• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.2
• /
• pp.925-928
• /
• 2014

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD=13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

• BMB Reports
• /
• v.51 no.11
• /
• pp.584-589
• /
• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.8
• /
• pp.4107-4111
• /
• 2016

Background: Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population. Materials and Methods: In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays. Results: The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060-3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C. Conclusions: The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.

• Korean Journal of Community Nutrition
• /
• v.2 no.5
• /
• pp.735-744
• /
• 1997

The effect of green tea drinking on the hepatocellular chemical cacinogenesis have been studied. Placental glutathione S-transferase(GST-P) positive foci area in a liver tissue, contents of thiobarbituric acid reactive substances(TBARS), total cytochrome P450 and glucose 6-phospphatase(G6P) activity in hepatic microsomes were investigated. Weaning Sprague-Dawley male rats were fed AIN-76A diet with deionized water or green tea infusion, Rats of CTR and CTR+ groups were provided deionized water while GTI and GTI+ groups were provided green tea instead of deionized water for the entire experimental period of 13weeks. Rats of GTP and GTP + groups had deionized water for the first 6 weeks and switched to green tea for the last 7weeks of the experimental period. CTR+, GTI +, and GTP + groups were carcinogen treated groups, Diethylnitrosamine(DEN) was injected as a single dose of 200mg/kg body weight intraperitoneally after 4 weeks of feeding. 2-Acetyla-minofluorene(AAF) was used as a carcinogen proliferater and suppled in the diets of carcinogen treated rats as 0.02% content for the last 6weeks starting from 2weeks after DEN injection. Rats were sacrificed after 13week weeks of feeding. The area and number of GST-P positive foci detected in carcinogen treated rats were decreased by green tea ingestion but when timing and duration of green tea ingestion was delayed after promotion period as in GTP + group, GST-P positive foci were not decreased as much as in GTI+ group. TBARS contents of carcinogen treated rats decreased by 13weeks of green tea ingestion but GTP groups did not show statiscally significant differences. G6P activities tended to decrease by carcinogen treatment but changes were not statiscally significant by green tea ingestion. Total cytochrome P450 contents were increased by carcinogen treatment. Thirteen weeks of green tea ingestion (GTI) also increased to total cytochrome P450 contents while 7weeks of green tea ingestion(GTP) did show any effects. These results suggest that green tea has suppressive effects on hepatocellular chemical carcinogenesis probably through the activities of antioxidant compounds. (Korean J Community utrition 2(5) : 735∼744, 1997)

• Microbiology and Biotechnology Letters
• /
• v.43 no.2
• /
• pp.150-157
• /
• 2015

This study was intended to evaluate the anti-atopic effect of Sargassum fulvellum water extract (SFWE). Atopic dermatitis (AD) was induced in BALB/c mice by spreading 2,4-dinitrochlorobenzene (DNCB) to the dorsal skin area. The production of IL-4 and total IgE of the SFWE treated group was significantly less than the DNCB only group. On the other hand, the production of the IFN-γ of SFWE treated group was greater than that of the DNCB only group. In addition, SFWE alleviated the AD symptoms when compared to the DNCB only group and reduced the epidermal thickness and the number of mast cells in histological analysis. In conclusion, these results suggest that the application of SFWE has an anti-atopic activity through the modulation of IL-4 and IFN-γ cytokines, and the total IgE in DNCB-induced BALB/c mice. Therefore, SFWE can be utilized with atopic disease therapies.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.1
• /
• pp.9-14
• /
• 2003

Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

• The Korean Journal of Nuclear Medicine
• /
• v.21 no.1
• /
• pp.9-16
• /
• 1987

It is well-known that hepatic scintigraphv have been found to be less sensitive and specific in the detection of the diffuse hepatocellular diseases than that of the space-occupying lesions. To obtain the higher diagnostic specificity and sensitivity, we, using the computer quantitation, have attempted to analyze hepatic and extrahepatic $^{99m}Tc-tin$ colloid uptake patterns in various diffuse hepatocellular diseases retrospectively. The studied groups consisted of 116 cases of normal, 67 cases of acute hepatitis, 112 cases of chronic hepatitis, 61 cases of liver cirrhosis, 47 cases of fatty liver, 12 cases of hepatoma and 9 cases of metastasis, making total 424 cases. Scintigraphic imagings were obtained in the anterior, right lateral and posterior projections using high-resolution collimation, and simultaneously these gamma data were acquisited into the computer system. Both large region of interest (ROI) using light pen and ROI computer program were placed over right lobe, left lobe of liver, spleen and cardiac blood pool. Total counts in ROI were divided by the number of pixels in the ROI, and mean count rate per pixels calculated. Mean right-lobe counts were divded by mean-left lobe counts to determine right-to-left hepatic lobe ratio and mean spleen counts were divided by mean liver counts to determine spleen to liver ratio. The results were as follows. 1) Of 424 cases, 292 were male and 132 were female. The majority of age distribution was in $30\sim49$ (54.5%). 2) Inter-observer between two independant operators and inter-method between drawing by light-pen and ROI computer program variations were not significant. 3) The uptake count values (per pixel) determined at each area in normal group were $106.53{\pm}18.35$ in right lobe, $79.00{\pm}13.82$ in left lobe, $17.52{\pm}8.31$ in spleen and $8.09{\pm}3.43$ in cardiac blood pool. 4) In liver cirrhosis, right lobe uptake was decreased but spleen and cardiac blood pool uptakes were increased (p<0.01). 5) Right-to-left hepatic lobe uptake ratio was $1.37{\pm}0.24$ in normal group and significantly low in chronic hepatitis, liver cirrhosis and fatty liver, and more or less low in acute hepatitis. 6) Spleen-to-right hepatic lobe uptake ratio was $0.17{\pm}0.09$ in normal group and high in chronic hepatitis and liver cirrhosis. 7) The computer-quantitation of hepatic and extrahepatic uptake patterns thought to be sensitive and useful method in the interpretation of liver scintigram.

