[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
Q Wang
Publications and source records attributed to Q Wang.
Plasmid-based gene therapy of diabetes mellitus.
Type I diabetes mellitus (T1D) is due to a loss of immune tolerance to islet antigen and thus, there is intense interest in developing therapies that can re-establish it. Tolerance is maintained by complex mechanisms that include inhibitory molecules and several types of regulatory T cells (Tr). A major historical question is whether gene therapy can be employed to generate Tr cells. This review shows that gene transfer of immunoregulatory molecules can prevent T1D and other autoimmune diseases. In our studies, non-viral gene transfer is enhanced by in vivo electroporation (EP). This technique can be used to perform DNA vaccination against islet cell antigens and when combined with appropriate immune ligands results in the generation of Tr cells and protection against T1D. In vivo EP can also be applied for non-immune therapy of diabetes. It can be used to deliver protein drugs such as glucagon-like peptide 1 (GLP-1), leptin or transforming growth factor beta (TGF-beta). These act in T1D or type II diabetes (T2D) by restoring glucose homeostasis, promoting islet cell survival and growth or improving wound healing and other complications. Furthermore, we show that in large animals EP can deliver peptide hormones, such as growth hormone releasing hormone (GHRH). We conclude that the non-viral gene therapy and EP represent a safe and efficacious approach with clinical potential.
Animals↗
Binding patterns of human norovirus-like particles to buccal and intestinal tissues of gnotobiotic pigs in relation to A/H histo-blood group antigen expression.
Histo-blood group antigen (HBGA) phenotypes have been associated with susceptibility to human noroviruses (HuNoVs). Our aims were: (i) to determine the patterns of A/H HBGA expression in buccal and intestinal tissues of gnotobiotic (Gn) pigs; (ii) to determine if virus-like particles (VLPs) of HuNoV genogroup I (GI) and GII bind to A- or H-type tissues; (iii) to compare A/H expression and VLP binding patterns and confirm their binding specificities by blocking assays; (iv) to develop a hemagglutination inhibition test using buccal cells from live pigs to determine the Gn pig's A/H phenotype and to match viral strains with previously determined HuNoV VLP binding specificities; and (v) to determine the A/H phenotypes and compare these data to the infection outcomes of a previous study of 65 Gn pigs inoculated with HuNoV GII/4 strain HS66 and expressing A and/or H or neither antigen on their buccal and intestinal tissues (S. Cheetham, M. Souza, T. Meulia, S. Grimes, M. G. Han, and L. J. Saif, J. Virol. 80:10372-10381, 2006). We found that the HuNoV GI/GII VLPs of different clusters bound to tissues from four pigs tested (two A+ and two H+). The GI/1 and GII/4 VLPs bound extensively to duodenal and buccal tissues from either A+ or H+ pigs, but surprisingly, GII/1 and GII/3 VLPs bound minimally to the duodenum of an A+ pig. The VLP binding was partially inhibited by A-, H1-, or H2-specific monoclonal antibodies, but was completely blocked by porcine mucin. Comparing the A/H phenotypes of 65 HS66-inoculated Gn pigs from our previous study, we found that significantly more A+ and H(+) pigs (51%) than non-A+ and non-H+ pigs (12.5%) shed virus. From the 22 convalescent pigs, significantly more A+ or H+ pigs (66%) than non-A+ or H+ pigs (25%) seroconverted.
Animals↗
Efficient green-blue-light-emitting cationic iridium complex for light-emitting electrochemical cells.
A highly luminescent novel cationic iridium complex [iridium bis(2-phenylpyridine)(4,4'-(dimethylamino)-2,2'-bipyridine)]PF6 was synthesized and characterized using NMR, UV-visible absorption, and emission spectroscopy and electrochemical methods. This complex displays intense photoluminescence maxima in the green-blue region of the visible spectrum and exhibits unprecedented phosphorescence quantum yields, 80 +/- 10% with an excited-state lifetime of 2.2 mus in a dichloromethane solution at 298 K. Single-layer light-emitting electrochemical cells with the charged complex as conducting and electroluminescent material sandwiched between indium-tin oxide and Ag electrodes were fabricated, which emit green-blue light with an onset voltage as low as 2.5 V. Density functional theory calculations were performed to provide insight into the electronic structure of the [iridium bis(2-phenylpyridine)(4,4'-(dimethylamino)-2,2'-bipyridine)]PF6 complex, comparing these results with those obtained for [iridium bis(2-phenylpyridine)(4,4'-tert-butyl-2,2'-bipyridine)]PF6.
