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Tumour-induced immunosuppressive microenvironments facilitate oncogenesis, with regulatory T cells (Tregs) serving as a crucial component. The significance of Treg-associated genes within the context of ovarian cancer (OC) remains elucidated insufficiently. Utilizing single-cell RNA sequencing (scRNA-Seq) for the identification of Treg-specific biomarkers, this investigation employed single-sample gene set enrichment analysis (ssGSEA) for the derivation of a Treg signature score. Weighted gene co-expression network analysis (WGCNA) facilitated the identification of Treg-correlated genes. Machine learning algorithms were employed to determine an optimal prognostic model, subsequently exploring disparities across risk strata in terms of survival outcomes, immunological infiltration, pathway activation and responsiveness to immunotherapy. Through WGCNA, a cohort of 365 Treg-associated genes was discerned, with 70 implicated in the prognostication of OC. A Tregs-associated signature (TAS), synthesized from random survival forest (RSF) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms, exhibited robust predictive validity across both internal and external cohorts. Low TAS OC patients demonstrated superior survival outcomes, augmented by increased immunological cell infiltration, upregulated immune checkpoint expression, distinct pathway enrichment and differential response to immunotherapeutic interventions. The devised TAS proficiently prognosticates patient outcomes and delineates the immunological milieu within OC, offering a strategic instrument for the clinical stratification and selection of patients.
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Neoplasias Ovarianas , Linfócitos T Reguladores , Humanos , Feminino , Prognóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Algoritmos , Imunoterapia , Microambiente Tumoral/genéticaRESUMO
Ovarian cancer (OC) is a malignancy associated with poor prognosis and has been linked to regulatory T cells (Tregs) in the immune microenvironment. Nevertheless, the association between Tregs-related genes (TRGs) and OC prognosis remains incompletely understood. The xCell algorithm was used to analyze Tregs scores across multiple cohorts. Weighted gene co-expression network analysis (WGCNA) was utilized to identify potential TRGs and molecular subtypes. Furthermore, we used nine machine learning algorithms to create risk models with prognostic indicators for patients. Reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining were used to demonstrate the immunosuppressive ability of Tregs and the expression of key TRGs in clinical samples. Our study found that higher Tregs scores were significantly correlated with poorer overall survival. Recurrent patients exhibited increased Tregs infiltration and reduced CD8+ T cell. Moreover, molecular subtyping using seven key TRGs revealed that subtype B exhibited higher enrichment of multiple oncogenic pathways and had a worse prognosis. Notably, subtype B exhibited high Tregs levels, suggesting immune suppression. In addition, we validated machine learning-derived prognostic models across multiple platform cohorts to better distinguish patient survival and predict immunotherapy efficacy. Finally, the differential expression of key TRGs was validated using clinical samples. Our study provides novel insights into the role of Tregs in the immune microenvironment of OC. We identified potential therapeutic targets derived from Tregs (CD24, FHL2, GPM6A, HOXD8, NAP1L5, REN, and TOX3) for personalized treatment and created a machining learning-based prognostic model for OC patients, which could be useful in clinical practice.
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Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Perfilação da Expressão Gênica , Terapia de Imunossupressão , Linfócitos T Reguladores , Microambiente Tumoral/genéticaRESUMO
This study explored the effect of Regenerating Islet-Derived 3-Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real-time polymerase chain reaction (qRT-PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 µM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit-8 and methyl-thiazolyl-tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT-PCR, Western blot and immunohistochemistry. As a result, REG3A was over-expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR-1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.
