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1.
ISA Trans ; 149: 394-408, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692975

RESUMO

Neural network (NN) controllers have shown great potential in solving complex control or decision-making tasks. However, most of the NN controllers either rely on the availability of large datasets or require dense interactions with the environment, which hinders their application in real systems. In this paper, we introduce a model-based reinforcement learning (MBRL) algorithm, aimed at realizing ultra-fast tuning of deep NN controller from a small sample set of real-world data. The algorithm uses Gaussian processes (GPs) to model the unknown dynamics of real system and updates controller parameters through stochastic gradient descent. By using particle-based method for long-term predictions, the algorithm can easily incorporate online state estimators and filters into controller learning, which is conductive to learning from systems with partially measurable states and stochastic control delay. We apply the algorithm to calibrate a deep NN controller for the path tracking of a full-size autonomous vehicle (AV). Simulation and field test results show that the deep NN controller can be well calibrated after only one interaction with the environment and can achieve similar tracking performance to optimization-based methods such as nonlinear model prediction control (NMPC) in various test scenarios by combining with a feed-forward pure pursuit (PP) controller.

2.
Front Oncol ; 14: 1395654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720809

RESUMO

Background: Cases of ALK-rearranged EGFR wild-type lung adenocarcinoma (LUAD) transforming into small cell lung cancer (SCLC) are rarely reported, and diagnosis is often delayed. The emergence of this transformation phenomenon is often regarded as a consequence of acquired resistance mechanisms. Case presentation: A 47-year-old male diagnosed with poorly differentiated adenocarcinoma of the right middle lung (pT2N2M0, stage IIIA) achieved a 46-month progression-free survival (PFS) following surgery and adjuvant chemotherapy. During routine follow-up, tumor recurrence and metastasis was detected. Genetic testing revealed ALK rearrangement and wild-type EGFR, prompting treatment with ALK-TKIs. In May 2023, abdominal CT scans showed significant progression of liver metastases and abnormal elevation of the tumor marker NSE. Immunohistochemical results from percutaneous liver biopsy indicated metastatic SCLC. Results: After resistance to ALK-TKIs and transformation to SCLC, the patient received chemotherapy combined with immunotherapy for SCLC, but the patient's disease progressed rapidly. Currently, the patient is being treated with albumin-bound paclitaxel in combination with oral erlotinib and remains stable. Conclusion: Histological transformation emerges as a compelling mechanism of resistance to ALK-TKIs, necessitating the utmost urgency for repeat biopsies in patients displaying disease progression after resistance. These biopsies are pivotal in enabling the tailor-made adaptation of treatment regimens to effectively counteract the assorted mechanisms of acquired resistance, thus optimizing patient outcomes in the battle against ALK-driven malignancies.

3.
Medicine (Baltimore) ; 103(17): e37759, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669410

RESUMO

This study aimed to identify risk factors for early death in elderly small cell lung cancer (SCLC) patients and develop nomogram prediction models for all-cause and cancer-specific early death to improve patient management. Data of elderly patients diagnosed with SCLC were extracted from the SEER database, then randomly divided into training and validation cohorts. Univariate and stepwise multivariable Logistic regression analyses were performed on the training cohort to identify independent risk factors for early death in these patients. Nomograms were developed based on these factors to predict the overall risk of early death. The efficacy of the nomograms was validated using various methods, including ROC analysis, calibration curves, DCA, NRI, and IDI. Among 2077 elderly SCLC patients, 773 died within 3 months, 713 due to cancer-specific causes. Older age, higher AJCC staging, brain metastases, and lack of surgery, chemotherapy, or radiotherapy increase the risk of all-cause early death, while higher AJCC staging, brain metastases, lung metastases, and lack of surgery, chemotherapy, or radiotherapy increase the risk of cancer-specific death (P < .05). These identified factors were used to construct 2 nomograms to predict the risk of early death. The ROC indicated that the nomograms performed well in predicting both all-cause early death (AUC = 0.823 in the training cohort and AUC = 0.843 in the validation cohort) and cancer-specific early death (AUC = 0.814 in the training cohort and AUC = 0.841 in the validation cohort). The results of calibration curves, DCAs, NRI and IDI also showed that the 2 sets of nomograms had good predictive power and clinical utility and were superior to the commonly used TNM staging system. The nomogram prediction models constructed in this study can effectively assist clinicians in predicting the risk of early death in elderly SCLC patients, and can also help physicians screen patients at higher risk and develop personalized treatment plans for them.


