Clinical under-staging was associated with poorer disease-free survival (P=0.003) and poorer overall survival (P=0.020) over a median follow-up of 43.9 months. CONCLUSION: Significant discrepancies were found between clinical staging and surgicopathologic findings in early-stage cervical cancer. Stage discrepancies were found to have prognostic significance, with clinical under-staging identified as a potential adverse prognostic factor.

Neurovascular and lymphatic vessels distribution in uterine ligaments based on a 3D reconstruction of histological study: to determine the optimal plane for nerve-sparing radical hysterectomy.

OBJECTIVE: To present the distribution of neurovascular and lymphatic vessels in uterine ligaments using 3D models based on the pathological staining of serial 2D sections of postoperative specimens. METHODS: Serial transverse sections of fresh uterine ligaments from a patient with stage IB1 cervical squamous cell carcinoma were studied using the computer-assisted anatomic dissection (CAAD) technique. The sections were stained with hematoxylin and eosin, Weigert elastic fibers, D2-40 and immunostainings (sheep anti-tyrosine hydroxylase and rabbit anti-vasoactive intestinal peptide). The sections were then digitalized, registered and reconstructed three-dimensionally. Then, the 3D models were analyzed and measured. RESULTS: The 3D models of the neurovascular and lymphatic vessels in uterine ligaments were created, depicting their precise location and distribution. The vessels were primarily located in the upper part of the ligaments model, while the pelvic autonomic nerves were primarily in the lower part; the lymphatic vessels were scattered in the uterine ligaments, without obvious regularity. CONCLUSION: CAAD is an effective anatomical method to study the precise distribution of neurovascular and lymphatic vessels in uterine ligaments. It can present detailed anatomical information about female pelvic autonomic innervation and the spatial relationship between nerves and vessels and may provide a better understanding of nerve-sparing radical hysterectomy.

RCC2, a regulator of the RalA signaling pathway, is identified as a novel therapeutic target in cisplatin-resistant ovarian cancer.

Currently, cisplatin (DDP) is the first-line chemotherapeutic agent used for treatment of ovarian cancer, but gradually acquired drug resistance minimizes its therapeutic outcomes. We aimed to identify crucial genes associated with DDP resistance in ovarian cancer and uncover potential mechanisms. Two sets of gene expression data were downloaded from Gene Expression Omnibus, and bioinformatics analysis was conducted. In our study, the differentially expressed genes between DDP-sensitive and DDP-resistant ovarian cancer were screened in GSE15709 and GSE51373 database, and chromosome condensation 2 regulator (RCC2) and nucleoporin 160 were identified as 2 genes that significantly up-regulated in DDP-resistant ovarian cancer cell lines compared with DDP-sensitive cell lines. Moreover, RCC2, Ral small GTPase (RalA), and Ral binding protein-1 (RalBP1) expression was found to be significantly higher in DDP-resistant ovarian cancer tissues than in DDP-sensitive tissues. RCC2 plays a positive role in cell proliferation, apoptosis, and migration in DDP-resistant ovarian cancer cell lines in vitro and in vivo. Furthermore, RCC2 could interact with RalA, thus promoting its downstream effector RalBP1. RalA knockdown could reverse the effects of RCC2 overexpression on DDP-resistant ovarian cancer cell proliferation, apoptosis, and migration. Similarly, RalA overexpression could alleviate the effects of RCC2 knockdown in DDP-resistant ovarian cancer cells. Taken together, RCC2 may function as an oncogene, regulating the RalA signaling pathway, and intervention of RCC2 expression might be a promising therapeutic strategy for DDP-resistant ovarian cancer.-Gong, S., Chen, Y., Meng, F., Zhang, Y., Wu, H., Li, C., Zhang, G. RCC2, a regulator of the RalA signaling pathway, is identified as a novel therapeutic target in cisplatin-resistant ovarian cancer.

Ultrasmall Ru/Cu-doped RuO2 Complex Embedded in Amorphous Carbon Skeleton as Highly Active Bifunctional Electrocatalysts for Overall Water Splitting.

Developing highly active electrocatalysts with superior durability for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in the same electrolyte is a grand challenge to realize the practical application of electrolysis water for producing hydrogen. In this work, an ultrasmall Ru/Cu-doped RuO2 complex embedded in an amorphous carbon skeleton is synthesized, through thermolysis of Ru-modified Cu-1,3,5-benzenetricarboxylic acid (BTC), as a highly efficient bifunctional catalyst for overall water splitting electrocatalysis. The ultrasmall Ru nanoparticles in the complex expose more activity sites for hydrogen evolution and outperform the commercial Pt/C. Meanwhile, the ultrasmall RuO2 nanoparticles exhibit superior oxygen evolution performance over commercial RuO2, and the doping of Cu into the ultrasmall RuO2 nanoparticles further enhances the oxygen evolution performance of the catalyst. The outstanding OER and decent HER catalytic activity endow the complex with impressive overall water splitting performance superior to that of the state-of-the-art electrocatalysts, which just require 1.47 and 1.67 V to achieve a current density of 10 mA cm-2 and 100 mA cm-2. The density functional theory calculations reveal that a Cu dopant could effectively tailor the d-band center, thereby tuning electronic structure of Ru activity sites on the RuO2 (110) plane and ultimately improving the OER performance of RuO2.