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Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Animais , Feminino , Humanos , Camundongos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Ovarian cancer has long been considered the second-highest cancer threat to women's reproductive system with high mortality. This is ascribed to the absence of highly efficient therapy and cancer metastasis. Accordingly, there is an urgent need for the development of new agents. Recently, Traditional Chinese medicine has gained extensive interest because of its safe use, validity, and distinct pharmacological effects. Polyphyllin E (PPE), as a major constituent in Rhizoma Paridis, is a promising cancer-fighting agent. However, the effect of PPE on ovarian cancers as well as associated latent mechanisms is still not completely understood. In this study, PPE was found to prohibit the proliferation of SK-OV-3 and OVCAR-3 ovarian cancer cells, causing marked cell death. Additionally, low-dose PPE could also inhibit motility and invasion of ovarian cancer cells. The mechanistic assessment revealed PPE-mediated matrix metalloproteinases, i.e., MMP2 and MMP9, inhibition via the AKT-nuclear factor kappa B (AKT/NF-κB) signaling pathway. Rescue experiments with transfection of AKT lentiviral particles remarkably reversed PPE inhibitory effects against ovarian cancer cells. In conclusion, PPE could inhibit proliferation of ovarian cancer cell migration and invasion by down-regulating the AKT/NF-κB pathway. Moreover, it has the potential to act as a novel agent for ovarian cancer treatment.
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Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , NF-kappa B/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
The catalytic properties of nanometals are strongly dependent on their electronic states which, are influenced by the interaction with the supports. However, a precise manipulation of the electronic interaction is lacking, and the nature of the interaction is still ambiguous. Herein, using Au/ZnFex Co2- x O4 (x = 0-2) as a model system with continuously tuned Fermi levels of supports, the electronic structure of the Au catalyst can be precisely controlled by changing the Fermi level of the support, which arises from the charge redistribution between the two phases. A higher Fermi level of ZnFe2 O4 support makes nano-Au negatively charged and thus facilitates the oxidation of CO, and in contrast, a lower Fermi level of ZnCo2 O4 support makes nano-Au positively charged and is preferential to the oxidation of benzyl alcohol. This work represents a solid step towards exploration of advanced catalysts with deliberate design of electronic structure and catalytic properties.
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Mitotic catastrophe (MC) is a novel form of cell death that plays an important role in the treatment and drug resistance of colon adenocarcinoma (COAD). However, MC related genes in COAD treatment and prognosis evaluation are rarely studied. In this study, the transcriptome data, somatic mutation and copy number variation data were obtained from The Cancer Genome Atlas (TCGA) database. The mitotic catastrophe related genes (MCRGs) were obtained from GENCARDS website. Differential gene analysis was conducted with LIMMA package. Univariate Cox regression analysis was used to identify prognostic related genes. Mutation analysis was performed and displayed by maftools package. RCircos package was used for localizing the position of genes on chromosomes. "Glmnet" R package was applied for constructing a risk model via the LASSO regression method. Consensus clustering analyses was implemented for clustering different subtypes. Functional enrichment analysis through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods, immune infiltration analysis via single sample gene set enrichment analysis (ssGSEA), tumor mutation burden and drug sensitivity analysis by pRRophetic R package were also carried out for risk model or molecular subtype's assessment. Additionally, the connections between the expression of hub genes and overall survival (OS) were obtained from online Human Protein Atlas (HPA) website. Real-Time Quantitative Polymerase Chain Reaction (RTqPCR) further validated the expression of hub genes. A total of 207 differentially expressed MCRGs were selected in the TCGA cohort, 23 of which were significantly associated with OS in COAD patients. Subsequently, we constructed risk score prognostic models with 5 hub MCRGs, including SYCE2, SERPINE1, TRIP6, LIMK1, and EEPD1. The high-risk patients suffered from poorer prognosis. Furthermore, we developed a nomogram that gathered age, sex, staging, and risk score to accurately forecast the clinical survival outcomes in 1, 3, and 5 years. The results of functional enrichment suggested a significant correlation between MCRGs characteristics and cancer progression, with important implications for the immune microenvironment. Moreover, patients who displayed high TMB and high risk score showed worse prognosis, and risk characteristics were associated with different chemotherapeutic agents. Finally, RTqPCR verified the increased expression of the five MCRGs in clinical samples. The five MCRGs in the prognostic signature were associated with prognosis, and could be treated as reliable prognostic biomarkers and therapeutic targets for COAD patients with distinct clinicopathological characteristics, thereby providing a foundation for the precise application of pertinent drugs in COAD patients.
