The clinical characteristics and treatment of ovarian malignant mesoderm mixed tumor: a systematic review.

BACKGROUND: Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical features, pathology and molecular biology characteristic of published cases. METHODS: The English and Chinese reported cases of OMMMT were selected from PubMed, Clinical Trials.gov and CNKI database from 2000 to December 15th, 2021 following the PRISMA guidelines. RESULTS: A total of 63 literatures including 199 OMMMT cases were included. The average age of patients at diagnosis was 56.46 years, the highest incidence age was 60-65 years, and 82% of them were menopausal women. Most patients were diagnosed in FIGO III stage (59.64%). The most common symptom of OMMMT was abdominal pain (60.5%). 61.6% of patients were accompanied by ascites, while ascites was not associated with metastatic tumor and local recurrence. The CA125 of 88.68% patients increased. The most common reported carcinomatous component and sarcomatous component were serous adenocarcinoma (44.96%) and chondrosarcoma (24.81%), respectively. Initial treatment included surgery (94.97%) and taxanes-based (55.10%) or platinum-based (85.71%) chemotherapy regimens. The median survival time of patients was 20 months. Heterologous sarcoma component did not shorten life expectancy. The optimal ovarian tumor cell debulking surgery (OOTCDS), radiotherapy and chemotherapy could significantly prolong the median survival time of patients. Furthermore, platinum drugs could significantly prolong the survival time after comparing various chemotherapy schemes. Besides, the combination of platinum and taxanes was therapeutically superior to the combination of platinum and biological alkylating agents. CONCLUSION: The OOTCDS and platinum-based chemotherapy regimen can improve the prognosis of OMMMT. Targeted therapy might become a new research direction in the future. Since the elderly patients are the majority, the toxicity of new drugs on the elderly patients is more noteworthy.

Necroptosis-related lncRNA signature predicts prognosis and immune response for cervical squamous cell carcinoma and endocervical adenocarcinomas.

Necroptosis, a programmed form of necrotic cell death, plays critical regulatory roles in the progression and metastatic spread of cancers such as cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, there are few articles systematically analyzing the necroptosis-related long non-coding RNAs (NRlncRNAs) correlated with CESC patients. Both RNA-sequencing and clinical data of CESC patients are downloaded from TCGA database in this study. Pearson correlation analysis, least absolute shrinkage, operator algorithm selection and Cox regression model are employed to screen and create a risk score model of eleven-NRlncRNAs (MIR100HG, LINC00996, SNHG30, LINC02688, HCG15, TUBA3FP, MIAT, DBH-AS1, ERICH6-AS1SCAT1, LINC01702) prognostic. Thereafter, a series of tests are carried out in sequence to evaluate the model for independent prognostic value. Gene set enrichment analytic paper, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analytic paper make it clear that immune-related signaling pathways are very rich in the high-risk subgroup. Additionally, the prognostic risk score model is correlated to immune cell infiltration, potential immune checkpoint, immune function, immune micro-environmental and m6A-related gene. Mutation frequency in mutated genes and survival probability trend are higher in the low-risk subgroup in most of test cases when compared to the high-risk subgroup. This study constructs a renewed prognostic model of eleven-NRlncRNAs, which may make some contribution to accurately predicting the prognosis and the immune response from CESC patients, and improve the recognition of CESC patients and optimize customized treatment regimens to some extent.

Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation.

Ovarian cancer is the most lethal gynecologic malignancy, and is usually diagnosed at an advanced stage. Most patients relapse within 12-24 months and die from progressive chemotherapy-resistant diseases. Significant progress has been made in developing new targeted therapies for human cancer, including ovarian cancer. However, an effective alternative to drug development is to repurpose drugs. The present study investigated the possibility of reusing the antibiotic monensin as an anti-ovarian cancer drug. After applying a series of titrated monensin on a panel of ovarian cancer cell lines, the growth, migration and invasion of cells were explored. Multiple signaling molecules associated with epithelial-to-mesenchymal transition were also regulated by monensin. The mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway was further found to be the key regulator affected by monensin. Additionally, monensin enhanced the MEK1 SUMOylation in vitro and in vivo, and the SUMOylation degree depended on time and dose. Xenograft studies verified that monensin effectively inhibited xenograft tumor growth by increasing the SUMOylation of MEK1. The aforementioned results suggested that monensin is a good candidate for anti-ovarian cancer by enhancing MEK1 SUMOylation and inhibiting the MEK-ERK pathway.

