scholarly journals Exosomes as Pleiotropic Players in Pancreatic Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 275
Author(s):  
Laura De Lellis ◽  
Rosalba Florio ◽  
Maria Cristina Di Bella ◽  
Davide Brocco ◽  
Francesca Guidotti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Drug Carriers ◽  
Multiple Roles ◽  
Bioactive Molecules ◽  
Therapeutic Approaches ◽  
Antitumor Effects ◽  
Onset Of Diabetes ◽  
Immune Enhancement ◽  
Potential Exploitation ◽  
Lines Of Evidence

Pancreatic cancer (PC) incidence is rising and due to late diagnosis, combined with unsatisfactory response to current therapeutic approaches, this tumor has an extremely high mortality rate. A better understanding of the mechanisms underlying pancreatic carcinogenesis is of paramount importance for rational diagnostic and therapeutic approaches. Multiple lines of evidence have showed that exosomes are actively involved in intercellular communication by transferring their cargos of bioactive molecules to recipient cells within the tumor microenvironment and systemically. Intriguingly, exosomes may exert both protumor and antitumor effects, supporting or hampering processes that play a role in the pathogenesis and progression of PC, including shifts in tumor metabolism, proliferation, invasion, metastasis, and chemoresistance. They also have a dual role in PC immunomodulation, exerting immunosuppressive or immune enhancement effects through several mechanisms. PC-derived exosomes also induce systemic metabolic alterations, leading to the onset of diabetes and weight loss. Moreover, exosomes have been described as promising diagnostic and prognostic biomarkers for PC. Their potential application in PC therapy as drug carriers and therapeutic targets is under investigation. In this review, we provide an overview of the multiple roles played by exosomes in PC biology through their specific cargo biomolecules and of their potential exploitation in early diagnosis and treatment of PC.

Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?

2019 ◽  
Vol 19 (2) ◽  
pp. 114-118
Author(s):  
Gian Luigi Mariottini ◽  
Irwin Darren Grice
Keyword(s):  
Biological Activity ◽  
Marine Species ◽  
Natural Compounds ◽  
Therapeutic Agents ◽  
Industrial Applications ◽  
Bioactive Molecules ◽  
Sea Anemones ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
Biological Compounds

Natural compounds extracted from organisms and microorganisms are an important resource for the development of drugs and bioactive molecules. Many such compounds have made valuable contributions in diverse fields such as human health, pharmaceutics and industrial applications. Presently, however, research on investigating natural compounds from marine organisms is scarce. This is somewhat surprising considering that the marine environment makes a major contribution to Earth's ecosystems and consequently possesses a vast storehouse of diverse marine species. Interestingly, of the marine bioactive natural compounds identified to date, many are venoms, coming from Cnidarians (jellyfish, sea anemones, corals). Cnidarians are therefore particularly interesting marine species, producing important biological compounds that warrant further investigation for their development as possible therapeutic agents. From an experimental aspect, this review aims to emphasize and update the current scientific knowledge reported on selected biological activity (antiinflammatory, antimicrobial, antitumoral, anticoagulant, along with several less studied effects) of Cnidarian venoms/extracts, highlighting potential aspects for ongoing research towards their utilization in human therapeutic approaches.

scholarly journals New Aspects of the Epigenetics of Pancreatic Carcinogenesis

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 18
Author(s):  
Murat Toruner ◽  
Martin E. Fernandez-Zapico ◽  
Christopher L. Pin
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Survival Rate ◽  
Epigenetic Mechanisms ◽  
Therapeutic Approaches ◽  
Cancer Epigenetics ◽  
Pancreatic Carcinogenesis ◽  
New Therapeutic Approaches ◽  
Environmental Events ◽  
Underlying Pathogenesis

