Ethane 1,2-Dimethane sulfonate(EDS), a toxin which specifically kills Leydig cells(LC), has been widely used to prepare the reversible testosterone(T) depletion rat model. Previous studies including our own clearly demonstrated that the dramatic weight loss of the T-dependent accessory sex organs such as epididymis and seminal vesicle in this 'LC knock-out' rats. These weight loss could be derived from massive and abrupt death of the cells via apoptotic process. The present study was performed to test the effect of EDS administration on the expression of some apoptotic genes in the rat epididymis. Adult male Sprague-Dawley rats($300{\sim}350$ g B.W.) were injected with single dose of EDS(75 mg/kg, i.p.) and sacrificed on Weeks 0, 1, 2, 3, 4, 5, 6 and 7. Tissue weights and the numbers of the epididymal sperm were measured. The transcriptional activities of the bcl-2, bax, Fas and Fas ligand(Fas-L) were evaluated by semi-quantitative RT-PCR. As expected, the weights and the sperm counts of epididymis declined progressively after the EDS treatment during Week 1 and 2. These decrements were discontinued with a gradual return towards normal during Weeks $5{\sim}7$, although the maximal recoveries of the epididymal weights(71%) and sperm count(38%) were subnormal on Week 7. The initial level of bcl-2 transcripts persisted to Week 6 then elevated significantly on Week 7. The level of bax transcripts significantly decreased on Week 6, and no remarkable change was found in the rest of the experimental period. The transcripts for the Fas in epididymis elevated during Weeks $1{\sim}2$, returned to normal on Week 3, and the level persisted to the Week 7. Similarly, the level of Fas-L transcripts elevated during Weeks $1{\sim}3$ and returned to normal after Week 4. Our results demonstrated the transient T depletion by EDS administration could induce the changes in expression of the apoptotic genes in rat epididymis. The activation of Fas and Fas-L in the epididymis of EDS-treated rats might be responsible for the initial apototic process and consequently the tissue damage and the sperm loss. Future studies will attempt to determine the precise molecular mechanism(s) of apoptosis in the rat epididymis.
Purpose : This study was done to evaluate the efficacy of low-dose radiation in reduction of thoracic vertebral metastases in patients with breast cancer. Materials and Methods : 109 patients who were treated for bone metastasis from breast cancer from June, 1988 to June, 1998 in the Department of Therapeutic Radiology, Seoul National University were included. Of the 109 patients, 40 patients had been previously treated by postoperative radiotherapy and 69 had not. Postoperative radiotherapy had been given using Co-60 teletherapy device in 30 patients or 6 MV linear accelerator in 10. Thoracic spines from 1 to 10 were usually irradiated except in 1 patient and cervical vertebrae 6 and/or 7 were partially included in ,: patients. A total of 50.4 Gy was given with 1.8 Gy fraction. Metastatic bone diseases were scored in 11 regions, i. e., skull, conical spine, thoracic spine from 1 to 4, from 5 to 8, 9 and 10, 11 and 12, lumbar spine, pelvis, femur, ribs and others. Results : In no postoperative parasternal irradiation group, lumbar vertebrae were the most common metastatic sites $(55.1\%)$ followed by pelvis $(44.9\%)$, ribs $(40.6\%)$, thoracic vertebrae 11 and 12 $(37.7\%)$, thoracic vertebrae between 5 and 8 $(36.2\%)$, thoracic vertebrae 9 and 10 $(34.8\%)$, and thoracic vertebrae between 1 and 4 $(26.1\%)$. In postoperative parasternal irradiation group, lumbar vertebrae and pelvis were also the most common sites of metastases ($55.0\%$, respectively) followed by ribs $(37.5\%)$, and thoracic vertebrae 11 and 12 $(32.5\%)$. But significant less metastases were seen at thoracic vertebrae from 1 to 10. Conclusion : We can find that the were significantly less bony metastases at thoracic vertebrae which had been previously irradiated postoperatively.