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Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Variações do Número de Cópias de DNA/genética , Prognóstico , Morte Celular , Microambiente Tumoral , Quinases Lim , Fatores de Transcrição , Proteínas Adaptadoras de Transdução de Sinal , Proteínas com Domínio LIMRESUMO
The electronic interaction between a metal and a support modulates the electronic structures of supported metals and plays an important role in manipulating their catalytic performance. However, this interaction is mainly realized in heterogeneous catalysts composed of reducible oxides. Herein, we demonstrate the electronic interaction between γ-Al2O3 and η-Al2O3 with varying acid-base properties and supported Pd nanoparticles (NPs) of 2 nm in size. The strength and number of acid-base sites on the supports and catalysts were systemically characterized by FT-IR spectroscopy and TPD. The supported Pd NPs exhibit electron-rich surface properties by receiving electrons from the electron-donating basic sites on γ-Al2O3, which are beneficial for catalyzing the hydrogenation of nitrobenzene. In contrast, Pd NPs loaded on η-Al2O3 are electron-deficient because of the rich electron-withdrawing acid sites of η-Al2O3. As a result, Pd/η-Al2O3 exhibits higher catalytic activity in phenylacetylene hydrogenation than Pd/γ-Al2O3. Our results suggest a promising route for designing high-performance catalysts by adjusting the acid-base properties of Al2O3 supports to maneuver the electronic structures of metals.
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PURPOSE: To evaluate the blood flow changes and their relationships to microvessel density (MVD) and thrombospondin-1 (TSP-1) by transvaginal colour Doppler sonography (TV-CDS) in the ovarian interstitium to predict ovarian interstitial microvascular injury in the pathological process of ovarian endometrial cysts (OEC). METHODS: TV-CDS was preoperatively performed to detect blood flow changes in 60 patients with 76 ovarian endometrioid cysts, and flow classification and resistance indices (RI) values were recorded for analysis. Ovarian interstitial specimens with blood flow signals were collected for postoperative pathologic examination. TSP-1 protein was evaluated by immunohistochemistry and Western blot, TSP-1 mRNA by reverse transcriptase polymerase chain reaction, microvessels by CD34 antibody, and MVD by image analysis. Thirty age-matched patients with benign ovarian tumours served as controls. RESULTS: Blood flow, most of star-shaped, within ovarian interstitial arteries in the OEC group was diminished; however, arterial spectra exhibited a high-resistance flow manifesting a significantly higher RI compared with that of the control group (P < 0.01). In ovarian interstitial specimens, there were significantly (P < 0.01) lower CD34-MVD and higher TSP-1 protein and mRNA in the OEC group than in the controls. CD34-MVD and TSP-1 showed remarkably negative correlation (rs = -0.76, P < 0.01). RI values correlated negatively with MVD values (rs = -0.91, P < 0.01), but positively with TSP-1 (rs = 0.81, P < 0.01), while flow classification correlated positively with MVD values (rs = 0.66, P < 0.01), but negatively with TSP-1 (rs = -0.54, P < 0.01). CONCLUSIONS: Changes in CD34-MVD and TSP-1 reflected ovarian interstitial microvascular injury of OEC, pathologically supported the findings of blood flow changes within ovarian interstitial arteries, and prospectively predicted OEC-induced ovarian interstitial vessel injury. This has important clinical value: early treatment, instead of allowing the cyst to become bigger, is of great importance for OEC patients, because a greater number of functional tissue blood vessels would be destroyed as the disease progresses.
