• Title/Summary/Keyword: Solid Tumor

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Combination Treatment with Arsenic Trioxide and Sulindac Induces Apoptosis of NCI-H157 Human Lung Carcinoma Cells via ROS Generation with Mitochondrial Dysfunction (NCI-H157 폐암 세포주에서 활성산소종의 생성과 미토콘드리아 기능변화를 한 Arsenic Trioxide와 Sulindac 병합요법의 세포고사효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • 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.

Laparoscopy-assisted Total Gastrectomy for Advanced Upper Gastric Cancer - Comparison with Open Total Gastrectomy - (진행위암의 복강경 보조 위 전절제술 - 개복 위 전절제술과의 후향적 비교 -)

  • Lee, Jun Hyun;Nam, Yoo Hee;Hur, Hoon;Jeon, Hae Myung;Kim, Wook
    • Journal of Gastric Cancer
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    • v.8 no.3
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    • pp.141-147
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    • 2008
  • Purpose: The aim of this study was to compare the short-term operative outcomes of laparoscopy-assisted total gastrectomy (LATG) with those of open total gastrectomy (OTG) for patients suffering with advanced upper gastric cancer. Materials and Methods: Of the 47 patients who underwent LATG with $D1+{\beta}$ or D2 lymphadenectomy from July 2004 to March 2008, 29 patients with pathologically proven advanced gastric cancer were compared with 35 patients who underwent conventional OTG during the same time period. The comparison was based on the clinicopathological characteristics, the surgical outcome, the follow-up survival and tumor recurrence. Results: The patients' age, gender and body mass index were similar between the two groups. However, there were statistically differences in tumor size ($9.2{\pm}3.9$ vs $6.1{\pm}3.6cm$, P=0.002) and the proximal resected margin ($2.1{\pm}2.0$ vs $3.6{\pm}2.1cm$ P=0.004). There was no significant difference in most of the peri- and post-operative courses such as the time to first flatus, the time to starting a solid diet and the length of the hospital stay, except for a longer operating time (289.0 vs. 361.3 minutes, P<0.001) in the LATG group. The complication rate was higher in the LATG group (13.8%) than that in the OTG group (5.7%). The mean overall survival and disease free survival times were 32 and 31 months, and 24 and 28 months, respectively, with an average 18.8 months follow-up duration. The main recurrent sites were peritoneum and lymph node in both groups. Conclusion: The early results of the current study suggest that LATG for AGC is technically feasible and it does not show any inferiorities of the postoperative outcomes as compared to those of conventional open total gastrectomy.

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The Radiation Therapy for Spinal Cord Compression in Hematologic Malignancy (혈암에서 발생한 척추압박증상의 방사선 치료)

  • Kim In Ah;Choi Ihl Bohng;Chung Su Mi;Kang Ki Mun;Kay Chul Seong;Choi Byung Ok;Jang Ji Young;Shinn Kyung Sub;Kim Chun Choo
    • Radiation Oncology Journal
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    • v.12 no.3
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    • pp.393-399
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    • 1994
  • Spinal cord compression, an oncologic emergency, is a rare complication of hematologic malignancy Our experience was obtained with a series 32 Patients following retrospective analysis for assessing the role of radiation therapy and identifying the prognostic factors affecting on treatment outcome. Diagnosis was usually made by means of radiologic study such as myelography or computerized tomography (CT) or magnetic resonance imaging (MRI) and neurologic examination. Five cases were diagnosed by subjective symptom only with high index of suspicion. In 31 cases, the treatment consisted in radiation therapy alone and the remained one patient had laminectomy before radiation therapy because of diagnostic doubts. Total treatment doses ranged from 800 cGy to 4000 cGy with median of 2000 cGy. Initially large fraction size more than 250 cGy were used in 13 patients with rapidly progressed neurologic deficit. The clinical parameters considered in evaluating the response to treatment were backache, motor-sensory performance and sphincter function. Half of all patients showed good response. Partial response and no response were noted in $37.5\%$ and $12.5\%$, respectively. Our results showed higher response rate than those of other solid tumor series. The degree of neurologic deficit at that time of diagnosis was the most important predictor of treatment outcome. The elapsed time from development of symptoms to start of treatment was significantly affected on the outcome. But histology of primary tumor total dose and use of initial large fraction size were not significantly affect on the outcome. These results confirmed the value of early diagnosis and treatment especially in radiosensitive hematologic malignancy.

