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1.
Life Sci Alliance ; 3(5)2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32234750

RESUMO

Osteosarcoma (OS) is a primary malignant bone neoplasm with high frequencies of tumor metastasis and recurrence. Although the Akt/PKB signaling pathway is known to play key roles in tumorigenesis, the roles of cyclin-dependent kinase-like 3 (CDKL3) in OS progression remain largely elusive. We have demonstrated the high expression levels of CDKL3 in OS human specimens and comprehensively investigated the role of CDKL3 in promoting OS progression both in vitro and in vivo. We found that CDKL3 regulates Akt activation and its downstream effects, including cell growth and autophagy. The up-regulation of CDKL3 in OS specimens appeared to be associated with Akt activation and shorter overall patient survival (P = 0.003). Our findings identify CDKL3 as a critical regulator that stimulates OS progression by enhancing Akt activation. CDKL3 represents both a biomarker for OS prognosis, and a potential therapeutic target in precision medicine by targeting CDKL3 to treat Akt hyper-activated OS.

2.
J Contam Hydrol ; : 103605, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-32111401

RESUMO

The effects of organic matter, free Fe oxides and Mn oxides in an alluvial soil on adsorption of Cd were studied through selective chemical extraction and adsorption experiments. Compared to untreated soil, after H2O2 treatment for removal of organic matter and NH2OH·HCl treatment for removal Mn oxides, the distribution coefficient (Kd) decreased by a maximum of 25.2% and 64.1%, respectively. After dithionite-citrate-bicarbonate treatment for removal of free Fe oxides, Kd increased by 1670.2%. After increasing the solution pH from 2 to 3, Kd increased by 2842.1%, whereas after increasing the solution pH from 3 to 7, the adsorption tended stabilize. As the ionic strength increased from 0.001 M to 0.1 M NaNO3, Kd gradually decreased, whereas at the same ionic strength, Kd decreased as the initial concentration of Cd increased. The effects of different background electrolytes on Cd adsorption was as follows: Ca2+ > Mg2+ > K+ > Na+ for cations and Cl- ≈ SO42- > NO3- for anions. The adsorption capacity of Cd increased as the increased of temperature, and it's a spontaneous endothermic process. The pseudo second-order rate model described the process of Cd adsorption well.

3.
Indian J Cancer ; 57(1): 13-17, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32129295

RESUMO

Objective: No effective and definitive chemotherapeutic regimen has been established in patients with non-small cell lung cancer (NSCLC) who failed second-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, as monotherapy in elderly patients with advanced metastatic NSCLC. Methods: We evaluated the efficacy and safety of apatinib in elderly patients (≥65 years old) with advanced metastatic NSCLC who failed second-line treatment from 2015 to 2016 in Huanggang Central Hospital. Survival analysis was performed by the Kaplan-Meier method. Toxicities were evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.0. Results: Twenty patients were included in the present study. Two patients achieved partial response, and 9 achieved stable disease, representing a response rate of 10% and a disease control rate of 55%. Median progression-free survival and overall survival were 2.8 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%. Conclusion: Apatinib is an optional choice as salvage treatment in elderly patients with advanced metastatic NSCLC, with modest efficacy and acceptable toxicities.

4.
Int Immunopharmacol ; 82: 106361, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32135492

RESUMO

Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma.

5.
Am J Surg ; 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32184007

RESUMO

BACKGROUND: To investigate whether the use of Pecs II block benefit patients with the respect to the immune functions. METHODS: Totally 196 patients were included in this study. These patients were randomized to two groups, general anesthesia alone group (G group) and Pectoral nerve (Pecs) II block under general anesthesia group (PG group). RESULTS: It was found that remifentanil consumption was less in PG group than it in G group. PG group showed a higher proportion of NK cells in peripheral blood mononuclear cell (PBMC) and an improved killing activity than G groups after surgery. We also found that postoperative interleukin (IL)-2 concentration in the plasma of PG group was dramatically higher than it of G group. Interestingly, there was even no significant change between preoperative and postoperative IL-2 levels in PG group, suggesting the less inhibitory effect of Pecs II block on immune system of those patients. CONCLUSIONS: In conclusion, these results indicate that Pecs II block use in patients may have an enhanced immunity compared with general anesthesia method.

