• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.432-441
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• 2016

Machaerium cuspidatum, a canopy liana, is a species of genus legume in the Fabaceae family and contributes to the total species richness in the tropical rain forests. In the present study, we investigated the antioxidative and anti-cancer effects of M. cuspidatum and its mode of action. The methanol extract of M. cuspidatum (MEMC) exhibited anti-oxidative activity with an $IC_{50}$ value of $1.66{\mu}g/ml$, and this was attributable to its 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. MEMC also exhibited a cytotoxic effect and induced morphological changes in a dose-dependent manner in several cancer cell lines including human lung adenocarcinoma A549 cells, human hepatocellular carcinoma HepG2 cells, and human colon carcinoma HT29 cells. Moreover, MEMC treatment induced the accumulation of subG1 population, which is indicative of apoptosis in A549 and HepG2 cells. MEMC-induced apoptosis was confirmed by the increase in Annexin V-positive apoptotic cells and apoptotic bodies using Annexin-V staining and DAPI staining, respectively. Further investigation showed that MEMC-induced apoptosis was associated with the increase in p53 and Bax expression, and the decrease in Bcl-2 expression. In addition, MEMC treatment led to proteolytic activation of caspase-3, 8, and 9 and degradation of poly-ADP ribose polymerase (PARP). Taken together, these results suggest that MEMC may exert a beneficial anti-cancer effect by inducing apoptosis via both the extrinsic and intrinsic pathways in A549 and HepG2 cells.

• Radiation Oncology Journal
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• v.26 no.3
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• pp.149-159
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• 2008

Purpose: To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial cancer, pelvic control, and overall survival rate was free of severe toxicity when pelvic radiation therapy or vaginal brachytherapy was performed. In the high-risk group, pelvic control rate was excellent, but the survival rate was poor due to distant metastases, in spite of the pelvic radiation therapy. The combined modality of chemotherapy and radiation therapy is recommended for high-risk groups. For the intermediate-risk group, a prospective randomized study is required to compare the efficacy between whole pelvic radiation therapy and vaginal brachytherapy.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.65-72
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• 1991

One hundred and thirty five patients with carcinoma of the nasopharyx were treated by radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University between August 1977 and July 1987. Of the 30 patients omitted: 8 had distant metastases at initial diagnosis or during radiotherapy; 18 Patients refused or did not receive a full course of radiation therapy, and four had not been confirmed histologically. The remaining 105 patients were analysed to determine the incidence and pattern of distant metastases. Diagnosis of distant metastases was made based on clinical signs and radiography, even though histologic confirmation was not made. Twenty-six patients developed distant metastases after definite irradiation of nasopharyx and neck, an incidence rate of $24.8\%$ . The common sites of distant metastases were, in descending order, bone, lung, liver, and brain. There was a strong correlation between Ho's N stage and distant metastases rate. But sex, age, histologic subtype (squamous cell and undifferentiated cell), AJC T and N stage, treatment modalities (radiotherapy alone and radiotherapy combined with chemotherapy) were not significant. Of those patients who developed distant metastases, $80.8\%$ were discovered within 2 years of their radical radiotherapy. The prognosis for nasopharyngeal carcinoma patients developing distant metastases was poor: median survival was nine months and $80\%$ of those patients died within two years of the initial diagnosis of distant metastasis.

• Journal of Radiation Protection and Research
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• v.28 no.3
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• pp.233-237
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• 2003

It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markdely radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/C-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation.

• Korean Journal of Medicinal Crop Science
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• v.12 no.4
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• pp.273-278
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• 2004

The anticancer activities of the extracts from Acanthopanax senticosus Harms, Ephedra sinica Stapf, Rubus coreanus Miq and Artemisia capillaris Thunb were compared according to extract systems. About 70% of the growth of human hepatocarcinoma cancer cell was inhibited in adding 1.0 mg/ml of the water extract from Rubus coreanus Miq with ultrasonification at $60^{\circ}C$. The growth of human normal lung cell was limited to 25% in adding the extracts with ultrasonification at $60^{\circ}C$. The effect of extracts obtained by only water and with ultrasonification on different of human promyelocytic leukemia cells was also observed.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.2
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• pp.288-298
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• 2016

Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS). The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549) against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value) compared to trolox and vitamin E since the concentration of resveratrol was more than $50{\mu}M$. Nanoparticles prepared from ${\beta}$-lactoglobulin (${\beta}$-lg) were successfully developed. The ${\beta}$-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with ${\beta}$-lg nanoparticles. Fluorescein isothiocynate-conjugated ${\beta}$-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored $H_2O_2$-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1) signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds.

• Radiation Oncology Journal
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• v.8 no.1
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• pp.59-64
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• 1990

From 1980 to 1986,26 patients with metastatic carcinoma of the neck node from an unknown primary site were seen in the Department of Therapeutic Radiology of Seoul National University Hospital. Among these, three patients were excluded from further analysis due to incomplete treatment. So a retrospective analysis was undertaken on 23 patients who had complete treat-ment with radiation therapy alone or in combination with surgical treatment and chemotherpay. The overall three year actuarial survival rate was $32\%$. According to the staging system of the American Joint Committee on Cancer, the three year survival rates with N2 and N3 patients were $43\%\;and\;13\%$, respectively. In 16 patients with squamous cell carcinoma and seven with non-squamous cell carcinoma, the three year survival rates were $34\%\;and\;29\%$, respectively. Analysis according to site of nodal involvement was also done. Patients with cervical node and supraclavicular node involvement recorded $44\%\;and\;17\%$ of three year survival, rate, respectively. In this study, six patients eventually manifested the primary sites (three in the lung, one in the esophagus, one in the stomach, one in the nasopharynx). Presence of the primary site seemed to influence the prognosis ($17\%\;vs\;38\%$). In analyzing the prognostic factors, the nodal stage and site of nodal involvement were important prognostic factors, and the presence of a primary site seemed to influence the patients' survival, but histology did not.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.647-657
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• 2024

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.6
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• pp.862-873
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• 2015

In this study, we investigated the physiochemical properties and biological activities of Gangwon-do endemic Makjang (MJ) products (12 types). The pH levels of all samples were in the range of 4.43 to 5.69, and MJ5 showed the highest pH (5.69). The salinities of all samples ranged from 11.1% to 16.9%. Hunter color values for L (lightness), a (redness), and b (yellowness) ranged from 26.2 to 36.9, 3.9 to 11.5, and 6.5 to 16.6, respectively. The amino nitrogen content of MJ2 was highest, whereas the total content of free amino acids of MJ11 (4,657.7 mg%) was highest. Total fatty acid contents of all samples ranged from 1,598.6 mg% to 2,874.4 mg%, with MJ10 showing the highest fatty acid content. The content of total polyphenolic compounds ranged from 401.48 to $746.67{\mu}g$ tannic acid equivalent/mL, with MJ11 showing the highest content. The 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) radical scavenging effects of MJ11, MJ8, and MJ4 were 51.30% and 82.5%, 41.29% and 67.0%, and 49.88% and 87.7%, respectively. MJ12 showed the strongest growth inhibitory effect on lung cancer A549 cells, whereas MJ5 showed the strongest growth inhibitory effect on AGS gastric cancer cell and MCF-7 breast cancer cell. MJ7 showed greater lipid accumulation inhibitory activity in HepG2 cells than the others. ACE inhibitory activity of MJ11 was the highest among the samples.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.291-301
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• 1998

Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.