• Title/Summary/Keyword: Non-Small Lung Cancer

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Wear behaviors of HVOF spray coating of Co-alloy T800

  • Cho, Tong-Yul;Yoon, Jae-Hong;Kim, Kil-Su;Park, Bong-Kyu;Youn, Suk-Jo;Back, Nam-Ki;Chun, Hui-Gon
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.16 no.3
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    • pp.121-126
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    • 2006
  • HVOF thermal spray coating of Co-alloy T800 is progressively replacing the classical hard coatings such as chrome plating because of the very toxic $Cr^{6+}$ ion known as carcinogen causing lung cancer. For the study of the possibility of replacing of chrome plating, the wear properties of HVOF Co-alloy T800 coatings are investigated using the reciprocating sliding tester both at room and at an elevated temperature of $1000^{\circ}F\;(538^{\circ}C)$. The possibility as durability improvement coating is studied for the application to the high speed spindles vulnerable to frictional heat and wear. Wear mechanisms at the reciprocating sliding wear test are studied for the application to the systems similar to the sliding test such as high speed spindles. Wear debris and frictional coefficients of T800 coatings both at room and at an elevated temperature of $1000^{\circ}F\;(538^{\circ}C)$ are drastically reduced compared to those of non-coated surface of parent substrate Inconel 718. This study shows that the coating is recommendable for the durability improvement coatings on the surfaces vulnerable to frictional heat. The sliding surfaces are weared by the mixed mechanisms such as oxidative wear, abrasion by the sliding ball slurry erosion by the mixture of solid particles and small drops of the melts and semi-melts of the attrited particles cavitation by the relative motions among the coating, sliding ball, the melts and semi-melts. and corrosive wear. The oxide particles and the melts and semi-melts play roles as solid and liquid lubricant reducing the wear and friction coefficient.

Gamma Knife Radiosurgery after Stereotactic Aspiration for Large Cystic Brain Metastases

  • Park, Won-Hyoung;Jang, In-Seok;Kim, Chang-Jin;Kwon, Do-Hoon
    • Journal of Korean Neurosurgical Society
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    • v.46 no.4
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    • pp.360-364
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    • 2009
  • Objective : Several treatment options have proven effective for metastatic brain tumors, including surgery and stereotactic radiosurgery. Tumors with cystic components, however, are difficult to treat using a single method. We retrospectively assessed the outcome and efficacy of gamma knife radiosurgery (GKRS) for cystic brain metastases after stereotactic aspiration of cystic components to decrease the tumor volume. Methods : The study population consisted of 24 patients (13 males, 11 females; mean age, 58.3 years) with cystic metastatic brain tumors treated from January 2002 to August 2008. Non-small cell lung cancer was the most common primary origin. After Leksell stereotactic frame was positioned on each patient, magnetic resonance images (MRI)-guided stereotactic cyst aspiration and GKRS were performed (mean prescription dose : 20.2 Gy). After treatment, patients were evaluated by MRI every 3 or 4 months. Results : After treatment, 13 patients (54.2%) demonstrated tumor control, 5 patients (20.8%) showed local tumor progression, and 6 patients (25.0%) showed remote progression. Mean follow-up duration was 13.1 months. During this period, 10 patients (41.7%) died, but only 1 patient (4.2%) died from brain metastases. The overall median survival after these procedures was 17.8 months. Conclusion : These results support the usefulness of GKRS after stereotactic cyst aspiration in patients with large cystic brain metastases. This method is especially effective for the patients whose general condition is very poor for general anesthesia and those with metastatic brain tumors located in eloquent areas.

Fluorometric Detection of Low-Abundance EGFR Exon 19 Deletion Mutation Using Tandem Gene Amplification

  • Kim, Dong-Min;Zhang, Shichen;Kim, Minhee;Kim, Dong-Eun
    • Journal of Microbiology and Biotechnology
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    • v.30 no.5
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    • pp.662-667
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    • 2020
  • Epidermal growth factor receptor (EGFR) mutations are not only genetic markers for diagnosis but also biomarkers of clinical-response against tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Among the EGFR mutations, the in-frame deletion mutation in EGFR exon 19 kinase domain (EGFR exon 19-del) is the most frequent mutation, accounting for about 45% of EGFR mutations in NSCLCs. Development of sensitive method for detecting the EGFR mutation is highly required to make a better screening for drug-response in the treatment of NSCLC patients. Here, we developed a fluorometric tandem gene amplification assay for sensitive detection of low-abundance EGFR exon 19-del mutant genomic DNA. The method consists of pre-amplification with PCR, thermal cycling of ligation by Taq ligase, and subsequent rolling circle amplification (RCA). PCR-amplified DNA from genomic DNA samples was used as splint DNA to conjugate both ends of linear padlock DNA, generating circular padlock DNA template for RCA. Long stretches of ssDNA harboring multiple copies of G-quadruplex structure was generated in RCA and detected by thioflavin T (ThT) fluorescence, which is specifically intercalated into the G-quadruplex, emitting strong fluorescence. Sensitivity of tandem gene amplification assay for detection of the EGFR exon 19-del from gDNA was as low as 3.6 pg, and mutant gDNA present in the pooled normal plasma was readily detected as low as 1% fraction. Hence, fluorometric detection of low-abundance EGFR exon 19 deletion mutation using tandem gene amplification may be applicable to clinical diagnosis of NSCLC patients with appropriate TKI treatment.

