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Optimal Scheme of Postoperative Chemoradiotherapy in Rectal Cancer : Phase III Prospective Randomized Trial (직장암의 근치적 수술 후 화학요법과 방사선치료의 순서)

  • Kim Young Seok;Kim Jong Hoon;Choi Eun Kyung;Ahn Seung Do;Lee Sang-Wook;Kim Kyoung-Ju;Lee Je Hwan;Kim Jin Cheon;You Chang Sik;Kim Hee Cheol
    • Radiation Oncology Journal
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    • v.20 no.1
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    • pp.53-61
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    • 2002
  • Purpose : To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, Patterns of failure, toxicities in early and late radiotherapy groups using a Phase III randomized prospective clinical trial. Materials and Methods : From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm 1)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU $375\;mg/m^2/day$, leucovorin $20\;mg/m^2$, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. Results : Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were $78.3\%\;and\;68.7\%$ in arm I, and $78.4\%\;and\;67.5\%$ in arm II. The local recurrence rate was $6.6\%\;and\;6.4\%$ (p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms ($23.8\%\;and\;29.5\%$, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in $63.0\%\;and\;58.2\%$ of the respective arms (p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only $1.3\%\;and\;2.6\%$ of patients in each respective arm. Conclusion : There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.

Results of Total Body Irradiation in Allogeneic Bone Marrow Transplantation for Acute Non-Lymphocytic Leukemia (급성 골수성 백혈병에서 동종골수이식을 위한 전신 방사선 조사의 치료 결과)

  • Chung Su Mi;Choi Ihl Bohng;Kim In Ah;Kim Sung Hwan;Kang Ki Mun;Shinn Kyung Sub;Kim Choon Choo;Kim Dong Jip
    • Radiation Oncology Journal
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    • v.10 no.2
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    • pp.247-253
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    • 1992
  • Between August 1987 and July 1991, 22 patients with acute nonlymphocytic leukemia have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. Of these patients, 12 patients were in first complete remission (CR) and 10 patients in second CR or greater or in relapse. All patients were treated with a preparative regimen consisting of cyclophosphamide (CTX, 60 mg/kg) or combined drugs, and 850 cGy single-dose or $150\~200$ cGy fractionated total body irradiation (TBI) administered twice daily for a total dose of $1200\~1320$ cGy. Survivors have been followed from 8 to 64.5 months (median, 24 months). The overall 2 year survival rate, relapse rate and incidence of radiation pneumonitis and graft versus host disease (GVHD) have been evaluated by age, phase of disease, initial WBC count, modality of TBI or conditioning chemotherapy. Overall 2 year survival was $58{\%}$. The median survival was 31 months and mean survival was 23.2 months. Overall survival have significant impact in patients of age >19 years old (p=0.008), patients in first CR (p=0.09). Two year survival rate is significantly correlated with age ( >19 vs $\leqq$19, $79.4\%$ vs $14.3\%$, p=0.0008), regimen of chemotherapy (CTX vs combined drug, $76.9\%\;vs\;33.3\%$, p=0.04), phase of disease (1st CR vs \geqq2nd$ CR or relapse, $83.3\%\;vs\;30\%$, p=0.01) and method of TBI (fractionated vs single dose, $70.7\%\;vs\;37.5\%$, p=0.05). The influence of French-American-British (FAB) subtypes on relapse rate is not significant, but initial WBC count > 20000/$mm^3$ is associated with increased relapse rate. There is difference in the rate of radiation pneumonitis ($14.3\%\;vs\;25\%$), GVHD ($14.3\%\;vs\;50\%$) and relapse ($21.4\%\;vs\;50\%$) according to fractionated versus single-dose TBI. As mentioned above, fractionated TBI is compatible for the preparative regimen combined with chemotherapy En allogeneic BMT of first CR patients under 41 years of age with suitable donor. Those results from a retrospective, non-randomized study clearly need additional clinical data, ideally from a randomized study.

