Publications by authors named "Haihong Yang"

37 Publications

Degradation models, structure, rheological properties and protective effects on erythrocyte hemolysis of the polysaccharides from Ribes nigrum L.

Int J Biol Macromol 2020 Dec 21;165(Pt A):738-746. Epub 2020 Sep 21.

College of Art and Science, Northeast Agricultural University, Harbin 150030, China. Electronic address:

The polysaccharides from blackcurrant (Ribes nigrum L.) fruits were degraded by ultrasonic irradiation. Results showed that viscosity-average molecular weight decreased with increasing ultrasonic time or power. The degradation was fitted to the second-order kinetics model and midpoint chain scission model. Gas chromatographic analysis demonstrated that the native polysaccharide and three degraded polysaccharides were composed of the same monosaccharides but in different ratios. Fourier transform infrared and nuclear magnetic resonance spectroscopic analyses revealed the presence of α-, β-pyranose rings and the same six sugar residues in the four blackcurrant polysaccharides. Compared to the native polysaccharide, three degraded polysaccharides displayed better rheological properties and stronger protective effects against erythrocyte hemolysis. Collectively, the results support the potential utility of blackcurrant polysaccharides as natural antioxidants.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.09.093DOI Listing
December 2020

Circularized blocker-displacement amplification for multiplex detection of rare DNA variants.

Chem Commun (Camb) 2020 Oct;56(82):12331-12334

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, P. R. China.

A superselective isothermal amplification technique, termed circularized blocker-displacement amplification, was developed for multiplex analysis of rare DNA variants.
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http://dx.doi.org/10.1039/d0cc05283cDOI Listing
October 2020

Characterization and inhibitory activities on α-amylase and α-glucosidase of the polysaccharide from blue honeysuckle berries.

Int J Biol Macromol 2020 Nov 30;163:414-422. Epub 2020 Jun 30.

College of Art and Science, Northeast Agricultural University, Harbin 150030, China; National-Local Joint Engineering Research Center for Development and Utilization of Small Fruits in Cold Regions, 150030, China. Electronic address:

An acidic heteropolysaccharide HEP-2 was obtained from blue honeysuckle berry extracts after purification using Sepharose 6B and Sephadex G-200 column chromatography. The molecular weight of HEP-2, determined with high-performance gel permeation chromatography, was 3.01 × 10 Da. Fourier transform infrared spectroscopy, gas chromatography and nuclear magnetic resonance analyses revealed the presence of α-, β-pyranose ring and six sugar residues in HEP-2. Amorphous aggregates of HEP-2 with irregular shape and lacking the triple helical structure were detected using the Congo red test, scanning electron and atomic force microscopy, and X-ray diffraction studies. Rheological characterization showed typical shear-thinning behavior and viscoelastic property of the polysaccharide. HEP-2 exerted significant inhibitory effects on α-amylase and α-glucosidase and displayed competitive inhibition kinetics. The collective results support the potential utility of HEP-2 as a hypoglycemic agent for enzyme-targeted treatment of diabetes or functional food.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.06.267DOI Listing
November 2020

A study on different therapies and prognosis-related factors for brain metastases in lung adenocarcinoma patients with driver mutation.

Clin Exp Metastasis 2020 06 30;37(3):391-399. Epub 2020 Apr 30.

Department of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, 151 Yanjiang Road, Guangzhou, 510120, China.

Brain metastases (BMs) are frequently occurred in lung adenocarcinoma with driver mutation. There is a need to explore multi-discipline treatments and prognostic factors in those patients with most frequent driver mutations: EGFR mutation and ALK fusion. In the retrospective study, different therapies and prognostic factors were compared between EGFR and ALK-driven lung adenocarcinoma with BMs. 516 patients with EGFR mutation and 76 with ALK fusion were screened for this study, 303 (58.7%) and 34 (44.7%) had BM respectively. In multivariate analyses, the pretreatment factors including delayed BMs and asymptomatic BMs, treatment strategies including the first-generation tyrosine kinase inhibitor (TKI) and cranial radiotherapy (RT) treatment, were associated with much better OS in EGFR mutation patients. Moreover, we found EGFR-mutation patients receiving erlotinib would achieve better survival than those receiving gefitinib (P = 0.032). However, BM patients with ALK fusion treated by only the first generation TKI (HR = 0.23, P = 0.036) or cranial RT (HR = 0.12, P = 0.003), had better OS. After balancing of baseline characteristics of the two groups, there was no significant difference in the survival between BM patients with EGFR mutation and ALK fusion. And only cranial RT was associated with better survival in those patients (HR = 0.52, P < 0.001). In the BM patients of lung adenocarcinoma with driver mutation, TKI underlie the therapy strategies, but cranial RT still plays an important role while receiving the first generation TKI.
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http://dx.doi.org/10.1007/s10585-020-10026-2DOI Listing
June 2020

Stochastic DNA Dual-Walkers for Ultrafast Colorimetric Bacteria Detection.

Anal Chem 2020 04 20;92(7):4990-4995. Epub 2020 Mar 20.

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China.

Rapid, sensitive, and reliable pathogen detection is growing in importance in human health and safety. In this work, we report a stochastic DNA dual-walker-based colorimetric biosensor for bacterial detection. In the presence of target bacteria, two kinds of released multiple walking strands are allowed for continuous walking on the Au nanoparticle (AuNP)-based 3D track, resulting in destabilized aggregation of AuNP-based probes. The induced color change from red to blue can serve as an analytical signal for colorimetric detection of target bacteria. We demonstrated that this mothed enables sensitive and specific bacterial detection within 15 min due to its ultrafast reaction kinetics and sensitive color change, showing a linear response ranging from 10 to 10 CFU/mL with a limit of detection of 1 CFU/mL. Moreover, we also realized analysis of practical samples using this colorimetric biosensor. Given its features of rapid, sensitive, specific, and reliable analysis, our stochastic dual-walker-based colorimetric biosensor shows much promise in point-of-care testing for bacteria detection.
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http://dx.doi.org/10.1021/acs.analchem.9b05149DOI Listing
April 2020

Genetic alteration profile of -mutant resected IIB-IIIA stage NSCLC and correlation to clinical outcomes.

