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51.
Mathematical modeling of tumor-induced angiogenesis 总被引:10,自引:0,他引:10
Journal of Mathematical Biology - 相似文献
52.
Monica Cattaneo Simona Baronchelli Davide Schiffer Marta Mellai Valentina Caldera Gloria Jotti Saccani Leda Dalpra Antonio Daga Rosaria Orlandi Pasquale DeBlasio Ida Biunno 《The Journal of biological chemistry》2014,289(5):2826-2838
Valproic acid (VPA), an histone deacetylase inhibitor, is emerging as a promising therapeutic agent for the treatments of gliomas by virtue of its ability to reactivate the expression of epigenetically silenced genes. VPA induces the unfolded protein response (UPR), an adaptive pathway displaying a dichotomic yin yang characteristic; it initially contributes in safeguarding the malignant cell survival, whereas long-lasting activation favors a proapoptotic response. By triggering UPR, VPA might tip the balance between cellular adaptation and programmed cell death via the deregulation of protein homeostasis and induction of proteotoxicity. Here we aimed to investigate the impact of proteostasis on glioma stem cells (GSC) using VPA treatment combined with subversion of SEL1L, a crucial protein involved in homeostatic pathways, cancer aggressiveness, and stem cell state maintenance. We investigated the global expression of GSC lines untreated and treated with VPA, SEL1L interference, and GSC line response to VPA treatment by analyzing cell viability via MTT assay, neurosphere formation, and endoplasmic reticulum stress/UPR-responsive proteins. Moreover, SEL1L immunohistochemistry was performed on primary glial tumors. The results show that (i) VPA affects GSC lines viability and anchorage-dependent growth by inducing differentiative programs and cell cycle progression, (ii) SEL1L down-modulation synergy enhances VPA cytotoxic effects by influencing GSCs proliferation and self-renewal properties, and (iii) SEL1L expression is indicative of glioma proliferation rate, malignancy, and endoplasmic reticulum stress statuses. Targeting the proteostasis network in association to VPA treatment may provide an alternative approach to deplete GSC and improve glioma treatments. 相似文献
53.
Peter A. Forsyth Niveditha Krishna Samuel Lawn J. Gerardo Valadez Xiaotao Qu David A. Fenstermacher Michelle Fournier Lisa Potthast Prakash Chinnaiyan Geoffrey T. Gibney Michele Zeinieh Philip A. Barker Bruce D. Carter Michael K. Cooper Rajappa S. Kenchappa 《The Journal of biological chemistry》2014,289(12):8067-8085
Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target. 相似文献
54.
This paper illustrates how to apply methods of systems analysis, control theory and simulation to the field of biology and medicine. For this purpose normal and abnormal cell growth has been modelled at different levels. It was possible to simulate three-dimensional tumor growth and different kinds of treatment. The paper shows how tumor treatment may be optimized in the long run using computer simulation experiments as a powerful new tool prior to clinical therapy. 相似文献
55.
K. Evangelou C. Balaskas E. Marinos T. Dosios C. Kittas V. G. Gorgoulis 《Biotechnic & histochemistry》2002,77(2):85-91
C-mos is a cytoplasmic upstream activator of the mitogen-activating protein kinase pathway with serine-threonine kinase activity. It plays a well established and vital role in oocyte maturation by participating in metaphase II arrest and meiotic asymmetric division, but little is known about its function in somatic cells. Recently, we observed overexpressed c-mos in a portion of non-small cell lung carcinomas (NSCLCS). In particular, c-mos immunoreactivity was detected in tumor cell nuclei in addition to its expected cytoplasmic localization, and c-mos overexpression was associated with chromosomal instability among other findings. To verify our earlier observations and to clarify further the role of c-mos in NSCLCS, we examined its distribution by both light and electron microscopy. We detected c-mos in the cytoplasm and/or nucleus of a portion of tumor cells and fibroblasts. In particular, granular immunoreactivity was observed in the cytoplasm closely associated with the rough endoplasmic reticulum. Nuclear staining was confirmed and was often found near the nuclear membrane, as well as in some large multilobular, possibly aneuploid, nuclei. C-mos positivity was also found in the nuclei of tumor cells undergoing apoptosis. Furthermore, c-mos was detected in areas with diminished vascularization. It should be noted that nuclear staining was found at the ultrastructural level more extensively than at the light microscope study. This suggests a masking effect by the hematoxylin nuclear counterstain. 相似文献
56.