Kang Ki Mun;Chai Gyu Young;Kim Jin Pyeong;Lee Won Seop
Radiation Oncology Journal
/
v.22
no.4
/
pp.247-253
/
2004
Purpose: Hypopharyngeal cancer is diagnosed at the advanced stage in most cases, which the prognosis known to be poor. Thus, the efficacy of induction chemotherapy followed by radiotherapy, with regards to the response and survival rate for stage IV hypopharyngeal cancer patients, was examined. Materials and Methods: From July 1998 to February 2000, 18 cases were diagnosedas AJCC stage IV hypopharyngeal cancer without distant metastasis. These patients were treated with induction chemotherapy followed by radiotherapy, and the results retrospectively analyzed. The regimen of the induction chemotherapy was the 5-FU and cisplatincombination, at 3-week intervals for, 2 cycles. The total radiation dose for the primary lesion and metastatic lymph nodes was $68.4\~72.0$Gy (median: 70.2 Gy). Results: The: The median follow up period was 28 months, ranging from 7 to 99 months. The 3-year overall survival and disease-free survival rate were 41.7 and $31.1\%$, respectively. In 6 cases ($33.3\%$), conservation of the larynx for over 3 years was possible. After the induction chemotherapy there were 16 partial responses ($88.8\%$), 1 complete response and 1 with no response ($5.6\%$ each), therefore, 17 of the 18 cases ($94.6\%$) showed responses. After the completion of the induction chemotherapy and radiotherapy, a complete response was noted in 13 cases ($72.2\%$), a partial response in 5 ($27.8\%$), with an overall response rate of $100\%$. In the analysis of the prognostic factors influencing the survival rate, the 3-year and disease-free survival rates for the complete and partial response groups were 43.1, and $20.0\%$, and 39.6, and $20.0\%$, respectively (p=0.0003, p=0.002). Only the final response after treatment completion was statistically significant. Conclusion: For stage IV hypopharyngeal cancer, induction chemotherapy followed by radiotherapy was an effective treatment, with no severe side effects.
Kay Chul Seung;Choi Ihl Bohng;Jang Ji Young;Kim In Ah
Radiation Oncology Journal
/
v.16
no.1
/
pp.27-33
/
1998
Purpose : To improve the therapeutic results of postoperative recurrent disease and inoperable disease of stomach cancer, we used the thermoradiotherapy. We conducted a retrospective analysis of the results and compared the results of hyperthermia before radiotherapy and those of hyperthermia after radiotherapy Materials and Methods : From July 1994 to November 1996, we treated twenty patients with locally advanced stomach cancer and recurrent stomach cancer with thermoradiotherapy. We divided those patients into two groups : hyperthermia before radiotherapy group (PreRT group : 13 Patients) and hyperthermia after radiotherapy group (PostRT group : 7 patients). We performed radiation therapy with the total tumor dose of 3000-5040cGy in a traction of 180-300cGy and 5 fractions per week. Hyperthermia was performed with 8 MHz radiofrequency apparatus. PreRT group patients were treated daily for 30 minutes before the radiation therapy within the interval of ten minutes. And PostRT group patients were treated with 1-2 sessions Per week for 40-60 minutes after the radiation therapy within the interval of 10 minutes. Results : Overall response rate was $33.3\%$. This response rate appeared the same in both groups. Mean survival and 1 rear survival rate were 10.3 months and $16.5\%$. In PreRT group, mean survival and 1 year survival rate were 6.8 months and $9.0\%$, and in PostRT group, mean survival and 1 year survival rate were 7.7 months and $34\%$. There were no statistically significant difference between the prognostic factors and therapeutic results. Conclusion : The thermoradiotherapy was a safe treatment method in advanced and recurrent gastric cancer when compared with other treatment. Because the number of patients we treated was small and the follow up period was short. we were not able to draw any conclusions about the therapeutic efficacy of the sequence of radiation therapy and hyperthermia. Therefore, further clinical trials of thermoradiotherauy for stomach cancer appear to be warranted.