Transl Lung Cancer Res 2019 Dec;8(6):838-846

Department of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.

Background: Genetic alteration profile of epidermal growth factor receptor () mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out.

Methods: Clinicopathological and follow-up information were collected for 99 -mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform.

Results: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0-12). and were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of (P=0.021), (P=0.002), (P<0.001), (P=0.015), (P=0.042), (P=0.006), and wildtype (P=0.032), (P=0.012), (P=0.035) were independent risk factors for the recurrence of resected mutant NSCLC.

Conclusions: and was the most common concurrent mutant driver gene. Mutations of , and wildtype were independent risk factors for the recurrence of resected mutant NSCLC.
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http://dx.doi.org/10.21037/tlcr.2019.10.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976375PMC
December 2019

Rack1 Controls Parallel Fiber-Purkinje Cell Synaptogenesis and Synaptic Transmission.

Front Cell Neurosci 2019 17;13:539. Epub 2019 Dec 17.

Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, China.

Purkinje cells (PCs) in the cerebellum receive two excitatory afferents including granule cells-derived parallel fiber (PF) and the climbing fiber. Scaffolding protein Rack1 is highly expressed in the cerebellar PCs. Here, we found delayed formation of specific cerebellar vermis lobule and impaired motor coordination in PC-specific Rack1 conditional knockout mice. Our studies further revealed that Rack1 is essential for PF-PC synapse formation. In addition, Rack1 plays a critical role in regulating synaptic plasticity and long-term depression (LTD) induction of PF-PC synapses without changing the expression of postsynaptic proteins. Together, we have discovered Rack1 as the crucial molecule that controls PF-PC synaptogenesis and synaptic plasticity. Our studies provide a novel molecular insight into the mechanisms underlying the neural development and neuroplasticity in the cerebellum.
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http://dx.doi.org/10.3389/fncel.2019.00539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927999PMC
December 2019

Predictive and prognostic value of phosphorylated c-KIT and PDGFRA in advanced non-small cell lung cancer harboring ALK fusion.

Oncol Lett 2019 Mar 25;17(3):3071-3076. Epub 2019 Jan 25.

Department of Thoracic Oncology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.

Secondary gene amplification leads to tyrosine kinase inhibitor resistance in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC). The presence of the 4q12 amplicon causes the activation of downstream mast/stem cell growth factor receptor Kit (c-Kit) or platelet-derived growth factor receptor α (PDGFRA) signaling pathways. Therefore, in the present study, the association between the functional proteins phosphorylated c-Kit (p-c-Kit) and phosphorylated PDGFRA (p-PDGFRA) and the prognosis of ALK fusion NSCLC was investigated. Advanced stage NSCLC samples with ALK fusion were tested for their p-c-Kit and p-PDGFRA content by immunohistochemical staining, and for its association with crizotinib efficacy and the survival of the patients. Of 64 eligible ALK-positive patients with NSCLC, 30 (46.9%) were p-c-Kit-positive and 10 (15.7%) were p-PDGFRA-positive. Brain metastases were more common in ALK-positive cases that were p-PDGFRA-positive compared with those who were p-PDGFRA-negative. ALK-positive patients treated with crizotinib, who exhibited high levels of p-c-Kit had significantly lower progression-free survival times than those with low levels. In addition, the patients with high levels of p-c-Kit exhibited lower overall survival times than those with low levels. Furthermore, multivariate analysis indicated that high levels of p-c-Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time. However, no statistically significant difference was observed in the survival of patients with different p-PDGFRA levels. p-PDGFRA was more frequently expressed in the ALK-positive cases with brain metastasis. c-Kit signaling activation may be associated with poor efficacy of crizotinib and poor prognosis in advanced ALK fusion NSCLC.
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http://dx.doi.org/10.3892/ol.2019.9972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396115PMC
March 2019

Opposite regulation of Wnt/β-catenin and Shh signaling pathways by Rack1 controls mammalian cerebellar development.

Proc Natl Acad Sci U S A 2019 03 14;116(10):4661-4670. Epub 2019 Feb 14.

Department of Neurobiology, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China;

The development of the cerebellum depends on intricate processes of neurogenesis, migration, and differentiation of neural stem cells (NSCs) and progenitor cells. Defective cerebellar development often results in motor dysfunctions and psychiatric disorders. Understanding the molecular mechanisms that underlie the complex development of the cerebellum will facilitate the development of novel treatment options. Here, we report that the receptor for activated C kinase (Rack1), a multifaceted signaling adaptor protein, regulates mammalian cerebellar development in a cell type-specific manner. Selective deletion of Rack1 in mouse NSCs or granule neuron progenitors (GNPs), but not Bergmann glial cells (BGs), causes severe defects in cerebellar morphogenesis, including impaired folia and fissure formation. NSCs and GNPs lacking Rack1 exhibit enhanced Wnt/β-catenin signaling but reduced Sonic hedgehog (Shh) signaling. Simultaneous deletion of β-catenin in NSCs, but not GNPs, significantly rescues the mutant phenotype. Interestingly, Rack1 controls the activation of Shh signaling by regulating the ubiquitylation and stability of histone deacetylase 1 (HDAC1)/HDAC2. Suppression of HDAC1/HDAC2 activity in the developing cerebellum phenocopies the mutant. Together, these results reveal a previously unknown role of Rack1 in controlling mammalian cerebellar development by opposite regulation of Wnt/β-catenin and Shh signaling pathways.
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http://dx.doi.org/10.1073/pnas.1813244116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410857PMC
March 2019

Nicotine enhances store‑operated calcium entry by upregulating HIF‑1α and SOCC components in non‑small cell lung cancer cells.

