• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.1677-1680
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• 2013

Background: Areas of Iran have among the highest incidences of esophageal cancer in the world. Definitive chemo-radiotherapy (DCRT) is used for locally advanced esophageal cancer and for inoperable tumors asan alternative to surgical treatment. Materials and Methods: This retrospective study was conducted in North-West Iran 2006-2011, including 267 consecutive patients with non-metastatic esophageal cancer. Eligible inoperable patients were treated with DCRT or definitive radiotherapy (DRT) alone. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. Results: The median survival was 12.7 months with 1, 3 and 5 year survival rates of 55%, 18% and 11%, respectively. On univariate analysis, relations with age at diagnosis (p=0.015), N-stage (p=0.04), total dose of RT (p=0.001), fraction (p<0.001), Gap status (p=0.025), chemotherapeutic regimens (P=0.027), and 5-Fu $Mg/m^2$ (P=0.004) were apparent. Comparing DCRT to DRT, there was a significant difference in survival. Multivariate analysis was performed for comparison between DCRT and DRT showed significant association with age group ${\geq}65$ to <65 (P=0.02; OR: 1.46), the total RT dose (Gy) ${\geq}50$ to <50 (P=0.01; OR: 0.65) and the fraction group ${\geq}25$ to <25 (P=<0.001; OR: 0.54). Conclusions: The survival rates of esophageal cancer treated with DCRT in North West of Iran is poor; therefore, early detection and improved treatment methods, with clinical trials are a high priority.

• 한국방사선학회논문지
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• 제10권7호
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• pp.483-487
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• 2016

이 연구는 ${\gamma}$선 및 x선 조사 시 AuNPs 입자의 방사선감수성의 향상을 생물물리학적으로 평가하기 위해 두 가지 실험을 시행하였다. 생물학적 방사선 감수성의 평가에 앞서 6시간, 12시간, 18시간, 24시간 incubation한 후 세포생존율(surviving Fraction, SF)값을 비교하여 AuNPs 입자의 독성 여부와 세포질에 입자의 균일 된 분포 여부를 확인 해 보았다. incubation time에 따라 세포생존율(surviving Fraction, SF)이 낮아지지 않음을 확인한 다음 ${\gamma}$선 및 x선 조사 후 Clonogenic assay 실시하고 세포생존율(surviving Fraction, SF)을 구하여 방사선 감수성을 비교 평가하였다. 방사선량 증가 시 세포생존율(surviving Fraction, SF)이 계속해서 낮아졌고 8Gy 조사 시 최대치로 약 30%의 차이가 있음을 확인하였다. 또한 Gate v6.1을 사용하여 몬테카를로 시뮬레이션 후 percent depth dose(PDD)를 구한 뒤 선량 평가하여 약 40% Dose Enhancement가 있음을 확인하였다. 두 가지 실험에 따라 생물물리학적으로 AuNPs 입자는 방사선 감수성이 향상되도록 하며 이는 nanoparticle을 이용한 방사선 병합 치료 시 치료 성적 향상에 큰 도움이 될 것으로 보인다.

• Tuberculosis and Respiratory Diseases
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• 제54권6호
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• pp.610-620
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• 2003

연구배경 : 폐암에서 가장 흔한 염색체 결손부위인 3p14.2 결손에 따른 FHIT 자체 기능 즉 암억제 기능의 소실이 폐암의 형성과정에 중요한 기능이 있으리라 생각된다. 흡연 여부, 병리조직학적, TNM 병기 진행에 따른 FHIT 소실여부를 확인하고, 또 흡연및 생존률과의 관계, FHIT의 기능 특히 암 세포의 세포고사, 세포분열에 미치는 영향을 확인하였다. 방 법 : 원발성 비소세포 폐암으로 근치적 절제술을 시행 받은 83례의 paraffin 보관 병리 조직을 절편하여 면역조직화학염색법으로 FHIT의 소실 여부를 확인한 후, 여러 임상적 인자들과의 관계를 파악하고, 유식세포 분석법에 의해, sub-G1 peak로서 세포고사의 정도를, S-phase fraction과 G1-phase fraction으로서 세포분열주기에 미치는 영향을 확인하였다. 결 과 : 전체 83례 중 36례(43%)에서 FHIT가 소실되었고, FHIT 소실율이 편평상피암 52%, 선암 22%; TNM I병기 30%, II병기 48%, III 병기 69%; 흡연경험자 54%, 비흡연자 22%로서, 선암보다는 편평상피암에서, TNM 병기가 진행할수록, 흡연의 경험이 있을수록 FHIT 소실율이 높았다. FHIT 소실군과 발현군의 중간 생존기간은 24개월, 25개월, 2년 생존율은 44%, 51%로서 FHIT 소실여부에 따른 생존율의 차이는 없었다. 세포고사율은 FHIT 소실군과 발현군에서 각각 50.72(${\pm}13.93$)%, 59.38(${\pm}14.33$)%로서 유의한 차이가 있었으며, FHIT 소실군과 발현군에서의 S-phase fraction은 각각 13.93(${\pm}7.35$)%, 15.65(${\pm}6.59$)% G1-phase fraction은 각각 51.50(${\pm}23.15$)%, 54.16(${\pm}20.25$)%로서 각 군간의 유의한 차이는 없었다. 결 론 : FHIT는 인체의 비소세포 폐암의 43%에서 소실되었고, 흡연의 경험이 있을수록, 선암보다는 편평상피암일수록, TNM 병기가 진행할수록 유의하게 FHIT 소실이 높았고, FHIT 소실여부에 따른 생존율의 차이는 없었다. FHIT 소실군에서 발현군보다 세포고사율이 유의하게 낮았으며, S 및 $G_1$ phase fraction의 차이는 없었다.