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Endometriose/complicações , Microvasos/lesões , Cistos Ovarianos/complicações , Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Adulto , Anticorpos/metabolismo , Antígenos CD34/imunologia , Distribuição de Qui-Quadrado , Endometriose/cirurgia , Feminino , Humanos , Microcirculação , Microvasos/metabolismo , Microvasos/patologia , Cistos Ovarianos/cirurgia , Ovário/metabolismo , Valor Preditivo dos Testes , RNA Mensageiro/metabolismo , Fluxo Sanguíneo Regional , Estatísticas não Paramétricas , Trombospondina 1/genética , Trombospondina 1/metabolismo , Ultrassonografia Doppler em CoresRESUMO
MicroRNA-650 (miR-650) has been shown to regulate the development of human cancers. The present study investigated the role of miR-650 in ovarian cancer by targeting Krüppel-like factor 12 (KLF12). The results showed a down-regulation of miR-650 in tissues and cell lines. Overexpression of miR-650 caused a substaining decrease in the viability of CAOV3 cells by promoting apoptotic cell death. In silico analysis and dual luciferase assay revealed KLF12 as a potential target of miR-650. Unlike miR-650, KLF12 showed a substantial up-regulation in ovarian cancer tissues and cell lines. However, miR-650 overexpression suppressed KLF12 expression posttranscriptionally. Intrestingly, KLF12 knockdown inhibited the viability of CAOV3 cells by promoting apoptotic cell death. However, the expression of KLF12 eliminated the tumor suppressing effects of miR-650 in CAOV3 cells. Additionally, KLF12 knockdown or miR-650 overexpression suppressed CAOV3 cell migration and invasion. However, KLF12 overexpression eliminated the inhibitory effects of miR-650 on the migration and invasion of CAOV3 cells. Taken together, these results suggest that miR-650/KLF12 axis regulates the viability, migration, and invasion of CAOV3 cells an0d may prove to be an important therapeutic taregt.
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MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Movimento Celular/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Long non-coding RNAs (lncRNAs) play a pivotal role in the genesis and development of cancer. The role and molecular mechanisms of SNHG25 in epithelial ovarian cancer (EOC) have not been investigated. In the present study, we showed that SNHG25 expression was up-regulated in EOC tissues relative to normal ovarian tissues. In vitro, functional experiments demonstrated that high expression of SNHG25 promoted proliferation, migration and invasion, and decreased apoptosis, in ovarian cancer cell lines. In vivo, downregulation of SNHG25 inhibited the growth (tumor volume) of subcutaneous xenografts in nude mice. High-throughput sequencing and western blot analysis showed a significant decrease in the expression of COMP mRNA and protein in SNHG25 knockdown compared to control ovarian cancer cells. These data suggest that SNHG25 promotes EOC progression by regulating COMP, serving as a potential biomarker for EOC.
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OBJECTIVE: To investigate efficacy of early prevention of complex decongestive therapy and rehabilitation exercise for prevention of postoperative lower limb extremity lymphedema for patients with gynecologic cancer. METHODS: 109 female patients were randomly divided into two groups, the control group who only received routine treatment and the CDT group who received both CDT and rehabilitation exercise. For rehabilitation exercise, patients received additional rehabilitation exercise strategy including professional education and full range exercise of hip joint. The incidence of lower extremity lymphedema was recorded. A simple scale for patients' lower extremity lymphedema was designed. The diameter of low limbs (both thighs and calves) was also measured The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Brief Fatigue Inventory (BFI) was used for measurement of quality of life. RESULTS: The incidence of lower extremity lymphedema was 15.09% cases of CDT group and 32.14% in the control group. K-M curve showed the lymphedema free time in CDT group was significantly longer. The subjective scores for heaviness of lower limbs, pain, numbness and dysfunction, as well as the diameters of both thighs and calves were lower in the CDT group. In both groups, the values of EORTC QLQ-C30-GHS and EORTC QLQ-C30-FS were significantly higher, and EORTC QLQ-C30-SS scores and BFI scores were remarkably lower. CONCLUSION: Early prevention of CDT combined with rehabilitation exercise reduced incidence of lower limb extremity lymphedema and improved patients' quality of life, as well as reduced the cancer-related fatigue.