Oncol Rep 2018 Oct 17;40(4):2097-2104. Epub 2018 Jul 17.

State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.

Store‑operated calcium entry (SOCE) is critical for regulating the proliferation and metastasis of various cancer types. The present study aimed to investigate the role of SOCE on nicotine‑promoted proliferation of non‑small cell lung cancer (NSCLC) A549 cells. Cell proliferation was evaluated by BrdU incorporation assay. The SOCE and basal [Ca2+]i in NSCLC A549 cells were determined using Fura‑2 fluorescence microscopy. The mRNA and protein expression levels were determined by real‑time quantitative PCR and western blotting, respectively. The results demonstrated that, in A549 cells, the detectable store‑operated calcium channel (SOCC) components were TRPC proteins 1, 3, 4 and 6 and Orail, among which TRPC1, TRPC6 and Orai1 are expressed at relatively high levels with TRPC3 and TRPC4 at relatively low levels. Nicotine upregulated the mRNA and protein expression of TRPC1, TRPC6 and Orai1, increased basal [Ca2+]i and enhanced SOCE. Promotion of cell proliferation but not migration was observed in the nicotine‑treated cells, which was inhibited by SOCE inhibitor SKF‑96365. Furthermore, nicotine upregulated HIF‑1α expression in the A549 and NCI‑H292 cells. Silencing of HIF‑1α abrogated the increases in TRPCs and Orail and reversed the increases in basal [Ca2+]i and SOCE. Meanwhile, suppression of proliferation was observed in cells following HIF‑1α silencing. In conclusion, the results indicate that nicotine promotes lung cancer cell proliferation likely by upregulating HIF‑1α and SOCC components and therefore enhancing SOCE and increasing basal [Ca2+]i.
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http://dx.doi.org/10.3892/or.2018.6580DOI Listing
October 2018

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer.

Genes Chromosomes Cancer 2018 04 30;57(4):211-220. Epub 2018 Jan 30.

State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, 510120, China.

Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors. In this study, we developed a next-generation sequencing (NGS)-based test for the detection of clinically relevant mutations in ctDNA and evaluated the feasibility of using this ctDNA NGS-based assay as an alternative to tissue genotyping. Tissue and matched blood samples were obtained from 72 patients with advanced nonsmall cell lung cancer (NSCLC). NGS-based testing was performed using plasma cell-free DNA (cfDNA) samples of all 72 patients as well as tumor DNA samples of 46 patients. Of the remaining 26 patients, tDNA was tested by amplification refractory mutation system PCR (ARMS-PCR) because of insufficient tissue sample or quality for NGS. Of the 46 patients who had tDNA and cfDNA NGS performed, we found 20 patients were concordant between tDNA and ctDNA alterations and 21 sample pairs were discordant because of additional alterations found in tDNA. Considering all clinically relevant alterations, the concordance rate between tDNA and ctDNA alterations was 54.9% with a sensitivity of 53.2% and a specificity of 75.0%. Our findings demonstrate that targeted NGS using cfDNA is a feasible approach for rapid and accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.
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http://dx.doi.org/10.1002/gcc.22522DOI Listing
April 2018

Erlotinib intercalating pemetrexed/cisplatin versus erlotinib alone in Chinese patients with brain metastases from lung adenocarcinoma: a prospective, non-randomised, concurrent controlled trial (NCT01578668).

ESMO Open 2017 7;2(Suppl 1):e000112. Epub 2017 Mar 7.

Department of Pharmacy, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: Erlotinib has a synergistic effect with pemetrexed for treating non-squamous non-small-cell lung cancer. We investigated the efficacy and safety of erlotinib (E) in combination with pemetrexed/cisplatin (E-P) in Chinese patients with lung adenocarcinoma with brain metastases.

Design: Patients who were erlotinib-naïve or pemetrexed-naïve were assigned in parallel to receive either E or E-P. The primary endpoint was the intracranial overall response rate (ORRi).

Results: Sixty-nine patients with lung adenocarcinoma with brain metastases received E (n=35) or E-P (n=34) from January 2012 to November 2014. Demographics and patient characteristics were well balanced between the two groups, including epidermal growth factor receptor () status, sex, age, smoking status, Eastern Cooperative Oncology Group (ECOG) performance status, brain metastases and number of prior treatments. ORRi in the E-P arm was superior to that in the E arm (79% vs 48%, p=0.008). Compared with E as the first-line treatment, E-P was associated with better intracranial progression-free survival (PFSi, median: 9 vs 2 months, p=0.027) and systemic PFS (median: 8 vs 2 months, p=0.006). The most frequent E-related adverse events were higher in the combination arm. No new safety signals were detected. The side effects were tolerable, and there were no drug-related deaths.

Conclusion: Our study suggests that the E-P combination may be effective in Chinese patients with lung adenocarcinoma with brain metastases, with improved PFS in treatment-naïve patients. Toxicities are tolerable, and there are more E-related side effects.
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http://dx.doi.org/10.1136/esmoopen-2016-000112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682358PMC
March 2017

Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.

FASEB J 2017 10 13;31(10):4347-4358. Epub 2017 Jun 13.

Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing, China;

It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX) neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1 mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.
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http://dx.doi.org/10.1096/fj.201700216RRDOI Listing
October 2017

Comparison of detection methods and follow-up study on the tyrosine kinase inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion rearrangement.

