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1.
Chemistry ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691394

RESUMO

The Fe-based transition metal oxides are competitive among anode candidates for lithium storage considering the high specific capacity, low-cost, and environmental compatibility. However, the poor electron/ion conductivity and obvious volume stress limit the cycle and rate performance. What's worse, the capacity rising and sudden decay phenomena of α-Fe2O3 have always appeared in most reports. Here, the uniform micro/nano α-Fe2O3 nanoaggregate conformably enclosed into ultrathin N-doped carbon network (denoted as M/N-α-Fe2O3@NC) is designed substantially. The M/N porous balls combine the merits of secondary nanoparticles to shorten Li+ transportation pathways as well as alleviate volume expansion and primary microball to stabilize the electrode/electrolyte interface. Furthermore, the ultrathin carbon shell favors for fast electron transfer and protects the electrode from electrolyte corrosions. Therefore, M/N-α-Fe2O3@NC electrode delivers an excellent reversible capacity of 901 mA h g-1 with capacity retention up to 94.0% after 200 cycles at 0.2 A g-1. Notably, the capacity raising does not happen during cycling. Moreover, the lithium storage mechanism is elucidated by ex-situ XRD and HRTEM. It is verified that the reversible phase transformation of α ↔ γ occurs during the first cycle while only α-Fe2O3 phase is reversibly transformed during subsequent cycles. This study offers a simple and scalable strategy for the practical application of high-performance Fe2O3 electrode.

2.
Cell Death Dis ; 10(11): 829, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685807

RESUMO

Metastasis is a well-known poor prognostic factor in cancer. However, the mechanisms how long non-coding RNAs (lncRNAs) regulate metastasis in colorectal cancer (CRC) remain largely unknown. Besides, tumor-associated macrophages (TAMs) play an important role in tumor progression, yet the contribution of lncRNA-mediated crosstalk between TAMs and CRC cells to tumor progression is not well understood. In this study, we report that lncRNA RPPH1 was significantly upregulated in CRC tissues, and the RPPH1 overexpression was associated with advanced TNM stages and poor prognosis. RPPH1 was found to promote CRC metastasis in vitro and in vivo. Mechanistically, RPPH1 induced epithelial-mesenchymal transition (EMT) of CRC cells via interacting with ß-III tubulin (TUBB3) to prevent its ubiquitination. Furthermore, CRC cell-derived exosomes transported RPPH1 into macrophages which mediate macrophage M2 polarization, thereby in turn promoting metastasis and proliferation of CRC cells. In addition, exosomal RPPH1 levels in blood plasma turned out to be higher in treatment-naive CRC patients but lower after tumor resection. Compared to CEA and CA199, exosomal RPPH1 in CRC plasma displayed a better diagnostic value (AUC = 0.86). Collectively, RPPH1 serves as a potential therapeutic and diagnostic target in CRC.

3.
Ann Surg Oncol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758282

RESUMO

In the original article, the word IMMUNOSCORE® was not displayed to reflect its trademark status. At every mention, IMMUNOSCORE® should be in all caps and with a registered trademark symbol.

4.
J Exp Clin Cancer Res ; 38(1): 442, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31666105

RESUMO

In the original publication of this article [1], the indicated stages (I-II III-IV) were missing in the clinical stage part at both Table 1 and Table 2.

5.
Nanotechnology ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731285

RESUMO

Two-dimensional (2D) materials such as graphene and MoS2 have shown great potential in photodetection platforms. Photoresponsivity and photoresponse speed are two important parameters illustrating photodetector performances. Although various hybrid structures have been designed, the trade-off between photoresponsivity and photoresponse speed has not been well balanced. In this work, MoS2 film and In(OH)xSe nanoparticles are combined together to form the hybrid phototransistor. Utilizing both the photoconducting and photogating effects, the photoresponsivity increases about one order of magnitude with a value of 102 A/W. The ratio of photocurrent and dark current increases to a value of 104. Considering the slow photo recovery speed, a 2 ms gate voltage pulse is applied after turning off the light, which results in a complete recovery of current. The photoconducting effect, photogating effect and gate voltage stimulation simultaneously promote the superior comprehensive photoresponse performances. This method can be further explored and utilized for realizing high performance photodetectors.

