High prognostic potential of glioblastoma stem cell analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10580-10580
Author(s):  
G. L. Banna ◽  
R. Pallini ◽  
L. Ricci-Vitiani ◽  
M. Signore ◽  
D. Lombardi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Outcome ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Long Term Culture ◽  
Cd133 Expression

10580 Background: Cancer stem cells (CSCs) are a rare cell population responsible for tumor development and maintenance. Recent studies have shown that glioblastoma stem cells express the CD133 marker and are resistant to radiotherapy and chemotherapy. However, clinical data based on the study of CSCs in patients with glioblastoma are not available yet. Methods: Glioblastoma samples from 44 patients treated with complete or partial tumorectomy, followed by radiotherapy and temozolomide were prospectively analyzed. Immunohistochemistry was performed to evaluate the prognostic value of the number of CD133+ cells present in tumors. Moreover, the relationship between the ability to generate long-term culture of tumorigenic cells in vitro and the clinical outcome of glioblastoma patients was tested. Results: CD133 expression did not show an overall prognostic value. CSC cultures were obtained from 14 of the 44 tumors (32%). The generation of CSCs emerged as significant independent prognostic factor by the Cox multivariate analyses, with an adjusted hazard ratio of 2.50 (95% CI, 1.04 to 6.06; P=0.004). The median overall survival among patients with tumors generating CSCs was 8.0 months (95% CI, 4.0 to 11.5), as compared with 15 months (95% CI, 11.0 to 19.0) among those without generation of CSCs (P=0.0002). The median progression-free survival was 3.5 months (95% CI, 2.0 to 6.0) for glioblastoma generating CSCs and 9.0 months (95% CI, 7.0 to 12.0) for glioblastoma not generating CSCs (P=0.0001). A higher CD133 expression significantly associated with tumors generating CSCs (P=0.006), and correlated with a higher risk of death in patients with tumors generating CSCs in vitro (hazard ratio of 1.65, 95% CI, 1.05 to 2.60; P=0.0285). Conclusions: Generation of long-term culture of tumorigenic CSCs in vitro from glioblastoma predicts a poor clinical outcome for patients, in terms of both overall and progression-free survival. In tumors generating CSCs, CD133 expression may have a prognostic value. No significant financial relationships to disclose.

cMET expression in HER2+ MBC patients with first-line lapatinib (L) treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1073-1073
Author(s):  
Y. Liu ◽  
L. Liu ◽  
H. Shi ◽  
J. G. Greger ◽  
K. D. Jackson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Los Angeles ◽  
Clinical Outcome ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Expression Levels ◽  
Combination Study ◽  
Her 2

1073 Background: Overexpression of MET correlates with poor prognosis in breast cancer (Garcia et al., 2007) and is a factor associated with decreased sensitivity to L in HER2+ breast tumor cell lines in vitro (Liu et al., submitted). To test whether MET expression was associated with resistance to L in the clinic we evaluated baseline tumor MET expression levels and clinical outcome to L in 64 patients who participated in the EGF20009 trial of monotherapy L as first-line treatment in HER2+ advanced or MBC. Methods: RNA was extracted from FFPE tumors and MET and HER-2 gene expression was measured by qRT-PCR (Response Genetics, Inc., Los Angeles, CA). The correlation between expression levels of MET, HER2, and clinical outcome (overall response and progression free survival) was performed using JMP software. Results: A trend towards an association with increased MET expression and decreased response (p < 0.054) was observed.. Patients with high HER2 and low MET gene expression had the longest PFS (median difference = ∼9 weeks) compared to patients with low HER2 and high MET gene expression (p < 0.0038). Conclusions: These data support investigating a combination study of L and GSK1363089, a multi-kinase MET inhibitor, in HER2+ BC patients with high MET gene expression. [Table: see text]

Reprogramming of Oncogene Expression in Gingival Mesenchymal Stem Cells Following Long-Term Culture In Vitro

2017 ◽  
Vol 19 (3) ◽  
pp. 159-170 ◽  
Author(s):  
Agnese Gugliandolo ◽  
Thangavelu Soundara Rajan ◽  
Domenico Scionti ◽  
Francesca Diomede ◽  
Placido Bramanti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture In Vitro ◽  
Long Term Culture ◽  
Oncogene Expression

scholarly journals qPCR analysis of mesenchymal stem cell marker expression during the long-term culture of canine adipocyte derived stem cells

