Abstract：
:The unsatisfactory results of current anti-cancer therapies require the active search for new drugs, new treatment strategies and a deeper understanding of the host-tumour relationship. From this point of view, the drugs with a capacity to substitute the functions of altered tumour suppressor genes are of prominent interest. Since one of the main functions of oncosuppressors is to mediate cell cycle arrest via modification of cyclin dependent kinases (CDKs) activity, the compounds with ability to substitute altered functions of these genes in neoplastic cells are of prominent interest. Synthetic inhibitors of cyclin dependent kinases (CDKIs) are typical representatives of such drugs. Olomoucine (OC), flavopiridol (FP), butyrolactone I (BL) and their derivatives selectively inhibit CDKs and thus constrain tumor cell proliferation under in vitro and/or in vivo conditions. We originally discovered OC and its inhibitory activity toward CDK1 family of CDKs, and recently reported the induction of apoptosis and tumor regression following OC application. Moreover, the OC family of synthetic CDKIs has the capacity of directly inhibit CDK7, the principal enzyme required for activating other CDKs, and thus these compounds are the first known CDK7 inhibitors. Its unique mechanism of action and potent anti-cancer activity under both in vitro and in vivo conditions provide a unique tool to inhibit tumour cell proliferation, and to selectively induce apoptosis in neoplastic tissues. The mechanisms of anti-cancer activities of FP, BL, OC and related synthetic CDKIs are compared and discussed in this paper.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Hajdúch M,Havlíèek L,Veselý J,Novotný R,Mihál V,Strnad Msubject
Has Abstractpub_date
1999-01-01 00:00:00pages
341-53eissn
0065-2598issn
2214-8019journal_volume
457pub_type
杂志文章,评审abstract：:Here, we have demonstrated potent inhibition of allergen-mediated pulmonary inflammation and airway hyper-responsiveness by a novel dual-pronged action of LX's. Moreover, these results indicate that LX's play pivotal and previously unappreciated roles in regulating allergy and pulmonary inflammation. ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4419-9194-2_5
更新日期：2003-01-01 00:00:00
abstract：:We have shown that urinary taurine level may be used as a biomarker of pathological and biochemical lesions. Detection of changes in the urinary concentration of this low molecular weight metabolite indicates biochemical lesions which may also be associated with pathological damage. Hepatotoxic compounds such as CCl4,...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4899-0182-8_15
更新日期：1996-01-01 00:00:00
abstract：:Proteinase inhibitor proteins in the families Solanaceae, Leguminosae and Graminae are stored in seeds and tubers and are also found to accumulate in leaves in response to pest attacks. The isolation of the proteinase Inhibitor I cDNA and its gene from tomato has provided information concerning proteinase inhibitor sy...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4757-0022-0_17
更新日期：1986-01-01 00:00:00
abstract：:In a mouse model of acute light-induced retinal degeneration, positive correlations between the levels of DHA, the levels of n3 PUFA lipid peroxidation, and the vulnerability to photooxidative stress were observed. On the other hand, higher sensitivity of the electroretinogram a-wave response, a measure of the amplifi...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4419-1399-9_65
更新日期：2010-01-01 00:00:00
abstract：:To assess whether the dipeptide N-epsilon-(gamma-L-glutamyl)-L-lysine (glutamyl-lysine) can serve as a nutritional source of lysine, we compared the growth of mice fed (a) an amino acid diet in which lysine was replaced by six dietary levels of glutamyl-lysine; (b) wheat gluten diets fortified with lysine; (c) a wheat...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4899-2626-5_30
更新日期：1991-01-01 00:00:00
abstract：:Proteolytic enzyme activity, present at both acid and neutral pH values, in cerebrospinal fluid, can be measured by a sensitive assay, which monitors the rate of 125I-basic protein breakdown on polyacrylamide gel electrophoresis. CSF cellular neutral proteinase and supernatant acid proteinase are increased in acute mu...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-2514-7_38
更新日期：1978-01-01 00:00:00
abstract：:Storage of fluorescent products, ceroid-like pigments was observed in P388D1 cells, an established macrophage-like cell line, when the cells were cultured in the presence of rat liver phosphatidylcholine liposomes containing polyunsaturated fatty acids. Some fluorescent products accumulated in the cells were extractab...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4899-5339-1_23
更新日期：1989-01-01 00:00:00
