scholarly journals The potential role of miRNAs and exosomes in chemotherapy in ovarian cancer

2018 ◽  
Vol 25 (12) ◽  
pp. R663-R685 ◽  
Author(s):  
Mona Alharbi ◽  
Felipe Zuñiga ◽  
Omar Elfeky ◽  
Dominic Guanzon ◽  
Andrew Lai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Potential Role ◽  
Chemotherapy Resistance ◽  
Predictive Biomarker ◽  
Response To Therapy ◽  
Target Cells ◽  
Repair Mechanisms ◽  
Drug Efflux Pumps

Chemoresistance is one of the major obstacles in the treatment of cancer patients. It poses a fundamental challenge to the effectiveness of chemotherapy and is often linked to relapse in patients. Chemoresistant cells can be identified in different types of cancers; however, ovarian cancer has one of the highest rates of chemoresistance-related relapse (50% of patients within 5 years). Resistance in cells can either develop through prolonged cycles of treatment or through intrinsic pathways. Mechanistically, the problem of drug resistance is complex mainly because numerous factors are involved, such as overexpression of drug efflux pumps, drug inactivation, DNA repair mechanisms and alterations to and/or mutations in the drug target. Additionally, there is strong evidence that circulating miRNAs participate in the development of chemoresistance. Recently, miRNAs have been identified in exosomes, where they are encapsulated and hence protected from degradation. These miRNAs within exosomes (exo-miRNAs) can regulate the gene expression of target cells both locally and systemically. Exo-miRNAs play an important role in disease progression and can potentially facilitate chemoresistance in cancer cells. In addition, and from a diagnostic perspective, exo-miRNAs profiles may contribute to the development of predictive models to identify responder and non-responder chemotherapy. Such model may also be used for monitoring treatment response and disease progression. Exo-miRNAs may ultimately serve as both a predictive biomarker for cancer response to therapy and as a prognostic marker for the development of chemotherapy resistance. Therefore, this review examines the potential role of exo-miRNAs in chemotherapy in ovarian cancer.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

scholarly journals Correction: Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
Author(s):  
Carine Bossard ◽  
Muriel Busson ◽  
David Vindrieux ◽  
Françoise Gaudin ◽  
Véronique Machelon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Tumor Suppressor ◽  
Epithelial Ovarian Cancer ◽  
Potential Role ◽  
Estrogen Receptor Beta ◽  
Receptor Beta ◽  
Correction Potential

scholarly journals Exosomal miRNAs in Lung Diseases: From Biologic Function to Therapeutic Targets

2019 ◽  
Vol 8 (9) ◽  
pp. 1345 ◽  
Author(s):  
Julien Guiot ◽  
Ingrid Struman ◽  
Edouard Louis ◽  
Renaud Louis ◽  
Michel Malaise ◽  
...  
Keyword(s):  
Lung Disease ◽  
Disease Progression ◽  
Lung Diseases ◽  
Potential Role ◽  
Protective Effects ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
Stress Signals ◽  
Therapeutic Tools

Increasing evidence suggests the potential role of extracellular vesicles (EVs) in many lung diseases. According to their subcellular origin, secretion mechanism, and size, EVs are currently classified into three subpopulations: exosomes, microvesicles, and apoptotic bodies. Exosomes are released in most biofluids, including airway fluids, and play a key role in intercellular communication via the delivery of their cargo (e.g., microRNAs (miRNAs)) to target cell. In a physiological context, lung exosomes present protective effects against stress signals which allow them to participate in the maintenance of lung homeostasis. The presence of air pollution alters the composition of lung exosomes (dysregulation of exosomal miRNAs) and their homeostatic property. Indeed, besides their potential as diagnostic biomarkers for lung diseases, lung exosomes are functional units capable of dysregulating numerous pathophysiological processes (including inflammation or fibrosis), resulting in the promotion of lung disease progression. Here, we review recent studies on the known and potential role of lung exosomes/exosomal miRNAs, in the maintaining of lung homeostasis on one hand, and in promoting lung disease progression on the other. We will also discuss using exosomes as prognostic/diagnostic biomarkers as well as therapeutic tools for lung diseases.

scholarly journals Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 780
Author(s):  
Kishor Pant ◽  
Estanislao Peixoto ◽  
Seth Richard ◽  
Sergio A. Gradilone
Keyword(s):  
Histone Deacetylases ◽  
Potential Role ◽  
Chemotherapy Resistance ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Cellular Proteins ◽  
Epigenetic Changes ◽  
Post Translational Modifications ◽  
Frequent Relapse

Cholangiocarcinoma (CCA) is a highly invasive and metastatic form of carcinoma with bleak prognosis due to limited therapies, frequent relapse, and chemotherapy resistance. There is an urgent need to identify the molecular regulators of CCA in order to develop novel therapeutics and advance diseases diagnosis. Many cellular proteins including histones may undergo a series of enzyme-mediated post-translational modifications including acetylation, methylation, phosphorylation, sumoylation, and crotonylation. Histone deacetylases (HDACs) play an important role in regulating epigenetic maintenance and modifications of their targets, which in turn exert critical impacts on chromatin structure, gene expression, and stability of proteins. As such, HDACs constitute a group of potential therapeutic targets for CCA. The aim of this review was to summarize the role that HDACs perform in regulating epigenetic changes, tumor development, and their potential as therapeutic targets for CCA.