6.
ACS Appl Mater Interfaces ; 11(47): 44007-44017, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31696699

RESUMO

Polymeric nanoparticles (NPs) have been widely established to deliver most of the hydrophobic chemo-drugs or photosensitizers (PSs) for cancer therapy. However, this strategy is usually hindered by the relatively low drug loading capacity and the undesired toxicity as well as the immunogenicity caused by the nontherapeutic, polymeric carriers. The carrier-free, drug self-delivery systems, in which the chemo-drugs or their prodrugs themselves formed the NPs without the addition of nontherapeutic carriers, have been extensively developed to achieve a high drug loading capacity and low systemic toxicity. However, most of the driving forces to form the NPs were based on the strong hydrophobic interactions, which were the undesired forces for the porphyrin-based hydrophobic PSs due to the parasitic aggregation-caused quenching effect. Herein, the zwitterionic, water-soluble, and reactive oxygen species (ROS)-cleavable poly-photosensitizers (pPSs) were prepared by the polymerization method, which spontaneously introduced different charges associated with the "desired electrostatic effect" and reduced the "undesired aggregation" by separating the PS monomers using flexible and ROS-cleavable linkers. The obtained pPS could be self-assembled into the nanocomplexes based on the electrostatic effect with a high PS loading capacity, improved singlet oxygen generation ability, and efficient phototoxicity. Upon poly(ethylene glycol) (PEG) or hyaluronic acid (HA) coating on the surface, both pPS/PEG and pPS/HA complexes exhibited enhanced stability under physiological environments and excellent in vivo antitumor efficacy. Moreover, HA-coated complexes also exhibited active tumor targeting. Such a polymerization strategy comprehensively addressed the parasitic issues for the hydrophobic PS self-delivery system in the photodynamic therapy area.

8.
ACS Sens ; 4(10): 2809-2818, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31566369

RESUMO

E-textiles are gaining growing popularity recently due to low cost, light weight, and conformable compatibility with clothes in wearable and portable smart electronics. Here, an easy-handing, low cost, and scalable fabricating strategy is reported to fabricate conductive, highly flexible, and mechanically stretchable/twisted fiber gas sensor with great wearability and knittability. The proposed gas sensor is built using commercially available cotton/elastic threads as flexible/stretchable templates and reduced graphene oxide/mesoporous zinc oxide nanosheets as sensing layers to form conducting fibers. The as-prepared fiber demonstrates sensitive sensing response, excellent long-term stability (84 days), low theoretical detection limit (43.5 ppb NO2), great mechanical deformation tolerance (3000 bending cycles, 1000 twisting cycles and 65% strain strength), and washing durability in room-temperature gas detection. More significantly, scalable wearable characteristics including repairability, reliability, stability, and practicability have been efficiently improved, which are achieved by knotting the fractured fibers, incorporating multiple sensors in series/parallel and weaving multisensor array networks integrated into clothes. The good sensing properties, superior flexibility, and scalable applications of wearable fibers may provide a broad window for widespread monitoring of numerous human activities in personal mobile electronics and human-machine interactions.

9.
J Neurol ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637489

RESUMO

BACKGROUND: Both REM sleep behavior disorder (RBD) and impulsive-compulsive behaviors (ICBs) are well-recognized non-motor features in patients with Parkinson's disease (PD). Studies have given contradictory results about the potential association between RBD and ICBs. METHODS: PubMed, Embase (via Ovid), and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases were systematically searched till August 20, 2019 to identify studies that explored the possible correlation between RBD and ICBs in patients with PD. Two authors independently screened records, extracted data and evaluated quality of included studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by employing a random or fixed-effects model. We performed subgroup and sensitivity analyses, and we assessed potential publication bias. RESULTS: A total of 134 references were screened and 10 studies involving 2781 PD patients were included. Overall, RBD was associated with a more than twofold higher risk of developing ICBs (OR 2.12, 95% CI 1.43-3.14, I2 = 56.7%, P < 0.01). Similar results were obtained in sensitivity analyses and in meta-analyses of subgroups stratified based on multivariable adjustment and methods for diagnosing RBD and ICBs. No significant risk of publication bias was found. CONCLUSION: RBD in PD is confirmed to be a risk factor for ICBs. Clinicians should be aware of this association to help them improve patient management.

