• Title/Summary/Keyword: 병용 투여

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Postoperative Radiotherapy for Locally Advanced Gastric Cancer (국소적으로 진행된 위암의 수술후 방사선 치료성적)

  • Lee Myung Za;Chun Ha Chung;Kim Insoon;Chung Tejune
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.113-119
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    • 1997
  • Purpose : Radical gastrectomy is main treatment of gastric cancer. But the result is not satisfactory with surgery alone. Most of pattern of failure remain locoregional recurrence. To improve 5 year survival postoperative chemotherapy with or without radiotherapy has been used. We analyzed patients with stage III and IV stomach cancer who had radical operation and received postoperative radiation therapy combined with or without chemotherapy retrospectively. Material and Method : From March 1985 to June 1993, 68 patients treated with curative resection and received postoperative adiuvant radiotherapy with 36Gy or more were evaluated. Median age was 60 years(range 28-66 yrs) . Patients were followed from 3 to 133 months with median follow up of 48 months. Thirty seven patients had non signet ring adenocarcinoma, 29 signet ring cell, 2 other cell. Patients with stage IIIA, IIIB, IV disease were 19, 25 and 24 respectively Chemotherapy was given to all patients except two. Results : Five-year overall survival and disease-free survival rate were 36.6% and 33.6%, respectively. Prognostic factor affecting survival were assessed. High ratio of jnvolved/dissected Iymph node, signet ring histology showed Poor Prognosis with statistical significance. Presence of residual tumor after surgery, stageIV. split course of radiation therapy, age, number of involved Iymph node, number of Iymph node dissection and grade of tumor affected survival without statistical significance, Type of chemotherapy did not affect survival. Recurrence was documented in 34 patients. High recurrence was seen in omentum and peritoneum with 23.5%, and remnant stomach, anastomosis site, A-loop and I-loop had also high recurrence with 13.2%. In field locoregional recurrence was 20.7% and total distant metastases were 39.7%. Total intraabdominal failure was 47.1% and extraabdominal failure was 13.2%. Treatment toxicity was considered to be acceptable. 22.1% of patients had grade 3 and only 1 patient had grade 4 leukopenia. Six Patients(8.8%) had weigh loss more than 10%. Conclusion : Treatment toxicity was acceptable with combined treatment with chemotherapy and radiotherapy. Locoregional recurrence was relatively low compared to distant failure with addition of irradiation. Peritoneal and omental seeding was high Five-rear surival was increased with combined modality. Radiation may eradicate minimal residual disease and improve survival, To evaluate role of radiation Prospective randomized study employing chemotherapy alone and chemotherapy plus radiation is necessary. Futhermore to reduce intraabdominal failure, role of intraabdominal chemotherapy in addition to combined chemotherapy plus radiation has to be explored.

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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.

Concurrent Chemoradiation with Weekly Paclitaxel in Locally Advanced Non-small Cell Lung Cancer (국소진행성 비소세포폐암에서 Paclitaxel 매주투여 및 방사선치료 동시요법)

  • Bae, Kang Woo;Song, Tak Ho;Yang, Joo Yeon;Kim, Yun Seup;Park, Jae Seok;Jee, Young Koo;Lee, Kye Young
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.4
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    • pp.351-357
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    • 2004
  • Background : Paclitaxel is highly beneficial anticancer drug for the treatment of non-small cell lung cancer and has shown remarkable radiosensitizing effect in vitro. We evaluated whether concurrent chemoradiation therapy with weekly paclitaxel (60 $mg/m^2$) could be tolerated and effective in the treatment of locally advanced non-small cell lung cancer (NSCLC). Methods : Twenty-two stage III (IIIA:6, IIIB:16) NSCLC patients were treated with weekly administration of paclitaxel (60 $mg/m^2$) on days 1, 8, 15, 22, 29, and 36 in addition to concurrent radiation therapy of 54 Gy. After the initial phase of concurrent chemoradiation, patients received additional two cycles of consolidation chemotherapy with paclitaxel (175 $mg/m^2$)/cisplatin (75 $mg/m^2$) or paclitaxel (175 $mg/m^2$)/carboplatin (6AUC) every 3 weeks. Results : Overall response rate was 81.8% (18/22) with 9.1% (2/22) of complete response and 72.7% (16/22) of partial response rate. Two patients (9.1%) died of chemoradiation-induced pneumonitis after completion of therapy. In total, grade 3 toxicities included pneumonitis (22.7%), esophagitis (22.7%), neuropathy (13.6%), and neutropenia (13.6%). The median survival time was 15 months and 2-year overall survival were 31.8%. Conclusion : Concurrent chemoradiation therapy with weekly paclitaxel in locally advanced NSCLC showed good local response, but survival rate was not completely satisfactory due to potentially fatal chemoradiation-induced pneumonitis.

