• Radiation Oncology Journal
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• v.25 no.3
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• pp.151-159
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• 2007

Purpose: The purpose of this study is to present the treatment results and to identify possible prognostic indicators in patients with locally advanced hypopharyngeal carcinoma. Materials and Methods: Between October 1985 to December 2000, 90 patients who had locally advanced stage IV hypopharyngeal carcinoma were studied retrospectively. Twelve patients were treated with radiotherapy alone, 65 patients were treated with a combination of chemotherapy and radiotherapy, and 13 patients were treated with surgery and postoperative radiotherapy with or without neoadjuvant chemotherapy. Total radiation dose ranged from 59.0 to 88.2 Gy (median 70 Gy) for radiotherpay alone. Most patients had ciplatin and 5-fluorouracil, and others had cisplatin and pepleomycin or vincristin. Median follow-up period was 15 months. Kaplan-Meier method was used for survival rate and Cox proportional hazard model for multivariate analysis of prognostic factors. Results: Overall 3-and 5-year survival rates were 27% and 17%, respectively. The 2-year locoregional control rates were 33% for radiotherapy alone, 32% for combined chemotherapy and radiotherapy, and 81 % for combined surgery and radiotherapy (p=0.006). The prognostic factors affecting overall survival were T stage, concurrent chemoradiation and treatment response. Overall 3-and 5-year laryngeal preservation rates in combined chemotherapy and radiotherapy were 26% and 22%, respectively. Of these, the 5-year laryngeal preservation rates were 52% for concurrent chemoradiation group (n=11), and 16% for neoadjuvant chemotherapy and radiotherapy (n=54, p=0.012). Conclusion: Surgery and postoperative radiotherapy showed better results than radiotherapy alone or with chemotherapy. Radiotherapy combined with concurrent chemotherapy is an effective modality to achieve organ preservation in locally advanced hypopharyngeal cancer. Further prospective randomized studies will be required.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.257-262
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• 2008

Purpose: Oral mucositis induced by radiotherapy to the head and neck area, is a common acute complication and is considered as the most severe symptom for cancer patients in the early stages of treatment. This study was proposed to establish the oral mucositis mouse model induced by a single dose of radiation for the facility of testing therapeutic candidates which can be used for the oral mucositis treatments. Materials and Methods: Fifty-five BALB/c mice were divided into four groups: control, 16 Gy, 18 Gy, and 20 Gy. Oral mucositis was induced by a single dose of radiation to the head and neck using 6 MV x-Ray from linear accelerator. After irradiation, body weight and physical abnormalities were checked daily. Tongue tissues from all groups were taken on days 1, 2, 3, 5, 7, 9, and 14, respectively and H&E staining was conducted to examine morphological changes. Results: Body weight dramatically decreased after day 5 in all irradiated mice. In the 16 Gy treatment group, body weight was recovered on day 14. The histology data showed that the thickness of the epithelial cell layer was decreased by the accumulated time after radiation treatment, up to day 9. Severe ulceration was revealed on day 9. Conclusion: A single dose of 16 Gy is sufficient dose to induce oral mucositis in Balb/C mice. Significant changes were observed in the Balb/C mice on days 7 and 9 after radiation. It is suggested that this mouse model might be a useful standard tool for studying oral mucositis induced by radiation.

• Journal of Veterinary Clinics
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• v.22 no.2
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• pp.94-99
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• 2005

