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Book ; Online ; E-Book: Diagnostic and therapeutic applications of exosomes in cancer

Amiji, Mansoor / Ramesh, Rajagopal

2018

Author's details	edited by Mansoor Amiji, Rajagopal Ramesh
Language	English
Size	1 Online-Ressource (xxii, 379 Seiten)
Publisher	Elsevier AP
Publishing place	London
Publishing country	Great Britain
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT019776297
ISBN	978-0-12-812804-6 ; 9780128127742 ; 0-12-812804-6 ; 0128127740
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer.

Mehta, Meghna / Raguraman, Rajeswari / Ramesh, Rajagopal / Munshi, Anupama

Advanced drug delivery reviews

2022 Volume 191, Page(s) 114569

Abstract: Traditionally majority of eukaryotic gene expression is influenced by transcriptional and post-transcriptional events. Alterations in the expression of proteins that act post-transcriptionally can affect cellular signaling and homeostasis. RNA binding ... ...

Abstract	Traditionally majority of eukaryotic gene expression is influenced by transcriptional and post-transcriptional events. Alterations in the expression of proteins that act post-transcriptionally can affect cellular signaling and homeostasis. RNA binding proteins (RBPs) are a family of proteins that specifically bind to RNAs and are involved in post-transcriptional regulation of gene expression and important cellular processes such as cell differentiation and metabolism. Deregulation of RNA-RBP interactions and any changes in RBP expression or function can lead to various diseases including cancer. In cancer cells, RBPs play an important role in regulating the expression of tumor suppressors and oncoproteins involved in various cell-signaling pathways. Several RBPs such as HuR, AUF1, RBM38, LIN28, RBM24, tristetrapolin family and Musashi play critical roles in various types of cancers and their aberrant expression in cancer cells makes them an attractive therapeutic target for cancer treatment. In this review we provide an overview of i). RBPs involved in cancer progression and their mechanism of action ii). the role of RBPs, including HuR, in breast cancer progression and DNA damage response and iii). explore RBPs with emphasis on HuR as therapeutic target for breast cancer therapy.
MeSH term(s)	Humans ; Female ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Gene Expression Regulation ; RNA ; Breast Neoplasms ; DNA Damage
Chemical Substances	RNA-Binding Proteins ; RNA (63231-63-0) ; RBM38 protein, human ; RBM24 protein, human
Language	English
Publishing date	2022-10-14
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2022.114569
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Article ; Online: Organically derived exosomes as carriers of anticancer drugs and imaging agents for cancer treatment.

Srivastava, Akhil / Rathore, Shipra / Munshi, Anupama / Ramesh, Rajagopal

Seminars in cancer biology

2022 Volume 86, Issue Pt 1, Page(s) 80–100

Abstract: Extracellular vesicles (EVs), is the umbrella term used for different types of vesicles produced by the cells, among which exosomes form the largest group. Exosomes perform intercellular communication by carrying several biologics from donor or parental ... ...

Abstract	Extracellular vesicles (EVs), is the umbrella term used for different types of vesicles produced by the cells, among which exosomes form the largest group. Exosomes perform intercellular communication by carrying several biologics from donor or parental cells and delivering them to recipient cells. Their unique cargo-carrying capacity has recently been explored for use as delivery vehicles of anticancer drugs and imaging agents. Being naturally produced, exosomes have many advantages over synthetic lipid-based nanoparticles currently being used clinically to treat cancer and other diseases. The finding of the role of exosomes in human diseases has led to numerous preclinical and clinical studies exploring their use as an amenable drug delivery vehicle and a theranostic in cancer diagnosis and treatment. However, there are certain limitations associated with exosomes, with the most important being the selection of the biological source for producing highly biocompatible exosomes on a large scale. This review article explores the various sources from which therapeutically viable exosomes can be isolated for use as drug carriers for cancer treatment. The methods of exosome isolation and the process of loading them with cancer therapeutics and imaging agents are also discussed in the follow-up sections. Finally, the article concludes with future directions for exosome-based applications in cancer diagnosis and treatment.
MeSH term(s)	Humans ; Exosomes ; Drug Carriers/therapeutic use ; Drug Delivery Systems ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Extracellular Vesicles ; Neoplasms/diagnostic imaging ; Neoplasms/drug therapy
Chemical Substances	Drug Carriers ; Antineoplastic Agents
Language	English
Publishing date	2022-02-19
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2022.02.020
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Article: Investigating Cancerous Exosomes' Effects on CD8+ T-Cell IL-2 Production in a 3D Unidirectional Flow Bioreactor Using 3D Printed, RGD-Functionalized PLLA Scaffolds.