Mechanism of gemcitabine-induced apoptosis (Gemcitabine의 세포사멸 기전 연구)

  • Seol, Jae-Won;Lee, You-Jin;Kang, Dong-Won;Kang, Hyung-Sub;Kim, Nam-Soo;Kim, In-Shik;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.45 no.4
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    • pp.495-500
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    • 2005
  • The nucleoside analogue gemcitabine (2', 2-difluorideoxycytide) is potential against a wide variety of solid tumors and considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the signals of gemcitabine-induced apoptosis, especially in point of caspase pathway in A549. We exposed A549 cells to gemcitabine for dose/time dependent manner and the results showed that gemcitabine induced apoptotic cell death in a time/dose-dependent manner. We also treated to gemcitabine and Z-VAD-fmk as a pan-caspase inhibitor for 24 hours. Gemcitabine alone induced 35.3% cell death, and co-treatment with gemcitabine and Z-VAD-fmk induced 15.1% apoptotic cell death. Our results demonstrated that Z-VAD-fmk as a pan-caspase did not completely block the gemcitabine-induced apoptosis. Western blotting analysis showed that gemcitabine increased caspase-3, active caspase-8, p21 and p53 protein expressions in A549. Co-treatment with Z-VAD-fmk completely blocked caspase-3 and active caspase-8 protein expressions, but did not change the level of p21 and p53 protein expressions. Our data indicate that gemcitabine induced apoptosis through caspase-dependent and -independent pathways in A549.

A Case of Subungal Abscess and Onycholysis Induced by Docetaxel (Docetaxel 투여 후 발생한 조갑하 농양 및 조갑 박리증 1예)

  • Jung, Han Young;Lee, Chang Youl;Kim, Hyung Jung;Ahn, Chul Min;Chang, Yoon Soo
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.2
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    • pp.125-128
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    • 2007
  • Docetaxel is a taxoid antineoplastic drug, which is widely used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). Among the adverse dermatological reactions, nail disorders such as bending, onycholysis, hypoor hyperpigmentation are rare. We report a case of a 62-year-old male with advanced NSCLC (cT4N3M1, stage IV), who developed purulent discharge and onycholysis in the nail of all his fingers and the left great toe after five courses of anti-neoplastic chemotherapy, which included docetaxel (cumulative dose: $370mg/m^2$, 590 mg). Seven days after the final session of chemotherapy, the patient had become aware of discoloration and swelling of the nail beds with out pain. Three days later, greenish-yellow purulent discharge oozed out from the involved nails. Microbiologic studies revealed Pseudomonas aeruginosa. Intravenous and topical antibiotics (mupirocin) were applied. After 2 weeks, regrown nails were observed and the onycholysis had improved.

Assessment and Analysis of Fidelity and Diversity for GAN-based Medical Image Generative Model (GAN 기반 의료영상 생성 모델에 대한 품질 및 다양성 평가 및 분석)

  • Jang, Yoojin;Yoo, Jaejun;Hong, Helen
    • Journal of the Korea Computer Graphics Society
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    • v.28 no.2
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    • pp.11-19
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    • 2022
  • Recently, various researches on medical image generation have been suggested, and it becomes crucial to accurately evaluate the quality and diversity of the generated medical images. For this purpose, the expert's visual turing test, feature distribution visualization, and quantitative evaluation through IS and FID are evaluated. However, there are few methods for quantitatively evaluating medical images in terms of fidelity and diversity. In this paper, images are generated by learning a chest CT dataset of non-small cell lung cancer patients through DCGAN and PGGAN generative models, and the performance of the two generative models are evaluated in terms of fidelity and diversity. The performance is quantitatively evaluated through IS and FID, which are one-dimensional score-based evaluation methods, and Precision and Recall, Improved Precision and Recall, which are two-dimensional score-based evaluation methods, and the characteristics and limitations of each evaluation method are also analyzed in medical imaging.

