• Title/Summary/Keyword: Cell fractionation

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Induction Chemotherapy and Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (국소 진행된 비소세포성 폐암에서 유도 화학요법 및 방사선치료)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.195-202
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    • 1999
  • Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

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Pro-apoptotic and Anti-adipogenic Effects of Proso Millet (Panicum miliaceum) Grains on 3T3-L1 Preadipocytes (기장(Panicum miliaceum)의 마우스 3T3-L1 세포에 대한 에폽토시스 유발 및 지방세포형성 억제 효능)

  • Jun, Do Youn;Lee, Ji Young;Han, Cho Rong;Kim, Kwan-Pil;Seo, Myung Chul;Nam, Min Hee;Kim, Young Ho
    • Journal of Life Science
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    • v.24 no.5
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    • pp.505-514
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    • 2014
  • To examine the anti-obese activity of miscellaneous cereal grains, 80% ethanol extracts from eight selected miscellaneous cereal grains were compared for their cytotoxic effects on 3T3-L1 murine preadipocytes. The ethanol extract of proso millet exhibited the highest cytotoxicity. Further fractionation of the ethanol extract with methylene chloride, ethyl acetate, and n-butanol showed that the cytotoxicity of the ethanol extract was mainly partitioned into the butanol fraction. As compared with differentiated mature adipocytes, 3T3-L1 preadipocytes were more susceptible to the cyctotoxicity of the butanol fraction. When each organic solvent fraction (25 ${\mu}g/ml$) was added during the differentiation period for 6 days, the cell viability was not affected significantly except for the butanol fraction, but the intracellular lipid accumulation declined to a level of 81.5%~50.3% of the control. The Oil Red O staining data also demonstrated that the ethanol extract as well as the butanol fraction could inhibit the differentiation of 3T3-L1 preadipocytes into mature adipocytes. The presence of the butanol extract during the induced adipocytic differentiation also resulted in a significant reduction in the expression levels of critical adipogenesis mediators $(C/EBP{\alpha}$, $PPAR{\gamma}$, aP2, and LPL) to a barely detectable or undetectable level and the cells retained the fibroblast-like morphology of 3T3-L1. In 3T3-L1 cells, the cytotoxicity of the butanol fraction (50-100 ${\mu}g/ml$) was accompanied by mitochondrial membrane potential (${\Delta}{\psi}m$) loss, caspase-3 activation, and PARP degradation. Taken together, these results indicate that proso millet grains possess pro-apoptotic and anti-adipocytic activities toward adipocytes, which can be applicable to prevention of obesity.

A study of the lipoprotein lipase inhibitory mechanism of Poncirus trifoliata water extracts (탱자 (Poncirus trifoliata)의 lipoprotein lipase 억제메커니즘)

  • Lee, Sung Mee;Kang, Yun Hwan;Kim, Kyoung Kon;Kim, Tae Woo;Choe, Myeon
    • Journal of Nutrition and Health
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    • v.48 no.1
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    • pp.9-18
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    • 2015
  • Purpose: Poncirus trifoliata has been reported to have anti-inflammatory, antioxidant, and immune activities. However, its anti-obesity activity and the mechanism by which the water extract of dried, immature fruit of Poncirus trifoliata (PF-W) acts are not clear. This study suggests a potential mechanism associated with the anti-obesity activity of PF-W. Methods: We measured the effect of PF-W on lipoprotein lipase (LPL) regulation using enzyme-linked immunosorbent assay (ELISA) and an activity assay. The LPL regulation mechanism was examined by reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression of biomarkers related to protein transport and by western blot for analysis of the protein expression of the transcription factor CCAAT-enhancer-binding protein ($C/EBP{\beta}$). Results: The total polyphenol and flavonoid content of PF-W was $52.15{\pm}4.02$ and $6.56{\pm}0.47mg/g$, respectively. PF-W treatment decreased LPL content in media to $58{\pm}5%$ of that in control adipocyte media, and increased LPL content to $117{\pm}3.5%$ of that in control adipocytes, but did not affect the mRNA expression of LPL. PF-W also increased the mRNA expression of sortilin-related receptor (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL, in a concentration- and time-dependent manner. Finally, cell fractionation revealed that PF-W treatment induced the expression of $C/EBP{\beta}$, a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. Conclusion: The LPL secretion and activity assay showed PF-W to be an LPL secretion inhibitor, and these results suggest the potential mechanism of PF-W involving inhibition of LPL secretion through $C/EBP{\beta}$-mediated induction of SorLA expression.