This prospective study aimed to assess the efficacy of dexamethasone to prevent xylazine induced emesis in dogs. The antiemetic effect of graded, single high-dose intravenous dexamethasone against xylazine hydrochloride was studied. Clinically healthy mixed breed dogs that weighed $ 4.64\pm1.25kg$ were used in this study. Food and water were given 3 hours before the experiment. Venous blood specimens were collected from all experimental animals for hema-tological and blood chemical test pre- and post-experiment. Twenty-eight experimental animals were randomly divided into 4 groups; the group treated with 0.2ml/kg of normal saline (Control group), the groups treated with 1mg/kg (D1 group), 2mg/kg (D2 group) and 4 mg/kg of dexamethasone (D4 group). Three doses of the dexamethasone or normal saline was administered intravenousely to each group and after 5 minutes, xylazine (2.2 mg/kg) was administered intramuscularly. The time until onset of the first emetic episode and rate of emesis were investigated. At the same time, the extent of sedation was scored subjectively 5, 15, 30 and 60 minutes after injection of xylazine hydrochloride using Visual Sedation Score. The time until onset of the first emetic episode was $203.25\pm11.35$ sec in Control group, $187.33\pm48.0l$ sec in D1 group and 218.33± 13.58 sec in D2 group. The rate of xylazine induced emesis were $57\%$ in Control group and $43\%$ in D1 and D2 group respectively. On the other hand, any emetic episodes were not observed in 04 group. At extent of sedation score, all experimental animals especially including the animals in D1 group were highly sedated at 15 minutes after administration of xylazine hydrochloride. Hematological and blood chemical values showed normal ranges pre- and post-experiment. We concluded that prior treatment with 4 mg/kg of dexamethasone hardly caused xylazine-induced emesis without disturbing the sedative effect of xylazine in dogs.

• Journal of Veterinary Clinics
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• v.22 no.3
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• pp.202-205
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• 2005

The present study was made in order to clarify the anti-emetic effect by needle-acupuncture (AP), injection-AP and moxibustion in xylazine - induced vomiting of dogs. Twelve mongrel dogs (4 months to 5 year old, 2 to 4 kg of body weight), eleven mongrel dogs (4 months to 5 years old, 2 to 10 kg of body weight) and twelve mongrel dogs (4 months to 1 year old, 2 to 4 kg of body weight) were used for clarification of anti-emetic effect by needle-AP, injection-AP and moxibustion, respectively. The experimental animals were devided into control(6 heads), BL-21(6 heads), CV-12(6 heads) and BL-21+CV-12(6 heads) groups using total 6 dogs with vomiting selected in preliminary experiment, respectively in needle-AP treatment. In addition, the experimental dogs were divided into control (11 heads), BL-21 (6 heads) and CV-12(6 heads) groups using 11 dogs, respectively in injection-AP treatment. In moxibustion treatment the experimental dogs were divided into control (6 heads), BL-21(6 heads) and CV-12(6 heads) groups using 6 dogs, respectively. Five days after the experiment of one group was finished, the other group was examined in each experiment. Acupuncture needle was maintained for 20 minutes in needle-AP treatment. Metoclopramide was used in injection-AP treatment. Commercial moxa was used in moxibustion treatment. Vomiting was induced by intramuscular injection with $2{\%}$ xylazine 20 minutes after treatments of needle-AP, injection-AP and moxibustion, respectively. The vomiting rates of BL-21($33.3{\%}$), CV-12($50{\%}$) and BL-21+CV-12($33.3{\%}$) were lower than that of control($66.7{\%}$) and vomiting times of experimental groups were similar to that of control in needle-AP treatment. The vomiting rates of BL-21 ($0{\%}$) and CV-12($16.4{\%}$) were lower than that of control($66.7{\%}$) and the vomiting time of CV-12 group was similar to that of control group in injection-AP treatment. The vomiting rates of BL-21($33.3{\%}$) and CV-12($33.3{\%}$) were lower than that of control ($66.7{\%}$) and vomiting times of experimental group were similar to that of control group in moxibustion treatment. In conclusion, it was considered that needle-AP, metoclopramide injection-AP and moxibustion at BL-21 and CV-12 were effective for anti-emesis in xylazine induced vomiting of dogs and metoclopramide injection-AP was the most effective method for anti-emesis among them.