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Treatment Outcome of Locally Advanced Non-small Cell Lung Cancer Patients Who Received Concurrent Chemoradiotherapy with Weekly Paclitaxel (Paclitaxel 매주 투여 및 방사선치료 동시요법을 받은 국소진행성 비소세포폐암 환자들의 치료 결과)

  • Kim, Su-Zy;Shim, Byoung-Yong;Kim, Chi-Hong;Song, So-Hyang;Ahn, Meyung-Im;Cho, Deog-Gon;Cho, Kyu-Do;Yoo, Jin-Young;Kim, Hoon-Kyo;Kim, Sung-Whan
    • Radiation Oncology Journal
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    • v.24 no.4
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    • pp.230-236
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    • 2006
  • $\underline{Purpose}$: To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. $\underline{Materials\;and\;Methods}$: Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total $55.4{\sim}64.8$ (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over $7{\sim}8$ weeks. 50 or $60\;mg/m^2$ of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel $135\;mg/m^2$ and cisplatin $75\;mg/m^2$ was administered every 3 weeks. $\underline{Results}$: Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. $\underline{Conclusion}$: Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity rate. But local failure occurred frequently after the remission and large tumor size was a poor prognostic factor. Further investigations are needed to improve the local control.

The 1998, 1999 Patterns of Care Study for Breast Irradiation after Mastectomy in Korea (1998, 1999년도 우리나라에서 시행된 근치적 유방 전절제술 후 방사선치료 현황 조사)

  • Keum,, Ki-Chang;Shim, Su-Jung;Lee, Ik-Jae;Park, Won;Lee, Sang-Wook;Shin, Hyun-Soo;Chung, Eun-Ji;Chie, Eui-Kyu;Kim, Il-Han;Oh, Do-Hoon;Ha, Sung-Whan;Lee, Hyung-Sik;Ahn, Sung-Ja
    • Radiation Oncology Journal
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    • v.25 no.1
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    • pp.7-15
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    • 2007
  • [ $\underline{Purpose}$ ]: To determine the patterns of evaluation and treatment in patients with breast cancer after mastectomy and treated with radiotherapy. A nationwide study was performed with the goal of improving radiotherapy treatment. $\underline{Materials\;and\;Methods}$: A web- based database system for the Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Randomly selected records of 286 eligible patients treated between 1998 and 1999 from 17 hospitals were reviewed. $\underline{Results}$: The ages of the study patients ranged from 20 to 80 years (median age 44 years). The pathologic T stage by the AJCC was T1 in 9.7% of the cases, T2 in 59.2% of the cases, T3 in 25.6% of the cases, and T4 in 5.3% of the cases. For analysis of nodal involvement, N0 was 7.3%, N1 was 14%, N2 was 38.8%, and N3 was 38.5% of the cases. The AJCC stage was stage I in 0.7% of the cases, stage IIa in 3.8% of the cases, stage IIb in 9.8% of the cases, stage IIIa in 43% of the cases, stage IIIb in 2.8% of the cases, and IIIc in 38.5% of the cases. There were various sequences of chemotherapy and radiotherapy after mastectomy. Mastectomy and chemotherapy followed by radiotherapy was the most commonly performed sequence in 47% of the cases. Mastectomy, chemotherapy, and radiotherapy followed by additional chemotherapy was performed in 35% of the cases, and neoadjuvant chemoradiotherapy was performed in 12.5% of the cases. The radiotherapy volume was chest wall only in 5.6% of the cases. The volume was chest wall and supraclavicular fossa (SCL) in 20.3% of the cases; chest wall, SCL and internal mammary lymph node (IMN) in 27.6% of the cases; chest wall, SCL and posterior axillary lymph node in 25.9% of the cases; chest wall, SCL, IMN, and posterior axillary lymph node in 19.9% of the cases. Two patients received IMN only. The method of chest wall irradiation was tangential field in 57.3% of the cases and electron beam in 42% of the cases. A bolus for the chest wall was used in 54.8% of the tangential field cases and 52.5% of the electron beam cases. The radiation dose to the chest wall was $45{\sim}59.4\;Gy$ (median 50.4 Gy), to the SCL was $45{\sim}59.4\;Gy$ (median 50.4 Gy), and to the PAB was $4.8{\sim}38.8\;Gy$, (median 9 Gy) $\underline{Conclusion}$: Different and various treatment methods were used for radiotherapy of the breast cancer patients after mastectomy in each hospital. Most of treatment methods varied in the irradiation of the chest wall. A separate analysis for the details of radiotherapy planning also needs to be followed and the outcome of treatment is needed in order to evaluate the different processes.