Assuntos
Neoplasias Pulmonares , Nomogramas , Programa de SEER , Carcinoma de Pequenas Células do Pulmão , Humanos , Masculino , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Idoso , Feminino , Fatores de Risco , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais , Fatores Etários , Curva ROC
4.
Oncol Lett ; 27(3): 96, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38288041

RESUMO

Origin recognition complexes (ORCs) are vital in the control of DNA replication and the progression of the cell cycle, however the precise function and mechanism of ORC6 in non-small cell lung cancer (NSCLC) is still not well understood. The present study used bioinformatics methods to assess the predictive significance of ORC6 expression in NSCLC. Moreover, the expression of ORC6 was further evaluated using reverse transcription-quantitative PCR and western blotting, and its functional significance in lung cancer was assessed via knockdown experiments using small interfering RNA. A significant association was demonstrated between the expression of ORC6 and the clinical features of NSCLC. In particular, elevated levels of ORC6 were significantly strongly correlated with an unfavorable prognosis. Multivariate analysis demonstrated that increased ORC6 expression independently contributed to the risk of overall survival (HR 1.304; P=0.015) in individuals diagnosed with NSCLC. Analysis of Kaplan-Meier plots demonstrated that ORC6 expression served as a valuable indicator for diagnosing and predicting the prognosis of NSCLC. Moreover, in vitro studies demonstrated that modified ORC6 expression had a significant impact on the proliferation, migration and metastasis of NSCLC cells. NSCLC cell lines (H1299 and mH1650) exhibited markedly higher ORC6 expression than normal lung cell lines. The results of the present study indicated a strong association between the expression of ORC6 and the clinicopathological characteristics of NSCLC, which suggested its potential as a reliable biomarker for predicting NSCLC. Furthermore, ORC6 may have important therapeutic implications in the management of NSCLC.

5.
Medicine (Baltimore) ; 102(45): e34877, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37960828

RESUMO

The aim of this study was to evaluate the difference in D-dimer (D-D) combined with the platelet lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before treatment in small cell lung cancer (SCLC) patients receiving first-line treatment and to analyze the efficacy and prognosis. We retrospectively collected the records of SCLC patients treated in our hospital from February 2019 to January 2023 and finally included 100 patients. A binary logistic regression analysis method was applied to analyze the relationship between D-D, PLR, and NLR and short-term efficacy. Univariate and multivariate Cox regression analyses were utilized to estimate the individual effect of plasma parameters on progression-free survival (PFS). The optimal cutoff values of D-D, PLR, and NLR for predicting survival outcome were determined by receiver operating characteristic curve analysis. Kaplan-Meier survival analysis was utilized to examine the correlation between D-D, PLR, and NLR the prognosis of SCLC patients. PLR was associated with a short-term curative effect in patients with SCLC (odds ratio: 0.326, 95% confidence interval [CI]: 0.135 0.790). Univariate Cox regression showed that D-D (hazard ratio [HR]: 0.495, 95% CI: 0.323-0.758), PLR (HR:0.420, 95% CI: 0.269-0.655) and NLR (HR: 0.407, 95% CI: 0.263-0.630) were associated with PFS in SCLC patients (P < .05). Multivariate Cox regression analysis showed that PLR (HR: 2.395, 95% CI: 1.468-3.906) and NLR (HR: 2.148, 95% CI: 1.319-3.499) correlated significantly with PFS (P < .05). The optimal cutoff values of D-D, PLR and NLR for predicting PFS were 0.88 mg/L (65.4% and 68.7%), 195.44 (61.5% and 81.2%) and 3.63 (63.5% and 81.2%), respectively, and the corresponding area under receiver (AUC) operating characteristic curve 0.691 (95% CI: 0.587-0.795), 0.721 (95% CI: 0.620-0.822) and 0.714 (95% CI: 0.614-0.815). When D-D was used in combination with PLR or NLR, the corresponding AUCs were 0.737 (95% CI: 0.640-0.835) and 0.761 (95% CI: 0.667-0.855). Pretreatment PLR is an independent predictor of short-term efficacy in SCLC patients. Pretreatment D-D, PLR and NLR are potential biochemical markers for predicting the prognosis of SCLC patients treated with first-line treatment. When D-D is combined with PLR and NLR, it shows stronger predictive ability.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/terapia , Neutrófilos , Estudos Retrospectivos , Linfócitos , Prognóstico , Plaquetas , Neoplasias Pulmonares/terapia
6.
Int J Mol Sci ; 24(10)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37240156