• Journal of Veterinary Clinics
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• v.23 no.1
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• pp.65-68
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• 2006

Two cases of canine intervertebral disc disease (IVDD) were treated twice a week with injection-acupuncture (injection-AP) using 0.1 ml/acupoint. In case 1, a paralysed dog with cervical intervertebral disc disease (C3-C4), was submitted to injection-AP with dexamethasone (1 mg/ml) at session 1-2 and thiamine (25 mg/ml) at session 3-5. Injected acupoints included GV-16, GB-20, BL-10, LU-7, LI-4 and SI-6. The acupoints GV-6, GV-20 and SP-6 were added at session 2-5. Trigger point (TP) therapy with 0.2 ml of 2% lidocaine was used in session 3-5 at TP in the infraspinatus and triceps muscles. Treatment was stopped when paralysis disappeared after 5 injection-AP treatments; there were no recurrent symptoms in the follow-up period of 5 months. In case 2, an ataxic dog with lumbar IVDD (L1-L2), was submitted to injection-AP with dexamethasone at session 1 and 2 and thiamine at session 3-4. Injected acupoints included GV-6 as the main point, ST-36, GB-30, ST-40, GB-34, ST-41 and BL-40. TP therapy with 0.2 ml of 2% lidocaine was used at TP in the ileocostorum lumborum and quadriceps muscles. Treatment was stopped when ataxia disappeared after 4 treatments; there were no recurrent symptoms In the fallow-up period of 5 months. Injection-AP using dexamethasone and thiamine, combined with TP therapy using lidocaine, effectively alleviate the symptoms of canine cervical and lumbar IVDD.

• Journal of Veterinary Clinics
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• v.24 no.1
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• pp.10-14
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• 2007

The present study was performed to elucidate the recovery effect of needle-acupuncture (needle-AP) and moxibustion treatments at Gan Shu (BL18) on $CCl_4$ induced hepatic injury in dogs, Total 9 clinically healthy experimental dogs (1 to 2 years old, 2.3-5.3kg body weight) were divided into control (3 dogs), needle-AP (3 dogs) and moxibustion (3 dogs) groups, respectively. Hepatic iniw was induced by intraperitoneal injection with $CCl_4$ (olive oil : $CCl_4=1:1,\;1ml/kg$, once/day). As far the treatments in each group, control group was not treated at all after induction of the hepatic injury till the end of experiment. Needle-Af group was treated by AP at BL18 (once/day, 20 minutes) from the next day of induction of the hepatic injury for 11 days. Moxibustion group was also treated with commercial moxa at BL18 (once/day, 20minutes) for 11days. The changes of the serum alanine transaminase(ALT), aspartate transaminase(AST) and gamma glutamyl transpeptidase (GGT) activities were investigated on pre, 0, 1, 3, 5, 7 and 11 days after hepatic injury, respectively. Histopathological changes were also investigated in the liver tissues on day 11 in experimental and control groups. The results obtained in the present study were as follows. In needle-AP group, they showed significant lower values on the 1st (p<0.05) and $3^{rd} day (p <0.05)$ in serum ALT activities, and the $11^{th}$ day in serum GGT activities, compared with those of control group, respectively. However, the significances were not detected in serum AST activities of needle-AP group by comparison with those of control group. In moxibustion group, they showed significant low values on the $1^{st}(p<0.05)$, 3rd day (p<0.05) and $5^{th}$ day (p<0.05) in serum ALT activities, compared with those of control group, respectively. However, significances were not detected in serum GGT and AST activities of moxibustion group by comparison with those of control group. Among the experimental groups, the significant low values were found on $1^{st}\;and\;3^{rd}$ day in serum ALT activities (p<0.05), and $3^{rd}\;and\;5^{th}$ day in serum GGT activities (p<0.05) in needle-AP group, compared by those of moxibustion group, respectively. In addition, the marked recovery findings of histopathological changes in experimental groups were found, compared by those of control group: mild vacuolar degeneration and necrosis findings in needle-AP group, and moderate vacuolar degeneration and necrotic findings in moxibustion group were found, in contrast to severe changes such as accumulation of bile juice, vacuolar degeneration and necrotic findings observed in control group. In conclusion, needle-AP and moxibustion treatments at BL-18 were effective for the recovery for $CCl_4$ induced hepatic injury and needle-AP was more effective than that of moxibustion in dogs.

