Rhim, Byung-Yong;Kim, Chi-Dae;Kim, Dong-Heon;Biancani, Piero;Behar, Jose
The Korean Journal of Pharmacology
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제32권1호
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pp.67-74
/
1996
Cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) and KCl caused a dose dependent contraction in muscle cells enzymatically digested from cat gallbladder. Maximal contraction was obtained at concentration of $10^{-9}M$ for CCK-8, $10^{-5}M$ for ACh and 20mM for KCl. CCK-8 induced contraction was unaffected in calcium free physiological salt solution (PSS) and was completely blocked by strontium substitution for calcium (p<0.001). In contrast, KCl evoked contraction was blocked in calcium free PSS (p<0.01) but was unaffected by strontium replacement of calcium. The contraction elicited by ACh was only slightly reduced in calcium free PSS (p<0.05) and was unaltered by strontium. Muscle cells permeabilized with saponin contracted in response to inositol 1,4.5-trisphosphate $(IP_3)$ and CCK-8. The contraction was blocked by the calmodulin antagonist CGS 9343B (p<0.001), whereas heparin completely blocked the effect of $IP_3$ (p<0.001). The protein kinase C (PKC) antagonist H7 had no effect on either agonist. We conclude that CCK-8 induced gallbladder muscle contraction is mediated by $IP_3$ dependent intracellular calcium release from intracellular stores and a calmodulin dependent pathway; ACh may utilize both extracellular and intracellular calcium. KCl causes muscle contracrion through influx of extracellular calcium and a calmodulin independent machanism.
From October 1989 to March 1992, ten patients diagnosed as primary central nervous system (CNS) lymphoma were treated with radiation therapy at Asan Medical Center. To obtain pathologic diagnosis, five patients had stereotactic biopsy and the others underwent craniotomy & tumor removal. According to the classification by International Working Formulation, seven of 10 patients showed diffuse large cell types and the remaining 3 had diffuse mixed cell types. Computed tomographic scans of the brain disclosed solitary (6 cases) or multiple (4 cases) intracranial lesions. All patients received 4000 cGy/20 fx to the whole brain followed by an additional 2000 cGy/10 fx boost to the primary lesion. Six patients with initial cerebrospinal fluid (CSF involvement were treated with whole brain irradiation and intrathecal Methotrexate (IT-MTX) chemotherapy. One of them received an additional spinal irradiation after 3 cycles of IT-MTX chemotherapy because of MTX induced arachnoiditis. One patient received 3 cycles of systemic chemotherapy prior to rodiation therapy and one received 5 cycles of salvage chemotherapy for recurrence. With a median follow up time of 8 months, all patients were followed from 7 to 26 months. Radiologically seven patients showed complete remission and the remaining three showed partial remission at one month after radiotherapy. The 1 and 2 year survival rate was $86{\%}\;and\;69{\%}$ respectively. Until now, two patients expired at 7 and 14 months. These patients developed extensive CSF seeding followed by local failure. Considering initial good response to radiation therapy and low incidence of extraneural dissemination in primary CNS lymphoma, we propose to increase total tumor dose to the primary lesion by hyperfractionated radiotherapy or stereotactic radiosurgery. For the patients with CSF involvement at diagnosis, we propose craniospinal irradiation with IT MTX chemotherapy.
There are a number of reports suggesting that there may be a correlation between the clinical response to radiotherapy in various tumors and the clonogenic survival of cell lines derived from these tumors following exposure to 2 Gy(SF2). Authors conducted this study to determine SF2 for cells in primary culture from surgical specimens. The tumor tissues with squamous cell carcinoma of uterine cervix and head and neck were obtained. The tumor tissues were disaggregated to single cells by incubating with collagenase type w for 2 hours with constant stirring. Single cell suspensions were inoculated in four 24-well plates precoated with cell adhesive matrix. After 24 hours of incubation at 37$ ^{\circ}C $, rows of four wells were then irradiated, consisting of control set and five other sets each receiving doses of 1,2,3,4, and 6 Gy. After incubation for a total of 13 days, the cultures were stained with crystal violet and survival at each dose was determined by quantitative image analysis system, To determine whether cell growth was of epithelial origin, immunocytochemical staining with a mixture of cytokeratin and epithelial monoclonal antibodies were performed on cell cultures. During the period of this study, we received 5 squamous cell carcinoma specimens of head and neck and 20 of uterine cervical carcinoma. Of these, 15 yielded enough cells for radiosensitivity testing. This resulted an overall success rate of 60$ \% $. The mean SF2 value for 15 tumours was 0.55$\pm$0.17 ranging from 0.20 to 0.79. These results indicate that there is a broad range of sensitivities to radiation in same histologic type. So with a large patient population, we plan to determine whether a different SF2 value is associated with tumours that are controlled with radiotherapy than those that are not.
