Stem cells for the treatment of glioblastoma: a 20-year perspective.
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ABSTRACT:
SUBMITTER: Calinescu AA
PROVIDER: S-EPMC8162173 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGranular data on gun sales has been historically difficult to obtain. In 2016, California (CA) made monthly data from 1996 to 2015 publically available. Control charts are a method to analyze how a process changes over time in response to nonroutine events. We utilized this technique to study the impact of US mass shootings on CA gun sales.MethodsMonthly gun sales were provided by the CA Department of Justice and monthly fatalities from the CDC Wonder Death Certificate Registry. Mass shooting events were obtained from after-action reports, news media, and court proceedings. Time-ordered data were analyzed with control charts with 95% confidence intervals (upper control limit, lower control limit) using QiMacros.ResultsIndividual gun sales of 9,917,811 occurred in CA with a median monthly rate of 41,324 (range, 20,057-132,903). A median of 263 people lost their lives monthly from firearms (124 homicides, 128 suicides), totaling 53,975 fatalities from 1999 to 2015. Fifteen of 21 current deadliest mass shootings occurred during this study period with 40% from 2012 to 2015. Also, 36 school shootings occurred during the study (mean, 5 deaths; range, 0-33; 6 injuries; range, 0-23) with 31% in 2012 to 2015 at rate of 3 events/year versus 1.4 events/year in the 17 prior years (p < 0.05). Sales were generally consistent from 1996 to 2011 (except post-Columbine, Col). Starting in 2011, sales exceeded the 95% predicted upper control limit every single month. Before October 2011, there was no statistically significant sustained effect of mass shootings on sales (except Col); however, since a statistically significant proportional spike in sales occurred in the months immediately following every single deadliest mass shooting event. Every year since 2012, CA has strengthened gun laws in response to mass shootings yet sales have risen immediately preceding enactment of these laws each January.ConclusionGun sales are more frequent since 2012, with an additional increase following both mass shootings and legislative changes enacted in response to these shootings.Level of evidenceEpidemiology, level III.
| S-EPMC7369030 | biostudies-literature
Project description:Hip resurfacing is an attractive concept because it preserves rather than removes the femoral head and neck. Most early designs had high failure rates, but one unique design had a femoral stem. Because that particular device appeared to have better implant survival, this study assessed the clinical outcome and long-term survivorship of a hip resurfacing prosthesis. Four hundred forty-five patients (561 hips) were retrospectively reviewed after a minimum of 20 years' followup or until death; 23 additional patients were lost to followup. Patients received a metal femoral prosthesis with a small curved stem. Three types of acetabular reconstructions were used: (1) cemented polyurethane; (2) metal-on-metal; and (3) polyethylene secured with cement or used as the liner of a two-piece porous-coated implant. Long-term results were favorable with the metal-on-metal combination only. The mean overall Harris hip score was 92 at 2 years of followup. None of the 121 patients (133 hips) who received metal-on-metal articulation experienced failure. The failure rate with polyurethane was 100%, and the failure rate with cemented polyethylene was 41%. Hip resurfacing with a curved-stem femoral component had a durable clinical outcome when a metal-on-metal articulation was used.
| S-EPMC2311483 | biostudies-other
Project description:ObjectivesTo evaluate the long-term treatment outcomes in intraocular retinoblastoma (RB) including the associated factors for eventual treatment with external beam radiotherapy (EBRT) and enucleation as well as to analyse the risk factors for metastasis and death in extraocular RB.MethodsRetrospective analysis of 390 eyes from 256 (89.8%) intraocular RB and 29 (10.2%) extraocular RB cases diagnosed and treated between October 1998 and May 2018 at one of the largest tertiary care centers in Turkey.ResultsOf 351 intraocular RB eyes, 53.3% had group D/E disease at presentation. 75 (21.4%) of 351 eyes underwent primary enucleation. Of the remaining 276 eyes undergoing eye-conserving treatments, 201 (72.8%) were salvaged. Most of these eyes were treated using intravenous chemotherapy and/or focal treatments [transpupillary thermotherapy (TTT) and cryotherapy] initially. EBRT was eventually required in 48 (17.4%) eyes and secondary enucleation in 75 (27.2%) eyes. At mean follow-ups of 76.7 and 39.7 months for intraocular and extraocular RB cohorts, respectively, 180 (46.2%) eyes underwent primary/secondary enucleation and exenteration. Overall, 13 cases developed metastasis and 9 died. Two patients with trilateral RB also expired. Multivariable risk factors for enucleation were the presence of vitreous seeds (p < 0.001), absence of EBRT administration (p = 0.033), 5-9 TTT applications compared with no TTT (p = 0.031), and each 1 mm increase in tumour base diameter (p < 0.001). Univariate factors predictive of metastasis were the presence of extraocular RB detected by imaging methods (p < 0.001) and extrascleral/optic nerve cut end involvement at histopathological examination (p < 0.001).ConclusionsIn our series, 72.8% of the intraocular RB eyes undergoing eye-conserving treatments were saved. The globe salvage rate for all intraocular and extraocular RB eyes was 53.8% and the overall survival rate was 96.1%.