10.
Int J Gynecol Cancer ; 29(8): 1280-1284, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570543

RESUMO

INTRODUCTION: The solute carrier family 12 member 5 (SLC12A5) gene is playing a putative oncogenic role in colorectal carcinoma. However, the status of SLC12A5 amplification and expression in ovarian carcinoma and its potential clinical and/or prognostic significance has not yet been investigated. METHODS: In the present study, semi-quantitative staining and fluorescence in situ hybridization were used to investigate SLC12A5 protein expression and gene amplification levels. Samples were obtained from archival, formalin-fixed, paraffin-embedded pathological specimens consisting of 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors, and 147 invasive ovarian carcinomas. SLC12A5 immunohistochemical staining results, pathological parameters, and patient prognosis were then evaluated using various statistical models. Patient survival rate was also assessed using receiver-operator curve analysis. RESULTS: Our results revealed no SLC12A5 protein overexpression in normal ovaries. However, 7% of cystadenomas had SLC12A5 protein overexpression along with 17% of borderline tumors and 37% of ovarian carcinomas (P<0.01). Amplification of SLC12A5 was detected in 10.3% of ovarian carcinomas. Further correlational analyses showed that SLC12A5 protein overexpression in ovarian carcinomas was significantly associated with ascending histological grade, pT/pN/pM status, as well as FIGO stage (P<0.05). A subsequent univariate survival analysis of our ovarian carcinoma cohorts resulted in a significant association between SLC12A5 protein overexpression and decreased patient survival (44.3 and 85.9 months for high and low SLC12A5 protein expression, respectively; P<0.001). Importantly, additional multivariate analysis revealed that SLC12A5 protein expression was a significant, independent prognostic factor for overall survival in ovarian carcinoma patients (P=0.003). CONCLUSIONS: Collectively, these findings support the conclusion that SLC12A5 protein overexpression could indicate an invasive and/or aggressive phenotype of ovarian carcinoma. Future work will need to investigate whether SLC12A5 protein can serve as an independent prognostic molecular marker in patients with ovarian carcinoma.

11.
J Agric Food Chem ; 67(45): 12538-12546, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638796

RESUMO

Cyanobacteria harmful algal blooms are of global concern, but all currently available algicides in the market are nonselective and have potential side effects on nontarget species. In the present work, two series of compounds (4 and 6) comprising 16 novel 1,2,3-triazole aminopyrimidines were rationally designed and synthesized as control agent for cyanobacteria. Our design focus was the inhibiting cyanobacteria by inhibition against pyruvate dehydrogenase complex E1 (PDHc-E1). Compounds 4 and 6 showed potent inhibition against Escherichia coli PDHc-E1 (IC50 = 4.13-23.76 µM) and also strong algicidal activities against Synechocystis sp. PCC 6803 (EC50 = 1.7-8.1 µM) and Microcystis sp. FACHB905 (EC50 = 2.1-11.8 µM). In particular, the algicidal activities of 6d against four algal species were not only higher than that of prometryn; they were also comparable to or higher than that of copper sulfate. The analogues 4c, 4d, 6d, and 6e displayed potent algicidal activities and inhibition of E. coli PDHc-E1 but exhibited negligible inhibition of porcine PDHc-E1. As revealed by molecular docking, site-directed mutagenesis, enzymatic assays, and an inhibition kinetic analysis, 4c and 6d inhibited PDHc-E1 in a competitive manner. Our results suggest that highly selective, effective algicides can be developed by rationally designing competitive PDHc-E1 inhibitors.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Herbicidas/farmacologia , Microcystis/efeitos dos fármacos , Pirimidinas/farmacologia , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Synechocystis/efeitos dos fármacos , Triazóis/farmacologia , Proteínas de Bactérias/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Herbicidas/síntese química , Herbicidas/química , Cinética , Microcystis/química , Microcystis/enzimologia , Simulação de Acoplamento Molecular , Pirimidinas/química , Piruvato Desidrogenase (Lipoamida)/química , Relação Estrutura-Atividade , Synechocystis/química , Synechocystis/enzimologia , Triazóis/química
12.
Lung Cancer ; 136: 129-135, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494531

RESUMO

OBJECTIVES: Current evidence suggests that microorganisms are associated with neoplastic diseases; however, the role of the airway microbiome in lung cancer remains unknown. To investigate the taxonomic profiles of the lower respiratory tract (LRT) microbiome in patients with lung cancer. MATERIALS AND METHODS: BALF samples were collected in a discovery set comprising 150 individuals, including 91 patients with lung cancer, 29 patients with nonmalignant pulmonary diseases and 30 healthy subjects, and an independent validation set including 85 participants. The samples were assessed by metagenomics analysis. Random forest regression analysis was performed to select a diagnostic panel. RESULTS: In the discovery set, richness was reduced in lung cancer patients compared with that in healthy subjects, and the microbiome of patients with nonmalignant diseases resembled that of patients with lung cancer. Interestingly, Bradyrhizobium japonicum was only found in patients with lung cancer, whereas Acidovorax was found in patients with cancer and nonmalignant pulmonary diseases. A microbiota-related diagnostic model consisting of age, pack year of smoking and eleven types of bacteria was built, and the area under the curve (AUC) for discriminating the patients with cancer was 0.882 (95%CI: 0.807-0.957) in the training set and 0.796 (95%CI: 0.673-0.920) in the independent validation set. CONCLUSION: Our study demonstrates that the LRT microbiome richness is diminished in lung cancer patients compared with that in healthy subjects and that microbiota-specific biomarkers may be useful for diagnosing patients for whom lung biopsy is not feasible.