Combination of nigericin with cisplatin enhances the inhibitory effect of cisplatin on epithelial ovarian cancer metastasis by inhibiting slug expression via the Wnt/ß-catenin signalling pathway.

Epithelial ovarian cancer (EOC) is the most lethal cancer among female genital tumours. Standard therapies, including postoperative chemotherapy, exhibit high proportions of recurrence and resistance. Novel therapeutic strategies are combined with chemotherapy. Emerging studies have demonstrated that nigericin, an H+, K+ and Pb2+ ionophore, exhibits promising anticancer activity in various types of malignancy, such as colorectal and epithelial ovarian cancer. Our previous study suggested that nigericin could regulate EOC cell proliferation, migration and invasion, and may be a novel chemotherapy candidate for EOC. However, to the best of our knowledge, the effects of combined therapy with cisplatin, and the associated underlying mechanisms, are not yet fully understood. The present study aimed to clarify the effects of combined chemical therapy with nigericin and cisplatin on EOC cells and to reveal its mechanism. Wound healing, Transwell, cell viability and colony formation assays were used to measure the migration, invasion and proliferation of EOC cells. Western blotting was used to detect protein expression. A slug overexpression lentivirus was used to create a slug overexpression model in SK-OV-3 cells. Small interfering RNA was used to knock down slug expression. Nigericin combined with cisplatin enhanced the inhibitory effects of cisplatin on the migration and colony formation of EOC cells. Nigericin also enhanced the inhibitory effects of cisplatin on the expression levels of MMP7, as well as the inhibitory effects of cisplatin on the expression levels of ß-catenin and GSK-3ß, indicating that nigericin and cisplatin regulated in the Wnt/ß-catenin signalling pathway. When slug was knocked down, the effect of nigericin was weakened. Overexpression of slug could repress the inhibitory effect of nigericin on the Wnt/ß-catenin signalling pathway. Furthermore, nigericin inhibited slug expression by enhancing its modification through small ubiquitin-like modifiers (SUMOs; referred to as SUMOylation). Overall, the present results demonstrated that nigericin combined with cisplatin might serve as a novel therapeutic strategy in patients with metastatic EOC because the combined therapy had higher effectiveness than single drug use. The underlying mechanism of combined therapy maybe the enhanced inhibitory effect of slug through its nigericin-induced SUMOylation.

Coupling SnS2 and rGO aerogel to CuS for enhanced light-assisted OER electrocatalysis.

In order to harvest more light wavelengths to improve the light-assisted electrochemical water splitting capacity, we developed a novel heterostructure of three-dimensional (3D) flower-like CuS architecture with accompanying SnS2 nanoparticles and reduced graphene oxide (rGO) aerogel for outstanding light-assisted electrocatalytic OER performance and good stability. The excellent catalytic kinetics, effective capturing of visible light, and rapid charge transfer of the CuS/SnS2/rGO (CSr) heterostructure were demonstrated. The overpotential (264 mV@10 mA cm-2) under light-assisted conditions is 20% lower than that under light-chopped conditions. SnS2 can harvest more light wavelengths and this boosts its intrinsic activity. However, with the increase of the SnS2 content, the OER activity decreases. The combination of the CS heterostructure and the rGO conductive aerogel achieves rapid charge transfer. Furthermore, the possible mechanism of the light-assisted electrocatalytic OER was also proposed. Overall, this work provides new insights into the simple and scalable fabrication of a highly efficient, low-cost, and stable non-noble-metal-based electrocatalyst.

Noble metal-free 0D-1D NiCoP/Mn0.3Cd0.7S nanocomposites for highly efficient photocatalytic H2 evolution under visible-light irradiation.

Efficient and noble metal-free co-catalyst loading is an effective solution for separating and transferring photo-generated carriers and lowering the overpotential in photocatalytic H2 evolution activity. In this work, we designed and prepared a series of novel NiCoP/Mn0.3Cd0.7S (NCP/MCS) composites by modifying MCS nanorods with the co-catalyst NCP using a simple calcination method. Notably, the 10-NCP/MCS composite displays the optimum photocatalytic H2 evolution rate of 118.5 mmol g-1 h-1 under visible-light irradiation. This is approximately 3.39 times higher than that of pure MCS. The corresponding apparent quantum efficiency is 10.2% at 420 nm. The superior photocatalytic activity of the NCP/MCS composites can be attributed to the efficient separation of photogenerated carriers caused by the intimate heterojunction interface between NCP and MCS, smaller transfer resistance, and lower overpotential of NCP. Moreover, the NCP/MCS composites exhibit remarkable photostability. A plausible mechanism is proposed.

