• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.1
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• pp.25-30
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• 2001

Viral safety is a prerequisite for manufacturing clinical albumin and immunoglobulins from human plasma pools. This study was designed to evaluate the efficacy of cold ethanol fractionation and pasteurization (60$\^{C}$ heat treatment for 10h) for the removal/inactivation of human immunodeficiency virus type 1 (HIV-1) during the manufacturing of albumin and immunoglobulins. Samples from the relevant stages of the production process were spiked with HIV-1, and the amount of virus in each fraction was quantified by the 50% tissue culture infectious dose(TCID(sub)50). Both fraction IV fractionation and pasteurization steps during albumin processing were robust and effective in inactivating HIV-1, titers of which were reduced from an initial 8.5 log(sub)10 TCID(sub)50 to undetectable levels. The log reduction factors achieved were $\geq$ 4.5 and $\geq$ 6.5, respectively. In addition, fraction III fractionation and pasteurization during immunoglobulins processing were robust and effective in eliminating HIV-1. HIV-1 titers were reduced from an initial 7.3 log(sub)10 TCID(sub)50 to undetectable levels. The log reduction factors achieved in this case were $\geq$ 4.9 and $\geq$ 5.3, respectively. These results indicate that the process investigated for the production of albumin and immunoglobulins have sufficient HIV-1 reducing capacity to achieve a high margin of safety.

• Radiation Oncology Journal
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• v.10 no.2
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• pp.267-275
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• 1992

Remote afterloading high dose rate brachytherapy (HDRB) is a new technology and needs new biological principle for time and dose schedule. Here, authors attempt to evaluate the technique and clinical outcome in 116 patients, 590 procedures peformed at Asan Medical Center for 3 years. From Sep. 1989 to Aug 1992, 471 procedures of intracavitary radiation in 58 patients of cervical cancer and 26 of nasopharyngeal cancer,79 intraluminal radiation in 12 of esophageal cancer, 11 of endobronchial cancer and 1 Klatskin tumor and 40 interstitial brachytherapy in 4 of breast cancer, 1 sarcoma and 1 urethral cancer were performed. Median follow-up was 7 months with range $1\~31$ months. All procedures except interstitial were performed under the local anesthesia and they were all well tolerated and completed the planned therapy except 6 patients. 53/58 patients with cervical cancer and 22/26 patients with nasopharynx cancer achieved CR. Among 15 patients with palliative therapy, $80{\%}$ achieved palliation. We will describe the details of the technique and results in the text. To evaluate biologic effects of HDRB and optimal time/dose/fractionation schedule, we need longer follow-up. But authors feel that HDRB with proper fractionation schedule may yield superior results compared to the low dose rate brachytherapy considering the advantages of HDRB in safety factor for operator, better control of radiation dose and volume and patients comfort over the low dose brachytherapy.

• Progress in Medical Physics
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• v.1 no.1
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• pp.43-49
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• 1990

On the basis of the review of radiobiological date, a formalism is developed for the analysis and prediction of iso-effect relations for tissue tolerance, which can be used as an alternative to the norminal standard dose(NSD) formaula of Ellis and its derived equations. An important feature of the described formalism is that directly based on radiobiological insights and it provides a more logical concept to account for the diversity of tissue responses. The NSD concept has subsequently been extended to the formalisms of timedose-fractionation(TDF) value. The authors deriveded TDF equation on the basis NSD of Ellis. TDF=0.07(NSD)-26.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.735-738
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• 2003

The methanolic extract of the twigs of Celtis chinensis was found to show inhibitory activity on acetylcholinesterase (AChE), an enzyme that plays a role in the metabolic hydrolysis of ACh. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of N-p-coumaroyl tyramine. as an inhibitor on AChE. This compound inhibited AChE activity in a dose-dependent manner, and the $IC_50$ value of trans-N-p-coumaroyl tyramine was 34.5 $\mu$g/mL (122 $\mu$M).

