• Journal of Life Science
• /
• v.31 no.9
• /
• pp.818-826
• /
• 2021

5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.

• Korean Journal of Clinical Laboratory Science
• /
• v.51 no.2
• /
• pp.245-251
• /
• 2019

This study examined the effects of 2-methoxy-1,4-naphthoquinone (MQ) on the monocyte chemoattractant protein-1 (MCP-1)-induced migration of monocytes, which is an important phenomenon for the body defense and immune response. MQ is a major component extracted from Impatiens balsamina leaves, which have been used for many years in Asian medicine for the treatment of a range of diseases and pain. The cytotoxicity of MQ began to appear at a concentration of $10{\mu}M$, and approximately 50% cytotoxicity was confirmed at $100{\mu}M$. The MCP-1 induced migration of the THP-1 monocyte cell line increased after MQ treatment in a dose dependent manner and the largest increase was observed at $0.1{\mu}M$. The level of cAMP expression decreased after a treatment with $0.1{\mu}M$ MQ. The phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), a key signaling protein involved in the signaling pathway of C-C motif chemokine receptor 2 (CCR2), a receptor for MCP-1, was increased by the simultaneous treatment of $0.1{\mu}M$ MQ. These results show that MQ increases the MCP-1-induced migration of THP-1, decreases the level of cAMP expression, and increases the level of Erk1/2 phosphorylation.

• Journal of Apiculture
• /
• v.34 no.3
• /
• pp.245-254
• /
• 2019

We investigated the anti-tumor effects and molecular mechanism of Brazil, China and Korean regional propolis on HeLa ovarian cancer cell line. Each propolis extracts was prepared by ethanol extraction method. Cytotoxicity of propolis extracts was determinated by EZ-cytox cell viability assay. To necessity of anti-tumor effect and molecular mechanism of propolis, we must be adjusting propolis concentration. Due to 100 ㎍/mL of propolis extract were reduced cell viability to less than 50%, we adjusted all of propolis concentration to 100 ㎍/mL. By Western blotting analysis, we confirmed that anti-tumor mechanism of Brazil, China and Korea regional propolis has significantly difference. All of propolis was activated apoptosis related molecules such as PARP, caspase-3. However, cell proliferation signaling molecules including Akt1, ERK and Bcl-2 were reduced the protein expression level. Especially, the expression of tumor suppressor protein p53 was significantly increased in propolis-treated group such as Gyeonggi, Chungbuk, Chungnam, Jeonbuk, Gyeongnam and China. The phosphorylation of Bax which as apoptosis indicator was appeared in propolis-treated group such as Gyeonggi, Gangwon, Chungnam, Gyeongbuk, China. In this results showed that the regional propolis has completely different mechanism in anti-tumor. Thus, propolis extracts may be useful source of functional materials on anti-cancer and it will be able to choose the suitable propolis for cancer therapy by analyzing individual characteristics.

• Radiation Oncology Journal
• /
• v.21 no.4
• /
• pp.261-268
• /
• 2003

Purpose: To report the results of curative treatment for patients with tonsil cancer by retrospective analysis. Materials and Methods: From Jan. 1995 till Dec. 2000, 27 patients with squamous cell carcinoma of the tonsil received curative treatment at Samsung Medical Center. Therapeutic decision was made through multidisciplinary conference, and curative radiation therapy was favored when, (1) the patient's condition was not fit for general anesthesia and surgery, (2) the patient refused surgery, (3) complete resection was presumed impossible, or (4) too severe disability was expected after surgery. Surgery was the main local modality in 17 patients (S$\pm$RT group), and radiation therapy in 10 (RT$\pm$CT group). The median follow-up period was 41 months. Results: AJCC stages were I/II in four, III in two, and IV in 21 patients. The 5-year disease-free survival rate was 73.3$\%$ in all patients, 70.6$\%$ in the S$\pm$RT group, and 77.8$\%$ in the RT$\pm$CT group. Treatment failure occurred in seven patients, all with stage III/IV, and all the failures occurred within 24 months of the start of treatment. Five patients among the S$\pm$CT group developed treatment failures; 2 local, 2 regional, and 1 distant (crude rate=29.4$\%$). Two patients among the RT$\pm$CT group developed failures; 1 synchronous local and regional, and 1 distant (crude rate=20.0$\%$). The 5-year overall survival rate was 77.0$\%$ in all patients, 80.9$\%$ in the S$\pm$RT group, and 70.0$\%$ in the RT$\pm$CT group. Conclusion: We could achieve favorable results that were comparable to previously reported data with respect to both the rates of local control and of survival by applying S$\pm$RT and RT$\pm$CT. RT$\pm$CT is judged to be an alternative option that can avoid the functional disability after surgical resection.