6.
Rev Sci Instrum ; 91(1): 014701, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012595

RESUMO

To study the damage and protection mechanism of an electromagnetic pulse to an electronic system, an all solid-state high-voltage pulse power with photoconductive semiconductor switch is developed, which is a component of the bounded wave electromagnetic pulse simulator. The output peak voltage of the prepared all solid-state pulsed power source was 74.5 kV, the risetime was 2.05 ns, and the pulse width was 22 ns. In addition, the peak voltage of the output pulse of the all solid-state pulsed power source could be regulated. The all solid-state electromagnetic pulse simulator developed in this work can generate an electromagnetic environment with a risetime of 2.2 ns and a pulse width of 23.5 ns.

7.
Int J Cancer ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017074

RESUMO

Highly tumorigenic, drug-resistant cancer stem-like cells drive cancer progression. These aggressive cells can arise repeatedly from bulk tumor cells independently of mutational events, suggesting an epigenetic mechanism. To test this possibility, we studied bladder cancer cells as they cyclically shifted to and from a cancer stem-like phenotype, and we discovered that these two states exhibit distinct DNA methylation and chromatin accessibility. Most differential chromatin accessibility was independent of methylation and affected the expression of driver genes such as E2F3, a cell cycle regulator associated with aggressive bladder cancer. Cancer stem-like cells exhibited increased E2F3 promoter accessibility and increased E2F3 expression that drove cell migration, invasiveness and drug resistance. Epigenetic interference using a DNA methylation inhibitor blocked the transition to a cancer stem-like state and reduced E2F3 expression. Our findings indicate that epigenetic plasticity plays a key role in the transition to and from an aggressive, drug-resistant phenotype.

8.
Mol Cell Probes ; : 101531, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32062018

RESUMO

The incidence of foodborne infections caused by Shigella spp. is still very high in every year, which poses a great potential threat to public health. Conventional quantification methods based on culture techniques, biochemical, and serological identification are time-consuming and labor-intensive. To develop a more rapid and efficient detection method of Shigella spp., we compared the sensitivity and specificity of three different polymerase chain reaction (PCR) methods, including conventional PCR, quantitative real-time PCR (RTQ-PCR), and droplet digital PCR (ddPCR). Our results indicated that ddPCR method exhibited higher sensitivity, and the limit of detection was 10-5 ng/µl for genomic DNA templates, 10-1 cfu/ml for Shigella bacteria culture. In addition, we found that ddPCR was a time-saving method, which required a shorter pre-culturing time. Collectively, ddPCR assay was a reliable method for rapid and effective detection of Shigella spp.

9.
Asian J Surg ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31964584

RESUMO

BACKGROUND: Despite the risk of lymph node metastasis (LNM), the indications of endoscopic submucosal dissection (ESD) has expanded to undifferentiated type (UD-type) early gastric cancer (EGC). There is debate as to whether the endoscopic resection can be used. This study was conducted to evaluate risk factors for LNM in undifferentiated early gastric cancer, implications for the indication of the ESD so as to providing evidence for proper clinical management for UD-type EGC. METHOD: We retrospectively analyzed 203 patients with UD-type EGC who underwent gastrectomy for primary gastric adenocarcinoma between 2012 and 2017. We evaluated the relationship between the clinicopathological factors and the presence of LNM using univariable and multivariable logistic regression analyses. RESULTS: A total of 203 UD-type EGC patients were enrolled, and LNM was positive in 40 cases (19.7%). Multivariable logistic regression analysis identified three independent risk factors for LNM, the tumor size (≥2.0 cm, P < 0.001), depth of invasion (P < 0.001), and lymphatic vessel involvement (LVI, P < 0.001). LNM was observed in 5.9% patients without the three predictive factors in UD-type EGC, whereas 7.7% and 37.7% of patients with one and two risk factors had LNM, respectively. In contrast, the LNM rate was up to be 66.7% in patients with three factors. Of 41 patients satisfying the expanded indication of ESD, 3 patients (7.3%) showed LNM. LNM was not found in any of 12 patients with small intramucosal lesions (<1.0 cm) without LVI. CONCLUSIONS: LNM-related risk factors were tumor larger than 2.0 cm, submucosal invasion, and the presence of LVI in UD-type EGC. ESD alone may be sufficient treatment for the intramucosal UD-type EGC that is smaller than 1.0 cm in size. When endoscopically resected specimens show unexpectedly larger tumor size, unexpected submucosal and LVI than that determined at pre-ESD endoscopic diagnosis, an additional gastrectomy with lymphadenectomy should be considered.