Park, Geum-Ju;Lee, Sang-Wook;Choi, Eun-Kyung;Kim, Jong-Hoon;Song, Si-Yeol;Youn, Sang-Min;Park, Sung-Ho;Park, Dong-Wook;Ahn, Seung-Do
Radiation Oncology Journal
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제27권3호
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pp.120-125
/
2009
Purpose: We wanted to present the preliminary results of intensity-modulated radiotherapy (IMRT) for the treatment of tonsillar cancer. Materials and Methods: We retrospectively analyzed 12 patients who underwent IMRT for tonsillar cancer at Asan Medical Center between November 2002 and February 2007. Seven patients (58%) received definitive treatment, and five (42%) were treated in the postoperative setting. Among the definitively treated patients, 6 patients received cisplatin-based chemotherapy regimens. Simultaneous modulated accelerated radiation therapy (SMART) was used in nine patients. The prescribed dose was 72 Gy at 2.4 Gy/fraction for the definitively treated cases and 61.6 Gy at 2.2 Gy/fraction for the postoperative cases. The median follow-up period was 34 months. Results: All twelve patients completed treatment without interruption, and eleven showed a complete response. One patient had persistent loco-regional disease after treatment. The three-year estimates of loco-regional control, disease-free survival and overall survival were 91.7%, 91.7%, and 100%. The worst acute mucositis was Grade 1 in four patients, Grade 2 in five patients, Grade 3 in two patients and Grade 4 in one patient. Grade 3 xerostomia was observed in six patients. Conclusion: Intensity-modulated radiotherapy was shown to be a safe and effective treatment modality for tonsillar cancer. Further studies with a larger number of patients and a longer follow-up period are needed to evaluate the ultimate tumor control and late toxicity of IMRT for treating tonsillar cancer.
This study was conducted to examine the levels of total and organic mercury in the scalp hair of the elementary school children and adults, and their relationship with the consumption pattern of fishes and shellfishes. The scalp hair samples were collected from the occipital part of 115 children and 131 adults in costal, urban and rural areas of Kyungpook province from June to August 1991. The mercury content was analysed by the atomic absorption spectrophotometer (model IL. 555) with atomic vapor accessory (model IL. 440). The total and organic mercury contents of hair were significantly higher (p<0.01) among the children who prefer fish and/or shellfish (7.728 ppm, 6.610 ppm), and canned fish and/or fish pastes (6.969 ppm, 5.885 ppm) than those who prefer meat (4.822 ppm, 3.905 ppm) and vegetables (3.974 ppm, 3.224 ppm). The children who prefer to eat the canned fish without cooking showed a higher mercury content than the children who prefer to eat it as stew or mixed with vegetables (p<0.01). There was a dose-response relationship between the intake frequency of canned fish, raw fish and cooked fish and the content of total and organic mercury of hair, the children who eat fish almost everyday showed 2 times higher than those who eat rarely (p<0.01). The mercury content in the hair of the children who eat raw fish was significantly higher than that of the children who eat boiled or broiled fish (p<0.01). The total and organic mercury contents of adult scalp hair increased with age up to the forties and slightly decreased in the fifties. The mercury contents of those who were engaged in the fishery and raw fish restaurant were 2 times higher than those of the farmers. The mercury content of the persons who were favorite dishes of fish and shellfish were most high, and who prefer raw fish were 2 times higher than those of the persons who prefer vegetables and broiled fish. The contents of total and organic mercury in adult scalp hair showed also a increasing tendency with the intake frequency of raw and cooked fish.
