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Proliferation Marker Ki-67 (proliferation + marker_ki-67)
Selected AbstractsAberrant expression of cell-cycle regulator cyclin D1 in breast cancer is related to chromosomal genomic instabilityGENES, CHROMOSOMES AND CANCER, Issue 3 2002Jia-Chyi Lung To account for the accumulation of genomic alterations required for tumor progression, it has been suggested that the genomes of cancer cells are unstable and that this instability results from defective mutators (the "mutator phenotype" theory). To examine the hypothesis that abnormal cell-cycle regulators act as the mutators contributing to genomic instability, the present study, based on primary tumor tissues from 71 patients with breast cancer, was performed to determine whether there was an association between aberrant expression of cell-cycle regulators (cyclin A, cyclin D1, cyclin E, RB1, p21, and p27) and chromosomal instability. Comparative genomic hybridization was used to measure chromosomal changes, reflecting genomic instability in individual tumors, whereas immunohistochemistry was used to detect aberrant expression of cell-cycle regulators. Overexpression of cyclin D1 was found to be significantly correlated with increased chromosomal instability (defined as harboring more than 7 chromosomal changes), with 63% of tumors overexpressing and 27% of tumors not overexpressing, with cyclin D1 showing chromosomal instability (P < 0.05). Interestingly, this relationship was independent of cell outgrowth (as detected by the proliferation marker Ki-67) and was particularly significant in tumors not expressing p27 or in tumors with detectable RB1. These results suggest that cyclin D1 plays an alternative role in the regulation of genomic stability. © 2002 Wiley-Liss, Inc. [source] Disruption of the hyaluronan-based extracellular matrix in spinal cord promotes astrocyte proliferationGLIA, Issue 1 2005Jaime Struve Abstract Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high-molecular-weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high-MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)-positive cells that also express the nuclear proliferation marker Ki-67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high- but not low-MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high-MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation. © 2005 Wiley-Liss, Inc. [source] Effect of aging on neurogenesis in the canine brainAGING CELL, Issue 3 2008Anton Pekcec Summary An age-dependent decline in hippocampal neurogenesis has been reported in laboratory rodents. Environmental enrichment proved to be a strong trigger of neurogenesis in young and aged laboratory rodents, which are generally kept in facilities with a paucity of environmental stimuli. These data raise the question whether an age-dependent decline in hippocampal cell proliferation and neurogenesis can also be observed in individuals exposed to diversified and varying surroundings. Therefore, we determined rates of canine hippocampal neurogenesis using post-mortem tissue from 37 nonlaboratory dogs that were exposed to a variety of environmental conditions throughout their life. Expression of the neuronal progenitor cell marker doublecortin clearly correlated with age. The analysis of doublecortin-labeled cells in dogs aged > 133 months indicated a 96% drop in the aged canine brain as compared to young adults. Expression of the proliferation marker Ki-67 in the subgranular zone decreased until dogs were aged 85,132 months. In the aging canine brain amyloid-beta peptide deposits have been described that might resemble an early pathophysiological change in the course of human Alzheimer's disease. Comparison of Ki-67 and doublecortin expression in canine brain tissue with or without diffuse plaques revealed no differences. The data indicate that occurrence of diffuse plaques in the aging brain is not sufficient to trigger enhanced proliferation or enhanced neurogenesis such as described in human Alzheimer's disease. In addition, this study gives first proof that an age-dependent decline also dominates hippocampal neurogenesis rates in individuals living in diversified environments. [source] Differential Effects of Stress on Adult Hippocampal Cell Proliferation in Low and High Aggressive MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2007A. H. Veenema Male wild house mice selected for a long (LAL) or a short (SAL) latency to attack a male intruder generally show opposing behavioural coping responses to environmental challenges. LAL mice, unlike SAL mice, adapt to novel challenges with a highly reactive hypothalamic-pituitary-adrenal axis and show an enhanced expression of markers for hippocampal plasticity. The present study aimed to test the hypothesis that these features of the more reactive LAL mice are reflected in parameters of hippocampal cell proliferation. The data show that basal cell proliferation in the subgranular zone (SGZ) of the dentate gyrus, assessed by the endogenous proliferation marker Ki-67, is lower in LAL than in SAL mice. Furthermore, application of