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1.
Org Lett ; 25(22): 4150-4155, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37252906

RESUMO

A convenient and efficient approach was developed to synthesize α-Kdo O-glycosides based on the Tf2O/(p-Tol)2SO preactivation strategy using peracetylated Kdo thioglycoside as a donor. Under the optimized reaction conditions, several O-glycoside products, including α-(2 → 1)-, α-(2 → 2)-, α-(2 → 3)-, and α-(2 → 6)-Kdo products, were stereoselectively synthesized in high yields. Remarkably, a series of aromatic α-Kdo O-glycosides were first and successfully constructed in high yields. An SN2-like mechanism was revealed by DFT calculations and experimental results.


Assuntos
Glicosídeos Cardíacos , Glicosídeos , Glicosilação , Açúcares Ácidos , Lipopolissacarídeos
2.
J Mater Chem B ; 10(29): 5602-5611, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35801534

RESUMO

Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the ex situ detection and in situ inhibition of amyloid fibrillation. Here, we reported a modular synthetic strategy to construct nine amphiphilic sugar-coated AIE-active fluorescent organic nanoparticles (FONs, TPE2/3/4X, X = G, M or S) with glucosamine (G), mannose (M) or sialic acid (S) as a hydrophilic moiety and tetraphenylethylene (TPE) as a hydrophobic AIE core. The carbohydrate-protein interactions between insulin and TPE2/3/4X were investigated by fluorescence spectroscopy, circular dichroism spectroscopy and transmission electron microscopy. Among the nine FON AIEgens, TPE2G was screened out as the best dual functional FON for the ex situ detection and in situ inhibition of the insulin fibrillation process, indicating that the glycosyl moiety exhibited a crucial effect on the detection/inhibition of insulin fibrillation. The molecular dynamics simulation results showed that the binding mechanism between TPE2G and native insulin was through weak interactions dominated by van der Waals interactions and supplemented by hydrogen bonding interactions to stabilize an α-helix of the insulin A chain, thereby inhibiting the insulin fibrillation process. This work provides a powerful protocol for the further research of amyloid-related diseases based on carbohydrate-protein interactions.


Assuntos
Amiloide , Nanopartículas , Amiloide/química , Proteínas Amiloidogênicas , Insulina/química , Insulina Regular Humana , Nanopartículas/química , Açúcares
3.
Gastroenterol Rep (Oxf) ; 9(4): 339-349, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34567566

RESUMO

BACKGROUND: Approximately 10% of patients with gastric cancer (GC) have a genetic predisposition toward the disease. However, there is scant knowledge regarding germline mutations in predisposing genes in the Chinese GC population. This study aimed to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. METHODS: A total of 40 GC patients from 40 families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands carrying pathogenic/likely pathogenic germline variants, Sanger sequencing was applied to validate the variants in the probands as well as their relatives. RESULTS: According to sequencing results, 25.0% (10/40) of the patients carried a combined total of 10 pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). In addition, 129 variants of uncertain significance were identified in 27 patients. CONCLUSIONS: This study indicates that approximately one in every four Chinese GC patients with hereditary high risk factors may harbor pathogenic/likely pathogenic germline alterations in cancer-susceptibility genes. The results further indicate a unique genetic background for GC among Chinese patients.

4.
Chem Asian J ; 16(15): 2014-2017, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34128347

RESUMO

A dilactosyl-dicyanovinyl-functionalized tetraphenylethene (TPELC) was designed, synthesized and used for ratiometric sensing of cyanide. TPELC was comprised of three moieties (tetraphenylethylene, dicyanovinyl group and lactose unit) in one molecule, making TPELC water-soluble and aggregation-induced emission (AIE)-active and selectively reactive to cyanide. Compared with other reported fluorescent probes containing dicyanovinyl group, TPELC is the first AIE luminogen to be assembled as fluorescent organic nanoparticles (FONs) for sensing of cyanide in water without the use of surfactant or the help of organic solvents based on the nucleophilic addition reaction. The detection mechanism was verified by liquid chromatograph mass spectrometry experiments and by protonation of cyanide to reduce the nucleophilicity of cyanide. In addition, TPELC was used for detection of the cyanide content of food samples and test strips were developed to simplify the detection procedure.