13.
Small ; 15(45): e1902789, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31544354

RESUMO

Palladium diselenide (PdSe2 ) is an emerging 2D layered material with anisotropic optical/electrical properties, extra-high carrier mobility, excellent air stability, etc. So far, ultrathin PdSe2 is mainly achieved via mechanical exfoliation from its bulk counterpart, and the direct synthesis is still challenging. Herein, the synthesis of ultrathin 2D PdSe2 on conductive Au foil substrates via a facile chemical vapor deposition route is reported. Intriguingly, an anisotropic growth behavior is detected from the evolution of ribboned flakes with large length/width ratios, which is well explained from the orthorhombic symmetry of PdSe2 . A unique even-layered growth mode from 2 to 20 layers is also confirmed by the perfect combination of onsite scanning tunneling microscopy characterizations, through deliberately scratching the flake edge to expose both even and odd layers. This even-layered, ribboned 2D material is expected to serve as a perfect platform for exploring unique physical properties, and for developing high-performance electronic and optoelectronic devices.

14.
Oncogene ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530934

RESUMO

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.

15.
Aging Clin Exp Res ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31538320

RESUMO

BACKGROUND: Accumulation of aggregated α-synuclein from the enteric nervous system is believed to be involved in the pathogenesis of Parkinson's disease (PD). The appendix contains abundant α-synuclein and lacks a blood-tissue barrier, suggesting that appendectomy might reduce α-synuclein aggregation, and therefore the risk of PD. Studies on this intriguing possibility have not come to consistent conclusions. METHODS: PubMed, Embase (via Ovid), and the Cochrane Controlled Register of Trials were searched for studies published through February 20, 2019 on the potential relationship between appendectomy and PD. Two reviewers independently screened literature, extracted data and evaluated the quality of included studies. Data were summarized as pooled effect sizes (RRs or SMDs) with 95% confidence intervals (CIs), which were calculated using the inverse variance method and a random-effects model. Heterogeneity was assessed using the I2 statistic and explored in subgroup analyses. RESULTS: Of the 408 references screened, six studies involving 3,554,540 people were included eventually. Appendectomy did not significantly affect PD risk (RR 1.02, 95% CI 0.87-1.20, I2 = 83.1%, P = 0.789) or delay its onset (SMD 0.21, 95% CI - 0.03 to 0.44, I2 = 43.4%, P = 0.083). CONCLUSION: The available evidence suggests no protective effect of appendectomy against PD. Future studies should seek to clarify the role of inflammation, α-synuclein pathology and the gut-brain axis in PD pathogenesis.

16.
BMC Genomics ; 20(1): 699, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506062

RESUMO

BACKGROUND: Successful social behavior requires real-time integration of information about the environment, internal physiology, and past experience. The molecular substrates of this integration are poorly understood, but likely modulate neural plasticity and gene regulation. In the cichlid fish species Astatotilapia burtoni, male social status can shift rapidly depending on the environment, causing fast behavioral modifications and a cascade of changes in gene transcription, the brain, and the reproductive system. These changes can be permanent but are also reversible, implying the involvement of a robust but flexible mechanism that regulates plasticity based on internal and external conditions. One candidate mechanism is DNA methylation, which has been linked to social behavior in many species, including A. burtoni. But, the extent of its effects after A. burtoni social change were previously unknown. RESULTS: We performed the first genome-wide search for DNA methylation patterns associated with social status in the brains of male A. burtoni, identifying hundreds of Differentially Methylated genomic Regions (DMRs) in dominant versus non-dominant fish. Most DMRs were inside genes supporting neural development, synapse function, and other processes relevant to neural plasticity, and DMRs could affect gene expression in multiple ways. DMR genes were more likely to be transcription factors, have a duplicate elsewhere in the genome, have an anti-sense lncRNA, and have more splice variants than other genes. Dozens of genes had multiple DMRs that were often seemingly positioned to regulate specific splice variants. CONCLUSIONS: Our results revealed genome-wide effects of A. burtoni social status on DNA methylation in the brain and strongly suggest a role for methylation in modulating plasticity across multiple biological levels. They also suggest many novel hypotheses to address in mechanistic follow-up studies, and will be a rich resource for identifying the relationships between behavioral, neural, and transcriptional plasticity in the context of social status.