RESUMO

Growing resistant rice cultivars is the most effective strategy to control bacterial blight (BB), a devastating disease caused by Xanthomonas oryzae pv. oryzae (Xoo). Screening resistant germplasm and identifying resistance (R) genes are prerequisites for breeding resistant rice cultivars. We conducted a genome-wide association study (GWAS) to detect quantitative trait loci (QTL) associated with BB resistance using 359 East Asian temperate Japonica accessions inoculated with two Chinese Xoo strains (KS6-6 and GV) and one Philippine Xoo strain (PXO99A). Based on the 55K SNPs Array dataset of the 359 Japonica accessions, eight QTL were identified on rice chromosomes 1, 2, 4, 10, and 11. Four of the QTL coincided with previously reported QTL, and four were novel loci. Six R genes were localized in the qBBV-11.1, qBBV-11.2, and qBBV-11.3 loci on chromosome 11 in this Japonica collection. Haplotype analysis revealed candidate genes associated with BB resistance in each QTL. Notably, LOC_Os11g47290 in qBBV-11.3, encoding a leucine-rich repeat receptor-like kinase, was a candidate gene associated with resistance to the virulent strain GV. Knockout mutants of Nipponbare with the susceptible haplotype of LOC_Os11g47290 exhibited significantly improved BB resistance. These results will be useful for cloning BB resistance genes and breeding resistant rice cultivars.


Assuntos
Oryza , Xanthomonas , Estudo de Associação Genômica Ampla , Oryza/genética , Oryza/microbiologia , Genes de Plantas , Melhoramento Vegetal , Locos de Características Quantitativas , Bactérias/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Resistência à Doença/genética
7.
Oncol Lett ; 24(4): 356, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36168315

RESUMO

The evolutionary properties of organisms lead to the issue of targeted drug resistance. Numerous clinical trials have shown that tumor-associated macrophages (TAMs) in patients with lung cancer adversely affect the clinical efficacy of epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanism by which TAMs influence the tumor cell response to TKIs remains unclear. The aim of the present study was to investigate the influence of TAM-derived exosomes on the sensitivity of PC9 and HCC827 lung adenocarcinoma cells to the EGFR inhibitor gefitinib. Multiple cytokines were used to induce the differentiation of THP-1 human leukemia monocytes into macrophages in vitro. The obtained cells were identified as TAMs by cytomorphology and flow cytometry. Exosomes were extracted from the TAM culture supernatants and identified using electron microscopy and nanoparticle tracking analysis. Flow cytometry was used to examine the apoptosis of lung adenocarcinoma cells when treated with gefitinib and/or TAM-derived exosomes. In addition, western blotting was used to detect the expression of the key proteins of the AKT, ERK1/2 and STAT3 signaling pathways. TAM-derived exosomes were successfully obtained. The TAM-derived exosomes were shown to affect the proliferation and apoptosis of lung adenocarcinoma cells. Furthermore, the killing effect of gefitinib on the tumor cells was attenuated. The mechanism underlying the effects of the TAM-derived exosomes may be associated with reactivation of the AKT, ERK1/2 and STAT3 signaling pathways. In conclusion, the findings indicate that TAM-derived exosomes promote resistance to gefitinib in non-small cell lung cancer (NSCLC), and the mechanism may be associated with reactivation of the AKT, ERK1/2 and STAT3 signaling pathways. This study may serve as a reference in the exploration of alternative strategies for NSCLC following the development of resistance to EGFR-targeted drugs.