Assuntos
Cianetos/análise , Corantes Fluorescentes/química , Contaminação de Alimentos/análise , Nanopartículas/química , Estilbenos/química , Poluentes Químicos da Água/análise , Corantes Fluorescentes/síntese química , Estrutura Molecular , Solubilidade , Espectrometria de Fluorescência , Estilbenos/síntese química , Água/química
5.
Transl Cancer Res ; 10(2): 779-789, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35116409

RESUMO

BACKGROUND: Programmed cell death protein 1 (PD-1) blockade is a major advance in the treatment of malignancies, but there remain many problems in efficacy evaluation. The aim of this study was to determine whether dynamic monitoring of serum specific tumor markers (SSTMs) could predict the response to PD-1 blockade and prognosis in patients with malignancies. METHODS: The dynamic changes in SSTMs in 27 patients between January 1, 2018 and July 31, 2019 were analyzed retrospectively. The association between the SSTM response and the radiological response was evaluated using the χ2 test and Spearman's correlation analysis. Kaplan-Meier estimates and the log rank test were used to explore the correlation of SSTM dynamics with progression-free survival (PFS) and overall survival (OS). RESULTS: In this study, 85.3% of patients with malignant tumors had detectable SSTM. According to the changes of SSTM within the first 12 weeks of treatment, the patients were divided into a tumor marker increased group and a tumor marker decreased group. The change in SSTM was strongly associated with the change in target lesions (χ2=15.326, P≤0.001), and there was a positive correlation between them (Pearson Correlation r=0.727, P<0.0001). Patients with SSTM reduction had a significantly longer median OS (417 days) when compared with patients with SSTM elevation (median OS, 235 days; log rank χ2=6.323, P=0.012). The PFS in the SSTM reduction group (median PFS, not reached) was significantly longer than that in the elevation group (127 days; log rank χ2=8.843, P=0.003). In the study, one patient showed pseudoprogression and one showed a delayed response in the initial stage of PD-1 blockade. The diameter of the target lesions increased according to the Reaction Evaluation Criteria in Solid Tumor criteria, but the symptoms of discomfort were relieved significantly, and the SSTMs continued to decline dramatically. CONCLUSIONS: Dynamic monitoring of SSTMs can be used as a necessary supplement to imaging examination to evaluate the response to PD-1 blockade and predict the prognosis of patients with malignancies; it may also be helpful for clinical judgment of pseudoprogression and delayed response.

6.
Cancer Biomark ; 29(4): 493-508, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831192

RESUMO

Growing evidence has underscored long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic tracking of a lncRNA signature for prognosis prediction in non-small cell lung cancer (NSCLC) has not been accomplished yet. Here, comprehensive analysis with differential gene expression analysis, univariate and multivariate Cox regression analysis based on The Cancer Genome Atlas (TCGA) database was performed to identify the lncRNA signature for prediction of the overall survival of NSCLC patients. A risk-score model based on a 14-lncRNA signature was identified, which could classify patients into high-risk and low-risk groups and show poor and improved outcomes, respectively. The receiver operating characteristic (ROC) curve revealed that the risk-score model has good performance with high AUC value. Multivariate Cox's regression model and stratified analysis indicated that the risk-score was independent of other clinicopathological prognostic factors. Furthermore, the risk-score model was competent for the prediction of metastasis-free survival in NSCLC patients. Moreover, the risk-score model was applicable for prediction of the overall survival in the other 30 caner types of TCGA. Our study highlighted the significant implications of lncRNAs as prognostic predictors in NSCLC. We hope the lncRNA signature could contribute to personalized therapy decisions in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/metabolismo , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Prognóstico , Análise de Sobrevida
7.
Int J Ophthalmol ; 13(1): 29-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31956567

RESUMO

AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis" on pathogenesis of human Marcus Gunn Syndrome (MGS). METHODS: Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus (III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN), following electric stimulation of the ipsilateral masseter nerve (MN) in rats. RESULTS: Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. CONCLUSION: A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.

