Adult Stem Cells and Anticancer Therapy

Kalvelytė, Audronė; Imbrasaitė, Aušra; Krestnikova, Natalija; Stulpinas, Aurimas

doi:10.1016/b978-0-12-812522-9.00004-x

Cited by 11 publications

(10 citation statements)

References 327 publications

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“…Advances in cancer modeling were nicely reviewed in publications [25,30,89,145,177,189,196,197]. In our previous publication [198], 3D drug testing models with end-point viability-measuring methods were presented, including scaffold-based 3D culture systems, tissue slices, cellular spheroids, organoids, and organs-on-chips. Having both models for normal tissues and a tumor from a single patient would improve the prediction of systemic toxicities to healthy stem cells.…”

Section: D In Vitro Modelsmentioning

confidence: 99%

Recent Approaches Encompassing the Phenotypic Cell Heterogeneity for Anticancer Drug Efficacy Evaluation

Stulpinas¹,

Imbrasaitė²,

Krestnikova³

et al. 2020

Tumor Progression and Metastasis

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Despite the advancements in biomarker-based personalized cancer therapy, the inadequacy of molecular and genetic profiling in identifying effective drug combinations was defined in most cases. Drug resistance remains a major limitation of the current predictive oncology. Emerging reports indicate that the success of anticancer therapy is usually limited by intratumoral heterogeneity which is not captured by the existing cancer cell biomarker-based approaches. Cell heterogeneity, not only genetic but also phenotypic, is considered to be the root cause of resistance to anticancer treatment, cancer progression, and the presence of cancer stem cells. Therefore, functional testing of live cells representing various cell types within the tumor exposed to potential therapies is needed for identification of effective drug combinations. Here we look at the different existing model systems, including ex vivo models of the patient's tumor cells, 2D/3D in vitro cultures/cocultures, patient-derived cellular organoids, single-cell models, ex vivo tumor platforms containing tumor microenvironment and extracellular matrix, etc., scoping at drug efficacy evaluation and solving the problem of cancer resistance.

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Section: D In Vitro Modelsmentioning

confidence: 99%

Recent Approaches Encompassing the Phenotypic Cell Heterogeneity for Anticancer Drug Efficacy Evaluation

Stulpinas¹,

Imbrasaitė²,

Krestnikova³

et al. 2020

Tumor Progression and Metastasis

Self Cite

View full text Add to dashboard Cite

show abstract

Section: D In Vitro Modelsmentioning

confidence: 99%

Tumor Progression and Metastasis

Lasfar¹,

Cohen‐Solal²

2020

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Tumor metastasis results from the spreading of a primary tumor and establishment of secondary tumors, mostly in vital organs such as the lung, liver, and brain. Tumor metastasis is responsible for the majority of cancer deaths, yet it remains the least understood stage of cancer.Metastatic tumor cells acquire new biological features allowing them to migrate, invade normal tissues, escape the immune system control, and develop drug resistance. Many mechanisms have been shown to play an important role in the metastatic process, particularly through the tumor microenvironment. Many factors present in the tumor microenvironment have been identified and demonstrated to play either a pro-or anti-metastatic role, allowing the development of new targeted therapies.However, despite an armamentarium of treatments, patients remain at a high risk for metastasis. Better understanding of the mechanisms leading to cancer metastasis is crucial for the development of novel and more efficacious therapies.Currently many research areas are involved in the identification of novel biological markers and therapeutic targets. Modern approaches including genomics, molecular biology, immunology, imaging and computational biology, are carried out in cancer research, leading to the development of novel therapeutic options. Many therapeutic options based on the manipulation or modulation of the immune system have shown unprecedented results and have provided new hope to cancer patients. The introduction of targeted and immune-based therapies have significantly improved the cancer survival rate. In addition to discussing relevant options of cancer treatment and ongoing clinical trials, recent breakthroughs in cancer development and metastasis are provided in this book.

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“…Mitochondrial membrane potential (MMP) is a marker of optimal mitochondrial function where mitochondrial depolarization can indicate mitochondrial dysfunction [15][16][17]. Depolarization and the loss of MMP impacts respiratory chain complexes, which interrupts cellular electron flow and results in ATP depletion [18][19][20][21]. Maintenance of MMP is fundamental for the normal performance and survival of cells that have a high-energy requirement [22], such as sensory neurons [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Antagonism of the Muscarinic Acetylcholine Type 1 Receptor Enhances Mitochondrial Membrane Potential and Expression of Respiratory Chain Components via AMPK in Human Neuroblastoma SH-SY5Y Cells and Primary Neurons

2022

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Impairments in mitochondrial physiology play a role in the progression of multiple neurodegenerative conditions, including peripheral neuropathy in diabetes. Blockade of muscarinic acetylcholine type 1 receptor (M1R) with specific/selective antagonists prevented mitochondrial dysfunction and reversed nerve degeneration in in vitro and in vivo models of peripheral neuropathy. Specifically, in type 1 and type 2 models of diabetes, inhibition of M1R using pirenzepine or muscarinic toxin 7 (MT7) induced AMP-activated protein kinase (AMPK) activity in dorsal root ganglia (DRG) and prevented sensory abnormalities and distal nerve fiber loss. The human neuroblastoma SH-SY5Y cell line has been extensively used as an in vitro model system to study mechanisms of neurodegeneration in DRG neurons and other neuronal sub-types. Here, we tested the hypothesis that pirenzepine or MT7 enhance AMPK activity and via this pathway augment mitochondrial function in SH-SY5Y cells. M1R expression was confirmed by utilizing a fluorescent dye, ATTO590-labeled MT7, that exhibits great specificity for this receptor. M1R antagonist treatment in SH-SY5Y culture increased AMPK phosphorylation and mitochondrial protein expression (OXPHOS). Mitochondrial membrane potential (MMP) was augmented in pirenzepine and MT7 treated cultured SH-SY5Y cells and DRG neurons. Compound C or AMPK-specific siRNA suppressed pirenzepine or MT7-induced elevation of OXPHOS expression and MMP. Moreover, muscarinic antagonists induced hyperpolarization by activating the M-current and, thus, suppressed neuronal excitability. These results reveal that negative regulation of this M1R-dependent pathway could represent a potential therapeutic target to elevate AMPK activity, enhance mitochondrial function, suppress neuropathic pain, and enhance nerve repair in peripheral neuropathy.

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Adult Stem Cells and Anticancer Therapy

Cited by 11 publications

References 327 publications

Recent Approaches Encompassing the Phenotypic Cell Heterogeneity for Anticancer Drug Efficacy Evaluation

Recent Approaches Encompassing the Phenotypic Cell Heterogeneity for Anticancer Drug Efficacy Evaluation

Tumor Progression and Metastasis

Antagonism of the Muscarinic Acetylcholine Type 1 Receptor Enhances Mitochondrial Membrane Potential and Expression of Respiratory Chain Components via AMPK in Human Neuroblastoma SH-SY5Y Cells and Primary Neurons

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