Therapeutic Potential of miR-494 in Thrombosis and Other Diseases: A Review

2016 ◽  
Vol 69 (10) ◽  
pp. 1078 ◽  
Author(s):  
Jasmine Tay ◽  
Jim Tiao ◽  
Quintin Hughes ◽  
Grace Gilmore ◽  
Ross Baker
Keyword(s):  
Nucleic Acids ◽  
Contraceptive Use ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Protein S ◽  
Oral Contraceptive Use ◽  
S Deficiency ◽  
Functional Nucleic Acids

Functional nucleic acids, such as microRNAs (miRNAs), have been implicated in the pathophysiology of many diseases. The miRNA expression profiles of various cancers including haematological malignancies are well defined, but the role of miRNAs in haemostasis and the regulation of coagulation is poorly understood. We identified that miR-494 is oestrogen responsive and directly targets the anticoagulant protein, Protein S, as a mechanism for acquiring Protein S deficiency under high oestrogenic conditions such as during pregnancy and oral contraceptive use. Furthermore, previous studies have also characterised miR-494 to be involved in many biological processes. This paper reviews the current knowledge in the role of miRNAs in regulating haemostatic proteins and the known biological functions of miR-494, highlighting miR-494 as an emerging therapeutic target, with an overview of the strategy we have employed in identifying functional nucleic acids such as miRNAs that target haemostatic factors and the therapeutic potential of miR-494-directed therapy for the treatment of thrombotic disorders.

scholarly journals The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3219 ◽  
Author(s):  
Balbina García-Reyes ◽  
Anna-Laura Kretz ◽  
Jan-Philipp Ruff ◽  
Silvia von Karstedt ◽  
Andreas Hillenbrand ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Transcriptional Elongation ◽  
Cyclin Dependent Kinases ◽  
Dismal Prognosis ◽  
The Family ◽  
Cycle Regulation

The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC’s resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

scholarly journals The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signaling Cascades ◽  
Cell Functions ◽  
Regulatory Circuits ◽  
Complex Functions ◽  
Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

scholarly journals The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1887 ◽  
Author(s):  
Francesco Bonollo ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Sofia Karkampouna
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Progression ◽  
Normal Prostate ◽  
Prostate Tumorigenesis

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.

scholarly journals The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1792 ◽  
Author(s):  
Rada Tazhitdinova ◽  
Alexander V. Timoshenko
Keyword(s):  
Cancer Biology ◽  
Cellular Differentiation ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Cell Types ◽  
Innovative Strategies ◽  
Protein Levels ◽  
Differentiated Cells ◽  
Independent Functions

Galectins are a family of soluble β-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. Human cells express twelve out of sixteen recognized mammalian galectin genes and their expression profiles are very different between cell types and tissues. In this review, we summarize the current knowledge on the changes in the expression of individual galectins at mRNA and protein levels in different types of differentiating cells and the effects of recombinant galectins on cellular differentiation. A new model of galectin regulation is proposed considering the change in O-GlcNAc homeostasis between progenitor/stem cells and mature differentiated cells. The recognition of galectins as regulatory factors controlling cell differentiation and self-renewal is essential for developmental and cancer biology to develop innovative strategies for prevention and targeted treatment of proliferative diseases, tissue regeneration, and stem-cell therapy.

scholarly journals Successful penile reconstruction following prior arteriovenous loop thrombosis due to undiagnosed protein-S deficiency and exogenous testosterone

2016 ◽  
Vol 49 (02) ◽  
pp. 268-270 ◽  
Author(s):  
Parameswaran Anoop ◽  
Vithal Malmande ◽  
M. N. Prakash Kumar ◽  
Naveen Rao
Keyword(s):  
Protein S ◽  
Protein S Deficiency ◽  
Thrombotic Occlusion ◽  
Flap Failure ◽  
S Deficiency ◽  
Testosterone Administration ◽  
Thrombogenic Potential ◽  
Arteriovenous Loop

ABSTRACTFlap failure from microvascular thrombotic occlusion is a rare but significant cause for unsuccessful reconstructive surgery. We encountered thrombosis of arteriovenous loop in a patient undergoing phallus reconstruction. Further investigations revealed underlying previously asymptomatic hypercoagulable state due to protein-S deficiency in addition to long-term exogenous testosterone administration. Role of thrombophilia testing, thrombogenic potential of testosterone and the need for therapeutic perioperative anti-coagulation in such situations are described here.

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehran Pashirzad ◽  
Reihaneh Khorasanian ◽  
Maryam Mahmoudi Fard ◽  
Mohammad-Hassan Arjmand ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Erk Signaling ◽  
Clinical Settings ◽  
Cancer Cell Proliferation ◽  
Resistance Mutations ◽  
Clinical Value

: The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

Parasite glycans and antibody-mediated immune responses inSchistosomainfection

Parasitology ◽  
2012 ◽  
Vol 139 (9) ◽  
pp. 1219-1230 ◽  
Author(s):  
ANGELA VAN DIEPEN ◽  
NIELS S. J. VAN DER VELDEN ◽  
CORNELIS H. SMIT ◽  
MONIEK H. J. MEEVISSEN ◽  
CORNELIS H. HOKKE
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Antibody Responses ◽  
Infection Rates ◽  
Immune Intervention ◽  
Protective Mechanisms ◽  
Future Directions ◽  
Slow Development

SUMMARYSchistosome infections in humans are characterized by the development of chronic disease and high re-infection rates after treatment due to the slow development of immunity. It appears that anti-schistosome antibodies are at least partially mediating protective mechanisms. Efforts to develop a vaccine based on immunization with surface-exposed or secreted larval or worm proteins are ongoing. Schistosomes also express a large number of glycans as part of their glycoprotein and glycolipid repertoire, and antibody responses to those glycans are mounted by the infected host. This observation raises the question if glycans might also form novel vaccine targets for immune intervention in schistosomiasis. This review summarizes current knowledge of antibody responses and immunity in experimental and natural infections withSchistosoma, the expression profiles of schistosome glycans (the glycome), and antibody responses to individual antigenic glycan motifs. Future directions to study anti-glycan responses in schistosomiasis in more detail in order to address more precisely the possible role of glycans in antibody-mediated immunity are discussed.

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