Journal Article↗
The ribosomal database project (RDP-II): introducing myRDP space and quality controlled public data.
Substantial new features have been implemented at the Ribosomal Database Project in response to the increased importance of high-throughput rRNA sequence analysis in microbial ecology and related disciplines. The most important changes include quality analysis, including chimera detection, for all available rRNA sequences and the introduction of myRDP Space, a new web component designed to help researchers place their own data in context with the RDP's data. In addition, new video tutorials describe how to use RDP features. Details about RDP data and analytical functions can be found at the RDP-II website (http://rdp.cme.msu.edu/).
Databases, Nucleic Acid↗
Developmental dependence, the role of the kinases p38 MAPK and PKC, and the involvement of tumor necrosis factor-R1 in the induction of mGlu-5 LTD in the dentate gyrus.
The mechanisms of mGluR-LTD were studied in the dentate gyrus in vitro. The most effective protocol for inducing mGluR-LTD in 6-8 week animals was brief high frequency stimulation (HFS) applied in the presence of the NMDAR antagonist AP5. Evidence for HFS inducing LTD via activation of perisynaptically located mGluRs was established, as an inhibitor of glutamate transporter potentiated HFS-LTD. HFS-LTD was mainly mediated by activation of mGluR5, although a partial involvement of mGluR1 was found. (RS)-3,5-Dihydroxyphenylglycine (DHPG) also induced LTD, but in an age dependent manner, being large in 2 week animals but absent in 6-8 week animals. DHPG-LTD in the dentate gyrus also had a much slower rise time than that in CA1, and unlike CA1, the expression/maintenance of mGluR-LTD was not inhibited by mGluR antagonists. The use of pharmacological inhibitors showed that the induction of HFS-LTD was partially dependent upon activation of L-type Ca channels, release of Ca from ryanodine receptor-sensitive intracellular Ca stores, and the kinases p38 mitogen-activated protein kinase (MAPK), protein kinase C (PKC), but not c-Jun N-terminal kinase or COX-2. Evidence for the involvement of tumor necrosis factor-receptor 1 (TNF-R1) in the induction of mGluR-LTD was presented in the present study, with both HFS-mGluR-LTD and DHPG-LTD being absent in mutant mice null for TNF-R1.
Aging↗
Gene therapy of diabetes using a novel GLP-1/IgG1-Fc fusion construct normalizes glucose levels in db/db mice.
Glucagon-like peptide (GLP-1), a major physiological incretin, plays numerous important roles in modulating blood glucose homeostasis and has been proposed for the treatment of type 2 diabetes. The major obstacles for using native GLP-1 as a therapeutic agent are that it must be delivered by a parenteral route and has a short half-life. In an attempt to develop a strategy to prolong the physiological t(1/2) and enhance the potency of GLP-1, a fusion protein consisting of active human GLP-1 and mouse IgG(1) heavy chain constant regions (GLP-1/Fc) was generated. A plasmid encoding an IgK leader peptide-driven secretable fusion protein of the active GLP-1 and IgG(1)-Fc was constructed for mammalian expression. This plasmid allows for expression of bivalent GLP-1 peptide ligands as a result of IgG-Fc homodimerization. In vitro studies employing purified GLP-1/Fc indicate that the fusion protein is functional and elevates cAMP levels in insulin-secreting INS-1 cells. In addition, it stimulates insulin secretion in a glucose concentration-dependent manner. Intramuscular gene transfer of the plasmid in db/db mice demonstrated that expression of the GLP-1/Fc peptide normalizes glucose tolerance by enhancing insulin secretion and suppressing glucagon release. This strategy of using a bivalent GLP-1/Fc fusion protein as a therapeutic agent is a novel approach for the treatment of diabetes.
