• Title/Summary/Keyword: Dose-response

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The Pattern of Failure after Definitive Radiotherapy for Squamous Cell Carcinoma of the Lung (편평상피 세포성 폐암의 방사선치료 실패 양상)

  • Jang Yang Suk;Kim Jae Cheol;Ryu Samuel;Park In Kyu
    • Radiation Oncology Journal
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    • v.7 no.1
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    • pp.45-50
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    • 1989
  • From Feb.1985 to Feb.1988,76 patients with squamous cell carcinoma of the lung treated at the Department of Therapeutic Radiology in Kyungpook National University Hospital were available for the analysis of this study. All patients received radiation of 4000cGy-6600cGy with curative aim. The overall rate of complete response was 25.0% and partial response was 452.6% The complete and partial regression of tumor was 14.3% in patients treated with dose below 5000cGy and 84.1% in the group treated with dose above 5000cGy (p<0.01). The complete response was seen only in the group of patients received radiation at least 6000cGy. The patterns of failure were as follows. The rate of initial intrathoracic recurrence was 52.6% in patients with complete response. The overall rate of failure was 68.8%. Distant metastasis was found in 47.4% of patients. Bone, contralateral lung, and brain were common metastatic sites in decreasing order All of the distant metastases and 80% of local recurrences were found within the first year after treatment.

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The Effects of Water Extract of Genus Panax on Rat Blood Vessels (Panax 속 한약재가 흰쥐 혈관운동성에 미치는 영향에 관한 비교 연구)

  • 유기덕;최호영;이재성;안덕균;김형환
    • The Journal of Korean Medicine
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    • v.25 no.1
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    • pp.60-71
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    • 2004
  • Objectives : We have examined the relaxational response to the water extract of genus Panax in rat thoracic aorta and mesenteric artery. Methods : Segments of thoracic aorta and mesenteric artery obtained from rats immediately after delivery were mounted in organ baths superfused on a polygraph. Results : We found that the thoracic aorta segments responded to the water extract of genus Panax with a dose-dependent vasorelaxation. At $10^{-5}m$ 5-hydroxytrptamine (5-HT), the maximal contraction force were 94.9% of the maximum KCl-response. At $10^{-5}m$ 5-HT - induced contraction, The contractile response of thoracic aortic rings were inhibited by 54.7%, 36.3% and 31.3% after addition of the high concentration (100 mg/ml) of water extract of Panax ginseng, Panax japonicus and Panax quinquefolium. The contractile response of mesenteric arteries were inhibited by 88.3%, 87.7%, and 70.3% after addition of the high concentration (100 mg/ml) of water extract of Panax ginseng, Panax japonicus and Panax quinquefolium. Conclusions : In conclusion, water extract of genus Panax - induced relaxation in the isolated rat thoracic aorta and mesenteric artery were composed of endothelium - independent relaxation and dose - dependent relaxation.

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Effects of Antiprogesterone (RU486) and Antiestrogen (Tamoxifen) on Ovulatory Response and Oocyte Quality in Rats Primed with Pregnant Mare Serum Gonadotropin (PMSG 전처리한 쥐에 있어서 Antiprogesterone(RU486)과 Antiestrogen(Tamoxifen)이 배란과 Oocyte에 미치는 영향)

  • 윤영원;권종국;유규연
    • Journal of Embryo Transfer
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    • v.4 no.1
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    • pp.46-55
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    • 1989
  • The effects of an antiprogesterone (RU 486) and an antiestrogen (tamoxifen) on ovulatory response and oocyte morphology were examined in pregnant mare serum gonadotropin (PMSG)-primed immatare female rats (28 days of age): a comparison has been made on two different regirnens primed with a "control" dose (4 IU) and a "superovulatory" dose (40 IU) of PMSG. Females for control control regimen received three consecutive injections of lmg RU486, lmg tamoxifen, or vehicle at 24, 36 and 48hr, and were killed at 72l'r after PMSG. Animals for superovalatory regimen received lmg RU486, 2.5mg tamoxifen, or vehicle fouowlag the injection schedule comparable to control regimen, and were killed at 60 and 72hr after PMSG. Compared to vehicle group, there was a significant reduction in ovulatory response as judged by the proportion of rats ovulating andi or by the mean number of oocytes per rat for each treatment of RU486 and tamoxifen in both regimens. The activity of tamoxifen in inhibiting the ovulatory response was greater in control, but less in superovulatory regimen than that of RU486 based on the dose employed for each antisteroid. In both regimens, RU 486 did not have any effect 6n the changes in the proportion of degenerate oocytes as well as ovarian weight, well tamoxifen treatment resulted in a marked promotion of oocyte degeneration as well as a great reduction in ovarian weight, compared to each parameter of vehicle group. RU486 treatment in each regimen did not alter the serum levels of any steroid hormones observed. Howerver, tamoxifen treatment was associated with significant increases in serum 17$\beta$-estradiol and decreases in progesterone in both regimens; also significant increases in androgens in superovulatory regimen. The results illustrate the relative inhibitory activity of RU486 and tamoxifen indicating major steroid hormone involved in PMSG-induced ovulation: 17$\beta$-estradiol for control and progesterone for superovulatory regimen. It also appears that tamoxifen-associated elevation of circulating 17$\beta$-estradiol andi or androgens could be in part, a contributing factor to the promotion of oocyte degeneration presumably by producing a hostile oviductal environment after ovulation.ent after ovulation.

