scholarly journals The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy

2021 ◽  
Vol 22 (8) ◽  
pp. 3863
Author(s):  
Vincenzo Mattei ◽  
Francesca Santilli ◽  
Stefano Martellucci ◽  
Simona Delle Monache ◽  
Jessica Fabrizi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Radical Surgery ◽  
Cellular Heterogeneity ◽  
Molecular Characteristics ◽  
Tumor Stem Cells ◽  
Current Standard ◽  
New Approach ◽  
Experimental Therapies ◽  
Technical Advances ◽  
New Anticancer Drugs

Glioblastoma (GBM) is known to be the most common and lethal primary malignant brain tumor. Therapies against this neoplasia have a high percentage of failure, associated with the survival of self-renewing glioblastoma stem cells (GSCs), which repopulate treated tumors. In addition, despite new radical surgery protocols and the introduction of new anticancer drugs, protocols for treatment, and technical advances in radiotherapy, no significant improvement in the survival rate for GBMs has been realized. Thus, novel antitarget therapies could be used in conjunction with standard radiochemotherapy approaches. Targeted therapy, indeed, may address specific targets that play an essential role in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Significant cellular heterogeneity and the hierarchy with GSCs showing a therapy-resistant phenotype could explain tumor recurrence and local invasiveness and, therefore, may be a target for new therapies. Therefore, the forced differentiation of GSCs may be a promising new approach in GBM treatment. This article provides an updated review of the current standard and experimental therapies for GBM, as well as an overview of the molecular characteristics of GSCs, the mechanisms that activate resistance to current treatments, and a new antitumor strategy for treating GSCs for use as therapy.

scholarly journals Brain tumor stem cells: Molecular characteristics and their impact on therapy

2014 ◽  
Vol 39 ◽  
pp. 82-101 ◽  
Author(s):  
David L. Schonberg ◽  
Daniel Lubelski ◽  
Tyler E. Miller ◽  
Jeremy N. Rich
Keyword(s):  
Stem Cells ◽  
Brain Tumor ◽  
Molecular Characteristics ◽  
Tumor Stem Cells ◽  
Brain Tumor Stem Cells

scholarly journals Tumor stem cells: A new approach for tumor therapy (Review)

2012 ◽  
Vol 4 (2) ◽  
pp. 187-193 ◽  
Author(s):  
MIN MENG ◽  
XIN-HAN ZHAO ◽  
QIAN NING ◽  
LEI HOU ◽  
GUO-HONG XIN ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Therapy ◽  
Tumor Stem Cells ◽  
New Approach

Therapeutic Role of Bmi-1 Inhibitors in Eliminating Prostate Tumor Stem Cells

2013 ◽  
Author(s):  
Isaac Y. Kim ◽  
Joseph Bertino ◽  
Hatem E. Sabaawy
Keyword(s):  
Stem Cells ◽  
Prostate Tumor ◽  
Tumor Stem Cells ◽  
Therapeutic Role

Recent approaches for isolating and culturing mouse bone marrow-derived mesenchymal stromal stem cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Basem M. Abdallah ◽  
Hany M. Khattab
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Molecular Mechanisms ◽  
Replicative Senescence ◽  
Cellular Heterogeneity ◽  
High Yield ◽  
Mouse Strains ◽  
Mouse Bone Marrow ◽  
Differentiation Potential ◽  
Stromal Stem Cells

: The isolation and culture of murine bone marrow-derived mesenchymal stromal stem cells (mBMSCs) have attracted great interest in terms of the pre-clinical applications of stem cells in tissue engineering and regenerative medicine. In addition, culturing mBMSCs is important for studying the molecular mechanisms of bone remodelling using relevant transgenic mice. Several factors have created challenges in the isolation and high-yield expansion of homogenous mBMSCs; these factors include low frequencies of bone marrow-derived mesenchymal stromal stem cells (BMSCs) in bone marrow, variation among inbred mouse strains, contamination with haematopoietic progenitor cells (HPCs), the replicative senescence phenotype and cellular heterogeneity. In this review, we provide an overview of nearly all protocols used for isolating and culturing mBMSCs with the aim of clarifying the most important guidelines for culturing highly purified mBMSC populations retaining in vitro and in vivo differentiation potential.

scholarly journals The Potential of Nail Mini-Organ Stem Cells in Skin, Nail and Digit Tips Regeneration

2021 ◽  
Vol 22 (6) ◽  
pp. 2864
Author(s):  
Anna Pulawska-Czub ◽  
Tomasz D. Pieczonka ◽  
Paula Mazurek ◽  
Krzysztof Kobielak
Keyword(s):  
Stem Cells ◽  
Critical Role ◽  
Nail Plate ◽  
Molecular Characteristics ◽  
Continuous Growth ◽  
Physiological Conditions ◽  
Morphogenetic Protein ◽  
Slow Cycling ◽  
Bifunctional Properties

Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.

scholarly journals DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4011
Author(s):  
Brianna Chen ◽  
Dylan McCuaig-Walton ◽  
Sean Tan ◽  
Andrew P. Montgomery ◽  
Bryan W. Day ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Critical Role ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Cellular Heterogeneity ◽  
Differentiation Potential ◽  
Glioblastoma Stem Cells ◽  
Glioblastoma Stem Cell

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Herein, we demonstrate that DYRK1A kinase is crucial for the differentiation commitment of glioblastoma stem cells. DYRK1A inhibition insulates the self-renewing population of GSCs from potent differentiation-inducing signals. Mechanistically, we show that DYRK1A promotes differentiation and limits stemness acquisition via deactivation of CDK5, an unconventional kinase recently described as an oncogene. DYRK1A-dependent inactivation of CDK5 results in decreased expression of the stemness gene SOX2 and promotes the commitment of GSC to differentiate. Our investigations of the novel DYRK1A-CDK5-SOX2 pathway provide further insights into the mechanisms underlying glioblastoma stem cell maintenance.

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