abstract：:Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic syndrome associated with hyperactivation of macrophages and impaired regulation of the immune system. Two forms of HLH are currently recognized: genetically determined or familial (FHLH), and secondarily developed in the course of primary diseases, like aut...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/5584_2016_210
更新日期：2016-01-01 00:00:00
abstract：:Ethanol has been shown to induce a shift in catecholamine metabolism peripherally from normally oxidative pathways to reductive pathways. The mechanisms of this effect may result from competitive inhibition of aldehyde dehydrogenase by acetaldehyde. The shift in metabolism cannot be found in brain and alterations in c...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4899-5181-6_33
更新日期：1977-01-01 00:00:00
abstract：:Fascioliasis is a major parasitic disease caused by the digenetic trematodes Fasciola hepatica and Fasciola gigantica. The disease is a well-known veterinary problem of worldwide distribution. Fascioliasis is the vector-borne parasitic disease presenting the widest latitudinal, longitudinal, and altitudinal distributi...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-18616-6_4
更新日期：2019-01-01 00:00:00
abstract：:Stem cells having the capability to differentiate into other type of cells and renewing themselves, gained so much importance in recent years. Investigations in stem cells revealed that mesenchymal stem cells can successfully differentiate into other type of cells like adipocytes, hepatocytes, osteocytes, neurocytes a...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/5584_2019_476
更新日期：2020-01-01 00:00:00
abstract：:Anthropogenic sounds come in different forms, varying not only in amplitude and frequency spectrum but also in temporal structure. Although fish are sensitive to the temporal characteristics of sound, little is known about how their behavior is affected by anthropogenic sounds of different temporal patterns. We invest...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4939-2981-8_93
更新日期：2016-01-01 00:00:00
abstract：:Lymphocyte differentiation from haematopoietic stem cells (HSCs) is a multi-step process in which lineage fate choices are made at crucial branch points. Plasticity of common precursors is evidenced by presence of transcriptionally favourable chromatin structures at several lineage-specific loci, making them poised fo...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4419-8216-2_3
更新日期：2011-01-01 00:00:00
abstract：:Herpes simplex virus and varicella-zoster virus have been treated for more that half a century using nucleoside analogues. However, there is still an unmet clinical need for improved herpes antivirals. The successful compounds, acyclovir; penciclovir and their orally bioavailable prodrugs valaciclovir and famciclovir,...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4614-5037-5_7
更新日期：2013-01-01 00:00:00
abstract：:Genetic studies have bestowed insight into the biological mechanisms underlying inter-individual differences in susceptibility to (or resistance to) organisms’ aging. Recent advances in molecular and genetic epidemiology provide tools to explore the genetic sources of the variability in biological aging in humans. To ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4939-2404-2_7
更新日期：2015-01-01 00:00:00
abstract：:Collective cell migration plays key roles in various physiological and pathological processes in multicellular organisms, including embryonic development, wound healing, and formation of cancer metastases. Such collective migration involves complex crosstalk among cells and their environment at both biochemical and me...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-17593-1_1
更新日期：2019-01-01 00:00:00
abstract：:The tumor microenvironment plays a determining role in cancer development through a plethora of interactions between the extracellular matrix and tumor cells. Decorin is a prototype member of the SLRP family found in a variety of tissues and is expressed in the stroma of various forms of cancer. Decorin has gained rec...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-48457-6_2
更新日期：2020-01-01 00:00:00
abstract：:We have isolated a series of five proteins which appear to possess characteristic individual capacities for synthesizing dextrans and binding dextrans. Our suggestion that these proteins comprise an isozyme-like distribution of lectin and enzyme activities is, of course, very speculative and remains to be rigourously ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-3369-2_84
更新日期：1978-01-01 00:00:00
abstract：:Thanks to recent improvements in NMR instrumentation, pulse sequence design, and sample preparation, a panoply of new NMR tools has become available for atomic resolution characterization of intrinsically disordered proteins (IDPs) that are optimized for the particular chemical and spectroscopic properties of these mo...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-20164-1_3
