scholarly journals Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 280
Author(s):  
Valerie Jacquemin ◽  
Mathieu Antoine ◽  
Geneviève Dom ◽  
Vincent Detours ◽  
Carine Maenhaut ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Population ◽  
Short Review ◽  
Cell Heterogeneity ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Clinical Diagnostic

Though heterogeneity of cancers is recognized and has been much discussed in recent years, the concept often remains overlooked in different routine examinations. Indeed, in clinical or biological articles, reviews, and textbooks, cancers and cancer cells are generally presented as evolving distinct entities rather than as an independent heterogeneous cooperative cell population with its self-oriented biology. There are, therefore, conceptual gaps which can mislead the interpretations/diagnostic and therapeutic approaches. In this short review, we wish to summarize and discuss various aspects of this dynamic evolving heterogeneity and its biological, pathological, clinical, diagnostic, and therapeutic implications, using thyroid carcinoma as an illustrative example.

scholarly journals Bioelectrical Analysis of Various Cancer Cell Types Immobilized in 3D Matrix and Cultured in 3D-Printed Well

Biosensors ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 136 ◽  
Author(s):  
Paivana ◽  
Mavrikou ◽  
Kaltsas ◽  
Kintzios
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Population ◽  
Cancer Cell Line ◽  
Immobilized Cell ◽  
Impedance Measurements ◽  
Hydrogel Matrix

Cancer cell lines are important tools for anticancer drug research and assessment. Impedance measurements can provide valuable information about cell viability in real time. This work presents the proof-of-concept development of a bioelectrical, impedance-based analysis technique applied to four adherent mammalian cancer cells lines immobilized in a three-dimensional (3D) calcium alginate hydrogel matrix, thus mimicking in vivo tissue conditions. Cells were treated with cytostatic agent5-fluoruracil (5-FU). The cell lines used in this study were SK-N-SH, HEK293, HeLa, and MCF-7. For each cell culture, three cell population densities were chosen (50,000, 100,000, and 200,000 cells/100 μL). The aim of this study was the extraction of mean impedance values at various frequencies for the assessment of the different behavior of various cancer cells when 5-FU was applied. For comparison purposes, impedance measurements were implemented on untreated immobilized cell lines. The results demonstrated not only the dependence of each cell line impedance value on the frequency, but also the relation of the impedance level to the cell population density for every individual cell line. By establishing a cell line-specific bioelectrical behavior, it is possible to obtain a unique fingerprint for each cancer cell line reaction to a selected anticancer agent.

The Tangled Mitochondrial Metabolism in Cancer: An Innovative Pharmacological Approach

2020 ◽  
Vol 27 (13) ◽  
pp. 2106-2117 ◽  
Author(s):  
Patrizia Bottoni ◽  
Roberto Scatena
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Oxidative Metabolism ◽  
Reactive Oxygen ◽  
Mitochondrial Metabolism ◽  
Oxygen Species ◽  
Therapeutic Approaches ◽  
Fundamental Step

Background: Mitochondria are remarkably gaining significant and different pathogenic roles in cancer (i.e., to sustain specific metabolism, to activate signaling pathways, to promote apoptosis resistance, to favor cancer cell dissemination, and finally to facilitate genome instability). Interestingly, all these roles seem to be linked to the fundamental activity of mitochondria, i.e. oxidative metabolism. Intriguingly, a typical modification of mitochondrial oxidative metabolism and reactive oxygen species production/ neutralization seems to have a central role in all these tangled pathogenic roles in cancer. On these bases, a careful understanding of the molecular relationships between cancer and mitochondria may represent a fundamental step to realize therapeutic approaches blocking the typical cancer progression. The main aim of this review is to stress some neglected aspects of oxidative mitochondrial metabolism of cancer cells to promote more translational research with diagnostic and therapeutic potential. Methods: We reviewed the available literature regarding clinical and experimental studies on various roles of mitochondria in cancer, with attention to the cancer cell mitochondrial metabolism. Results: Mitochondria are an important source of reactive oxygen species. Their toxic effects seem to increase in cancer cells. However, it is not clear if damage depends on ROS overproduction and/or defect in detoxification. Failure of both these processes is likely a critical component of the cancer process and is strictly related to the actual microenvironment of cancer cells. Conclusions: Mitochondria, also by ROS production, have a fundamental pathogenetic role in promoting and maintaining cancer and its spreading. To carefully understand the tangled redox state of cancer cells mitochondria represents a fundamental step to realize therapeutic approaches blocking the typical cancer progression.