8.
Front Pediatr ; 10: 840617, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844729

RESUMO

Background: An increasing number of studies have suggested that vitamin D can be used to treat childhood asthma, but its clinical effects are still unclear. We conducted this meta-analysis to examine the latest estimates of the effectiveness and safety of using vitamin D to treat childhood asthma. Methods: The PubMed, The Cochrane Library, ScienceDirect, Embase, Scopus, Ovid MEDLINE, Web of Science, and Google Scholar databases were searched for randomized controlled trials (RCTs) describing vitamin D supplementation interventions for asthmatic children. Asthma exacerbation, vitamin D levels, the predicted percentage of forced expiratory volume in the first second (FEV1%) and adverse effects (AEs) were analyzed as the main outcome measures. Results: After screening, eight RCTs with 738 children were included. Compared with placebos, vitamin D supplementation had a stronger effect on serum vitamin D levels [mean difference (MD) = 13.51 (4.24, 22.79), p = 0.004]. The pooled results indicated that no significant changes were found between the groups in asthma control, as measured by adopting the following indicators: asthma exacerbation [risk ratio (RR) = 0.92 (0.68, 1.25), p = 0.60]; Childhood Asthma Control Test (CACT) scores [MD = 0.15 (-0.43, 0.74), p = 0.61]; hospitalizations for asthma exacerbation [RR = 1.20 (0.48, 2.96), p = 0.70]; acute care visits [RR = 1.13 (0.77, 1.65), p = 0.63]; steroid use [RR = 1.03 (0.41, 2.57), p = 0.95]; and fractional exhaled nitric oxide (FeNO) [MD =-3.95 (-22.87, 14.97), p = 0.68]. However, vitamin D supplementation might reduce the FEV1% [MD = -4.77 (-9.35, -0.19), p = 0.04] and the percentage of predicted forced vital capacity (FVC%) [MD =-5.01 (-9.99, -0.02), p = 0.05] in patients. Subgroup analysis revealed no difference in AEs between the two groups. Conclusions: Vitamin D supplementation significantly increased patients' serum vitamin D levels, but it had no benefit for asthma control. However, vitamin D supplementation might reduce patients' lung function. It is essential to systemically search for more large-scale, rigorous, and well-designed RCTs to fully confirm these conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021288838, PROSPERO CRD42021288838.

9.
Medicine (Baltimore) ; 101(49): e32217, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36626448

RESUMO

The prognosis of metastatic lung adenocarcinoma (MLUAD) varies greatly. At present, no studies have constructed a satisfactory prognostic model for MLUAD. We identified 44,878 patients with MLUAD. The patients were randomized into the training and validation cohorts. Cox regression models were performed to identify independent prognostic factors. Then, R software was employed to construct a new nomogram for predicting overall survival (OS) of patients with MLUAD. Accuracy was assessed by the concordance index (C-index), receiver operating characteristic curves and calibration plots. Finally, clinical practicability was examined via decision curve analysis. The OS time range for the included populations was 0 to 107 months, and the median OS was 7.00 months. Nineteen variables were significantly associated with the prognosis, and the top 5 prognostic factors were chemotherapy, grade, age, race and surgery. The nomogram has excellent predictive accuracy and clinical applicability compared to the TNM system (C-index: 0.723 vs 0.534). The C-index values were 0.723 (95% confidence interval: 0.719-0.726) and 0.723 (95% confidence interval: 0.718-0.729) in the training and validation cohorts, respectively. The area under the curve for 6-, 12-, and 18-month OS was 0.799, 0.764, and 0.750, respectively, in the training cohort and 0.799, 0.762, and 0.746, respectively, in the validation cohort. The calibration plots show good accuracy, and the decision curve analysis values indicate good clinical applicability and effectiveness. The nomogram model constructed with the above 19 prognostic factors is suitable for predicting the OS of MLUAD and has good predictive accuracy and clinical applicability.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Pesquisa , Nomogramas , Programa de SEER
10.
Accid Anal Prev ; 152: 105991, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33508697