8.
Front Mol Neurosci ; 12: 174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427925

RESUMO

Malocclusion is an important risk factor for temporomandibular disorder (TMD), a series of disorders characterized by dysfunction in the orofacial region involving the temporomandibular joint (TMJ) and jaw muscles. We recently showed that experimental unilateral anterior crossbite (UAC) produced masseter hyperactivity through a circuit involving the periodontal proprioception, trigeminal mesencephalic nucleus (Vme), and trigeminal motor nucleus (Vmo). Anxiety is a common complication in patients with TMD. The lateral habenula (LHb) is involved in emotional modulation and has direct projections to the Vme. Therefore, the present research examined whether UAC facilitates excitatory input from the LHb to the Vme and, subsequently, anxiety-like behaviors in rats. The LHb activation was evaluated by the electrophysiological recording, assessment of vesicular glutamate transporter-2 (VGLUT2) mRNA expression, and measurement of anxiety-like behaviors. The effects of LHb activity on Vme were evaluated by electrophysiological recording from Vme neurons and local changes in VGLUT2 protein density. UAC produced anxiety in modeled rats and increased neuronal activity in the LHb. VGLUT2 mRNA expression was also increased in the LHb. Further, VGLUT2-positive boutons were observed in close apposite upon parvalbumin (PV)-labeled Vme neurons. VGLUT2 protein expression was also increased in the Vme. Significantly, injection of VGLUT2-targeted shRNA into the LHb reduced the expression of VGLUT2 protein in the Vme, attenuated UAC-associated anxiety-like behaviors, and attenuated electrophysiological changes in the Vme neurons. In conclusion, we show that UAC activates the LHb neurons as well as the periodontal proprioceptive pathway to provide excitatory input to the Vme and produce anxiety in rats. These findings provide a rationale for suppressing activity of the LHb to attenuate both the physical and psychological effects of TMD.

9.
Int J Surg Case Rep ; 53: 137-139, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30391739

RESUMO

INTRODUCTION: Rectal endometriosis is rare in women and imaging characteristics are similar with that of rectal cancer, which is one of the most common malignancies. PRESENTATION OF CASE: A 36 years old woman with a suspicious diagnosis of cervical carcinoma in a tertiary hospital visited our hospital, complaining about vaginal bleeding after copulation for six months, accompanying with constipation and diameter-thinning stool. Vaginal and cervical biopsy only showed chronic inflammation. Colonoscopy found a mass at the rectum 4 cm from the anus, but the biopsy showed different diagnoses. Partial resection was eventually operated and the final diagnosis was confirmed as rectal endometriosis. DISCUSSION: Rectal endometriosis is prone to be misdiagnosed as rectal cancer. Small specimen is sometimes insufficient to make a correct diagnosis. Extensive examination should be done to confirm the diagnosis and rash decision should never be encouraging. CONCLUSION: Rectal endometriosis should always be considered as one of the differential diagnoses in female who have a mass at the rectum. An adequate specimen should be obtained to confirm the histopathological diagnosis.

10.
Nanoscale Res Lett ; 13(1): 275, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30203173

RESUMO

Sodium-ion batteries have been widely used in energy storage owing to its high sodium content and low cost. This study proves that mesoporous silicon microspheres (MSMs) with the homogeneously distributed mesopores ranging from 1 to 10 nm can be used as anodes of NIBs. In situ magnesiothermic reduction of silicon oxide was carried out to synthesize the MSM samples. An anode in NIBs was tested, and it was observed that the MSMs sample which was calcined at 650 °C had a good rate performance of 160 mAh g-1 at 1000 mAg-1 and a high reversible capacity of 390 mAh g-1 at 100 mAg-1 after 100 cycles. Moreover, its long-term cycling performance was 0.08 mAh g-1 decay per cycle for 100 cycles, which was quite excellent. MSMs have high reversibility, good cycling performance, and excellent rate capability, which are related to its ultrafine particle size and mesoporous morphology.

