scholarly journals Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

2021 ◽  
Vol 22 (22) ◽  
pp. 12586
Author(s):  
Viviana De Martino ◽  
Michela Rossi ◽  
Giulia Battafarano ◽  
Jessica Pepe ◽  
Salvatore Minisola ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Scientific Community ◽  
Therapeutic Agents ◽  
Tumor Proliferation ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Diagnostic Agents ◽  
Metastatic Process

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.

MicroRNAs as Therapeutic Agents: The Future of the Battle Against Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2544-2554 ◽  
Author(s):  
Sumit Biswas
Keyword(s):  
Drug Resistance ◽  
Cancer Biology ◽  
Therapeutic Agents ◽  
Nucleotide Level ◽  
Target Mrnas ◽  
Sequencing Technologies ◽  
Tumour Suppressors ◽  
The Future ◽  
New Strategies

Since their discovery in the 1990’s, the study of a class of non-coding, single-stranded RNAs, christened the microRNAs has opened up new vistas in the field of cancer biology. MicroRNAs bind to their target mRNAs to act as either oncogenes or tumour suppressors. With the near-complete elucidation of the biogenesis pathway, and the advent of rapid sequencing technologies, microRNAs have slowly cemented their place as essential biomarkers for delineating the progression, metastasis, relapse or drug resistance of cancer. Being crucial players in the cancer pathway, there has been considerable urgency in designing molecules - both at the nucleotide and non-nucleotide level to counter the effects of their binding. A number of different approaches have yielded quite a body of compounds which have been found to be effective in the treatment of various tumours across many different organs. In this study, the focus is on the review of the timeline of discovery and characterization of microRNAs, underlining their importance in different cancers, shedding light on the discovery of anti-microRNA compounds and illustrating their uses in deriving new strategies to combat cancer.

scholarly journals Neuroinflammatory Nexus of Pediatric Epilepsy

2018 ◽  
Vol 07 (02) ◽  
pp. 032-039
Author(s):  
Shruti Bagla ◽  
Alan Dombkowski
Keyword(s):  
Inflammatory Mediators ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Recent Literature ◽  
Refractory Epilepsy ◽  
Genetic Mutation ◽  
Pediatric Epilepsy ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

AbstractA rapidly growing body of evidence supports the premise that neuroinflammation plays an important role in initiating and sustaining seizures in a range of pediatric epilepsies. Clinical and experimental evidence indicates that neuroinflammation is both an outcome and a contributor to seizures. In this manner, seizures that arise from an initial insult (e.g., infection, trauma, and genetic mutation) contribute to an inflammatory response that subsequently promotes recurrent seizures. This cyclic relationship between seizures and neuroinflammation has been described as a “vicious cycle.” Studies of human tissue resected for surgical treatment of refractory epilepsy have reported activated inflammatory and immune signaling pathways, while animal models have been used to demonstrate that key inflammatory mediators lead to increased seizure susceptibility. Further characterization of the molecular mechanisms involved in this cycle may ultimately enable the development of new therapeutic approaches for the treatment of epilepsy. In this brief review, we focus on key inflammatory mediators that have become prominent in recent literature of epilepsy, including newly characterized microRNAs and their potential role in neuroinflammatory signaling.

A rapid and simple procedure for the isolation and cultivation of fibroblast-like cells from medaka and zebrafish embryos and fin clip biopsies

2021 ◽  
pp. 002367722110454
Author(s):  
Lars Beedgen ◽  
Andreas Hüllen ◽  
Sevinç Gücüm ◽  
Thomas Thumberger ◽  
Jochen Wittbrodt ◽  
...  
Keyword(s):  
Drug Testing ◽  
Simple Procedure ◽  
Model Organisms ◽  
Cell Culture System ◽  
Therapeutic Approaches ◽  
Simple Method ◽  
New Therapeutic Approaches ◽  
Alternative Test ◽  
Rice Fish

In many human diseases, the molecular pathophysiological mechanisms are not understood, which makes the development and testing of new therapeutic approaches difficult. The generation and characterization of animal models such as mice, rats, fruit flies, worms or fish offers the possibility for in detail studies of a disease’s development, its course and potential therapies in an organismal context, which considerably minimizes the risk of therapeutic side effects for patients. Nevertheless, due to the high numbers of experimental animals used in research worldwide, attempts to develop alternative test systems will help in reducing their count. In this regard, the cell culture system displays a suitable option due to its potential of delivering nearly unlimited material and the good opportunities for high-throughput studies such as drug testing. Here, we describe a quick and simple method to isolate and cultivate vital fibroblast-like cells from embryos and adults of two popular teleost model organisms, the Japanese rice fish medaka ( Oryzias latipes) and the zebrafish ( Danio rerio).

