scholarly journals The role of NOTCH1 signaling in T-ALL

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 353-361 ◽  
Author(s):  
Adolfo A. Ferrando
Keyword(s):  
Molecular Mechanisms ◽  
Notch Signaling Pathway ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
Leukemic Cells ◽  
Combination Therapies ◽  
Activating Mutations ◽  
Notch1 Signaling ◽  
Major Interest

AbstractThe identification of activating mutations in NOTCH1 in over 50% of T-cell acute lymphoblastic leukemias (T-ALL) has generated major interest in the elucidation of the mechanisms of transformation downstream of oncogenic NOTCH and in the targeting of the NOTCH signaling pathway in this disease. Small molecule γ-secretase inhibitors (GSIs) block NOTCH1 signaling in T-ALL lymphoblasts, yet the clinical development of GSIs has been held back by the development of gastrointestinal toxicity and their weak antileukemic effects against human T-ALL. However, new therapeutic strategies aiming to optimize the use of anti-NOTCH1 therapies for T-ALL, including combination therapies with molecularly targeted drugs and glucocorticoids, have started to emerge as a result of improved understanding of the molecular mechanisms that mediate the effects of GSIs in leukemic cells and the intestinal epithelium. This review focuses on the molecular basis of NOTCH1-induced transformation, the mechanisms of action of oncogenic NOTCH1 and clinical significance of NOTCH1 mutations in T-ALL.

scholarly journals MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3026
Author(s):  
Hyuk Moon ◽  
Simon-Weonsang Ro
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Erk Signaling ◽  
Health Concern ◽  
Alternative Mechanism ◽  
Major Health ◽  
Activating Mutations ◽  
Genetic Events

Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

scholarly journals The Role of MicroRNAs in Hepatoblastoma Tumors

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 409 ◽  
Author(s):  
Ion Cristóbal ◽  
Marta Sanz-Álvarez ◽  
Melani Luque ◽  
Cristina Caramés ◽  
Federico Rojo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Strategies ◽  
Substantial Contribution ◽  
Hepatic Malignancy ◽  
Recent Advances

Hepatoblastoma is the most common hepatic malignancy during childhood. However, little is still known about the molecular mechanisms that govern the development of this disease. This review is focused on the recent advances regarding the study of microRNAs in hepatoblastoma and their substantial contribution to improv our knowledge of the pathogenesis of this disease. We show here that miRNAs represent valuable tools to identify signaling pathways involved in hepatoblastoma progression as well as useful biomarkers and novel molecular targets to develop alternative therapeutic strategies in this disease.

scholarly journals Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1135 ◽  
Author(s):  
Francesca Bonomini ◽  
Elisa Borsani ◽  
Gaia Favero ◽  
Luigi Rodella ◽  
Rita Rezzani
Keyword(s):  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Therapeutic Strategies ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Positive Effect ◽  
And Oxidative Stress

In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

scholarly journals Carboplatin: molecular mechanisms of action associated with chemoresistance

2014 ◽  
Vol 50 (4) ◽  
pp. 693-701 ◽  
Author(s):  
Graziele Fonseca de Sousa ◽  
Samarina Rodrigues Wlodarczyk ◽  
Gisele Monteiro
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
Rational Drug Design ◽  
Full Potential ◽  
Mechanisms Of Resistance ◽  
Development Of Resistance ◽  
Rational Drug ◽  
Biochemical Mechanisms ◽  
Tumor Types

Carboplatin is a derivative of cisplatin; it has a similar mechanism of action, but differs in terms of structure and toxicity. It was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several tumor types. This agent is characterized by its ability to generate lesions in DNA through the formation of adducts with platinum, thereby inhibiting replication and transcription and leading to cell death. However, its use can lead to serious inconvenience arising from the development of resistance that some patients acquire during treatment, limiting the scope of its full potential. Currently, the biochemical mechanisms related to resistance are not precisely known. Therefore, knowledge of pathways associated with resistance caused by carboplatin exposure may provide valuable clues for more efficient rational drug design in platinum-based therapy and the development of new therapeutic strategies. In this narrative review, we discuss some of the known mechanisms of resistance to platinum-based drugs, especially carboplatin.

scholarly journals Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies

Open Biology ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 200286
Author(s):  
Niraj Kumar Jha ◽  
Ankur Sharma ◽  
Saurabh Kumar Jha ◽  
Shreesh Ojha ◽  
Dinesh Kumar Chellappan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Hiv Infections ◽  
Therapeutic Strategies ◽  
Toxic Substances ◽  
Brain Disorder ◽  
Persistent Inflammation ◽  
Potential Link

Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood–brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.

scholarly journals lncRNA SNHG15 Induced by SOX12 Promotes the Tumorigenic Properties and Chemoresistance in Cervical Cancer via the miR-4735-3p/HIF1a Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Jiang Yang ◽  
Mei Yang ◽  
Huabing Lv ◽  
Min Zhou ◽  
Xiaogang Mao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Luciferase Reporter ◽  
Major Health ◽  
Tumor Tissues ◽  
High Prevalence ◽  
Reporter Assays