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Terapia por Exercício/métodos , Neoplasias dos Genitais Femininos/cirurgia , Extremidade Inferior , Linfedema/prevenção & controle , Linfedema/reabilitação , Modalidades de Fisioterapia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/reabilitação , Adulto , Idoso , Bandagens Compressivas , Fadiga/etiologia , Fadiga/prevenção & controle , Feminino , Neoplasias dos Genitais Femininos/complicações , Articulação do Quadril/fisiologia , Humanos , Linfedema/epidemiologia , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Cisplatin resistance is one of the main reasons for treatment failure in ovarian cancer (OC). Here, the effects of LINC00184 on cisplatin-resistant OC were studied. PATIENTS AND METHODS: LINC00184, miR-1305 and CNTN1 expression in tissues from 70 OC patients was determined by qRT-PCR, in situ hybridization and Western blot. OC cell lines and OC cisplatin-resistant cell lines were cultured. Cells were transfected using Lipofectamine 2000 and treated with 100 nM cisplatin. Cell proliferation and apoptosis were researched by the CCK-8 assay and flow cytometry. A dual-luciferase reporter gene assay and RNA pull-down were performed to explore the relationship between two genes. LINC00184, miR-1305 and CNTN1 expression in cells was detected by qRT-PCR and Western blot. An in vivo experiment was conducted using nude mice. Ki67 and CNTN1 expression and apoptosis of xenograft tumors were investigated using immunohistochemistry and a TUNEL assay. RESULTS: LINC00184 was up-regulated in OC clinical tissues and OC cells, especially in cisplatin-resistant OC patients and cells (p<0.01 or p<0.0001). LINC00184 overexpression significantly enhanced OC cell proliferation and cisplatin resistance, and inhibited OC cell apoptosis (p<0.05 or p<0.01). LINC00184 elevated CNTN1 expression via sponging miR-1305. LINC00184 overexpression markedly exacerbated the malignant phenotype of OC cells and cisplatin-resistant OC cells via the miR-1305/CNTN1 axis (p<0.01). Silencing of LINC00184 significantly suppressed OC cell growth and cisplatin resistance in vivo (p<0.01). LINC00184 silencing inhibited Ki67 and CNTN1 expression and promoted apoptosis of xenograft tumors. CNTN1 overexpression promoted proliferation and cisplatin resistance, and reduced apoptosis of OC cells (p<0.05 or p<0.01). CONCLUSION: LINC00184 promoted OC cell proliferation and cisplatin resistance by elevating CNTN1 expression via sponging miR-1305.
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BACKGROUND: Ovarian cancer is a severe gynecological malignancy. Paraneoplastic Ma antigen 5 (PNMA5) is a confirmed tumor onconeural antigen, which has been screened as a female fertility factor. PNMA5 overexpression might serve as a marker of poor prognosis in colon cancer. Our earlier study showed that PNMA5 was essential for meiosis in mouse oocytes. In this study, we investigate the role and probable mechanism of PNMA5 in the occurrence and development of epithelial ovarian cancer (EOC). METHODS: Immunochemistry and western blot analyses were used to verify PNMA5 overexpression in clinical EOC tissues and EOC cell line HO8910. A specific siRNA was used to reduce PNMA5 levels, and several proliferation and migration-related indexes were assessed. We also examined mitochondria, microfilaments, and several essential kinases. RESULTS: We found that the expression of PNMA5 in EOC tissues was significantly higher than that in benign ovarian tumors and healthy normal ovarian tissues and that this was strictly related to the FIGO stage and histological grade. PNMA5 expression in ovarian cancer cell line HO8910 was higher than that in the normal healthy ovarian cell line Moody. PNMA5 knockdown in HO8910 cells not only inhibited the proliferation, migration, invasion, cell cycle, and F-actin polymerization of HO8910 cells but also promoted early apoptosis and led to abnormal distribution and accumulation of mitochondria. PNMA5 phosphorylation was found to be positively regulated by Src activity, and PNMA5 phosphorylation promoted the downstream glycogen synthase kinase-3ß (GSK-3ß) signaling pathway. CONCLUSIONS: PNMA5 plays a pivotal role in the occurrence and development of EOC and is a potential marker of this disease.
