Pongtheerat T.,Rangsit University |
Pakdeethai S.,Rangsit University |
Purisa W.,National Cancer Institute of Thailand |
Chariyalertsak S.,National Cancer Institute of Thailand |
Petmitr S.,Mahidol University
Asian Pacific Journal of Cancer Prevention | Year: 2011
The GSTP1 gene encodes for a detoxification enzyme involved in protecting cells from carcinogens. In breast cancer, GSTP1 polymorphisms may produce lower effective enzyme detoxification properties and GSTP1 promoter hypermethylation may result in inactivation of GSTP1 expression. We therefore hypothesized an influence on progression of breast cancer. To study the effect of GSTP1 polymorphisms and CpG-island hypermethylation on GSTP1 promoter, PCR-RFLP and methylation-specific PCR techniques were used with 41 Thai breast-cancer patients. Associations between the codon 105 (A to G) genetic polymorphism, CpG-island hypermethylation, and clinico-pathological parameters were analyzed. GSTP1 hypermethylation was found in 26% of cases and the GSTP1 polymorphism in 14%. GSTP1 hypermethylation was significantly associated with breast cancer; lymph-node metastasis (P = 0.02) while GSTP1 polymorphism status significantly varied with progesterone receptor positivity (P = 0.04). No association was found between the GSTP1 polymorphism and methylation status. The results indicated that CpG-island hypermethylation of the GSTP1 promoter is associated with a biologically aggressive phenotype, but may not be related to the codon 105 (A to G) gene polymorphism in breast-cancer patients.
PubMed | Tokyo Women's Medical University, Juntendo University, Nagahama Institute of Bio-Science and Technology, Osaka University and 6 more.
Type: Journal Article | Journal: Analytical chemistry | Year: 2015
Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus, qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 L of sera. The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC.
PubMed | Karolinska Institutet, University of Cologne, Genome Institute of Singapore, Ministry of Public Health and 89 more.
Type: Journal Article | Journal: Nature genetics | Year: 2015
Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining 14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.
Kimman M.,University of Sydney |
Jan S.,University of Sydney |
Kingston D.,University of New South Wales |
Monaghan H.,University of Sydney |
And 9 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2012
Cancer can be a major cause of poverty. This may be due either to the costs of treating and managing the illness as well as its impact upon people's ability to work. This is a concern that particularly affects countries that lack comprehensive social health insurance systems and other types of social safety nets. The ACTION study is a longitudinal cohort study of 10,000 hospital patients with a first time diagnosis of cancer. It aims to assess the impact of cancer on theeconomic circumstances of patients and their households, patients' quality of life, costs of treatment and survival. Patients will be followed throughout the first year after their cancer diagnosis, with interviews conducted at baseline (after diagnosis), three and 12 months. A cross-section of public and private hospitals as well as cancer centers across eight member countries of the Association of Southeast Asian Nations (ASEAN) will invite patients to participate. The primary outcome is incidence of financial catastrophe following treatment for cancer, defined as out-of-pocket health care expenditure at 12 months exceeding 30% of household income. Secondary outcomes include illness induced poverty, quality of life, psychological distress, economic hardship, survival and disease status. The findings can raise awareness of theextent of the cancer problem in South East Asia and its breadth in terms of its implications for households and the communities in which cancer patients live, identify priorities for further research and catalyze political action to put inplace effective cancer control policies.
Inhibition of EGFR, HER2, and HER3 signaling with AZD8931 in combination with anastrozole as an anticancer approach: Phase II randomized study in women with endocrine-therapy-naïve advanced breast cancer
PubMed | The Ottawa Hospital Cancer Center, National Cancer Institute of Thailand, University of Pretoria, Northwestern University and 5 more.
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2016
AZD8931 is an orally bioavailable, reversible tyrosine kinase inhibitor of EGFR, HER2, and HER3 signaling. The Phase II MINT study (ClinicalTrials.gov NCT01151215) investigated whether adding AZD8931 to endocrine therapy would delay development of endocrine resistance in patients with hormone-sensitive advanced breast cancer.Patients were randomized 1:1:1 to receive daily anastrozole (1mg) in combination with AZD8931 20mg twice daily (bid), AZD8931 40mg bid, or placebo. The primary objective was evaluation of progression-free survival (PFS) in patients treated with combination AZD8931 and anastrozole versus anastrozole alone. Secondary objectives included assessment of safety and tolerability, objective response rate, and overall survival.At the interim analysis, 359 patients were randomized and received anastrozole in combination with AZD8931 20mg (n=118), 40mg (n=120), or placebo (n=121); 39% of patients (n=141) had a progression event. Median PFS (HR; 95% CI vs placebo) in the AZD8931 20, 40mg, and placebo arms was 10.9 (1.37; 0.91-2.06, P=0.135), 13.8 (1.16; 0.77-1.75, P=0.485), and 14.0months, respectively. No indication of clinical benefit was observed following treatment with AZD8931 for the secondary endpoints. Safety findings showed a greater incidence of diarrhea (40, 51, and 12% for AZD8931 20, 40mg, and placebo, respectively), rash (32, 48, and 12%), dry skin (19, 25, and 2%), and acneiform dermatitis (16, 28, and 2%) in patients treated with AZD8931 versus placebo.AZD8931, in combination with endocrine therapy, does not appear to enhance endocrine responsiveness and is associated with greater skin and gastrointestinal toxicity.
Taokaew S.,Chulalongkorn University |
Seetabhawang S.,Chulalongkorn University |
Siripong P.,National Cancer Institute of Thailand |
Phisalaphong M.,Chulalongkorn University
Materials | Year: 2013
A nanocellulose-gelatin (bacterial cellulose gelatin (BCG)) film was developed by a supplement of gelatin, at a concentration of 1%-10% w/v, in a coconut-water medium under the static cultivation of Acetobacter xylinum. The two polymers exhibited a certain degree of miscibility. The BCG film displayed dense and uniform homogeneous structures. The Fourier transform infrared spectroscopy (FTIR) results demonstrated interactions between the cellulose and gelatin. Incorporation of gelatin into a cellulose nanofiber network resulted in significantly improved optical transparency and water absorption capacity of the films. A significant drop in the mechanical strengths and a decrease in the porosity of the film were observed when the supplement of gelatin was more than 3% (w/v). The BCG films showed no cytotoxicity against Vero cells. © 2013 by the authors; licensee MDPI, Basel, Switzerland.