Targeting the molecular mechanisms of glioma stem cell resistance to chemotherapy

2021 ◽  
pp. 587-634
Author(s):  
Jawad Fares ◽  
Deepak Kanojia ◽  
Alex Cordero ◽  
Ilya Ulasov ◽  
Maciej S. Lesniak
Keyword(s):  
Stem Cell ◽  
Molecular Mechanisms ◽  
Cell Resistance ◽  
Glioma Stem Cell ◽  
Resistance To Chemotherapy

scholarly journals OPTC-2. Identification of enriched genes and pathways associated to hypoxia induced migration in patient-derived glioma stem cell lines by RNAseq

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Olivia Morris Hanon ◽  
Yamil Mahmoud ◽  
Mariana Vera ◽  
Romina Girotti ◽  
Gabriel Rabinovich ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Migratory Behavior ◽  
Pathway Enrichment Analysis ◽  
Glioma Stem Cell ◽  
Diffuse Infiltration ◽  
Stem Cell Lines ◽  
The Individual

Abstract Glioblastomas (GBM), the most prevalent and lethal primary brain tumors, are characterized by high intertumoral heterogeneity, diffuse infiltration, and resistance to conventional therapies. Notably, the ability of tumor cells to invade surrounding tissues is one of their most damaging characteristics, it not only causes resistance to therapies such as surgery and radiotherapy but is ultimately the primary cause of death. Therapies that cause hypoxia (e.g. anti-angiogenic therapies) have been shown to increase invasiveness, leading to resistance to the therapy itself and further complications for the patients. Using patient-derived glioma stem cell lines (GSCL) we have discovered cell lines that display heterogeneous migratory behavior in response to hypoxia. As expected we observed that four GSCLs studied had increased migration in hypoxia. Strikingly, two other cell lines studied showed decreased migration in hypoxia. This unforeseen result reflects the heterogeneous nature of GBM and the difference between these GSCLs could be key to understanding this variable. To delve into the molecular context that could explain these differences we performed an exploratory RNAseq analysis on four of the GSCLs, two that showed hypoxia-induced migration and two with decreased migration in hypoxia, and evaluated genes differentially expressed in hypoxia versus normoxia. We also carried out gene ontology and pathway enrichment analysis to discover molecular and pathway patterns consistent with the migratory behaviors observed in each group of GSCLs. The results show how that a similar migratory response to hypoxia coincides with particular sets of enriched genes and pathways. Specifically, we found NOTCH and WNT signaling pathways upregulated in GSCLs which showed increased migration in hypoxia while the IFN-gamma pathway upregulated in GSCLs with decreased migration in hypoxia. Knowing the individual molecular mechanisms responsible for the migratory behavior could allow for tailor-made therapies that reduce the dissemination of these tumors.

scholarly journals Secondary Data Analytics of Aquaporin Expression Levels in Glioblastoma Stem-Like Cells

2015 ◽  
Vol 14 ◽  
pp. CIN.S22058 ◽  
Author(s):  
Raphael D. Isokpehi ◽  
Katharina C. Wollenberg Valero ◽  
Barbara E. Graham ◽  
Maricica Pacurari ◽  
Jennifer N. Sims ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Data Analytics ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
Secondary Data ◽  
Tumor Formation ◽  
Stem Cell Marker ◽  
Glioma Stem Cell ◽  
Expression Levels

Glioblastoma is the most common brain tumor in adults in which recurrence has been attributed to the presence of cancer stem cells in a hypoxic microenvironment. On the basis of tumor formation in vivo and growth type in vitro, two published microarray gene expression profiling studies grouped nine glioblastoma stem-like (GS) cell lines into one of two groups: full (GSf) or restricted (GSr) stem-like phenotypes. Aquaporin-1 (AQP1) and aquaporin-4 (AQP4) are water transport proteins that are highly expressed in primary glial-derived tumors. However, the expression levels of AQP1 and AQP4 have not been previously described in a panel of 92 glioma samples. Therefore, we designed secondary data analytics methods to determine the expression levels of AQP1 and AQP4 in GS cell lines and glioblastoma neurospheres. Our investigation also included a total of 2,566 expression levels from 28 Affymetrix microarray probe sets encoding 13 human aquaporins (AQP0–AQP12); CXCR4 (the receptor for stromal cell derived factor-1 [SDF-1], a potential glioma stem cell therapeutic target]); and PROM1 (gene encoding CD133, the widely used glioma stem cell marker). Interactive visual representation designs for integrating phenotypic features and expression levels revealed that inverse expression levels of AQP1 and AQP4 correlate with distinct phenotypes in a set of cell lines grouped into full and restricted stem-like phenotypes. Discriminant function analysis further revealed that AQP1 and AQP4 expression are better predictors for tumor formation and growth types in glioblastoma stem-like cells than are CXCR4 and PROM1. Future investigations are needed to characterize the molecular mechanisms for inverse expression levels of AQP1 and AQP4 in the glioblastoma stem-like neurospheres.