Optimizing the synthesis of SnO2/TiO2/RGO nanocomposites with excellent visible light photocatalytic and antibacterial activities.

Multifunctional SnO2/TiO2/RGO nanocomposites with enhanced photocatalytic degradation and antibacterial activity have been successfully synthesized by a facile one-pot environmentally friendly green hydrothermal route using titanium tetrabutoxide (TBOT), Na2SnO3 and graphene oxide (GO) without reducing agents and any structure-directing agents. The results demonstrate that the reaction pH conditions play important roles in the control of the crystallographic phases of TiO2 and SnO2. In addition, the visible-light-active photocatalytic and antibacterial activities of the synthesized composites were measured for the degradation of rhodamine B (RhB) and the growth inhibition of the Gram-negative bacteria Escherichia coli (E. coli), which are strongly affected by the SnO2 loading content, the crystal structure of TiO2 and the appropriate addition of graphene. The superior photocatalytic and antibacterial activities of the nanocomposites were attributed to their great optical adsorption capability and excellent charge separation and transfer efficiency. This study may provide new insights into the fabrication of efficient visible-light-active SnO2/TiO2/RGO nanocomposites and expand their applications in the environmental remediation and water disinfection fields.

Upstream transcription factor 1 prompts malignancies of cervical cancer primarily by transcriptionally activating p65 expression.

Cervical cancer is the third-most common cause of female cancer-related mortality worldwide. In cervical cancer, aberrant activation of nuclear factor (NF)-κB signaling is widely reported. However, the transcriptional regulation of NF-κB signaling remains unclear. The present study aimed to explore the underlying mechanism in which NF-κB signaling was activated in cervical cancer cells. Initially, the expression of p65 was demonstrated to be markedly enhanced in grade II, III or IV cervical cancer tissues compared with that of normal cervical tissues, indicating that p65 expression was correlated with tumor grade. In HeLa and CaSki cells, overexpression of p65 markedly enhanced cervical cancer cell invasion and migration. Further experiments demonstrated that p65 overexpression significantly increased the phosphorylation levels of protein kinase B (AKT) and p38. Dual luciferase reporter and chromatin immunoprecipitation assays demonstrated that USF1 was able to bind the promoter region of p65, thereby enhancing the transcriptional activation of p65. Notably, when p65 was silenced, the phosphorylation levels of AKT and p38 were suppressed even in cells transfected with adenovirus vectors expressing upstream transcription factor 1 (USF1). These data indicated that USF1 prompted cervical cancer progression primarily by transcriptionally activating p65. In conclusion, the present study demonstrated that USF1 was able to activate the transcription of p65, thereby enhancing the malignancy of cervical cancer cells.

MicroRNA-217 functions as a tumor suppressor in cervical cancer cells through targeting Rho-associated protein kinase 1.

The abnormal expression of microRNAs (miRNAs/miRs) has been widely reported in various tumor types. miR-217 was demonstrated to be aberrantly expressed in a number of tumors, including pancreatic adenocarcinoma and osteosarcoma; however, its specific expression pattern has never been investigated in cervical cancer cells. Compared with normal control, the level of Rho-associated protein kinase 1 (ROCK1) expression was markedly increased in cervical cancer tissues and cells compared with that in non-cancerous tissues and cells. The expression of miR-217 was significantly reduced in cervical cancer tissues and cell lines. Overexpression of miR-217 could suppress colony formation and the cell invasion capacity of SiHa and HeLa cells. Flow cytometry indicated that miR-217 significantly increased cell apoptosis in SiHa and HeLa cells. Dual-luciferase reporter assays demonstrated that ROCK1 was a target gene of miR-217. In addition, overexpression of ROCK1 also led to an increased invasion capacity in SiHa cells, even when miR-217 was inhibited, indicating that the anti-invasive effects of miR-217 were mediated through ROCK1. In summary, the results of the present study indicated that miR-217 functions as a tumor suppressor in cervical cancer cells, primarily by targeting ROCK1.