| S-EPMC7608123 | biostudies-literature
Project description:Among all cancers, glioblastoma (GBM) remains one of the least treatable. One key factor in this resistance is a subpopulation of tumor cells termed glioma stem cells (GSCs). These cells are highly resistant to current treatment modalities, possess marked self-renewal capacity, and are considered key drivers of tumor recurrence. Further complicating an understanding of GBM, evidence shows that the GSC population is not a pre-ordained and static group of cells but also includes previously differentiated GBM cells that have attained a GSC state secondary to environmental cues. The metabolic behavior of GBM cells undergoing plasticity remains incompletely understood. To that end, we probed the connection between GSCs, environmental cues, and metabolism. Using patient-derived xenograft cells, mouse models, transcriptomics, and metabolic analyses, we found that cell state changes are accompanied by sharp changes in metabolic phenotype. Further, treatment with temozolomide, the current standard of care drug for GBM, altered the metabolism of GBM cells and increased fatty acid uptake both in vitro and in vivo in the plasticity driven GSC population. These results indicate that temozolomide-induced changes in cell state are accompanied by metabolic shifts-a potentially novel target for enhancing the effectiveness of current treatment modalities.
| S-EPMC7693784 | biostudies-literature
Project description:Glioblastoma stem cells after treatment with sulconazole.
| PRJNA628508 | ENA
Project description:Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research. We have previously demonstrated that PIM1 is involved in survival of GBM cells and in GBM growth in a mouse model. However, little is known about the importance of PIM1 in cancer stem cells. Here, we report on the role of PIM1 in GBM stem cell behavior and killing. PIM1 inhibition negatively regulates the protein expression of the stem cell markers CD133 and Nestin in GBM cells (LN-18, U-87 MG). In contrast, CD44 and the astrocytic differentiation marker GFAP were up-regulated. Furthermore, PIM1 expression was increased in neurospheres as a model of GBM stem-like cells. Treatment of neurospheres with PIM1 inhibitors (TCS PIM1-1, Quercetagetin, and LY294002) diminished the cell viability associated with reduced DNA synthesis rate, increased caspase 3 activity, decreased PCNA protein expression, and reduced neurosphere formation. Our results indicate that PIM1 affects the glioblastoma stem cell behavior, and its inhibition kills glioblastoma stem-like cells, pointing to PIM1 targeting as a potential anti-glioblastoma therapy.
| S-EPMC8541331 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
| S-ECPF-GEOD-46016 | biostudies-other
Project description:Comparison between glioblastoma stem cell lines driven to endothelial differentiation and endothelial cell cultures
| S-ECPF-MEXP-2891 | biostudies-other
Project description:When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues-the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells. In addition, menstrual blood stem cells are extracted in a non-invasive and painless manner. In our study, we analyzed the characteristics and the potential for decidualization of menstrual blood stem cells isolated from healthy volunteers and women diagnosed with infertility. We demonstrated that MenSCs express CD44, CD166, CD16, CD15, BMSC, CD56, CD13 and HLA-ABC surface markers, have proliferative properties, and after induction of menstrual stem cell differentiation into epithelial direction, expression of genes related to decidualization (PRL, ESR, IGFBP and FOXO1) and angiogenesis (HIF1, VEGFR2 and VEGFR3) increased. Additionally, the p53, p21, H3K27me3 and HyperAcH4 proteins' expression increased during MenSCs decidualization, they secrete proteins that are involved in the regulation of the actin cytoskeleton, estrogen and relaxin signaling pathways and the management of inflammatory processes. Our findings reveal the potential use of MenSCs for the treatment of reproductive disorders.
| S-EPMC8268036 | biostudies-literature
Project description:AimTo identify and characterize cancer stem cells (CSC) in glioblastoma multiforme (GBM).MethodsFour-micrometer thick formalin-fixed paraffin-embedded GBM samples from six patients underwent 3,3-diaminobenzidine (DAB) and immunofluorescent (IF) immunohistochemical (IHC) staining for the embryonic stem cell (ESC) markers NANOG, OCT4, SALL4, SOX2, and pSTAT3. IF IHC staining was performed to demonstrate co-expression of these markers with GFAP. The protein expression and the transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4, and STAT3 were investigated using Western blotting (WB) and NanoString gene expression analysis, respectively.ResultsDAB and IF IHC staining demonstrated the presence of a CSC population expressing NANOG, OCT4, SOX2, SALL4, and pSTAT3 with the almost ubiquitous presence of SOX2 and a relatively low abundance of OCT4, within GBM. The expression of NANOG, SOX2 and, pSTAT3 but, not OCT and SALL4, was confirmed by WB. NanoString gene analysis demonstrated transcriptional activation of NANOG, OCT4, SALL4, STAT3, and SOX2 in GBM.ConclusionThis study demonstrated a population of CSCs within GBM characterized by the expression of the CSC markers NANOG, SALL4, SOX2, pSTAT3 and OCT4 at the protein and mRNA levels. The almost ubiquitous presence of SOX2 and a relatively low abundance of OCT4 would support the putative existence of a stem cell hierarchy within GBM.
| S-EPMC5001191 | biostudies-literature