bromodeoxyuridine (BrdU) over 3 days showed an almost two-fold lower cell proliferation rate in the SGZ in LAL versus SAL mice. Exposure to forced swimming resulted, 24 h later, in a significant reduction in BrdU + cell numbers in LAL mice, whereas cell proliferation was unaffected by this stressor in SAL mice. Plasma corticosterone and dentate gyrus glucocorticoid receptor levels were higher in LAL than in SAL mice. However, no differences between the SAL and LAL lines were found for hippocampal NMDA receptor binding. In conclusion, the data suggest a relationship between coping responses and hippocampal cell proliferation, in which corticosterone may be one of the determinants of line differences in cell proliferation responses to environmental challenges. [source] Correlation of visinin-like-protein-1 expression with clinicopathological features in squamous cell carcinoma of the esophagusMOLECULAR CARCINOGENESIS, Issue 8 2006Carla Wickborn Abstract EF-hand Ca2+ -sensor proteins are key molecules for transducing Ca2+ signals into physiological answers and changes in cytosolic Ca2+ concentration control a variety of cellular responses, including proliferation, migration, and differentiation, which are relevant for tumor progression. The Ca2+ -sensor visinin-like protein-1 (VILIP-1) has recently attracted major interest due to its putative tumor suppressor function. Whereas VILIP-1 is expressed in normal skin, it is downregulated in skin tumors in a murine tumor model. The aim of this study was to investigate the expression of the Ca2+ -sensor VILIP-1 in squamous cell carcinoma of the esophagus and to correlate expression levels with clinicopathological features of the tumor. We examined VILIP-1 expression in 54 specimens of esophageal squamous cell carcinomas and 24 normal esophagus tissues, with immunohistochemical staining and immunofluorescence co-staining techniques. VILIP-1 expression was completely lost or significantly reduced in esophageal tumor tissue compared with normal squamous epithelium. Correlation with clinicopathological features indicated that there was significantly less VILIP-1 expression in lymph node positive (N,=,1) versus lymph node negative (N,=,0) tumors (P,=,0.002). Although there was no significant difference between highly (G1), moderately (G2) and poorly differentiated (G3) tumors (P,=,0.177), VILIP-1 expression in tumors is significantly correlated with the depth of tumor invasion (P,=,0.028 between T1, T2, T3, and T4). In contrast, co-staining with the proliferation marker Ki-67 indicated no significant correlation with proliferation rates in tumors (Ki-67 index of the tumor). In summary, the expression of the Ca2+ -sensor VILIP-1 was found to be lost during development of squamous cell carcinoma of the esophagus. The protein expression level significantly correlates with invasive features, such as depth of tumor invasion and local lymph node metastasis, but not with proliferation rate of tumor cells. © 2006 Wiley-Liss, Inc. [source] Effect of Long-Term Testosterone Administration on the Endometrium of Female-to-Male (FtM) TranssexualsTHE JOURNAL OF SEXUAL MEDICINE, Issue 11 2009Anna Myriam Perrone MD ABSTRACT Introduction., Long term safety of testosterone (T) administration in women is still unknown. In particular few and discordant data exists on the effects of T on the endometrium. Aim., The aim of this study was to investigate the effects of long-term T treatment on endometrium histology and proliferation in female to male transsexual subjects (FtM). We compared these endometria with those of young women in the proliferative phase (PM) of the cycle and with those of post menopausal women (M). Method., Endometrial samples from 27 FtM treated with T (intramuscular injection of 100 mg Testoviron Depot /10 days for at least one year), 30 M undergoing vaginal hysterectomy, and 13 PM undergoing hysteroscopy for infertility problems were collected. Endometrial proliferation was evaluated on the basis of histopathology and expression of the proliferation marker Ki-67. Both M and PM women had not received any hormonal treatment for at least one year. Main Outcome Measure., Circulating total testosterone (TT), estradiol (E), progesterone (P), insulin and glucose levels were measured in FtM and PM subjects. Results., FtM had received T for 33.6 ± 21.3 months (mean ± SD). In FtM subjects, histological analysis found inactive endometrium similar to the atrophic menopausal endometrium. The expression of Ki-67 in the glands, stroma and glands and stroma together was significantly (p < 0.0005) lower in FtM than in PM women and was similar in the FtM and M groups. Small polyps were detected in 5 of the 27 FtM subjects. Conclusions., In conclusion our data suggest that exogenous T administration does not stimulate endometrial proliferation in FtM transsexuals and indeed may have atrophic effects. Perrone AM, Cerpolini S, Salfi NCM, Ceccarelli C, Badiali De Giorgi L, Formelli G, Casadio P, Ghi T, Pelusi G, Pelusi C, and Meriggiola MC. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med 2009;6:3193,3200. [source] | |||||||||||||