10.
Fitoterapia ; 141: 104472, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31917303

RESUMO

Three pairs of new germacranolides, (+)/(-)-chlogermacrones A-C, along with two known analogues were obtained from the roots of Chloranthus henryi. Spectroscopic techniques and single-crystal X-ray crystallographic analyses were used for the structure elucidation of the compounds. All of the isolated compounds were tested for their neuroprotective effects on H2O2 damaged PC12 cells, compounds 3 and 5 increased cell viability from 43.4 ± 1.3% to 99.6 ± 8.7 and 68.1 ± 4.8% at 10 µM, respectively.

11.
J Exp Clin Cancer Res ; 39(1): 23, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992359

RESUMO

BACKGROUND: Tripartite motif-containing proteins (TRIM) play a crucial role in carcinogenesis. Little attention has been focused on the possible functions of TRIM6 on carcinogenesis. METHODS: The expression levels of TRIM6 were assessed in colorectal cancer (CRC) samples. TRIM6 expression was knocked down in CRC cell lines, and subjected to Cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation and cell cycle assays. Immunoprecipitation and proteomics analysis was performed to identify potential associated proteins of TRIM6. RESULTS: TRIM6 expression was up-regulated in CRC samples and TRIM6 expression may be an independent prognostic marker for CRC. Knocking down TRIM6 expression suppressed CRC cell proliferation, induced cell cycle arrested at G2/M phase and increased sensitivity to 5-fluorouracil and oxaliplatin. TIS21, an anti-proliferative protein involved in the regulation of G2/M arrest, was identified as an interaction partner of TRIM6. Moreover, CRC cells with TRIM6 overexpression showed decreased TIS21 protein stability. TIS21 ubiquitination was increased in CRC cells overexpressing TRIM6, but not in those overexpressing TRIM6 E3 catalytic mutant (C15A). Further, Lys5 was essential for TRIM6 mediated TIS21 ubiquitination. TIS21 overexpression reversed the induced effects of TRIM6 overexpression on CRC cell proliferation, and the levels of forkhead box M1 (FoxM1), phosphorylated FoxM1, Cyclin B1 and c-Myc. Thiostrepton, a specific inhibitor for FoxM1, was less effective in anti-proliferative activity against CRC cells with lower level of TRIM6 in vitro and in vivo. CONCLUSIONS: Our study suggests that TRIM6 promotes the progression of CRC via TIS21/FoxM1.

12.
J Biol Chem ; 295(2): 584-596, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31806707

RESUMO

Heat shock proteins of 70 kDa (Hsp70s) are ubiquitous and highly conserved molecular chaperones. They play multiple essential roles in assisting with protein folding and maintaining protein homeostasis. Their chaperone activity has been proposed to require several rounds of binding to and release of polypeptide substrates at the substrate-binding domain (SBD) of Hsp70s. All available structures have revealed a single substrate-binding site in the SBD that binds a single segment of an extended polypeptide of 3-4 residues. However, this well-established single peptide-binding site alone has made it difficult to explain the efficient chaperone activity of Hsp70s. In this study, using purified proteins and site-directed mutagenesis, along with fluorescence polarization and luciferase-refolding assays, we report the unexpected discovery of a second peptide-binding site in Hsp70s. More importantly, the biochemical analyses suggested that this novel binding site, named here P2, is essential for Hsp70 chaperone activity. Furthermore, cross-linking and mutagenesis studies indicated that this second binding site is in the SBD adjacent to the first binding site. Taken together, our results suggest that these two essential binding sites of Hsp70s cooperate in protein folding.

