共查询到20条相似文献,搜索用时 62 毫秒
1.
Oleksiewicz U Liloglou T Field JK Xinarianos G 《Cellular and molecular life sciences : CMLS》2011,68(23):3869-3883
Since the discovery of cytoglobin (Cygb) a decade ago, growing amounts of data have been gathered to characterise Cygb biochemistry,
functioning and implication in human pathologies. Its molecular roles remain under investigation, but nitric oxide dioxygenase
and lipid peroxidase activities have been demonstrated. Cygb expression increases in response to various stress conditions
including hypoxia, oxidative stress and fibrotic stimulation. When exogenously overexpressed, Cygb revealed cytoprotection
against these factors. Cygb was shown to be upregulated in fibrosis and neurodegenerative disorders and downregulated in multiple
cancer types. CYGB was also found within the minimal region of a hereditary tylosis with oesophageal cancer syndrome, and its expression was
reduced in tylotic samples. Recently, Cygb has been shown to inhibit cancer cell growth in vitro, thus confirming its suggested
tumour suppressor role. This article aims to review the biochemical and functional aspects of Cygb, its involvement in various
pathological conditions and potential clinical utility. 相似文献
2.
Margherita Ratti Andrea Lampis Jens C. Hahne Rodolfo Passalacqua Nicola Valeri 《Cellular and molecular life sciences : CMLS》2018,75(22):4151-4162
Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient. 相似文献
3.
The inherited susceptibility to cancer 总被引:1,自引:0,他引:1
Guilford P 《Cellular and molecular life sciences : CMLS》2000,57(4):589-603
The study of inherited cancer syndromes has led to the identification of over 25 genes directly involved in tumorigenesis. These genes have functions as diverse as signal transduction, cell cycle control, cell-to-cell adhesion, control of apoptosis, DNA repair and the maintenance of genome stability. Most cancer syndromes have a dominant pattern of inheritance, due to germline loss-of-function mutation of a tumour suppressor gene. All the recessively inherited genes have been implicated in the maintenance of genome stability. This review summarises our current understanding of the functions of the major cancer susceptibility genes. 相似文献
4.
Paige AJ 《Cellular and molecular life sciences : CMLS》2003,60(10):2147-2163
Knudsons two-hit model of tumour suppressor genes supposes that two mutations are required to cause a tumour, one occurring in each of the two alleles of the gene. Many such cancer genes exhibiting biallelic disruption and truncating point mutations have been identified, revealing the success of the model. Despite changes in our concept of cancer genes, two inactivating point mutations are still considered the hallmark of tumour suppressor genes. Recently, however, more and more reports describe candidate tumour suppressors that do not conform to this standard definition, including haploinsufficient genes requiring inactivation of only one allele, and genes inactivated not by mutation but rather epigenetic hypermethylation. This review describes some of these exceptions and proposes a revised tumour suppressor gene definition to facilitate the identification of this new generation of tumour suppressor loci.Received 21 January 2003; received after revision 26 March 2003; accepted 1 April 2003 相似文献
5.
Recent insights into the role of integrins in cancer metastasis 总被引:11,自引:0,他引:11
P. Clezardin 《Cellular and molecular life sciences : CMLS》1998,54(6):541-548
Integrins have been repeatedly found involved in cancer metastasis. The past two years have seen considerable evolution in
our knowledge on the role of these integrins in tumour cells. This includes the elucidation of different signalling pathways
by which integrins dictate the anchorage-independent growth, survival and motility of tumour cells. Moreover, integrins may
have a more complex role in cancer metastasis as they cooperate with serine proteases and metalloproteases to promote tumour
cell invasion and angiogenesis. Finally, integrins favour tumor cell extravasation. 相似文献
6.
Hedgehog signalling in cancer 总被引:13,自引:0,他引:13
Toftgård R 《Cellular and molecular life sciences : CMLS》2000,57(12):1720-1731
7.