Animals↗
Metabolic activation of glucose low-responsive beta-cells by glyceraldehyde correlates with their biosynthetic activation in lower glucose concentration range but not at high glucose.
Insulin synthesis and release activities of beta-cells can be acutely regulated by glucose through its glycolytic and mitochondrial breakdown involving a glucokinase-dependent rate-limiting step. Isolated beta-cell populations are composed of cells with intercellular differences in acute glucose responsiveness that have been attributed to differences in glucokinase (GK) expression and activity. This study first shows that glyceraldehyde can be used as GK-bypassing oxidative substrate and then examines whether the triose can metabolically activate beta-cells with low glucose responsiveness. Glyceraldehyde 1 mm induced a similar cellular (14)CO(2) output and metabolic redox state as glucose 4 mM. Using flow cytometric analysis, glyceraldehyde (0.25-2 mM) was shown to concentration-dependently increase the percent metabolically activated cells at all tested glucose concentrations (2.5-20 mM). Its ability to activate beta-cells that are unresponsive to the prevailing glucose level was further illustrated in glucose low-responsive cells that were isolated by flow sorting. Metabolic activation by glyceraldehyde was associated with an activation of nutrient-driven translational control proteins and an increased protein synthetic response to glucose, however not beyond the maximal rates that are inducible by glucose alone. It is concluded that glucose low-responsive beta-cells can be metabolically activated by the GK-bypassing glyceraldehyde, increasing their acute biosynthetic response to glucose but not their maximal glucose-inducible biosynthetic capacity, which is considered subject to chronic regulation.
Animals↗
Organic carbon and nitrogen stable isotopes in the intertidal sediments from the Yangtze Estuary, China.
The natural isotopic compositions and C/N elemental ratios of sedimentary organic matter were determined in the intertidal flat of the Yangtze Estuary. The results showed that the ratios of carbon and nitrogen stable isotopes were respectively -29.8 per thousand to -26.0 per thousand and 1.6 per thousand-5.5 per thousand in the flood season (July), while they were -27.3 per thousand to -25.6 per thousand and 1.7 per thousand-7.8 per thousand in the dry season (February), respectively. The delta(13)C signatures were remarkably higher in July than in February, and gradually increased from the freshwater areas to the brackish areas. In contrast, there were relatively complex seasonal and spatial changes in stable nitrogen isotopes. It was also reflected that delta(15)N and C/N compositions had been obviously modified by organic matter diagenesis and biological processing, and could not be used to trace the sources of organic matter at the study area. In addition, it was considered that the mixing inputs of terrigenous and marine materials generally dominated sedimentary organic matter in the intertidal flat. The contribution of terrigenous inputs to sedimentary organic matter was roughly estimated according to the mixing balance model of stable carbon isotopes.
Carbon Isotopes↗
Puerarin injection for unstable angina pectoris.
BACKGROUND: Puerarin is extracted from the Chinese herb puerariae lobata. Many users of Chinese herbal medicine believe that puerarin has positive effects in the treatment of coronary heart disease (CHD). In recent years puerarin injection has been widely used to treat CHD and angina pectoris. OBJECTIVES: To assess the benefits and harms of puerarin injection for unstable angina. SEARCH STRATEGY: The following electronic databases were searched: The Cochrane Controlled Trials Register on The Cochrane Library (Issue 3, 2004), MEDLINE (1995 to 2004), EMBASE (1995 to 2004), CBM (1995 to 2004), Chinese Cochrane Centre Controlled Trials Register (to 2004), Current Controlled Trials (www.controlled-trials.com) and The National Research Register. We also hand searched 60 Chinese traditional medicine journals. SELECTION CRITERIA: Randomised controlled trials undertaken on adults with unstable angina evaluating the following types of interventions: Puerarin injection compared to western drugs or placebo, or puerarin injection used with western drugs compared to western drugs alone. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed independently by two reviewers. Differences in data extraction and analysis were resolved by consensus, referring back to the original article. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: 20 trials involving 1240 people were included. All trials identified were classified as having a high risk of bias because of poor reported methodology. The duration of treatment was 7-20 days and no information supplied suggested longer follow-ups were conducted for any trials. This limited the observation to participants who were not undertaking normal activities of daily living. The primary outcome (death) was not report in any trial. For all the secondary outcome measures, frequency of acute angina attacks, improvements in ECG, doses and incidence of nitroglycerine needed and levels of plasma endothelin, there was no evidence that puerarin had better or worse effects to other conventional treatments. There was strong evidence to suggest that puerarin injection plus western drugs was a better treatment option than western drugs alone. AUTHORS' CONCLUSIONS: Puerarin injection may be effective in unstable angina when used in addition to conventional treatments. However, these finding should be interpreted with care because of the very low methodological quality of studies and potential publication bias. In the light of the findings, a more rigorously designed, randomised double-blind placebo-controlled trial is needed.