• Radiation Oncology Journal
• /
• v.19 no.4
• /
• pp.327-334
• /
• 2001

Purpose : To find out the role of postoperative adjuvant radiotherapy in the treatment of rectal cancer by comparing survival, pelvic control, complication rate, and any prognostic factor between surgery alone and postoperative radiotherapy group. Materials and methods : From Feb. 1982 to Dec. 1996 total 212 patients were treated by radical surgery with or without postoperative radiotherapy due to rectal carcinoma of modified Astler-Coiler stage $B2\~C3$. Of them, 18 patients had incomplete radiotherapy and so the remaining 194 patients were the database analyzed in this study. One hundred four patients received postoperative radiotherapy and the other 90 patients had surgery only. Radiotherapy was peformed in the range of $39.6\~55.8\;Gy$ (mean: 49.9 Gy) to the whole pelvis and if necessary, tumor bed was boosted by $5.4\~10\;Gy$. Both survival and pelvic control rates were calculated by Kaplan-Meier method and their statistical significance was tested by Log-rank test. Multivariate analysis was peformed by Cox proportional hazards model. Results : 5-year actuarial survival rate (5YSR) and 5-year disease-free survival rate (5YDFSR) of entire patients were $53\%\;and\;49\%$, respectively. 5YSRs of surgery alone group and adjuvant radiotherapy group were $63\%\;vs\;45\%$, respectively (p=0.03). This difference is thought to reflect uneven distribution of stages between two treatment groups (p<0.05 by $\chi^2-test$) with more advanced disease patients in adjuvant radiotherapy group. 5YSRs of surgery alone vs adjuvant radiotherapy group in MAC B2+3, C1, C2+3 were $68\%\;vs\;55\%$ (p=0.09), $100\%\;vs\;100\%$, $40\%\;vs\;33\%$ (p=0.71), respectively. 5YDFSRs of surgery alone vs adjuvant radiotherapy group in above three stages were $65\%\;vs\;49\%$ (p=0.14), $100\%\;vs\;100\%$, $33\%\;vs\;31\%$ (p=0.46), respectively. 5-year pelvic control rate (5YPCR) of entire patients was $72.5\%$. 5YPCRs of surgery alone and adjuvant radiotherapy group were $71\%\;vs\;74\%$, respectively (p=0.41). 5YPCRs of surgery alone vs adjuvant radiotherapy group in B2+3, C1, C2+3 were $79\%\;vs\;75\%$ (p=0.88), $100\%\;vs\;100\%$, $44\%\;vs\;68\%$ (p=0.01), respectively. Multivariate analysis showed that only stage was significant factor affecting overall and disease-free survival in entire patients and also in both treatment groups. In view of pelvic control, stage and operation type were significant in entire patients and only stage in surgery alone group but in adjuvant radiotherapy group, operation type instead of stage was the only significant factor in multivariate analysis as a negative prognostic factor in abdominoperineal resection cases. Conclusion : Our retrospective study showed that postoperative adjuvant radiotherapy could improve the pelvic control in MAC C2+3 group. To improve both pelvic control and survival in all patients with MAC B2 or more, other treatment modality such as concurrent continuous infusion of 5-FU, which is the most standard agent, with radiotherapy should be considered.

• Radiation Oncology Journal
• /
• v.18 no.2
• /
• pp.92-100
• /
• 2000

Purpose :This study was performed to determine the optimal treatment velum of Patients treating with radiation therapy for intracranial germ cell tumor. Materials and Methods : From 1993 to 1998, 19 patients with intracranial germ cell tumors treated by gamma knife radiosurgery were analyzed. The location of tumor was as follows; 9 cases on pineal region, 1 case on suprasellar region, and 9 cases of multiple lesion. 7 patients were pathologically verified; 5 cases of germ cell tumor and 2 cases of non germinomatous germ cell tumor. Tumor volume was ranged from 2.4 cm$^{3}$ to 74 cm$^{3}$. Irradiation dose was 10 Gy to 20 Gy with 50% isodose curve. Follow up period was 10 months to 54 months. Results : Recurrences were observed in 14 cases among 19 (74%) patients. Complete remission and partial remission were achieved in 2 (11%) and 10 (53%) respectively. No response was observed in 7 (36%). 2 cases were recurred within original tumor bed. 6 cases were recurred beyond but contiguous with tumor bed. Ventricular relapses separated from pretreatment tumor bed were 3. Spinal recurrences were 4. Among 8 recurred cases of which tumor volume is smaller than 20 cm$^{3}$, 2 were recurred within original tumor bed, 4 were recurred beyond but contiguous with tumor bed, and 1 spinal recurrence. Meanwhile, 6 cases of which tumor volume larger than 20 cm3, 1 case was recurred beyond but contiguous with tumorbed, 2 ventricular recurrences separated with original tumor bed, and 3 spinal recurrences. 5 cases which did not show any recurrence sign showed characteristics of single lesion, tumor volume smaller than 20 cm$^{3}$ and normal tumor marker. All of 4 cases of spinal recurrences happened in the case having ventricular invasion or lesion. Among 9 cases having multiple lesion, only 3 cases recurred within original tumor bed or around tumor bed, the other 6 cases recurred separated from pretreatment tumor bed. Conclusion : Gamma knife radiosurgery is not recommended for the treatment of intracranial germ cell tumor. It is because of small treatment volume and inadequate radiation dose that are characteristics of gamma knife radiosurgery. Tumor volume, ventricular invasion or ventricular lesion in multiple lesion are important factors to be considered for the wide field radiation therapy Tumor volume smaller than 20 cm$^{3}$, single lesion, no ventricular lesion or invasion, and normal tumor marker are ideal indications for small involved field radiation therapy. Prophylactic spinal irradiation seems to be necessary when there is ventricular lesion, ventricular invasion, and multiple lesions. When the tumor volume is larger than 20 cm$^{3}$, multiple lesions, abnormal tumor marker, and whole ventricular irradiation or partial brain irradiation would be possible and neoadjuvant chemotherapy would be most beneficial in these group.