The effects of combined garlic and medicinal plant extracts such as Gyeolmyeongja (Cassia obtusifolia Linne), Hasuo (Polygoni multiflori Radix), Youngji (Ganoderma lucium) and Sansayuk (Crataegus pinnatifida Bunge) on the antioxidant activity and lipid levels in the livers of rats fed a high cholesterol diet were analyzed. Total phenol and flavonoid contents were the highest in the Gyeolmyeongja by $151.02{\pm}5.20\;mg$/100 g and $43.69{\pm}5.58\;mg$/100 g. Electron donating ability, reducing power and hydroxyl radical scavenging activity were significantly increased when over 0.3% garlic extract was added. The antioxidant activity of linoleic acid in $\beta$- carotene increased in a dose dependant manner in response to the concentration of garlic extract. In livers of rats, the content of total lipids was significantly decreased by feeding garlic and medicinal plants composites; in particular, the group in which 0.7% garlic extract was added was the lowest. Total cholesterol was 14.95 mg/g in the control group; its level was lower in the groups fed garlic and medicinal plants composites, ranging from 11.47 to 11.86 mg/g. Triglyceride concentration was significantly decreased in the group fed 0.7% garlic extracts, with 46.42 mg/g compared to groups fed 0.3% and 0.5%. TBARS content showed a 15.8~17.6% decrease in groups fed 0.5~0.7% garlic extract and medicinal plants composites. Antioxidant activity was significantly increased in groups fed over 0.5% garlic extract compared to the control group. This study shows that garlic and medicinal plant composites intake is able to reduce the levels of liver lipids in hypercholesterolemic rats.
Sorghum bicolor L. is one of the important minor cereals in Asia, Africa, and the central United States, and it is considered a rich source of polyphenols, flavonoids, and dietary fiber. However, there is a lack of data on the anti-cancer activity of Sorghum in prostate cancer cells and immune activity in macrophages. This study aims to investigate the potential effects of an ethanol extract of S. bicolor L. (SE) on inducing apoptosis in RC-58T/h/SA#4 cells and immunomodulatory activity in RAW 264.7 cells. SE significantly inhibited the viability of RC-58T/h/SA#4 primary prostate cancer cells in a dose-dependent manner. The morphology of RC-58T/h/SA#4 cells treated with SE was shrunken and involved the formation of an apoptotic body and nuclear condensation. In addition, SE markedly activated caspase-8, -9, and -3; increased the protein levels of Bax, p53, cleaved PARP, and cytosolic cytochrome c; and decreased Bcl-2 protein expression. Furthermore, the inhibition of caspases in RC-58T/h/SA#4 cells with z-VAD-fmk attenuated SE-induced cell growth inhibition. The production of nitric oxide (NO) was also elevated by SE treatment, as revealed by immune response parameters. These results suggest that SE inhibits growth and induces apoptosis in primary human prostate cancer cells in a caspase-dependent manner, and it modulates the immune functions in macrophages. Therefore, Sorghum bicolor L. may be used as a functional food to prevent prostate cancer and enhance immune activity.
The retrospective analysis was performed on 37 patients with stage III non small cell lung cancer who received the radiotherapy from Feb. 1986 to Dec. 1990 at the Dept. of Radiation Oncology, National Medical Center. This analysis, with 29 patients $(78.4\%)$ having been followed from 10 to 60 months, was done to know the survival rate and significant prognostic factor. The actuarial 2,5-year survival rates were $20.6\%,6.9\%$ in our all patients and median survival time was 10 months. Of patients with KPS (Karnofsky prformance status) greater than $80\%,$ the 2, 5 year survival rate and median survival time were $29.2\%,9.7\%$ and 13 months, respectively. The 2-year survival rate and median survival time of patients with KPS less than $80\%\;were\;13.7\%$ and 7 months, respectively. The survival difference according to performance status was statisticaly significant $(29.2\%\;vs.\;13.7\%)(p<0.05).$ In stage IIIa, the 2,5-year survival rate and median survival rate and median survival time were $29.2\%,9.7\%$ and 12 months, respectively. The 2-year survival rate and metian survival time of stage IIIb were $8.6\%$ and 10 months, respectively. The survival difference between stage IIIa and IIIb did not show statistical significance (p>0.1). Of the prognostic factors, the difference of survival rate by initial performance status was statistically significant (p<0.05). But the difference of survival rates by pathologic cell type, stage, total radiation dose, radiotherapy response, and cmbination with chemotherapy were not statistically significant.