Purpose : Metabolic bone diseases have been mai or problems in children with renal diseases and steroid treatment is the main precipitating factor reducing bone mineral density(BMD). This study was performed to assess the prevalence of osteoporosis and to evaluate the clinical factors associated with decreased BMD in children with renal diseases. Methods : Forty-four children with renal diseases who were diagnosed at the Pediatric no phrology division of Ajou University hospital since Oct. 1994 were included. Using a new quantitative ultrasound device, BMD and the prevalence of osteoporosis were evaluated. The clinical and serological data were analyzed in association with decreased BMD. Results : A total of 44 patients were evaluated. The age at initial diagnosis was 6.7$\pm$4.2 years. At the time of evaluation, the chronological and bone age was 9.3$\pm$4.2 years and 8.2 $\pm$ 4.6 years, respectively. The renal diseases included nephrotic syndrome 24(54.5%), Henoch Schonlein purpura nephritis 7(15.9%), IgA nephropathy 6(13.9%), reflux nephropathy(RN) 2 (4.5%), and other renal disease 5(%). The prevalence of osteoporosis was 11%. There was no difference in the clinical factors between the long-term and the short-term treated steroid groups. Conclusion : The prevalence of osteoporosis was 12% in 44 children with renal diseases No significant factor was found in association with decreased BMD and there was no relationship between osteoporosis and steroid usage duration or cumulative dose. A new quantitative ultrasound, which is relatively easy to perform, especially in children, is expected to be in common use and will enable clinicians to evaluate metabolic bone disorders with ease.
In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent $Ca^{2+}$ channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned $Ca^{2+}$ channel subtypes such as ${\alpha}_{1C}$(L)-, ${\alpha}_{1B}$(N)-, ${\alpha}_{1A}$(P/Q)-, ${\alpha}_{1E}$(R)- and ${\alpha}_{1G}$(T) have not been identified. Here, we used the two-microelectrode voltage clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on $Ba^{2+}$ currents ($I_{Ba}$) in Xenopus oocytes expressing five different $Ca^{2+}$ channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the ${\alpha}_{1G}$-type. Of the various ginsenosides, $Rb_1$, Rc, Re, Rf, $Rg_1$, $Rg_3$, and $Rh_2$, ginsenoside $Rg_3$ also inhibited all five channel subtypes and ginsenoside $Rh_2$ had most effect on the ${\alpha}_{1C}$- and ${\alpha}_{1E}$-type $Ca^{2+}$ channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the ${\alpha}_{1G}$-type of $Ca^{2+}$ channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. $Rg_3$, $Rh_2$, and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the ${\alpha}_{1B}$- and ${\alpha}_{1A}$-types. These results reveal that $Rg_3$, $Rh_2$ and CK are the major inhibitors of $Ca^{2+}$ channels in Panax ginseng, and that they show some $Ca^{2+}$ channel selectivity.
Purpose: A prospective comparison was made between imaging with Tc-99m pertechnetate (Tc-99m) and Ioine-131 (I-131) for the detection of residual and metastatic tissue after total thyroidectomy in patients with well-differentiated thyroid carcinoma. Materials and Methods: Initially our patients had imaging with Tc-99m, followed by I-131 within 3 days. The study included 21 patients who had ablation with high dose of I-131 ranging from 100 mCi to 150 mCi. Planar and pinhole images were acquired for both Tc-99m and I-131. Diagnostic images of Tc-99m and I-131 were compared with post-therapy images. Degree of uptake on Tc-99m and I-131 images was scored by four point scale and compared. Results: The results of the Tc-99m study were: 16 of 19 studies (84%) were positive on simple planar images, but 19 of 20 studies (95%) were positive on pinhole images. Conventional I-131 diagnostic imaging on the other hand showed that all studies (100%) were positive on both planar and pinhole images. There was a significant difference in degree of uptake between Tc-99m and I-131 planar images (p<0.05). Only one case of Tc-99m scintigraphy was negative on both planar and pinhole studies (false negative). There was no distant metastasis on the therapeutic I-131 images. Conclusion: Tc-99m scan using pinhole in certain clinical situations is an alternative to the I-131 scan in detecting thyroid or lymph node metastasis prior to the first ablative treatment after thyroidectomy for well-differentiated thyroid carcinoma.