Cervical cancer (CC) is one of the most common malignancies in females, with high prevalence and mortality globally. Despite advances in diagnosis and therapeutic strategies developed in recent years, CC is still a major health burden worldwide. The molecular mechanisms underlying the development of CC need to be understood. In this study, we aimed to demonstrate the role of lncRNA SNHG15 in CC progression. Using qRT-PCR, we determined that lncRNA SNHG15 is highly expressed in CC tumor tissues and cells. lncRNA SNHG15 knockdown also reduces the tumorigenic properties of CC in vitro, as determined using the MTT, EdU, flow cytometry, and transwell assays. Using bioinformatics analysis, RNA pull-down, ChIP, and luciferase reporter assays, we verified the molecular mechanisms of lncRNA SNHG15 in CC progression and found that lncRNA SNHG15 expression in CC cells is transcriptionally regulated by SOX12; moreover, lncRNA SNHG15 promotes CC progression via the miR-4735-3p/HIF1a axis. This study can provide a potential target for CC diagnosis or therapeutic strategies in the future.

The role of overweight and obesity on severe Covid-19: the evidence and possible mechanisms of action

2020 ◽  
Vol 1 (1) ◽  
pp. 1-5
Author(s):  
Rafael Rangel-Aldao
Keyword(s):  
Mechanical Ventilation ◽  
Risk Factor ◽  
Causal Relationship ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Mechanisms Of Action ◽  
Overweight And Obesity ◽  
Relationship Of

This commentary addresses three fundamental questions, 1) How solid is the evidence regarding obesity as a risk factor to Covid-19, in particular to the most serious form of the disease requiring hospitalization and mechanical ventilation? 2) What cellular and/or molecular mechanisms could explain a possible enhancement of the disease by obesity? 3) Given a probable and causal relationship of overweight and obesity with severe Covid-19, the question then arises on whether it may be possible to use as therapy well know drugs that work on fat metabolism?

scholarly journals Peripheral Mechanisms of Dental Pain: The Role of Substance P

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Paola Sacerdote ◽  
Luca Levrini
Keyword(s):  
Substance P ◽  
Molecular Mechanisms ◽  
Dental Pain ◽  
Therapeutic Strategies ◽  
Current Evidence ◽  
Trigeminal Ganglia ◽  
Clinical Observations ◽  
P Concentration ◽  
Inflammatory Processes

Current evidence supports the central role of neuropeptides in the molecular mechanisms underlying dental pain. In particular, substance P, a neuropeptide produced in neuron cell bodies localised in dorsal root and trigeminal ganglia, contributes to the transmission and maintenance of noxious stimuli and inflammatory processes. The major role of substance P in the onset of dental pain and inflammation is increasingly being recognised. Well-grounded experimental and clinical observations have documented an increase in substance P concentration in patients affected by caries, pulpitis, or granulomas and in those undergoing standard orthodontic or orthodontic/dental care procedures. This paper focuses on the role of substance P in the induction and maintenance of inflammation and dental pain, in order to define future lines of research for the evaluation of therapeutic strategies aimed at modulating the complex effects of this mediator in oral tissues.

scholarly journals An Overview of Long Non-Coding (lnc)RNAs in Neuroblastoma

2021 ◽  
Vol 22 (8) ◽  
pp. 4234
Author(s):  
Francesca Baldini ◽  
Matilde Calderoni ◽  
Laura Vergani ◽  
Paola Modesto ◽  
Tullio Florio ◽  
...  
Keyword(s):  
Recent Progress ◽  
Molecular Mechanisms ◽  
Mechanisms Of Action ◽  
Biological Functions ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Definitive Therapy ◽  
Sporadic Cases ◽  
Non Coding Rnas

Neuroblastoma (NB) is a heterogeneous developmental tumor occurring in childhood, which arises from the embryonic sympathoadrenal cells of the neural crest. Although the recent progress that has been done on this tumor, the mechanisms involved in NB are still partially unknown. Despite some genetic aberrations having been identified, the sporadic cases represent the majority. Due to its wide heterogeneity in clinical behavior and etiology, NB represents a challenge in terms of prevention and treatment. Since a definitive therapy is lacking so far, there is an urgent necessity to unveil the molecular mechanisms behind NB onset and progression to develop new therapeutic approaches. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides. Whether lncRNAs are destined to become a protein or not, they exert multiple biological functions such as regulating gene expression and functions. In recent decades, different research has highlighted the possible role of lncRNAs in the pathogenesis of many diseases, including cancer. Moreover, lncRNAs may represent potential markers or targets for diagnosis and treatment of diseases. This mini-review aimed to briefly summarize the most recent findings on the involvement of some lncRNAs in NB disease by focusing on their mechanisms of action and possible role in unveiling NB onset and progression.

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