scholarly journals Role of Extracellular Vesicles (EVs) in Cell Stress Response and Resistance to Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 136 ◽  
Author(s):  
Clodagh O’Neill ◽  
Katie Gilligan ◽  
Róisín Dwyer
Keyword(s):  
Disease Progression ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Underlying Disease ◽  
Cell Stress ◽  
Response To Therapy ◽  
Nanosized Particles ◽  
Resistance To Therapy ◽  
Cell Stress Response

Extracellular vesicles (EVs) are nanosized particles released by all cells that have been heralded as novel regulators of cell-to-cell communication. It is becoming increasingly clear that in response to a variety of stress conditions, cells employ EV-mediated intercellular communication to transmit a pro-survival message in the tumor microenvironment and beyond, supporting evasion of cell death and transmitting resistance to therapy. Understanding changes in EV cargo and secretion pattern during cell stress may uncover novel, targetable mechanisms underlying disease progression, metastasis and resistance to therapy. Further, the profile of EVs released into the circulation may provide a circulating biomarker predictive of response to therapy and indicative of microenvironmental conditions linked to disease progression, such as hypoxia. Continued progress in this exciting and rapidly expanding field of research will be dependent upon widespread adoption of transparent reporting standards and implementation of guidelines to establish a consensus on methods of EV isolation, characterisation and nomenclature employed.

scholarly journals PD-L1 Expression in TNBC: A Predictive Biomarker of Response to Neoadjuvant Chemotherapy?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Bruna Cerbelli ◽  
Angelina Pernazza ◽  
Andrea Botticelli ◽  
Lucio Fortunato ◽  
Massimo Monti ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Biomarker ◽  
Complete Response ◽  
Response To Therapy ◽  
Neoplastic Progression ◽  
Infiltrating Lymphocytes

Triple negative breast cancer (TNBC) has an aggressive clinical behaviour, with a poorer prognosis compared to other subtypes. Recently, tumor-infiltrating lymphocytes (TILs) have been proposed as a predictive biomarker for a better clinical outcome and pathological response (pR) after neoadjuvant chemotherapy (NACT) in TNBC. These data confirm the role of the immune system in the neoplastic progression and in the response to therapy. We performed a retrospective analysis of 54 pre-NACT biopsies of TNBC and compared both the percentage of stromal TILs and the degree of PD-L1 expression with the extent of pR to standard NACT. A pathological complete response (pCR) was achieved in 35% of cases. Univariate analysis showed (i) a significant association between PD-L1 expression in ≥25% of neoplastic cells and the achievement of a pCR (p=0.024); (ii) a significantly higher frequency of pCR in cases showing ≥50% stromal TILs (p<0.001). However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01–1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.

Immunologic Approaches to Ovarian Cancer Treatment

2007 ◽  
Vol 25 (20) ◽  
pp. 2884-2893 ◽  
Author(s):  
Paul Sabbatini ◽  
Kunle Odunsi
Keyword(s):  
Ovarian Cancer ◽  
Immune Surveillance ◽  
Chemotherapy Resistance ◽  
Optimal Strategies ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Rejection ◽  
Phase Iii ◽  
Minimal Disease ◽  
Infiltrating Lymphocytes

The clinical course of ovarian cancer is often marked by periods of relapse and remission until chemotherapy resistance develops. Patients in remission with minimal disease burdens are ideally suited for the evaluation of immune-based strategies. The role of immune surveillance in improving outcome has been supported by the correlation of increased survival with the presence or absence of tumor-infiltrating lymphocytes in a given patient. Major obstacles to the development of successful immune strategies include the identification of tumor-restricted immunogenic targets, generation of a sufficient immune response to cause tumor rejection, and approaches to overcome evasion of immune attack. As optimal strategies are being developed, many questions remain. Some of the questions are as follows: What is the best antigen form (eg, peptides, proteins, or tumor lysates)? What are the appropriate adjuvants? Are monovalent or multivalent vaccines likely to be more effective? What is the optimal frequency and duration of vaccination? How should antigen-specific responses be monitored? How should the anticancer response be maintained? In this review, we will explore representative examples of immune strategies under investigation for patients with ovarian carcinoma that illustrate many of these issues. We will review ongoing phase III studies for patients in first clinical remission. Basic principles generic to all these immunotherapeutic approaches will be discussed in the hopes of yielding the most promising results as the field continues to evolve.

scholarly journals Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44787 ◽  
Author(s):  
Carine Bossard ◽  
Muriel Busson ◽  
David Vindrieux ◽  
Françoise Gaudin ◽  
Véronique Machelon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Tumor Suppressor ◽  
Epithelial Ovarian Cancer ◽  
Potential Role ◽  
Estrogen Receptor Beta ◽  
Receptor Beta
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