13.
Fitoterapia ; 140: 104422, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31756377

RESUMO

Peniterester (1), a new tricyclic sesquiterpene, together with 6 known compounds (2-7) were isolated from the secondary metabolites of an artificial mutant Penicillium sp. T2-M20 which was obtained from the parental strain Penicillium sp. T2-8 via UV irradiation as well as nitrosoguanidine (NTG) induction. Peniterester was only produced by the mutant T2-M20 on the basis of LC-MS analysis. Meanwhile, the results of in vitro bioactivities screening indicated that peniterester owned obvious antibacterial activities against Bacillus subtilis, Escherichia coli and Staphylococcus aureus with MICs of 8.0, 8.0 and 4.0 µg/mL, respectively.


Assuntos
Antibacterianos/farmacologia , Penicillium/química , Sesquiterpenos/farmacologia , Antibacterianos/isolamento & purificação , Bacillus subtilis/efeitos dos fármacos , Linhagem Celular Tumoral , China , Escherichia coli/efeitos dos fármacos , Gastrodia/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Rizoma/microbiologia , Metabolismo Secundário , Sesquiterpenos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
14.
Bioorg Chem ; 95: 103503, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855825

RESUMO

An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1-5) and three aryl esters (6-8), together with six known analogues (9-14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculatedelectronic circular dichroism(ECD)data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compound 4 is the first example of an ent-protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Compound 6 exhibited moderate in vitro cytotoxic activities against five human cancer cell lines (HL-60, A549, MCF-7, SMMC-7721, and SW480) with IC50 values ranging from 15.80 to 23.03 µM. Moreover, 6 showed weak acetylcholinesterase inhibitory activity (IC50 value of 23.85 µM).

15.
Huan Jing Ke Xue ; 40(8): 3477-3488, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854753

RESUMO

In order to determine the concentrations and size distributions of total airborne microbes in atmospheric bioaerosols, bioaerosol samples were collected in the coastal region of Qingdao, China, from Sep. 2016 to Jul. 2017 using size-fractionated bioaerosol samplers. The concentrations of total airborne microbes were then measured using an epifluorescence microscope after staining with DAPI (4', 6-diamidino-2-phenylindole). The results showed that the concentrations of total airborne microbes were in the range of 1.86×105-2.54×106 cells·m-3 in Qingdao during the sampling period, with an average of (6.84±4.83)×105 cells·m-3. The concentrations of total airborne microbes showed seasonal variation, with the highest values occurring in spring and winter, and the lowest values in summer and fall. Statistical analysis showed that the concentrations of total airborne microbes in autumn had a significant seasonal difference with spring and summer (P<0.05). The monthly averaged concentrations of total airborne microbes ranged from 2.65×105 cells·m-3 to 1.12×106 cells·m-3, with the highest values in Feb. 2017 and the lowest in Sep. 2016. Total microbe concentrations also varied greatly over a diurnal timescale in fall and winter during the period of 2015 to 2017, but this variation was not statistically significant (P>0.05). Overall, the size distribution of total airborne microbes was skewed, with the highest ratio occurring at >7.0 µm with a ratio of 20.5%-27.3%. The monthly averaged size distribution of total airborne microbes varied between months, showing two main distribution types, specifically bimodal and skewed patterns, respectively. Spearman's rank correlation analysis showed that the AQI and the concentrations of CO, PM2.5, and PM10 had a significant positive correlation with the concentrations of total airborne microbes (P<0.05), while air temperature, wind speed and direction, NO2, SO2, and O3 were not significantly correlated with the airborne microbe concentration during the sampling period (P>0.05). Multiple linear regression showed that 20.6% of the variation in the total microbe concentrations in bioaerosols correlated with relative humidity and PM2.5.