Oxidative Pathway of $C^{14}-glucose$ in Various Human Cancer Tissues (각종 인체 암조직의 당의 산화경로 분석)

  • Lee, Bong-Kee;Lee, Sang-Don
    • The Korean Journal of Physiology
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    • v.2 no.1
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    • pp.23-30
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    • 1968
  • Tissue homogenates of 12 kinds of human cancer tissues were incubated separately in medium containing $C^{14}-1-glucose$ and $C^{14}-6-glucose$ as a substrate in order to observe the oxidative pathway of glucose in the tumor tissues. At the end of 3 hours incubation in the Dubnuff metabolic shaking incubator, respiratory $CO_2$ samples trapped by alkaling which was placed in the center well of incubation flask were analysed for total $CO_2$ production rates and their radioactivities. The tissue homogenate samples after incubation were analyzed for their concentrations of glucose, lactate and pyruvate. Calculations were made on the glucose consumption rate and accumulation rates of lactate and pyruvate. Fractionation of oxidative pathway of glucose was carried out by calculating $C^{14}O_2 yields from C-1 and C-6 carbon of glucose. The following results were obtained. 1. In 12 kinds of human cancer, total $CO_2$ production rates were less than $8{\mu}M/gm$ except 2 cases. These lower values impressed that oxidative metabolism in the tumor tissues generally inhibited as compared with that in normal tissues. On the other hand, fractions of $CO_2$ derived from glucose to total $CO_2$ production rates (RSA) were less than 10% in every case. These facts showed that oxidation of glucose into $CO_2$ was remarkably inhibited in the tumor tissues. 2. Factions of glucose disappeared into $CO_2\;(RGD_{CO_2})$, lactate $(RGD_L)$, pyruvate $(RGD_P)$ to glucose consumption rates were as follows. $RGD_{CO_2}$ were less than 2% in cases of in this experiment and $RGD_L$ showed more than 5% except in 2 cases. These facts showed that anaerobic degradation of glucose into 3 carbon compounds was easily proceeded but further degradation into $CO_2$ via the TCA cycle was greatly inhibited resulting in accumulation of lactate. There are large variation in values of $RGD_P$ in different kinds of tumor tissue but relatively higher values in $RGD_{CO_2}$ were obtained in the tumor tissues as compared with those of normal tissues. 3. The oxidative pathway of glucose in tumor tissues were analyzed from the values of RSA which were obtained in $C^{14}-1\;and\;C^{14}-6-glucose$ incubation experiments. It was found that 3% of $CO_2$ derived from glucose were oxidized via the principal EMP-TCA cycle and the remainder were via alternate pathway such as HMP in the liver cancer and values in other cancer tissues were as follows; 4% in the tongue cancer, 6% in the colon cancer, 6% in the lung cancer, 9% in the stomach cancer, 11% in the ovarian cancer, 12% in the neck tumor, 22% in the uterine cancer, 22% in the bladder tumor, 32% in the spindle cell sarcoma and 65% in the brain tumor. These values except later 2 cases showed less than 30% which is the lowest value among the normal tissues. Even in the brain tumor in which showed highest value in the tumor group. It is reasonable to suppose that this fraction was remarkably decreased because values in normal brain tissue was more than 90%. From the above data, it was concluded that in tumor tissues, oxidation of glucose via TCA cycle was greatly inhibited but correlation between degree of inhibited oxidation of glucose via TCA cycle and malignancy of tumor were not clarified in this experiments.