Karami, Daniel / Srivastava, Akhil / Ramesh, Rajagopal / Sikavitsas, Vassilios I

Journal of functional biomaterials

2022 Volume 13, Issue 1

Abstract: Exosomes from cancer cells are implicated in cancer progression and metastasis, carrying immunosuppressive factors that limit the antitumor abilities of immune cells. The development of a real-time, 3D cell/scaffold construct flow perfusion system has ... ...

Abstract	Exosomes from cancer cells are implicated in cancer progression and metastasis, carrying immunosuppressive factors that limit the antitumor abilities of immune cells. The development of a real-time, 3D cell/scaffold construct flow perfusion system has been explored as a novel tool in the study of T-cells and exosomes from cancer cells. Exosomes from human lung cancer (H1299 and A549) cells were co-cultured in a unidirectional flow bioreactor with CD8+ T-cells immobilized onto 3D-printed RGD-functionalized poly(L-lactic) acid (PLLA) scaffolds and assessed for IL-2 production. The IL-2 production was investigated for a wide range of T-cell to exosome ratios. With the successful incorporation of the RGD binding motif onto the PLLA surface at controllable densities, CD8+ T-cells were successfully attached onto 2D disks and 3D printed porous PLLA scaffolds. T-cell attachment increased with increasing RGD surface density. The diameter of the attached T-cells was 7.2 ± 0.2 µm for RGD densities below 0.5 nmoles/mm
Language	English
Publishing date	2022-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2648525-4
ISSN	2079-4983
ISSN	2079-4983
DOI	10.3390/jfb13010030
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Article: Interleukin (IL)-24: Reconfiguring the Tumor Microenvironment for Eliciting Antitumor Response.

Ramesh, Rajagopal / Ahmed, Rebaz / Munshi, Anupama

Advances in experimental medicine and biology

2021 Volume 1290, Page(s) 99–110

Abstract: Interleukin (IL)-24 is a member of the IL-10 family of cytokines. Due to its unique ability to function as both a tumor suppressor and cytokine, IL-24-based cancer therapy has been developed for treating a broad spectrum of human cancers. Majority of the ...

Abstract	Interleukin (IL)-24 is a member of the IL-10 family of cytokines. Due to its unique ability to function as both a tumor suppressor and cytokine, IL-24-based cancer therapy has been developed for treating a broad spectrum of human cancers. Majority of the studies reported to date have focused on establishing IL-24 as a cancer therapeutic by primarily focusing on tumor cell killing. However, the ability of IL-24 treatment on modulating the tumor microenvironment and immune response is underinvestigated. In this article, we summarize the biological and functional properties of IL-24 and the benefits of applying IL-24-based therapy for cancer.
MeSH term(s)	Apoptosis ; Cell Line, Tumor ; Genes, Tumor Suppressor ; Humans ; Immunity ; Interleukins/genetics ; Neoplasms/therapy ; Tumor Microenvironment
Chemical Substances	Interleukins ; interleukin-24
Language	English
Publishing date	2021-02-09
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-55617-4_7
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Article ; Online: Therapeutic approaches targeting molecular signaling pathways common to diabetes, lung diseases and cancer.

Raguraman, Rajeswari / Srivastava, Akhil / Munshi, Anupama / Ramesh, Rajagopal

Advanced drug delivery reviews

2021 Volume 178, Page(s) 113918

Abstract: Diabetes mellitus (DM), is the most common metabolic disease and is characterized by sustained hyperglycemia. Accumulating evidences supports a strong association between DM and numerous lung diseases including chronic obstructive pulmonary disease (COPD) ...