• Journal of Periodontal and Implant Science
• /
• v.26 no.2
• /
• pp.531-541
• /
• 1996

Periodontal disease is characterized by destruction of supporting tissues caused by invasion of plaque bacteria and defense mechanism of host. Many dentists are very interested in laser therapy on various intraoral soft tissue lesions including inflammatory periodontal pocket. In order to determine the therapeutic effect of intrapocket irradiation of a pulsed- Nd : YAG laser on the inflammatory periodontal pockets, bilateral 60 teeth with 4-6mm in probing pocket depth and gingival inflammation were selected and evaluated by sulcus bleeding index(SBI), and plaque index(pI) for baseline record. Intrapocket irradiation($300{\mu}m$ fiber optic, I.5W power, for 2 min.) of a pulsed-Nd : YAG laser(EL.EN.EN060, Italy) was applied on half of them. As the control group, the same procedure except power-off was repeated on the contralateral 30 teeth. At 1-, 2-, 3-, and 4-week after intrapocket manipulation, every tooth was reevaluated by the same clinical indices. And the difference between the lased group and control group was statistically analyzed by paired t-test and Chi-square test in Microstat program. Following results were obtained: 1. Until I-week and 2-week after intrapocket manipulation, SBI was lowered in both lased group and control group, compared to baseline SBI, but from 3-week after, the recovering tendency toward baseline was noted, and at only 2-week after, the number of teeth showing lowered SBI was significantly more in lased group than in control group(p<0.05). 2. PI of both lased group and control group was lowered through whole experimental period from I-week to 4-week after, compared to baseline PI(p<0.05), but there was no significant difference between lased group and control group(p>0.1). The results suggest that intrapocket irradiation of a pulsed-Nd:YAG laser may lead somewhat remission of gingival inflammation, but for more favorable therapeutic result the thorough root planing should be necessarily accompanied with gingival curettage.

• Tuberculosis and Respiratory Diseases
• /
• v.62 no.3
• /
• pp.217-222
• /
• 2007

Talc pleurodesis is a safe and effective treatment for a recurrent malignant pleural effusion. However, acute hypoxemia, pulmonary edema or acute respiratory failure can develop in a small number of patients. We report 2 patients who developed fatal hypoxemia after talc pleurodesis which was necessary the control recurrent pleural effusion. The first case was an 18-year old male diagnosed with Ewing's sarcoma with bilateral lung metastases and pleural effusion. The performance status was ECOG (Eastern Cooperative Foncology Group) grade 3. Fever along with hypoxemia and leukocytosis developed 10 hours after the second talc pleurodesis on the right side for an uncontrolled pleural effusion, The patient died from respiratory failure after 13 days. The second case was a 66-year old female diagnosed with non-small cell lung cancer with a bone metastasis. Two weeks after systemic chemotherapy, she complained of dyspnea, and a pleural effusion was observed on the right side. Her performance status was ECOG grade 3. Talc pleurodesis was performed for recurrent pleural effusion, but hypoxemia developed 6 days after pleurodesis and she died from respiratory failure 10 days after pleurodesis. In conclusion, talc pleurodesis should be performed very carefully in patients with a poor performance status, in cases with repeated pleurodesis, bilateral pleural effusion, recent chemotherapy, radiotherapy and when there are parenchymal metastatic lesions present.

• Journal of Chest Surgery
• /
• v.33 no.1
• /
• pp.32-37
• /
• 2000

Background: Reconstruction surgery of mitral valve regurgitation is now considered as an effective operative technique and has shown good long-term results. Although reconstructive surgery of mitral valve has been performed since 1970s, we have started only in early 1990s in full scale because of small number of the mitral regurgitation compared to mitral stenosis and lack of knowledge from the viewpoint of patients and physicians. Material and Method: From January 1992 to December 1996, 100 patients underwent repair of the mitral valve for mitral regurgitation with or without mitral stenosis in Seoul National University Hospital. 45(45%) of the patients were men and 55(55%) were women. The mean age was 39.9$\pm$14.4 years. The causes of the mitral regurgitation were rheumatic in 61, degenerative in 28 and others in 11. According to the Carpentier's pathological classification of mitral regurgitation 5 patients were type I. 55 patients were type II and 40 patients were type III. 7 patients underwent concomitant aortic valvuloplasty and 8 patients underwent aortic valve replacement. 7 patients underwent Maze operation or pulmonary vein isolation. Result: There were no operative death but 3 major operative complications: 2patients were postoperative low cardiac output syndrome(needed intra-aortic ballon pump support) and 1 patient was postoperative bleeding. There was one late death(1.0%) The cause of death was sepsis secondary to acute bacterial endocarditis. 3 patients required reoperation for recurred mitral regurgitation. There were no statistically significant risk factors for reoperation. The other 96 patients showed no or mild degree of mitral regurgitation 99 survivors were in NYHA functional class I or II. There were two throumboembolisms but no anticoagulation-related complications. Conclusion: We concluded that mitral valve repair could be performed successfully in most cases of mitral regurgitation even in the rheumatic and combined lesions with very low operative mortality and morbidity. The early results are very promising.