• Biomedical Science Letters
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• v.11 no.4
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• pp.455-463
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• 2005

Resistance to isoniazid (INH), which is one of the most important drugs in Mycobacterium tuberculosis chemotherapy, has been associated with mutations in genes encoding the mycobacterial catalse-peroxidase (katG), the enoyl acyl carrier protein (ACP) reductase (inhA), alkyl hydroperoxide reductase (ahpC), beta-ketoacyl acyl carrier protein synthase (kasA), and NADH dehydrogenase (ndh). In this study, we examined INH-resistance related genes in 50 INH-resistant and 24 INH-susceptible isolates by PCR-sequence analysis. In brief, mutations at the katG gene were found at codon 315 alone (2/50), at codon 463 alone (19/50), and both at 315 and 463 (29/50). However, while mutations at codon 315 were only detected in INH-resistant isolates, mutations at codon 463 were also detected in INH-susceptible isolates indicating mutations at 463 alone do not seem to confer resistance to INH. Similar to the case of katG 463, some of inhA mutations were also found among INH-susceptible isolates. For example, whereas mutations at 8 upstream of the start codon (UPS) and 15 UPS of the inhA gene were detected only in INH-resistant isolates, mutations at 101, 115, and 125 UPS were detected only in INH-susceptible isolates. Many different kinds of mutations were detected in INH­resistant isolates at ahpC, oxyR gene, and intergenic region of the oxyR-ahpC genes. Howerver, the mutations were not found oxyR and the intergenic regions in INH-susceptible isolates. No mutations were found at either kasA or at ndh gene among INH-resistant isolates. In conclusion, some of mutations such as katG 315, inhA promotor region, and oxyR-ahpC seem to be strongly related to INH-resistance. Currently we are developing a molecular diagnostic method based on these results.

• Radiation Oncology Journal
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• v.33 no.2
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• pp.109-116
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• 2015

Purpose: To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. Materials and Methods: Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors. Results: The 5-year disease-free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS. Conclusion: PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered.

• Radiation Oncology Journal
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• v.35 no.3
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• pp.208-216
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• 2017

Purpose: To evaluate the feasibility of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for preoperative concurrent chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC), by comparing with 3-dimensional conformal radiotherapy (3D-CRT). Materials and Methods: Patients who were treated with PCRT for LARC from 2015 January to 2016 December were retrospectively enrolled. Total doses of 45 Gy to 50.4 Gy with 3D-CRT or SIB-IMRT were administered concomitantly with 5-fluorouracil plus leucovorin or capecitabine. Surgery was performed 8 weeks after PCRT. Between PCRT and surgery, one cycle of additional chemotherapy was administered. Pathologic tumor responses were compared between SIB-IMRT and 3D-CRT groups. Acute gastrointestinal, genitourinary, hematologic, and skin toxicities were compared between the two groups based on the RTOG toxicity criteria. Results: SIB-IMRT was used in 53 patients, and 3D-CRT in 41 patients. After PCRT, no significant differences were noted in tumor responses, pathologic complete response (9% vs. 7%; p = 1.000), pathologic tumor regression Grade 3 or higher (85% vs. 71%; p = 0.096), and R0 resection (87% vs. 85%; p = 0.843). Grade 2 genitourinary toxicities were significantly lesser in the SIB-IMRT group (8% vs. 24%; p = 0.023), but gastrointestinal toxicities were not different across the two groups. Conclusion: SIB-IMRT showed lower GU toxicity and similar tumor responses when compared with 3D-CRT in PCRT for LARC.

• Proceedings of the Korean Journal of Food and Nutrition Conference
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• 2000.05a
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• pp.1-3
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• 2000

A kind of traditional herbal prescription, Sip-Jeon-Dae-Bo-Tang (TJ-48), has been reported to improve the general condition of cancer patients receiving chemotherapy and /or radiation therapy, and to accelerate hematopoietic recovery from bone marrow injury by mitomycin C. In the present studies, we found that hot-water extract from Atractylodes lancea DC. rhizomes contributed mainly to intestinal immune modulating activity of TJ-48 on Peyer's patch cells mediated-hematopoietic response. After the fractionation, ALR-5 II a-1-1, 5 II b-2-2 and 5 II c-3-1 were further purified from crude polysaccharide fraction. Chemical analyses of each fraction indicated that ALR-5 II a-1-1 mainly contained arabinogalactan fraction whereas ALR-5 II b-2-2 and 5 II c-3-1 mostly comprised pectic polysaccharide fractions as the active polysaccharide ingredients. In order to analyze the essential structure of the activity, ALR-5 II a-1-1 was treated by sequential enzymatic digestion using exo-${\alpha}$-L-arabinofuranosidase and exo-${\beta}$-D-(1\longrightarrow3)-galactanase. Based upon the results of chemical and MALDI-TOF-MS analyses and activity on the digested fractions, the galactosyl side chains consisting of 6-linked Galf and Galp over tetrasaccharide in ALR-5 II a-1-1 might be responsible for the potent intestinal immune modulating activity. To characterize moiety of ALR-5 II c-3-1 for the expression of activity, endo-${\alpha}$-D-(1\longrightarrow4)-polygal acturonase (GL-PGase) purified from dried leaves of Panax ginseng digested ALR-5 II c-3-1. The results of structural analyses and activity on the digested fractions showed that PG-2, which structurally resembles to rhamnogalacturonan II (RG II), and PG-3 (galacturono-oligosaccharides) contained potent intestinal immune modulating activity. Further purification of the other acidic fraction (ALR-5 II b-2-2) indicated that ALR-5 II b-2-2Bb showed that the most potent activity. ALR-5 II b-2-2Bb also contained the unusual component sugars characteristics in RG- II as well as PG-2 derived from ALR-5 II c-3-1, but it could not be digested with GL-PGase. The present studies of relationship between structures and intestinal immune modulating activity of the active polysaccharides purified from A. lancea DC. rhizomes suggested that neutral galactosyl chains consisting mainly of (1\longrightarrow6)-linked Galf and Galp, and RG- II -like moiety with unique component sugars, such as 2-Me-Xyl, 2-Me-Fuc, Api, AceA, Kdo and Dha should play an important role in the potent intestinal immune modulating action of A. lancea DC. rhizomes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10439-10444
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• 2015