[ $\beta$ ]-Glucans (AG) were prepared from Agaricus blazei cultured in the medium fortified with the roots of Pueraria spp. by repeated extraction with hot water, gel filtration chromatography and DEAE ion exchange chromatography. Oligosaccharides (AO) were derived from the hydrolysis of AG by an endo-$\beta$-(1$\rightarrow$6)-glucanase from Bacillus megaterium. The anti-HT-29 human colon cancer activity of AG or AO was investigated using MTT assay, apoptosis assay, cell cycle analysis, and cDNA microairay. AG and AO both inhibited proliferation and growth of HT-29 cells, and stimulated apoptosis of the cells in a dose-dependent manner. In cell cycle analysis, treating HT-29 cells with AG or AO resulted in the increase of cells in the G0 (sub-G1) and G1 phase. Especially, AO was more effective in inducing G0/G1 cell cycle arrest than AG. To screen the genes involved in the increase of apoptosis, the gene expression profile of the HT-29 cells treated with AO was examined by cDNA microarray. While several genes involved in cell cycle progression (CCND2 and CDK2) were down-regulated, many genes involved in apoptosis (TNFSF9, TNFRSF9, FADD, CASP8, BAD, CRADD, CASP9 etc), cell cycle inhibitor (CDKN2A), immune response (IL6, IL18, IL6R etc), and tumor suppressor (CEACAM1, TP53BP2, IRF1, and PHB) were up-regulated. These results suggest that AO could inhibit the proliferation and growth of HT-29 cells by G0/G1 cell cycle arrest and induction of apoptosis.
Kim, I.A.;Jin, E.J.;Cho, E.J.;Sohn, S.H.;Lee, C.Y.
Journal of Animal Science and Technology
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제46권4호
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pp.563-570
/
2004
The insulin-like growth factor(IGF) system, consisting of IGFs-I and -II ligands and their receptors and six IGF-binding proteins(IGFBPs), plays an important role in survival, proliferation and differentiation of a variety of cell types. Lithium is a known modulator of survival and proliferation of many cell types in vitro. The present study was undertaken to investigate the relationship between LiCI-induced changes in cell survival and growth and the expression of the IGF system components in C6 rat glioma cell line which, besides IGF-I and its receptor, is known to express IGFBP-3 as its major IGF carrier. When C6 cells were cultured for 24h in the absence or presence of 2mM or 5mM LiCl in a 10% serwn-containing medium, the viability and the number of cells were not affected by added lithium. In 72-h culture, however, C6 cells clearly exhibited a dose-dependent response to added LiCl. The cells cultured for 72h in the presence of 0, 2mM and 5mM LiCl exhibited a typical mitotic, a growth-arrested and an apoptotic appearances, respectively. Moreover, the apoptotic cells were accompanied by reduced expression of IGF-I, IGF-I receptor and IGFBP-3 as examined by semi-quantitative reverse transcription-polymerase chain reaction. Interestingly, blockade of IGFBP-3 mRNA translation by addition of 101${\mu}M$ IGFBP-3 anti-sense oligodeoxyribonucleotide in serum-free, 24-h culture resulted in a decrease in the number of cells as well as relative abundance of the target mRNA. In summary, results suggest that the cytotoxic effect of lithium in C6 cell is likely to be mediated, in part, by suppression by this agent of the expression of the IGF system components. In this regard, IGFBP-3 may play at least a 'permissive' role in normal proliferation of this cell.
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