Adult↗
Measurement of forces inside a three-dimensional pile of frictionless droplets.
We present systematic and detailed measurements of interparticle contact forces inside three-dimensional piles of frictionless liquid droplets. We measured long-range chainlike correlations of the directions and magnitudes of large forces, thereby establishing the presence of force chains in three dimensions. Our correlation definition provides a chain persistence length of 10 mean droplet diameters, decreasing as load is applied to the pile. We also measured the angles between contacts and showed that the chainlike arrangement arises from the balance of forces. Moreover, we found that piles whose height was comparable to the chain persistence length exhibited substantially greater strain hardening than did tall piles, which we attributed to the force chains. Together, the results establish a connection between the microscopic force network and the elastic response of meso- or macroscopic granular piles. The conclusions drawn here should be relevant in jammed systems generally, including concentrated emulsions and piles of sand or other heavy particles.
Journal Article↗
Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI).
OBJECTIVE: To study whether emergent intracoronary autologous bone marrow cell transplantation (BMT) is applicable for the treatment of acute myocardial infarction (AMI). METHODS: 20 patients admitted within 24 h after the onset of a first AMI were randomly allocated to receive intracoronary autologous BMT (n = 10) or bone marrow supernatant (controls, n = 10) immediately after primary percutaneous coronary intervention. Left ventricular ejection fraction (LVEF), left ventricular end diastolic internal diameter (LVDd) and myocardial perfusion defect scores were examined respectively by echocardiography and single-photon emission computed tomography at one week and six months after AMI. RESULTS: From one week to six months after AMI, LVEF was enhanced from mean 53.8 (SD 9.2)% to 58.6 (9.9)% (p < 0.05) in the BMT group but was unchanged in the control group (58.2 (7.5)% v 56.3 (3.5)%, p > 0.05); LVDd remained unchanged (52.5 (2.8) v 52.1 (3.2) mm, p > 0.05) in the BMT group but was significantly enlarged in the control group (50.4 (6.0) v 55.2 (7.1) mm, p < 0.05). Additionally, myocardial perfusion defect scores decreased from 21 (11) to 13 (10) (p < 0.01) in the BMT group but were unchanged in the control group (20 (14) v 17 (15), p > 0.05). CONCLUSION: Emergent intracoronary transplantation of bone marrow mononuclear cells after AMI is practicable, and it improved cardiac function, prevented myocardial remodelling and increased myocardial perfusion at six months' follow up.
Bone Marrow Transplantation↗
Endogenous overproduction of beta-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells.