miR-148a-3p suppresses epithelial ovarian cancer progression primarily by targeting c-Met.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that modulate post-transcriptional gene expression. It has been demonstrated that various miRNAs may be expressed at different levels in different types of tumors. The present study assessed the role of microRNA-148a-3p (miR-148a-3p) in epithelial ovarian cancer (EOC). The results demonstrated that miR-148a-3p was decreased in EOC tissues and that a lower miRa-148-3p concentration was associated with a higher overall survival rate. Transfection of miR-148a-3p suppressed the invasive and proliferative capacity of SKOV3 cells. The induced overexpression of miR-148a-3p significantly inhibited the relative luciferase activity of the pmirGLO-c-Met-3'untranslated region compared with an empty vector. In addition, c-Met silencing led to a decrease in the invasive and proliferative capacity of EOC cells. The inhibition of miR-148a-3p did not increase the invasiveness of SKOV3 cells, even when c-Met was silenced. To the best of our knowledge, the present study is the first to demonstrate that miR-148a-3p expression is decreased in EOC cancer tissues and cell lines. The present study therefore demonstrated that miR-148a-3p may serve as a tumor suppressor in EOC by targeting c-Met.

Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity.

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T-lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression.

Nigericin Inhibits Epithelial Ovarian Cancer Metastasis by Suppressing the Cell Cycle and Epithelial-Mesenchymal Transition.

Epithelial ovarian cancer (EOC) has the highest mortality among various types of gynecological malignancies. Most patients die of metastasis and recurrence due to cisplatin resistance. Thus, it is urgent to develop novel therapies to cure this disease. CCK-8 assay showed that nigericin exhibited strong cytotoxicity on A2780 and SKOV3 cell lines. Flow cytometry indicated that nigericin could induce cell cycle arrest at G0/G1 phase and promote cell apoptosis. Boyden chamber assay revealed that nigericin could inhibit migration and invasion in a dose-dependent manner by suppressing epithelial-mesenchymal transition (EMT) in EOC cells. These effects were mediated, at least partly, by the Wnt/ß-catenin signaling pathway. Our results demonstrated that nigericin could inhibit EMT during cell invasion and metastasis through the canonical Wnt/ß-catenin signaling pathway. Nigericin may prove to be a novel therapeutic strategy that is effective in patients with metastatic EOC.

Citrate-Complexation Synthesis and Photoluminescence Properties of Y6MoO12:Eu Nanocrystalline.

Y6MoO12 doped with Eu3+ was synthesized using a citrate-complexation route, and was calcined at 800 °C and 1400 °C, respectively. The structure, morphology and photoluminescence (PL) properties of the samples, and their dependence on the crystallite size were investigated. XRD patterns indicate that the Y6MoO12:Eu3+ powder was obtained at both calcination temperatures, and had a cubic structure. The results also suggest that Y6MoO12:Eu3+ calcined at 800 °C was in the nanocrystalline phase, which was confirmed by the SEM microimage. The crystalline size was about 140 nm. Both phosphors could be excited via three channels: f-f excitation of Eu3+ by blue light, MoO groups excitation by near-UV light, and charge transfer state excitation of Eu3+ by UV light. Both samples yielded red light emissions dominated by the 5D0-7F2 transition at 613 nm. The excitation efficient of the three channels depended on the calcination temperature. The energy transfer from the MoO groups to the Eu3+ ions was more effective in the nanocrystalline phase. The temporal decay feature of the phosphor was also characterized.

[The development of Clonorchis sinensis in mice].

Freshwater fish were caught from Nenjiang River in Qiqihaer City, and examined for metacercariae of Clonorchis sinensis by the artificial digestion (pepsin-HCl) method. The metacercariae (35-40) were given orally into stomach to each Kunming mouse of infection group (50 mice). The mice in control group were given the same amount of normal saline. The mice were sacrificed on the 5th, 10th, 15th, 20th, 25th, and 30th day after infection. Worms were collected, fixed and stained with carmine acetate, and observed under microscope. The egg-laying capacity of C. sinensis was observed in mice. 96%(48/50) mice were infected with metacercariae of C. sinensis. The recovery rate of adult worms on the 5th, 10th, 15th, 20th, 25th, and 30th day post-infection was 42.1%, 52.6%, 63.2%, 62.2%, 63.3%, and 63.2%, respectively. The first appearance of eggs in utero and feces was on the 15th and 20th day after infection, respectively. The branch of testis in worms was observed after 20 days of infection.

Density functional theory study on the reaction mechanism of synthesizing 1,3-dimethyl-2-imidazolidinone by urea method.