BMC Cancer 2016 08 4;16:599. Epub 2016 Aug 4.

Department of Pathology, the First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiangxi Road, Guangzhou, 510120, China.

Background: The screening of ROS proto-oncogene 1, receptor tyrosine kinase(ROS1) fusion rearrangement might be potentially beneficial for an effective therapy against non-small cell lung cancer (NSCLC). However, the three main ROS1 rearrangement detection methods have limitations, and no routine protocol for the detection of ROS1 rearrangement in NSCLC is available. In this study, our aims were to compare immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in their ability to detect ROS1 rearrangement in NSCLC, and discuss the clinical characteristics and histopathology of the patients with ROS1 rearrangement. Moreover, the effects of tyrosine kinase inhibitors (TKIs) therapy on the patients with ROS1 rearrangement and advanced stage disease (III b-IV) were investigated.

Methods: Patients with a previously diagnosed NSCLC were recruited in this study from November 2013 to October 2015. IHC was performed using the D4D6 monoclonal antibody (mAb) in an automatic IHC instrument, while FISH and qRT-PCR were carried out to confirm the IHC results. FISH and qRT-PCR positive cases underwent direct sequencing. After detection, patients with advanced ROS1 rearranged NSCLC had received TKI therapy.

Results: Two hundred and thirty-eight patients were included in this study. ROS1 rearrangement was detected in 10 patients. The concordant rate of FISH and qRT-PCR results was 100 %, while in the FISH and IHC results high congruence was present when IHC showed a diffusely (≥60 % tumor cells) 2-3+ cytoplasmic reactivity pattern. Patients harboring ROS1 rearrangement were mostly young (8/10), females (7/10) and non-smokers (7/10) with adenocarcinoma (10/10) and acinar pattern. Most of their tumor were in intermediate grade (6/8). Among these 10 patients, three of them in stage IV with ROS1 rearrangement gained benefits from ROS1 TKI therapy.

Conclusions: IHC, FISH and qRT-PCR can reliably detect ROS1 rearrangement in NSCLC, while IHC can be used as a preliminary screening tool. These results supported the efficacy of ROS1 TKI therapy in treating advanced NSCLC patients with ROS1 rearrangement.
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http://dx.doi.org/10.1186/s12885-016-2582-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973062PMC
August 2016

Evaluation on efficacy and safety of the addition of X-knife therapy to gefitinib in NSCLC patients with symptomatic brain metastases.

Oncotarget 2017 Aug 6;8(34):57470-57476. Epub 2016 Jul 6.

Department of oncology, Guangdong 999 Brain Hospital, Guangzhou, China.

Background: Stereotactic radiosurgery (SRS) is a widely used therapy for brain metastases(BMs) in Non-small cell lung cancer(NSCLC). However, its role in symptomatic patients with EGFR mutation remains unclear. We have retrospectively reviewed the clinical data of patients with symptomatic BMs whom received SRS as a salvage approach and concurrent gifitinib therapy.

Methods: Seven patients with primary NSCLC, symptomatic BMs, and EGFR mutation were identified in a retrospective review of patients treated with SRS using X-knife at Guangdong 999 Brain Hospital between 1 January 2012 and 31 August 2014. The median follow-up of these patients was 16 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain, and critical brain structures. Toxicities and complications were identified by clinical records.

Results: SRS(X-knife) was selected to be performed on seven patients (two males and five females) diagnosed with NSCLC and EGFR mutation due to the presence of encephaledema, compression of ventricles, or other complications. Neurological symptoms (such as paresis, aphasia, sensory and visual disturbances) were not present in any patients before or after SRS treatment, and the postoperative Karnofsky performance status(KPS) was improved in all patients. Median overall survival(OS) was 16 months and median progression free survival(PFS) was 10 months.

Conclusions: The improvement of KPS and survival were reliable by SRS(X-knife) with concurrent gifitinib therapy in NSCLC patients with symptomatic BMs, and EGFR mutation. Given the small sample size, further prospective studies with a greater number of patients are warranted to confirm our results.
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http://dx.doi.org/10.18632/oncotarget.10420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593658PMC
August 2017

Assessment of gene fusions in lung cancer using the differential expression and exon integrity methods.

Oncol Lett 2016 Mar 27;11(3):1651-1656. Epub 2016 Jan 27.

Department of Thoracic Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.

Anaplastic lymphoma kinase (ALK) gene fusion is a driving mutation underlying the development of non-small cell lung cancer (NSCLC). Accurate detection of ALK fusion is critical for the use of ALK inhibitors in the treatment of NSCLC. Commonly utilized methods for ALK detection include fluorescence hybridization (FISH) and immunohistochemistry (IHC). However, these methods are time-consuming and costly. In the present study, a method for assessing ALK gene fusion based on the differential expression levels of the ALK kinase and non-kinase domains was developed and evaluated, with the aim of providing a convenient and reliable method for the detection of fusion. In addition, another method was established to determine the integrity of exons 19-20 and 20-21 of ALK, two genomic loci that are typically broken in ALK fusions. These novel methods were applied to detect fusion in 100 NSCLC patients, and were compared with IHC and FISH methods. The novel methods developed in the present study successfully detected ALK fusions in 10 samples. The concordances between the novel methods and IHC and FISH were 100%. Furthermore, the differential expression method was able to detect ALK fusions in cell-free urine samples, which was advantageous over FISH and IHC. The novel methods developed in the present study are cost-effective and easy to perform, and may provide simple and convenient techniques for the clinical assessment of ALK fusions, facilitating the use of targeted therapy for NSCLC.
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http://dx.doi.org/10.3892/ol.2016.4157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774594PMC
March 2016

Improving Selection Criteria for ALK Inhibitor Therapy in Non-Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry.