Cristina Maccalli Samantha Scaramuzza Giorgio Parmiani 《Cancer immunology, immunotherapy : CII》2009,58(5):801-808
Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety
of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including
most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B,
ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression
of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses.
Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging
both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell
clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression
of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore,
through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that
still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance
of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs
expression by tumor cells.
This paper is a focused research review based on a presentation given at the sixth annual meeting of the Association for Immunotherapy
of Cancer (CIMT), held in Mainz, Germany, 15–16 May 2008. 相似文献
57.
DNA methylation of embryogenic carrot cell cultures and its variations as caused by mutation,differentiation, hormones and hypomethylating drugs 总被引:7,自引:0,他引:7
F. LoSchiavo L. Pitto G. Giuliano G. Torti V. Nuti-Ronchi D. Marazziti R. Vergara S. Orselli M. Terzi 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1989,77(3):325-331
Summary The level of auxin - both natural and synthetic — in the medium has a strong effect on the level of 5-methyl-cytosine in the DNA of carrot cells in culture. This level may vary from approximately 15% to 70% of total cytosine without apparent effects on growth rate and cell morphology. No effect was seen with cytokinin. During somatic embryogenesis, in the absence of hormones, variations were seen in the level of methylation according to a characteristic pattern. If hypomethylation is induced with drugs such as azacytidine, ethionine or ethoxy-carbonyl-pyrimidine, embryogenesis is immediately blocked. A mutant was isolated which is resistant to the action of hypomethylating drugs. It shows variations in the methylation pattern and variations in indole-acetic acid metabolism. In addition its regeneration is often associated with the production of tumors.Deceased 相似文献
58.
BackgroundIntravoxel incoherent motion (IVIM) plays an important role in predicting treatment responses in patient with nasopharyngeal carcinoma (NPC). The goal of this study was to develop and validate a radiomics nomogram based on IVIM parametric maps and clinical data for the prediction of treatment responses in NPC patients.MethodsEighty patients with biopsy-proven NPC were enrolled in this study. Sixty-two patients had complete responses and 18 patients had incomplete responses to treatment. Each patient received a multiple b-value diffusion-weighted imaging (DWI) examination before treatment. Radiomics features were extracted from IVIM parametric maps derived from DWI image. Feature selection was performed by the least absolute shrinkage and selection operator method. Radiomics signature was generated by support vector machine based on the selected features. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) values were used to evaluate the diagnostic performance of radiomics signature. A radiomics nomogram was established by integrating the radiomics signature and clinical data.ResultsThe radiomics signature showed good prognostic performance to predict treatment response in both training (AUC = 0.906, P<0.001) and testing (AUC = 0.850, P<0.001) cohorts. The radiomic nomogram established by integrating the radiomic signature with clinical data significantly outperformed clinical data alone (C-index, 0.929 vs 0.724; P<0.0001).ConclusionsThe IVIM-based radiomics nomogram provided high prognostic ability to treatment responses in patients with NPC. The IVIM-based radiomics signature has the potential to be a new biomarker in prediction of the treatment responses and may affect treatment strategies in patients with NPC. 相似文献
59.
在过去的一个世纪,许多肿瘤指标被发现,其中包括Galectin-3,它在肿瘤的发生与发展过程中所起的作用正日益受到重视。Galectin-3是凝集素超家族中的一员,它涉及多种生物功能,包括肿瘤细胞的粘附、增殖、分化及凋亡等过程。迄今为止,已有多项研究报道了galectin-3在不同肿瘤中的表达情况的相关性。本综述查阅了大量中外文献报道,旨在说明galectin-3的生物学特性以及它在各个系统肿瘤的发生、发展中所起到的作用。半乳糖凝集素-3在多种人恶性肿瘤细胞中都呈现出高表达的特性,与其在相应组织的正常细胞中的低表达或不表达相比有明显的差异,正是由于它的这种特性,使其有可能作为肿瘤诊断及治疗的一个可靠检测指标,并且为癌症在基因方面的治疗增加了新的内容,它可以成为治疗的靶基因。 相似文献