scholarly journals Targeting autophagy to overcome drug resistance: further developments

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Haocai Chang ◽  
Zhengzhi Zou
Keyword(s):  
Drug Resistance ◽  
Cell Death ◽  
Cell Survival ◽  
Tumor Therapy ◽  
Chemotherapeutic Drugs ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Tumor Drug Resistance ◽  
Tumor Survival ◽  
Cellular Organelles

AbstractInhibiting cell survival and inducing cell death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins and damaged or aged cellular organelles to recycle their constituent metabolites that enable the maintenance of cell survival and genetic stability and even promotes the drug resistance, which severely limits the efficacy of chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect to suppress and promote tumor survival, which makes the effect of targeting autophagy on drug resistance more confusing and fuzzier. In the review, we summarize the regulation of autophagy by emerging ways, the action of targeting autophagy on drug resistance and some of the new therapeutic approaches to treat tumor drug resistance by interfering with autophagy-related pathways. The full-scale understanding of the tumor-associated signaling pathways and physiological functions of autophagy will hopefully open new possibilities for the treatment of tumor drug resistance and the improvement in clinical outcomes.

scholarly journals The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1141 ◽  
Author(s):  
Cristina P. R. Xavier ◽  
Hugo R. Caires ◽  
Mélanie A. G. Barbosa ◽  
Rui Bergantim ◽  
José E. Guimarães ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Genetic Material ◽  
Human Tumor ◽  
Current Evidence ◽  
Drug Resistant ◽  
Intercellular Signaling ◽  
Therapeutic Approaches ◽  
Intercellular Exchange

Extracellular vesicles (EVs) mediate intercellular signaling and communication, allowing the intercellular exchange of proteins, lipids, and genetic material. Their recognized role in the maintenance of the physiological balance and homeostasis seems to be severely disturbed throughout the carcinogenesis process. Indeed, the modus operandi of cancer implies the highjack of the EV signaling network to support tumor progression in many (if not all) human tumor malignancies. We have reviewed the current evidence for the role of EVs in affecting cancer hallmark traits by: (i) promoting cell proliferation and escape from apoptosis, (ii) sustaining angiogenesis, (iii) contributing to cancer cell invasion and metastasis, (iv) reprogramming energy metabolism, (v) transferring mutations, and (vi) modulating the tumor microenvironment (TME) by evading immune response and promoting inflammation. Special emphasis was given to the role of EVs in the transfer of drug resistant traits and to the EV cargo responsible for this transfer, both between cancer cells or between the microenvironment and tumor cells. Finally, we reviewed evidence for the increased release of EVs by drug resistant cells. A timely and comprehensive understanding of how tumor EVs facilitate tumor initiation, progression, metastasis and drug resistance is instrumental for the development of innovative EV-based therapeutic approaches for cancer.

scholarly journals Extracellular Vesicles in Viral Pathogenesis: A Case of Dr. Jekyll and Mr. Hyde

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Lada Purvinsh ◽  
Andrey Gorshkov ◽  
Aleksandra Brodskaia ◽  
Andrey Vasin
Keyword(s):  
Extracellular Vesicles ◽  
Protective Factor ◽  
Fundamental Property ◽  
Molecular Composition ◽  
Biologically Active ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Physiological Processes ◽  
Infected Cells

Secretion of extracellular vesicles (EVs) is a fundamental property of living cells. EVs are known to transfer biological signals between cells and thus regulate the functional state of recipient cells. Such vesicles mediate the intercellular transport of many biologically active molecules (proteins, nucleic acids, specific lipids) and participate in regulation of key physiological processes. In addition, EVs are involved in the pathogenesis of multiple diseases: infectious, neurodegenerative, and oncological. The current EV classification into microvesicles, apoptotic bodies, and exosomes is based on their size, pathways of cellular biogenesis, and molecular composition. This review is focused on analysis of the role of EVs (mainly exosomes) in the pathogenesis of viral infection. We briefly characterize the biogenesis and molecular composition of various EV types. Then, we consider EV-mediated pro- and anti-viral mechanisms. EV secretion by infected cells can be an important factor of virus spread in target cell populations, or a protective factor limiting viral invasion. The data discussed in this review, on the effect of EV secretion by infected cells on processes in neighboring cells and on immune cells, are of high significance in the search for new therapeutic approaches and for design of new generations of vaccines.

scholarly journals Worms and the Treatment of Inflammatory Bowel Disease: Are Molecules the Answer?