11.
Int J Ophthalmol ; 11(3): 382-388, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29600170

RESUMO

AIM: To investigate a possible trigeminal proprioceptive-oculomotor neural pathway and explore possible synaptic connections between neurons in this pathway. Attempt to bring a new insight to mechanism of Marcus Gunn syndrome (MGS). METHODS: Anterograde and retrograde tract tracing was applied and combined with immunofluorescent stain in rats. After electrophysiological identifying mesencephalic trigeminal nucleus (Vme) neurons, intracellular injection of tracer was performed to trace axon trajectory. RESULTS: Following injections of anterograde tracers into the Vme, labeled terminals were observed ipsilateral in oculomotor and trochlear nuclei (III/IV), as well as in their premotor neurons in interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN). Combining with choline acetyltransferase (ChAT) immunofluorescent stain, it showed that Vme projecting terminals contact upon ChAT positive III/IV motoneurons under confocal microscope. By retrograde labeling premotor neurons of the III, it showed that Vme neuronal terminals contact with retrogradely labeled pre-oculomotor neurons in the INC/DN. Axons of intracellularly labeled Vme neurons that respond to electric stimuli of the masseter nerve traveled into the ipsilateral III. CONCLUSION: There may exist a trigeminal proprioceptive-oculomotor system neural circuit in the rat, which is probably related to vertical-torsional eye movements. Possible association of this pathway with MGS etiology was discussed.

12.
J Biomed Res ; 32(2): 136-144, 2018 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-29358565

RESUMO

Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke. Axon degeneration and demyelination can activate microglia; however, it is unclear whether early microglia activation can impair the function of white matter tracts and lead to injury. Rat corpus callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS + Rhodobacter sphaeroides (RS)-LPS that is a toll-like receptor 4 (TLR-4) antagonist. Functional changes reflected by the change of axon compound action potentials (CAPs) and the accumulation of ß-amyloid precursor protein (ß-APP) in CC nerve fibers. Microglia activation was monitored by ionized calcium binding adaptor-1 immunofluorescent stain, based on well-established morphological criteria and paralleled proportional area measurement. Input-output (I/O) curves of CAPs in response to increased stimuli were significantly downshifted in a dose-dependent manner in LPS (0.2, 0.5 and 1.0 µg/mL)-treated slices, implying that axons neurophysiological function was undermined. LPS caused significant ß-APP accumulation in CC tissues, reflecting the deterioration of fast axon transport. LPS-induced I/O curve downshift and ß-APP accumulation were significantly reversed by the pre-treatment or co-incubation with RS-LPS. RS-LPS alone did not change the I/O curve. The degree of malfunction was correlated with microglia activation, as was shown by the measurements of proportional areas. Function of CC nerve fibers was evidently impaired by microglia activation and reversed by a TLP-4 antagonist, suggesting that the TLP-4 pathway lead to microglia activation.

13.
Neurosci Bull ; 34(1): 85-97, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28534262

RESUMO

Injury to peripheral nerves can lead to neuropathic pain, along with well-studied effects on sensory neurons, including hyperexcitability, abnormal spontaneous activity, and neuroinflammation in the sensory ganglia. Neuropathic pain can be enhanced by sympathetic activity. Peripheral nerve injury may also damage sympathetic axons or expose them to an inflammatory environment. In this study, we examined the lumbar sympathetic ganglion responses to two rat pain models: ligation of the L5 spinal nerve, and local inflammation of the L5 dorsal root ganglion (DRG), which does not involve axotomy. Both models resulted in neuroinflammatory changes in the sympathetic ganglia, as indicated by macrophage responses, satellite glia activation, and increased numbers of T cells, along with very modest increases in sympathetic neuron excitability (but not spontaneous activity) measured in ex vivo recordings. The spinal nerve ligation model generally caused larger responses than DRG inflammation. Plasticity of the sympathetic system should be recognized in studies of sympathetic effects on pain.