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The present study was meant for the discovery of the underlying functions of miR-485-5p in ovarian cancer concerning cisplatin resistance in vitro. RT-qPCR assessed the miR-485-5p expression in ovarian cancer cell lines, normal cells and cisplatin-resistant Cell line OVCA433-CR. After OVCA433-CR treated with 0,3,5umol/L cisplatin, miR-485-5p expressions were determined. MTT observed the cell cytotoxicity in OVCA433-CR after regulation of miR-485-5p. Targets can predicted the putative binding between miR-485-5p and PAK1 and Luciferase Assay verified this. RT-qPCR decided the inhibitory effect in between. MTT tested the cytotoxicity in different combinations of miR-485-5p and PAK1. Western Blot tested the phosphorylation of Pi3k and Akt in response to miR-485-5p and PAK1 interplay. We evaluated the role of Pi3k/Akt signaling in regulation of miR-485-5p and cisplatin resistance with Wortmannin. miR-485-5p was lower expressed in ovarian cancer cells than normal ones and even lower in OVCA433-CR than OVCA433. As the cisplatin concerntration increased, miR-485-5p decreased. miR-485-5p mimics induced lower cisplatin resistance while miR-485-5p inhibitor caused higher resistance. PAK1 targeted miR-485-5p and inhibited miR-485-5p. PAK1 inhibitor helped to lower the resistance to cisplatin caused by miR-485-5p upregulation. miR-485-5p mimics silenced Pi3k/Akt signaling and PAK1 inhibitor aggravated the silencing. Inhibition of Pi3k/Akt signaling increased miR-485-5p, thereby decreasing the cisplatin-resistance in OVCA433-CR. miR-485-5p decreased cisplatin resistance in ovarian cancer cells via Pi3k/Akt signaling, suggesting that miR-485-5p upregulation might alleviate the cisplatin resistance in ovarian patients.
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Carcinoma Epitelial do Ovário/tratamento farmacológico , Cisplatino/uso terapêutico , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , Piridonas/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Wortmanina/farmacologia , Quinases Ativadas por p21/metabolismoRESUMO
BACKGROUND: Reports of the prognostic significance of anaplastic lymphoma kinase (ALK) rearrangement in early stage lung adenocarcinoma have been contradictory. This study aimed to identify the associations of ALK rearrangement with clinicopathologic features and prognosis in patients with surgically resected stage I-IIIA lung adenocarcinoma. METHODS: Analysis of ALK status was performed by a fully-automated immunochemistry assay (with rabbit monoclonal Ventana D5F3 antibody) in tissue sections of 2,103 patients with surgically-resected stage I-IIIA lung adenocarcinoma. ALK positive patients were matched with negative patients in a 1:1 ratio using propensity score matching (PSM). Clinical outcomes were assessed by disease-free survival (DFS) and overall survival (OS) after surgery. Initial recurrence pattern was also investigated according to ALK status. RESULTS: Among 2,103 stage I-IIIA lung adenocarcinoma cases, 81 (3.9%) were ALK positive. ALK positivity was significantly associated with younger age (P<0.001), solid predominant adenocarcinoma (P<0.001), variants of invasive adenocarcinoma (P<0.001), higher frequency of pleura invasion (P=0.040), smaller tumor size (P=0.014), mediastinal lymph node involvement (N2; P<0.001) and later pathologic stage (IIIA; P=0.001). In the match cohort, ALK positivity was not associated with DFS [hazard ratio (HR), 0.58; 95% confidence interval (CI): 0.33-1.03, P=0.063] or OS (HR, 0.61; 95% CI: 0.22-1.67, P=0.334). Lymph node involvement (HR: 5.36, 95% CI, 3.01-9.65, P<0.001) and solid predominant adenocarcinoma subtype (HR, 2.02; 95% CI: 1.07-3.79; P=0.029) were the independent prognostic factors of inferior DFS, and lymph node involvement was the independent prognostic factors of worse OS (HR, 6.61; 95% CI: 2.43-17.94; P<0.001). ALK positive patients had a higher risk of developing tumor recurrence in liver (P=0.043). CONCLUSIONS: ALK rearrangement was not an independent prognostic factor in stage I-IIIA lung adenocarcinoma patients but leaded to a higher risk of developing recurrence in liver.