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.199.2-199.2
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• 2003

The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root bark of Paeonia suffruticosa led to the isolation of ten known compounds: paeonol (1), 2,5-dihydroxy-4-methoxyacetophenone (2) methyl 3-hydroxy-4- methoxybenzoate (3), acetovanillone (4), benzoic acid (5), benzoylpaeoniflorin (6), paeonoside (7), paeoniflorin (8), oxypaeoniflorin (9) and apiopaeonoside (10). Among them, 4 exhibited the highest survival rate in a dose-dependent manner (100% with a dose of 30 mg/kg versus 16.7% for the control experiment) and showed reduction of plasma alanine aminotransferase (ALT) value on the in vivo assay model of sepsis induced by LPS/GalN.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.127-132
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• 1993

Total of 53 patients of unresectable and recurrent rectal cancer treated with neutron beam during the period from Oct.1987 to Apr.1992 were analyzed. Dose fractionation for the neutron only group was 1.5 Gy per fraction,3 fraction per week,21 Gy/41/2 wks for 42 patients out of 53 ($76{\%}$). Neutron only but modified fractionation schedule ($10{\%}$ more or less of total dose) was applied for 9 patients, and mixed beam (neutron boost) was for 4 patients, Complete tumor response was obtained in 40 patients ($76{\%}$, response rate). Local control rate was 28 out of 53 ($53{\%}$). Statistically significant better prognostic factors for local control were age below 49 years old (15/22, $68{\%}$) than above 50 years old (13/31, $42{\%}$), male (20/32, $63{\%}$) than female (8/21, $38{\%}$), tumor size less than 5 cm and non-metastatic (16/24, $67{\%}$) than size more than 5 cm or metastatic (12/29, $41{\%}$). Major complication had developed in 7 patients ($13{\%}$). Two year overall survival rate by Kaplan-Meier method was $30{\%}$, but it was rised to, $47{\%}$ when the turner was less than 5 cm non-metastatic.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.33-39
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• 1996

Purpose : This study was done to analyze survivals, patterns of failure, and complications of early uterine cervix cancer after curative radiotherapy. Materials and Methods : Eighty patients with uterine cervix cancer FIGO Stage IB (48 cases) and Stage IIA (32 cases) treated with radiotherapy were analyzed retrospectively. Patients were treated from November 1985 to May 1993, and minimum follow up period was 24 months and 6 cases were lost to follow up. All of them were treated with external radiotherapy and different fractions of high dose rate intracavitary radiotherapy, Survival rates, failure patterns, complication rates and degrees of severity were analyzed according to several factors. Results : Overall 5 year survival rate and relapse free survival rate were $72.3\%$, and $72.8\%$ respectively. Prognostic factors were stage, size, pathology, RT response and there was no significant survival difference among the reasons of radiotherapy choice. There were 19 cases of treatment failure, another 3 cases were not tumor related death, and most of treatment related failure occurred within 24 months Late complication rate of bladder and rectum were $8.8\%,\;15\%$ respectively, frequency and severity of complication were correlated with ICR fractionation dose and total dose. Conclusion : These results showed that survival rates of early stage radiation treated cervix cancer patients were comparable to surgical series, but more aggressive treatment methods needed for stage IIA poor prognostic patients. To decrease late complication, choice of proper ICR dose and meticulous vaginal packing is needed.

• Radiation Oncology Journal
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• v.4 no.2
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• pp.89-97
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• 1986

Using as assay for jejunal crypt stem cell survival, dose-response curves for the reproductive capacity of crypt stem cells of mouse jejunum exposed to multifractionated gamma-ray irradiation (single, 2, 3, 4, 5, 8, 10, 12, and 16 fractions) were analyzed and single-dose survival curve of these cells was constructed. The following conclusion were drawn: 1) Survival curves for higher numbers of dose fractions were displaced to higher dose, and characterized by increasingly shallower slopes. 2) The single-dose survival curve had broad shoulder, Dq=460 cGy, remaining near-exponential over initial dose range 0 to 300 cGy, with initial slope 1Do=474 cGy. 3) At fractionated dose En the range of 180 to 450 cGy, the average recovered dose per fraction interval was approximately $50\%$ of the dose per fraction. 4) The value of $\alpha/\beta$ ratio by using of linear regression analysis for the reciprocal dose plots was 8.3 Gy which lied in the range of 6-14 Gy for early-reacting tissues. 5) The linear-quadratic model for dose-response formula offers valid approximations for at 1 doses to be used in radiotherapy, only two parameters to be determined, and considerable convenience in practical applications.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.165-173
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• 1994