Am J Surg Pathol 2016 May;40(5):697-703

Departments of *Thoracic Surgery ‡Oncology §Pathology, The First Affiliated Hospital of Guangzhou Medical University †Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou, Guangdong Province, P.R. China.

Lung cancer is often diagnosed by molecular markers for prediction and treatment. To date, the golden standard for detection of anaplastic lymphoma kinase (ALK) rearrangements is fluorescence in situ hybridization (FISH). We performed a pooled-data analysis on the diagnostic operating characteristics of immunohistochemistry (IHC) assay on non-small cell lung cancer (NSCLC). We searched Embase, Pubmed, and Springer databases. The results of IHC were evaluated using a modified H-score. We used a 2-level bivariate meta-analysis following a random effect model to summarize sensitivity and specificity and fit hierarchical summary receiver-operating characteristic curves. We also performed sensitivity analysis using different antibodies to investigate potential heterogeneity. Twelve studies consisting of a total of 3754 NSCLC specimens were analyzed. When we defined 1+/2+/3+, 2+/3+, and 3+ as ALK positive, we found the sensitivities to be 99% (95% confidence interval [CI], 97%-100%), 86% (95% CI, 73%-93%), and 56% (95% CI, 36%-74%) and the specificities to be 98% (95% CI, 95%-99%), 99% (95% CI, 99%-100%), and 100% (95% CI, 100%-100%), respectively. We demonstrated that when defining 3+ as positive and 0 as negative the sensitivity was 99% and specificity was 100%. In our sensitivity analysis, we found the sensitivity of D5F3 and 5A4 antibodies to be much higher than that of ALK1. We concluded that IHC scores 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors.
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http://dx.doi.org/10.1097/PAS.0000000000000604DOI Listing
May 2016

Synthesis of Bimetallic Ni-Cr Nano-Oxides as Catalysts for Methanol Oxidation in NaOH Solution.

J Nanosci Nanotechnol 2015 May;15(5):3743-9

Bimetallic Ni-Cr nano-oxide catalysts were synthesized by thermal decomposition method and were investigated as the anode electrocatalysts for the oxidation of methanol. The catalysts were characterized by X-ray diffraction and transmission electron microscopy. The electroactivity of the catalysts towards methanol oxidation in a solution containing 0.25 M NaOH and 1.0 M MeOH was examined using cyclic voltammetry and chronoamperometry. The results indicate that a mixture of rhombohedral-structured NiO and Cr2O3 nanocrystals generated at the calcination temperature of 500-700 degrees C while octahedral-structured spinel NiCr2O4 formed at higher temperature. The influence of metallic molar ratio on the electrocatalytic performance of the catalysts was studied. The Ni-Cr nano-oxides prepared at comparatively low temperature displayed significantly higher catalytic activity and durability in alkaline solution toward electrooxidation of methanol compared with the pure nano NiO. The results indicate a synergy effect between NiO and Cr2O3 enhancing the electrocatalytic properties of the bimetallic Ni-Cr nano-oxide catalysts. Meanwhile, NiCr2O4 hardly increased the activity and durability of the catalyst. In addition, the Ni-Cr catalyst also exhibited excellent stability and good reproducibility. Therefore, Ni-Cr nano-oxide catalyst may be a suitable and cheap electrocatalyst for methanol oxidation in alkaline medium.
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http://dx.doi.org/10.1166/jnn.2015.9528DOI Listing
May 2015

Prognostic value of ERCC1 mRNA expression in non-small cell lung cancer, breast cancer, and gastric cancer in patients from Southern China.

Int J Clin Exp Pathol 2014 1;7(12):8312-21. Epub 2014 Dec 1.

Ningbo University School of Medicine Ningbo, China.

Background: Excision repair cross complementation group 1 (ERCC1) is a nucleotide excision repair pathway gene which provides protection against platinum-based chemotherapy-induced DNA damage.

Methods: ERCC1 mRNA expression was quantified by quantitative real-time reverse-transcription PCR in paraffin-embedded non-small cell lung cancer (NSCLC; n = 357), gastric cancer (n = 106), and breast cancer (n = 363) tissues. Survival curves were generated by Kaplan-Meier analysis; Cox proportional multivariate regression analysis was applied.

Results: ERCC1 mRNA expression was significantly higher in breast cancer than gastric cancer or NSCLC (both P < 0.0001), but not significantly different in NSCLC and gastric cancer (P = 0.119). In NSCLC, the low ERCC1 group had significantly longer disease free survival (DFS) than the high ERCC1 group (29.1 vs. 21.0 months, P < 0.0001); in the surgery alone and postoperative platinum-containing chemotherapy subgroups, DFS was significantly longer for the low ERCC1 groups than high ERCC1 groups (30.2 vs. 25.1 months, P = 0.018; 27.0 vs. 19.4 months, P < 0.0001, respectively). In gastric cancer patients receiving surgery alone, the low ERCC1 group had significantly longer overall survival than the high ERCC1 group (47.54 vs. 27.47 months, P = 0.018).

Conclusions: High ERCC1 mRNA expression of the NSCLC tumor tissues was associated with poor disease-free survival (DFS), in both the surgery alone and postoperative platinum-containing chemotherapy subgroups. Meanwhile, low ERCC1 mRNA expression had significantly longer overall survival in gastric cancer patients receiving surgery alone. Therefore, ERCC1 expression was a prognostic factor and predictive marker in NSCLC, and gastric cancer after surgery alone, but was not a prognostic factor in breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314004PMC
October 2015

[Tenofovir rescue therapy for chronic hepatitis B patients after suboptimal response to treatment with lamivudine plus adefovir dipivoxil].