Antagonistic Interaction between Quinclorac and Bensulfuron-methyl on Growth of the Rice Plants (Quinclorac과 Bensulfuron-methyl의 혼합처리(混合處理)에서 벼의 생장(生長)에 대한 제초제간(除草劑間) 길항작용(拮抗作用))

  • Kwon, Oh-Yeon;Kwon, Yong-Woong
    • Korean Journal of Weed Science
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    • v.17 no.3
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    • pp.288-294
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    • 1997
  • Field and pot expeiments were carried out to evaluate the interaction between quinclorac and bensulfuron-methyl on growth of the rice plants(Oryza sativa L. cv. Choocheongbyeo) at 20, 45, 65 days-old stages. Quinclorac and bensulfuron-methyl showed antagonistic interaction at both stages, which were detected by the Chisaka's method at isobles of 10% growth inhibition. The antagonism indices were -0.63 and -1.67 at 20 and 65 days-old seedling stages, respectively. Leaf-rolling of rice occurred when quinclorac was applied at 600g ai/ha or more at 20 days-old seedling stage, while it occured at the dose of 900g ai/ha at 65 days-old stage. Bensulfuron-methyl reduced plant height and dry weight as well as tiller production at both stages. Leaf-rolling of rice was reduced when mixture of quinclorac and bensulfuron-methyl was applied due to antagonism of the two herbicides. High temperatures increased the phytotoxicity of bensulfuron-methyl, while the phytotoxicity caused by quinclorac alone was not responsive to temperature. The antagonistic effect between quinclorac and bensulfuron-methyl increased at low temperature as tested by the Colby's method.

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Status and Prospect of Herbicide Resistant Weeds in Rice Field of Korea (한국 논에서 제초제 저항성잡초 발생 현황과 전망)