RESUMO

High-level autonomous vehicles (AVs) are likely to improve the quality of children's travel to and from school (such as improve travel safety and increase travel mobility). These expected benefits will not be presented if parents are not willing to use AVs. Therefore, it is necessary to explore parents' intentions of using AVs to transport children to and from school (parents' intentions). This study has two primary aims: 1) Exploring parents' intentions and their potential determinants. 2) Making recommendations for manufacturers to develop and market AVs suitable for school travel based on the research results. Research results show that face consciousness with Chinese characteristics can significantly affect parents' intentions. Knowledge of AVs is the most significant factor in influencing parents' intentions. Perceived usefulness, attitude towards school travel in AVs, and perceived risk can significantly affect parents' intentions. The direct impact of perceived ease of use and public engagement on parents' intentions is not significant. Finally, this research could provide decision-making support for governments and manufacturers to formulate relevant policies and marketing strategies, promoting parents' acceptance of AVs.


Assuntos
Atitude , Tomada de Decisões , Intenção , Pais/psicologia , Robótica/tendências , Instituições Acadêmicas , Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/estatística & dados numéricos , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Oncol Lett ; 20(1): 868-876, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32566014

RESUMO

The tumor stromal microenvironment is an integral part of the occurrence and development of tumor. Cancer-associated fibroblasts (CAFs) are a key component of most tumor stromal microenvironments. The present study aimed to investigate the use of CAFs-targeted immunotherapy to fibroblast activation protein-α (FAP-α) expressed in CAFs. Recombinant adenoviral vectors containing the mouse FAP-α cDNA (rAd-FAP-α) were constructed. C57BL/6 mice were immunized with rAd-FAP-α infected dendritic cells (DCs) against FAP-α, which is overexpress in CAFs. The results demonstrated that mice vaccinated with rAd-FAP-α DCs gave rise to potent FAP-α-specific cytotoxic T lymphocytes capable of lysing Lewis lung cancer (LLC) CAFs. Furthermore, mice vaccinated with rAd-FAP-α-transduced DCs induced an effective therapeutic or protective antitumor immunity to LLC in a subcutaneous model, and prolonged overall survival time compared with mice vaccinated with the control recombinant adenovirus-transduced DCs (rAd-c DCs) or DCs alone. The results of the present study suggested that FAP-α, which is preferentially expressed in CAFs, may be considered as a potential target for killing or destroying CAFs within the tumor stromal microenvironment, and may be exploited to develop immunogenic tumor vaccines.