Although neurofibrillary tangles and senile plaques have been identified as the hallmark pathological changes in the brain of Alzheimer's disease (AD), the relationship between them is still not fully understood. In the present study, we have studied the effect of endogenously overproduced amyloid beta (A beta) on tau by using wild type amyloid precursor protein (APP) transfected (N2a/APP695), or Swedish mutant APP plus Delta 9 deleted presenilin-1 co-transfected (N2a/APPswe.Delta 9) and APP vector transfected (N2a/vector) cell lines. We measured the secreted and intracellular A beta, including A beta(1-40) and A beta(1-42), by Sandwich ELISA assay. It was shown that the levels of A beta were increased time-dependently in N2a/APP695 and N2a/APPswe.Delta 9 but not in N2a/vector upon butyric acid (BA) treatment. Compared with N2a/vector cells, tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was not extracted by RIPA buffer, and the SDS-extracted tau protein was hyperphosphorylated at Tau-1 and PHF-1 epitopes upon BA treatment. Obvious accumulation of the hyperphosphorylated tau in N2a/APP695 and N2a/APPswe.Delta 9 cells was observed at 48 h after BA treatment. The total level of the extracted tau was reduced in N2a/APP695 and N2a/APPswe.Delta 9 lines compared with N2a/vector cells by Western blot, and this reduction of total tau was also detected by immunofluorescence staining. No obvious alteration of tau mRNA was observed in both N2a/APP695 and N2a/APPswe.Delta 9 cells compared with N2a/vector. This study provides direct evidence demonstrating that endogenously overproduced A beta not only induces tau hyperphosphorylation but also decreases the level and solubility of tau in N2a cell lines.
Amyloid beta-Peptides↗
Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern.
Administration of non-steroidal anti-inflammatory agents reduces the risk of developing Alzheimer's disease in normal aging populations, an effect that may occur from inhibition of the cyclooxygenases, the rate-limiting enzymes in the formation of prostaglandins. In this study, we investigated whether increased activity of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, potentiates disease progression in a transgenic mouse model of Alzheimer's disease. To study the functional effects of COX-2 activity, male and female bigenic mice (amyloid precursor protein with Swedish mutation [APPswe]-presenilin-1 protein with deletion of exon 9 [PS1dE9] and trigenic COX-2/APPswe-PS1dE9) were behaviorally tested +/-administration of the selective COX-2 inhibitor celecoxib. Behavioral testing included a three-trial Y maze that measures spatial working and recognition memories and an open field task that tested levels of hyperactivity. Overexpression of COX-2 in APPswe-PS1dE9 mice resulted in specific deficits in spatial working memory in female but not male mice. These sex-specific deficits were abolished by pharmacological inhibition of COX-2 activity. Importantly, COX-2-associated deficits were dependent on co-expression of all three transgenes since COX-2 single transgenic and APPswe-PS1dE9 bigenic mice showed normal memory. Quantification of amyloid plaque load and total Abeta 40 and 42 peptides did not reveal significant differences in trigenic versus bigenic mice treated with either vehicle or celecoxib. Taken together, these data indicate an interaction between the effects of COX-2 and Abeta peptides on cognition that occurs in a sex-specific manner in the absence of significant changes in amyloid burden. These findings suggest that pathological activation of COX-2 may potentiate the toxicity of Abeta peptides, particularly in females, without significantly affecting Abeta accumulation.
Alzheimer Disease↗
Centrosomal proteins Nde1 and Su48 form a complex regulated by phosphorylation.
The centrosome modulates spindle formation and plays a critical role in guiding proper segregation of chromosomes during cell division. Centrosome aberrations, frequently seen in human tumors, may cause abnormal chromosome segregation and contribute to malignant transformation. To explore the components of the centrosomes, we previously identified a novel centrosomal protein called Su48. To further characterize the Su48-containing protein ensemble in the centrosome, we performed yeast two-hybrid screens and isolated a number of Su48-interacting molecules, including the centrosomal protein Nde1. Here, we demonstrate that Su48 can associate with Nde1. Moreover, we found that Nde1 is subjected to phosphorylation in vivo. In particular, we identified six putative Cdc2 phosphorylation sites in Nde1 and found that alteration of these sites diminishes phosphorylation by Cdc2 in vitro and affects the stability of Su48-Nde1 interactions and the centrosomal localization of Nde1. Ablation of Nde1 by gene specific small interfering RNA causes mitotic delay and cell death, coupled with a modest decrease in the incidence of the cells that harbor excessive centrosomes. Collectively, our findings indicate that Nde1 can form a protein complex with Su48 in the centrosome and plays an important role for successful mitosis.
Carrier Proteins↗
Thrombolytic therapy for pulmonary embolism.
