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Zhao Bo - - 2010
Telomerase-negative immortalized cells maintain their telomeres through a telomerase-independent pathway termed alternative lengthening of telomeres (ALT). The mechanism of ALT is based on homologous recombination (HR). A hallmark of ALT cells is presence of a nuclear structure termed ALT-associated promyelocytic leukemia body (APB). Here, we demonstrated that hRAD21, an important ...
Raghuram Gorantla Venkata - - 2010
Ovarian surface epithelium is under constant physiological pressure to maintain its integrity. Environmental toxic exposure can contribute to degenerative pathologies including ovarian cancer. Based on our current understanding, we aimed at listing mechanistic insights that contribute to ovarian carcinogenesis after exposure to methyl isocyanate, an ubiquitous environmental pollutant. Ovarian epithelial ...
Takubo Kaiyo - - 2010
Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere dysfunction in the surrounding background epithelium of squamous cell carcinoma in situ (CIS) of the oesophagus, we measured telomere lengths of basal and parabasal cells of epithelia with and without ...
Moon Dong-Oh - - 2010
Up-regulation of telomerase activity is associated with immortalization and unlimited cell division in most cancer cells. Therefore, telomerase represents a particularly attractive target for anticancer therapy. Recent reports have suggested that beta-lapachone (LAPA), the product of the South American Tabebuia avellanedae tree, inhibits growth of tumor cells. However, the underlying ...
De Vos W H - - 2010
Telomeres are the complex end structures that confer functional integrity and positional stability to human chromosomes. Telomere research has long been dominated by length measurements and biochemical analyses. Recently, interest has shifted towards the role of their three-dimensional organization and dynamics within the nuclear volume. In the mammalian interphase nucleus, ...
Korotchkina Lioubov G - - 2010
Transient induction of p53 can cause reversible quiescence and irreversible senescence. Using nutlin-3a (a small molecule that activates p53 without causing DNA damage), we have previously identified cell lines in which nutlin-3a caused quiescence. Importantly, nutlin-3a caused quiescence by actively suppressing the senescence program (while still causing cell cycle arrest). ...
Wang Qin Q Seattle Institute for Biomedical and Clinical Research, VA Puget Sound Health Care System, Seattle, Washington. - - 2011
Therapy-induced accelerated cellular senescence (ACS) is a reversible tumor response to chemotherapy that is likely detrimental to the overall therapeutic efficacy of cancer treatment. To further understand the mechanism by which cancer cells can escape the sustained cell cycle arrest in ACS, we established a tissue culture model, in which ...
Ho Chin-Chin - - 2011
Metastasis suppressors and associated other regulators of cell motility play a critical initial role in tumor invasion and metastases. Benzyl isothiocyanate (BITC) is a hydrolysis compound of glucotropaeolin in dietary cruciferous vegetables. BITC has been found to exhibit prevention of cancers in laboratory animals and might also be chemoprotective in ...
Mariani Melissa M - - 2010
Originally identified in cultured cells, oncogenic cellular senescence is a growth-arrest mechanism which may inhibit tumor development by limiting the ability of cells to divide. However, literature shows that these cells secrete tumor-inducing and tumor-suppressing proteins leading to poor prognosis. Understanding the progression of oncogenic cellular senescence and associated mechanisms ...
Oh W - - 2010
In this study, we identified posttranslational regulation of human telomerase reverse-transcriptase (hTERT) by the E3 ligase Hdm2. The telomerase activity generated by exogenous hTERT in U2OS cells was reduced on adriamycin treatment. The overexpressed levels of hTERT were also decreased under the same conditions. These processes were reversed by treatment ...
Kikuchi Ikue - - 2010
Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells ...
Liu Yan - - 2010
Telomerase activity is found in various cell types including stem cells, neoplastic cells, and immortalized cells, suggesting a close association with their proliferation capacity. The telomeric repeat amplification protocol (TRAP) has been traditionally used to detect semi-quantitatively the telomerase activity by polyacrylamide gel electrophoresis (PAGE), which is difficult to apply ...