  • Park, Tae-Seon;Lee, In-Yong;Seong, Ki-Yeong;Cho, Hyeon-Suk;Park, Hong-Kyu;Ko, Jae-Kwon;Kang, Ui-Gum
    • Korean Journal of Weed Science
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    • v.31 no.2
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    • pp.119-133
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    • 2011
  • Sulfonylurea (SU)-resistant weeds include seven annual weeds such as Monochoria vaginalis, Scirpus juncoides and Cyperus difformis, etc., and three perennial weeds of Scirpus planiculmis, Sagittaria pigmaea and Eleocharis acicularis as of 2010 since identification Monochoria korsakowii in the reclaimed rice field in 1998. The Echinochloa oryzoides resistant to acetyl CoA carboxylase (ACCase) and acetolactate synthase (ALS) inhibitors has been confirmed in wet-direct seeding rice field of the southern province, Korea in 2009. In the beginning of occurrence of SU-resistant weeds the M. vaginalis, S. juncoides and C. difformis were rapidly and individually spreaded in different fields, however, theses resistant weeds have been occurring simultaneously in the same filed as time goes by. The resistant biotype by weed species demonstrated about 10- to 1,000-fold resistance, base on $GR_{50}$ (50% growth reduction) values of the SU herbicides tested. And the resistant biotype of E. oryzoides to cyhalofop-butyl, pyriminobac-methyl, and penoxsulam was about 14, 8, and 11 times more resistant than the susceptible biotype base on $GR_{50}$ values. In history of paddy herbicides in Korea, the introduction of SU herbicides including besulfuron-metyl and pyrazosulfuron-ethyl that control many troublesome weeds at low use rates and provide excellent crop safety gave farmers and many workers for herbicide business refreshing jolt. The products and applied area of SU-included herbicides have been rapidly increased, and have accounted for about 69% and 96%, respectively, in Korea. The top ten herbicides by applied area were composed of all SU-included herbicides by 2003. The concentrated and successive treatment of ACCase and ALS inhibitors for control of barnyardgrass in direct-seeded rice led up to the resistance of E. oryzoides. Also, SU-herbicides like pyrazosulfuron-ethyl and imazosulfuron which are effective to barnyardgrass can be bound up with the resistance of E. oryzoides. The ALS activity isolated from the resistant biotype of M. korsakowii to SU-herbicides tested was less sensitive than that of susceptible biotype. The concentration of herbicide required for 50% inhibition of ALS activity ($I_{50}$) of the SU-resistant M. korsakowii was 14- to 76-fold higher as compared to the susceptible biotype. No differences were observed in the rates of [$^{14}C$]bensulfuron uptake and translocation. ALS genes from M. vaginalis resistant and susceptible biotypes against SU-herbicides revealed a single amino acid substitution of proline (CCT), at 197th position based on the M. korsakowii ALS sequence numbering, to serin (TCT) in conserved domain A of the gene. Carfentrazone-ethyl and pyrazolate were used mainly to control SU-resistant M. vaginalis by 2006, the early period, in Korea. However, the alternative herbicides such as benzobicyclone, to be possible to control simultaneously the several resistant weeds, have been developing and using broadly because the several resistant weeds have been occurring simultaneously in the same filed. The top ten herbicides by applied area in Korea have been occupied by products of 3-way mixture type including herbicides with alternative mode of action for the herbicide resistant weeds. Mefenacet, fentrazamide and cafenstrole had excellent controlling effects on the ACCase and ALS inhibitors resistant when they were applied within 2 leaf stage.

Facters Affecting Recurrence after Video-assisted Thoracic Surgery for the Treatment of Spontaneous Pneumothotax (자연기흉에 대한 비디오흉강경수술후 재발에 영향을 미치는 요인들)