We report a first-principles density functional theory investigation on tailoring the fundamental reaction mechanism of synthesizing 1,3-dimethyl-2-imidazolidinone (DMI) through the urea method with water serving as both solvent and catalyst. The nucleophilic cyclization reaction is implemented by two ammonia removal steps. One -NH group of dimethylethylenediamine (DMEDA) first attacks the carbon atom of urea, eliminating one -NH3 group and forming an intermediate state CH3NHC2H4N(CH3)CONH2 (IMI). IMI subsequently undergoes the cyclization process through a secondary ammonia removal via similar manner. Without water, the two ammonia removal steps are both slightly exothermic with high activation barriers (~50 kcal mol(-1)). As water participated in the reaction, the kinetics of the two steps can be significantly improved, respectively. The role that water plays, beside as solvent, more importantly, is to serve as a proton exchange bridge. Due to the spatial configuration, the direct proton migration from the N atoms of ethylenediamine to urea is difficult to occur. The water bridge facilitates the proton migration by shortening the migration distance. As a consequence, the activation barriers are considerably lowered down to ~30 kcal mol(-1), indicating a strong catalytic effect from water. In contrast, the three possible side reactions of IM(I), even catalyzed by water, have higher activation barriers due to strong steric inhibitive effect and consequently become difficult to occur at the same condition. The current computational understanding on the prototypical reaction to DMI can be extended to guide developing more efficient routes to synthesize imidazolidinone derivatives through the urea method.

Hydrogen sequential dissociative chemisorption on Ni n(n = 2~9,13) clusters: comparison with Pt and Pd.

Hydrogen dissociative chemisorption and desorption on small lowest energy Ni(n) clusters up to n=13 as a function of H coverage was studied using density functional theory. H adsorption on the clusters was found to be preferentially at edge sites followed by 3-fold hollow sites and on-top sites. The minimum energy path calculations suggest that H(2) dissociative chemisorption is both thermodynamically and kinetically favorable and the H atoms on the clusters are mobile. Calculations on the sequential H(2) dissociative chemisorption on the clusters indicate that the edge sites are populated first and subsequently several on-top sites and hollow sites are also occupied upon full cluster saturation. In all cases, the average hydrogen capacity on Ni(n) clusters is similar to that of Pd(n) clusters but considerably smaller than that of Pt(n) clusters. Comparison of hydrogen dissociative chemisorption energies and H desorption energies at full H-coverage among the Ni family clusters was made.

Advances in the research on lymphangiogenesis in carcinoma tissues (Review).

Metastatic spread of tumors is an important prognostic factor for cancer patients. The effect of angiogenesis on cancer cell proliferation and metastatic spread has been confirmed. However, less attention has been focused on research involving tumor lymphangiogenesis as opposed to research on tumor angiogenesis, due to the lack of specific markers for lymphatic vessel endothelial cells (LVECs). Recently, the improvement of isolation techniques for LVECs and the discovery of specific LVEC markers such as vascular endothelial growth factor receptor-3 (VEGFR-3), podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and Prox1 have led to advances in research involving lymphangiogenesis in carcinoma tissues. New lymphatic vessels in tumor tissues may originate from bone marrow endothelial progenitor cells, directly from the preexisting lymphatic vessels, and even by cell transformation. Peritumoral lymphatic vessels play a more important role in the process of tumor metastasis by providing more channels for lymphatic invasion and metastatic spread. The molecular mechanism of tumor lymphangiogenesis is complicated, and numerous factors such as VEGF-A, platelet-derived growth factors (PDGFs), hepatocyte growth factor (HGF), fibroblast growth factor-2 (FGF-2), and angiopoietins (Ang) are directly or indirectly involved in the process. However, it has been demonstrated that the VEGF-C/VEGF-D/VEGFR-3 signaling pathways are the most important mechanism underlying tumor lymphangiogenesis.

Hydrogen dissociative chemisorption and desorption on saturated subnano palladium clusters (Pdn, n = 2-9).

H2 sequential dissociative chemisorption on small palladium clusters was studied using density functional theory. The chosen clusters Pdn (n = 2-9) are of the lowest energy structures for each n. H2 dissociative chemisorption and subsequent H atom migration on the bare Pd clusters were found to be nearly barrierless. The dissociative chemisorption energy of H2 and the desorption energy of H atom in general decrease with the coverage of H atoms and thus the catalytic efficiency decreases as the H loading increases. These energies at full cluster saturation were identified and found to vary in small energy ranges regardless of cluster size. As H loading increases, the clusters gradually change their bonding from metallic character to covalent character. For the selected Pd clusters, the capacity to adsorb H atoms increases almost proportionally with cluster size; however, it was found that the capacity of Pd clusters to adsorb H atoms is, on average, substantially smaller than that of small Pt clusters, suggesting that the catalytic efficiency of Pt nanoparticles is superior to Pd nanoparticles in catalyzing dissociative chemisorption of H2 molecules.