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Quality Characteristics and Antioxidant Activity of Prickly Pear Cactus Cladodes (손바닥 선인장 엽상경의 품질 특성과 항산화 효과)

  • Hwang, Joon-Ho;Yi, Mi-Ran;Kim, Jae-Won;Bu, Hee-Jung;Kang, Chang-Hee;Lim, Sang-Bin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.356-362
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    • 2015
  • Prickly pear cactus cladodes were extracted with hot water and 70% ethanol, followed by fractionation with n-hexane (HF), ethyl acetate (EF), n-butanol (BF), and distilled water. Total phenolics and total flavonoid contents as well as antioxidative and anti-inflammatory activities were then measured. Total phenolic contents were 784, 452, and 220 mg gallic acid equivalents (GAE)/g, whereas total flavonoid contents were 214, 76, and 113 mg quercetin equivalents (QE)/g in EF, BF, and HF, respectively. DPPH and ABTS radical scavenging activities ($IC_{50}$) were 103 and $105{\mu}g/mL$ in EF, 359 and $379{\mu}g/mL$ in BF, and 469 and $605{\mu}g/mL$ in HF, respectively. Oxygen radical absorbance capacity was highest at $391{\mu}M$ TE in EF (in decreasing order of $117{\mu}M$ TE in BF and $64{\mu}M$ TE in HF), whereas superoxide anion radical scavenging activity ($IC_{50}$) was highest at $40{\mu}g/mL$ in EF (in decreasing order of $69{\mu}g/mL$ in BF and $98{\mu}g/mL$ in 70% ethanol extract). Inhibitory activity ($IC_{50}$) of nitric oxide (NO) production induced by LPS-activated RAW264.7 cells was highest at $62{\mu}g/mL$ in HF (in decreasing order of $104{\mu}g/mL$ in EF and $465{\mu}g/mL$ in BF). The selectivity index (ratio of inhibitory activity of NO production to cell cytotoxicity) was highest at 4.63 in EF (in decreasing order of 3.37 in HF and 2.14 in BF). In conclusion, EF showed potent antioxidant and anti-inflammatory effects with high phenolic and flavonoid contents.

Enzymological Evaluation of Oral Inflammation inhibitory activity by Aloe vera peel extract (Aloe vera peel 추출물에 의한 구강염증 저해 효과의 효소학적 평가)

  • Pack, Chung-Sun;Ryu, Il-Hwan;Lee, Kap-Sang
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.753-759
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    • 2001
  • To evaluate antiinflammation of Aloe vera peel, antiimflammation substances were extracted from Aloe vera peel and identified, and we investigated the effect of the its substance the inhibitory effect on the activity of hyaluoronidase, elastase, collagenase and prostaglandin endoperoxide synthase. The water extract from Aloe vera peel were successfully purified with solvent fractionation, silica gel column chromatography, preparative thin layer chromatography and UV spectrometer. Two purified active substances were identified as aloe-emodin and barbaloin by Mass Spectrometer, $^1H-NMR$ and FT-IR. Aloe-emodin and barbaloin. $IC_{50}$ values of aloe-emodin and barbaloin against hyaluronidase activity were 40 and $70\;{\mu}g/mL$, respectively. Leuckocyte elastase, which is related to the destruction of various tissue, $IC_{50}$ values of them were 50 and $60\;{\mu}g/mL$, respectively. $IC_{50}$ values of aloe-emodin and barbaloin against collagenase activity were 40 and $60\;{\mu}g/mL$, respectively. and $IC_{50}$ values of aloe-emodin and barbaloin aganist the prostaglandin endoperoxide synthase, which play an important role in inflammatory reactions, were 40 and $70\;{\mu}g/mL$, respectively. Inhibitory effects of aloe-emodin, barbaloin and aspirin against carrageenan paw edema were 74.9, 52.9 and 51.9% as inhibiton percentage, respectively, at dose of 100 mg/kg and that of indomethancin was 49.7 at dose of 10 mg/kg. Cell cytotoxicity of barbaloin against human gingival cells was lower than that of aloe-emodin. Aloe-emodin and barbaloin did not show cytotoxicity against human gingival cells at concentration of 1.0 and $5.0\;{\mu}g/mL$, However, aloe-emodin and barbaloin showed less cytotoxicity than chlorhexidine, which usually have been used as the agent of anticaries and antiinflammation. These results suggested that aloe-emodin and barbaloin from Aloe vera peel have the effect of anticaries and antiinflammation.