Assuntos
Gânglios Simpáticos/patologia , Inflamação Neurogênica/etiologia , Dor/etiologia , Dor/patologia , Traumatismos dos Nervos Periféricos/complicações , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/etiologia , Ligadura/efeitos adversos , Macrófagos/patologia , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo
14.
Injury ; 48(2): 548-551, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27923475

RESUMO

BACKGROUND: The objective of this study was to compare the outcomes of pediatric femoral shaft fractures treated with titanium elastic nail (TEN) by pediatric orthopedists and non-pediatric orthopedists. METHODS: From May 2006 to June 2014, 88 children with femoral shaft fractures were randomized to operative stabilization either by pediatric orthopedists (Group A, 44 cases) or by non-pediatric orthopedists (Group B, 44 cases). Demographic data and clinical characteristics (age, sex, weight, fracture side and type, cause of injury, associated injuries and interval from injury to surgery) were comparable between the two groups before surgery. Peri-operative data, clinical and functional outcomes between the two groups were recorded. RESULTS: The mean follow-up period was 20.9±4.5months for Group A and 20.0±3.6months for Group B (P=0.356). There was no significant difference in the time to union, length of hospitalization, full weight-bearing time and TEN scores between the two groups (P=0.785, P=0.835, P=0.803, P=0.940, respectively). However, the mean operating time and radiation time was longer in Group B than in Group A (P=0.001 and P=0.047, respectively). Also, there was a trend for patients of Group B to have a higher rate of open reduction (P=0.047). When comparing the total complications, no significant difference existed between the groups (P=0.978). CONCLUSIONS: This study indicated that both pediatric and non-pediatric orthopedists provided satisfactory clinical and functional results in treating these common injuries.


Assuntos
Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas , Complicações Pós-Operatórias/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Radiografia , Pinos Ortopédicos , Criança , China , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/fisiopatologia , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Consolidação da Fratura , Humanos , Masculino , Duração da Cirurgia , Cirurgiões Ortopédicos , Pediatria , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Prospectivos , Resultado do Tratamento
15.
Shanghai Kou Qiang Yi Xue ; 25(4): 465-468, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27858072

RESUMO

PURPOSE: To investigate the effect of minocycline hydrochloride combined with Vitapex in treating senile chronic periodontal-endodontic combined lesions. METHODS: One hundred twenty patients with senile chronic periodontitis and endodontic lesions patients treated in our hospital between Jun.2012 to Jun.2014 were selected. They were divided into experimental group (n=60) and control group (n=60). Patients in the control group were given conventional root canal therapy, while patients in the experimental group were given Vitapex and minocycline hydrochloride. The clinical effect between two groups was compared. SPSS18.0 software package was used for statistical analysis. RESULTS: Compared with pre-treatment, the levels of IL-17, TNF-α and CRP in serum were decreased in two groups, but the levels in the experimental group were significantly lower than those in the control group(P<0.05). Compared with pre-treatment, PD, GI, BI, PLI were decreased in two groups, but the levels in the experimental group were significantly lower than those in the control group(P<0.05). The effective rate of experimental group was 83.33% and the control group was 68.33%, the difference was statistically significant (P<0.05). CONCLUSIONS: For chronic periodontitis and endodontic lesions, besides conventional root canal therapy, Vitapex combined with minocycline hydrochloride can significantly improve the clinical effect.


Assuntos
Antibacterianos/uso terapêutico , Hidróxido de Cálcio/uso terapêutico , Periodontite Crônica/terapia , Raspagem Dentária , Minociclina/uso terapêutico , Silicones/uso terapêutico , Humanos , Interleucina-17 , Materiais Restauradores do Canal Radicular/uso terapêutico , Tratamento do Canal Radicular , Fator de Necrose Tumoral alfa
16.
Sci Rep ; 6: 33710, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27641368