BACKGROUND: Thrombolytic therapy is usually reserved for patients with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clot more rapidly than heparin and might reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhages. OBJECTIVES: To assess the effectiveness and safety of thrombolytic therapy in patients with acute PE. SEARCH STRATEGY: We sought trials through the Cochrane Peripheral Vascular Diseases Group's Specialised Register (January 18, 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (January 1966 to December 2004), EMBASE, CINAHL, LILACS and SCISEARCH (all November 2004). We also searched individual trial collections and private databases, along with bibliographies of relevant articles. Relevant medical journals were handsearched. The most recent search was on February 6, 2006. SELECTION CRITERIA: Randomised controlled trials that compared thrombolytic therapy with placebo or heparin or surgical intervention in patients with acute PE. We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two authors (DB and WQ) assessed the eligibility and quality of trials and extracted data. MAIN RESULTS: Results were similar between thrombolytics compared with heparin alone or placebo and heparin in terms of:a) death rate: odds ratio (OR) 0.89; 95% confidence interval (CI) 0.45 to 1.78; b) recurrence of pulmonary embolism: OR 0.63; 95% CI 0.33 to 1.20;c) major haemorrhagic events: OR 1.61; 95% CI 0.91 to 2.86;d) minor haemorrhagic events: OR 1.98; 95% CI 0.68 to 5.75. We found no trials comparing thrombolytic therapy to surgical intervention. Using recombinant tissue-type plasminogen activator (rt-PA) and heparin together compared to heparin alone appeared to reduce the need for further treatment for in-hospital events (OR 0.35; 95% CI 0.17 to 0.71). Thrombolytics improved haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment and echocardiograms to a greater extent than heparin alone. AUTHORS' CONCLUSIONS: We cannot conclude whether thrombolytic therapy is better than heparin for pulmonary embolism based on the limited evidence found. More double-blind RCTs, with subgroup analysis of patients presenting with haemodynamically stable acute pulmonary embolism compared to those patients with a haemodynamic unstable condition, are required.
Fibrinolytic Agents↗
p78/MCRS1 forms a complex with centrosomal protein Nde1 and is essential for cell viability.
The centrosome, an organelle that functions as the major microtubule-organizing center, plays an essential role in the formation of the mitotic spindle and guiding accurate chromosome segregation. Centrosome aberrations are frequently associated with various forms of human cancers and it is thought that defects in this organelle contribute to genomic instability and malignant transformation. We recently identified and characterized a centrosome-localized protein complex that is comprised of Su48 and Nde1. Disruption of the normal function of these proteins leads to abnormal cell division. To extend our understanding of how this protein complex operates, we sought to identify Nde1-interacting molecules by the yeast two-hybrid screening method. Here, we demonstrate that both Nde1 and Su48 can associate with p78/MCRS1, a protein implicated in cancer development. We found that, whereas the majority of p78 localizes to the nucleus as reported in earlier studies, a fraction of the p78 protein can be detected in the centrosome. Moreover, we determined that a region containing the forkhead-associated domain of p78 is involved in association with Nde1 and Su48, as well as in centrosomal localization. We also provide evidence that the association between p78 and Nde1 is regulated by phosphorylation on Nde1. Furthermore, abrogation of the endogenous p78 function by small interfering RNA knockdown causes cell death and a modest delay in mitosis. These results indicate that a subset of the p78 proteins comprises a component of the centrosome and that p78 is essential for cell viability.
Carrier Proteins↗
TRF2 inhibition promotes anchorage-independent growth of telomerase-positive human fibroblasts.
Although telomere instability is observed in human tumors and is associated with the development of cancers in mice, it has yet to be established that it can contribute to the malignant transformation of human cells. We show here that in checkpoint-compromised telomerase-positive human fibroblasts an episode of TRF2 inhibition promotes heritable changes that increase the ability to grow in soft agar, but not tumor growth in nude mice. This transforming activity is associated to a burst of telomere instability but is independent of an altered control of telomere length. Moreover, it cannot be recapitulated by an increase in chromosome breaks induced by an exposure to gamma-radiations. Since it can be revealed in the context of telomerase-proficient human cells, telomere dysfunction might contribute to cancer progression even at late stages of the oncogenesis process, after the telomerase reactivation step.
Alleles↗