The mammary gland undergoes major developmental changes during puberty and pregnancy. It is thought that stem cells drive mammary gland development during puberty and are responsible for tissue maintenance as well as the major growth and remodelling that occurs with every pregnancy. The use of sophisticated cell separation procedures has facilitated the prospective isolation of mammary epithelial stem and differentiated cell subpopulations from the mouse mammary gland, while studies of primary human breast cancers have described sub-populations of tumourigenic cells capable of initiating tumour growth in immuno-compromised mice. These potential tumour 'stem cells' constitute an important therapeutic target population with respect to cancer therapy, as these are likely to be the cells which maintain tumour growth. Understanding the origin of these cells, their relationship to breast cancer subtypes, and how and why they differ from normal breast stem cells will lead to a revolution in tumour understanding, treatment and prevention. (Part of a Multi-author Review). 相似文献
8.
The p53 protein was discovered 20 years ago, as a cellular protein tightly bound to the large T oncoprotein of the SV40 DNA
tumour virus. Since then, research on p53 has developed in many exciting and sometimes unexpected directions. p53 is now known
to be the product of a major tumour suppressor gene that is the most common target for genetic alterations in human cancer.
The nonmutated wild-type p53 protein (wtp53) is often found within cells in a latent state and is activated in response to
various intracellular and extracellular signals. Activation involves an increase in overall p53 protein levels, as well as
qualitative changes in the protein. Upon activation, wtp53 can induce a variety of cellular responses, most notable among
which are cell cycle arrest and apoptosis. To a great extent, these effects are mediated by the ability of p53 to activate
specific target genes. In addition, the p53 protein itself possesses biochemical functions which may facilitate DNA repair
as well as apoptosis. The role of p53 in normal development and particularly in carcinogenesis has been elucidated in depth
through the use of mouse model systems. The insights provided by p53 research over the years are now beginning to be utilized
towards better diagnosis, prognosis and treatment of cancer. 相似文献
9.
Bignold LP 《Cellular and molecular life sciences : CMLS》2002,59(6):950-958
Almost all solid malignancies exhibit complex cytological and architectural abnormalities, which vary from cell to cell and
area to area within the same tumour, and between tumours of the same type. The degrees of these abnormalities do not correlate
perfectly with the biological behaviour (especially growth rate and metastatic potential) among the various tumour types.
These features of tumours have long been considered to invalidate simple mutational or 'abnormal gene expression' (epigenetic)
theories of carcinogenesis. The 'mutator phenotype/clonal selection' hypothesis is based on the now well-established phenomenon
of genetic instability of cancer cells, and proposes that this instability is an essential requirement for the development
of tumours, and not an irrelevant side-effect of some other process. This paper argues that this hypothesis can provide a
satisfactory explanation for the diverse histological and biological features of solid malignancies. Further, because virtually
all solid tumours are histologically abnormal, genetic instability is likely to be essential for the malignant process. The
concepts of mutator phenotype and clonal selection are therefore supported.
Received 8 April 2002; accepted 25 April 2002 相似文献
10.
11.
Clinical implications of p53 mutations 总被引:5,自引:0,他引:5
The ultimate goal of basic cancer research is to provide a theoretical foundation for rational approaches to improve cancer
therapy. Our extensive insight into the biology of the p53 tumour suppressor and the clinical behaviour of tumours harbouring
p53 mutations indicates that information concerning p53 will be useful in diagnosis and prognosis, and may ultimately produce
new therapeutic strategies. At the same time, efforts to understand the clinical implications of p53 mutations have revealed conceptual and technical limitations in translating basic biology to the clinic. The lessons learned
from p53 may lay the groundwork for future efforts to synthesize cancer gene function, cancer genetics and cancer therapy. 相似文献
12.
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14.