RESUMO

Various forms of oncogenic ALK proteins have been identified in various types of human cancers. While Crizotinib, an ALK inhibitor, has been found to be therapeutically useful against a subset of ALK(+) tumours, clinical resistance to this drug has been well recognized and the mechanism of this phenomenon is incompletely understood. Using the cellular thermal shift assay (CETSA), we measured the Crizotinib-ALK binding in a panel of ALK(+) cell lines, and correlated the findings with the ALK structure and its interactions with specific binding proteins. The Crizotinib IC50 significantly correlated with Crizotinib-ALK binding. The suboptimal Crizotinib-ALK binding in Crizotinib-resistant cells is not due to the cell-specific environment, since transfection of NPM-ALK into these cells revealed substantial Crizotinib-NPM-ALK binding. Interestingly, we found that the resistant cells expressed higher protein level of ß-catenin and siRNA knockdown restored Crizotinib-ALK binding (correlated with a significant lowering of IC50). Computational analysis of the crystal structures suggests that ß-catenin exerts steric hindrance to the Crizotinib-ALK binding. In conclusion, the Crizotinib-ALK binding measurable by CETSA is useful in predicting Crizotinib sensitivity, and Crizotinib-ALK binding is in turn dictated by the structure of ALK and some of its binding partners.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Expressão Gênica , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Crizotinibe , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Conformação Molecular , Mutação , Ligação Proteica , Inibidores de Proteínas Quinases/química , Pirazóis/química , Piridinas/química , RNA Interferente Pequeno/genética , Receptores Proteína Tirosina Quinases/química , Receptores Proteína Tirosina Quinases/metabolismo , Relação Estrutura-Atividade , beta Catenina/metabolismo
17.
J BUON ; 20(3): 800-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26214633

RESUMO

PURPOSE: Several clinical trials have suggested that adjuvant chemotherapy improves the survival of patients with resected gastric cancer, but the optimal time at which to initiate post-operative adjuvant chemotherapy has not been studied. This study investigated the association between time to adjuvant chemotherapy and survival in gastric cancer. METHODS: We retrospectively identified 266 patients with stage IB-IIIC gastric cancer who received fluorouracil-based adjuvant chemotherapy after radical gastrectomy. Overall survival (OS) was compared between patients grouped according to time from surgery to adjuvant chemotherapy (<45 and ≥45 days). The Cox proportional hazards model was used to analyze the effects of time to initiation of chemotherapy and other clinical covariates on survival. RESULTS: Of 266 patients, 141 (53%) started adjuvant chemotherapy within 45 days after surgery and 125 (47%) started adjuvant chemotherapy more than 45 days after surgery. The 3-year OS rates were 81.2 and 65.8% for patients starting chemotherapy within 45 days and after 45 days, respectively (p=0.006). Multivariate analysis identified early initiation of adjuvant chemotherapy, completion of the planned chemotherapy, and early-stage disease as favorable prognostic factors in terms of OS (p<0.05). Subgroup analysis suggested that starting chemotherapy within 45 days after surgery was associated with significant OS benefit compared with initiation of chemotherapy after 45 days from surgery in most subgroups. CONCLUSIONS: This retrospective analysis suggests that delaying adjuvant chemotherapy for longer than 45 days after surgery may be associated with poorer survival in patients with resected gastric cancer.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Fluoruracila/administração & dosagem , Gastrectomia , Neoplasias Gástricas/terapia , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento
18.
PLoS One ; 10(6): e0128540, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26075713