Vaziri H - - 2010
AIM: To determine whether transcriptional reprogramming is capable of reversing the developmental aging of normal human somatic cells to an embryonic state. MATERIALS & METHODS: An isogenic system was utilized to facilitate an accurate assessment of the reprogramming of telomere restriction fragment (TRF) length of aged differentiated cells to that ...
Joseph Immanual S - - 2010
Preventing the formation of dysfunctional telomeres is essential for genomic stability. In most organisms, the ribo-nucleoprotein reverse transcriptase telomerase is responsible for telomere GT-strand elongation. However, in telomerase-negative cells, low-frequency recombination mechanisms can avert lethality by elongating critically short telomeres. This study focuses on the involvement of the budding yeast ...
Chen W - - 2010
BACKGROUND AND PURPOSE: Telomere length must be maintained throughout cancer cell progression and proliferation. In most tumours, telomerase activity maintains telomere length. Therefore, telomerase is a target for cancer treatments. However, some cancer cells maintain telomere length through an alternative mechanism termed 'alternative lengthening of telomeres'. To determine how telomerase ...
Kujuro Yuki - - 2010
Mammalian aging is thought to be partially caused by the diminished capacity of stem/precursor cells to undergo self-renewing divisions. Although many cell-cycle regulators are involved in this process, it is unknown to what extent cell senescence, first identified as irreversible growth arrest in vitro, contributes to the aging process. Here, ...
Zhao Chen-Fu - - 2010
Immortal bovine mammary epithelial cell lines are useful for providing an efficient indicator for transgene expression and for the technological improvement of genetic modification. The preparation of hTERT (human telomerase reverse transcriptase)-mediated immortalized MECs (mammary epithelial cells) requires a down-regulation of p16(INK4a). Here, we report the establishment of two immortal ...
Giuliano Sandy - - 2010
Apoptosis and senescence are cellular failsafe programs that counteract excessive mitogenic signaling observed in cancer cells. Melanoma is known for its notorious resistance to apoptotic processes; therefore, senescence, which remains poorly understood in melanomas, can be viewed as a therapeutic alternative. Microphthalmia-associated transcription factor (MITF), in which its M transcript ...
George Joseph - - 2010
Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase that facilitates tumor cell invasion and proliferation. Telomerase and hTERT are remarkably upregulated in majority of cancers including glioblastoma. Interferon-gamma (IFN-gamma) modulates several cellular activities including cell cycle and multiplication through transcriptional regulation. The present investigation was designed to ...
Davoli Teresa T Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, - - 2010
Tetraploidization has been proposed as an intermediate step toward aneuploidy in human cancer but a general mechanism for the induction of tetraploidy during tumorigenesis is lacking. We report that tetraploidization occurs in p53-deficient cells experiencing a prolonged DNA damage signal due to persistent telomere dysfunction. Live-cell imaging revealed that these ...
Ding Caifeng - - 2010
On the basis of the extension reaction of a telomerase substrate (TS) primer in the presence of the telomerase, the inherent signal-transduction mechanism of the hairpin fluorescence probe, and the strand-displacement property of polymerase, an amplified fluorescence detection of telomerase activity in the cancer cells was described in this manuscript. ...
Kovalenko Olga A - - 2010
Telomerase is a reverse transcriptase specialized in telomere synthesis. The enzyme is primarily nuclear where it elongates telomeres, but many reports show that the catalytic component of telomerase (in humans called hTERT) also localizes outside of the nucleus, including in mitochondria. Shuttling of hTERT between nucleus and cytoplasm and vice ...
Wagner Wolfgang - - 2010
Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long-term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, ...
Zalzman Michal - - 2010
Exceptional genomic stability is one of the hallmarks of mouse embryonic stem (ES) cells. However, the genes contributing to this stability remain obscure. We previously identified Zscan4 as a specific marker for two-cell embryo and ES cells. Here we show that Zscan4 is involved in telomere maintenance and long-term genomic ...
Zahnreich Sebastian - - 2010
In the present study, we set out to investigate cytogenetic changes in the progeny of two normal human fibroblast cell strains after exposure to sparsely or densely ionizing irradiation (X-rays or 9.8 MeV u(-1) carbon ions). The cells were regularly subcultured up to senescence. The transition to senescence was determined ...