A. Truini S. Coco A. Alama C. Genova C. Sini M. G. Dal Bello G. Barletta E. Rijavec G. Burrafato F. Boccardo F. Grossi 《Cellular and molecular life sciences : CMLS》2014,71(15):2865-2878
Malignant mesothelioma (MM) is an aggressive tumor, mainly derived from the pleura, which is predominantly associated with exposure to asbestos fibers. The prognosis of MM patients is particularly severe, with a median survival of approximately 9–12 months and latency between exposure and diagnosis ranging from 20–50 years (median 30 years). Emerging evidence has demonstrated that tumor aggressiveness is associated with genome and gene expression abnormalities; therefore, several studies have recently focused on the role of microRNAs (miRNAs) in MM tumorigenesis. miRNAs are small non-protein coding single-stranded RNAs (17–22 nucleotides) involved in numerous cellular processes that negatively regulate gene expression by modulating the expression of downstream target genes. miRNAs are often deregulated in cancer; in particular, the differential miRNA expression profiles of MM cells compared to unaffected mesothelial cells have suggested potential roles of miRNAs as either oncogenes or tumor suppressor genes in MM oncogenesis. In this review, the mechanism of MM carcinogenesis was evaluated through the analysis of the published miRNA expression data. The roles of miRNAs as diagnostic biomarkers and prognostic factors for potential therapeutic strategies will be presented and discussed. 相似文献
15.
Ada Collura Laetitia Marisa Diletta Trojan Olivier Buhard Anaïs Lagrange Arnaud Saget Marianne Bombled Patricia Méchighel Mira Ayadi Martine Muleris Aurélien de Reynies Magali Svrcek Jean-François Fléjou Jean-Claude Florent Florence Mahuteau-Betzer Anne-Marie Faussat Alex Duval 《Cellular and molecular life sciences : CMLS》2013,70(4):729-742
Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of “stemness”. These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copy-number. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse. 相似文献
16.
D Szeinfeld 《Experientia》1988,44(3):232-234
The variation of adenosine-5'-triphosphate (ATP) content per unit mass of tumour, versus tumour volume was measured in vivo under normoxic conditions, using CaNT and Fib/t murine tumours grown in CBA and WHT mice respectively. A monotonically decreasing relation was found. Artificially induced tumour hypoxia resulting from 15 min of clamping was accompanied by reduced ATP levels. 相似文献
17.
Hepatocyte growth factor in invasive growth of carcinomas 总被引:2,自引:0,他引:2
Desiderio MA 《Cellular and molecular life sciences : CMLS》2007,64(11):1341-1354
18.
The urokinase receptor and integrins in cancer progression 总被引:2,自引:0,他引:2
Enhanced levels of expression of urokinase receptor (uPAR) and certain integrins have been linked to cancer cell progression. This has classically been attributed to matrix degradation via the activation of the urokinase (uPA)/plasmin system and modulation of cell motility and survival through integrin engagement. More recently, uPAR has been shown to play multiple roles independent of protease activity. Specifically, uPAR has been shown to be intimately involved in the regulation of cell adhesion, migration and proliferation in part through interactions with other membrane partners, including integrins. The goal of this review is to summarize recent insights in the function of uPAR/integrin interactions, to provide a framework for understanding the importance of these interactions in the context of cancer, and to highlight its potential as a target for therapeutic intervention. 相似文献
19.
The inhibitor of growth (ING) family of tumor suppressors has five members and is implicated in the control of apoptosis,
senescence, DNA repair, and cancer progression. However, little is known about ING activity in the regulation of cancer progression.
ING members and splice variants seem to behave differently with respect to cancer invasion and metastasis. Interaction with
histone trimethylated at lysine 4 (H3K4me3), hypoxia inducible factor-1 (HIF-1), p53, and nuclear factor kappa-B (NF-κB) are
potential mechanisms by which ING members exert effects on invasion and metastasis. Subcellular mislocalization, rapid protein
degradation, and to a lesser extent ING gene mutation are among the mechanisms responsible for inappropriate ING levels in cancer cells. The aim of this review is
to summarize the different roles of ING family tumor suppressors in cancer progression and the molecular mechanisms involved. 相似文献
20.
Poly-ADP-ribosylation in health and disease 总被引:4,自引:0,他引:4