scholarly journals Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2746
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cell ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Therapeutic Strategy ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Effective Therapeutic Strategy ◽  
Cancer Types ◽  
The Brain

The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

scholarly journals Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Prakash Chinnaiyan ◽  
Alexander ARA Anderson ◽  
Anita Hjelmeland ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals The Gut Ecosystem: A Critical Player in Stroke

2020 ◽  
Author(s):  
Rosa Delgado Jiménez ◽  
Corinne Benakis
Keyword(s):  
Current Knowledge ◽  
Critical Factor ◽  
Intestinal Microbiome ◽  
Brain Disorders ◽  
Therapeutic Approaches ◽  
Health And Disease ◽  
Brain Stroke ◽  
The Brain ◽  
Improve Patient

AbstractThe intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

scholarly journals Glutamate and γ-aminobutyric acid differentially modulate glymphatic clearance of amyloid β through pulsation- and aquaporin-4 dependent mechanisms

2020 ◽  
Author(s):  
Cheng Wu ◽  
Yi-wei Feng ◽  
Qun Zhang ◽  
Feng-yin Liang ◽  
Yue Lan ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Amyloid Β ◽  
Aquaporin 4 ◽  
Aminobutyric Acid ◽  
Dependent Manner ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Effective Therapeutic Strategy ◽  
Glymphatic Pathway ◽  
The Brain

AbstractThe glymphatic system contributes to a large proportion of brain waste clearance, including removal of amyloid β (Aβ). We have demonstrated that glutamate and γ-aminobutyric acid (GABA) influence glymphatic clearance through distinct mechanisms whereby GABA exerts modulatory effects in an aquaporin-4 (AQP4)-dependent manner while the actions of glutamate are pulsation-dependent. The efficacy of GABA and glutamate in alleviating Aβ in APP-PS1 and Angiotensin-II (Ang-II) induced hypertension mouse models was further evaluated. Notably, increasing GABA or inhibiting glutamate levels led to reduced binding of Aβ to pre-labeled plaques to similar extents in APP-PS1 mice while GABA appeared more efficient in Aβ clearance in hypertensive animals than the glutamate inhibitor. Our findings support the modulation of neurotransmitters that influence the glymphatic pathway via distinct mechanisms as a potentially effective therapeutic strategy for clearance of Aβ deposits from the brain.

scholarly journals Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Prakash Chinnaiyan ◽  
Alexander ARA Anderson ◽  
Anita Hjelmeland ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals A Roadmap to Immunotherapy: Lesson from the Hallmarks and Signaling Pathways of Cancer

2020 ◽  
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Sina Taefehshokr ◽  
Neda Jalili Tabrizi ◽  
...  
Keyword(s):  
Single Cell ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Therapeutic Approaches ◽  
The Road ◽  
Profiling Techniques ◽  
Novel Biomarkers ◽  
Shed Light

Cancer is the second leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. Although traditional molecular profiling techniques, i.e., bulk sequencing, can identify common mutations and gene expression patterns in cancer cells, they cannot detect tumour heterogeneity. However, single-cell technology has provided an ample opportunity to overcome this difficulty. Since this technology allows us to detect the heterogeneous properties of all cancer cells, this can further our knowledge of the signaling pathways in cancer cells. Indeed, single-cell transcriptomics technology has paved the road for identifying novel biomarkers and signaling pathways, which can serve as targets. This study aims to review the current knowledge about pathways involved in developing cancer cells and shed light on single-cell studies as promising therapeutic approaches.

scholarly journals Modelling of Protein Kinase Signaling Pathways in Melanoma and Other Cancers

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 465 ◽  
Author(s):  
Manfred Kunz ◽  
Julio Vera
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Strong Dependence ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Single Chain ◽  
Network Modelling

Melanoma is a highly aggressive tumor with a strong dependence on intracellular signaling pathways. Almost half of all melanomas are driven by mutations in the v-Raf murine sarcoma viral oncogene homolog B (BRAF) with BRAFV600E being the most prevalent mutation. Recently developed targeted treatment directed against mutant BRAF and downstream mitogen-activated protein kinase (MAPK) MAP2K1 (also termed MEK1) have improved overall survival of melanoma patients. However, the MAPK signaling pathway is far more complex than a single chain of consecutively activated MAPK enzymes and it contains nested-, inherent feedback mechanisms, crosstalk with other signaling pathways, epigenetic regulatory mechanisms, and interacting small non-coding RNAs. A more complete understanding of this pathway is needed to better understand melanoma development and mechanisms of treatment resistance. Network reconstruction, analysis, and modelling under the systems biology paradigm have been used recently in different malignant tumors including melanoma to analyze and integrate ‘omics’ data, formulate mechanistic hypotheses on tumorigenesis, assess and personalize anticancer therapy, and propose new drug targets. Here we review the current knowledge of network modelling approaches in cancer with a special emphasis on melanoma.