Kim, Eun-Ji;Park, Hee-Sook;Lim, Soon-Sung;Kim, Jong-Sang;Shin, Hyun-Kyung;Yoon, Jung-Han
Korean Journal of Food Science and Technology
/
v.40
no.2
/
pp.207-214
/
2008
In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.
The objective of the study was to observe the effect of n-3 PUFA on cell proliferation and apoptosis by determining mRNA and protein of COX-2 and eicosanoid product and the mRNA and protein of Bu and Bcl-2 related to apoptosis in colon carcinogenesis of 1,2- dimethylhydrazine (DMH)-treated rats. Ninety male Sprague Dawley rats weighing about 170g were divided into 3 groups, control and n-3 PUFA supplemented groups (FO group: 6.2 mmoles n-3 PUFA; 2FO group: 12.4 mmoles n-3 PUFA) and fed experimental diet for 14 weeks. All rats were intramuscularly injected with DMH 15 mg/kg twice a week for 6 weeks to deliver total dose of 180 mg/kg body weight. Compared with the control group, 6.2 mmoles n-3 PUFA significantly reduced the levels of mRNA and protein expression of COX-2 and 2-series eicosanoids ($TXB_{2}$ and $PGE_{2}$) and decreased cell proliferation in colonic mucosa. However, high levels of n-3 PUFA supplementation significantly increased the levels of mRNA and protein expression of COX-2, TXB2 and PGE2. and increased cell proliferation which was similar level to that of control group. Compared with the control group, n-3 PUFA, regardless of the amount, significantly increased apoptotic index in colonic mucosa. Western blot and RT-PCR analyses showed that the levels of mRNA and protein expression of Bax were significantly increased by 6.2 mmoles n-3 PUFA, but decreased by 12.4 mmoles n-3 PUFA. The analyses also showed the levels of mRNA and protein expression of Bcl-2 were significantly reduced by 6.2 mmoles n-3 PUFA, but increased by 12.4 mmoles n-3 PUFA. The ratio of Bcl-2/Bax in mRNA and protein was significantly reduced by 6.2 mmoles n-3 PUFA but increased by 12.4 mmoles n-3 PUFA. Overall, these results indicate that n-3 PUFA could be effective in preventing colon carcinogenesis by reducing cell proliferation with lower level of COX-2 and 2-series eicosanoid, and increasing apoptosis by inducing pro-apoptotic gene, Bax and inhibiting anti-apoptotic gene, Bcl-2 in the colonic mucosa of DMH-treated rats. However, high level of n-3 PUFA supplementation could stimulate colon carcinogenesis by increasing cell proliferation and inhibiting apoptosis. (Korean J Nutrition 38(10): 807$\sim$816,2005)
To study the effect of alginic acid on modulation of the aging process, Sprague-Dawley(SD) male rats were fed the diets containing 0, 3, 6 and $9\%$ alginic acid isolated from brown algae(Undaria pinnatifida) for 16 weeks. The effects of alginic acid on body weight, malondialdehyde(MDA) content, peroxidizability index, cholesterol and phospholipid levels, cholesterol/phospholipid(Ch/Ph) molar ratio, and fatty acid compositions in liver membranes were investigated. Increasing alginic acid level in diets did not alter food intakes but effectively decreased body weights gain(p<0.01-0.005). Malondialdehyde(MDA) contents of diets containing 6 and $9\%$ alginic acid were effectively decreased in ranges of $54.1-43.0\%$ in mitochondria, and $65.5-87.7\%$ in microsome compared with $100\%$ of control group. Cholesterol levels of all diets containing alginic acid were significantly decreased in ranges of $87.0-72.3\%$ in mitochondria, and $87.4-68.1\%$ in microsome compared with $100\%$ of control group. Phopholipid levels in microsome were significantly decreased by diets containing 3 and $ 6\%$ alginic acid but Ch/Ph molar ratios in both membranes were decreased by diets containing 3 and $6\%$ alginic acid. Increasing alginic acid level in diets significantly decreased total fatty acid but effectively increased linoleic acid in microsome except for diet containing $9\%$ alginic acid. These data on liver membranes suggest that alginic acid added to diets can modulate the physiological changes if the aging process.
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