• Culinary science and hospitality research
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• v.21 no.5
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• pp.160-170
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• 2015

In accordance to the increasing number of death due to cancer and side effects of chemotherapy, attention has recently focused on combined treatment of natural component and anti-tumor agent. Therefore development of safe and effective functional substances derived from natural materials is required. The emergence of various functional activities of Rubus coreanus Miquel, such as antioxidant, anticancer, anti-inflammatory, etc. is continuously increasing its consumption. To utilize the above activities, many products developed by using Rubus coreanus Miquel extracts in the areas of foods, liquors, and cosmetics and medicines. In this review, anti-cancer, anti-inflammatory activity and patents of Rubus coreanus Miquel are summarized. Further studies are needed to search for development of functional material from natural origin and various application possibility using stem, leaf and fruit of Rubus coreanus Miquel.

• Toxicological Research
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• v.35 no.2
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• pp.167-179
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• 2019

Ovarian cancer is the fifth main cause of pre-senescent death in women. Although chemotherapy is generally an efficient treatment, its side effects and the occurrence of chemotherapeutic resistance have prompted the need for alternative treatments. In this study, ${\alpha}$-mangostin and apigenin were evaluated as possible anticancer alternatives to the chemotherapeutic drug doxorubicin, used herein as a positive control. The ovarian adenocarcinoma cell line SKOV-3 (ATCC No. HTB77) was used as model ovarian cancer cells, whereas the skin fibroblast line CCD-986Sk (ATCC No. CRL-1947) and lung fibroblast line WI-38 (ATCC No. CCL-75) were used as model untransformed cells. Apigenin and doxorubicin inhibited the growth of SKOV-3 cells in a dose- and time-dependent manner. After 72 hr exposure, doxorubicin was mostly toxic to SKOV-3 cells, whereas apigenin was toxic to SKOV-3 cells but not CCD-986Sk and WI-38 cells. ${\alpha}$-Mangostin was more toxic to SKOV-3 cells than to CCD-986Sk cells. A lower cell density, cell shrinkage, and more unattached (floating round) cells were observed in all treated SKOV-3 cells, but the greatest effects were observed with ${\alpha}$-mangostin. With regard to programmed cell death, apigenin caused early apoptosis within 24 hr, whereas ${\alpha}$-mangostin and doxorubicin caused late apoptosis and necrosis after 72 hr of exposure. Caspase-3 activity was significantly increased in ${\alpha}$-mangostin-treated SKOV-3 cells after 12 hr of exposure, whereas only caspase-9 activity was significantly increased in apigenin-treated SKOV-3 cells at 24 hr. Both ${\alpha}$-mangostin and apigenin arrested the cell cycle at the $G_2/M$ phase, but after 24 and 48 hr, respectively. Significant upregulation of BCL2 (apoptosis-associated gene) and COX2 (inflammation-associated gene) transcripts was observed in apigenin- and ${\alpha}$-mangostin-treated SKOV-3 cells, respectively. ${\alpha}$-Mangostin and apigenin are therefore alternative options for SKOV-3 cell inhibition, with apigenin causing rapid early apoptosis related to the intrinsic apoptotic pathway, and ${\alpha}$-mangostin likely being involved with inflammation.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.331-338
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• 1995

Purpose : To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. Materials and Methods : From Nov 1989 to Mar 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histolgy and stage distribution was as follows: stage II, 4($20{\%}$)patients; III, 15 ($75{\%}$)patients; IV, 1($5{\%}$)patients. A dose of S-12Gy/1-3weeks with intraluminal brachytherapy (3-5Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate Iridium-192 remotely afterloading brachytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles), Response rate, local control rate, survival and complications were analysed retrospectively. Results : Two-year overall survival rate and median survival were $15.8{\%}$ and 13.5 months. Response rates were as follows complete remission(CR) 5($25{\%}$): partial remission a(PRa) 7($35{\%}$): partial remission b(PRb) 7($35{\%}$), no response(NR) 1($5{\%}$). Patterns of failure were as follows; local failure 13($65{\%}$), local and distant failure 3($15{\%}$), distant failure 0($0{\%}$). Ultimate local control rate was $20{\%}$. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. Conclusion : Though poor local conrol rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemoradiation combined treatment(11 months) in Yonsei Cancer Center High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.447-454
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• 1998

Purpose : This study evaluated the survival, local control, prognostic factor, and failure pattern of patients with esophageal cancer treated with operation and adjuvant radiation therapy to use as fundermental data of postoperative radiation therapy. Materials and Methods : A retrospective analysis was undertaken of 82 patients who had locally advanced esophageal cancer treated with operation and adjuvant radiation therapy from January 1988 to December 1995. According to AJCC staging, stage IIA were in 26 patients, stage IIB in 4 patients, and stage III in 52 patients. Squamous cell carcinoma were in 77 patients, adenosquamous carcinoma in 3 patients, and adenocarcinoma in 2 patients. The patients received radiation therapy ranging from 41.0 Gy to 64.8 Gy. Five patients received neoadjuvant chemotherapy. Results : Two-year survival and local control rates for all patients were 36.8$\%$ and 30.4$\%$ respectively. And they were 9.3$\%$ and 26.3$\%$ respectively at 5 years. According to stages, 2-year survival rates were 50.2$\%$ in IIA, 0$\%$ in IIB and 23.3$\%$ in III (p=0.004). Two-year local control rates were 49.2 $\%$ in IIA, 66.6$\%$ in IIB and 24.7$\%$ in III (p=0.01). Sixty patients developed recurrence, which were 3 tumor margin, 23 lymph node recurrence, 4 tumor margin and lymph node, 1 tumor margin and distant metastasis, 9 lymph node and distant metastasis, 17 distant metastasis and 3 unknown metastatic site. Prognostic factors affecting survival were smoking (p=0.02), T-staging (p=0.0092), N-staging (p=0.0045). Prognostic factors affecting local control were T-staging (p=0.019), N-staging (p=0.047). Conclusion : In spite of post-operative radiation therapy, predominant failure pattern was local failure. Especially regional lymph node failure was major cause of local failure. So strategy of aggresive adjuvant radiation therapy to regional lymph node area in post operative treatment should be proposed.