A clinical study of deep neck abscess in children (소아 심경부 농양의 임상적 고찰)

  • Lee, Soo Jung;Shin, Mee Yong;Kim, Chang Hwi;Koh, Yoon Woo
    • Clinical and Experimental Pediatrics
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    • v.50 no.4
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    • pp.363-368
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    • 2007
  • Purpose : It has been reported that deep neck abscesses are recently increasing again. We analyzed pediatric cases with deep neck abscesses during the last several years to contribute to the treatment of the disease. Methods : The clinical data of 30 children under 16 years of age with deep neck abscess from February 2001 to July 2006 were analysed retrospectively. Results : The mean age was 9 years (2-16 years), and the male/female ratio was 19/11. Abscesses in the peritonsillar space were most common (57%), followed by the retropharyngeal (30%) and parapharyngeal (13%) spaces. Upper respiratory infection in 10 cases (33%), dental infection in four case (14%), cervical lymphadenitis in three case (10%) and sinusitis in two case (6%) contributed to the development of deep neck infections. The frequent symptoms were fever in 16 case (53%), sore throat in 15 case (50%), poor oral intake in 10 (33%), odynophagia in eight (27%), and neck pain in eight (27%). Unilateral tonsillar hypertrophy and displacement in 15 case (50%) were most common. Neck mass in 13 patients (43%), neck stiffness in three (10%) and trismus in three (10%) were also found. Bacteria were isolated in 8 among 10 pus cultures; Streptococcus species 7 and Micrococcus luteus 1. All of those bacteria except Micrococcus luteus were sensitive to penicillin G. Surgical intervention was applied to 12 cases (40%), and the remaining 18 patients (60%) were treated with antibiotics only. There were no differences between the two groups in the duration of admission and antibiotic treatment. No complicated cases were observed. Conclusion : Peritonsillar abscesses were most frequent. Upper respiratory infection was the most common predisposing factor, followed by dental infection and sinusitis. Symptoms of respiratory tract obstruction were not found. The most common pathogens were Streptococcus species. Deep neck abscesses in children, if diagnosed at the early stage, possibly can be treated by antibiotics only, without surgical intervention.

Comparison of Gangjihwan and Combination of Gangjihwan and Gamisochehwan in the Improvement Effects of Weight Loss in a High Fat Diet-Fed Obese Mice (고지방식이 비만마우스 모델에서 파키스탄산 마황으로 조성된 강지환(降脂丸)의 단독 투여와 강지환합가미소체환(降脂丸合加味消滯丸)의 병용 투여의 체중감량 효과 비교)

  • Seok, Hoa Jun;Yoo, Jae Sang;Ku, Ja Ryong;Yoon, Ki Hyeon;Jo, Ju Heum;Jang, Du Hyon;Jung, Yang Sam;Kim, Jong Hoon;Kim, Byeong Chul;Roh, Jong Seong;Lee, Hye Rim;Lee, Hyunghee;Yoon, Michung;Shin, Soon Shik
    • Herbal Formula Science
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    • v.22 no.2
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    • pp.105-120
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    • 2014
  • Objectives : This study was investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on obesity in a high fat diet-fed obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into four groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and DF and DF+GSH groups given a high fat diet with DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : 1. Body weight gain and fat mass were significantly decreased in DF and DF+GSH groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Feeding efficiency ratio and circulating concentration of leptin were decreased in DF and DF+GSH groups compared with control. These decreases were significant in DF+GSH group. 3. Consistent with their effects on body weight gain and fat mass, circulating concentrations of triglyceride, glucose and insulin were decreased in DF and DF+GSH groups compared with control. 4. The size of adipocytes was decreased by DF and DF+GSH compared with control, whereas the adipocyte number per unit area was increased by them, suggesting that DF and DF+GSH decreased the number of large adipocytes. 5. Consistent with their effects on body weight gain, liver fibrosis was also improved in DF and DF+GSH groups compared with control. Conclusions : In conclusion, these results suggest that DF and DF+GSH groups decrease feeding efficiency ratio, plasma leptin concentration, blood anti-obesity biomarkers and fat mass, improves body weight gain contributing to the inhibition of liver fibrosis. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

The Effect of Ginkgo Biloba Extract on the Fractionsted Radiation Therapy in C3H Mouse Fibrosarcoma (Ginkgo Biloba Extract가 C3H 마우스 섬유육종의 분할 방사선치료에 미치는 영향)

