• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.668-675
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• 2001

Background : Non-smalll lung cancer(NSCLC) develops as a result of the accumulation of multiple genetic abnormalities. Loss of heterozygosity(LOH) is one of the most frequent genetic alterations that is found in NSCLC, and the chromosomal regions that display a high rate of LOH are thought to harbor tumor suppressor genes(TSGs). This study was done to determine the frequency of LOH in 21q with the aim of identifying potential TSG loci. Method : Thirty-nine surgically resected NSCLCs were analysed. Patients peripheral lymphocytes were used as the source of the normal DNA. Five microsatellite Inarkers of 21q were used to study LOH : 21q21.1(D21S1432, and D21S1994); 21q21.2-21.3(D21S1442) ; 21q22.1(21S1445) ; and 21q22.2-22.3(D21S266). The fractional allelic loss(FAL) in a tumor was calculated as the ratio of the number of markers showing LOH to the number of informative markers. Result : LOH for at least one locus was detected in 21 of 39 tumors(53.8%). Among the 21 tumors with LOH, 5(21.8%) showed LOH at almost all informative loci. Although statistically not significant, LOH was found more frequently in squamous cell carcinomas(15 of 23, 65.2%) than in adenocarcinomas(6 of 16, 37.5%). In the squamous cell carcinomas the frequency of LOH was higher in stage II-III (80.0%) than in stage I (53.8%). The FAL value in squamous cell carcinomas($0.431{\pm}0.375$) was significantly higher than that found in adenocarcinomas($0.l92{\pm}0.276$). Conclusion : These results suggest that LOH on 21q may be involved in the development of NSCLC, and that TSG(s) that contribute to the pathogenesis of NSCLC may exist on 21q.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2717-2722
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• 2013

Background: The objective of this research is the computed axial tomography (CT) imaging grading of radiation induced pneumonitis (RP) and its correlation with clinical and radiotherapeutic parameters. Materials and Methods: The chest CT films of 20 patients with non-small cell lung cancer who have undergone threedimensional conformal radiation therapy were reviewed. The proposed CT grading of RP is supported on solely radiological diagnosis criteria and distinguishes five grades. The manifestation of RP was also correlated with any positive pre-existing chronic obstructive pulmonary disease (COPD) history, smoking history, the FEV1 value, and the dosimetric variable V20. Results: The CT grading of RP was as follows: 3 patients (15%) presented with ground glass opacity (grade 1), 9 patients (45%) were classified as grade 2, 7 patients (35%) presented with focal consolidation, with or without elements of fibrosis (grade 3), and only one patient (5%) presented with opacity with accompanying atelectasis and loss of pulmonary volume (grade 4). Both univariate and multivariate analysis revealed as prognostic factors for the radiological grading of RP the reduction of FEV1 and the V20 (P=0.026 and P=0.003, respectively). There was also a significant (P<0.001) correlation of radiological grading of RP with FEV1 and V20 (spearman rho 0.92 and 0.93, respectively). Conclusions: The high correlation of the proposed radiological grading with the FEV1 and the V20 is giving a satisfactory clinical validity. Although the proposed grading scale seems relevant to clinical practice, further studies are needed for the confirmation of its validity and reliability.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4623-4627
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• 2014

Background: The epidermal growth factor receptor (EGFR) plays a vital role in the activation and inactivation of receptor tyrosine kinases. Mutations in exons 19 and 21 of EGFR are commonly found to be associated with non small cell lung carcinoma and triple negative breast cancer, enhancing sensitivity to EGFR targeting chemotherapeutic agents. Since amplification and prolonged activation of EGFR molecules have been identified in oral squamous cell carcinomas (OSCC), we investigated whether OSCCs carried mutations in exons 19 and 21 of EGFR to their incidence. Materials and Methods: Tumor chromosomal DNA isolated from forty surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking exons 19 and 21 of the EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Data analysis of the EGFR exon 19 and 21 coding sequences did not show any mutations in the forty OSCC samples that were analyzed. Conclusions: To the best of our knowledge, this is the first study to have investigated the genetic status of exons 19 and 21 of EGFR in Indian OSCCs and identified that mutation in EGFR exon 19 and 21 may not contribute towards their genesis. The absence of mutations also indicates that oral cancerous lesions may not be as sensitive as other cancers to chemotherapeutic agents targeting EGFR.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.553-558
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• 2017

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

• Natural Product Sciences
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• v.25 no.4
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• pp.311-316
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• 2019