Waki Koji - - 2010
We previously reported that the telomere-targeting drug telomestatin induces apoptosis accompanied by G-tail reduction and dissociation of binding protein TRF2 from telomeres in cancer cell lines but not normal or human telomerase reverse transcriptase (hTERT)-immortalized cells. Because telomere-targeting drugs induce growth arrest in normal cells at higher doses, their development ...
Peeper Daniel S - - 2010
Senescence is increasingly recognized as a critical feature of mammalian cells to suppress tumorigenesis, acting together with cell death programs. Whether senescence, like programmed cell death, can be exploited therapeutically has been unclear. Pandolfi and coworkers now propose that PTEN-loss-induced cellular senescence (PICS) may be triggered in vivo for therapy.
Watanabe Shin - - 2010
Out of normal human fibroblasts OUMS-36 and three clones (T1, T2 and T3) of telomere reverse transcriptase gene (hTERT)-transfectants, telomere length is in order: T3 >T2 >T1 >>OUMS-36 (young) >>OUMS-36 (old), and telomerase activity is in order: T2 >T3 >T1 >>OUMS-36 (young, old), suggesting that telomere length may be roughly ...
Diener Thomas - - 2010
Mitotic cells in culture show a limited replicative potential and after extended subculturing undergo a terminal growth arrest termed cellular senescence. When cells reach the senescent phenotype, this is accompanied by a significant change in the cellular phenotype and massive changes in gene expression, including the upregulation of secreted factors. ...
Rodriguez-Brenes Ignacio A - - 2010
In normal somatic cells, telomere length shortens with each cell replication. This progressive shortening is associated with cellular senescence and apoptosis. Germ cells, stem cells, and the majority of cancer cells express telomerase, an enzyme that extends telomere length and, when expressed at sufficient levels, can immortalize or extend the ...
Shalaby T - - 2010
Embryonal tumours most commonly occur in the first few years of life and account for approximately 30% of childhood malignancies. Knowledge of these tumours' genetics has already impacted on their clinical management and further knowledge of their cellular immortalization will hopefully result in novel therapies. The ends of human chromosomes ...
Marión Rosa M - - 2010
Reprogramming of adult differentiated cells to a more pluripotent state has been achieved by various means, including somatic cell nuclear transfer (SCNT) and, more recently, by over expression of specific transcription factors to generate the so-called induced pluripotent stem (iPS) cells. Since telomeres play an important role in the maintenance ...
Yoon Jihee - - 2010
Lysosomes are a cell organelle type processing antimicrobial activity. Here, we investigate the lysosomal activity in a primary cell line, bovine aortic endothelial cells (BAECs), during cellular aging, based on the antimicrobial activity of lysosomes isolated from BAECs at cell passages 4, 6, 8, and 10. Cytochemical analysis of lysosomes ...
Calado Rodrigo T - - 2010
In this issue of Blood, Ugel and colleagues provide evidence that, in murine models, telomerase is an efficient target for adoptive cell therapy against a variety of cancer cells, but also can elicit an autoimmune response against B cells.(1).
Maehara Kayoko - - 2010
Cellular senescence is an irreversible growth arrest and is presumed to be a natural barrier to tumor development. Like telomere shortening, certain defects in chromosome integrity can trigger senescence; however, the roles of centromere proteins in regulating commitment to the senescent state remains to be established. We examined chromatin structure ...
Knecht Hans - - 2010
In Epstein-Barr virus (EBV) negative Hodgkin's cell lines and classical EBV-negative Hodgkin's lymphoma (HL), Reed-Sternberg cells (RS cells) represent end-stage tumor cells, in which further nuclear division becomes impossible because of sustained telomere loss, shortening and aggregation. However, the three-dimensional (3D) telomere organization in latent membrane protein 1 (LMP1)-expressing RS ...
Shin Dong-Myung - - 2011
Genetic material in the nucleus governs mechanisms related to cell proliferation, differentiation, and function. Thus, senescence and aging are directly tied to the change of nuclear function and structure. The most important mechanisms that affect cell senescence are: (i) telomere shortening; (ii) environmental stress-mediated accumulation of DNA mutations, and (iii) ...
