scholarly journals The Role of Hypoxia in Glioblastoma Radiotherapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 542
Author(s):  
Agathe L. Chédeville ◽  
Patricia A. Madureira
Keyword(s):  
Clinical Trials ◽  
Tumor Recurrence ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Patient Death ◽  
O2 Partial Pressure ◽  
Comprehensive Examination ◽  
Radiotherapy Resistance ◽  
Combinational Therapies

Glioblastoma (GB) (grade IV astrocytoma) is the most malignant type of primary brain tumor with a 16 months median survival time following diagnosis. Despite increasing attention regarding the development of targeted therapies for GB that resulted in around 450 clinical trials currently undergoing, radiotherapy still remains the most clinically effective treatment for these patients. Nevertheless, radiotherapy resistance (radioresistance) is commonly observed in GB patients leading to tumor recurrence and eventually patient death. It is therefore essential to unravel the molecular mechanisms underpinning GB cell radioresistance in order to develop novel strategies and combinational therapies focused on enhancing tumor cell sensitivity to radiotherapy. In this review, we present a comprehensive examination of the current literature regarding the role of hypoxia (O2 partial pressure less than 10 mmHg), a main GB microenvironmental factor, in radioresistance with the ultimate goal of identifying potential molecular markers and therapeutic targets to overcome this issue in the future.

scholarly journals The Role of Curcumin in Cancer Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1086
Author(s):  
Vasiliki Zoi ◽  
Vasiliki Galani ◽  
Georgios D. Lianos ◽  
Spyridon Voulgaris ◽  
Athanasios P. Kyritsis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Curcuma Longa ◽  
Immune Modulators ◽  
Anticancer Properties ◽  
Stat3 Signaling ◽  
Anticancer Effects ◽  
Transcription 3 ◽  
Light Chain Enhancer

Curcumin is a polyphenol extracted from the rhizomes of the turmeric plant, Curcuma longa which has anti-inflammatory, and anticancer properties. Chronic inflammation is associated with the development of cancer. Curcumin acts on the regulation of various immune modulators, including cytokines, cyclooxygenase-2 (COX-2), and reactive oxygen species (ROS), which partly explains its anticancer effects. It also takes part in the downregulation of growth factors, protein kinases, oncogenic molecules and various signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (STAT3) signaling. Clinical trials of curcumin have been completed or are ongoing for various types of cancer. This review presents the molecular mechanisms of curcumin in different types of cancer and the evidence from the most recent clinical trials.

scholarly journals Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Sylvie Hermouet ◽  
Edith Bigot-Corbel ◽  
Betty Gardie
Keyword(s):  
Clinical Trials ◽  
Chronic Inflammation ◽  
Molecular Diagnosis ◽  
Molecular Mechanisms ◽  
Myeloproliferative Neoplasms ◽  
Heterogeneous Group ◽  
Genetic Defects ◽  
Jak Inhibitor ◽  
Recent Advances

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in theJAK2, MPL,orCALRgenes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in theJAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients withJAK2-mutated MPNs may not be the consequence ofJAK2mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.

scholarly journals Inflammatory and Non-Inflammatory Mechanisms Controlling Cirrhosis Development

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5045
Author(s):  
Paula Sánchez Sánchez ◽  
MarÃa del Mar Rigual ◽  
Nabil Djouder
Keyword(s):  
Molecular Mechanisms ◽  
Liver Disorder ◽  
The Body ◽  
Patient Death ◽  
Medical Needs ◽  
Liver Cancers ◽  
Environmental Agents ◽  
Regenerative Nodules ◽  
The Relationship

Because the liver is considered to be one of the most important metabolic organs in the body, it is continuously exposed to damaging environmental agents. Upon damage, several complex cellular and molecular mechanisms in charge of liver recovery and regeneration are activated to prevent the failure of the organ. When liver injury becomes chronic, the regenerative response goes awry and impairs the liver function, consequently leading to cirrhosis, a liver disorder that can cause patient death. Cirrhosis has a disrupted liver architecture and zonation, along with the presence of fibrosis and parenchymal nodules, known as regenerative nodules (RNs). Inflammatory cues contribute to the cirrhotic process in response to chronic damaging agents. Cirrhosis can progress to HCC, the most common and one of the most lethal liver cancers with unmet medical needs. Considering the essential role of inflammatory pathways in the development of cirrhosis, further understanding of the relationship between immune cells and the activation of RNs and fibrosis would guide the design of innovative therapeutic strategies to ameliorate the survival of cirrhotic and HCC patients. In this review, we will summarize the inflammatory mechanisms implicated in the development of cirrhosis.

scholarly journals Myo-inositol – A potential prophylaxis against premature onset of labour and preterm birth

2021 ◽  
pp. 1-19
Author(s):  
Neha Sharma ◽  
Oliver C. Watkins ◽  
Anne H.Y. Chu ◽  
W. Cutfield ◽  
Keith M. Godfrey ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Preterm Birth ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Secondary Outcome ◽  
Critical Threshold ◽  
Membrane Rupture ◽  
Labour Onset ◽  
Small Clinical Trials