• Journal of Life Science
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• v.33 no.9
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• pp.713-723
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• 2023

Lung cancer is a type of cancer that has the highest mortality rate. It is mainly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Chemotherapy is used to treat lung cancer, but long-term treatment causes side effects and drug resistances. Curcumin is a bright yellow polyphenol extracted from the root of turmeric. It has biological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory effects. In this study, we observed differential cell death in human lung cancer cells. Based on the results, curcumin at 10, 30, and 50 μM exhibited a dose-dependent inhibition on the cell survival of several lung cancer cells, with minor differential phenotypes. In addition, apoptosis, autophagy, and reactive oxygen species (ROS) regeneration were observed through flow cytometry. Curcumin dose-dependently increased these phenotypes in A549 (NSCLC) and DMS53 (SCLC), which were restored by corresponding inhibitors. Western blotting was performed to measure the level of expression of apoptosis- and autophagy-related proteins. The results indicate that Bax, PARP, pro-caspase-3, and Bcl-2 were dose-dependently regulated by curcumin, with seemingly higher Bax/Bcl-2 ratios in DMS53. In addition, autophagic proteins, p-AKT, p62, and LC3B, were dose-dependently regulated by curcumin. ROS inhibition by diphenyleneiodonium reduced the induction of apoptosis and autophagy generated by curcumin. Taken together, it is suggested that curcumin induces apoptosis and autophagy via ROS generation, leading to cell death, with minor differences between human lung cancer cells.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.84-90
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• 2009

Purpose: The effect of concurrent chemoradiotherapy was analyzed in elderly patients when used in the treatment of locally advanced esophageal cancer. Materials and Methods: The retrospective analysis included 28 elderly patients aged 65 or older, with histopathologically confirmed squamous cell carcinoma of the esophagus, underwent concurrent chemoradiotherapy from January 2001 to July 2007. The squamous cell carcinoma disease stages included 8 patients (28.8%) in stage IIa, 10 patients (35.7%) in stage IIb, and 10 patients (35.7%) in stage III. Fractionated radiotherapy was performed with a 6 MV or 10 MV X-ray for 45~63 Gy (median: 59.4 Gy). Chemotherapy was applied concurrently with the initiation of radiotherapy. A 75 mg/$m^2$ dose of Cisplatin was intravenously administered on day 1. Further, 5-FU 1,000 mg/$m^2$ was continuously administered intravenously from days 1 to 4. This regimen was performed twice at 3-week intervals during radiotherapy. Two cycles of consolidation chemotherapy was performed after radiotherapy. Results: The follow-up period was 3~72 months (median: 19 months). The treatment responses after concurrent chemoradiotherapy included a complete response in 11 patients (39.3%), a partial response in 14 patients (50.0%), and no response in 3 patients (10.7%). The overall response rate was 89.3% (25 patients). The overall 1-, 2- and 3-year survival rates were 55.9%, 34.6% and 24.2%, respectively. The median survival time was 15 months. Two-year survival rates of patients with a complete response, partial response, and no response were 46.2%, 33.0%, and 0%, respectively. The stage and tumor response after concurrent chemoradiotherapy were statistically significant prognostic factors related with survival. No treatment-related deaths occurred in this study. Conclusion: Concurrent chemoradiotherapy is a relatively effective treatment without serious complications in elderly patients with locally-advanced esophageal cancer.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.166-179
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• 2000

Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.417-423
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• 2006

Purpose : The objectives of this study were to assess ventricular function by tissue Doppler imaging in children who were receiving chemotherapy or who had received chemotherapy, and to apply repeated tissue Doppler imaging to make an early assessment in cardiac toxicity studies. Methods : This study was conducted on 23 oncology patients on-treatment or off-treatment from April 2005 to July 2005 at Dongsan Medical Center, Keimyung University. All patients(group 1) were divided into two groups, fractional shortening(FS) over 29 percent(group 2) and FS under 28 percent (group 3) in the first category. These same patients were also divided into the following groups : group treated with anthracyclin(group 4) and group treated without anthracyclin(group 5). Deceleration time(DT), isovolumic relaxation time(IVRT), FS, peak early diastolic(E), and peak late diastolic (A) velocity of transmitral flow were measured by M-mode and pulsed wave Doppler. Systolic(Sm), peak early diastolic(Em), and peak late diastolic(Am) velocity in apical 4-chamber and 2-chamber views were measured by tissue Doppler imaging. The author calculated a modified Tei index, E/A, E/Em ratio by using measured values. Results : Twenty three patients were enrolled : 12 boys and 11 girls. The average age of patients was 8 years and 4 months. Thirteen out of 23 patients were in the group treated with anthracyclin (group 4) and 6 had FS under 28 percent(group 3). E/Em ratio showed a significant difference between group 1 and control group($6.46{\pm}1.85$ vs $7.06{\pm}1.64$, P<0.05). Other parameters had no difference statistically. Conclusion : This study showed that the change of cardiac function developed earlier in diastolic function than in systolic function, as E/Em ratio reflecting the mean LV diastolic pressure showed a significant difference between the control group and chemotherapy groups. Echocardiography using tissue Doppler imaging is a non-invasive, comfortable and reliable method for post-chemotherapy follow up.