• Radiation Oncology Journal
• /
• v.27 no.4
• /
• pp.181-188
• /
• 2009

Purpose: The aim of this study was to evaluate the results of postoperative radiotherapy in a case of perihilar cholagiocarcinoma by analyzing overall survival rate, patterns of failure, prognostic factors for overall survival, and toxicity. Materials and Methods: Between January 1998 and March 2008, 38 patients with perihilar cholangiocarcinoma underwent a surgical resection and adjuvant radiotherapy. The median patient age was 59 years (range, 28 to 72 years), which included 23 men and 15 women. The extent of surgery was complete resection in 9 patients, microscopically positive margins in 25 patients, and a subtotal resection in 4 patients. The tumor bed and regional lymphatics initially received 45 Gy or 50 Gy, but was subsequently boosted to a total dose of 59.4 Gy or 60 Gy in incompletely resected patients. The median radiotherapy dose was 59.4 Gy. Concurrent chemotherapy was administered in 30 patients. The median follow-up period was 14 months (range, 6 to 45 months). Results: The 3-year overall survival and 3-year progression free survival rates were 30% and 8%, respectively. The median survival time was 28 months. A multivariate analysis showed that differentiation was the only significant factor for overall survival. The 3-year overall survival was 34% in R0 patients and 20% in R1 patients. No statistically significant differences in survival were found between the 2 groups (p=0.3067). The first site of failure was local in 18 patients (47%). No patient experienced grade 3 or higher acute toxicity and duodenal bleeding developed in 2 patients. Conclusion: Our results suggest that adjuvant RT might be a significant factor in patients with a positive margin following a radical resection. However, there was still a high locoregional recurrence rate following surgery and postoperative radiotherapy. Further study is necessary to enhance the effect of the adjuvant radiotherapy.

• Radiation Oncology Journal
• /
• v.13 no.4
• /
• pp.339-348
• /
• 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.

• Radiation Oncology Journal
• /
• v.22 no.3
• /
• pp.165-176
• /
• 2004

Purpose: Firstly, to analyze facto in terms of radiation treatment that might potentially cause subfrontal relapse in two patients who had been treated by craniospinal irradiation (CSI) for medulloblastoma, Secondly, to explore an effective salvage treatment for these relapses. Materials and Methods: Two patients who had high-risk disease (T3bMl, T3bM3) were treated with combined chemoradiotherapy CT-simulation based radiation-treatment planning (RTP) was peformed. One patient who experienced relapse at 16 months after CSI was treated with salvage surgery followed by a 30.6 Gy IMRT (intensity modulated radiotherapy). The other patient whose tumor relapsed at 12 months after CSI was treated by surgery alone for the recurrence. To investigate factors that might potentially cause subfrontal relapse, we evaluated thoroughly the charts and treatment planning process including portal films, and tried to find out a method to give help for placing blocks appropriately between subfrotal-cribrifrom plate region and both eyes. To salvage subfrontal relapse in a patient, re-irradiation was planned after subtotal tumor removal. We have decided to treat this patient with IMRT because of the proximity of critical normal tissues and large burden of re-irradiation. With seven beam directions, the prescribed mean dose to PTV was 30.6 Gy (1.8 Gy fraction) and the doses to the optic nerves and eyes were limited to 25 Gy and 10 Gy, respectively. Results: Review of radiotherapy Portals clearly indicated that the subfrontal-cribriform plate region was excluded from the therapy beam by eye blocks in both cases, resulting in cold spot within the target volume, When the whole brain was rendered in 3-D after organ drawing in each slice, it was easier to judge appropriateness of the blocks in port film. IMRT planning showed excellent dose distributions (Mean doses to PTV, right and left optic nerves, right and left eyes: 31.1 Gy, 14.7 Gy, 13.9 Gy, 6.9 Gy, and 5.5 Gy, respectively. Maximum dose to PTV: 36 Gy). The patient who received IMRT is still alive with no evidence of recurrence and any neurologic complications for 1 year. Conclusion: To prevent recurrence of medulloblastoma in subfrontal-cribriform plate region, we need to pay close attention to the placement of eye blocks during the treatment. Once subfrontal recurrence has happened, IMRT may be a good choice for re-irradiation as a salvage treatment to maximize the differences of dose distributions between the normal tissues and target volume.

• Radiation Oncology Journal
• /
• v.26 no.2
• /
• pp.104-112
• /
• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.