ABSTRACT
Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24 iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carrier Proteins/physiology , Cell Transformation, Neoplastic , Glucose/metabolism , Mammary Glands, Human/pathology , Animals , Breast Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cells, Cultured , Energy Metabolism/genetics , Female , HEK293 Cells , Humans , MCF-7 Cells , Mammary Glands, Human/metabolism , Mice , Mice, NudeABSTRACT
Vitamin B12 (cyancobalamin, Cbl) has two active co-enzyme forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). There has been a paradigm shift in the treatment of vitamin B12 deficiency such that MeCbl is being extensively used and promoted. This is despite the fact that both MeCbl and AdCbl are essential and have distinct metabolic fates and functions. MeCbl is primarily involved along with folate in hematopiesis and development of the brain during childhood. Whereas deficiency of AdCbl disturbs the carbohydrate, fat and amino-acid metabolism, and hence interferes with the formation of myelin. Thereby, it is important to treat vitamin B12 deficiency with a combination of MeCbl and AdCbl or hydroxocobalamin or Cbl. Regarding the route, it has been proved that the oral route is comparable to the intramuscular route for rectifying vitamin B12 deficiency.
Subject(s)
Cobamides/therapeutic use , Hydroxocobalamin/therapeutic use , Vitamin B 12/analogs & derivatives , Administration, Oral , Cobamides/administration & dosage , Cobamides/pharmacokinetics , Drug Therapy, Combination , Humans , Hydroxocobalamin/administration & dosage , Hydroxocobalamin/pharmacokinetics , India , Injections, Intramuscular , Vitamin B 12/administration & dosage , Vitamin B 12/pharmacokinetics , Vitamin B 12/therapeutic use , Vitamin B 12 Deficiency/drug therapySubject(s)
Animal Experimentation/ethics , Perception , Students, Medical/psychology , Animals , Cross-Sectional Studies , Humans , India , Research , Schools, MedicalABSTRACT
BACKGROUND: Abdominal pain is the most common indication for oesophagogastroduodenoscopy (OGD) in children. However, existing studies examining the diagnostic outcomes of OGD in children with abdominal pain are limited. AIM: To examine the diagnostic yield of OGD with biopsy in the evaluation of abdominal pain and to describe the endoscopic and histological findings in patients undergoing OGD for abdominal pain of unclear aetiology. METHODS: We performed a retrospective cross-sectional cohort study in children under 18 years of age who had OGD for the primary indication of abdominal pain, at Texas Children's Hospital and Children's Hospital of The King's Daughters from 1 January 2002 to 30 June 2005. RESULTS: Overall, OGD was diagnostic in 454 (38.1%) of the 1191 procedures, including reflux oesophagitis (23%, n = 271), Helicobacter pylori infections (5%, n = 55), peptic ulcers (3%, n = 32), eosinophilic oesophagitis (2%, n = 25), celiac disease (1%, n = 9) and Crohn's disease (0.5%, n = 7). Male gender, older age, elevated C-reactive protein and vomiting were associated with increased diagnostic yield. CONCLUSIONS: Our findings suggest that OGD is valuable for the evaluation of chronic abdominal pain in children, with a diagnostic yield of 38%. The majority of alarm symptoms and routine laboratory tests are not significantly associated with diagnostic yield.
Subject(s)
Abdominal Pain/diagnosis , Endoscopy, Digestive System/standards , Gastrointestinal Diseases/diagnosis , Abdominal Pain/ethnology , Adolescent , Age Factors , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies , Sex FactorsABSTRACT
Radiation field during accidental electron beam loss near electron storage rings comprises of high-energy electrons and bremsstrahlung photons. Due to high-energy nature of the radiation, the absorbed dose is expected to build up with depth of the body of an exposed worker and hence absorbed dose measurements in 30 cm water/tissue equivalent phantom is essential. Carrying out the measurements with in such phantoms is not practically feasible for routine applications and hence the use of an equivalent solid material around the dosemeters would be convenient. Monte Carlo calculations have been carried out in order to determine the dose-build-up thickness required in copper and lead, corresponding to the maximum absorbed within 30 cm depth of water in such radiation fields. Equivalent build-up thickness calculated for a case was verified by measurement using an ion chamber detector. The results are found to be in agreement within +/-20%.
Subject(s)
Electrons , Photons , Radiation Monitoring/instrumentation , Aluminum/chemistry , Computer Simulation , Copper/chemistry , Lead/chemistry , Models, Statistical , Monte Carlo Method , Radiation Dosage , Water/chemistryABSTRACT
Conventional radiation monitors have been found to underestimate the personal dose equivalent in the high-energy bremsstrahlung photon radiation fields encountered near electron storage rings. Depth-dose measurements in a water phantom were carried out with a radiation survey meter in the bremsstrahlung photon radiation fields from a 450 MeV electron storage ring to find out the magnitude of the underestimation. Dose equivalent indicated by the survey meter was found to build up with increase in thickness of water placed in front of the meter up to certain depth and then reduce with further increase in thickness. A dose equivalent build up factor was estimated from the measurements. An absorbed dose build up factor in a water phantom was also estimated from calculations performed using the Monte Carlo codes, EGS-4 and EGSnrc. The calculations are found to be in very good agreement with the measurements. The studies indicate inadequacy of commercially available radiation monitors for radiation monitoring within shielded enclosures and in streaming high-energy photon radiation fields from electron storage rings, and the need for proper correction for use in such radiation fields.
Subject(s)
Algorithms , Artifacts , Models, Biological , Photons , Radiation Monitoring/instrumentation , Radiation Monitoring/methods , Computer Simulation , Humans , Linear Energy Transfer , Models, Statistical , Monte Carlo Method , Radiation Dosage , Radiation Protection/methods , Reproducibility of Results , Scattering, Radiation , Sensitivity and SpecificityABSTRACT
A series of hydroxylated trans-stilbenes related to the antileukemic natural product trans-3,3',4,5'-tetrahydroxystilbene (piceatannol) (1) has been prepared and tested for inhibition of the lymphoid cell lineage-specific protein-tyrosine kinase p56lck, which plays an important role in lymphocyte proliferation and immune function. A number of the analogues displayed enhanced enzyme inhibitory activity relative to the natural product. Reduction of the double bond bridging the two aromatic rings and benzylation of the phenolic hydroxyl groups was found to decrease activity significantly. The most potent compounds in the series proved to be trans-3,3',5,5'-tetrahydroxystilbene, trans-3,3',5-trihydroxystilbene, and trans-3,4,4'-trihydroxystilbene.
