scholarly journals Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies

2008 ◽  
Vol 29 (2) ◽  
pp. 234-252 ◽  
Author(s):  
Murielle Mimeault ◽  
Parmender P. Mehta ◽  
Ralph Hauke ◽  
Surinder K. Batra
Keyword(s):  
Progenitor Cells ◽  
Cancer Progression ◽  
Prostatic Cancer ◽  
Molecular Mechanisms ◽  
Prostate Gland ◽  
Cancer Recurrence ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Beneficial Effects ◽  
Stromal Cell Derived Factor

Abstract This review summarizes the recent advancements that have improved our understanding of the functions of prostatic stem/progenitor cells in maintaining homeostasis of the prostate gland. We also describe the oncogenic events that may contribute to their malignant transformation into prostatic cancer stem/progenitor cells during cancer initiation and progression to metastatic disease stages. The molecular mechanisms that may contribute to the intrinsic or the acquisition of a resistant phenotype by the prostatic cancer stem/progenitor cells and their differentiated progenies with a luminal phenotype to the current therapies and disease relapse are also reviewed. The emphasis is on the critical functions of distinct tumorigenic signaling cascades induced through the epidermal growth factor system, hedgehog, Wnt/β-catenin, and/or stromal cell-derived factor-1/CXC chemokine receptor-4 pathways as well as the deregulated apoptotic signaling elements and ATP-binding cassette multidrug transporter. Of particular therapeutic interest, we also discuss the potential beneficial effects associated with the targeting of these signaling elements to overcome the resistance to current treatments and prostate cancer recurrence. The combined targeted strategies toward distinct oncogenic signaling cascades in prostatic cancer stem/progenitor cells and their progenies as well as their local microenvironment, which could improve the efficacy of current clinical chemotherapeutic treatments against incurable, androgen-independent, and metastatic prostate cancers, are also described.

scholarly journals Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction

2012 ◽  
Vol 303 (5) ◽  
pp. H605-H618 ◽  
Author(s):  
Lanfang Li ◽  
Heng Zeng ◽  
Jian-Xiong Chen
Keyword(s):  
Progenitor Cells ◽  
Functional Recovery ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Beneficial Effects ◽  
Postmyocardial Infarction ◽  
Stromal Cell Derived Factor

Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and has beneficial effects against myocardial ischemia-reperfusion injury. Little is known about the role of apelin in the homing of vascular progenitor cells (PCs) and cardiac functional recovery postmyocardial infarction (post-MI). The present study investigated whether apelin affects PC homing to the infarcted myocardium, thereby mediating repair and functional recovery post-MI. Mice were infarcted by coronary artery ligation, and apelin-13 (1 mg·kg−1·day−1) was injected for 3 days before MI and for 14 days post-MI. Homing of vascular PCs [CD133+/c-Kit+/Sca1+, CD133+/stromal cell-derived factor (SDF)-1α+, and CD133+/CXC chemokine receptor (CXCR)-4+] into the ischemic area was examined. Myocardial Akt, endothelial nitric oxide synthase (eNOS), VEGF, jagged1, notch3, SDF-1α, and CXCR-4 expression were assessed at 24 h and 14 days post-MI. Functional analyses were performed on day 14 post-MI. Mice that received apelin-13 treatment demonstrated upregulation of SDF-1α/CXCR-4 expression and dramatically increased the number of CD133+/c-Kit+/Sca1+, CD133+/SDF-1α+, and c-Kit+/CXCR-4+ cells in infarcted hearts. Apelin-13 also significantly increased Akt and eNOS phosphorylation and upregulated VEGF, jagged1, and notch3 expression in ischemic hearts. This was accompanied by a significant reduction of myocardial apoptosis. Furthermore, treatment with apelin-13 promoted myocardial angiogenesis and attenuated cardiac fibrosis and hypertrophy together with a significant improvement of cardiac function at 14 days post-MI. Apelin-13 increases angiogenesis and improves cardiac repair post-MI by a mechanism involving the upregulation of SDF-1α/CXCR-4 and homing of vascular PCs.

scholarly journals Statin use and breast cancer survival: A Swedish nationwide study

