scholarly journals Targeting hypoxia in tumor: a new promising therapeutic strategy

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Maria Carla Bosco ◽  
Gabriella D’Orazi ◽  
Donatella Del Bufalo
Keyword(s):  
Cardiovascular Disease ◽  
Therapeutic Strategy ◽  
Metabolic Diseases ◽  
Therapeutic Strategies ◽  
Low Oxygen ◽  
Radio Therapy ◽  
Oxygen Condition ◽  
Negative Role ◽  
Patient Prognosis

AbstractLow oxygen condition (hypoxia) is considered a hallmark of rapidly growing solid tumors. The presence of hypoxia renders tumor cells resistant to conventional chemo- and radio-therapy, selecting a more malignant and invasive phenotype and playing a negative role in patient prognosis. This commentary wishes to recognize the 2019 Nobel Prize in Medicine awarded to three physicians-scientists, Prof. William G. Kaelin Jr., Prof. Sir Peter J. Ratcliffe, and Prof. Gregg L. Semenza, for their discovery of the mechanisms mediating cell ability to sense and adapt to changes in oxygen availability. Their studies established the basis for our understanding of the role of hypoxia in a variety of diseases, including anemia, renal failure, cardiovascular disease, metabolic diseases, and cancer, paving the way for new promising therapeutic strategies through the development of drugs that can either activate or block the oxygen-sensing machinery.

scholarly journals Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies

2020 ◽  
Vol 11 ◽  
Author(s):  
Lihui Chen ◽  
Jie Li ◽  
Wu Zhu ◽  
Yehong Kuang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Therapeutic Strategies ◽  
Intestinal Microbiome ◽  
Core Microbiome ◽  
The Core ◽  
The World ◽  
Novel Therapeutic Strategies ◽  
Insight Into ◽  
Gaining Insight

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.

scholarly journals Roles and Clinical Applications of Exosomes in Cardiovascular Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Dong Guo ◽  
Yuerong Xu ◽  
Jian Ding ◽  
Jiaying Dong ◽  
Ning Jia ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Large Body ◽  
Bilayer Membrane ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Signal Molecules ◽  
Mortality And Morbidity ◽  
Causes Of Mortality ◽  
Bioactive Agents

Despite substantial improvements in therapeutic strategies, cardiovascular disease (CVD) is still among the leading causes of mortality and morbidity worldwide. Exosomes, extracellular vesicles with a lipid bilayer membrane of endosomal origin, have been the focus of a large body of research in CVD. Exosomes not only serve as carriers for signal molecules responsible for intercellular and interorgan communication underlying CVD pathophysiology but also are bioactive agents which are partly responsible for the therapeutic effect of stem cell therapy of CVD. We here review recent insights gained into the role of exosomes in apoptosis, hypertrophy, angiogenesis, fibrosis, and inflammation in CVD pathophysiology and progression and the application and mechanisms of exosomes as therapeutic agents for CVD.

scholarly journals Integrated Role of Nutrition and Physical Activity for Lifelong Health

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1437 ◽  
Author(s):  
Karsten Koehler ◽  
Clemens Drenowatz
Keyword(s):  
Physical Activity ◽  
Diabetes Mellitus ◽  
Cardiovascular Disease ◽  
Body Composition ◽  
Metabolic Diseases ◽  
Musculoskeletal Health ◽  
Healthy Nutrition ◽  
Improve Body Composition ◽  
Nutrition And Physical Activity

It is well established that healthy nutrition and physical activity (PA) are key lifestyle factors that modulate lifelong health through their ability to improve body composition, musculoskeletal health, and physical and cognitive performance, as well as to prevent metabolic diseases including obesity, diabetes mellitus, and cardiovascular disease across the lifespan [...]

scholarly journals Tumor-Associated Microglia and Macrophages in the Glioblastoma Microenvironment and their Implications for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4255
Author(s):  
Rikke Sick Andersen ◽  
Atul Anand ◽  
Dylan Scott Lykke Harwood ◽  
Bjarne Winther Kristensen
Keyword(s):  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Therapeutic Strategies ◽  
The Poor ◽  
Temozolomide Chemotherapy

Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months. The poor prognosis is associated with an increased abundance of tumor-associated microglia and macrophages (TAMs), which are known to play a role in creating a pro-tumorigenic environment and aiding tumor progression. Most treatment strategies are directed against glioblastoma cells; however, accumulating evidence suggests targeting of TAMs as a promising therapeutic strategy. While TAMs are typically dichotomously classified as M1 and M2 phenotypes, recent studies utilizing single cell technologies have identified expression pattern differences, which is beginning to give a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas. In this review, we evaluate the role of TAMs in the glioblastoma microenvironment and discuss how their interactions with cancer cells have an extensive impact on glioblastoma progression and treatment resistance. Finally, we summarize the effects and challenges of therapeutic strategies, which specifically aim to target TAMs.

scholarly journals WNT and β-Catenin in Cancer: Genes and Therapy

2020 ◽  
Vol 4 (1) ◽  
pp. 177-196 ◽  
Author(s):  
Rene Jackstadt ◽  
Michael Charles Hodder ◽  
Owen James Sansom
Keyword(s):  
Tumor Microenvironment ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Pathway ◽  
Therapeutic Strategy ◽  
Wnt Signaling Pathway ◽  
Therapeutic Strategies ◽  
Tissue Homeostasis ◽  
Cancer Genes

The WNT pathway is a pleiotropic signaling pathway that controls developmental processes, tissue homeostasis, and cancer. The WNT pathway is commonly mutated in many cancers, leading to widespread research into the role of WNT signaling in carcinogenesis. Understanding which cancers are reliant upon WNT activation and which components of the WNT signaling pathway are mutated is paramount to advancing therapeutic strategies. In addition, building holistic insights into the role of WNT signaling in not only tumor cells but also the tumor microenvironment is a vital area of research and may be a promising therapeutic strategy in multiple immunologically inert cancers. Novel compounds aimed at modulating the WNT signaling pathway using diverse mechanisms are currently under investigation in preclinical/early clinical studies. Here, we review how the WNT pathway is activated in multiple cancers and discuss current strategies to target aberrant WNT signaling.

scholarly journals Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Eunhee Kim ◽  
Dong Min Lee ◽  
Min Ji Seo ◽  
Hong Jae Lee ◽  
Kyeong Sook Choi
Keyword(s):  
Therapeutic Strategy ◽  
Ion Homeostasis ◽  
Proteasome Inhibitors ◽  
Therapeutic Strategies ◽  
Regulatory Mechanisms ◽  
Mediated Communication ◽  
Flux System ◽  
Intracellular Ca ◽  
Potential Cancer

Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Since paraptosis is morphologically and biochemically different from apoptosis, understanding its regulatory mechanisms may provide a novel therapeutic strategy in malignant cancer cells that have proven resistant to conventional pro-apoptotic treatments. Relatively little is known about the molecular basis of paraptosis, but perturbations of cellular proteostasis and ion homeostasis appear to critically contribute to the process. Ca2+ transport has been shown to be important in the paraptosis induced by several natural products, metal complexes, and co-treatment with proteasome inhibitors and certain Ca2+-modulating agents. In particular, the Ca2+-mediated communication between the ER and mitochondria plays a crucial role in paraptosis. Mitochondrial Ca2+ overload from the intracellular Ca2+-flux system located at the ER–mitochondrial axis can induce mitochondrial dilation during paraptosis, while the accumulation of misfolded proteins within the ER lumen is believed to exert an osmotic force and draw water from the cytoplasm to distend the ER lumen. In this process, Ca2+ release from the ER also critically contributes to aggravating ER stress and ER dilation. This review focuses on the role of Ca2+ transport in paraptosis by summarizing the recent findings related to the actions of Ca2+-modulating paraptosis-inducing agents and discussing the potential cancer therapeutic strategies that may effectively induce paraptosis via Ca2+ signaling.

scholarly journals Role of Polyphenols and Carotenoids in Endothelial Dysfunction: An Overview from Classic to Innovative Biomarkers

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Natalia Di Pietro ◽  
Maria Pompea Antonia Baldassarre ◽  
Angelo Cichelli ◽  
Assunta Pandolfi ◽  
Gloria Formoso ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Metabolic Diseases ◽  
Complementary Therapy ◽  
Platelet Activity ◽  
Main Challenge ◽  
Obesity And Diabetes ◽  
Dietary Nutrients ◽  
Health Promoting