HPLC, NMR Based Characterization, Antioxidant and Anticancer Activities of Chemical Constituents from Therapeutically Active Fungal Endophytes

  • Waqas Hussain Shah;Wajiha Khan;Sobia Nisa;Michael H.J. Barfuss;Johann Schinnerl;Markus Bacher;Karin Valant-Vetschera;Ashraf Ali;Hiba-Allah Nafidi;Yousef A. Bin Jardan;John P. Giesy
    • Journal of Microbiology and Biotechnology
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    • v.34 no.7
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    • pp.1452-1463
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    • 2024
  • Fungi generate different metabolites some of which are intrinsically bioactive and could therefore serve as templates for drug development. In the current study, six endophytic fungi namely Aspergillus flavus, Aspergillus tubigenesis, Aspergillus oryzae, Penicillium oxalicum, Aspergillus niger, and Aspergillus brasiliensis were isolated and identified from the medicinal plant, Silybum marianum. These endophytic fungi were identified through intra transcribed sequence (ITS) gene sequencing. The bioactive potentials of fungal extracts were investigated using several bioassays such as antibacterial activity by well-diffusion, MIC, MBC, anti-biofilm, antioxidant, and haemolysis. The Pseudomonas aeruginosa PAO1 was used to determine the antibiofilm activity. The ethyl acetate extract of Aspergillus flavus showed strong to moderate efficacy against Staphylococcus aureus, Escherichia coli, P. aeruginosa, and Bacillus spizizenii. Aspergillus flavus and Aspergillus brasiliensis exhibited significant antibiofilm activity with IC50 at 4.02 and 3.63 mg/ml, while A. flavus exhibited maximum antioxidant activity of 50.8%. Based on HPLC, LC-MS, and NMR experiments kojic acid (1) and carbamic acid (methylene-4, 1-phenylene) bis-dimethyl ester (2) were identified from A. flavus. Kojic acid exhibited DPPH free radical scavenging activity with an IC50 value of 99.3 ㎍/ml and moderate activity against ovarian teratocarcinoma (CH1), colon carcinoma (SW480), and non-small cell lung cancer (A549) cell lines. These findings suggest that endophytic fungi are able to produce promising bioactive compounds which deserve further investigation.

Meta-analysis of Seven Randomized Control Trials to Assess the Efficacy and Toxicity of Combining EGFR-TKI with Chemotherapy for Patients with Advanced NSCLC who Failed First-Line Treatment

  • Xiao, Bing-Kun;Yang, Jian-Yun;Dong, Jun-Xing;Ji, Zhao-Shuai;Si, Hai-Yan;Wang, Wei-Lan;Huang, Rong-Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2915-2921
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    • 2015
  • Background: Some recent clinical trials have been conducted to evaluate a combination of EGFR- TKI with chemotherapy for advanced NSCLC patients as second-line therapy, but the results on the efficacy of such trials are inconsistent. The aim of this meta-analysis was to evaluate the efficacy and safety of combination of EGFR-TKI and chemotherapy for patients with advanced NSCLC who failed first-line treatment. Materials and Methods: We searched relative trials from PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, Cochrane Library and Clinical Trials.gov. Outcomes analyzed were overall response rate (ORR), progression- free survival (PFS), overall survival (OS) and major toxicity. Results: Seven trails eventually were included in this meta-analysis, covering 1,168 patients. The results showed that the combined regimen arm had a significant higher ORR (RR 1.76 [1.16, 2.66], p=0.007) and longer PFS (HR 0.75 [0.66-0.85], p<0.00001), but failed to show effects on OS (HR 0.88 [0.68-1.15], p=0.36). In terms of subgroup results, continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance confered no improvement in ORR (RR 0.95 [0.68, 1.33], p=0.75) and PFS (HR 0.89[0.69, 1.15], p=0.38), and OS was even shorter (HR1.52 [1.05-2.21], p=0.03). However, combination therapy with EGFR-TKI and chemotherapy after failure of first-line chemotherapy significantly improved the ORR (RR 2.06 [1.42, 2.99], p=0.0002), PFS (HR 0.71 [0.61, 0.82], p<0.00001) and OS (HR 0.74 [0.62-0.88], p=0.0008), clinical benefit being restricted to combining EGFR-TKI with pemetrexed, but not docetaxel. Grade 3-4 toxicity was found at significantly higher incidence in the combined regimen arm. Conclusions: Continuation of EGFR-TKI in addition to chemotherapy after first-line EGFR-TKI resistance should be avoided. Combination therapy of EGFR-TKI and pemetrexed for advanced NSCLC should be further investigated for prognostic and predictive factors to find the group with the highest benefit of the combination strategy.

Expression and Clinical Significance of mTOR in Surgically Resected Non-small Cell Lung Cancer Tissues: a Case Control Study

  • Liu, Zhe;Wang, Liang;Zhang, Li-Na;Wang, Yue;Yue, Wen-Tao;Li, Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6139-6144
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    • 2012
  • Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients

  • Chen, Jia;Zheng, Xin;Liu, Dong-Yang;Zhao, Qian;Wu, Yi-Wen;Tan, Fen-Lai;Wang, Yin-Xiang;Jiang, Ji;Hu, Pei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7195-7200
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    • 2014
  • Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.