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Relationship between S-Phase Fraction and Survival Time in Patients with Primary Squamous Lung Cancer (편평상피성 폐암에 있어서 S-Phase Fraction과 생존기간과의 관계)

  • Jung, Byung-Hak;Kang, Jeong-Seong;Chang, Keun;Jeong, Eun-Taik;Chung, Hun-Taeg;Moon, Hyung-Bae
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.6
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    • pp.669-676
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    • 1993
  • Background: DNA content analysis of human solid tumor is now widely performed by flow cytometric study. One of the most interesting and potentially important observation in this field is that proliferative activity(S-Phase fraction of cell cycle) may profoundly affect prognosis. Method: S-Phase fraction(SPF) have been measured by flow cytometric method using tumor cells isolated from paraffin embedded tissue. To evaluate the prognostic significance, SPF of squamous lung cancer cell was assessed in 21 patients who died without any specific treatment. Results: 1) Mean survival time of squamous lung cancer patients was 225(${\pm}162$) days. Survival time were shortened, when TNM stage and PS scale were advanced. 2) Mean value of SPF of squamous lung cancer patients was 23.4(${\pm}11.3$)%. SPF had nothing to do with advance of TNM stage and PS scale. 3) Mean survival time of high SPF group(more than 20% of cell proliferation cycle) and low SPF group were 153(${\pm}99$) days and 342(${\pm}180$) days(p<0.01). In each identical TNM stage and PS scale, there were also statistic significant differences in mean survival time between high and low SPF group. Conclusion: On multivariate analysis including TNM stage and performance status, SPF was the significant and independent prognostic factor in the primary squamous lung cancer patients group.

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Optimal Level for the Protection of Carbon Tetrachloride-induced Sprague-Dawley Rat Liver Damage by Mycelial Cultures of Lentinus edodes (Sprague-Dawley 쥐의 사염화탄소 유도 간 손상에 대한 표고버섯균사체의 효과)

  • Jang, Wook-J.;Kim, Young-S.;Ha, Yeong-L.;Park, Cherl-W.;Ha, Young-K.;Kim, Jeong-O.
    • Journal of Life Science
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    • v.20 no.5
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    • pp.782-788
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    • 2010
  • The protective effects of a powder mixed with solid-cultured and liquid-cultured Lentinus edodes mycelia (2 : 1, w/w) (designate LED) with different doses of carbon tetrachloride ($CCl_4$) on induced hepatotoxicity in male Sprague-Dawley (SD) rats was investigated. The rats were divided into seven groups (6 rats/group) and the following substances were administered orally to each group: Vehicle (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 100, 200, 300 and 400 mg/kg BW in 0.2 ml distilled water), and Silymarin (200 mg/Kg BW in 0.2 ml distilled water). After two weeks of daily administration, all groups except for the Vehiclegroup were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1 : 1 v/v; 0.5 ml/kg BW). One day later, blood and liver samples were collected to analyze biomarkers. All LED treatments elevated hepatic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH peroxidase) activities, and reduced thiobarbituric reactive substances (TBARS), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6), resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic acid dehydrogenase (LDH) activities in plasma. These results indicate that LED effectively protected SD rat hepatotoxicity induced by $CCl_4$ through its antioxidative activity and reduction of some cytokines. The highest efficacy was found in LED 200 mg/kg BW, showing potential as a useful material for protection from hepatotoxicity in humans.

Expression of Oncogene Product in the Colorectal Carcinoma (결장암 및 직장암에서 암유전자 산물의 발현)

  • Shim, Young-Ran;Jang, Woo-Young;Choi, Kyoung-Chan;Choi, Joon-Hyuk;Choi, Won-Hee;Shim, Min-Chul
    • Journal of Yeungnam Medical Science
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    • v.12 no.2
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    • pp.210-225
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    • 1995
  • The expression of $p62^{c-myc}$ and $p21^{ras}$ can be seen in many solid tumor, but the pattern and incidence of expression were different according to organ, countries, and examiners, thus it is not definitely defined. Total 67 colorectal carcinoma in paraffin sections are analysed by immunohistochemically for evaluation of the $p62^{c-myc}$ and $p21^{ras}$ expression according to the age, sex, chief complaints, location, differentiation, modified Dukes stage, using the specific monoclonal antibodies. The results were summarized as follows : The age of patients ranged from 32 years to 82 years. The mean age was 57.6 years. The expression of $p62^{c-myc}$ and $p21^{ras}$ was not correlated with age. Male was 29 cases(43.3%) and female was 38 cases(56.7%). The male to female ratio was 1:1.31. The expression of $p21^{ras}$ was increased in female(p<0.05). Abdominal pain(43.7%) was the most frequent chief complaint. The most frequent tumor location was rectum(44.8%). The expression of $p62^{c-myc}$ was increased in the rectum(p<0.05). The 65 cases(97.0%) out of 67 cases showed positive reaction of $p62^{c-myc}$ in the nucleus, cytoplasmic membrane, and cytoplasm. The 62 cases(92.5%) out of 67 cases showed positive reaction of $p21^{ras}$ in the cytoplasmic membrane and cytoplasm. The positive rate of $p62^{c-myc}$ and $p21^{ras}$ was 97.0% and 91.4% in well differentiated adenocarcinoma, 100.0% and 95.0% in moderately differentiated adenocarcinoma, 90.0% and 90.0% in poorly differentiated adenocarcinoma, 100.0% and 100.0% in mucinous carcinoma. The positive rate of $p62^{c-myc}$ and $p21^{ras}$ was 94.1% and 88.2% in Dukes stage $B_1$, 96.0% and 96.0% in Dukes stage $B_2$, 100.0% and 100.0% in Dukes stage $C_1$, 100.0% and 88.9% in Dukes stage $C_2$, and 100.0% and 100.0% in Dukes stage D. The expression of $p62^{c-myc}$ in metastatic colorectal carcinoma showed diffuse and strongly positive reaction than primary colorectal carcinoma. The expression of $p21^{ras}$ in primary colorectal carcinoma showed diffuse and strongly positive reaction than metastatic colorectal carcinoma.