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4781-4786
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• 2014

Background: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. Materials and Methods: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. Results: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). Conclusions: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab-based treatments in mCRC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1399-1405
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• 2001

Objectives : Gliomatosis cerebri is an uncommon primary brain tumor characterized by diffuse neoplastic proliferation of glial cells, with the preservation of the underlying cytoarchitecture. The aim of this study is to evaluate clinical features, outcome of surgical treatment and adjuvant therapy of gliomatosis cerebri. Methods : Between Jan. 1990 and Dec. 2000, 12 patients were diagnosed with gliomatosis cerebri based on characteristic radiological and histological findings. The patients' age ranged from 18 to 77(mean 44) years and the male to female ratio was 7 : 5. Nine patients underwent decompressive surgery and three, biopsy only. Postoperative radiation therapy was given in all cases except three. In addition to radiation therapy, four patients received chemotherapy. The mean duration of follow-up period was 18.8 months. Results : The most common presenting symptom were seizure and motor weakness. The mean duration of symptom was 5.9 months. There was 5 bilateral lesions and tumor involved corpus callosum in 5, basal ganglia-thalamus in 4, and brain stem in 2. There was no operative mortality but four patients died during the follow-up. The mean survival period for 11 patients was 20.5 months from the time of diagnosis. In univariate analysis, the lesion involving corpus callosum, basal ganglia-thalamus and brain stem correlated significantly with the short length of survival(p<0.05). Also, postoperative radiation as a adjuvant therapy prolonged the patient's survival(p<0.05). Conclusions : In the management of gliomatosis cerebri patients, early detection by MR imaging, active management of increased intracranial pressure, decompressive surgical removal and postoperative adjuvant therapy such as radiation is thought to be a good treatment modality.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.12
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• pp.270-284
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• 2016

The purpose of this study was to understand the essential structure and meaning of self-management intervention for breast cancer survivors by using non-pharmacological approaches. The study participants were 10 breast cancer survivors who were completing cancer treatment that involved surgery, chemotherapy, and radiation therapy. Data collected between August 2014 and February 2015 at E Hospital in S city were analyzed by using Colaizzi's phenomenological method. Outcomes were classified into seven essential themes: 1) application of comfort measures to alleviate ongoing symptoms, 2) movement to change physical conditions, 3) special herbal intake to prevent recurrence, 4) a specially designed diet plan for health self-management, 5) constant awareness of complementary and alternative medicine, 6) unmet needs treated by one's own doctor's prescription, and 7) future life toward a nature-friendly environment. The study results contribute to a deeper understanding of self-management interventions in the daily lives of Korean breast cancer survivors. In addition, results provide an essential resource, based on actual self-management styles, that will help survivors to obtain guidance and participate in appropriate programs.

• Tuberculosis and Respiratory Diseases
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• v.75 no.2
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• pp.52-58
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• 2013

Background: More than half of cases for advanced non-small-cell lung cancer (NSCLC) occur in elderly patients with a median age at diagnosis of 70 years. The aim of our study was to examine the clinical features and prognostic factors contributing to mortality in elderly patients with advanced NSCLC. Methods: Following a retrospective review of clinical data, 122 patients aged 70 years and over with a histopathological diagnosis of locally advanced (stage IIIB, n=32) and metastatic (stage IV, n=90) NSCLC between 2005 and 2011 were enrolled. Results: The median age was 76 years (interquartile range, [IQR], 72-80 years), and 85 (70%) patients were male. Fifty-seven (46%) patients had never smoked, and 17 (19%) were in a malnourished state with a body mass index (BMI) of <$18.5kg/m^2$. The initial treatments included chemotherapy (40%) and radiotherapy (7%), but 57% of the patients received supportive care only. The 1-year survival rate was 32%, and the 3-year survival rate was 4%, with a median survival duration of 6.2 months (IQR, 2.5-15.3 months). Male gender (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p=0.005), low BMI (HR, 2.3; 95% CI, 1.3-3.9; p=0.004), and supportive care only (HR, 1.9; 95% CI, 1.2-2.9; p=0.007) were independent predictors of shorter survival based on a Cox proportional hazards model. Conclusion: Elderly patients with advanced NSCLC had a poor prognosis, particularly male patients, those with a low BMI, and those who received supportive care only.