Nowadays, the dramatically increased prevalence of metabolic diseases, such as obesity and diabetes mellitus and their related complications, including endothelial dysfunction and cardiovascular disease, represents one of the leading causes of death worldwide. Dietary nutrients together with healthy lifestyles have a crucial role in the endothelium health-promoting effects. From a growing body of evidence, active natural compounds from food, including polyphenols and carotenoids, have attracted particular attention as a complementary therapy on atherosclerosis and cardiovascular disease, as well as preventive approaches through the attenuation of inflammation and oxidative stress. They mainly act as radical scavengers by promoting a variety of biological mechanisms, such as improvements in endothelial function, blood pressure, platelet activity, and insulin sensitivity, and by modulating various known biomarkers. The present review highlights the role of polyphenols and carotenoids in early endothelial dysfunction with attention to their beneficial effect in modulating both classical and recent technologically generated emerging biomarkers. These, alone or in combination, can play an important role in the prediction, diagnosis, and evolution of cardiovascular disease. However, a main challenge is to speed up early and prompt new interventions in order to prevent or slow down disease progression, even with an adequate intake of bioactive compounds. Hence, there is an urgent need of new more validated, appropriate, and reliable diagnostic and therapeutic biomarkers useful to diagnose endothelial dysfunction at an earlier stage.

scholarly journals Arachidonic Acid Metabolites in Cardiovascular and Metabolic Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3285 ◽  
Author(s):  
Thomas Sonnweber ◽  
Alex Pizzini ◽  
Manfred Nairz ◽  
Günter Weiss ◽  
Ivan Tancevski
Keyword(s):  
Cardiovascular Disease ◽  
Arachidonic Acid ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Nutrient Metabolism ◽  
Alcoholic Fatty Liver ◽  
Acid Metabolites ◽  
Immune Pathways ◽  
Alcoholic Fatty Liver Disease

Lipid and immune pathways are crucial in the pathophysiology of metabolic and cardiovascular disease. Arachidonic acid (AA) and its derivatives link nutrient metabolism to immunity and inflammation, thus holding a key role in the emergence and progression of frequent diseases such as obesity, diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. We herein present a synopsis of AA metabolism in human health, tissue homeostasis, and immunity, and explore the role of the AA metabolome in diverse pathophysiological conditions and diseases.

scholarly journals Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4831
Author(s):  
Jiaqi Li ◽  
Jie Qing Eu ◽  
Li Ren Kong ◽  
Lingzhi Wang ◽  
Yaw Chyn Lim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Therapeutic Strategy ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Cancer Associated Fibroblasts ◽  
Tumour Metabolism

Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells. This metabolic rewiring and crosstalk with the tumour microenvironment play a key role in cell proliferation, metastasis, and the development of treatment resistance. In this review, we will discuss therapeutic opportunities, which arise from dysregulated metabolism and metabolic crosstalk, highlighting strategies that may aid in the precision targeting of altered tumour metabolism with a focus on combinatorial therapeutic strategies.

scholarly journals Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1599 ◽  
Author(s):  
Marta Pérez-Hernández ◽  
Alain Arias ◽  
David Martínez-García ◽  
Ricardo Pérez-Tomás ◽  
Roberto Quesada ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Therapeutic Strategy ◽  
Nutrient Recycling ◽  
Clinical Results ◽  
Therapeutic Strategies ◽  
Combination Therapies ◽  
Novel Therapeutic Strategies ◽  
Cellular Components ◽  
Catabolic Process

Autophagy is a tightly regulated catabolic process that facilitates nutrient recycling from damaged organelles and other cellular components through lysosomal degradation. Deregulation of this process has been associated with the development of several pathophysiological processes, such as cancer and neurodegenerative diseases. In cancer, autophagy has opposing roles, being either cytoprotective or cytotoxic. Thus, deciphering the role of autophagy in each tumor context is crucial. Moreover, autophagy has been shown to contribute to chemoresistance in some patients. In this regard, autophagy modulation has recently emerged as a promising therapeutic strategy for the treatment and chemosensitization of tumors, and has already demonstrated positive clinical results in patients. In this review, the dual role of autophagy during carcinogenesis is discussed and current therapeutic strategies aimed at targeting autophagy for the treatment of cancer, both under preclinical and clinical development, are presented. The use of autophagy modulators in combination therapies, in order to overcome drug resistance during cancer treatment, is also discussed as well as the potential challenges and limitations for the use of these novel therapeutic strategies in the clinic.

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