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Factors Related to Serum Level of Carbohydrate Antigen 19-9 and Cancer Antigen 125 in Healthy Rural Populations in Korea (일부 농촌지역 주민에서 혈청 CA19-9 및 CA125 농도에 영향을 미치는 인자에 관한 연구)

  • Lee, SK;Yoo, KY;Park, SK;Kang, DH;Kim, JQ;Chung, JK;Lee, MC
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.1
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    • pp.71-80
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    • 1998
  • This study examines the levels of carbohydrate antigen 19-9(CA19-9) and cancer antigen 125(CA125) in serum and its related factors in healthy Korean population. Although CA19-9 and CA125 have been widely used tumor markers for gastroenteric cancers and ovarian cancer in Western countries, there are no information available on the serum levels of CA19-9 and CA125 in healthy population and the factors affecting the levels of these tumor markers in Korea. A cross-sectional study was performed to measure CA19-9 and CA125 among 76 healthy males and 95 healthy females in Korea. CA19-9 and CA125 were quantitated using solid-phase radioimmunoassay kits. Informations on the factors which might be related to the levels of these markers were collected by questionnaire(e.g., smoking, alcohol consumption, menstruation, oral pill use, breast-feeding history, etc.). There was no statistically significant difference in the mean of CA19-9 concentration between men(10.4 u/ml) and women(10.1 u/ml), whereas the mean of CA125 levels(11.2 u/ml) was higher in women than that(2.5 u/ml) in men. Although there was a statistically significant association between CA19-9 and average number of cigarette consumed per day(r=0.59, p=0.026) and total number of cigarettes consumed in women(r=0.74, p=0.003), the significance disappeared by multiple regression analysis after adjusting age and body mass index. Later age of menopause(p=0.035) and longer duration of breast-feeding(p=0.050) were significant predictors for CA125 levels in women by multiple regression analysis after adjusting age and body mass index. In conclusion, CA19-9 can be used as a stable tumor marker in clinical practices, however, menstruation and breast-feeding should be considered when CA125 is used in women.

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Radiation Therapy for Bone Metastases from Hepatocellular Carcinoma: Effect of Radiation Dose Escalation (간세포암에 의한 뼈전이의 방사선치료: 고선량 방사선치료의 효과)

  • Kim, Tae-Gyu;Park, Hee-Chul;Lim, Do-Hoon;Kim, Cheol-Jin;Lee, Hye-Bin;Kwak, Keum-Yeon;Choi, Moon-Seok;Lee, Joon-Hyoek;Koh, Kwang-Cheol;Paik, Seung-Woon;Yoo, Byung-Chul
    • Radiation Oncology Journal
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    • v.29 no.2
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    • pp.63-70
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    • 2011
  • Purpose: To evaluate the extent of pain response and objective response to palliative radiotherapy (RT) for bone metastases from hepatocellular carcinoma according to RT dose. Materials and Methods: From January 2007 to June 2010, palliative RT was conducted for 103 patients (223 sites) with bone metastases from hepatocellular carcinoma. Treatment sites were divided into the high RT dose and low RT dose groups by biologically effective dose (BED) of 39 $Gy_{10}$. Pain responses were evaluated using the numeric rating scale. Pain scores before and after RT were compared and categorized into 'Decreased', 'No change' and 'Increased'. Radiological objective responses were categorized into complete response, partial response, stable disease and progression using modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria; the factors predicting patients' survival were analyzed. Results: The median follow-up period was 6 months (range, 0 to 46 months), and the radiologic responses existed in 67 RT sites (66.3%) and 44 sites (89.8%) in the high and low RT dose group, respectively. A dose-response relationship was found in relation to RT dose (p=0.02). Pain responses were 75% and 65% in the high and low RT dose groups, respectively. However, no statistical difference in pain response was found between the two groups (p=0.24). There were no differences in the toxicity profiles between the high and low RT dose groups. Median survival from the time of bone metastases diagnosis was 11 months (range, 0 to 46 months). The Child-Pugh classification at the time of palliative RT was the only significant predictive factor for patient survival after RT. Median survival time was 14 months under Child-Pugh A and 2 months under Child-Pugh B and C. Conclusion: The rate of radiologic objective response was higher in the high RT dose group. Palliative AT with a high dose would provide an improvement in patient quality of life through enhanced tumor response, especially in patients with proper liver function.