12.
Rice (N Y) ; 12(1): 93, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31853678

RESUMO

BACKGROUND: Sheath blight (ShB), caused by Rhizoctonia solani Kühn, is one of the most destructive rice diseases. Developing ShB-resistant rice cultivars represents the most economical and environmentally sound strategy for managing ShB. RESULTS: To characterize the genetic basis for ShB resistance in rice, we conducted association studies for traits related to ShB resistance, namely culm length (CL), lesion height (LH), and relative lesion height (RLH). Combined a single locus genome-wide scan and a multi-locus method using 2,977,750 single-nucleotide polymorphisms to analyse 563 rice accessions, we detected 134, 562, and 75 suggestive associations with CL, LH, and RLH, respectively. The adjacent signals associated with RLH were merged into 27 suggestively associated loci (SALs) based on the estimated linkage disequilibrium blocks. More than 44% of detected RLH-SALs harboured multiple QTLs/genes associated with ShB resistance, while the other RLH-SALs were putative novel ShB resistance loci. A total of 261 ShB resistance putative functional genes were screened from 23 RLH-SALs according to bioinformatics and haplotype analyses. Some of the annotated genes were previously reported to encode defence-related and pathogenesis-related proteins, suggesting that quantitative resistance to ShB in rice is mediated by SA- and JA-dependent signalling pathways. CONCLUSIONS: Our findings may improve the application of germplasm resources as well as knowledge-based ShB management and the breeding of ShB-resistant rice cultivars.

13.
Oncol Lett ; 18(2): 1840-1846, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423252

RESUMO

Tumor associated macrophages (TAMs) are a major type of inflammatory cell in a tumor microenvironment. Previous evidence has suggested that TAMs promote tumorigenesis, growth, invasion and metastasis, thereby affecting tumor metabolism. The mechanisms through which they affect the invasion and metastasis of lung cancer cells remain unclear. The present study investigated the effects and molecular mechanisms of TAMs on the proliferation, invasion and migration of lung adenocarcinoma A549 cells. Human mononuclear leukemia THP-1 cells were induced into TAMs. The morphological changes that occurred during the induction of the THP-1 cells were examined with a light microscope. Successful TAM formation was confirmed via flow cytometry. Proliferation, invasion and migration of the lung adenocarcinoma A549 cells were detected by EDU proliferation, scratch wound and Transwell invasion and migration assays, respectively. The expression levels of key proteins involved in the PI3K/AKT signaling pathway were detected by western blot analysis. It was identified that treatment with interleukin (IL)-4, IL-13 and Phorbol-12-myristate-13-acetate successfully induced THP-1 to form TAMs. The indirect coculture model of TAMs was established by Transwell chamber detection, and the proliferation, invasion and migration ability of lung adenocarcinoma A549 cells were enhanced. Western blot analysis indicated that the expression levels of phosphorylated (p)-PI3K and p-AKT proteins were significantly upregulated in the TAMs coculture group compared with that of the blank control group. In summary, the present study demonstrated that TAMs may promote the proliferation, invasion and migration of lung adenocarcinoma A549 cells in vitro, perhaps through the activation of the PI3K/AKT signaling pathway.

14.
Zhongguo Fei Ai Za Zhi ; 21(12): 912-917, 2018 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-30591099

RESUMO

Over the past decade, the management model of cancer patients has gradually shifted to individual mode based on molecular mutation detection. Epidermal growth factor receptor (EGFR) gene mutation is an important driving factor in non-small cell lung cancer (NSCLC). Compared with traditional chemotherapy, EGFR-targeted therapy shows significant safety and efficacy. However, not all patients with EGFR mutations are eligible for EGFR-targeted therapy, and different types of mutations often indicate different clinical outcomes, such as the sensitive mutations EGFR 19-Del, L858R, and the resistance mutation. In addition, the third-generation TKI drugs Osimertinib (AZD9291) and Rociletinib (CO-1686) have been developed to further benefit patients with primary TKI resistance caused by T790M mutation of EGFR. Therefore, detection of the EGFR mutation status of patients before treatment, and continuously monitoring the mutation of drug resistance genes during the treatment process is useful for the management of targeted drugs in NSCLC patients. In recent years, the rapid development of "liquid biopsy" technology has made it possible to use non-invasive methods to monitor drug resistance mutations in real time. In this paper, we reviewed the clinical application of various non-invasive detection techniques for EGFR mutations in NSCLC in different liquid samples.
.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , Mutação , Animais , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo
15.
Zhongguo Fei Ai Za Zhi ; 20(11): 775-780, 2017 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-29167008