2020 ◽  
Vol 8 (4) ◽  
pp. 139-145
Author(s):  
Rut Bryl ◽  
Claudia Dompe ◽  
Maurycy Jankowski ◽  
Katarzyna Stefańska ◽  
Afsaneh Golkar Narenji ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
Stem Cell Marker ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Long Term Culture ◽  
Marker Expression

AbstractDue to its availability and accessibility, adipose tissue has been the subject of various studies in many different medical fields and is believed to be a useful source of stem cells. The ability of ASCs to differentiate towards different cell lineages, with possibility of directing this differentiation, increases their possible clinical applications, and they have been widely employed in multiple therapies and treatment of different pathologies. However, a deeper understanding of the molecular mechanisms underlying the ASCs osteoblastic and chondrocyte differentiation may lead to novel applications treating a multitude of different bone-related diseases through techniques more likely meeting worldwide consensus. In this study, the RT-qPCR method was used to determine the changes in expression of ASC specific markers (CD105, CD73, CD14, CD34, CD90 and CD45) before and after long-term (14-day) in vitro cultures. To confirm the identity of the investigated cells, flow cytometry was used to evaluate the presence of positive (CD44, CD90) and negative (CD45, CD34) ASC markers. Overall, the results of the PCR analysis showed a significant change in expression of most of the marker genes, indicating significant changes in the cultured cells caused by their long-term culture, potentially altering their original stem-like characteristics.Running title: ASC marker expression during long-term in vitro culture

scholarly journals Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

2012 ◽  
Vol 6 (5) ◽  
pp. 1183-1189 ◽  
Author(s):  
XUE-YI LI ◽  
JIN DING ◽  
ZHAO-HUI ZHENG ◽  
XIAO-YAN LI ◽  
ZHEN-BIAO WU ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Immunosuppressive Activity ◽  
Culture In Vitro ◽  
Long Term Culture

Human placental decidua basalis-derived mesenchymal stem cells differentiate into dopamine neuron-like cells with no response to long-term culture in vitro

Neuroreport ◽  
2012 ◽  
Vol 23 (8) ◽  
pp. 513-518 ◽  
Author(s):  
Guo-hui Lu ◽  
Wang-shi Yong ◽  
Zhi-min Xu ◽  
Yi-quan Ke ◽  
Xiao-dan Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dopamine Neuron ◽  
Culture In Vitro ◽  
Long Term Culture ◽  
Decidua Basalis

scholarly journals Culture of spermatogonial stem cells and use of surrogate sires as a breeding technology to propagate superior genetics in livestock production: A systematic review

2021 ◽  
pp. 3235-3248
Author(s):  
Wilkister Nakami ◽  
Ambrose Ng'eno Kipyegon ◽  
James Nguhiu-Mwangi ◽  
Christian Tiambo ◽  
Stephen Kemp
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Data Extraction ◽  
Transgenic Animals ◽  
Spermatogonial Stem Cells ◽  
Published Data ◽  
Long Term Culture ◽  
Future Possibility

Background and Aim: Spermatogonial stem cells (SSCs) have previously been isolated from animals' testes, cultured in vitro, and successfully transplanted into compatible recipients. The SSC unique characteristic has potential for exploitation as a reproductive tool and this can be achieved through SSC intratesticular transplantation to surrogate sires. Here, we aimed at comprehensively analyzing published data on in vitro maintenance of SSC isolated from the testes of livestock animals and their applications. Materials and Methods: The literature search was performed in PubMed, Science Direct, and Google Scholar electronic databases. Data screening was conducted using Rayyan Intelligent Systematic Review software (https://www.rayyan.ai/). Duplicate papers were excluded from the study. Abstracts were read and relevant full papers were reviewed for data extraction. Results: From a total of 4786 full papers screened, data were extracted from 93 relevant papers. Of these, eight papers reported on long-term culture conditions (>1 month) for SSC in different livestock species, 22 papers on short-term cultures (5-15 days), 10 papers on transfection protocols, 18 papers on transplantation using different methods of preparation of livestock recipients, and five papers on donor-derived spermatogenesis. Conclusion: Optimization of SSC long-term culture systems has renewed the possibilities of utilization of these cells in gene-editing technologies to develop transgenic animals. Further, the development of genetically deficient recipients in the endogenous germline layer lends to a future possibility for the utilization of germ cell transplantation in livestock systems.