  • 이송암;김광택;이일현;백만종;최영호;이인성;김형묵;김학제
    • Journal of Chest Surgery
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    • v.32 no.5
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    • pp.448-455
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    • 1999
  • Background: Recent developments in techniques of video-assisted thoracic surgery(VATS) and endoscopic equipment has expanded the application of video-assisted surgical procedures in the field of thoracic surgery. Especially, it will probably become the treatment of choice of spontaneous pneumothorax(SP). There is, however, a high recurrence rate, high cost, and paucity of long-term results. We report the results of postoperative follow-up and analyze perioperative parameters affected to recurrence, retrospectively. Material and Method: From march 1992 to march 1997, 276 patients with spontaneous pneumothorax underwent 292 VATS procedures. Conversion to open thoracotomy was necessitated in eight patients, and this patients excluded from the study. Result: The sex distribution was 249 males and 31 females. The mean age was 28.1 12.2 years(range, 15 to 69 years). Primary SP was 237cases(83.5%) and secondary SP was 47cases(16.5%). The major underlying lung diseases associated with secondary SP were tuberculosis 27cases(57.4%) and emphysema 8cases (38.3%). Operative indications included Ipsilateral recurrence 123(43.9%), persistent air-leak 53(18.9%), x-ray visible bleb 40(14.3%), tension 30(10.7%), contralateral recurrence 21(7.5%), uncomplicated first episode 8(2.9%), bilateral 3(1.1%), complicated episode 2(0.7%). Blebs were visualized in 247cases(87%) and 244cases(85.9%) performed stapled blebectomy. Early postoperative complications occurred in 33 cases(11.6%): 16 prolonged air-leak more than 5 days(four of them were required a second operation and found missed blebs); 5 bleeding; 5 empyema; 2 atelectasis; 1 wound infection. No deaths occured. The mean operative time was 52.8 23.1 minutes(range, 20 to 165 minutes). The mean d ration of chest tube drainage was 5.0 4.5 days(range, 2 to 37 days). The mean duration ofhospital stay was 8.2 5.5 days (range, 3 to 43days). At a mean follow-up 22.3 18.4 months(range, 1 to 65 months), 12 patients(4.2%) were lost to follow-up. There were 24 recurrences and seven patients underwent second operation and 6 patients(85.7%) were found the missed blebs. 12 perioperative parameters(age, sex, site, underlying disease, extent of collapse, operative indication, size of bleb, number of bleb, location of bleb, bleb management, pleural procedure, prolonged postoperative air-leak) were analyzed statistically to identify significant predictors of recurrence. The significant predictors of recurrence was the underlying disease[17.0%(8/47): 6.8%(16/237), p=0.038], prolonged postoperative air-leakage[37.5%(6/16): 6.7%(18/268), p=0.001], and pleural procedure [11.4%(19/167): 4.3%(5/117), p=0.034]. Blebectomy has less recurrence rate then non-blebectomy [8.2%(20/244) : 10.0%(4/40), p>0. 5]. However, this difference was not statistically significant(p=0.758). Conclusion: We conclude that it is important that we shoud careful finding of bleb during VATS due to reducing of recurrnece, and cases of no bleb identified and secondary spontaneous pneumothorax were indicated of pleurodectomy. VATS is a valid alternative to open procedure for the treatment of spontaneous pneumothorax with less pain, shorter hospital stay, more rapid return to work, high patient acceptance, less scar and exellent cosmetics. But, there is high recurrence rate and high cost, and than it is necessary to evaluate of long-term results for recurrence and to observate carefully during VATS.

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The Hepatoprotective Effect of Active Compounds of Kochiae fructus on D-Galactosamine-Intoxicated Rats (지부자 활성성분이 D-Galactosamine 투여에 의한 흰쥐의 간손상에 미치는 영향)

  • Kim, Na-Young;Lee, Jeong-Sook;Park, Myoung-Ju;Lee, Kyung-Hee;Kim, Seok-Hwan;Choi, Jong-Won;Park, Hee-Juhn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.8
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    • pp.1286-1293
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    • 2004
  • This study was conducted to investigate the biological activity and hepatoprotective effect of various fractions and isolated compounds from Kochiae fructus (KF) extract on D-galactosamine (GaIN)-intoxicated rats. Male Sprague-Dawley rats were divided into control, GaIN treated group (GaIN), GaIN plus KF methanol extract treated group (KFM 200-GaIN), GaIN plus KF butanol extract treated group (KFB 200-GaIN), GaIN plus momordin Ic treated group (Momordin Ic 30-GaIN) and GaIN plus oleanolic acid treated group (Oleanolic acid 30-GaIN). KFM (200 mg/kg BW), KFB (200 mg/kg BW), momordin Ic (30 mg/kg BW) and oleanolic acid (30 mg/kg BW) were orally administered once a day for 14 days. GaIN (400 mg/kg BW) was injected at 30 minutes after the final administration of the compounds. The activities of serum aspartate aminotransferase and alanine aminotransferase were increased in the GaIN group compared to the control group and significantly lower in the KFB 200-GaIN, momordin Ic 30-GaIN and oleanolic acid 30-GaIN group than in the GaIN group. Hepatic lipid peroxide level was increased in the GaIN group compared to the control group and was lower in the KFM 200-GaIN, KFB 200-GaIN, momordin Ic 30-GaIN and oleanolic acid 30-GaIN group than in the GaIN group. Activities of xanthine oxidase and aldehyde oxidase in liver were higher in the GaIN group than in the control group and were significantly decreased in the KFB 200-GaIN, momordin Ic 30-GaIN and oleanolic acid 30-GaIN group compared to the GaIN group. Hepatic glutathione, ${\gamma}$-glutamylcysteine synthetase and catalase activities were decreased in the GaIN group compared to the control group and were higher in the KFB 200-GaIN, momordin Ic 30-GaIN and oleanolic acid 30-GaIN group than in the GaIN group. Activities of hepatic glutathione reductase, glutathione S-transferase, superoxide dismutase and glutathione peroxidase were lower in the GaIN group than in the control group and were improved in the KFM 200-GaIN, KFB 200-GaIN, momordin Ic 30-GaIN and oleanolic acid 30-GaIN group compared to the GaIN group. Therefore, the current results indicate that momordin Ic administration alleviated the GaIN-induced adverse effect through enhancing the antioxidant enzyme activities.