Sasaki Motoko - - 2010
We investigated the pathologic significance of ductular reactions in chronic liver diseases with respect to cellular senescence. The expression of senescence-associated markers (p16(INK4a) and p21(WAF1/Cip1)), cell proliferation, cell cycle markers (cyclin D and cyclin A), and neural cell adhesion molecule (NCAM) was examined immunohistochemically in primary biliary cirrhosis (PBC, n ...
Yuan Furong F Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78245, - - 2010
Werner syndrome (WS) results from defects in the gene encoding WRN RecQ helicase. WS fibroblasts undergo premature senescence in culture. Because cellular senescence is a tumor suppressor mechanism, we examined whether WS fibroblasts exhibited reduced tumorigenicity, in comparison to control cells, in a model of experimental conversion of normal human ...
Kim Sahn-Ho - - 2010
The telomeric complex, shelterin, plays a critical role in protecting chromosome ends from erosion, and disruption of these complexes can lead to chromosomal instability culminating in cell death or malignant transformation. We reported previously that dominant-negative mutants of one of the telomeric proteins called TIN2 cause death of androgen receptor ...
Guarente Leonard - - 2010
Propagation of a species requires periodic cell renewal to avoid clonal senescence. Liu et al. (2010) now describe a new mechanism of cell renewal in budding yeast, in which damaged protein aggregates are transported out of the daughter buds along actin cables to preserve youthfulness.
Lim Jae Sung - - 2010
Elderly individuals have an increased susceptibility to microbial infections because of age-related anatomical, physiological, and environmental factors. However, the mechanism of aging-dependent susceptibility to infection is not fully understood. Here, we found that caveolae-dependent endocytosis is elevated in senescent cells. Thus, we focused on the implications of caveolae-dependent endocytosis using ...
Vidacek Nikolina Skrobot - - 2010
Aging is one of the most basic properties of living organisms. Abundant evidence supports the idea that cell senescence underlies organismal aging in higher mammals. Therefore, examining the molecular mechanisms that control cell and replicative senescence is of great interest for biology and medicine. Several discoveries strongly support telomere shortening ...
Li Guorong - - 2010
To investigate the alterations in microRNA (miRNA) expression during replicative senescence (RS) in human trabecular meshwork (HTM) cells. Two HTM cell lines were serially passaged until they reached RS. Changes in expression of 30 miRNAs were assessed by real-time quantitative (q)-PCR. The effects of miR-146a on gene expression were analyzed ...
Cogan Nicola - - 2010
The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem ...
Young Andrew Rj - - 2010
Cellular senescence is an extremely stable form of cell cycle arrest activated in response to stress. Autophagy, a lysosome-dependent cellular catabolic process, can also be triggered by cellular stresses. Both senescence and autophagy have been implicated in a similar range of pathophysiologies, including cancer, aging and age-related symptoms. Senescence is ...
Choi Mi Jin - - 2010
The anti-aging effects of cyanidin were investigated under stress-induced premature senescence (SIPS) using WI-38 human diploid fibroblasts. WI-38 cells that were treated with 300 microM H(2)O(2) showed losses of cell viability, increased lipid peroxidation, and shortened cell lifespans. However, treatment with cyanidin attenuated cellular oxidative stress through increase of cell ...
Karimi-Busheri Feridoun - - 2010
INTRODUCTION: A subpopulation of cancer cells, tumor-initiating cells, is believed to be the driving force behind tumorigenesis and resistance to radiation and chemotherapy. The persistence of tumor-initiating cells may depend on altered regulation of DNA damage and checkpoint proteins, as well as a reduced propensity to undergo apoptosis or senescence. ...
Yoshitake Kazutoshi - - 2010
The ends of chromosomes, termed telomeres consist of repetitive DNA. The telomeric sequences shorten with cell division and, when telomeres are critically abbreviated, cells stop proliferating. However, in cancer cells, by the expression of telomerase which elongates telomeres, the cells can continue proliferating. Many approaches for telomere shortening have been ...
Wesbuer Simone - - 2010
BACKGROUND: Telomerase activity compensates shortening of telomeres during cell division and enables cancer cells to escape senescent processes. It is also supposed, that telomerase is associated with radio- and chemoresistance. In the here described study we systematically investigated the influence of telomerase activity (TA) and telomere length on the outcome ...
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