  • Kim, Jong-Hoon;Ha, Sung-Whan;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.155-164
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    • 2002
  • Purpose : A ginkgo biloba extract (GBE) has been known as a hypoxic cell radiosensitizer. Its mechanisms of action are increase of the red blood cell deformability, decrease the blood viscosity, and decrease the hypoxic cell fraction in the tumor. The aims of this study were to estimate the effect of GBE on fractionated radiotherapy and to clarify the mechanism of action of the GBE by estimating the blood flow in tumor and normal muscle. Materials and Methods : Fibrosarcoma (FSall) growing in a C3H mouse leg muscle was used as the tumor model. When the tumor size reached 7 mm in diameter, the GBE was given intraperitoneally at 1 and 25 hours prior to irradiation. The tumor growth delay was measured according to the various doses of radiation (3, 6, 9, 12 Gy and 15 Gy) and to the fractionation (single and fractionated irradiation) with and without the GBE injection. The radiation dose to the tumor the response relationships and the enhancement ratio of the GBE were measured. In addition, the blood flow of a normal muscle and a tumor was compared by laser Doppler flowmetry according to the GBE treatment. Results : When the GBE was used with single fraction irradiation with doses ranging from 3 to 12 Gy, GBE increased the tumor growth delay significantly (p<0.05) and the enhancement ratio of the GBE was 1.16. In fractionated irradiation with 3 Gy per day, the relationships between the radiation dose (D) and the tumor growth delay (TGD) were TGD $(days)=0.26{\times}D$ (Gy)+0.13 in the radiation alone group, and the TGD $(days)=0.30{\times}D$ (Gy)+0.13 in the radiation with GBE group. As a result, the enhancement ratio was 1.19 ($95\%$ confidence interval; $1.13\~1.27$). Laser Doppler flowmetry was used to measure the blood flow. The mean blood flow was higher in the muscle (7.78 mL/100 g/min in tumor and the 10.15 mL/100 g/min in muscle, p=0.005) and the low blood flow fraction (less than 2 mL/100 g/min) was higher in the tumor $(0.5\%\;vs.\;5.2\%,\;p=0.005)$. The blood flow was not changed with the GBE in normal muscle, but was increased by $23.5\%$ ( p=0.0004) in the tumor. Conclusion : Based on these results, it can be concluded that the GBE enhanced the radiation effect significantly when used with fractionated radiotherapy as well as with single fraction irradiation. Furthermore, the GBE increased the blood flow of the tumor selectively.

Outcomes after Radiotherapy in Inoperable Patients with Squamous Cell Lung Cancer (수술이 불가능한 편평상피성 폐암의 방사선치료 성적)

  • Ahn Sung-Ja;Chung Woong-Ki;Nah Byung-Sik;Nam Tack-Keun;Kim Young-Chul;Park Kyung-Ok
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.216-223
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    • 2001
  • Purpose : We evaluated retrospectively the outcomes of inoperable squamous cell lung cancer patients treated with radiotherapy to find out prognostic factors affecting survival. Materials and methods : Four hundred and eleven patients diagnosed as squamous cell lung cancer between November 1988 and December 1997 were the basis of this analyses. The planned dose to the gross tumor volume was ranged from 30 to 70.2 Gy. Chemotherapy was combined in 72 patients $(17.5\%)$ with the variable schedule and drug combination regimens. Follow-up period ranged from 1 to 113 months with the median of 8 months and survival status was identified in 381 patients $(92.7\%)$. Overall survival rate was calculated using the Kaplan-Meier method. Results : Age ranged from 23 years to 83 years with the median 63 years. The male to female ratio was about 16:1. For all 411 patients, the median overall survival was 8 months and the 1-year survival rate (YSR), 2-YSR, and 5-YSR were $35.6\%,\;12.6\%,\;and\;3.7\%$, respectively. The median and 5-YSR were 29 months and $33.3\%$ for Stage IA, 13 months and $6.3\%$ for Stage IIIA, and 9 months and $3.4\%$ for Stage IIIB, respectively(p=0.00). The median survival by treatment aim was 11 months in radical intent group and 5 months in palliative, respectively (p=0.00). Of 344 patients treated with radical intent, median survival of patients (N=247) who received planned radiotherapy completely was 12 months while that of patients (N=97) who did not was 5 months (p=0.0006). In the analyses of the various prognostic factors affecting to the survival outcomes in 247 patients who completed the planned radiotherapy, tumor location, supraclavicular LAP, SVC syndrome, pleural effusion, total lung atelectasis and hoarseness were statistically significant prognostic factors both in the univariate and multivariate analyses while the addition of chemotherapy was statistically significant only in multivariate analyses. The acute radiation esophagitis requiring analgesics was appeared in 49 patients $(11.9\%)$ and severe radiation esophagitis requiring hospitalization was shown in 2 patients $(0.5\%)$. The radiation pneumonitis requiring steroid medication was shown in 62 patients $(15.1\%)$ and severe pneumonitis requiring hospitalization was occurred in 2 patients $(0.5\%)$. During follow-up, 114 patients $(27.7\%)$ had progression of local disease with 10 months of median time to recur (range : $1\~87\;months$) and 49 patients $(11.9\%)$ had distant failure with 7 months of median value (range : $1\~52\;months$). Second malignancy before or after the diagnosis of lung cancer was appeared in 11 patients Conclusion : The conventional radiotherapy in the patients with locally advanced squamous cell lung cancer has given small survival advantage over supportive care and it is very important to select the patient group who can obtain the maximal benefit and to select the radiotherapy technique that would not compromise the life quality in these patients.