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Expression patterns of innate immunity-related genes in response to polyinosinic:polycytidylic acid (poly[I:C]) stimulation in DF-1 chicken fibroblast cells

  • Jang, Hyun-Jun;Song, Ki-Duk
    • Journal of Animal Science and Technology
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    • v.62 no.3
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    • pp.385-395
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    • 2020
  • Polyinosinic:polycytidylic acid (poly[I:C]) can stimulate Toll-like receptor 3 (TLR3) signaling pathways. In this study, DF-1 cells were treated with poly(I:C) at various concentrations and time points to examine the comparative expression patterns of innate immune response genes. The viability of DF-1 cells decreased from 77.41% to 38.68% when cells were treated different dose of poly(I:C) from 0.1 ㎍/mL to 100 ㎍/mL for 24 h respectively. The expressions of TLR3, TLR4, TLR7, TLR15, TLR21, IL1B, and IL10 were increased in dose- and time-dependent manners by poly(I:C) treatment. On the contrary, the expression patterns of interferon regulatory factors 7 (IRF7), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), Nuclear Factor Kappa B Subunit 1 (NF-κB1), and IL8L2 were varied; IRF7 and IL8L2 were increasingly expressed whereas the expressions of JUN and NF-κB1 were decreased in a dose-dependent manner after they were early induced. In time-dependent analysis, IRF7 expression was significantly upregulated from 3 h to 24 h, whereas JUN and NF-κB1 expressions settled down from 6 h to 24 h after poly(I:C) treatment although they were induced at early time from 1 h to 3 h. Poly(I:C) treatment rapidly increased the expression of IL8L2 from 3 h to 6 h with a plateau at 6 h and then the expression of IL8L2 was dramatically decreased until 24 h after poly(I:C) treatment although the expression level was still higher than the non-treated control. These results may provide the basis for understanding host response to viral infection and its mimicry system in chickens.

The Response of Parenchymal Mass and Airway Obstruction from Lung Cancer to Radiation Therapy (단순 흉부 X-선 사진상 폐암 소견에 대한 방사선 치료의 효과 -단기 추적 조사를 중심으로-)

  • Kang, Cheol-Hoon;Shin, Sei-One;Kim, Myung-Se
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.227-233
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    • 1989
  • From April 1986 to Dec 1988, fifty one patients with carcinoma of lung were treated by radiation therapy in Department of Therapeutic Radiology, Yeungnam University Hospital Of the 51 patients, $31(61\%)$ were squamous cell ca, $8(15.7\%)$ were small cell ca, and remained $4(7.9\%)$ were other cell types. Total radiation dose was average $64Gy (60\~75 Gy)$ for group A and 45Gy $(40\~59Gy)$ for group B. The mass regression and the response of airway obstruction to radiation therapy was established on the basis of follow up chest X-ray. The mass regression above $50\%$ of total volume was noted in 23 patients $(74.2\%)$ among 31 patients and the difference between two groups was not seen. In squamous cell ca, however, the mass regression rate (above $50\%$ of total volume) was $83.3\%$ (10/12) in group A compared to $50\%$ (3/6) in group B(p<0.05). The alleviation of airway obstruction was noted as follows. In group A, CR $42.9\%$, PR $35.7\%$, no response $21.4\%$ and in group B, CR $55.6\%,\;PR\;33.3\%$, no response $11.1\%$. But, in squamous cell ca, responsiveness is higher than group B. The study indicates that the importance of higher radiation dose in the management of primary tumor mass and airway obstruction caused by lung cancer especially squamous cell ca. So, meticulous treatment planning and multimodality combination therapy without increasing si.do elect or complication is recommended in management of inoperable bronchogenic carcinoma.

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Relationship between Bronchial Sensitivity and Bronchial Reactivity in Asthma (기관지천식 환자에서 기관지 감수성과 기관지 반응성에 관한 연구)

