Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tea has been shown to inhibit chemically induced tumorigenesis in many animal models, but the effects of tea consumption on human carcinogenesis are not conclusive. In order to develop biomarkers for tea consumption, we developed methods for the analysis of tea polyphenols in human plasma and urine samples using HPLC with the coulochem electrode array detection system. (-)-Epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epicatechin (EC) are the major polyphenols in green tea. Most of the tea polyphenols were in their conjugated forms in the plasma and urine. The samples were incubated with a mixture of beta-glucuronidase and sulfatase to generate the free form of tea polyphenols. After extraction into ethyl acetate and separation by reversed-phase chromatography, EGCG, EGC, and EC were identified on the basis of their retention times and electrochemical characteristics. Due to the high selectivity of the detection mode, interference was minimized. Good quantitative relationships were established for a large concentration range of tea polyphenols. The limits of detection for EGCG, EGC, ECG, and EC were from 0.5 to 1.5 ng/ml of plasma or urine sample. After ingestion of 1.2 g of decaffeinated green tea in warm water, the plasma samples collected at 1 h from 4 human volunteers contained 46-268 ng/ml of EGCG, 82-206 ng/ml of EGC, and 48-80 ng/ml of EC. ECG was not detected in plasma samples. The maximum urinary excretion of EGC and EC occurred at 3-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Analysis of plasma and urinary tea polyphenols in human subjects. 765 36

Gastric cancer is the second most lethal cancer worldwide. Despite the current surgical and adjuvant therapies, 5-year survival remains less than 20-25% in the US, Europe and China. Therefore, there is an urgent need to identify new therapeutic targets for treating this malignant disease. Accumulating evidence has supported that aberrant activation of the Hedgehog signaling pathway plays a crucial role in tumorigenesis and progression of gastric cancer. Human sulfatase-1 (HSulf-1) is a recently identified enzyme that desulfates cell surface heparan sulfate proteoglycans (HSPGs), which is critical for Hedgehog signal transduction under a highly sulfated state. HSulf-1 has recently emerged as a tumor suppressor gene in certain types of cancer, including ovarian, breast, myeloma and hepatocellular carcinoma; however, its role in gastric cancer remains to be elucidated. Therefore, we established HSulf-1-expressing monoclonal MKN28 gastric cancer cells to investigate its function in gastric cancer. Expression of HSulf-1 significantly suppressed cellular proliferation and growth in MKN28 gastric cancer cells. Notably, HSulf-1 inhibits Gli-mediated transcription and down-regulates the expression of Hedgehog target genes, including GLI1, PTCH1/2, HHIP, CCND1, C-MYC and BCL-2. Collectively, the study provides evidence that HSulf-1 may function as a tumor suppressor in gastric cancer. It suppresses gastric cancer cell proliferation, possibly through abrogating the Hedgehog signaling pathway. The study provides new mechanistic insight into HSulf-1- mediated tumor suppression, and supports the use of HSulf-1 as a potential new therapeutic target in treating gastric cancer.
 ...
PMID:HSulf-1 suppresses cell growth and down-regulates Hedgehog signaling in human gastric cancer cells. 2284 4

Sulfatase 2 (SULF2), an extracellular sulfatase that alters sulfation on heparan sulfate proteoglycans, is involved in the tumorigenesis and progression of several carcinomas. SULF2 expression has not been evaluated in squamous cell carcinoma of the head and neck (HNSCC). Here we report results of IHC of SULF2 expression in HNSCC tissue. SULF2 was detected in 57% of tumors (n = 40) with a significant increase in intensity and number of stained cells compared to adjacent cancer-free tissue (p-value < 0.01), increasing with cancer stage when comparing stages 1 and 2 to stages 3 and 4 (p-value 0.01). SULF2 was not detected in epithelial cells of cancer-free controls, and expression was independent of patient demographics, tumor location and etiological factors, smoking and HPV infection by p16 IHC analysis. Sandwich ELISA was performed on serum of HNSCC patients (n = 28) and controls (n = 35), and although SULF2 was detectable, no change was observed in HNSCC. Saliva, collected by mouthwash, from HNSCC patients (n = 8) and controls (n = 8) was also tested by ELISA in a preliminary investigation and an increase in SULF2 was observed in HNSCC (p-value 0.041). Overall, this study shows that SULF2 is increased in HNSCC independent of tissue location (oral cavity, oropharynx, larynx and hypopharynx), patient demographics and etiology. Although no change in SULF2 was detected in HNSCC serum, its detection in saliva makes it worthy of further investigation as a potential HNSCC biomarker.
 ...
PMID:Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck. 2722 83

The telomeric protein TRF2 is overexpressed in several human malignancies and contributes to tumorigenesis even though the molecular mechanism is not completely understood. By using a high-throughput approach based on the multiplexed Luminex X-MAP technology, we demonstrated that TRF2 dramatically affects VEGF-A level in the secretome of cancer cells, promoting endothelial cell-differentiation and angiogenesis. The pro-angiogenic effect of TRF2 is independent from its role in telomere capping. Instead, TRF2 binding to a distal regulatory element promotes the expression of SULF2, an endoglucosamine-6-sulfatase that impairs the VEGF-A association to the plasma membrane by inducing post-synthetic modification of heparan sulfate proteoglycans (HSPGs). Finally, we addressed the clinical relevance of our findings showing that TRF2/SULF2 expression is a worse prognostic biomarker in colorectal cancer (CRC) patients.
 ...
PMID:TRF2 positively regulates SULF2 expression increasing VEGF-A release and activity in tumor microenvironment. 3069 37

Estrogen evidently involves critically in the pathogenesis of gynaecological-cancers. Reports reveal that interference in estrogen-signalling can influence cell-cycle associated regulatory-processes in female reproductive-organs. The major determinants that influence E2-signallings are estrogen-receptor (ER), estrogen-sulfotransferase (SULT1E1), sulfatase (STS), and a formylglycine-generating-enzyme (FGE) which regulates STS activity. The purpose of this mini review was to critically analyze the correlation between oxidative-threats and redox-regulation in the process of estrogen signalling. It is extensively investigated and reported that oxidative-stress is linked to cancer. But no definite mechanism has been explored till date. The adverse effects of oxidative-threat/free-radicals (like genotoxic-effects, gene-regulation, and mitochondrial impairment) have been linked to several diseases like diabetes/cardiovascular-syndrome/stroke and cancer. However, a significant correlation between oxidative-stress and gynaecological-cancers are repeatedly reported without pointing a definite mechanism. For the first time in our study we have investigated the relationship between oxidative stress and the regulation of estrogen via estrogen metabolizing proteins. Reports reveal that ER, SULT1E1, STS and FGE are target-molecules of oxidative-stress and may function differently in oxidizing and reducing environment. In addition, estrogen itself can induce oxidative-stress. This fact necessitates identifying the critical connecting events between oxidative-stress and regulation of estrogen-associated-molecules (ER, SULT1E1, STS, and FGE) that favors tumorigenesis/carcinogenesis. The current review focus is on unique redox-regulation of estrogen and its regulatory-molecules via oxidative-stress. This mechanistic-layout may identify new therapeutic-targets and open further scopes to treat gynecological-cancers more effectively.
 ...
PMID:Impaired redox regulation of estrogen metabolizing proteins is important determinant of human breast cancers. 3111 46