Artocarpus heterophyllus has been used as traditional medicine. This plant is one of the sources of flavonoid. Flavonoid compounds possessed a wide range of biological properties including anticancer. This study was performed to investigate the cytotoxic effect of flavonoids from A. heterophyllus on H460 and MCF-7 cell lines. The interaction of flavonoids and cisplatin against tested cancer cells was also evaluated. MTT assay was used to determine the cytotoxic effect of flavonoid. Isobologram analysis was selected to evaluate the synergistic effect between flavonoid and cisplatin, their interaction was then confirmed using AO/PI staining method. Amongst of flavonoid compounds, artocarpin exhibited strong cytotoxic effect on both MCF-7 and H460 cell lines with IC₅₀ values of 12.53 ㎍/mL (28.73 μM) and 9.77 ㎍/mL (22.40 μM), respectively. This compound enhanced anticancer activity of cisplatin against H460 and MCF-7. The combination produced a synergistic effect on H460 and MCF-7 cell lines with a combination index (CI) values of 0.2 and 0.18, respectively. The AO/PI stained demonstrated that the combination of artocarpin and cisplatin caused morphological changes that indicated apoptosis. Moreover, artocarpanone also significantly increased cytotoxic effect of cisplatin compared to its single concentration with CI below than 1. This result suggested the potency of flavonoid named artocarpin to enhance the anticancer activity of cisplatin on H460 and MCF-7 cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6765-6768
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• 2015

Aims: To study the effectiveness of human recombinant endostatin injection (Endostar(R)) combined with cisplatin doublets in treating advanced non-small cell lung cancer (NSCLC), and to evaluate outcome by CT perfusion imaging. Methods: From April 2011 to September 2014, 76 patients with advanced NSCLC who were treated with platinum-based doublets were divided into group A (36 patients) and group B (40 patients). Endostar(R) 15mg/day was administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A, and combined with chemotherapy from the first day in Group B. Endostar(R) in the two groups was injected intravenously for 14 days. Results: Treatment effectiveness in the two groups differed with statistical significance (p<0.05). Effectiveness evaluated by CT perfusion imaging, BF, BV, MTT and PS also demonstrated significant differences (all p<0.05). Adverse reactions in the two groups did not significantly vary (p> 0.05). Conclusions: The response rate with Endostar(R) administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A was better than Endostar(R) combined with chemotherapy from the first day, and CT perfusion imaging could be a reasonable method for evaluation of patient outcomes.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.88-94
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• 2018

Background: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. Methods: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. Results: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). Conclusion: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

• BMB Reports
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• v.54 no.11
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• pp.563-568
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• 2021

Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical applications have not been successful for unclear reasons. In this study, endogenous PDHA1 in A549 cells was silenced by the CRISPR/Cas9 system, and PDHA1^WT and PDHA1^3SD were transduced. Since PDHA1^3SD cannot be phosphorylated by PDKs, it was used to evaluate the specific activity of PDK inhibitors. This study highlights that PDHA1^WT and PDHA1^3SD A549 cells can be used as a cell-based PDK inhibitor-distinction system to examine the relationship between PDH activity and cell death by established PDK inhibitors. Leelamine, huzhangoside A and otobaphenol induced PDH activity-dependent apoptosis, whereas AZD7545, VER-246608 and DCA effectively enhanced PDHA1 activity but little toxic to cancer cells. Furthermore, the activity of phosphomimetic PDHA1 revealed the complexity of its regulation, which requires further in-depth investigation.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.615-623
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• 2009

Background: We evaluated the feasibility and the efficacy of Video-Assisted Thoracic Surgery (VATS) lobectomy for treating patients with non-small cell lung cancer (NSCLC) and we compared the outcomes of VATS lobectomy with those of open lobectomy. Material and Method: From 2003 to March 2008, 133 NSCLC patients underwent VATS lobectomy. The patients were selected on the basis of having clinical stage I disease on the chest CT and PET scan. The outcomes of 202 patients who underwent open lobectomy (OL group) for clinical stage I NSCLC were evaluated to compare their results with those of the patients who underwent VATS lobectomy (the VL group). Result: The number of females and the number of patients with adenocarcinoma and stage IA disease were greater in VL group (p<0.05). There was no operative mortality or major complications in the VL group. Conversion to thoracotomy was needed in 8 cases (6%), which was mostly due to bleeding. The chest tube indwelling time and the length of the postoperative hospital stay were significantly shorter in the VL group (p<0.001). The number of dissected lymph nodes and the size of tumor were significantly smaller in the VL group (p<0.001). For the pathologic stage I patients, there was no significant difference in the three-year survival rates between the two groups (p=0.15). Conclusion: VATS lobectomy is a safe procedure with low operative mortality and morbidity. VATS lobectomy is feasible for early stage NSCLC and it provides outcomes that are comparable to those for open lobectomy. Further long-term data are needed.

• Journal of Chest Surgery
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• v.41 no.4
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• pp.447-456
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• 2008

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).