Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2.
Irritation fibroma (IF) is the most common tumor-like oral lesion that is evolved by proliferation of collagen in response to chronic irritation. Oral leukoplakia (OL) is considered as precancerous lesion characterized by proliferation of epithelial cells due to chronic irritation, smoking and drinking. TGF-${\beta}1$ and EGFR are important factors that play an essential role in extracellular matrix remodeling during normal wound healing process. The epithelial reaction by chronic irritation may be connected with pathogenesis of IF and OL. In the present study, we examined the expression of TGF-${\beta}1$ and EGFR in the IF and OL using immunohistochemistry. We used 88 cases of IF, 44 cases of OL and 9 cases of normal oral mucosa as normal control. TGF-${\beta}1$ was decreased in the epithelium of IF and OL. As for EGFR, the epithelial cells revealed the increased positive expression in IF and OL. In case of OL, the Spearman correlation coefficient of TGF-${\beta}1$ and EGFR was -0.10 (p< 0.05), which showed weak correlation. In the fibrous tissue, TGF-${\beta}1$ was increased only in IF. The expression difference of TGF-${\beta}1$ and EGFR may be involved in the pathogenesis of IF and OL.
Objective: To determine the effectiveness and toxicity of chemoradiation therapy in nasopharyngeal carcinoma by comparing with radiation therapy alone. Materials and Methods: Between October 1989 and July 2000, One hundred eleven patients with newly diagnosed and histologically proven nasopharyngeal carcinoma treated in Department of Radiation Oncology, Asan Medical Center were retrospectively reviewed. Forty-five patients were treated with radiation therapy alone (Group I) and 66 patients were treated with radiation therapy and concurrent cisplatin (Group II). Cisplatin was administered once a week, on the first day of each successive week of treatment, starting on day 1 of radiation therapy and given as a intravenous bolus at a dose of $20mg/m^2$ of body-surface area. Radiation therapy was given in doses of 1.8Gy, once a day, 5 days per week with 4MV or 6 MV photons. Initial field was received a total of 60Gy and a primary tumor and enlarged lymph nodes were boosted with an high dose intracavitory brachytherapy and 3D conformal therapy. Results: The complete response rate was 86.7% in Group I, and was 90.9% in Group II. The 5 year overall survival rate for Group I was 60% and for Group II was 45% (p=0.2520). The 5 year disease free survival rate was 52% versus 45%, respectively (p=0.7507). The median follow up was 44 months versus 34 months, respectively. Conclusion: Analysis of the III patients showed no significant difference in disease free survival and overall survival in two treatment group. This retrospective analysis did not demonstrate benefit with concurrent chemoradiation using cisplatin at a dose of $20mg/m^2$ of body-surface area in treatment result than radiation alone.
Cho Kwan Ho;Park Kyung Ran;Oh Won Yong;Chun Mison;Suh Chang Ok;Kim Gwi Eon;Loh John J.K.
Radiation Oncology Journal
/
v.4
no.1
/
pp.45-50
/
1986
RTOG proposed a multivariate modelling system predicting the response of head and neck cancers to radiation therapy in 1984. The aim of this study was to veri(y whether PPC (Probaility of primary clearance calculated by a multivariate modelling system) had any correlation with the survival in the patients with carcinoma of the nasopharynx following radiation therapy Analysing 81 patients with carcinoma of the nasopharynx treated with radiotherapy between January 1, 1971 and December 31, 1983 at Yonsei University College of Medicine, Yonsei Cancer Center the actuarial 5 year survival rate was $36\%$ and median survival was 39 months. The survivals for Group 1 (27 who had more than $80\%$ of PPC), Group 2 (20 who had between 71 and $80\%$ of PPC), and Group 3 (29 who had less than $71\%$ of PPC) were $66\%$ (median survival months : more than 72), $27\%$ (31), and $4\%$ (12) respectively. There was a definite correlation between PPC and survival among the three groups.
Lim, Hyeon Woo;Kim, Tae Hyun;Choi, Il Ju;Kim, Chan Gyoo;Lee, Jong Yeul;Cho, Soo Jeong;Eom, Hyeon Seok;Moon, Sung Ho;Kim, Dae Yong
Radiation Oncology Journal
/
v.34
no.3
/
pp.193-201
/
2016
Purpose: To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods: Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results: All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, $D_{max}$ and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and $D_{mean}$ and V15 for right kidney and $D_{mean}$ for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion: Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.