Abstract	Diabetes mellitus (DM), is the most common metabolic disease and is characterized by sustained hyperglycemia. Accumulating evidences supports a strong association between DM and numerous lung diseases including chronic obstructive pulmonary disease (COPD), fibrosis, and lung cancer (LC). The global incidence of DM-associated lung disorders is rising and several ongoing studies, including clinical trials, aim to elucidate the molecular mechanisms linking DM with lung disorders, in particular LC. Several potential mechanisms, including hyperglycemia, hyperinsulinemia, glycation, inflammation, and hypoxia, are cited as plausible links between DM and LC. In addition, studies also propose a connection between the use of anti-diabetic medications and reduction in the incidence of LC. However, the exact cause for DM associated lung diseases especially LC is not clear and is an area under intense investigation. Herein, we review the biological links reported between DM and lung disorders with an emphasis on LC. Furthermore, we report common signaling pathways (eg: TGF-β, IL-6, HIF-1, PDGF) and miRNAs that are dysregulated in DM and LC and serve as molecular targets for therapy. Finally, we propose a nanomedicine based approach for delivering therapeutics (eg: IL-24 plasmid DNA, HuR siRNA) to disrupt signaling pathways common to DM and LC and thus potentially treat DM-associated LC. Finally, we conclude that the effective modulation of commonly regulated signaling pathways would help design novel therapeutic protocols for treating DM patients diagnosed with LC.
MeSH term(s)	Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/metabolism ; Humans ; Hypoglycemic Agents/chemistry ; Hypoglycemic Agents/pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/metabolism ; Lung Diseases/diagnosis ; Lung Diseases/drug therapy ; Lung Diseases/metabolism ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; MicroRNAs ; Nanomedicine ; Platelet-Derived Growth Factor/antagonists & inhibitors ; Platelet-Derived Growth Factor/metabolism ; Signal Transduction/drug effects ; Transforming Growth Factor beta/antagonists & inhibitors ; Transforming Growth Factor beta/metabolism
Chemical Substances	Antineoplastic Agents ; HIF1A protein, human ; Hypoglycemic Agents ; Hypoxia-Inducible Factor 1, alpha Subunit ; IL6 protein, human ; Interleukin-6 ; MicroRNAs ; Platelet-Derived Growth Factor ; Transforming Growth Factor beta
Language	English
Publishing date	2021-08-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2021.113918
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Article ; Online: Extracellular Vesicles in Oncology: from Immune Suppression to Immunotherapy.

Srivastava, Akhil / Rathore, Shipra / Munshi, Anupama / Ramesh, Rajagopal

The AAPS journal

2021 Volume 23, Issue 2, Page(s) 30

Abstract: Exosomes are involved in cell-to-cell communication and play a crucial role in cellular physiology. The role of exosomes in cancer has been widely explored. Tumor cells have evolved and adapted to evade the immune response. The study of the immune system' ...

Abstract	Exosomes are involved in cell-to-cell communication and play a crucial role in cellular physiology. The role of exosomes in cancer has been widely explored. Tumor cells have evolved and adapted to evade the immune response. The study of the immune system's modulations in favor of rogue tumor cells led to the development of a novel immunotherapeutic strategy targeting the immune checkpoint proteins (ICPs). In clinical settings, the response to ICP therapy has been inconsistent and is difficult to predict. Quantitating the targeted ICPs through immunohistochemistry is one approach, but is not pragmatic in a clinical setting and is often not sensitive. Examining the molecules present in bodily fluids to determine ICP treatment response, "liquid biopsy" is a convenient alternative. The term "liquid biopsy" refers to circulating tumor cells (CTCs), extracellular vesicles (EVs), non-coding (nc) RNA, circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), etc. EVs includes exosomes, microvesicles, and oncosomes. Herein, we focus on exosomes isolated from bodily fluids and their use in liquid biopsy. Due to their unique ability to transfer bioactive molecules and perturb the physiology of recipient cells, exosomes have garnered attention for their immune modulation role and as a resource to identify molecules associated with liquid biopsy-based diagnostic methods. In this review, we examine the putative role of exosomes and their cargo in influencing the immune system. We discuss the immune and tumor cells present in the tumor microenvironment (TME), and the exosomes derived from these cells to understand how they participate in creating the immune-suppressive TME. Additionally, use of exosomes in liquid biopsy-based methods to measure the treatment response elicited by immunotherapy is discussed. Finally, we describe how exosomes have been used to develop immune therapies, especially cell-free vaccines, for cancer treatment.
MeSH term(s)	Biomarkers, Tumor ; Cancer Vaccines/administration & dosage ; Exosomes/immunology ; Exosomes/metabolism ; Exosomes/transplantation ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Proteins/metabolism ; Immunotherapy/methods ; Immunotherapy/trends ; Liquid Biopsy/methods ; Medical Oncology/methods ; Medical Oncology/trends ; Neoplasms/blood ; Neoplasms/diagnosis ; Neoplasms/immunology ; Neoplasms/therapy ; Neoplastic Cells, Circulating/immunology ; Tumor Escape ; Tumor Microenvironment/immunology
Chemical Substances	Biomarkers, Tumor ; Cancer Vaccines ; Immune Checkpoint Inhibitors ; Immune Checkpoint Proteins
Language	English
Publishing date	2021-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	1550-7416
ISSN (online)	1550-7416
DOI	10.1208/s12248-021-00554-4
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Article ; Online: Tumor-targeted exosomes for delivery of anticancer drugs.

Raguraman, Rajeswari / Bhavsar, Dhaval / Kim, Dongin / Ren, Xiaoyu / Sikavitsas, Vassilios / Munshi, Anupama / Ramesh, Rajagopal

Cancer letters

2023 Volume 558, Page(s) 216093

Abstract: Exosomes are small phospholipid bilayer vesicles that are naturally produced by all living cells, both prokaryotes and eukaryotes. The exosomes due to their unique size, reduced immunogenicity, and their ability to mimic synthetic liposomes in carrying ... ...