scholarly journals Mechanisms of Resistance to Chemotherapy in Breast Cancer and Possible Targets in Drug Delivery Systems

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1193
Author(s):  
Patrícia de Faria Lainetti ◽  
Antonio Fernando Leis-Filho ◽  
Renee Laufer-Amorim ◽  
Alexandre Battazza ◽  
Carlos Eduardo Fonseca-Alves
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Integrative Approach ◽  
Cell Resistance ◽  
Chemotherapy Treatment ◽  
Mechanisms Of Resistance ◽  
Literature Information ◽  
Therapeutic Perspective ◽  
Resistance To Chemotherapy ◽  
Tumor Cell Resistance

Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involved in BC chemoresistance and extract from the previous literature information regarding the use of nanoparticles as potential treatment for chemoresistant breast cancer.

scholarly journals Glucocorticoids promote a glioma stem cell-like phenotype and resistance to chemotherapy in human glioblastoma primary cells: Biological and prognostic significance

2017 ◽  
Vol 142 (6) ◽  
pp. 1266-1276 ◽  
Author(s):  
Ourania N. Kostopoulou ◽  
Abdul-Aleem Mohammad ◽  
Jiri Bartek ◽  
Julia Winter ◽  
Masany Jung ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Significance ◽  
Primary Cells ◽  
Glioma Stem Cell ◽  
Human Glioblastoma ◽  
Resistance To Chemotherapy

Endometrial Regeneration in Asherman's Syndrome: Clinical and Translational evidence of Stem Cell Therapies

2019 ◽  
Vol 14 (6) ◽  
pp. 454-459
Author(s):  
Xuejing Hou ◽  
Ying Liu ◽  
Isabelle Streuli ◽  
Patrick Dällenbach ◽  
Jean Dubuisson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Mechanisms ◽  
Uterine Cavity ◽  
Stem Cell Therapies ◽  
Intrauterine Adhesions ◽  
Asherman’S Syndrome ◽  
Cell Therapies ◽  
Fibrotic Process ◽  
Physical Barriers

Asherman’s Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman’s syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman’s Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

scholarly journals The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 453
Author(s):  
Susana M. Chuva de Sousa Lopes ◽  
Marta S. Alexdottir ◽  
Gudrun Valdimarsdottir
Keyword(s):  
Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cell Model ◽  
Embryonic Stem ◽  
Model Systems ◽  
Special Focus ◽  
Placental Development

Emerging data suggest that a trophoblast stem cell (TSC) population exists in the early human placenta. However, in vitro stem cell culture models are still in development and it remains under debate how well they reflect primary trophoblast (TB) cells. The absence of robust protocols to generate TSCs from humans has resulted in limited knowledge of the molecular mechanisms that regulate human placental development and TB lineage specification when compared to other human embryonic stem cells (hESCs). As placentation in mouse and human differ considerably, it is only with the development of human-based disease models using TSCs that we will be able to understand the various diseases caused by abnormal placentation in humans, such as preeclampsia. In this review, we summarize the knowledge on normal human placental development, the placental disease preeclampsia, and current stem cell model systems used to mimic TB differentiation. A special focus is given to the transforming growth factor-beta (TGFβ) family as it has been shown that the TGFβ family has an important role in human placental development and disease.

scholarly journals Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Physical Exercise ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Stem Cell Biology ◽  
Myocardial Repair ◽  
Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

scholarly journals Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

2021 ◽  
Vol 22 (3) ◽  
pp. 1201
Author(s):  
Hsuan Peng ◽  
Kazuhiro Shindo ◽  
Renée R. Donahue ◽  
Ahmed Abdel-Latif
Keyword(s):  
Stem Cell ◽  
Immune Responses ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Current Knowledge ◽  
Cell Delivery ◽  
Cardiac Cell Therapy ◽  
Stem Cell Treatment

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

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