• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Journal of Chest Surgery
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• v.47 no.5
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• pp.483-486
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• 2014

A 76-year-old male underwent a left upper lobectomy with wedge resection of the superior segment of the left lower lobe using video-assisted thoracoscopic surgery (VATS) for non-small-cell lung cancer of the left upper lobe. He presented with shortness of breath, fever, and leukocytosis. Chest radiography showed atelectasis at the remaining left lower lobe. Bronchoscopy revealed narrowing of the left lower bronchus with purulent secretion, and computed tomography showed downward kinking of the left lower lobar bronchus. He underwent exploratory VATS, and intraoperative findings showed an inferiorly kinked left lower lobar bronchus with upward displacement of the left lower lobe. After adhesiolysis, the kinked bronchus was straightened, and bronchopexy was performed to the pericardium to prevent the recurrence of bronchial kinking. Also, the inferior pulmonary ligament was reattached to prevent upward displacement. Postoperative follow-up bronchoscopy revealed no evidence of residual bronchial obstruction, and chest radiography showed no atelectasis thereafter.

• 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.

• 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.

• Journal of Chest Surgery
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• v.25 no.12
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• pp.1383-1390
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• 1992

This is the result of the annual statistic analysis of thoracic and cardiovascular surgical cases in 1991, Korea. 14,715 cases of surgery[thoracic 8,995/cardiovascular 5,720] were done by 53 institutes replied. The order of frequency of cell type in primary lung cancer was squamous [62.3%] / adeno [23.9%] / small [6.4%] / adenosquamous [3.0%], and in mediastinal tumor, neurogenic[27.l%] / thymoma [27.1%] / teratoma[26.4%] / congenital cystic[12.0%]. Surgery for tuberculosis was decreased to 15.8% of overall infectious disease from the recent 6 year`s average 35.7%. In general thoracic surgery, the single most frequent operation was closed thoracostomy[4,047 cases] for pleural pathology. The ratio of congenital to acquired heart disease was 2:1, and acyanotic to cyanotic was 3:1. The order of frequency of congenital acyanotic heart disease was VSD [45.6%] / ASD [25.6%] / PDA [20.4%] / PS [2.9%], and that of cyanotic heart disease was TOF [42.6%] / PA [12.9%] / TGA [9.9%] / DORV [8.8%]. In 1,364 cases of valvular surgery, single mitral pathology was the most frequent candidate[729 cases, 53.4%]. In 243 cases of coronary surgery, bypassing graft materials were great saphenous vein[41.6%], internal mammary [39.5%], and artificial vessel[18.9%]. There were no specific differences in aortic surgery, assisted device implantation, and antiarrhythmic surgery as compared to previous study. This nation-wide inquiry will be continued and reported annually by KTCS Society.

• 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.

• 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.

• 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.

• 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.

• 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.