scholarly journals Quantum Dots Based in-Vitro Co-Culture Cancer Model for Identification of Rare Cancer Cell Heterogeneity

2021 ◽  
Author(s):  
Satyanarayana Swamy Vyshnava ◽  
Gayathri Pandluru ◽  
Dileep Kumar Kanderi ◽  
Shiva Prasad Panjala ◽  
Swathi Banapuram ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Modern Medicine ◽  
Cell Heterogeneity ◽  
Rare Cancer ◽  
Hek 293 ◽  
Model Study ◽  
Vitro Model

Abstract Cancer cell heterogeneity (CCH) is a key element in understanding cancer progression and metastasis. CCH is one of the challenges in therapeutics and diagnostics stumbling block in modern medicine. An in-vitro model of co-culture systems of MCF-7, HeLa, HEK-293, with THP-1 cells showed the occurrence of CTCs like cells with EpCAM+ and other cancer cell heterogenetic types with the Quantum Dot antibody conjugates (QDAb). This in-vitro model study could provide insights into the role of rare cancer cells and heterogeneity in metastasis, as well as the severity of infections in these patients. We successfully reported the presence of CCH based on the fluorescence ratios of the co-culture cancer cells. These short-term mimic co-cultures give a compelling and quite associated model for estimating early treatment responses in various types of cancers.

scholarly journals Mesenchymal Stem/Stromal Cell Engulfment by Breast Cancer Cells Generates a Hybrid Cancer Cell Population with Dormancy and Chemoresistance

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Giuseppina Augimeri ◽  
Maria E. Gonzalez ◽  
Daniela Bonofiglio ◽  
Sebastiano Andò ◽  
Celina G. Kleer
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Population ◽  
Breast Cancer Cells ◽  
Stromal Cell ◽  
Cancer Cell Population ◽  
Cell Engulfment

scholarly journals Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4145
Author(s):  
Biljana Ristic ◽  
Ljubica Harhaji-Trajkovic ◽  
Mihajlo Bosnjak ◽  
Ivana Dakic ◽  
Srdjan Mijatovic ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Graphene Quantum Dots ◽  
Cancer Therapeutics ◽  
Mitogen Activated Protein Kinase ◽  
Autophagic Flux ◽  
Therapeutic Implications

Graphene-based nanomaterials (GNM) are plausible candidates for cancer therapeutics and drug delivery systems. Pure graphene and graphene oxide nanoparticles, as well as graphene quantum dots and graphene nanofibers, were all able to trigger autophagy in cancer cells through both transcriptional and post-transcriptional mechanisms involving oxidative/endoplasmic reticulum stress, AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein kinase, and Toll-like receptor signaling. This was often coupled with lysosomal dysfunction and subsequent blockade of autophagic flux, which additionally increased the accumulation of autophagy mediators that participated in apoptotic, necrotic, or necroptotic death of cancer cells and influenced the immune response against the tumor. In this review, we analyze molecular mechanisms and structure–activity relationships of GNM-mediated autophagy modulation, its consequences for cancer cell survival/death and anti-tumor immune response, and the possible implications for the use of GNM in cancer therapy.

scholarly journals Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Lan Thi Hanh Phi ◽  
Ita Novita Sari ◽  
Ying-Gui Yang ◽  
Sang-Hyun Lee ◽  
Nayoung Jun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Therapeutic Agents ◽  
Therapeutic Approaches ◽  
Tumor Initiating Cells ◽  
Therapeutic Implications ◽  
Key Features

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are suggested to be responsible for drug resistance and cancer relapse due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Thus, it is important to understand the characteristics and mechanisms by which CSCs display resistance to therapeutic agents. In this review, we highlight the key features and mechanisms that regulate CSC function in drug resistance as well as recent breakthroughs of therapeutic approaches for targeting CSCs. This promises new insights of CSCs in drug resistance and provides better therapeutic rationales to accompany novel anticancer therapeutics.