Yun, Sook Jung;Lee, Jee Bum;Kim, Kyu Sik;Kim, Young Chul
Tuberculosis and Respiratory Diseases
/
v.61
no.2
/
pp.150-156
/
2006
Background: Gefitinib (ZD 1839, Iressa) is a new anticancer agent; more specifically, it is a selective epidermal growth factor receptor tyrosine kinase inhibitor that is, widely used for various solid cancers, including lung cancer. Cutaneous adverse reactions induced by gefitinib have recently been reported; however, not much on this topic has been reported in the Korean literature. Method: We studied cutaneous adverse reactions of gefitinib in 23 patients who suffered with non-small cell lung cancer at Chonnam National University Hwasun Hospital from October 2004 to September 2005. Result: The patients ranged from 23-72 years old, and there were 17 patients with adenocarcinoma, 5 with squamous cell carcinoma and 1 with bronchioloalveolar carcinoma. The most common adverse reaction was acneiform eruptions in 15 patients (65.2%). This reaction appeared within 2 months after medication, and it didn't correlate with the therapeutic response and tumor type. Pruritus was the second most common reaction (39.1%), which was mild and generalized, especially around eyelid area. Xerosis (26.1%), exfoliation on palm and sole (21.7%), and paronychia (21.7%) followed. Hair breakage and intertrigo were rare adverse reactions. Conclusion: Various cutaneous adverse reactions were observed in patients with non-small cell lung carcinoma after gefitinib treatment. The skin complications could be alleviated with dermatologic consultations and treatments, skin complications could be alleviated.
Lu, Yan-Yan;Huang, Xin-En;Wu, Xue-Yan;Cao, Jie;Liu, Jin;Wang, Lin;Xiang, Jin
Asian Pacific Journal of Cancer Prevention
/
v.15
no.7
/
pp.3335-3341
/
2014
Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.
Chu, Xiao Ting;Cruz, Joseph Dela;Hwang, Seong Gu;Hong, Heeok
Asian Pacific Journal of Cancer Prevention
/
v.15
no.13
/
pp.5117-5121
/
2014
Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.
Background: Due to the paucity of oceanic resources utilized in the preparation of diets for cultured fish, commercial feed producers have been trying to replace fishmeal (FM) using alternative protein sources such as vegetable protein meals (VMs). One of the main drawbacks of using VMs in fish feed is related to the presence of a variety of anti-nutritional factors, which could trigger an inflammation process in the distal intestine. This reduces the capacity of the enterocytes to absorb nutrients leading to reduced fish growth performances. Methods: We evaluated the mitigating effects of butyrate and taurine used as feed additives on the morphological abnormalities caused by a soybean meal (SBM)-based diet in the distal intestine of sea bass (Dicentrarchus labrax). We used three experimental diets, containing the same low percentage of FM and high percentage of SBM; two diets were supplemented with either 0.2% sodium butyrate or taurine. Histological changes in the intestine of fish were determined by light and transmission electron microscopy. Infiltration of $CD45^+$ leucocytes in the lamina propria and in the submucosa was assessed by immunohistochemistry. We also quantified by One-Step Taqman$^{(R)}$ real-time RT-PCR the messenger RNA (mRNA) abundance of a panel of genes involved in the intestinal mucosa inflammatory response such as $TNF{\alpha}$ (tumor necrosis factor alpha) and interleukins: IL-8, IL-$1{\beta}$, IL-10, and IL-6. Results: Fish that received for 2 months the diet with 30% soy protein (16.7% SBM and 12.8% full-fat soy) developed an inflammation in the distal intestine, as confirmed by histological and immunohistochemistry data. The expression of target genes in the intestine was deeply influenced by the type of fish diet. Fish fed with taurine-supplemented diet displayed the lowest number of mRNA copies of IL-$1{\beta}$, IL-8, and IL-10 genes in comparison to fish fed with control or butyrate-supplemented diets. Dietary butyrate caused an upregulation of the $TNF{\alpha}$ gene transcription. Among the quantified interleukins, IL-6 was the only one to be not influenced by the diet. Conclusions: Histological and gene expression data suggest that butyrate and taurine could have a role in normalizing the intestinal abnormalities caused by the SBM, but the underling mechanisms of action seem different.
Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.
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