Zhonghua Nei Ke Za Zhi 2014 Sep;53(9):697-700

Department of Infectious Disease, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Email:

Objective: To evaluate the efficacy of tenofovir (TDF) 300 mg/d, comparing with entecavir (ETV), in adults with chronic HBV infection who had previously virologic failure with lamivudine(LAM) and failed with rescue treatment of LAM combined adefovir(ADV).

Methods: Fifty-seven patients of chronic hepatitis B on rescue treatment with TDF were analyzed retrospectively. The serum HBV DNA levels, HBeAg, ALT and serum creatinine (Cr) were detected after treatment for 12, 24 and 48 weeks respectively. In addition, data of 40 cases treated with ETV 1 mg per day as a control group were also collected.

Results: The baseline characteristics including HBV viral loads, median age, serum levels of ALT and Cr were compatible between TDF group and ETV group. At the time point of 24 weeks, there was only one patient (2.5%) in ETV group with HBV DNA<100 IU/ml, which means negative viral replication, while 49 patients in TDF group reached HBV negativity (86.0% vs 2.5%, χ(2) = 22.26, P < 0.001). At the time point of 48 weeks, the proportion of patients with HBV DNA<100 IU/ml in TDF group was significantly higher than that in ETV group (87.7% vs 12.5%,χ(2) = 24.17, P < 0.001). The ratios of ALT normalization (84.2% vs 77.5%, P = 0.431) and HBeAg seroconversion were similar in both groups. Elevated Cr was not found in both cohorts at the end of treatment.

Conclusions: Tenofovir (300 mg/d) is an effective and safe rescue therapy in chronic hepatitis B patients who failed initial treatment with LAM and secondary treatment of LAM plus ADV.
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September 2014

[Analysis on the relationship between adolescent myopia and serum sex hormone].

Zhonghua Yi Xue Za Zhi 2014 May;94(17):1294-7

The Institute for Public Policy and Social Development, Wenzhou Medical University, Wenzhou 325035, China. Email:

Objective: To investigate the quantitative changes of the serum sex hormone levels in juvenile myopia patients.

Methods: In January 2013, investigation of Wenzhou middle school 822 adolescents, including 432 male patients and 390 female patients were involved in the study Visual acuity ≥ 5 was set as the normal value. The subjects were divided into two groups, the myopia group and the non-myopia group. Chemiluminescence immunoassay analyzer was used to detect the subjects' sex hormone concentration of estradiol (E2), testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Results: The follicle stimulating hormone and luteinizing hormone of the female patients were significantly higher than those of male counterparts (P < 0.01); among the two groups consisting female myopia and non-myopia patients, a significant difference in luteinizing hormone and follicle stimulating hormone was shown (P < 0.05); the distinct differences in the level of luteinizing hormone and testosterone level showed in the male myopia group and non-myopia group were of outstanding statistics significance (P < 0.01), showing the result that the level of sex hormone in myopia group was higher than that in the non-myopia group.

Conclusion: A close relationship perhaps between the level of sex hormone with gender differences and juvenile myopia is confirmed.
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May 2014

Sensitive detection of EGFR mutations in cerebrospinal fluid from lung adenocarcinoma patients with brain metastases.

J Mol Diagn 2014 Sep 30;16(5):558-563. Epub 2014 Jun 30.

Respiratory Oncology Center, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Epidermal growth factor receptor (EGFR) mutations in cerebrospinal fluid (CSF) might be useful predictive markers for EGFR tyrosine kinase inhibitor treatment of intracranial metastatic tumors. In this retrospective study, amplification refractory mutation system (ARMS)-PCR assays were used to investigate the EGFR gene status in 30 lung adenocarcinoma patients with brain metastases. A total of 16 patients tested positive for EGFR-activating mutations in CSF or tumor tissues. These included L858R mutation in exon 21 in six CSF samples and exon 19 deletions in seven CSF samples. EGFR mutations were detected between CSF and primary tumor samples with a 75% positive predictive value (95% CI, 0.45-1.00), 75% negative predictive value (95% CI, 0.51-0.99), 67% sensitivity (95% CI, 0.36-0.97), and 82% specificity (95% CI, 0.59-1.00). Most of the patients who had EGFR mutations in CSF achieved good responses with EGFR-tyrosine kinase inhibitor treatment. In conclusion, ARMS-PCR could be a sensitive method of detecting EGFR mutations in the CSF of patients with lung adenocarcinoma with brain metastases. As such, ARMS-PCR could play an important role in guiding EGFR-tyrosine kinase inhibitor treatments of intracranial tumors and for diagnosing brain metastases in patients with lung adenocarcinoma.
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http://dx.doi.org/10.1016/j.jmoldx.2014.04.008DOI Listing
September 2014

Erlotinib in combination with pemetrexed/cisplatin for leptomeningeal metastases and cerebrospinal fluid drug concentrations in lung adenocarcinoma patients after gefitinib faliure.

Target Oncol 2015 Mar 2;10(1):135-40. Epub 2014 Jul 2.

Department of Respiratory Oncology, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, 510120, Guangzhou, China.