Assuntos
Aerossóis , Poluentes Atmosféricos , Microbiologia do Ar , China , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado , Estações do Ano
16.
Aging (Albany NY) ; 11(24): 12708-12732, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31884419

RESUMO

Epidemiological studies have indicated that blood vitamin D levels are linked to cancer. Here we conducted a dose-response meta-analysis based on published observational studies to evaluate the association of vitamin D intake and blood vitamin D levels with breast cancer susceptibility. PubMed, EMBASE, and Web of Science databases were searched up to January 2019. The pooled odds ratio (OR) and 95% confidence intervals (CIs) were extracted to estimate the risk. We identified 70 relevant studies on blood vitamin D levels (50 studies) and vitamin D intake (20 studies), respectively. Linear and nonlinear trend analyses were performed and showed that an increase in blood vitamin D levels by 5 nmol/l was associated with a 6% decrease in breast cancer risk (OR = 0.94, 95% CI = 0.93-0.96). Similar results were obtained for premenopausal (OR = 0.96, 95% CI = 0.93-0.99) and postmenopausal women (OR = 0.96, 95% CI = 0.94-0.98). The pooled OR of breast cancer risk for a 400IU/day increase in vitamin D intake was 0.97 (95% CI = 0.92-1.02). In conclusion, we found that breast cancer risk was inversely related to blood vitamin D levels; however, no significant association was observed in vitamin D intake.

17.
Medicine (Baltimore) ; 98(44): e17605, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689766

RESUMO

Some postoperative gastric cancer patients have to terminate systemic intravenous chemotherapy early due to adverse drug reactions. We performed a retrospective study to explore the efficacy and feasibility of sequential therapy.We retrospectively analyzed 55 postoperative gastric cancer patients (Group A) who received sequential therapy (intravenous chemotherapy and S-1) and 53 patients (Group B) who received intravenous chemotherapy from January 2012 to December 2013 in our hospital. The therapeutic effect (including 1-year, 5-year tumor recurrence and survival rate) and the incidence of adverse reactions were analyzed.When death and survival for more than 5 years was regarded as the end point of follow-up, the mean follow-up period was 40.6 months (34.7-46.4) in Group A and 39.2 months (33.0-45.3) in Group B. The 1-year tumor recurrence after the operation was 23.6% (13/55, Group A) and 28.3% (15/53, Group B). The 5-year tumor recurrence was 45.5% (25/55, Group A) and 49.1% (26/53, Group B). There was no significant difference in the 1- and 5-year tumor recurrence rates between these two groups (P > .05). The 1-year survival rates of Group A and Group B were 81.8% (45/55) and 79.2% (42/53), respectively, and the 5-year survival rates of Group A and Group B were 47.3% (26/55) and 45.3% (24/53), respectively. No significant difference was observed between these two treatments at either the 1- or 5-year survival benefit (P > .05). However, the patients in Group A had a lower incidence of gastrointestinal reactions (such as nausea and vomiting), leukopenia and liver function damage (P < .05). We also found that patients who underwent sequential therapy might show lower levels of adverse reactions.Our retrospective study provided some evidence to suggest that sequential treatment is effective and safe for postoperative gastric cancer patients who are intolerant to intravenous chemotherapy.


Assuntos
Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Administração Oral , Adulto , Idoso , Quimioterapia Adjuvante , Combinação de Medicamentos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos
18.
Cancer Cell Int ; 19: 279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31719794