Pancreatic cancer remains among the deadliest forms of cancer with a 5 year survival rate less than 10%. With increasing numbers being observed, there is an urgent need to elucidate the pathogenesis of pancreatic cancer. While both contribute to disease progression, neither genetic nor environmental factors completely explain susceptibility or pathogenesis. Defining the links between genetic and environmental events represents an opportunity to understand the pathogenesis of pancreatic cancer. Epigenetics, the study of mitotically heritable changes in genome function without a change in nucleotide sequence, is an emerging field of research in pancreatic cancer. The main epigenetic mechanisms include DNA methylation, histone modifications and RNA interference, all of which are altered by changes to the environment. Epigenetic mechanisms are being investigated to clarify the underlying pathogenesis of pancreatic cancer including an increasing number of studies examining the role as possible diagnostic and prognostic biomarkers. These mechanisms also provide targets for promising new therapeutic approaches for this devastating malignancy.

scholarly journals Targeting Hedgehog Signalling through the Ubiquitylation Process: The Multiple Roles of the HECT-E3 Ligase Itch

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 98 ◽  
Author(s):  
Paola Infante ◽  
Ludovica Lospinoso Severini ◽  
Flavia Bernardi ◽  
Francesca Bufalieri ◽  
Lucia Di Marcotullio
Keyword(s):  
E3 Ligase ◽  
Multiple Roles ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Hedgehog Signalling ◽  
Promising Target ◽  
Important Pathway ◽  
Multiple Levels

Hedgehog signalling (Hh) is a developmental conserved pathway strongly involved in cancers when deregulated. This important pathway is orchestrated by numerous regulators, transduces through distinct routes and is finely tuned at multiple levels. In this regard, ubiquitylation processes stand as essential for controlling Hh pathway output. Although this post-translational modification governs proteins turnover, it is also implicated in non-proteolytic events, thereby regulating the most important cellular functions. The HECT E3 ligase Itch, well known to control immune response, is emerging to have a pivotal role in tumorigenesis. By illustrating Itch specificities on Hh signalling key components, here we review the role of this HECT E3 ubiquitin ligase in suppressing Hh-dependent tumours and explore its potential as promising target for innovative therapeutic approaches.

In vitro and in vivo antitumor effects of doxorubicin loaded with bacterial magnetosomes (DBMs) on H22 cells: The magnetic bio-nanoparticles as drug carriers

2007 ◽  
Vol 258 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Jian-Bo Sun ◽  
Jin-Hong Duan ◽  
Shun-Ling Dai ◽  
Jun Ren ◽  
Yan-Dong Zhang ◽  
...  
Keyword(s):  
Drug Carriers ◽  
Antitumor Effects

scholarly journals Pancreatic Cancer Small Extracellular Vesicles (Exosomes): A Tale of Short- and Long-Distance Communication

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4844
Author(s):  
Mareike Waldenmaier ◽  
Tanja Seibold ◽  
Thomas Seufferlein ◽  
Tim Eiseler
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Vesicles ◽  
Drug Carriers ◽  
Tumor Formation ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Long Distance ◽  
Diagnosis And Prognosis ◽  
Recent Advances ◽  
Biomarker Analysis

Even with all recent advances in cancer therapy, pancreatic cancer still has a dismal 5-year survival rate of less than 7%. The most prevalent tumor subtype is pancreatic ductal adenocarcinoma (PDAC). PDACs display an extensive crosstalk with their tumor microenvironment (TME), e.g., pancreatic stellate cells, but also immune cells to regulate tumor growth, immune evasion, and metastasis. In addition to crosstalk in the local TME, PDACs were shown to induce the formation of pre-metastatic niches in different organs. Recent advances have attributed many of these interactions to intercellular communication by small extracellular vesicles (sEVs, exosomes). These nanovesicles are derived of endo-lysosomal structures (multivesicular bodies) with a size range of 30–150 nm. sEVs carry various bioactive cargos, such as proteins, lipids, DNA, mRNA, or miRNAs and act in an autocrine or paracrine fashion to educate recipient cells. In addition to tumor formation, progression, and metastasis, sEVs were described as potent biomarker platforms for diagnosis and prognosis of PDAC. Advances in sEV engineering have further indicated that sEVs might once be used as effective drug carriers. Thus, extensive sEV-based communication and applications as platform for biomarker analysis or vehicles for treatment suggest a major impact of sEVs in future PDAC research.