Abstract The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour-onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour-onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production, and secretion of pro-inflammatory chemocytokines, that overall dampen the pro-labour uteroplacental environment responsible for labour-onset and progress, thus, reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.

scholarly journals Clinical significance of checkpoint regulator “Programmed death ligand-1 (PD-L1)” expression in meningioma: review of the current status

2021 ◽  
Vol 151 (3) ◽  
pp. 443-449
Author(s):  
Shirin Karimi ◽  
Sheila Mansouri ◽  
Farshad Nassiri ◽  
Severa Bunda ◽  
Olivia Singh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Tumor Heterogeneity ◽  
Checkpoint Inhibitors ◽  
Primary Brain Tumor ◽  
Current Status ◽  
High Grade ◽  
Programmed Death Ligand 1 ◽  
Multiple Tumor ◽  
Programmed Death

Abstract Introduction Meningioma is the most common primary brain tumor. Most meningiomas are benign; however, a subset of these tumors can be aggressive, presenting with early or multiple tumor recurrences that are refractory to neurosurgical resection and radiotherapy. There is no standard systemic therapy for these patients, and post-surgical management of these patients is usually complicated due to lack of accurate prediction for tumor progression. Methods In this review, we summarise the crucial immunosuppressive role of checkpoint regulators, including PD-1 and PD-L1 interacting in the tumor microenvironment, which has led to efforts aimed at targeting this axis. Results Since their discovery, checkpoint inhibitors have significantly improved the outcome in many types of cancers. Currently, targeted therapy for PD-1 and PD-L1 proteins are being tested in several ongoing clinical trials for brain tumors such as glioblastoma. More recently, there have been some reports implicating increased PD-L1 expression in high-grade (WHO grades II and III) meningiomas. Several clinical trials are underway to assess the efficacy of checkpoint inhibitors in the therapeutic management of patients with aggressive meningiomas. Here, we review the immune suppressive microenvironment in meningiomas, and then focus on clinical and pathological characterization and tumor heterogeneity with respect to PD-L1 expression as well as challenges associated with the assessment of PD-L1 expression in meningioma. Conclusion We conclude with a brief review of ongoing clinical trials using checkpoint inhibitors for the treatment of high-grade and refractory meningiomas.

scholarly journals The Cholecystokinin Type 2 Receptor, a Pharmacological Target for Pain Management

2021 ◽  
Vol 14 (11) ◽  
pp. 1185
Author(s):  
Amandine Bernard ◽  
Aurore Danigo ◽  
Sylvie Bourthoumieu ◽  
Mohamad Mroué ◽  
Alexis Desmoulière ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pain Management ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Pain Perception ◽  
Pain Modulation ◽  
Comprehensive Overview ◽  
Sensory Nervous System

Over the past decades, accumulating evidence has demonstrated a pivotal role of cholecystokinin type 2 receptor (CCK2R) in pain modulation. The established role of CCK2R activation in directly facilitating nociception has led to the development of several CCK2R antagonists, which have been shown to successfully alleviate pain in several rodent models of pain. However, the outcomes of clinical trials are more modest since they have not demonstrated the expected biological effect obtained in animals. Such discordances of results between preclinical and clinical studies suggest reconsidering our knowledge about the molecular basis of the pharmacology and functioning of CCK2R. This review focuses on the cellular localization of CCK2R specifically in the sensory nervous system and discusses in further detail the molecular mechanisms and signal transduction pathways involved in controlling pain perception. We then provide a comprehensive overview of the most successful compounds targeting CCK2R and report recent advances in pharmacological strategies used to achieve CCK2R modulation. We purposely distinguish between CCK2R benefits obtained in preclinical models and outcomes in clinical trials with different pain etiologies. Lastly, we emphasize the biological and clinical relevance of CCK2R as a promising target for the development of new treatments for pain management.

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Bridging the Knowledge Gaps in Arrhythmogenic Cardiovascular Conditions: The Critical Role of Registries

2016 ◽  
Vol 10 (2) ◽  
pp. 1 ◽  
Author(s):  
Melody Hermel ◽  
Rebecca Duffy ◽  
Alexander Orfanos ◽  
Isabelle Hack ◽  
Shayna McEnteggart ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Risk Stratification ◽  
Critical Role ◽  
Knowledge Gaps ◽  
Level Of Evidence ◽  
The Future

Cardiac registries have filled many gaps in knowledge related to arrhythmogenic cardiovascular conditions. Despite the less robust level of evidence available in registries when compared with clinical trials, registries have contributed a range of clinically useful information. In this review, the authors discuss the role that registries have played – related to diagnosis, natural history, risk stratification, treatment, and genetics of arrhythmogenic cardiovascular conditions – in closing knowledge gaps, and their role in the future.

Sign in / Sign up

Export Citation Format

Share Document