RESUMO

Background: Radiation sensitive 52 (RAD52) is an important protein that mediates DNA repair in tumors. However, little is known about the impact of RAD52 on hepatocellular carcinoma (HCC). We investigated the expression of RAD52 and its values in HCC. Some proteins that might be coordinated with RAD52 in HCC were also analyzed. Methods: Global RAD52 mRNA levels in HCC were assessed using The Cancer Genome Atlas (TCGA) database. RAD52 expression was analyzed in 70 HCC tissues and adjacent tissues by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry. The effect of over-expressed RAD52 in Huh7 HCC cells was investigated. The String database was then used to perform enrichment and functional analysis of RAD52 and its interactome. Cytoscape software was used to create a protein-protein interaction network. Molecular interaction studies with RAD52 and its interactome were performed using the molecular docking tools in Hex8.0.0. Finally, these DNA repair proteins, which interact with RAD52, were also analyzed using the TCGA dataset and were detected by qRT-PCR. Based on the TCGA database, algorithms combining ROC between RAD52 and RAD52 interactors were used to diagnose HCC by binary logistic regression. Results: In TCGA, upregulated RAD52 related to gender was obtained in HCC. The area under the receiver operating characteristic curve (AUC) of RAD52 was 0.704. The results of overall survival (OS) and recurrence-free survival (RFS) indicated no difference in the prognosis between patients with high and low RAD52 gene expression. We validated that RAD52 expression was increased at the mRNA and protein levels in Chinese HCC tissues compared with adjacent tissues. Higher RAD52 was associated with older age, without correlation with other clinicopathological factors. In vitro, over-expressed RAD52 significantly promoted the proliferation and migration of Huh7 cells. Furthermore, RAD52 interactors (radiation sensitive 51, RAD51; X-ray repair cross complementing 6, XRCC6; Cofilin, CFL1) were also increased in HCC and participated in some biological processes with RAD52. Protein structure analysis showed that RAD52-RAD51 had the firmest binding structure with the lowest E-total energy (- 1120.5 kcal/mol) among the RAD52-RAD51, RAD52-CFL1, and RAD52-XRCC6 complexes. An algorithm combining ROC between RAD52 and its interactome indicated a greater specificity and sensitivity for HCC screening. Conclusions: Overall, our study suggested that RAD52 plays a vital role in HCC pathogenesis and serves as a potential molecular target for HCC diagnosis and treatment. This study's findings regarding the multigene prediction and diagnosis of HCC are valuable.

19.
J Cancer ; 10(25): 6225-6232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772655

RESUMO

Background: Currently, there is still some controversy regarding whether early breast cancer patients with a tumor size of ≤5 cm and 1-3 positive lymph nodes should undergo postoperative radiotherapy (PRT). Materials and Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Then, we conducted propensity score matching (PSM), according to the radiotherapy record. The Kaplan-Meier and Cox regression analysis were conducted to explore prognostic factors in breast cancer. Results: A total of 6,777 patients aged 75+ years old were eligible and 2,361 patients were included after PSM. We found PRT could improve patient overall survival (OS) (P = 0.01, hazard ratio [HR] = 0.88, 95% confidence interval [CI], 0.80-0.97). Subgroup analysis revealed PRT could improve OS in patients with hormone receptor positive (HR+) (P = 0.001, HR = 0.84, 95% CI, 0.76 - 0.94) or white patients (P =0.004, HR = 0.86, 95% CI, 0.77 - 0.95). Conclusions: PRT may benefit for elderly women with early breast cancer, especially in HR+ patients or white patients. These findings may inform future optimized options whether elderly female patients with early breast cancer should undergo postoperative radiotherapy.

20.
Exp Anim ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31748426

RESUMO

Piwi-interacting RNAs (piRNAs), a novel class of noncoding RNAs, are involved in the carcinogenesis. However, the functional significance of piRNAs in oral squamous cell carcinoma (OSCC) remains unknown. In the present study, we used chemical carcinogen 4NQO to induced OSCC mouse model. piRNAs and mRNAs were profiled using next-generation sequencing in the tongue tumor tissues from 4NQO induction and healthy tongue tissues from control mice. Furthermore, we analyzed the differential gene expression of human OSCC in GEO database. According to the common differentially expressed genes in the 4NQO model and human OSCC tissues, piRNAs and mRNAs network were established based on informatics method. A total of 14 known piRNAs and 435 novel predicted piRNAs were differently expressed in tumor tissue compared to healthy tissue. Among differently expressed piRNAs 260 were downregulated, and 189 were upregulated. The mRNA targets for the differentially expressed piRNAs were identified using RNAhybrid software. Primary immunodeficiency and herpes simplex infection were the most enriched pathways. A total of 22 mRNAs overlapped in human and mice OSCC. Moreover, we established the regulatory network of 11 mRNAs, including Tmc5, Galnt6, Spedf, Mybl2, Muc5b, Six31, Pigr, Lamc2, Mmp13, Mal, and Mamdc2, and 11 novel piRNAs. Our data showed the interaction between piRNAs and mRNAs in OSCC, which might provide new insights in the development of diagnostic biomarkers and therapeutic targets of OSCC.

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