Tc-99m ECD Brain SPECT in MELAS Syndrome and Mitochondrial Myopathy: Comparison with MR findings (MELAS 증후군과 미토콘드리아 근육병에서의 Tc-99m ECD 뇌단일 광전자방출 전산화단층촬영 소견: 자기공명영상과의 비교)

  • Park, Sang-Joon;Ryu, Young-Hoon;Jeon, Tae-Joo;Kim, Jai-Keun;Nam, Ji-Eun;Yoon, Pyeong-Ho;Yoon, Choon-Sik;Lee, Jong-Doo
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.6
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    • pp.490-496
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    • 1998
  • Purpose: We evaluated brain perfusion SPECT findings of MELAS syndrome and mitochondrial myopathy in correlation with MR imaging in search of specific imaging features. Materials and Methods: Subjects were five patients (four females and one male; age range, 1 to 25 year) who presented with repeated stroke-like episodes, seizures or developmental delay or asymptomatic but had elevated lactic acid in CSF and serum. Conventional non-contrast MR imaging and Tc-99m-ethyl cysteinate dimer (ECD) brain perfusion SPECT were Performed and imaging features were analyzed. Results: MRI demonstrated increased T2 signal intensities in the affected areas of gray and white matters mainly in the parietal (4/5) and occipital lobes (4/5) and in the basal ganglia (1/5), which were not restricted to a specific vascular territory. SPECT demonstrated decreased perfusion in the corresponding regions of MRI lesions. In addition, there were perfusion defects in parietal (1 patient), temporal (2), and frontal (1) lobes and basal ganglia (1) and thalami (2). In a patient with mitochondrial myopathy who had normal MRI, decreased perfusion was noted in left parietal area and bilateral thalami. Conclusion: Tc-99m ECD SPECT imaging in patients with MELAS syndrome and mitochondrial myopathy showed hypoperfusion of parieto-occipital cortex, basal ganglia, thalamus and temporal cortex, which were not restricted to a specific vascular territory. There were no specific imaging features on SPECT. The significance of abnormal perfusion on SPECT without corresponding MR abnormalities needs to be evaluated further in larger number of patients.

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Reversal of Multidrug Resistance with KR-30035: Evaluated with Biodistribution of Tc-99m MIBI in Nude Mice Bearing Human Tumor Xenografts (이종이식된 인체종양에서 KR-30035가 Tc-99m MIBI체내 분포에 미치는 영향으로 평가한 다약제내성 역전가능성)

  • Kim, Jung-Kyun;Lee, Byung-Ho;Choi, Sang-Woon;Yoo, Sung-Eun;Lee, Sang-Woo;Chun, Kyung-Ah;Ahn, Byeong-Cheol;Park, Jae-Young;Suh, Jang-Soo;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.3
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    • pp.168-184
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    • 2001
  • Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

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