19 research outputs found
The concept of "compartment allergy": prilocaine injected into different skin layers
We herein present a patient with delayed-type allergic hypersensitivity against prilocaine leading to spreading eczematous dermatitis after subcutaneous injections for local anesthesia with prilocaine. Prilocaine allergy was proven by positive skin testing and subcutaneous provocation, whereas the evaluation of other local anesthetics - among them lidocaine, articaine and mepivacaine - did not exhibit any evidence for cross-reactivity
Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy
Background:Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target.
Methods:Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC).
Results:Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180âmM) or lonidamine (300âÎŒM) with 10âJâcm-2 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24âh, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24âh). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA.
Conclusion:As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PD
Mitochondrial Genomic Instability in Colorectal Cancer: No Correlation to Nuclear Microsatellite Instability and Allelic Deletion of hMSH2, hMLH1, and p53 Genes, but Prediction of Better Survival for Dukesâ Stage C Disease
Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC
Expression of mitochondrial genes MT-ND1, MT-ND6, MT-CYB, MT-COI, MT-ATP6, and 12S/MT-RNR1 in colorectal adenopolyps
The Sensitive and Selective Enzyme-Free Electrochemical H2O2 Sensor Based on rGO/MnFe2O4 Nanocomposite
Impact of dietary Mannan-oligosaccharide and ÎČ-Glucan supplementation on growth, histopathology, E-coli colonization and hepatic transcripts of TNF-α and NF- Ï°B of broiler challenged with E. coli O78
Absence of the Birt-Hogg-Dube gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility
Under conditions of reduced tissue oxygenation, hypoxia-inducible factor (HIF) controls many processes, including angiogenesis and cellular metabolism, and also influences cell proliferation and survival decisions. HIF is centrally involved in tumour growth in inherited diseases that give rise to renal cell carcinoma (RCC), such as Von HippelâLindau syndrome and tuberous sclerosis complex. In this study, we examined whether HIF is involved in tumour formation of RCC in BirtâHoggâDubĂ© syndrome. For this, we analysed a BirtâHoggâDubĂ© patient-derived renal tumour cell line (UOK257) that is devoid of the BirtâHoggâDubĂ© protein (BHD) and observed high levels of HIF activity. Knockdown of BHD expression also caused a threefold activation of HIF, which was not as a consequence of more HIF1α or HIF2α protein. Transcription of HIF target genes VEGF, BNIP3 and CCND1 was also increased. We found nuclear localization of HIF1α and increased expression of VEGF, BNIP3 and GLUT1 in a chromophobe carcinoma from a BirtâHoggâDubĂ© patient. Our data also reveal that UOK257 cells have high lactate dehydrogenase, pyruvate kinase and 3-hydroxyacyl-CoA dehydrogenase activity. We observed increased expression of pyruvate dehydrogenase kinase 1 (a HIF gene target), which in turn leads to increased phosphorylation and inhibition of pyruvate dehydrogenase. Together with increased protein levels of GLUT1, our data reveal that UOK257 cells favour glycolytic rather than lipid metabolism (a cancer phenomenon termed the âWarburg effectâ). UOK257 cells also possessed a higher expression level of the L-lactate influx monocarboxylate transporter 1 and consequently utilized L-lactate as a metabolic fuel. As a result of their higher dependency on glycolysis, we were able to selectively inhibit the growth of these UOK257 cells by treatment with 2-deoxyglucose. This work suggests that targeting glycolytic metabolism may be used therapeutically to treat BirtâHoggâDubĂ©-associated renal lesions
Preferential expression of the transcription coactivator HTIF1α gene in acute myeloid leukemia and MDS-related AML
Do reactive oxygen species play a role in myeloid leukemias?
Reactive oxygen species (ROS) are a heterogeneous group of molecules that are generated by mature myeloid cells during innate immune responses, and are also implicated in normal intracellular signaling. Excessive production of ROS (and/or a deficiency in antioxidant pathways) can lead to oxidative stress, a state that has been observed in several hematopoietic malignancies including acute and chronic myeloid leukemias (AML and CML). Currently it is unclear what the cause of oxidative stress might be and whether oxidative stress contributes to the development, progression, or maintenance of these diseases. This article reviews the current evidence suggesting a role for ROS both in normal hematopoiesis and in myeloid leukemogenesis, and discusses the usefulness of therapeutically targeting oxidative stress in myeloid malignancy