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Clinical Characteristics and Prognostic Factors of Severe Community-Acquired Pneumonia (중증 지역사회획득 폐렴의 임상상 및 예후 예측인자에 관한 연구)

  • Oh, Heung-Kook;Seo, Ji-Young;Kim, Dong-Kyu;Choi, Jeong-Eun;Mo, Eun-Kyung;Park, Myung-Jae;Lee, Myung-Goo;Hyun, In-Gyu;Jung, Ki-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.5
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    • pp.1072-1082
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    • 1997
  • Background : To characterize the clinical features and determine the prognostic factors of severe community-acquired pneumonia. This study is the first of its kind in Korea. Methods : Recruited were 40 patients diagnosed as severe community-acquired pneumonia in Hallym University Hospital from January 1, 1989 through July 31, 1996. Patients were analysed retrospectively for age, sex, underlying disease, respiration rate, hypoxemia, requirement of mechanical ventilation, involvement on chest radiograph, shock, and the serum concentration of BUN and albumin. All parameters were compared between survived and dead group. Results : Male to female ratio was 2.07 : 1. The mean age was $63.1{\pm}17.5$years(range 25~90years) with 65% of patients aged equal to or more than 60. The major underlying diseases were old pulmonary tuberculosis(12.5%), chronic obstructive pulmonary disease(7.5%), bronchial asthma(5%), bronchiectasis(2.5%), and diabetes mellitus(22.5%). Microbiologic diagnosis was made in 26 out of 40 patients(65%). The most common causative organism was S. pneumoniae(17.5%, 7/40) followed by S. aureus(15.0%, 6/40), K. Pneumoniae(12.5%, 5/40), M. tuberculosis(7.5%, 3/40), H. influenzae(2.5%, 1/40), coagulase negative staphylococcus(2.5%, 1/40), P. aeruginosa(2.5%. 1/40), E. cloaceae(2.5%, 1/40), and E. coli(2.5%, 1/40). M. pneumoniae was detected in no patient. The most frequent drugs administered in single or combination therapy were aminoglycosides(75%, 30/40), second- and third-generation cephalosporin(40%, 16/40 and 27.5%, 11/40), macrolides(27.5%, 11/40), and amoxicillin/clavulanic acid(22.5%, 9/40). Of the 40 patients, 14 died of severe community-acquired pneumonia(37.5%). Among them, seven patients (50%) expired within 72h of hospital arrival. According to multivariate analysis, mortality was significantly associated with requirement of mechanical ventilation, bilateral pulmonary involvement, and serum albumins$\leq$3.0g/dl. Conclusion : An understanding of the clinical characteristics and prognostic factors in severe community-acquired pneumonia identified in this study will optimize therapeutic approach in this disease and help decreasing its notorious mortality rate.

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The Effect of Local Irradiation in Prevention and Reversal of Acute Rejection of Transplanted Kidney with High-dose Steroid Pulse (국소적 방사선조사의 신장이식 후 거부반응에 대한 예방적 및 치료적 효과)

  • Kim I. H.;Ha S. W.;Park C. I.;Kim S. T.
    • Radiation Oncology Journal
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    • v.4 no.1
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    • pp.15-20
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    • 1986
  • From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in $71\%$. When the pre-irradiation level of serum creatinine was below $5.5mg\%$, the reversal rate was $93\%$, but above $5.5mg\%$ the reversal rate was only $17\%$ (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, $7(47\%)$ had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were $70\%,\;65\%,\; 54\%,\;and\;54\%$, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below $5.5mg\%$ (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001).

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Radiation Response Modulation of GW572016 (EGFR/HER2 Dual Tyrosine Kinase Inhibitor) in Human Breast Cancer Xenografts (인간 유방암 세포 이식마우스에서 EGFR/HER2 복합 Tyrosine Kinase 억제제인 GW572016에 의한 방사선증진효과)

  • Kim, Yeon-Sil;Roh, Kwang-Won;Chae, Soo-Min;Mun, Seong-Kwon;Yoon, Sei-Chul;Jang, Hong-Seok;Chung, Su-Mi
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.233-241
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    • 2007
  • Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstream signaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results suggest that a better predictor of radiation response would be inhibition of a crucial signaling pathway than inhibition of a receptor.