• 제어로봇시스템학회논문지
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• 제10권12호
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• pp.1155-1163
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• 2004

Extracellular signal-regulated kinase (ERK) signaling pathway is one of the mitogen-activated protein kinase (MAPK) signal transduction pathways. This pathway is known as pivotal in many signaling networks that govern proliferation, differentiation and cell survival. The ERK signaling pathway comprises positive and negative feedback loops, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level. In this paper, we attempt to model the ERK pathway by considering both of the positive and negative feedback mechanisms based on Michaelis-Menten kinetics. In addition, we propose a fraction ratio model based on the mass action law. We first develop a mathematical model of the ERK pathway with fraction ratios. Secondly, we analyze the dynamical properties of the fraction ratio model based on simulation studies. Furthermore, we propose a concept of an inhibitor, catalyst, and substrate (ICS) controller which regulates the inhibitor, catalyst, and substrate concentrations of the ERK signal transduction pathway. The ICS controller can be designed through dynamical analysis of the ERK signaling transduction pathway within limited concentration ranges.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2011년도 추계학술논문집 1부
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• pp.170-173
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• 2011

Therapeutic hypothermia(TH) improves neurological outcomes and reduces mortality among survivors of out-of-hospital cardiac arrest. Animal and human studies have shown that TH results in improved salvage of the myocardium, reduced infarct size, reduced left ventricular remodeling and better long-term left ventricular function in settings of regional myocardial ischemia. This study is to investigate the effect of TH on post-resuscitation myocardial dysfunction and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction (MI). Thoracotomies were performed in 10 Male Sprague-Dawley rats weighing 450-550 g. MI was induced by ligation of the left anterior descending coronary artery (LAD). Ninety min after LAD ligation, ventricular fibrillation induction and subsequent cardiopulmonary resuscitation was performed before defibrillation attempts. Animals were randomized to two groups: a) Acute MI-Normothermia b) Acute MI-Hypothermia ($32^{\circ}C$ for 4 h). Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured echocardiographically together with duration of survival. Ejection fraction, cardiac output and myocardial performance index were $54.74{\pm}9.16$, $89.00{\pm}8.89$, $1.30{\pm}0.09$ respectively and significantly better in the TH group than those of the normothermic group at the first 4 h after resuscitation($32.20{\pm}1.85$,$41.60{\pm}8.62$,$1.77{\pm}0.19$)(p=0.00). The survival time of the hypothermic group ($31.8{\pm}14.8$ h) was greater than that of the normothermic group($12.3{\pm}6.5$ h, p<0.05). This study suggested that TH attenuated post resuscitation myocardial dysfunction in acute MI and would be a potential strategy in post resuscitation care.

• 한국간담췌외과학회지
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• 제26권1호
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• pp.47-57
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• 2022

Backgrounds/Aims: It is challenging to assess the efficacy of partial hepatectomy (PH) as a treatment option for patients with hepatocellular carcinoma (HCC) accompanied by cirrhosis. This study aimed to determine the cure fraction of PH for HCC accompanied by cirrhosis compared to that for HCC without cirrhosis. Methods: A systematic review was performed on outcomes of previous studies that compared recurrence-free survival (RFS) after PH in patients with HCC with or without cirrhosis. A meta-analysis was conducted to obtain the cumulative hazard ratio for two patient groups: cirrhosis and non-cirrhosis. Cure fractions after PH in both groups were determined using a cure model analysis. Results: A total of 18 studies were eligible for meta-analysis and 13 studies were selected for the cure model analysis. The cumulative hazard ratio for RFS of the cirrhosis group compared to that of the non-cirrhosis group was 1.66 (95% confidence interval [CI], 1.43-1.93). Survival data of 3,512 patients in both groups were reconstructed from survival curves of original articles for cure model analysis. The probability of being statistically cured after PH for HCC was 14.1% (95% CI, 10.6%-18.1%) in the cirrhosis group lower than that (32.5%) in the non-cirrhosis group (95% CI, 28.6%-36.4%). Conclusions: The prognosis after PH for HCC accompanied by cirrhosis is inferior to that for HCC without cirrhosis. However, a cure can be expected for one-seventh of patients with HCC accompanied by cirrhosis after PH.