Roflumilast enhances cisplatin-sensitivity and reverses cisplatin-resistance of ovarian cancer cells via cAMP/PKA/CREB-FtMt signalling axis.

OBJECTIVE: We previously demonstrated the roflumilast inhibited cell proliferation and increased cell apoptosis in ovarian cancer. In this study, we aimed to investigate the roles of roflumilast in development of cisplatin (DDP)-sensitive and -resistant ovarian cancer. METHODS: OVCAR3 and SKOV3 were selected and the corresponding DDP-resistant cells were constructed. Cell viability, proliferation, apoptosis, cycle were performed. Expression cAMP, PKA, CREB, phosphorylation of CREB and FtMt were detected. The roles of roflumilast in development of DDP-sensitive and -resistant ovarian cancer were confirmed by xenograft model. RESULTS: Roflumilast + DDP inhibited cell proliferation, and induced cell apoptosis and G0/G1 arrest in OVCAR3 and SKOV3 cells, roflumilast induced expression of FtMt, the activity of cAMP and PKA and phosphorylation of CREB in ovarian cancer cells and the above-effect were inhibited by H89. Downregulation of CREB inhibited the roflumilast-increased DDP sensitivity of ovarian cancer cells, and the roflumilast-induced FtMt expression and phosphorylation of CREB. Also, roflumilast reversed cisplatin-resistance, and induced expression of FtMt and activation of cAMP/PKA/CREB in DDP-resistant ovarian cancer cells. Similarly, treated with H89 or downregulation of CREB inhibited the changes induced by roflumilast. In vivo, roflumilast inhibited the development of SKOV3 or SKOV3-DDP-R xenograft models. CONCLUSIONS: Roflumilast enhanced DDP sensitivity and reversed the DDP resistance of ovarian cancer cells via activation of cAMP/PKA/CREB pathway and upregulation of the downstream FtMt expression, which has great promise in clinical treatment.

Tuning the Activity of Carbon for Electrocatalytic Hydrogen Evolution via an Iridium-Cobalt Alloy Core Encapsulated in Nitrogen-Doped Carbon Cages.

Graphene, a 2D material consisting of a single layer of sp2 -hybridized carbon, exhibits inert activity as an electrocatalyst, while the incorporation of heteroatoms (such as N) into the framework can tune its electronic properties. Because of the different electronegativity between N and C atoms, electrons will transfer from C to N in N-doped graphene nanosheets, changing inert C atoms adjacent to the N-dopants into active sites. Notwithstanding the achieved progress, its intrinsic activity in acidic media is still far from Pt/C. Here, a facile annealing strategy is adopted for Ir-doped metal-organic frameworks to synthesize IrCo nanoalloys encapsulated in N-doped graphene layers. The highly active electrocatalyst, with remarkably reduced Ir loading (1.56 wt%), achieves an ultralow Tafel slope of 23 mV dec-1 and an overpotential of only 24 mV at a current density of 10 mA cm-2 in 0.5 m sulfuric acid solution. Such superior performance is even superior to the noble-metal catalyst Pt. Surface structural and computational studies reveal that the superior behavior originates from the decreased ΔGH* for HER induced by the electrons transferred from the alloy core to the graphene layers, which is beneficial for enhancing CH binding.

[Diagnostic value of CA125, HE4 and Copenhagen Index in differentiating benign from malignant epithelial ovarian tumors].