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Nathalie E. Ruyssers ◽  
Benedicte Y. De Winter ◽  
Joris G. De Man ◽  
Alex Loukas ◽  
Arnold G. Herman ◽  
...  
Keyword(s):  
Therapeutic Approaches ◽  
Regulatory Pathways ◽  
New Therapeutic Approaches ◽  
Helminth Infections ◽  
Immunological Diseases ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms ◽  
Developed World ◽  
Identification And Characterization

The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of IBD in the developed world. Epidemiological, experimental, and clinical data sustain the idea that helminths could provide protection against IBD. Studies investigating the underlying mechanisms by which helminths might induce such protection have revealed the importance of regulatory pathways, for example, regulatory T-cells. Further investigation on how helminths influence both innate and adaptive immune reactions will shed more light on the complex pathways used by helminths to regulate the hosts immune system. Although therapy with living helminths appears to be effective in several immunological diseases, the disadvantages of a treatment based on living parasites are explicit. Therefore, the identification and characterization of helminth-derived immunomodulatory molecules that contribute to the protective effect could lead to new therapeutic approaches in IBD and other immune diseases.

scholarly journals Antibody Conjugates for Sarcoma Therapy: How Far along Are We?

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 978
Author(s):  
Letizia Polito ◽  
Giulia Calafato ◽  
Massimo Bortolotti ◽  
Cecilia Chiarelli Olivari ◽  
Stefania Maiello ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Surface Antigens ◽  
Therapeutic Agents ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Antibody Conjugates ◽  
Hematological Tumors ◽  
Preclinical And Clinical Studies ◽  
Patients Experience ◽  
Sarcoma Treatment

Sarcomas are one of the most difficult type of cancer to manage and treat because of their extremely heterogeneous molecular and morphological features. Despite the progress made over the years in the establishment of standard protocols for high and low grading/staging sarcoma patients, mostly with chemotherapy and/or radiotherapy, 50% of treated patients experience relapse episodes. Because of this, in the last 20 years, new therapeutic approaches for sarcoma treatment have been evaluated in preclinical and clinical studies. Among them, antibody-based therapies have been the most studied. Immunoconjugates consist of a carrier portion, frequently represented by an antibody, linked to a toxic moiety, i.e., a drug, toxin, or radionuclide. While the efficacy of immunoconjugates is well demonstrated in the therapy of hematological tumors and more recently also of epithelial ones, their potential as therapeutic agents against sarcomas is still not completely explored. In this paper, we summarize the results obtained with immunoconjugates targeting sarcoma surface antigens, considering both preclinical and clinical studies. To date, the encouraging results obtained in preclinical studies allowed nine immunoconjugates to enter clinical trials, demonstrating the validity of immunotherapy as a promising pharmacological tool also for sarcoma therapy.

scholarly journals New aptamer-based approaches for the targeting of cancer associated fibroblast in NSCLC

2021 ◽  
Author(s):  
G Ciccone ◽  
◽  
M.L. Ibba ◽  
G Coppola ◽  
G Petrillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Normal Lung ◽  
Therapeutic Approaches ◽  
Cell Growth And Migration ◽  
Innovative Strategies ◽  
Cancer Associated Fibroblast ◽  
Primary Nsclc ◽  
And Migration

The aim of the research. Non-small cell lung cancer (NSCLC) represents about 80 % of all lung cancer cases and is oft en associated with drug resistance, relapses and a poor prognosis. Th erefore, the identifi cation of eff ective therapeutic strategies represents a crucial challenge in oncology. A key limit of conventional anticancer treatments is that they do not target the permissive tumor microenvironment, of which key components are cancer‐associated fibroblasts (CAFs). It has been shown that CAFs are able to regulate malignant progression and drug resistance. However, a detailed characterization of CAF profile and the targeting of their pro-tumor eff ects still remain an ambitious challenge and have a primary importance for the identifi cation of new eff ective therapies. Material and methods. We aimed to develop innovative strategies based on nucleic acid aptamers to address these fundamental issues. Firstly, we applied an aptamer conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the PDGFRβ, to specifi cally silence STAT3 reported as a fundamental player in the cross-talk between CAFs and epithelial NSCLC cells. Results. We demonstrated that this molecule eff ectively delivers STAT3 siRNA in NSCLC cells, blocking CAF-induced cell growth and migration in both continous and primary NSCLC coltures. In addition, in order to address CAF specifi c targeting and profi ling, we developed an innovative diff erential cell-SELEX approach by using primary NSCLC CAFs as selection target. Such a strategy allowed the isolation of diff erent aptamers discriminating NSCLC CAFs from normal lung fi broblasts. Th e analyses of aptamer specifi city and functionality is curently ongoing. Conclusion. Our data represent the fi rst ever attempt in CAF targeting using aptamer-based drugs, and can open innovative horizons in the current therapeutic approaches forNSCLC.

Sign in / Sign up

Export Citation Format

Share Document