RESUMO

Prognostic models are generally used to predict gastric cancer outcomes. However, no model combining patient-, tumor- and host-related factors has been established to predict outcomes after radical gastrectomy, especially outcomes of patients without nodal involvement. The aim of this study was to develop a prognostic model based on the systemic inflammatory response and clinicopathological factors of resectable gastric cancer and determine whether the model can improve prognostic accuracy in node-negative patients. We reviewed the clinical, laboratory, histopathological and survival data of 1397 patients who underwent radical gastrectomy between 2007 and 2013. Patients were split into development and validation sets of 1123 and 274 patients, respectively. Among all 1397 patients, 545 had node-negative gastric cancer; 440 were included in the development set, 105 were included in the validation set. A prognostic model was constructed from the development set. The scoring system was based on hazard ratios in a Cox proportional hazard model. In the multivariate analysis, age, tumor size, Lauren type, depth of invasion, lymph node metastasis, and the neutrophil--lymphocyte ratio were independent prognostic indicators of overall survival. A prognostic model was then established based on the significant factors. Patients were categorized into five groups according to their scores. The 3-year survival rates for the low- to high-risk groups were 98.9%, 92.8%, 82.4%, 58.4%, and 36.9%, respectively (P < 0.001). The prognostic model clearly discriminated patients with stage pT1-4N0M0 tumor into four risk groups with significant differences in the 3-year survival rates (P < 0.001). Compared with the pathological T stage, the model improved the predictive accuracy of the 3-year survival rate by 5% for node-negative patients. The prognostic scores also stratified the patients with stage pT4aN0M0 tumor into significantly different risk groups (P = 0.004). Furthermore, the predictive value of this model was validated in an independent set of 274 patients. This model, which included the systemic inflammatory markers and clinicopathological factors, is more effective in predicting the prognosis of node-negative gastric cancer than traditional staging systems. Patients in the high-risk group might be good candidates for adjuvant chemotherapy.


Assuntos
Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Seguimentos , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Carga Tumoral
19.
Tumour Biol ; 36(1): 177-81, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25179837

RESUMO

The aim of this study was to investigate the relationship of the PARP-1 Val762Ala (rs1136410 T>C) polymorphism and the risk of lung cancer. A population-based case-control study of 373 lung cancer patients and 360 healthy control subjects (individually matched on age and gender) in a Chinese population was conducted. Genomic DNA was extracted by the phenol-chloroform method from the peripheral blood. PARP-1 Val762Ala polymorphism was identified using polymerase chain reaction-restriction fragments length polymorphism technique. After adjusting for age, tobacco smoking, gender, smoking index, and drinking status, logistic regression analysis demonstrated that CC genotype in PARP-1 Val762Ala polymorphism had an increased risk of lung cancer compared with TT genotype (OR = 1.59, 95 % CI = 1.03 ~ 2.50, P = 0.048), a statistically difference that still existed when merging CC and TC genotypes (OR = 1.56, 95 % CI = 1.03 ~ 2.44, P = 0.042). However, no obvious difference was found between TT and TC (OR = 1.54, 95 % CI = 0.96 ~ 2.44, P = 0.073). Subgroup analysis by histological type indicated that adenocarcinoma patients had higher frequencies of CC or TC+CC genotypes than healthy controls (CC: OR = 1.85, 95 % CI = 1.12 ~ 3.03, P = 0.015; TC+CC: OR = 1.67, 95 % CI = 1.06 ~ 2.63, P = 0.027, respectively), but no statistically significant difference within each genotype in squamous cell carcinoma or small cell lung cancer (all P > 0.05). Our findings support the view that PARP-1 Val762Ala polymorphism may contribute to an increased risk of lung cancer in the Chinese population, especially for adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Poli(ADP-Ribose) Polimerases/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adulto , Substituição de Aminoácidos , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerase-1 , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
20.
Appl Opt ; 53(23): 5117-22, 2014 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-25320919

RESUMO

We have demonstrated the passive Q-switching mode-locking operation in an erbium-doped fiber (EDF) laser by using topological insulator Bi(2)Se(3) deposited on fiber taper, whose damage threshold can be further increased by the large evanescent field interacting length. Due to the low saturation intensity, stable Q-switched mode-locked fiber lasers centered at 1562 nm can be generated at a pump power of 10 mW. The temporal and spectral characteristics for different pump strengths have also been investigated. To the best of our knowledge, it is the first time a Q-switched mode-locked EDF laser based on the fiber taper deposited by Bi(2)Se(3) was generated.


Assuntos
Bismuto/química , Érbio/química , Tecnologia de Fibra Óptica/instrumentação , Lasers de Estado Sólido , Selênio/química , Análise Espectral Raman/instrumentação , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento
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