2018 ◽  
Author(s):  
Signe Borgquist ◽  
Per Broberg ◽  
Jasaman Tojjar ◽  
Håkan Olsson
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Lower Risk ◽  
Cancer Survival ◽  
Cox Regression ◽  
Cancer Recurrence ◽  
Beneficial Effects ◽  
Breast Cancer Outcome ◽  
Cancer Outcome ◽  
Statin Use

AbstractBackgroundA sizeable body of evidence suggests that statins can cease breast cancer progression and prevent breast cancer recurrence. The latest studies have, however, not been supportive of such clinically beneficial effects. These discrepancies may be explained by insufficient power. This considerably sized study investigates the association between both pre- and post-diagnostic statin use and breast cancer outcome.MethodsA Swedish nation-wide retrospective cohort study of 20,559 Swedish women diagnosed with breast cancer (July 1st, 2005 through 2008). Dispensed statin medication was identified through the Swedish Prescription Registry. Breast cancer related death information was obtained from the national cause-of-death registry until December 31st, 2012. Cox regression models yielded hazard ratios (HR) and 95% confidence intervals (CI) regarding associations between statin use and breast cancer-specific and overall mortality.ResultsDuring follow-up, a total of 4,678 patients died, of which 2,669 were considered breast cancer related deaths. Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer related deaths (HR=0.77; 95% CI 0.63–0.95, P=0.014). Similarly, post-diagnostic statin use compared to non-use was associated with lower risk of breast cancer related deaths (HR=0.83; 95% CI 0.75–0.93, P=0.001).ConclusionThis study evidently supports the notion that statin use is protective regarding breast cancer related mortality in agreement with previous Scandinavian studies, although less so with studies in other populations. These disparities should be further investigated to pave the way for future clinical trials investigating the role of statins in breast cancer.

Antimetastatic effects of Citrus-derived bioactive ingredients: Mechanistic insights

2021 ◽  
Vol 67 (2) ◽  
pp. 178-186
Author(s):  
Ammad Ahmad Farooqi ◽  
Fatima Tahir ◽  
Maham Fakhar ◽  
Ghazala Butt ◽  
Tatiana Colombo Pimentel ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Signaling Cascades ◽  
Citrus Fruits ◽  
Bioactive Components ◽  
Oncogenic Signaling ◽  
Oncogenic Pathways ◽  
Metastasis Research ◽  
Bioactive Ingredients ◽  
Underlying Mechanisms ◽  
Shed Light

The growing complexity of metastasis has sparked tremendous interest in unraveling of the underlying mechanisms which play fundamental role in cancer progression and metastasis. Ground-breaking discoveries in metastasis research have greatly enhanced our understanding about intricate nature of metastasis. Bioactive chemicals obtained from citrus fruits have gained noteworthy appreciation because of significant cancer chemopreventive roles. Deregulated oncogenic signaling cascades play central role in metastasis. Emerging evidence has started to shed light on the metastasis inhibitory properties of naringin, naringenin, tangeretin, nobiletin, hesperidin and hesperetin in different cancer cell lines and xenografted mice. Wnt/?-catenin, TGF/SMAD and NOTCH signaling cascades have been shown to play linchpin role in carcinogenesis and metastasis. There is emerging evidence related to pharmacological targeting of Wnt/?-catenin, TGF/SMAD and NOTCH by citrus-derived bioactive components. These findings are indeed encouraging and will enable researchers to gain further insights into pharmacological targeting of oncogenic pathways to inhibit and prevent metastasis.

scholarly journals Negative Cross Talk between NFAT1 and Stat5 Signaling in Breast Cancer

2011 ◽  
Vol 25 (12) ◽  
pp. 2054-2064 ◽  
Author(s):  
Jiamao Zheng ◽  
Feng Fang ◽  
Xianke Zeng ◽  
Terry R. Medler ◽  
Alyson A. Fiorillo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Cross Talk ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Tumor Formation ◽  
Signaling Cascades ◽  
Activated T Cells ◽  
Downstream Target