OBJECTIVE: To analyze diagnostic value of Copenhagen Index based on pretreatment serum CA125, HE4 and age in differentiating benign and malignant epithelial ovarian tumors. METHODS: The clinical data were analyzed for 208 consecutive patients with epithelial ovarian tumors (including 100 with malignant and 108 with benign tumors) treated in our department between September, 2014 and September, 2016. The receiver-operating characteristic curve was drawn based on the golden standard of pathological diagnosis for calculation of the diagnostic sensitivity and specificity of CA125, HE4 and the Copenhagen Index. RESULTS: In the overall cases, early stage cases and advanced stage cases, the prediction probabilities of CA125, HE4 and Copenhagen Index were all significantly higher for malignant than in benign tumors (P<0.001). The sensitivities of CA125, HE4, Copenhagen Index for differentiating benign and malignant tumors were 81.0%, 86.0% and 91.0% in the overall cases, 64.0%, 68.0% and 72.0% in early stage cases, and 86.7%, 92.0% and 97.3% in advanced stage cases, and their diagnostic specificities were 88.0%, 93.5% and 96.3%, respectively. Copenhagen Index had the highest diagnostic sensitivity (but not in early stage cases) and specificity followed by HE4 and then by CA125 (P<0.001) (P>0.05). CONCLUSION: Copenhagen Index combined with CA125, HE4 and age hase better diagnostic value than HE4 or CA125 alone for differentiation between benign and malignant epithelial ovarian tumors, and can be used clinically to improve the early diagnostic rate of epithelial ovarian cancer.

Roflumilast restores cAMP/PKA/CREB signaling axis for FtMt-mediated tumor inhibition of ovarian cancer.

The abrogation of cAMP generation by overexpression of PDE isoforms promotes the inflammatory pathology, and the PDE inhibitors have showed the potential anti-inflammation effects in clinical. However, the function of PDE inhibitors in cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest in two ovarian cancer cell lines OVCAR3 and SKOV3. Meanwhile, the cAMP/PKA/CREB signals was activated by Roflumilast, which was accompanied by the up-regulation of mitochondrial ferritin (FtMt) level. Interestingly, forced expression of FtMt in ovarian cancer enhanced the apoptosis and inhibited tumor growth and the PKA inhibitor H89 and knockdown of CREB significantly repressed the expression of FtMt to restore the tumor proliferation and inhibit apoptosis. In addition, we found that Roflumilast-induced phosphorylated CREB directly promoted transcription of FtMt, indicating that Roflumilast up-regulated the expression of FtMt in ovarian cancer via cAMP/PKA/CREB signals. The anti-tumor role of Roflumilast in vivo was also demonstrated, the treatment of roflumilast effectively inhibited tumor proliferation and elevated the FtMt expression to restrict the tumor growth via the activation of cAMP/PKA/CREB signals in ovarian cancer.

Outcomes in Adenomyosis Treated with Uterine Artery Embolization Are Associated with Lesion Vascularity: A Long-Term Follow-Up Study of 252 Cases.

PURPOSE: To study the therapeutic effects of uterine artery embolization (UAE) on adenomyosis and to investigate the association between uterine blood supply and artery embolization treatment outcomes. METHODS: Using digital subtraction angiography (DSA) imaging data, we retrospectively evaluated the vascular features of 252 adenomyosis patients treated with UAE. The cases were classified based on the equality of uterine blood supply (equal and unequal subgroups) and the degree of vascularity at the adenomyosis lesion site (hypervascular, isovascular and hypovascular subgroups). Patients were followed-up for 5 years after UAE. Improvements in dysmenorrhea and menorrhagia were evaluated based on the relief of the patients' symptoms. The improvement rates among the different subgroups were analyzed and compared. RESULTS: The improvement rates of dysmenorrhea and menorrhagia were 74.0% and 70.9%, respectively, at the short-term (12-month) follow-up and 70.4% and 68.8%, respectively, at the long-term (5-year) follow-up. No statistically significant differences were observed in the improvement rates for dysmenorrhea or menorrhagia between the equal and unequal blood supply subgroups at either the short- or long-term follow-up. The improvement rates for dysmenorrhea among the hypervascular, isovascular and hypovascular subgroups were 86.5%, 71.8% and 58.8%, respectively, at the short-term follow-up (p = 0.002) and 83.6%, 67.3% and 52.8%, respectively, at the long-term follow-up (p = 0.005). The improvement rates for menorrhagia in the hypervascular, isovascular and hypovascular subgroups were 81.0%, 68.3% and 60.7%, respectively, at the short-term follow-up (p = 0.024) and 79.4%, 61.4% and 62.2%, respectively, at the long-term follow-up (p = 0.052). CONCLUSION: UAE is effective in treating patients with adenomyosis in both the short and long term. The outcomes of patients with adenomyosis were significantly correlated with lesion vascularity.

[Effects of docosahexaenoic acid on cell apoptosis, invasion and migration of cervical cancer cells in vitro].