scholarly journals Lung Cancer Stem Cells

2008 ◽  
Vol 24 (4-5) ◽  
pp. 257-266 ◽  
Author(s):  
Sharon R. Pine ◽  
Blair Marshall ◽  
Lyuba Varticovski
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Signaling ◽  
Current Knowledge ◽  
Lung Cancer Stem Cells ◽  
Multipotent Differentiation ◽  
Cancer Types ◽  
Active Research

Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

scholarly journals Pancreatic Cancer Signaling Pathways, Genetic Alterations, and Tumor Microenvironment: The Barriers Affecting the Method of Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 373
Author(s):  
Darya Javadrashid ◽  
Amir Baghbanzadeh ◽  
Afshin Derakhshani ◽  
Patrizia Leone ◽  
Nicola Silvestris ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Signaling Pathways ◽  
Immune Checkpoint ◽  
Therapeutic Strategy ◽  
Genetic Alterations ◽  
Ductal Adenocarcinoma ◽  
Therapeutic Approaches ◽  
Ras Mutation ◽  
Direct Targeting

Genetic alterations, especially the K-Ras mutation, carry the heaviest burden in the progression of pancreatic precursor lesions into pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment is one of the challenges that hinder the therapeutic approaches from functioning sufficiently and leads to the immune evasion of pancreatic malignant cells. Mastering the mechanisms of these two hallmarks of PDAC can help us in dealing with the obstacles in the way of treatment. In this review, we have analyzed the signaling pathways involved in PDAC development and the immune system’s role in pancreatic cancer and immune checkpoint inhibition as next-generation therapeutic strategy. The direct targeting of the involved signaling molecules and the immune checkpoint molecules, along with a combination with conventional therapies, have reached the most promising results in pancreatic cancer treatment.

scholarly journals Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7710
Author(s):  
Ying-Chieh Wu ◽  
Tuuli-Maria Sonninen ◽  
Sanni Peltonen ◽  
Jari Koistinaho ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Induced Pluripotent Stem Cell ◽  
Brain Barrier ◽  
Blood Brain ◽  
Induced Pluripotent ◽  
The Brain

The blood–brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.

scholarly journals Co-mutation and exclusion analysis in human tumors, a means for cancer biology studies and treatment design

2017 ◽  
Author(s):  
Soledad Ochoa ◽  
Elizabeth Martínez-Pérez ◽  
Diego Javier Zea ◽  
Miguel Angel Molina-Vila ◽  
Cristina Marino-Buslje
Keyword(s):  
Cancer Biology ◽  
Somatic Mutations ◽  
Malignant Tumors ◽  
Single Gene ◽  
Mutual Exclusion ◽  
Therapeutic Approaches ◽  
Systematic Analysis ◽  
Cancer Types ◽  
Treatment Design ◽  
Selection Of

AbstractBackgroundMalignant tumors originate from genomic and epigenomic alterations, which lead to loss of control of the cellular circuitry. These alterations relate with each other in patterns of mutual exclusion and co-occurrence that affect prognosis and treatment response and highlight the need for multitargeted therapy. However, to the best of our knowledge, there are no systematic reports in the literature of co-dependent and mutually exclusive mutations across all types of cancer. In addition, the studies reported so far generally deal with whole genes instead of specific mutations, ignoring the fact that different alterations in the same gene can have widely different effects.ResultsHere we present a systematic analysis of co-dependencies of somatic mutations across all cancer types. Combining multi testing with conditional and expected mutational probabilities, we have found pairs and networks of co-mutations and exclusions, some of them in particular types of cancer and others widespread. We have also determined that driver loci are present in more types of cancer than non driver loci, that they tend to pair within a single gene and that those pairs are more often exclusions than co-mutations.ConclusionsBased on this properties, we propose new drivers that warrant experimental validation. Our analysis is potentially relevant for cancer biology and classification, as well as for the rational selection of multitargeted therapeutic approaches.

Sign in / Sign up

Export Citation Format

Share Document