Search results for "ALK"
showing 10 items of 4314 documents
Analysis of linear alkylbenzene samples with a camera-based equipment
2017
Nestemäisiä tuikeaineita hyödyntävät ilmaisimet ovat saaneet jalansijaa neutriinofysiikassa viime vuosikymmeninä. Perinteisiin Cherenkovin ilmaisimiin niiden etu on suurempi hiukkasten vuorovaikutuksesta aiheutuvan valon tuotto. Lisäksi edullisten, suhteellisen ympäristöystävällisten ja optisesti kirkkaiden tuikeaineyhdisteiden (bentseenin alkyylijohdannaiset) saatavuus mahdollistaa yhä suurempien ilmaisimien rakennuksen. Nestemäisten tuikeaineiden ongelmana on kuitenkin niiden taipumus kerätä epäpuhtauksia itseensä ja niiden muutosalttius UV-säteilyn ja korkeiden lämpötilojen vaikutuksesta. Muutokset heikentävät tuikeaineiden valon tuottoa, ja siksi nestemäisten tuikeaineiden puhdistusta j…
Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base ex…
1996
Repair of alkylated bases in DNA is performed by O6-methylguanine-DNA methyltransferase (MGMT) and a set of enzymes of the base excision repair pathway involving N-methylpurine-DNA glycosylase (MPG), apurinic endonuclease (APE), DNA polymerase beta (Pol beta) and DNA ligase. The level of expression of these enzymes may exert a profound effect on resistance of cells towards alkylating drugs. We have comparatively analyzed the expression of MGMT and the different base excision repair genes in rat hepatoma cells (line H4IIE) after exposure to alkylating agents, X-rays and the glucocorticoid hormone dexamethasone. Furthermore, the effect of these agents on the activity of the cloned human MGMT …
Crosstalk between leukemia-associated proteins MOZ and MLL regulates HOX gene expression in human cord blood CD34+ cells
2010
MOZ and MLL, encoding a histone acetyltransferase (HAT) and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. In MOZ (MOnocytic leukemia Zinc-finger protein)/CBP- or mixed lineage leukemia (MLL)-rearranged leukemias, abnormal levels of HOX transcription factors have been found to be critical for leukemogenesis. We show that MOZ and MLL cooperate to regulate these key genes in human cord blood CD34+ cells. These chromatin-modifying enzymes interact, colocalize and functionally cooperate, and both are recruited to multiple HOX promoters. We also found that WDR5, an adaptor protein essential fo…
Influence of nitric oxide on the generation and repair of oxidative DNA damage in mammalian cells
2002
We have analysed the effects of endogenously and exogenously generated nitric oxide (NO) in cultured mammalian fibroblasts on: (i) the steady-state (background) levels of oxidative DNA base modifications; (ii) the susceptibility of the cells to the induction of additional DNA damage and micronuclei by H(2)O(2); and (iii) the repair kinetics of various types of DNA modifications. Steady-state levels of oxidative DNA base modifications, measured by means of an alkaline elution assay in combination with the repair endonuclease Fpg protein, were similar in NO-overproducing B6 mouse fibroblasts stably transfected with an inducible NO synthase (iNOS) and in control cells. Increased oxidative dama…
Acquired resistance of melanoma cells to the antineoplastic agent fotemustine is caused by reactivation of the DNA repair gene mgmt
2001
Acquired resistance to antineoplastic agents is a frequent obstacle in tumor therapy. Malignant melanoma cells are particularly well known for their unresponsiveness to chemotherapy; only about 30% of tumors exhibit a transient clinical response to treatment. In our study, we investigated the molecular mechanism of acquired resistance of melanoma cells (MeWo) to the chloroethylating drug fotemustine. Determination of O6-methylguanine-DNA methyltransferase (MGMT) activity showed that MeWo cells that acquired resistance to fotemustine upon repeated treatment with the drug display high MGMT activity, whereas the parental cell line had no detectable MGMT. The resistant cell lines exhibit cross-…
Molecular aspects of carcinogenesis. Part B
1989
Nitrogen mustards represent a major group of alkylating agents that are used in the chemotherapy of cancer. It is commonly accepted that they exert their cytotoxic effects by their ability to produce interstrand crosslinks in DNA. The main target site of the two identical alkylating moieties is the N-7 position of guanine. By a Maxam-Gilbert-type reaction it is possible to identify "hot spots" for alkylation by nitrogen mustards. Analysis of data obtained reveal the importance of the DNA context for efficient alkylation. For most of~ the compounds the highest reactivity is observed ila regions of G clusters, while in the neighbourhood of cytosine residues alkylation is reduced. As a consequ…
EML4-ALK translocation identification in RNA exosomal cargo (ExoALK) in NSCLC patients: A novel role for liquid biopsy
2019
Abstract: The introduction of druggable targets has significantly improved the outcomes of non-small cell lung cancer patients (NSCLC). EML4-ALK translocation represents 4-6% of the druggable alterations in NSCLC. With the approval of Crizotinib, first discovered drug for the EML4-ALK translocation, on first line treatment for patients with detected mutation meant a complete change on the treatment landscape. The current standard method for EML4-ALK identification is immunohistochemistry or FISH in a tumor biopsy. However, a big number of NSCLC patients have not tissue available for analysis and others are not suitable fir biopsy due to their physical condition or the location of the tumor.…
Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase
2009
Abstract Introduction We reinvestigated the synthesis of [ N -methyl- 11 C]vorozole, a radiotracer for aromatase, and discovered the presence of an N -methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [ N -methyl- 11 C]vorozole. Methods Norvorozole was alkylated with [ 11 C]methyl iodide as previously described and also with unlabeled methyl iodide. A high-performance liquid chromatography (HPLC) method was developed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ( 13 C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign s…
Impact of Undernutrition on the Pharmacokinetics and Pharmacodynamics of Anticancer Drugs: A Literature Review
2017
The etiology of undernourishment in cancer patients is multifactorial: tumor-related mechanisms (such as obstruction, metabolic abnormalities, and functionality changes) in addition to the influence of anticancer therapies, which can induce or worsen undernutrition. The evident role of undernutrition in cancer treatment outcomes suggests the need of considering nutritional status when evaluating anticancer drugs. In order to merge the available data and offer researchers and clinicians a global view of this phenomenon, the present manuscript reviews on a drug-by-drug basis the undernutrition-related pharmacokinetic and pharmacodynamic aspects of anticancer treatments. This review notes inte…
Inactivation of O(6)-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors.
2001
The DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a decisive determinant of resistance of tumor cells to methylating and chloroethylating anti-cancer drugs. Therefore, selective inhibition of MGMT in tumors is expected to cause tumor sensitization. Several inhibitors of MGMT have been developed which function in both tumors and normal tissue. To deplete MGMT preferentially in tumors, strategies to target the inhibitor to the tumor tissue need to be developed. Here, we report on the properties of glucose-conjugated MGMT inhibitors that might be useful for tumor targeting since tumor cells frequently over-express glucose transporter. O6-Benzylguanine (O6BG), 8-aza-O6-ben…