| 1. |
- Bryukhovetskiy, Igor, et al.
(författare)
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Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies : From theory to experiment (Review)
- 2018
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Ingår i: International Journal of Molecular Medicine. - : SPANDIDOS PUBL LTD. - 1107-3756 .- 1791-244X. ; 42:2, s. 691-702
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Forskningsöversikt (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and similar to 20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy. However, the prognosis of GBM is usually poor, with a median survival of 15 months. Resistance of GBM to treatment can be explained by the presence of cancer stem cells (CSCs) among the GBM cell population. At present, there are no effective therapeutic strategies for the elimination of CSCs. The present review examined the nature of human GBM therapeutic resistance and attempted to systematize and put forward novel approaches for a personalized therapy of GBM that not only destroys tumor tissue, but also regulates cellular signaling and the morphogenetic properties of CSCs. The CSCs are considered to be an informationally accessible living system, and the CSC proteome should be used as a target for therapy directed at suppressing clonal selection mechanisms and CSC generation, destroying CSC hierarchy, and disrupting the interaction of CSCs with their microenvironment and extracellular matrix. These objectives can be achieved through the use of biomedical cellular products.
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| 2. |
- Wikvall, Kjell
(författare)
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Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review)
- 2001
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Ingår i: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 7:2, s. 201-209
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Forskningsöversikt (refereegranskat)abstract
- The formation of 1alpha,25-dihydroxyvitamin D3 requires a 25-hydroxylation followed by a 1alpha-hydroxylation catalyzed by cytochrome P450 (CYP) enzymes in liver and kidney. The aim of this review is to give a brief summary of our research on the cytochrome P450 enzymes catalyzing the 25-hydroxylation and 1alpha-hydroxylation and to discuss the results in relation to other published literature on these enzymes. Two hepatic P450 enzymes catalyzing 25-hydroxylation of vitamin D3 exist in mammalian liver - one mitochondrial and one microsomal. The mitochondrial vitamin D3 25-hydroxylase is apparently identical with CYP27A, an obligatory enzyme in bile acid biosynthesis in liver. The microsomal 25-hydroxylase has been purified to apparent homogeneity from pig liver. The enzyme catalyzed 25-hydroxylation of vitamin D3, 1alpha-hydroxyvitamin D3, vitamin D2 and 1alpha-hydroxyvitamin D2. A cDNA encoding pig liver microsomal vitamin D3 25-hydroxylase has been isolated in this laboratory. The primary structure of vitamin D3 25-hydroxylase shows 70-80% identity with members of the CYP2D subfamily and has been designated CYP2D25. Three different 1alpha-hydroxylating cytochromes P450 in kidney, i.e. CYP27A, CYP27B and a microsomal 1alpha-hydroxylase, have been described. Mitochondrial cytochrome P450, catalyzing 1alpha-hydroxylation and 27-hydroxylation but not 24-hydroxylation of 25-hydroxyvitamin D3, was partially purified from pig kidney. Purification and inhibition experiments as well as experiments with a monoclonal antibody against CYP27A indicated that one single enzyme catalyzes both 1alpha- and 27-hydroxylation. Treatment of rats with a single i.v. dose of 1alpha,25-dihydroxyvitamin D3 resulted in a marked suppression of CYP27A mRNA levels in kidney. The results suggest a role for CYP27A as a renal mitochondrial 1alpha-hydroxylase. Subsequently, several research groups reported the isolation of cDNA encoding mouse, rat and human kidney 25-hydroxyvitamin D3 1alpha-hydroxylase. The amino acid sequences deduced from these cDNA clones were similar but differed from that of CYP27A. This 1alpha-hydroxylase constitutes a new CYP27 subfamily, CYP27B. The expression of CYP27B was found to be influenced by vitamin D status and parathyroid hormone. Mutations in the CYP27B gene have been identified in patients with pseudovitamin D-deficiency rickets. A microsomal P450 catalyzing 1alpha-hydroxylation of 25-hydroxyvitamin D3 has been purified to apparent homogeneity from pig kidney. This finding demonstrate the presence of a microsomal 1alpha-hydroxylase in addition to the mitochondrial 1alpha-hydroxylases in kidney. The relative importance and regulation of the different renal 1alpha-hydroxylases in the bioactivation of vitamin D3 under normal and pathological conditions will be subject for future studies.
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| 3. |
- Buchwald, Pamela, et al.
(författare)
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Vitamin D in normal and pathological parathyroid glands: New prospects for treating hyperparathyroidism (Review)
- 2005
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Ingår i: International Journal of Molecular Medicine. - 1791-244X. ; 15:4, s. 701-706
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Forskningsöversikt (refereegranskat)abstract
- The secosteroid hormone active vitamin D [1,25(OH)(2)D-3] is a key player in the regulation of calcium homeostasis and bone mineralization. In addition, it has antiproliferative and prodifferentiating effects on various cells in vitro and in vivo. The action of 1,25(OH)(2)D-3 is mediated through the vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. VDR is expressed in the intestine, bone, kidney, parathyroid glands, and in many other tissues and cell types. In the parathyroid glands, 1,25(OH)(2)D-3 markedly decreases parathyroid hormone gene transcription and parathyroid cell proliferation and induces parathyroid cell differentiation. Diminished VDR expression is frequent in parathyroid tumors and probably contributes to parathyroid tumorigenesis. The enzyme responsible for catalyzing synthesis of 1,25(OH)(2)D-3 (1 alpha-hydroxylase) has lately been demonstrated in the parathyroid glands. This indicates a new role for 1 alpha-hydroxylase as an intracrine modulator of vitamin D function in non-renal tissues, which recently has been recognized as crucial in parathyroid tumor development. The growth-inhibitory properties of 1,25(OH)(2)D-3 are prospects for treatment of hyperparathyroidism.
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