The Role of Radiotherapy in Patients with Brain Metastasis (고형암의 뇌전이시 방사선치료 효과)

  • Lee Soon Nam;Choo Mi-Soon;Lee Kyung-Ja;Nam Eunmi
    • Radiation Oncology Journal
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    • v.17 no.4
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    • pp.281-286
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    • 1999
  • Purpose : Brain metastases are the most frequent metastatic neurologic complication of systemic cancer. Even if the prognosis of brain metastases is grave, with available treatments, most patients experience effective palliation of neurologic symptoms and meaningful extension of life. We evaluated the clinical features and prognostic factors of the patients who were diagnosed as solid tumors with brain metastasis and received radiotherapy for brain metastases. Materials and Methods: Between January 1987 and January 1998, 71 patients with brain metastases from solid malignancy were included. We reviewed neurologic symptoms and signs of patients and evaluated improvememt of neurologic symptoms and signs. Survival durations after brain metastasis were ana lysed according to several factors such as age, performance status, primary malignancies, the pre-sence of brain metastasis at initial diagnosis of primary tumor, multiplicity of brain metastass, the presence of metastases other than brain, and treatment method. Results: Frequent symptoms associated with brain metastasis were headache (47.9$\%$), motor weakness (40.8$\%$), nausea and vomiting (19.7$\%$) and mental change (19.7%). Palliation of these symptoms was accomplished in 64.9$\%$ of cases. The overall median survival time was 16 weeks and 1- and 2-year survival rates were 15.0$\%$ and 5.1$\%$ respectively. Patients without extracranial metastases (n=27) had longer median survival than patients with extracranial metastases (33 weeks vs 10 weeks, p=0.0018). In patients with single brain metastasis (n=37), the median survival time was longer in patients treated with surgery plus radiotherapy than in patients treated with radiotherapy alone (40 weeks vs 16 weeks, p=0.0438). Conclusion: Patients who has brain metastases only constitute a prognostically favorable group and they may be benefited from radiotherapy and surgery if indicated.

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Association between Bone Marrow Hypermetabolism on 18F-Fluorodeoxyglucose Positron Emission Tomography and Response to Chemotherapy in Non-Small Cell Lung Cancer (비소세포폐암 환자의 양전자방출 단층촬영에서 골수 대사활성도의 항암화학요법에 대한 반응 예측)

  • Seol, Hee Yun;Mok, Jeong Ha;Yoon, Seong Hoon;Kim, Ji Eun;Kim, Ki Uk;Park, Hye-Kyung;Kim, Seong Jang;Kim, Yun Seong;Lee, Min Ki;Park, Soon Kew
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.1
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    • pp.20-26
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    • 2009
  • Background: $^{18}F$-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used for the diagnosis and staging of non-small cell lung cancer (NSCLC). The aim of this study is to determine whether the bone marrow hypermetabolism seen on FDG-PET predicts a response to chemotherapy in patients with NSCLC. Methods: We evaluated the patients with advanced NSCLC and who were treated with combination chemotherapy. For determination of the standardized uptake value (SUV) of the bone marrow (BM SUV) on FDG-PET, regions of interest (ROIs) were manually drawn over the lumbar vertebrae (L1, 2, 3). ROIs were also drawn on a homogenous transaxial slice of the liver to obtain the bone marrow/ liver SUV ratio (BM/L SUV ratio). The response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria after three cycles of chemotherapy. Results: Fifty-nine NSCLC patients were included in the study. Multivariate analysis was performed using a logistic regression model. The BM SUV and the BM/L SUV ratio on FDG-PET were not associated with a response to chemotherapy in NSCLC patients (p=0.142 and 0.978, respectively). Conclusion: The bone marrow hypermetabolism seen on FDG-PET can not predict a response to chemotherapy in NSCLC patients.