OBJECTIVE: To investigate the effect of docosahexaenoic acid (DHA) on apoptosis, migration and invasion of cervical cancer cell lines. METHODS: cervical cancer cell lines Hela and Siha in logarithmic phase were treated different concentrations of DHA. The morphological changes of the cells were observed microscopically and cell apoptosis was observed using Hoechst 33258 fluorescent staining. MTT assay was used to evaluate the effect of DHA in suppressing cell growth, and flow cytometry was employed to analyze the changes of cell apoptotic rate following DHA stimulations. Wound healing assay and Transwell migration assay were used to evaluate the migration of the cell lines. The expression levels of Bax, Bcl-2 cleaved caspase3, MMP-9 and VEGF proteins were detected by Western blotting. RESULTS: DHA exposure of the cells caused obvious morphological changes and dose-dependently increased the number of apoptotic bodies in the cells. MTT assay showed that DHA inhibited the growth of the cancer cells in a time- and concentration-dependent manner. DHA also effectively suppressed migration and invasion of the cancer cells. The cells exposed to DHA showed significantly down-regulation of Bcl-2, MMP-9 and VEGF proteins and up-regulation of cleaved-caspase 3 and Bax. CONCLUSION: DHA can promote cervical carcinoma cell apoptosis by down-regulating the anti-apoptotic proteins Bax, Bcl-2 and cleaved-caspase3 and suppress cell invasion by decreasing MMP-9 and VEGF expressions.

[Protective effect of estrogen on acute lung injury after hemorrhagic shock in pregnant rabbit].

OBJECTIVE: The paper is an attentative effort to evaluate the reaction and mechanism of estrogen on pregnant rabbits with acute lung injury caused by hemorrhagic shock. METHODS: Sixty pregnant New Zealand white rabbits were randomly divided into 6 groups, with 10 rabbits in each group, namely normal control group (NG group, with anesthesia only), estrogen group (E(2)G group, with additional estrogen injection at 60 min) and the other four hemorrhagic shock groups underwent hemorrhagic shock (i.e. E(2)SG, FSG, SBSG, E(2)SBSG group; mean blood pressure- 40 mmHg (1 mmHg = 0.133 kPa) by phlebotomy for 15 min. After maintenance of the pressure for 45 min, the rabbits were treated with E(2) (0.37 mg/kg), fructose injection (5%, 2 ml/kg), the p38 mitogen-activated protein kinases (p38MAPK) inhibitor SB-203580 (2 mg/kg) or E(2) plus SB-203580. Tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) were measured at different time points (0 min, 60 min, 80 min and 260 min), lung tissue methane dicarboxylic aldehyde (MDA) level, lung tissue myeloperoxidase (MOP), superoxide dismutase (SOD) activity, lung tissue dry weight/wet weight (DW/WW) value were measured after the experiment was finished, pulmonary pathology of the rabbits was observed. RESULT: (1) Serum TNF-α level of NG group and E(2)SG group were not significantly different compared with the other four groups at the 0 min and 60 min. At 80 min and 260 min of experiment, serum TNF-α level of all the four shock groups were increased, E(2)SG group [(172.4 ± 16.0) and (216.7 ± 18.6) ng/L], FSG group [(171.6 ± 9.1) and (263.9 ± 7.8) ng/L], SBSG group [(172.8 ± 7.2) and (300.6 ± 4.8) ng/L], E(2)SBSG group [(167.9 ± 4.8 ) and (261.8 ± 9.6) ng/L], and significantly higher than NG group and E(2)G group, separately (P < 0.05). (2) Serum IL-6 level of NG group and E(2)SG group were not significantly different compared with the other four groups at the 0 min, 60 min and 80 min. At 260 min, the serum IL-6 level [(98.3 ± 0.9) and (110.4 ± 1.8) ng/L; (120.9 ± 2.3) and (109.8 ± 2.6) ng/L] of the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) were significantly higher than NG group and E(2)G group (P < 0.05). (3) Lung tissue MDA level [(2.20 ± 0.12), (2.57 ± 0.11), (3.17 ± 0.08), (2.75 ± 1.09) nmol/mg] and MPO activity [(4.45 ± 0.25), (6.65 ± 0.56), (9.55 ± 0.30), (6.78 ± 0.11) U/mg] of the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) were higher than NG group and E(2)G group (P < 0.05). (4) Lung tissue SOD activity [(51.8 ± 1.8), (40.2 ± 1.5), (30.0 ± 1.7), (41.2 ± 2.0) U/mg] was significantly higher in the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (5) Lung tissue DW/WW value (0.143 ± 0.008, 0.127 ± 0.008, 0.109 ± 0.006, 0.125 ± 0.008) was significantly lower in the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (6) Lung tissue of the rabbits in NG group and E(2)G group is basically normal without obvious pathology changes. Lung tissue pathological damage of rabbits was observed in the four shock groups, and the pathological damage of rabbits in SBSG group was most serious. CONCLUSION: Estrogen can reduce acute lung injury of pregnant rabbits with hemorrhagic shock, the p38MAPK pathway plays a critical role in mediating the salutary effects of E(2) on shock-induced acute lung injury.