Abstract The molecular mechanisms that modulate the activity of the signal transducers and activators of transcription 5 (Stat5) during the progression of breast cancer remain elusive. Here, we present evidence that the calcineurin/nuclear factor of activated T cells (NFAT) pathway negatively regulates the activation of Stat5, and vice versa in breast cancer. NFAT1 interacts with Stat5 in breast cancer cells, and their physical association is mediated by the DNA binding and transactivation domains of Stat5. Ectopically expressed NFAT1 is capable of inhibiting Stat5-dependent functions, including Stat5 transactivation, Stat5-mediated transcription of the downstream target gene expression, and binding of Stat5a to the Stat5 target promoter. By contrast, overexpression of a selective NFAT inhibitor VIVIT reversed NFAT1-mediated suppression of Stat5-dependent gene expression, whereas silencing of NFAT1 through RNA interference enhanced prolactin-induced, Stat5-mediated gene transcription, and breast cancer cell proliferation. A reciprocal inhibitory effect of Stat5 activity on NFAT1 signaling was also observed, implying these two signaling cascades antagonize each other in breast cancer. Importantly, analysis of a matched breast cancer progression tissue microarray revealed a negative correlation between levels of NFAT1 and Stat5 (pY694) during the progression of breast cancer. Taken together, these studies highlight a novel negative cross talk between the NFAT1- and Stat5-signaling cascades that may affect breast tumor formation, growth, and metastasis.

scholarly journals The Role of Omics Approaches to Characterize Molecular Mechanisms of Rare Ovarian Cancers: Recent Advances and Future Perspectives

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1481
Author(s):  
Yashwanth Subbannayya ◽  
Riccardo Di Fiore ◽  
Silvana Anna Maria Urru ◽  
Jean Calleja-Agius
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Delayed Diagnosis ◽  
Cancer Recurrence ◽  
Potential Candidate ◽  
Ovarian Cancers ◽  
Current Review ◽  
Mechanisms Of Carcinogenesis ◽  
Underlying Mechanisms

Rare ovarian cancers are ovarian cancers with an annual incidence of less than 6 cases per 100,000 women. They generally have a poor prognosis due to being delayed diagnosis and treatment. Exploration of molecular mechanisms in these cancers has been challenging due to their rarity and research efforts being fragmented across the world. Omics approaches can provide detailed molecular snapshots of the underlying mechanisms of these cancers. Omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, can identify potential candidate biomarkers for diagnosis, prognosis, and screening of rare gynecological cancers and can aid in identifying therapeutic targets. The integration of multiple omics techniques using approaches such as proteogenomics can provide a detailed understanding of the molecular mechanisms of carcinogenesis and cancer progression. Further, omics approaches can provide clues towards developing immunotherapies, cancer recurrence, and drug resistance in tumors; and form a platform for personalized medicine. The current review focuses on the application of omics approaches and integrative biology to gain a better understanding of rare ovarian cancers.

scholarly journals Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 965
Author(s):  
Sixuan Li ◽  
Hongquan Zhang ◽  
Xiaofan Wei
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Prognostic Indicators ◽  
Breast Cancer Patients ◽  
Oncogenic Signaling

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

scholarly journals Physical Exercise Modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p Expression in Progenitor Cells Promoting Osteogenesis

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 742 ◽  
Author(s):  
Maria Teresa Valenti ◽  
Michela Deiana ◽  
Samuele Cheri ◽  
Monica Dotta ◽  
Francesco Zamboni ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Osteogenic Differentiation ◽  
Progenitor Cells ◽  
Molecular Mechanisms ◽  
Adipogenic Differentiation ◽  
Marathon Runners ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Smad4 Protein ◽  
Smad7 Expression