Limited treatment options are available for lung cancer with brain metastases. Recent reports indicated that erlotinib and pemetrexed had synergistic effects in lung adenocarcinoma. Thus, we speculated that erlotinib plus pemetrexed/cisplatin may be more effective for the treatment of refractory central nervous system metastases in patients after gefitinib failure. Six lung adenocarcinoma patients with leptomeningeal metastasis (LM) who showed initial good response to gefitinib and subsequent gefitinib resistance were enrolled in this retrospective study. Five of the six patients had an epidermal growth factor receptor (EGFR) mutation in the primary tumor tissues or plasma. One patient showed complete remission, two patients showed a partial response, and two patients had stable disease. Performance and symptoms improved in the six patients. The survival time after the combination therapy was from 8 to 15 months (median, 9 months). There was no significant difference in cerebrospinal fluid (CSF) penetration rates of erlotinib between the erlotinib-only and the combination groups (P = 0.44). Erlotinib combined with pemetrexed/cisplatin may be effective in the treatment of LM in EGFR mutation patients after gefitinib failure. Small but measurable penetration of erlotinib and pemetrexed into the CSF was observed.
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http://dx.doi.org/10.1007/s11523-014-0326-9DOI Listing
March 2015

Erlotinib with pemetrexed/cisplatin for patients with wild-type lung adenocarcinoma with brain metastases.

Mol Clin Oncol 2014 May 11;2(3):449-453. Epub 2014 Feb 11.

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China ; State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.

Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer. Recent reports indicated that erlotinib and pemetrexed exerted synergistic effects against lung adenocarcinoma. The available treatment options for lung cancer with brain metastases (BM) are currently limited. In the present study, we investigated the efficacy of the combined administration of erlotinib and pemetrexed in 9 patients with epidermal growth factor receptor () wild-type lung adenocarcinoma with BM. Pemetrexed (500 mg/m) and cisplatin (20 mg/m) were administered on day 1 and days 1-3, respectively. Erlotinib (150 mg) was administered daily on days 4-20. The 9 patients harbored wild-type mutation in the primary tumor tissues. With regard to the BM, no patients achieved complete remission, 7 patients exhibited a partial response (PR), 1 had stable disease (SD) and 1 had progressive disease (PD). As regards the extracranial tumors, 3 patients exhibited a PR, 2 had SD, 3 had PD and 1 was not applicable. The performance status and the symptoms improved in 3 patients following treatment. The median progression-free survival for intracranial and extracranial disease control was 179 and 146.5 days, respectively. The median overall survival was 197.4 days. Therefore, erlotinib combined with pemetrexed/cisplatin, was found to be effective in the treatment of patients with wild-type lung adenocarcinoma.
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http://dx.doi.org/10.3892/mco.2014.256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999131PMC
May 2014

Association between epidermal growth factor receptor gene copy number and ERCC1, BRCA1 protein expression in Chinese patients with non-small cell lung cancer.

Med Oncol 2014 Mar 23;31(3):803. Epub 2014 Jan 23.

Department of Cardiothoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Mutation in epidermal growth factor receptor (EGFR) gene may predict response to chemotherapy in non-small cell lung cancer (NSCLC). However, the correlation between EGFR gene copy status and protein levels of drug-resistant genes, such as excision repair cross-complementing 1 (ERCC1) and breast cancer 1 (BRCA1), remains unclear. We retrospectively analyzed formalin-fixed, paraffin-embedded tumor tissues from 109 Chinese patients with NSCLC. EGFR gene copy number was evaluated by fluorescence in situ hybridization (FISH), and protein levels of platinum-resistance-associated genes, including ERCC1 and BRCA1, were determined by immunohistochemical staining. High EGFR gene copy (EGFR FISH-positive) was found in 21.1% of the patients (amplification in 7.3% and high polysomy in 13.8%, respectively). Immunohistochemical analysis revealed that ERCC1 protein expression was not associated with clinicopathological factors, whereas a significantly higher BRCA1 positive rate was found in poorly differentiated tumors (P=0.02). Further association studies demonstrated that EGFR gene copy number status was not correlated with protein levels of ERCC1 or BRCA1; however, expression of ERCC1 was significantly associated with that of BRCA1 in this set of Chinese patients with NSCLC (P<0.001, r=0.484). Our study demonstrated that EGFR gene copy number status was not correlated with ERCC1 or BRCA1 protein expression, but ERCC1 protein levels were significantly correlated to BRCA1 protein expression levels in tumor tissues from Chinese patients with NSCLC.
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http://dx.doi.org/10.1007/s12032-013-0803-5DOI Listing
March 2014

High expression levels of class III β-tubulin in resected non-small cell lung cancer patients are predictive of improved patient survival after vinorelbine-based adjuvant chemotherapy.

Oncol Lett 2013 Jul 29;6(1):220-226. Epub 2013 Apr 29.

Southern Medical University, Guangzhou, Guandong 510515; ; Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guandong 510120;

The aim of the present study was to determine the frequency and predictive value of the expression of tumor microtubule components in patients with resected non-small cell lung cancer (R-NSCLC) subsequently treated with vinorelbine-based adjuvant chemotherapy. The expression of the microtubule components was evaluated in 85 R-NSCLC tumor samples using immunohistochemistry. All patients received vinorelbine-based chemotherapy. The predictive value of microtubule protein expression for disease-free survival (DFS) and overall survival (OS) was assessed. The expression of the microtubule components was not associated with any baseline clinicopathological factors in the R-NSCLC patients. High tumor expression levels of class III β-tubulin were correlated with an improved DFS (P=0.033) and a trend towards a longer OS (P=0.226). Class II and IV β-tubulins were not correlated with patient outcome. Multivariate analysis of factors, including gender, age, histology, stage and class II, III and IV β-tubulin expression demonstrated that high levels of class III β-tubulin expression were correlated independently with DFS (P= 0.031). These findings suggest that high class III β-tubulin expression levels in resected tumors are predictive of improved DFS in R-NSCLC patients receiving vinorelbine-based chemotherapy.
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http://dx.doi.org/10.3892/ol.2013.1323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742788PMC
July 2013

Bilateral pneumothorax after bevacizumab-containing chemotherapy in fibrosarcoma.