scholarly journals The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein

2020 ◽  
Vol 21 (3) ◽  
pp. 702
Author(s):  
Raffaela Mariarosaria Mariniello ◽  
Francesca Maria Orlandella ◽  
Anna Elisa De Stefano ◽  
Paola Lucia Chiara Iervolino ◽  
Giovanni Smaldone ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Biological Effects ◽  
Tumour Suppressor ◽  
Human Thyroid ◽  
Migration And Invasion ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cells

Thyroid carcinoma is the most common endocrine cancer and includes different forms. Among these, anaplastic thyroid carcinoma (ATC) is the rarest but the most lethal subtype, compared to papillary thyroid carcinoma (PTC) which shows an overall good prognosis. We have previously showed that Tumor Suppressor Candidate 2 (TUSC2), a known tumour suppressor gene, is downregulated in human PTC and ATC compared to normal thyroid samples. The aim of this study was to gain insight into the molecular mechanisms induced by TUSC2 in thyroid cancer cells. Here, we stably transfected TUSC2 in papillary (TPC-1) and in anaplastic (8505C) thyroid cancer cell lines and studied its effects on several biological processes, demonstrating that TUSC2 overexpression decreased thyroid cancer cell proliferation, migration and invasion. Through the proteome profiler apoptosis array, we observed that TUSC2 increased sensitivity to apoptosis by increasing the SMAC/DIABLO and CYTOCHROME C proteins. On the other hand, transient silencing of TUSC2, by siRNA, in an immortalized thyroid follicular epithelial cell line (Nthy-ori 3-1) showed the opposite effect. Finally modulation of SMAC/DIABLO partially rescued the biological effects of TUSC2. Thus, our data highlight a tumour suppressor role of TUSC2 in thyroid carcinogenesis, suggesting that it could be a promising target and biomarker for thyroid carcinoma.

scholarly journals Mathematical Modeling Reveals the Factors Involved in the Phenomena of Cancer Stem Cells Stabilization

2018 ◽  
Author(s):  
N. Bessonov ◽  
G. Pinna ◽  
A. Minarsky ◽  
A. Harel-Bellan ◽  
N. Morozova
Keyword(s):  
Mathematical Model ◽  
Stem Cells ◽  
Population Dynamics ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Population ◽  
Cell Population Dynamics ◽  
Cancer Cell Population ◽  
Population Stabilization

AbstractCancer Stem Cells (CSC), a subset of cancer cells resembling normal stem cells with self-renewal and asymmetric division capabilities, are present at various but low proportions in many tumors and are thought to be responsible for tumor relapses following conventional cancer therapies. In vitro, most intriguingly, when isolated, CSCs return to their original proportion level as shown by various investigators. This phenomenon still remains to be explained.We suggest a mathematical model of cancer cell population dynamics, based on the main parameters of cell population dynamics, including the proliferation rates, the rates of cell death and the frequency of symmetric and asymmetric cell divisions both in CSCs and in non-CSCs. This model should help elucidating some important factors underlying the dynamics of the two populations, first of all, the phenomena of cancer stem cell population stabilization.Author SummaryCancer Stem Cells (CSC) present a subset of cancer cells which is thought to be responsible for tumor growth. That is why CSC are also named “tumor initiation cells”. Additionally, it was shown that CSC are resistant to chemo- and radio-therapies which suggests that these cells can be responsible for tumor relapses after these treatments. Experimental data in cancer cell lines have shown the intriguing phenomena of CSC population stability, which means that isolated CSC population rapidly stabilizes at its characteristic level (the relative proportion of CSC in a whole cancer population). We suggest a mathematical model of cancer cell population dynamics, based on experimentally measured dynamics of CSC population stabilization and including main parameters of cell population growth.We have computationally predicted probability of different scenarios of cancer cell behavior for each experimental case with measurable growth parameters. Moreover, we provide an analytical tool for elucidating important biochemical factors responsible for a particular dynamics of CSC population.The results may have important implications in therapeutic, because the destroying of a set of factors underlying CSC stability may help to avoid tumor relapses.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

Sign in / Sign up

Export Citation Format

Share Document