The Long-term Outcome After Resection of Intraspinal Nerve Sheath Tumors

Neurosurgery ◽  
2015 ◽  
Vol 77 (4) ◽  
pp. 585-593 ◽  
Author(s):  
Charlotte Marie Halvorsen ◽  
Pål Rønning ◽  
John Hald ◽  
Tom Børge Johannesen ◽  
Frode Kolstad ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Progression Free Survival ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Total Resection ◽  
Free Survival ◽  
Nerve Sheath Tumors ◽  
Nerve Sheath

Abstract BACKGROUND: The existing literature on recurrence rates and long-term clinical outcome after resection of intraspinal nerve sheath tumors is limited. OBJECTIVE: To evaluate progression-free survival, overall survival, and long-term clinical outcome in a consecutive series of 131 patients with symptomatic intraspinal nerve sheath tumors. METHODS: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status. RESULTS: Follow-up data are 100% complete; median follow-up time was 6.1 years. All patients (100%) had surgery as the first line of treatment; gross total resection was performed in 112 patients (85.5%) and subtotal resection in 19 patients (14.5%). Five-year progression-free survival was 89%. The following risk factors for recurrence were identified: neurofibroma, malignant peripheral nerve sheath tumor, subtotal resection, neurofibromatoses/schwannomatosis, and advancing age at diagnosis. More than 95% of patients had neurological function compatible with an independent life at follow-up. The rate of tumor recurrence in nonneurofibromatosis patients undergoing total resection of a single schwannoma was 3% (3/93), in comparison with a recurrence rate of 32% (12/38) in the remaining patients. CONCLUSION: Gross total resection is the gold standard treatment for patients with intraspinal nerve sheath tumors. In a time of limited health care resources, we recommend that follow-up be focused on the subgroup of patients with a high risk of recurrence. The benefit of long-term, yearly magnetic resonance imaging follow-up with respect to recurrence in nonneurofibromatosis patients undergoing gross total resection of a single schwannoma is, in our opinion, questionable.

scholarly journals Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

2019 ◽  
Vol 37 (31) ◽  
pp. 2815-2824 ◽  
Author(s):  
Emmanuel Bachy ◽  
John F. Seymour ◽  
Pierre Feugier ◽  
Fritz Offner ◽  
Armando López-Guillermo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Long Term Results ◽  
Induction Treatment ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
To Receive

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

scholarly journals Epigenetic drift during long-term culture of cells in vitro

2018 ◽  
Author(s):  
Julia Franzen ◽  
Theodoros Georgomanolis ◽  
Anton Selich ◽  
Chao-Chung Kuo ◽  
Reinhard Stöger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amplicon Sequencing ◽  
Cell Types ◽  
Ctcf Binding ◽  
Chromatin Conformation ◽  
Long Term Culture ◽  
Induced Pluripotent ◽  
Genomic Regions

AbstractCulture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. These changes might be due to an directly regulated epigenetic process, or to gradual deregulation of the epigenetic state, which is often referred to as “epigenetic drift”. We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated in the course of culture expansion of mesenchymal stem cells (MSCs) and other cell types. During reprogramming into induced pluripotent stem cells (iPSCs) particularly the culture-associated hypomethylation is reversed simultaneously with age-associated and pluripotency-associated DNAm changes. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated that upon passaging the DNAm patterns of neighboring CpGs become more complex without evidence of continuous pattern development and without association to oligoclonal subpolulations of MSCs at later passages. Circularized chromatin conformation capture (4C) revealed reproducible changes in nuclear organization between early and late passages, while there was no preferential interaction with other genomic regions that also harbor culture-associated DNAm changes. Chromatin immunoprecipitation of CTCF did not show significant differences during long-term culture of MSCs, however culture-associated hypermethylation was enriched at CTCF binding sites and hypomethylated CpGs were devoid of CTCF. Taken together, our results indicate that DNAm changes during culture-expansion resembles epigenetic drift, which seems to occur in relation to chromatin conformation.

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