J Thorac Dis 2012 Apr;4(2):229-31

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, No. 151, Yanjiang Rd, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.3978/j.issn.2072-1439.2012.01.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378222PMC
April 2012

Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and non-invasive BIPAP-ventilation.

J Thorac Dis 2012 Jun;4(3):316-9

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, No. 151, Yanjiang Rd, Guangzhou, 510120, China.

This is the case of a 63 year-old male who was diagnosed adenocarcinoma in the left upper lung with ipsilateral malignant pleural effusion. At diagnosis it had already spread to left pulmonary HLN (hilar lymph node) and left supraclavicular lymph node and mediastinal lymph nodes. The patient received combined chemotherapy with bevacizumab and GP (gemcitabine and carboplatin) for 6 courses. Disease progression on chest CT scan was recognized, daily treatment with oral gefitinib (250 mg/day) was commenced. One week later, he was admitted under the impression of gefitinib-related interstitial pneumonitis, gefitinib was discontinued immediately and methylprednisolone with BIPAP assisted ventilation were used. The patient was followed up for 2 months after the start of treatment with corticosteroids and BIPAP assisted ventilation and remained well.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2012.03.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378190PMC
June 2012

The expression of p33(ING1), p53, and autophagy-related gene Beclin1 in patients with non-small cell lung cancer.

Tumour Biol 2011 Dec 22;32(6):1113-21. Epub 2011 Jul 22.

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Rd, Guangzhou, 510120, Guangdong Province, People's Republic of China.

The purpose of this study was to investigate the expressions of tumor inhibitor of growth (ING1) gene p33ING1, p53, and autophagy-related gene Beclin1 in human non-small cell lung cancer (NSCLC), and the correlation between their expressions with clinical pathological features and clinical significance. The research can provide new ideas and experimental evidence for early diagnosis and biotherapy for NSCLC in the future. The human NSCLC tissues and surrounding non-cancerous tissues were collected from surgical operation. The expressions of mRNA or protein of p33ING1, p53, and Beclin1 were detected by using of reverse transcription polymerase chain reaction or Western blot in these tissues. The results were used to analyze the relationships between these gene expressions with the developing of NSCLC and clinical pathological features. The expressions of mRNA or protein of p33ING1 and Beclin1 in NSCLC tissues were significantly lower than that in surrounding noncancerous tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in well- and middle-differentiated NSCLC tissues were lower than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in presence of lymph nodes metastasis were lower than those in absence of lymph nodes metastasis (p < 0.05). The expressions of mRNA or protein of p33ING1 and Beclin1 in patients of pathological stage (stages I-II) were higher than those in pathological stage (stages III-IV) (p < 0.05). But the expression of protein of mutant-type p53 in NSCLC tissues was significantly higher than that in surrounding non-cancerous tissues (p < 0.05). The expressions of protein of mutant-type p53 in well- and middle-differentiated NSCLC tissues were higher than those in poor-differentiated NSCLC tissues (p < 0.05). The expressions of protein of mutant-type p53 in presence of lymph nodes metastasis were higher than those in absence of lymph nodes metastasis (p < 0.05). The expressions of protein of mutant-type p53 in patients of pathological stage (stages I-II) were lower than those in pathological stage (stages III-IV) (p < 0.05). These expression changes of p33ING1, p53, and autophagy-related Beclin1 genes were associated with tumor cell differentiation, lymph nodes metastasis, and pathological stage of NSCLC. But these expression changes of these three genes were not associated with gender, age, size of primary carcinoma, histological type of NSCLC (p > 0.05). The expression of mRNA of p53 and Beclin1 were correlated with p33ING1 mRNA expression in NSCLC tissues (p < 0.05). The activity changes of tumor inhibitor of growth, autophagy, and apoptosis may be related to the emergence and the development of NSCLC. The combined detection of p33ING1, p53, and Beclin1 genes and proteins will be helpful for early diagnosis and prognosis judgment for NSCLC, and can provide experimental evidence for biotherapy of NSCLC.
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http://dx.doi.org/10.1007/s13277-011-0211-4DOI Listing
December 2011

The role of NF-E2-related factor 2 in predicting chemoresistance and prognosis in advanced non-small-cell lung cancer.

Clin Lung Cancer 2011 May 28;12(3):166-71. Epub 2011 Apr 28.

Department of Cardiothoracic Surgery, State Key Laboratory of Respiratory Disease, Guangzhou Institution of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.

Background: NF-E2-related factor 2 (Nrf2) plays an important role in platinum chemoresistance by activating transcription of target genes through binding to the antioxidant response element (ARE) in gene promoters, moreover it could stimulate tumor growth in non-small-cell lung cancer (NSCLC). The objective of this study was to elucidate the correlation between Nrf2 expression and platinum-based chemotherapy response as well as the prognostic significance of Nrf2 levels.

Patients And Methods: Immunohistochemical analysis of Nrf2 in tumor specimens was performed in a total of 60 patients with stage IIIB or IV NSCLC.

Results: Positive staining for Nrf2 was found in nearly all cases, just at different levels. High Nrf2 expression was noted in 34 of 60 patients (56.7%). The expression of Nrf2 correlated with age (P = .014), stage (P = .017), and performance status (P = .014). The response rate of platinum-based chemotherapy in patients with < 75% positive staining was significantly higher than that in patients with 75%-100% positive staining (P = .003; r = 0.447). Furthermore, a high percentage of Nrf2 staining was the independent prognostic factor in progression survival (P = .000) analysis.

Conclusion: We suggest that the assessment of Nrf2 expression may be useful for evaluating chemoresistance and tumor progression in patients with advanced stage NSCLC.
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http://dx.doi.org/10.1016/j.cllc.2011.03.012DOI Listing
May 2011