Abstract	Exosomes are small phospholipid bilayer vesicles that are naturally produced by all living cells, both prokaryotes and eukaryotes. The exosomes due to their unique size, reduced immunogenicity, and their ability to mimic synthetic liposomes in carrying various anticancer drugs have been tested as drug delivery vehicles for cancer treatment. An added advantage of developing exosomes as a drug carrier is the ease of manipulating their intraluminal content and their surface modification to achieve tumor-targeted drug delivery. In the past ten-years, there has been an exponential increase in the number of exosome-related studies in cancer. Preclinical studies demonstrate exosomes-mediated delivery of chemotherapeutics, biologicals and natural products produce potent anticancer activity both, in vitro and in vivo. In contrast, the number of exosome-based clinical trials are few due to challenges in the manufacturing and scalability related to large-scale production of exosomes and their storage and stability. Herein, we discuss recent advances in exosome-based drug delivery for cancer treatment in preclinical and clinical studies and conclude with challenges to be overcome for translating a larger number of exosome-based therapies into the clinic.
MeSH term(s)	Humans ; Exosomes ; Drug Delivery Systems ; Drug Carriers ; Neoplasms/drug therapy ; Antineoplastic Agents/therapeutic use
Chemical Substances	Drug Carriers ; Antineoplastic Agents
Language	English
Publishing date	2023-02-21
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2023.216093
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Article ; Online: Harnessing small extracellular vesicles for pro-oxidant delivery: novel approach for drug-sensitive and resistant cancer therapy.

Kang, Changsun / Ren, Xiaoyu / Lee, Dongwon / Ramesh, Rajagopal / Nimmo, Susan / Yang-Hartwich, Yang / Kim, Dongin

Journal of controlled release : official journal of the Controlled Release Society

2023 Volume 365, Page(s) 286–300

Abstract: Multidrug resistance (MDR) is an inevitable clinical problem in chemotherapy due to the activation of abundant P-glycoprotein (P-gp) that can efflux drugs. Limitations of current cancer therapy highlight the need for the development of a comprehensive ... ...

Abstract	Multidrug resistance (MDR) is an inevitable clinical problem in chemotherapy due to the activation of abundant P-glycoprotein (P-gp) that can efflux drugs. Limitations of current cancer therapy highlight the need for the development of a comprehensive cancer treatment strategy, including drug-resistant cancers. Small extracellular vesicles (sEVs) possess significant potential in surmounting drug resistance as they can effectively evade the efflux mechanism and transport small molecules directly to MDR cancer cells. One mechanism mediating MDR in cancer cells is sustaining increased levels of reactive oxygen species (ROS) and maintenance of the redox balance with antioxidants, including glutathione (GSH). Herein, we developed GSH-depleting benzoyloxy dibenzyl carbonate (B2C)-encapsulated sEVs (BsEVs), which overcome the efflux system to exert highly potent anticancer activity against human MDR ovarian cancer cells (OVCAR-8/MDR) by depleting GSH to induce oxidative stress and, in turn, apoptotic cell death in both OVCAR-8/MDR and OVCAR-8 cancer cells. BsEVs restore drug responsiveness by inhibiting ATP production through the oxidation of nicotinamide adenine dinucleotide with hydrogen (NADH) and inducing mitochondrial dysfunction, leading to the dysfunction of efflux pumps responsible for drug resistance. In vivo studies showed that BsEV treatment significantly inhibited the growth of OVCAR-8/MDR and OVCAR-8 tumors. Additionally, OVCAR-8/MDR tumors showed a trend towards a greater sensitivity to BsEVs compared to OVCAR tumors. In summary, this study demonstrates that BsEVs hold tremendous potential for cancer treatment, especially against MDR cancer cells.
MeSH term(s)	Humans ; Antineoplastic Agents/pharmacology ; Reactive Oxygen Species/metabolism ; Pharmaceutical Preparations ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents ; Reactive Oxygen Species ; Pharmaceutical Preparations
Language	English
Publishing date	2023-11-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2023.11.031
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Article ; Online: Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy.

Babu, Anish / Ramesh, Rajagopal

Marine drugs

2017 Volume 15, Issue 4

Abstract: Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and ... ...

Abstract	Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/chemistry ; Chitosan/chemistry ; Drug Delivery Systems/methods ; Gene Transfer Techniques ; Genetic Therapy/methods ; Humans ; Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents ; Chitosan (9012-76-4)
Language	English
Publishing date	2017-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2175190-0
ISSN	1660-3397 ; 1660-3397
ISSN (online)	1660-3397
ISSN	1660-3397
DOI	10.3390/md15040096
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