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PURPOSE: Exosomes are key mediators of cellular communication by transporting molecules, including long noncoding RNAs (lncRNAs), and have been regarded as promising non-invasive biomarkers. This study aimed to evaluate the expression pattern and clinical significance of serum exosomal lncRNA antisense hypoxia inducible factor (aHIF) in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Sixty-two EOC patients in Obstetrics and Gynecology Hospital of Fudan University were enrolled. The expression levels of aHIF in tissues and serum exosomes were examined by RT-qPCR. The origin of serum exosomal aHIF was explored in vitro and in vivo. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic factors of EOC. A prognostic predictive nomogram was formulated in R software. RESULTS: We isolated exosomes, identified exosomal aHIF in the serum of EOC patients. The expression of serum exosomal aHIF was higher in EOC patients and was correlated with the aHIF level in EOC tissues. In vitro and in vivo, the results indicated that serum exosomal aHIF was derived from tumor cells. Kaplan-Meier survival analysis demonstrated that EOC patients with higher serum exosomal aHIF expression had poorer overall survival. Cox multivariate regression model revealed that FIGO stage, residual tumor size, and serum exosomal aHIF level were independent prognostic factors of EOC. Based on the prognostic value of serum exosomal aHIF, we established a nomogram model that showed a good predictive ability for EOC patients. CONCLUSION: Serum exosomal aHIF is overexpressed in EOC and can serve as a noninvasive predictive biomarker for unfavorable prognosis.
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A sodium carboxy-methylcellulose (CMC)/chitosan (CS) composite sponge as drug carrier was prepared, and its structure and functions were investigated. Samples with different CMC/chitosan ratios and under different pH conditions were synthesized via a freeze-drying method. The microstructure of the dried sponges was analyzed by Scanning Electron Microscope (SEM). Molecule interactions between polymers were confirmed by Fourier transform infrared (FTIR) spectra and Thermal gravimetric analyze (TGA). The swelling degree, weight loss, in vitro drug release behavior and antibacterial property of the sponges were determined as well. The results showed that the CMC/chitosan ratio and the pH value significantly affected the appearance of the blending solution and the microstructure of the final product, and also affected the sponge's degradation behavior, drug-loading capacity and the antibacterial activity. Gentamicin (GEN) as a hydrophilic model drug was remarkably superior to the other two hydrophobic drugs, ibuprofen (IBU) and roxithromycin (ROX), with respect to in vitro releasing. Moreover, higher CMC content and lower pH value of the sponge were confirmed to lead a larger loading for GEN. The bacteriostatic experiment showed a strong antimicrobial ability of GEN-loaded sponges on inhibiting Escherichia coli.
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Carboximetilcelulose Sódica/química , Quitosana/química , Portadores de Fármacos/química , Preparações Farmacêuticas/química , Bandagens , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Liofilização , Gentamicinas/química , Gentamicinas/metabolismo , Gentamicinas/farmacologia , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ibuprofeno/química , Ibuprofeno/metabolismo , Microscopia Eletrônica de Varredura , Preparações Farmacêuticas/metabolismo , Roxitromicina/química , Roxitromicina/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , ViscosidadeRESUMO
We developed a bathroom safety management information system to decrease adverse nursing events, and observed the application of the self-developed safety management information system in neonatal bathroom.A total of 3482 newborns receiving neonatal bath and rooming in between May 2015 and May 2017, were enrolled in this study. Of the 3482 newborns, 1727 that did not use the safety management information system from May 1, 2015 to May 31, 2016, were considered as control group; and other 1755 that used the safety management information system from June 1, 2016 to May 31, 2017 were entered in observation group. The accident rate of adverse nursing events, the duration to check wristbands, response time of urgency call, quantitative data recording for nursing procedures, and pregnant women's and their families' satisfaction degree were compared between the 2 groups.The management information system possesses 4 functions including personal identification, nursing operation quantification, monitoring alarm and music function, and guidance on specialized knowledge and skills. The accident rate of adverse nursing events was significantly lower in the observation than in the control group (Pâ<â.05). The duration to check wristbands and the response time of urgency call were all significantly shorter in the observation group than in the control group (all Pâ<â.05). Quantitative data recording was significantly better in the observation than in the control group (Pâ<â.05). Satisfaction degree was significantly higher in the observation group (96.47%) than in the control group (89.69%) (Pâ<â.05). The wireless transmission information was exact and safe, and the system was sensitive and reliable.The system not only is clinically practical but also can enhance the safety of newborns and improve pregnant women's and their families' satisfaction degree.