scholarly journals Gene Therapy for Pancreatic Diseases: Current Status

2018 ◽  
Vol 19 (11) ◽  
pp. 3415 ◽  
Author(s):  
Kenya Kamimura ◽  
Takeshi Yokoo ◽  
Shuji Terai
Keyword(s):  
Pancreatic Cancer ◽  
The Body ◽  
Therapeutic Options ◽  
Current Status ◽  
Endocrine Tumors ◽  
Therapeutic Approaches ◽  
Islet Cell Tumors ◽  
Pancreatic Diseases ◽  
Gene Therapies ◽  
New Strategies

The pancreas is a key organ involved in digestion and endocrine functions in the body. The major diseases of the pancreas include pancreatitis, pancreatic cancer, cystic diseases, pancreatic divisum, islet cell tumors, endocrine tumors, diabetes mellitus, and pancreatic pain induced by these diseases. While various therapeutic methodologies have been established to date, however, the improvement of conventional treatments and establishment of novel therapies are essential to improve the efficacy. For example, conventional therapeutic options, including chemotherapy, are not effective against pancreatic cancer, and despite improvements in the last decade, the mortality rate has not declined and is estimated to become the second cause of cancer-related deaths by 2030. Therefore, continuous efforts focus on the development of novel therapeutic options. In this review, we will summarize the progress toward the development of gene therapies for pancreatic diseases, with an emphasis on recent preclinical studies and clinical trials. We aim to identify new areas for improvement of the current methodologies and new strategies that will lead to safe and effective gene therapeutic approaches in pancreatic diseases.

scholarly journals Lipid Nanostructured Particles as Emerging Carriers for Targeted Delivery of Bioactive Molecules: Applications in Food and Biomedical Sciences (An Overview)

2020 ◽  
Vol 77 (1) ◽  
pp. 37
Author(s):  
Patricia MUNTEAN ◽  
Carmen SOCACIU ◽  
Mihai Adrian SOCACIU
Keyword(s):  
Targeted Delivery ◽  
Drug Carriers ◽  
Lipid Nanoparticles ◽  
Bioactive Molecules ◽  
Biomedical Sciences ◽  
Nanostructured Particles ◽  
Drug Conjugates ◽  
Carrier Systems

Lipid nanoparticles are getting a growing scientific and technological interest, worldwide. Either Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), Lipid Drug Conjugates (LDCs) or Polymer-Lipid Nanoparticles (PLNs) have been produced and investigated last years, being reccomended as emerging carrier systems for many food and biomedical applications. An overview of the last publications, mainly since 2017 is presented, underlying the most important methods and techniques used for their preparation (e.g. high shear homogenization in hot and cold conditions, ultrasound assisted melt emulsification) as well techniques applied for measuring the size, calorimetric properties, zeta-potential, etc. Most relevant data related to the use of food-grade ingredients and designed lipid nanoparticles as delivery systems for organic and inorganic bioactive molecules in food or packaging’s are presented. The major reason for this trend in food science is the aim to overcome problems associated with the low bioavailability of many lipophilic bioactive compounds which are claimed to bring benefits to human health (carotenoid or anthocyanin pigments, sterols, vitamins). Finally, the recent applications of different formulas of lipid nanoparticles as drug carriers for in vitro experiments or for in vivo therapy (oral, parenteral or transdermal formulas) are presented.

scholarly journals Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Brian M. Wolpin ◽  
Aram F. Hezel ◽  
Thomas Abrams ◽  
Lawrence S. Blaszkowsky ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Single Agent ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Antitumor Effects ◽  
Gemcitabine Refractory

PurposeThe PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine.Patients and MethodsThirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival.ResultsTreatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as ≥ 50% reduction in serum CA19-9.ConclusionAlthough well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

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