  • Seo, Ki-Youl;Chang, Jung-Hyun;Cheon, Seon-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.2
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    • pp.341-350
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    • 1998
  • Background: Airway hyperreponsiveness is a cardinal feature of asthma. It consists of both an increased sensitivity of the airways, as indicated by a smaller concentration of a constrictor agonist needed to initiate the brochoconstrictor response and an increased reactivity, increments in response induced subsequent doses of constrictor, as manifested by slopes of the dose-response curve. The purpose of this study is to observe the relationship between bronchial sensitivity and reactivity in asthmatic subjects. Method: Inhalation dose-response curves using methacholine were plotted in 56 asthmatic subjects. They were divided into three groups(mild, moderate and severe) according to clinical severity of bronchial asthma. PC20 were determined from the dose-response curve as the provocative concentration of the agonist causing a 20% fall in FEVl. PC40 were presumed or determined from the dose response curve, using the PC20 and the one more dose after PC20. Reactivity was calculated from the dose-response curve regression line, connecting PC20 with PC40. Results: PC20 were 1.83mg/ml in mild group, 0.96mg/ml in moderate, and 0.34mg/ml in severe. PC40 were 7.l7mg/ml in mild group, 2.34mg/ml in moderate, and 0.75mg/ml in severe. Reactivity were $24.7{\pm}17.06$ in mild group, $46.1{\pm}22.l0$ in moderate, and $59.0{\pm}5.82$ in severe. There was significant negative correlation between PC20 and reactivity (r= -0.70, P<0.01). Conclusion: Accordingly, there was significant negative correlation between bronchial sensitivity and brochial reactivity in asthmatic subjects. However, in some cases, there were wide variations in terms of the reactivity among the subjects who have similar sensitivity. So both should be assessed when the bronchial response tor bronchoconstrictor agonists is measured.

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Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation (방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-Hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.571-578
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    • 2001
  • To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and a significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

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Low Dose Cisplatin as a Radiation Sensitizer in Management of Locally Advanced Scluamous Cell Carcinoma of the Uterine Cervix : Evaluation of Acute Toxicity and Early Response (국소 진행된 자궁경부암의 방사선치료와 저용량 cisplatin 항암요법 동시치료시 급성독성 밀 초기반응 평가)

  • Kim Hunjung;Cho Young Kap;Kim Chulsu;Kim Woo Chul;Lee Sukho;Loh J K
    • Radiation Oncology Journal
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    • v.17 no.2
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    • pp.113-119
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    • 1999
  • Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

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The Effect of External Radiation Therapy in Management of Malignant Obstructive Jaundice due to Porta Hepatis Metastasis from Stomach Cancer (위암의 간문맥 전이로 발생한 악성 폐쇄성 황달에 대한 외부 방사선치료 효과)

  • Yang, Kwang-Mo;Kim, Joon-Hee;Kim, Chul-Soo;Suh, Hyun-Suk;Kim, Re-Hwe
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.339-348
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    • 1995
  • Purpose : Since 1983, authors have conducted a study to evaluate the effect of external radiation therapy and to determine affected factors in management of the patients with malignant obstructive jaundice due to porta hepatis metastasis from stomach cancer. Materials and Methods : Thirty two patients with malignant obstructive jaundice due to porta hepatis metastasis from gastric cancer were presented. We have analysed 23 patients who were treated with external radiation therapy of more than 3000cGy. The radiation dose, disease extent at developement of jaundice, total bilirubin levels before radiation therapy, differentiation of histology, combind treatment, intent of primary surgery, initial stage of gastric cancer were analyzed to determine affected factors in radiation therapy. External radiation therapy was delivered with a daily dose of 180-300cGy, 5 times a week fractionation using 4 MeV linear accelerator. The radiation field included the porta hepatis with tumor mass by the abdominal ultrasonography or CT scan. In twenty three patients received more than 3000cGy, total irradiation dose was ranged from 3000cGy to 5480cGy, median 3770cGy. Among 23 patients, 13 patients were delivered more than equivalant dose of TDF 65(4140cGy/23fx). Results : Among 23 patients, complete, partial and no response were observed in 13, 5, 5 patients, respectively. The median survival for all patients was 5 momths. The significant prolongation of median survival was observed in complete responders(11 months) as compared to partial and no responders(5 months, 5 months respectively) Out of 13 patients with complete response, 6 patients lived more than a year Among 13 patients receiving more than 4140cGy equivalent dose, complete, partial and no response were observed in 10, 2 and 1 patients, respectively. The median survival for all these patients was 9.5 months. The median survival for complete responders(10/13) was 11.5 months. Among 10 patients receiving less than 4140cGy equivalent dose, complete, partial and no response were observed in 3, 3, 4 patients, respetively. The median survival for all these patients was 4.3 months Therefore, the radiation dose affected the results of treatment. For the complete response with prolongation of survival duration, at least 4140cGy equivalant dose should be delivered to porta hepatis. In evaluation of the disease extent, 7 patients of 13 complete responders showed localized disease in porta hepatis or peripancreatic area, but all patients with partial and no response showed wide extensive disease or persistant disease of primary gastric cancer. Therefore. the patients with the localized disease were the higher probability of complete response and long term survival. This study suggested that the radiation dose and the disease extent at developement of jaundice affected in radiation therapy for malignant obstructive jaundice. There were no serious complications related to external radiation therapy. Conclusion : External radiation therapy only could achieve the palliative effect in the patients with malignant obstructive jaundice due to porta hepatis metastasis from stomach cancer. This study suggested that the prolongation of survival duration could be achived in complete responders and radiation dose, extent of disease affected the results of treatment of malignant obstructive jaundice.

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