• 한국방사선학회논문지
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• 제11권3호
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• pp.147-151
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• 2017

HFL-I 세포를 이용하여 immediate assay를 시행하였다. 발생한 repair의 양이 없기 때문에 $LogSn=-n{\gamma}({\alpha}d+{\beta}d^2$)에서 ${\gamma}$의 값은 1이며 이는 LQ model과 같다. 그리고 세포생존율의 데이터를 바탕으로 ${\alpha}$, ${\beta}$, ${\alpha}/{\beta}$의 값을 얻었다. 또한 12시간, 36시간, 48시간 후 delayed assay를 시행하여 marchese model 통해 ${\gamma}$값을 도출한 후 Pot entially lethal damage repair (PLDR)가 발생한 양을 확인하였다. delay time이 길어질수록 ${\gamma}$값은 감소함으로써 PLDR의 양이 증가함을 확인하였고 이에 따라 세포생존율은 상승됨을 보였다. 탄소빔의 1분할, 2분할, 3분할, 4분할 조사 시 각각의 interval 시간동안 나타나는 ${\gamma}$값 역시 감소하고 있음을 확인하여 PLDR의 발생을 확인할 수 있었지만 ${\gamma}$값만 감안한 marchese model을 surviving fraction값에 적용 시 오류 발생함을 보였다. 이는 탄소빔 분할조사 시 다른 회복의 매커니즘이 존재함을 뜻하여 이를 적용할 수 있는 새로운 파라미터가 고려되어져야 할 것이다.

• Tuberculosis and Respiratory Diseases
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• 제46권1호
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• pp.36-43
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• 1999

연구배경: bcl-2는 apoptosis를 억제하여 세포 수명을 연장시켜 종양세포의 생존기간 중 다른 암유전자의 추가척인 영향을 받을 수 있는 기회를 증가시켜 암을 유발하는 암유전자이다. 이러한 bcl-2는 apoptosis 억제에도 불구하고, 임상적으로 bcl-2 양성인 경우에 그 기전은 아직 확실치 않으나 오히려 예후가 양호하다는 보고가 있다. 이에 저자들은 비소세포 폐암에서 bcl-2의 발현률을 계측하고, 세포분열주기와 비교한 후 생존률과의 관계를 검색하였다. 방 법: 원발성 비소세포 폐암으로 확진받고, 외과적 절제술후 paraffin에 보관된 57례의 병리조직에서 면역조직화학 염색법으로 bcl-2의 발현을 확인하고, bcl-2와 병리조직형, TNM 병기, 유식세포분석법에 의한 세포주기비율(S-and $G_1$-phase fraction) 그리고 생존기간과의 관계를 분석하였다. 결 과: 57례 중 남녀비는 43:14 였고, 조직학적 분류는 편평상피암 34례, 선암 19례, 대세포암 4례였으며, TNM I 병기 14례, II 병기 21례, III 병기 22례였다. bcl-2는 43.8% (25/57)에서 발현되었으며 면평상피암 47%(16/34), 선암 32%(6/19)였으나, 유의한 차이는 없었고, TNM I 병기 28.6%(4/14), II 병기 52.3% (11/21), III 병기 45.5%(10/22)로서 역시 유의한 차이는 없었다. bcl-2 발현군과 비발현군에서의 $G_1$-주기비율은 75.5($\pm10.8$)%, 65.5($\pm11.4$)% 로서 유의한 차이가 있었으며 (p<0.05), S-주기비율은 14.1($\pm7.8$)%, 24.7($\pm10.5$)%로서 역시 유의하게 bcl-2 발현군의 세포분열능이 저하되어 있었다 (p<0.005). bcl-2 발현군과 비발현군에서의 2년 생존률은 65%, 71%, 3년 생존률은 54%, 52%, 5년 생존률은 41%, 46% 그리고 중간 생존기간은 53개월, 37개월이었으나 통계적 유의성에 이르지는 못하였다. (p>0.05, Kaplan-Meier, log rank) 결 론: 비소세포 폐암에서 bcl-2는 43.8%에서 발현되었으며, 병리조직형, TNM 병기에 따른 발현률의 차이는 없었다. bcl-2 발현군은 비발현군에 비하여 S-주기비율은 유의하게 감소하고, $G_1$-주기비율은 유의하게 증가되었다. bcl-2 발현군의 중간 생존기간은 53개월로서 비발현군의 37개월보다 연장되었으나 통계적 유의성에 이르지는 못하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9673-9678
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• 2014

Background: Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Materials and Methods: Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. Results: The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Conclusions: Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.617-622
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• 2014

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MPI fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.