Purpose : Metastatic cancer to the brain is a major problem for the patients with bronchogenic carcinoma, and most of these patients have a limited survival expectancy. To increase tumor control and / or to decrease late morbidity with possible shortening in over-all treatment period, multiple daily fraction technique for brain metastasis was performed. The author reperesented the results of accelerated fractionation radiotherapy in patients with brain metastases from non-small cell lung cancer. Materals and Methods : Twenty-six patients with brain metastases from non-small cell lung cancer between 1991 and 1993 received brain radiotherapy with a total dose of 48 Gy, at 2 Gy per fraction, twice a day with a interfractional period of 6 hours, and delivered 5 days a week. The whole brain was treated to 40 Gy and boost dose escalated to 8 Gy for single metastatic lesion by reduced field. Twenty-four of the 26 patients completed the radiotherapy. Radiotherapy was interupted in two patients suggesting progressive intracerebral diseases. Results : This radiotherapy regimen appears to be comparable to the conventional scheme in relief from symptoms. Three of the 24 patients experienced nausea and or vomiting during the course of treatment because of acute irradiation toxicity. The author observed no excessive toxicity with escalating dose of irradiation. An increment in median survival, although not statistically significant(p>0.05), was noted with escalating doses(48 Gy) of accelerated fractionation(7 months) compared to conventional treatment(4.5 months). Median survival also increased in patients with brain solitary metastasis(9 months) compared to multiple extrathoracic sites(4 months), and in patients with good performance status(9 months versus 3.5 months), they were statistically significant (p<0.01). Conclusion : The increment in survival in patients with good prognostic factors such as controlled primary lesion, metastasis in brain only and good perfomance status appeared encouraging. Based on these results, a multi-institutional prospective randomized trial should be initiated to compare the twice-a-day and once-a-day radiotherapy schemes on patients with brain metastasis with careful consideration for the patients' quality of life.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.321-330
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• 1993

Purpose: A retrospective analysis was performed to evaluate the incidence of radiation induced lung damage after the radiation therapy for the patients with carcinoma of the lung. Method and Materials: Sixty-six patients with lung cancer (squamous cell carcinoma 27, adenocarcinoma 14, large cell carcinoma 2, small cell carcinoma 13, unknown 10) were treated with definitive, postoperative or palliative radiation therapy with or without chemotherapy between July 1987 and December 1991. There were 50 males and 16 females with median age of 63 years (range: 33~80 years). Total lung doses ranged from 500 to 6,660 cGy (median 3960 cGy) given in 2 to 38 fractions (median 20) over a range or 2 to 150 days (median in days) using 6 MV or 15 MV linear accelerator. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, $ED=D{\dot}N^{-0.377}{\dot}T^{-0.058}$ was used in which D was the lung dose in cGy, N was the number of fractions, and T was the overall treatment time in days. The range of ED was 370 to 1357. The endpoint was a visible increase in lung density within the irradiated volume on chest X-ray as observed independently by three diagnostic radiologists. Patients were grouped according to ED, treatment duration, treatment modality and age, and the percent incidence of pulmonary damage for each group was determined. Result: In 40 of 66 patients, radiation induced change was seen on chest radiographs between 11 days and 314 days after initiation of radiation therapy. The incidence of radiation pneumonitis was increased according to increased ED, which was statistically significant (p=0.001). Roentgenographic changes consistent with radiation pneumonitis were seen in $100\%$ of patients receiving radiotherapy after lobectomy or pneumonectomy, which was not statistically significant. In 32 patients who also received chemotherapy, there was no difference in the incidence of radiation induced change between the group with radiation alone and the group with radiation and chemotherapy, among the sequence of chemotherapy No correlation was seen between incidence of radiation pneumonitis and age or sex. Conclusions: The occurrence of radiation pneumonitis varies. The incidence of radiation pneumonitis depends on radiation total dose, nature of fractionation, duration of therapy, and modifying factors such as lobectomy or pneumonectomy.