更新日期：2015-01-01 00:00:00
abstract：:In order to define the ischemic myocardial injury in terms of the possible alteration of cardiac membrane properties, Rb+ uptake and 3H-ouabain binding to cardiac tissue were compared in normal and ischemic rabbit hearts. In isolated Langendorff or working rabbit hearts, a global ischemia was produced by reducing the ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-4895-5_45
更新日期：1984-01-01 00:00:00
abstract：:The clinical challenge on surface engineering of medical devices to prevent microorganisms adhesion and biofilm formation, has become an essential aspect for medical implants. Antibacterial properties of Graphene Oxide (GO) have been demonstrated across a broad spectrum of bacteria, and the different mechanisms of act...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/5584_2019_434
更新日期：2020-01-01 00:00:00
abstract：:The failure of complete remissions to reliably translate into cures in acute myeloid leukemia (AML) can be explained by the leukemia stem cell (LSC) paradigm, which hypothesizes that rare leukemia cells with stem cell features, including self-renewal capacity and drug resistance, are primarily responsible for both dis...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-14366-4_9
更新日期：2019-01-01 00:00:00
abstract：:In hospitals, human milk is subjected to heat treatment to reduce risk of transmission of infectious agents such as human immunodeficiency virus (HIV), hepatitis B, cytomegalovirus, and bacterial contamination, especially during feeding of banked milk to preterm infants. Fat losses due to heat treatment have been exte...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4615-1371-1_60
更新日期：2001-01-01 00:00:00
abstract：:An unknown, but significant subgroup (perhaps the majority), of patients who have undergone chemotherapy treatment for their cancer report a subsequent decline in cognitive performance (e.g., difficulty in balancing a checkbook; forgetting or mixing up names of friends or relatives, etc.). The condition has been terme...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：
更新日期：2010-01-01 00:00:00
abstract：:An allosteric mechanism refers to the biological regulation process wherein macromolecules propagate the effect of ligand binding at one site to a spatially distant orthosteric locus, thus affecting activity. The theory has remained a trending topic in biology research for over 50 years, since the understanding of all...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-981-13-8719-7_4
更新日期：2019-01-01 00:00:00
abstract：:Pioneered by the classical mouse embryonic stem cells (ESCs), various stem cell lines representing the peri- and postimplantation stages of embryogenesis have been established. To gain insight into the gene regulatory network operating in these cells, we first investigated epiblast stem cells (EpiSCs), performing ChIP...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-981-10-7311-3_17
更新日期：2018-01-01 00:00:00
abstract：:Polymyxin B is another clinically available polymyxin that has re-emerged in clinical practice to treat infections caused by multi-drug (MDR) or extensively-drug-resistant (XDR) Gram-negative bacteria (GNB). Its chemical structure is very similar to the structure of polymyxin E (colistin). However, since the latter is...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-16373-0_14
更新日期：2019-01-01 00:00:00
abstract：:Laminins are major components of all basement membranes surrounding nerve or vascular tissues. In particular laminin-111, the prototype of the family, facilitates a large spectrum of fundamental cellular responses in all eukaryotic cells. Laminin-111 is a biomaterial frequently used in research, however it is primaril...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-981-13-0947-2_1
更新日期：2018-01-01 00:00:00
abstract：:CA19-9 (carbohydrate antigen 19-9, also called cancer antigen 19-9 or sialylated Lewis a antigen) is the most commonly used and best validated serum tumor marker for pancreatic cancer diagnosis in symptomatic patients and for monitoring therapy in patients with pancreatic adenocarcinoma. Normally synthesized by normal...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-94-017-7215-0_15
更新日期：2015-01-01 00:00:00
abstract：:The origin of some non communicable disease (NCDs) is in early life. Evidence has shown that early life nutrition is associated with the risk of developing chronic non communicable diseases. Pregnancy and infancy are the most critical stages that influence the risks of NCDs in childhood and adult life. Prenatal matern...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-3-030-10616-4_4
更新日期：2019-01-01 00:00:00