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Once vs. Twice Daily Thoracic Irradiation in Limited Stage Small Cell Lung Cancer (국한성 병기 소세포폐암의 방사선치료시 분할 조사방식에 따른 치료성적)

  • Kim, Jun-Sang;Kim, Jae-Sung;Kim, Ju-Ock;Kim, Sun-Young;Cho, Moon-June
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.291-301
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    • 1998
  • Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

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Investigation of Study Items for the Patterns of Care Study in the Radiotherapy of Laryngeal Cancer: Preliminary Results (후두암의 방사선치료 Patterns of Care Study를 위한 프로그램 항목 개발: 예비 결과)

  • Chung Woong-Ki;Kim I1-Han;Ahn Sung-Ja;Nam Taek-Keun;Oh Yoon-Kyeong;Song Ju-Young;Nah Byung-Sik;Chung Gyung-Ai;Kwon Hyoung-Cheol;Kim Jung-Soo;Kim Soo-Kon;Kang Jeong-Ku
    • Radiation Oncology Journal
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    • v.21 no.4
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    • pp.299-305
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    • 2003
  • Purpose: In order to develop the national guide-lines for the standardization of radiotherapy we are planning to establish a web-based, on-line data-base system for laryngeal cancer. As a first step this study was performed to accumulate the basic clinical information of laryngeal cancer and to determine the items needed for the data-base system. Materials and Methods: We analyzed the clinical data on patients who were treated under the diagnosis of laryngeal cancer from January 1998 through December 1999 In the South-west area of Korea. Eligiblity criteria of the patients are as follows: 18 years or older, currently diagnosed with primary epithelial carcinoma of larynx, and no history of previous treatments for another cancers and the other laryngeal diseases. The items were developed and filled out by radiation oncologlst who are members of forean Southwest Radiation Oncology Group. SPSS vl0.0 software was used for statistical analysis. Results: Data of forty-five patients were collected. Age distribution of patients ranged from 28 to 88 years(median, 61). Laryngeal cancer occurred predominantly In males (10 : 1 sex ratio). Twenty-eight patients (62$\%$) had primary cancers in the glottis and 17 (38$\%$) in the supraglottis. Most of them were diagnosed pathologically as squamous cell carcinoma (44/45, 98$\%$). Twenty-four of 28 glottic cancer patients (86$\%$) had AJCC (American Joint Committee on Cancer) stage I/II, but 50$\%$ (8/16) had In supraglottic cancer patients (p=0.02). Most patients(89$\%$) had the symptom of hoarseness. indirect laryngoscopy was done in all patients and direct laryngoscopy was peformed in 43 (98$\%$) patients. Twenty-one of 28 (75$\%$) glottic cancer cases and 6 of 17 (35$\%$) supraglottic cancer cases were treated with radiation alone, respectively. The combined treatment of surgery and radiation was used in 5 (18$\%$) glottic and 8 (47$\%$) supraglottic patients. Chemotherapy and radiation was used in 2 (7$\%$) glottic and 3 (18$\%$) supraglottic patients. There was no statistically significant difference in the use of combined modality treatments between glottic and supraglottic cancers (p=0.20). In all patients, 6 MV X-ray was used with conventional fractionation. The iraction size was 2 Gy In 80$\%$ of glottic cancer patients compared with 1.8 Gy in 59$\%$ of the patients with supraglottic cancers. The mean total dose delivered to primary lesions were 65.98 ey and 70.15 Gy in glottic and supraglottic patients treated, respectively, with radiation alone. Based on the collected data, 12 modules with 90 items were developed or the study of the patterns of care In laryngeal cancer. Conclusion: The study Items for laryngeal cancer were developed. In the near future, a web system will be established based on the Items Investigated, and then a nation-wide analysis on laryngeal cancer will be processed for the standardization and optimization of radlotherapy.