17.
Molecules ; 24(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366048

RESUMO

As aberrant activity of protein kinases is observed in many disease states, these enzymes are common targets for therapeutics and detection of activity levels. The development of non-natural protein kinase substrates offers an approach to protein substrate competitive inhibitors, a class of kinase inhibitors with promise for improved specificity. Also, kinase activity detection approaches would benefit from substrates with improved activity and specificity. Here, we apply a substrate-mediated selection to a peptidomimetic DNA-encoded chemical library for enrichment of molecules that can be phosphorylated by the protein tyrosine kinase, c-Src. Several substrates were identified and characterized for activity. A lead compound (SrcDEL10) showed both the ability to serve as a substrate and to promote ATP hydrolysis by the kinase. In inhibition assays, compounds displayed IC50's ranging from of 8-100 µM. NMR analysis of SrcDEL10 bound to the c-Src:ATP complex was conducted to characterize the binding mode. An ester derivative of the lead compound demonstrated cellular activity with inhibition of Src-dependent signaling in cell culture. Together, the results show the potential for substrate-mediated selections of DNA-encoded libraries to discover molecules with functions other than simple protein binding and offer a new discovery method for development of synthetic tyrosine kinase substrates.

18.
Ann Surg Oncol ; 26(12): 4148-4156, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376036

RESUMO

BACKGROUND: Increasing evidence suggests that cancer progression is strongly influenced by the host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based Immunoscore is reported to be a reliable prognostic factor in colon cancer, but its significance in urothelial carcinoma of the bladder (UCB) is at an early stage of exploration. This study aimed to determine whether the tumor immune infiltrate, as evaluated by the Immunoscore, could act as a useful prognostic marker for UCB patients who have undergone radical cystectomy (RC). METHODS: In this study, immunohistochemistry was used to examine the Immunoscore of 221 UCB patients who underwent RC. The Immunoscore of the patients was determined by the densities of CD3+ and CD8+ T cells at the tumor center and the invasive margin. RESULTS: A highly significant association between a low Immunoscore and a shortened patient survival (P < 0.001, log-rank test) was demonstrated. In different subsets of UCB patients, a low Immunoscore also was a prognostic indicator of pT ≤ 2, pN(-)-status tumors, negative vascular invasion, or both (P < 0.05). Importantly, the Immunoscore together with the patient's pT status provided significant independent prognostic parameters in the multivariate analysis (P < 0.05). Furthermore, a significant correlation (P = 0.003) of a low Immunoscore with an increased UCB labeling index of Ki-67 (a cell proliferation marker) was observed in this UCB cohort. CONCLUSIONS: The findings suggest that the Immunoscore, as examined by immunohistochemistry, might serve as a novel prognostic marker for UCB patients who have undergone RC.

19.
J Natl Compr Canc Netw ; 17(7): 805-811, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31319395

RESUMO

BACKGROUND: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti-epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. PATIENTS AND METHODS: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. RESULTS: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66-0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78-1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57-0.86, and OR, 3.28; 95% CI, 1.95-5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59-0.99, and OR, 1.78; 95% CI, 1.08-2.93, respectively). CONCLUSIONS: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.

20.
Anticancer Res ; 39(7): 3677-3686, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262894

RESUMO

BACKGROUND/AIM: Peroxiredoxin (Prx) V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS). Also, Prx V has been shown to mediate cell apoptosis in various cancers. However, the mechanism of Prx V-induced apoptosis in colon cancer cells remains unknown. Thus, in this study we analyzed the effects of Prx V in ß-lapachone-induced apoptosis in SW480 human colon cancer cells. MATERIALS AND METHODS: ß-lapachone-induced apoptosis was analyzed by the MTT assay, western blotting, fluorescence microscopy, Annexin V staining and flow cytometry. RESULTS: Overexpression of Prx V, significantly decreased ß-lapachone-induced cellular apoptosis and Prx V silencing increased ß-lapachone-induced cellular apoptosis via modulating ROS scavenging activity compared to mock SW480 cells. In addition, to further explore the mechanism of Prx V regulated ß-lapachone-induced SW480 cells apoptosis, the Wnt/ß-catenin signaling was studied. The Wnt/ ß-catenin signaling pathway was found to be induced by ß-lapachone. CONCLUSION: Prx V regulates SW480 cell apoptosis via scavenging ROS cellular levels and mediating the Wnt/ß-catenin signaling pathway, which was induced by ß-lapachone.


Assuntos
Apoptose , Neoplasias do Colo/metabolismo , Naftoquinonas , Peroxirredoxinas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Colo/metabolismo , Humanos
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