• Nutrition Research and Practice
• /
• v.2 no.2
• /
• pp.55-61
• /
• 2008

We investigated the combinatorial effects of different doses of dietary soy isoflavones (SI) and fructooligosaccharide (FOS) in a rat model of colon cancer. We hypothesized that increased bioavailability of SI metabolites due to dietary FOS may increase production of bioactive equol and affect colon carcinogenesis in a dose-dependent manner. Sprague-Dawley male rats were injected with 12-dimethylhydrazine (DMH) and were providec experimental diets that contained 0, 10, 50, 150, or 500 mg SI per kg of diet and 6% FOS for 12 weeks. The number of aberrant crypt foci (ACF) and the expression of cyclooxygenase-2 (COX-2) in colonic tissues were significantly decreased in the 6% FOS-fed groups compared to the control group. Gut transit time and fecal pH were significantly lower, and fecal concentrations of bifidobacteria were increased with 6% FOS. However, dietary SI supplementation in combination with 6% dietary FOS did not affect ACF formation or COX-2 expression. Plasma equol concentrations were dose-dependently increased by supplementation of SI up to 500 mg/kg of diet. In conclusion, SI supplementation up to 500 mg/kg of diet appeared to have no additive beneficial effects in rats with chemically-induced colon cancer that were fed 6% FOS, although plasma equol was dose-dependently increased.

• Molecules and Cells
• /
• v.46 no.3
• /
• pp.176-186
• /
• 2023

The oxidative balance of a cell is maintained by the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. This cytoprotective pathway detoxifies reactive oxygen species and xenobiotics. The role of the KEAP1/NRF2 pathway as pro-tumorigenic or anti-tumorigenic throughout stages of carcinogenesis (including initiation, promotion, progression, and metastasis) is complex. This mini review focuses on key studies describing how the KEAP1/NRF2 pathway affects cancer at different phases. The data compiled suggest that the roles of KEAP1/NRF2 in cancer are highly dependent on context; specifically, the model used (carcinogen-induced vs genetic), the tumor type, and the stage of cancer. Moreover, emerging data suggests that KEAP1/NRF2 is also important for regulating the tumor microenvironment and how its effects are amplified either by epigenetics or in response to co-occurring mutations. Further elucidation of the complexity of this pathway is needed in order to develop novel pharmacological tools and drugs to improve patient outcomes.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.10
• /
• pp.4117-4123
• /
• 2014

Background: To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). Materials and Methods: The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. Results: There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). Conclusions: ERCC1 was identified as poor prognostic factor in patients with MPM.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.133.2-134
• /
• 2003

The major hurdle of conventional chemotherapeutics is the toxicity to normal tissue. The possible therapeutic advantage(s) of nano-particle encapsulated chemotherapeutics (nano-molecules) may be the enhanced permeability and retention (EPR) effect. Nano-molecules with increase volume may incorporated into the tumor tissue selectively, which is composed of rather sparse structure. EPR effect may cause of increased effectiveness with lower tixicity to normal tissue of nano-chemotherapeutics. (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2891-2896
• /
• 2013

Background: To illustrate multiple approaches and to assess participation rates adopted for a community based smoking cessation intervention programme in rural Kerala. Materials and Methods: Resident males in the age group 18-60 years who were 'current daily smokers' from 4 randomly allocated community development blocks of rural Thiruvananthapuram district, Kerala (2 intervention and 2 control groups) were selected. Smoking status was assessed through house-to-house survey using trained volunteers. Multiple approaches included awareness on tobacco hazards during baseline survey and distribution of multicolour anti-tobacco leaflets for intervention and control groups. Further, the intervention group received a tobacco cessation booklet and four sessions of counselling which included a one-time group counselling cum medical camp, followed by proactive counselling through face-to-face (FTF) interview and mobile phone. In the second and fourth session, motivational counselling was conducted. Results: Among 928 smokers identified, smokers in intervention and control groups numbered 474 (mean age: 44.6 years, SD: 9.66 years) and 454 respectively (44.5 years, SD: 10.30 years). Among the 474 subjects, 75 (16%) had attended the group counselling cum medical camp after completion of baseline survey in the intervention group, Among the remaining subjects (n=399), 88% were contacted through FTF and mobile phone (8.5%). In the second session (4-6 weeks time period), the response rate for individual counselling was 94% (78% through FTF and 16% through mobile phone). At 3 months, 70.4% were contacted by their mobile phone and further, 19.6% through FTF (total 90%) while at 6 months (fourth session), the response rate was 74% and 16.4% for FTF and mobile phone respectively, covering 90.4% of the total subjects. Overall, in the intervention group, 97.4% of subjects were being contacted at least once and individual counselling given. Conclusion: Proactive community centred intervention programmes using multiple approaches were found to be successful to increase the participation rate for intervention.

• IMMUNE NETWORK
• /
• v.11 no.3
• /
• pp.175-181
• /
• 2011

Background: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concavabalin-A (ConA) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. Methods: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. Results: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin $E_2(PGE_2)$. In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. Conclusion: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.

• Radiation Oncology Journal
• /
• v.34 no.3
• /
• pp.230-238
• /
• 2016

Purpose: Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Materials and Methods: Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Results: Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. Conclusion: In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

• Molecules and Cells
• /
• v.22 no.2
• /
• pp.228-232
• /
• 2006

The Drosophila protein, Rbp9, is homologous to human Hu, which is reported to be involved in small cell lung cancer. Rbp9 functions in cystocyte differentiation, and mutations in Rbp9 cause ovarian tumors. Here we show that the antimicrobial peptide, Attacin, is upregulated in Rbp9 mutants, especially in ovaries where tumors form. Upregulation seems to result from activation of the NF-${\kappa}B$ pathway since we detected nuclear localization of Relish in Rbp9 mutant ovaries but not in wild type ovaries. Inactivation of NF-${\kappa}B$ in the Rbp9 mutant allows prolonged survival of malformed egg chambers. We conclude that Drosophila initiates an anti-tumor defense response via activation of NF-${\kappa}B$.

• Journal of Life Science
• /
• v.32 no.2
• /
• pp.167-174
• /
• 2022

In modern society, interest in antioxidants is increasing as the stress caused by oxidants increases. However, the demand for synthetic antioxidants is decreasing because some studies have confirmed that they are harmful when consumed in large quantities; thus, studies on antioxidants derived from natural substances are actively being conducted to replace synthetic antioxidants. Blueberry, known as one of the world's top ten long-lived foods, is a plant of the Vaccinium (Ericaceae) family, and various pharmacological activities of blueberry including antioxidant activity have been studied. Vaccinium oldhamii (VO) is a deciduous broad-leaved shrub in the same genus as blueberries, and in this paper, we summarize the studies on the efficacy analysis of VO extracts and purified products. The content of phenolic compounds in VO fruits was proportional to antioxidant and anti-influenza activity such as the inhibition of NO production, and the total content of polyphenols and anthocyanin was higher than that in blueberries. VO fruit extracts showed anti-inflammatory activity and anti-cancer activity against human acute leukemia; in contrast, VO branch extracts showed anti-inflammatory activity, activity to inhibit osteoclast differentiation and bone resorption due to inflammatory response, and anti-cancer activity against several human cancer cell lines. Compared to blueberries, VO showed higher phenolic compound content, antioxidant activity, and various physiological activities. In addition, VO is considered to have sufficient value as an alternative crop to blueberries, such as it can be grown natively in Korea, with simple mass cultivation and no need to pay royalties for commercialization.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2911-2916
• /
• 2014

Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.