RESUMO

In recent years, targeted therapy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) is the leading treatment modality for patients with advanced non-small cell lung cancer (NSCLC) and EGFR gene mutation. However, with the prolongation of the medication time, most of the patients appeared drug resistance. Tumor microenvironment is the internal environment for the survival and development of tumor cells. The immune response which mediated by immune cells, like regulatory T (Treg), dendritic cells, macrophages, fibroblasts, etc. And the programmed cell death receptor 1 (PD-1) with its ligand PD-1L/PD-2L may participate in the drug resistance of EGFR-TKIs. This review will elaborate the possible mechanism of the interaction of immune cells on EGFR-TKIs in the tumor microenvironment, in order to seek new targets, and further improve the anti-tumor efficacy and prolong the effective time of EGFR-TKIs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico
16.
Cancer Immunol Res ; 5(10): 908-919, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28851693

RESUMO

To understand why vaccine-activated tumor-specific T cells often fail to generate antitumor effects, we studied two α-fetoprotein-specific CD8+ T cells (Tet499 and Tet212) that had different antitumor effects. We found that Tet499 required high antigen doses for reactivation, but could survive persistent antigen stimulation and maintain their effector functions. In contrast, Tet212 had a low threshold of reactivation, but underwent exhaustion and apoptosis in the presence of persistent antigen. In vivo, Tet499 cells expanded more than Tet212 upon reencountering antigen and generated stronger antitumor effects. The different antigen responsiveness and antitumor effects of Tet212 and Tet499 cells correlated with their activation and differentiation states. Compared with Tet212, the population of Tet499 cells was less activated and contained more stem-like memory T cells (Tscm) that could undergo expansion in vivo The TCR signaling strength on Tet499 was weaker than Tet212, correlating with more severe Tet499 TCR downregulation. Weak TCR signaling may halt T-cell differentiation at the Tscm stage during immune priming and also explains why Tet499 reactivation requires a high antigen dose. Weak TCR signaling of Tet499 cells in the effector stage will also protect them from exhaustion and apoptosis when they reencounter persistent antigen in tumor lesion, which generates antitumor effects. Further investigation of TCR downregulation and manipulation of TCR signaling strength may help design cancer vaccines to elicit a mix of tumor-specific CD8+ T cells, including Tscm, capable of surviving antigen restimulation to generate antitumor effects. Cancer Immunol Res; 5(10); 908-19. ©2017 AACR.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/imunologia , Memória Imunológica , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Animais , Antígenos de Neoplasias/imunologia , Apoptose/imunologia , Modelos Animais de Doenças , Epitopos de Linfócito T/imunologia , Antígenos H-2/imunologia , Humanos , Camundongos , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Peptídeos/imunologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , alfa-Fetoproteínas/química , alfa-Fetoproteínas/imunologia
17.
J Environ Sci (China) ; 42: 9-18, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27090690

RESUMO

Guangzhou is the capital and largest city (land area: 7287 km(2)) of Guangdong province in South China. The air quality in Guangzhou typically worsens in November due to unfavorable meteorological conditions for pollutant dispersion. During the Guangzhou Asian Games in November 2010, the Guangzhou government carried out a number of emission control measures that significantly improved the air quality. In this paper, we estimated the acute health outcome changes related to the air quality improvement during the 2010 Guangzhou Asian Games using a next-generation, fully-integrated assessment system for air quality and health benefits. This advanced system generates air quality data by fusing model and monitoring data instead of using monitoring data alone, which provides more reliable results. The air quality estimates retain the spatial distribution of model results while calibrating the value with observations. The results show that the mean PM2.5 concentration in November 2010 decreased by 3.5 µg/m(3) compared to that in 2009 due to the emission control measures. From the analysis, we estimate that the air quality improvement avoided 106 premature deaths, 1869 cases of hospital admission, and 20,026 cases of outpatient visits. The overall cost benefit of the improved air quality is estimated to be 165 million CNY, with the avoided premature death contributing 90% of this figure. The research demonstrates that BenMAP-CE is capable of assessing the health and cost benefits of air pollution control for sound policy making.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Modelos Químicos , Recreação , Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , China , Cidades , Conservação dos Recursos Naturais/economia , Monitoramento Ambiental/economia , Monitoramento Ambiental/métodos , Política Ambiental , Humanos
18.
J Environ Sci (China) ; 41: 69-80, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26969052