Physical exercise is known to promote beneficial effects on overall health, counteracting risks related to degenerative diseases. MicroRNAs (miRNAs), short non-coding RNAs affecting the expression of a cell’s transcriptome, can be modulated by different stimuli. Yet, the molecular effects on osteogenic differentiation triggered by miRNAs upon physical exercise are not completely understood. In this study, we recruited 20 male amateur runners participating in a half marathon. Runners’ sera, collected before (PRE RUN) and after (POST RUN) the run, were added to cultured human mesenchymal stromal cells. We then investigated their effects on the modulation of selected miRNAs and the consequential effects on osteogenic differentiation. Our results showed an increased expression of miRNAs promoting osteogenic differentiation (miR-21-5p, miR-129-5p, and miR-378-5p) and a reduced expression of miRNAs involved in the adipogenic differentiation of progenitor cells (miR-188-5p). In addition, we observed the downregulation of PTEN and SMAD7 expression along with increased AKT/pAKT and SMAD4 protein levels in MSCs treated with POST RUN sera. The consequent upregulation of RUNX2 expression was also proven, highlighting the molecular mechanisms by which miR-21-5p promotes osteogenic differentiation. In conclusion, our work proposes novel data, which demonstrate how miRNAs may regulate the osteogenic commitment of progenitor cells in response to physical exercise.

scholarly journals The Role of Endothelial Progenitor Cells in Coronary Artery Disease: Basic Molecular Mechanisms and Its Clinical Potentials

2021 ◽  
Vol 13 (2) ◽  
pp. 106-13
Author(s):  
Yudi Her Oktaviono ◽  
Suryo Ardi Hutomo ◽  
Kevin Luke
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Molecular Mechanisms ◽  
Endothelial Progenitor ◽  
Beneficial Effects ◽  
Endothelial Colony Forming Cells ◽  
Artery Disease ◽  
Universal Definition

BACKGROUND: Coronary artery disease (CAD) remains as the world number one cause of morbidity and mortality. Endothelial progenitor cells (EPCs) are known to be involved in vascular biology. Current review briefly summarizes the basics of EPCs and its clinical use in CAD.CONTENT: EPCs were firstly isolated in 1997 and involved in neovascularization. Further evidence defined EPCs into two distinguishable groups, namely: myeloid angiogenic cells (MACs) and endothelial colony forming cells (ECFCs). Common cardiovascular drugs, statin, angiotensin-converting enzyme (ACE) inhibitor, and their combinations, showed beneficial effects on EPCs. Likewise, the incorporation of EPCs upon CAD intervention management had been recently studied. Intramyocardial EPCs implementation and anti-CD34 antibody-coated stents could provide a promising option for refractory symptoms in CAD.SUMMARY: Association between EPCs and CAD is very dynamic and complex. EPCs could serve as both therapeutic target and agent in CAD patients. Subsequently, a universal definition of EPCs is needed for greater research in the future.KEYWORDS: atherosclerosis, coronary artery disease, endothelial progenitor cells, neovascularization

scholarly journals Systemic and local effect of the Drosophila headcase gene and its role in stress protection of Adult Progenitor Cells

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009362
Author(s):  
Panagiotis Giannios ◽  
Jordi Casanova
Keyword(s):  
Progenitor Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Local Effect ◽  
Tissue Growth ◽  
Prothoracic Gland ◽  
Additional Stress ◽  
Holometabolous Insect ◽  
Stress Protection

During the development of a holometabolous insect such as Drosophila, specific group of cells in the larva survive during metamorphosis, unlike the other larval cells, and finally give rise to the differentiated adult structures. These cells, also known as Adult Progenitor Cells (APCs), maintain their multipotent capacity, differentially respond to hormonal and nutritional signals, survive the intrinsic and environmental stress and respond to the final differentiation cues. However, not much is known about the specific molecular mechanisms that account for their unique characteristics. Here we show that a specific Drosophila APC gene, headcase (hdc), has a dual role in the normal development of these cells. It acts at a systemic level by controlling the hormone ecdysone in the prothoracic gland and at the same time it acts locally as a tissue growth suppressor in the APC clusters, where it modulates the activity of the TOR pathway and promotes their survival by contributing in the regulation of the Unfolded Protein Response. We also show that hdc provides protection against stress in the APCs and that its ectopic expression in cells that do not usually express hdc can confer these cells with an additional stress protection. Hdc is the founding member of a group of homolog proteins identified from C. elegans to humans, where has been found associated with cancer progression. The finding that the Drosophila hdc is specifically expressed in progenitor cells and that it provides protection against stress opens up a new hypothesis to be explored regarding the role of the human Heca and its contribution to carcinogenesis.

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