• Journal of Life Science
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• v.19 no.11
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• pp.1629-1636
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• 2009

Pine trees (Pinus densiflora Sieb. et Zacc.) have been used as a traditional health-promoting medicinal food in Korea. This research was performed to determine the antioxidative and antibacterial activities, tyrosinase, nitric oxide synthesis, angiotensin converting enzyme (ACE), and xanthine oxidase inhibition effects of the pine bud ethanol extract (PBE). Antioxidative activities of PBE were measured by using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging activity and superoxide dismutase-like activity (SODA). DPPH radical scavenging and SOD-like activities of PBE were remarkably increased in a dose-dependent manner, and were about 88.9% and 47.9% at 1 mg/ml and 10 mg/ml, respectively. The xanthine oxidase and angiotensin converting enzyme activities were inhibited about 71.9% and 60.8% at 1 mg/ml and $100{\mu}g/ml$ of PBE, respectively. The tyrosinase inhibitory activities of PBE were slightly increased in a dose-dependent manner. The PBE showed strong antimicrobial activities on Escherichia coli (E. coli) and Vibrio paraheamolyticus. Stimulation of the macrophages RAW264.7 cells with lipopolysaccharide (LPS) resulted in increased production of nitric oxide (NO) in the medium. However, NO synthesis was reduced up to 54% by addition of PBE at $200{\mu}g/ml$. These results revealed that pine buds have a strong antioxidative and anti-inflammatory activity, and exhibit angiotensin converting enzyme and xanthine oxidase inhibitory activities. This suggests that pine buds have the greatest property as a source for natural health products.

• Journal of Life Science
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• v.19 no.8
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• pp.1073-1080
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• 2009

A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

• Journal of Life Science
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• v.24 no.3
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• pp.329-335
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• 2014

Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus have been widely used in folk medicine for several inflammatory disorders in Korea and China. In this study, we compared the anti-inflammatory effects of the ethanol extracts of S. flavescens (EESF), G. uralensis (EEGU) and D. dasycarpus (EEDS), and their mixtures (medicinal herber mixtures, MHMIXs) on production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Our data indicated that treatment with EESF, EEGU and EEDD significantly inhibited the excessive production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in LPS-stimulated RAW 264.7 cells. The ethanol extracts and MHMIXs also attenuated the production of pro-inflammatory cytokines, including interleukin-$1{\beta}$ ($IL-1{\beta}$) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) by suppressing their protein expression, respectively. Interestingly, MHMIX-1, which basic ingredients are EESF, EEGU and EEDS in the proportion 3:1:1, more safely and effectively inhibits the LPS-induced inflammatory status in LPS-stimulated RAW 264.7 macrophages compared to ethanol extracts of each medicinal herb and other MHMIXs without causing any cytotoxic effects. Our study provides scientific evidence to support that a berbal mixture, MHMIX-1 may be useful in the treatment of inflammatory diseases by inhibiting inflammatory regulator responses in activated macrophages.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.1-10
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• 1997

Purpose : To evaluate the role of radiotherapy in the management of incompletely resected supratentorial low grade astrocytoma with the analysis of the survival, the Pattern of failure, and the prognostic variables affecting survival. Material and methods : Between January 1990 and December 1995, fifty-one patients with supratentorial low grade astrocytoma received radiotherapy after subtotal resection(16 patients) or stereotactic biopsy(35 patients) at Asan Medical Center, External radiotherapy was done by conventional fractionation with the total dose of 4820cGy to 6000cGy(median 5580cGy) and partial brain volume. The follow-up was done from 6 to 79 months(median 48 months) Result : Overall actuarial survival rate at 2 and 5 years were $83.4\%\;and\;54.8\%$, respectively. Progression free survival at 2 and 5 years were $67.4\%\;and\;48.7\%$, respectively The significant prognostic factors affecting overall survival rate were the performance status, 1 stage, histologic subtype, radiation field and radiation response. The major pattern of failure was local failure, such as Progressive disease and primary site recurrence in 23 patients $(45.1\%)$. Progression free survivors excluding 2 patients were physically and intellectually intact without major neurologic deficit. Conclusion : Although the follow-up period of this study was relatively short, overall actuarial and progression free survival rate were encouraging. Patients with good performance status, lower T stage, pilocytic subtype, patients treated with small radiation field and radiation responder showed better survival. As the local failure was the major pattern of failure, the various efforts to decrease the local failure is necessary.