RESUMO

This article describes the development and application of a streamlined air control and response modeling system with a novel response surface modeling-linear coupled fitting method and a new module to provide streamlined model data for PM2.5 attainment assessment in China. This method is capable of significantly reducing the dimensions required to establish a response surface model, as well as capturing more realistic response of PM2.5 to emission changes with a limited number of model simulations. The newly developed module establishes a data link between the system and the Software for Model Attainment Test-Community Edition (SMAT-CE), and has the ability to rapidly provide model responses to emission control scenarios for SMAT-CE using a simple interface. The performance of this streamlined system is demonstrated through a case study of the Yangtze River Delta (YRD) in China. Our results show that this system is capable of reproducing the Community Multi-Scale Air Quality (CMAQ) model simulation results with maximum mean normalized error<3.5%. It is also demonstrated that primary emissions make a major contribution to ambient levels of PM2.5 in January and August (e.g., more than 50% contributed by primary emissions in Shanghai), and Shanghai needs to have regional emission control both locally and in its neighboring provinces to meet China's annual PM2.5 National Ambient Air Quality Standard. The streamlined system provides a real-time control/response assessment to identify the contributions of major emission sources to ambient PM2.5 (and potentially O3 as well) and streamline air quality data for SMAT-CE to perform attainment assessments.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Monitoramento Ambiental/métodos , Modelos Teóricos , Material Particulado/análise , China , Tamanho da Partícula
19.
Cell Immunol ; 297(1): 46-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26140980

RESUMO

Transduction with recombinant, replication-defective adenoviral (rAd) vectors encoding a transgene is an efficient method for gene transfer into human dendritic cells (DCs). Livin is a good candidate for cancer immunotherapy since it is overexpressed in most common human cancers, poorly expressed in most normal adult tissues. Two splicing variants of livin, designated livin α and livin ß, have been identified. In this study, we used human livin α recombinant adenovirus (rAd-hlivin α) to transduced DCs. We found that DCs transduced with rAd-hlivin α (rAd-hlivin α DCs) could effectively induce human livin α specific cytotoxic T lymphocytes (CTL) in vitro against various tumor cell lines.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Citotoxicidade Imunológica/imunologia , Células Dendríticas/imunologia , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenoviridae , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Vetores Genéticos , Células HEK293 , Humanos , Imunoterapia/métodos , Proteínas Inibidoras de Apoptose/metabolismo , Interferon gama/biossíntese , Ativação Linfocitária/imunologia , Células MCF-7 , Proteínas de Neoplasias/metabolismo , Neoplasias/imunologia , Isoformas de Proteínas/genética , Transdução Genética/métodos
20.
J Environ Sci (China) ; 29: 178-88, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25766027

RESUMO

Due to the increasingly stringent standards, it is important to assess whether the proposed emission reduction will result in ambient concentrations that meet the standards. The Software for Model Attainment Test-Community Edition (SMAT-CE) is developed for demonstrating attainment of air quality standards of O3 and PM2.5. SMAT-CE improves computational efficiency and provides a number of advanced visualization and analytical functionalities on an integrated GIS platform. SMAT-CE incorporates historical measurements of air quality parameters and simulated air pollutant concentrations under a number of emission inventory scenarios to project the level of compliance to air quality standards in a targeted future year. An application case study of the software based on the U.S. National Ambient Air Quality Standards (NAAQS) shows that SMAT-CE is capable of demonstrating the air quality attainment of annual PM2.5 and 8-hour O3 for a proposed emission control policy.


Assuntos
Poluentes Atmosféricos/química , Ozônio/química , Tamanho da Partícula , Material Particulado/química
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