scholarly journals Podocyte Sphingolipid Signaling in Nephrotic Syndrome.

2021 ◽  
Vol 55 (S4) ◽  
pp. 13-34
Keyword(s):  
Nephrotic Syndrome ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Genetic Disorders ◽  
Therapeutic Strategies ◽  
Vital Role ◽  
Sphingolipid Metabolism ◽  
Current Evidence ◽  
Glomerular Permeability ◽  
Novel Therapeutic Strategies

Podocytes play a vital role in the pathogenesis of nephrotic syndrome (NS), which is clinically characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and peripheral edema. The pathogenesis of NS has evolved through several hypotheses ranging from immune dysregulation theory and increased glomerular permeability theory to the current concept of podocytopathy. Podocytopathy is characterized by dysfunction or depletion of podocytes, which may be caused by unknown permeability factor, genetic disorders, drugs, infections, systemic disorders, and hyperfiltration. Over the last two decades, numerous studies have been done to explore the molecular mechanisms of podocyte injuries or NS and to develop the novel therapeutic strategies targeting podocytopathy for treatment of NS. Recent studies have shown that normal sphingolipid metabolism is essential for structural and functional integrity of podocytes. As a basic component of the plasma membrane, sphingolipids not only support the assembly of signaling molecules and interaction of receptors and effectors, but also mediate various cellular activities, such as apoptosis, proliferation, stress responses, necrosis, inflammation, autophagy, senescence, and differentiation. This review briefly summarizes current evidence demonstrating the regulation of sphingolipid metabolism in podocytes and the canonical or noncanonical roles of podocyte sphingolipid signaling in the pathogenesis of NS and associated therapeutic strategies.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

scholarly journals Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 114
Author(s):  
Lisa Linck-Paulus ◽  
Claus Hellerbrand ◽  
Anja K. Bosserhoff ◽  
Peter Dietrich
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
The Future ◽  
Associated Proteins ◽  
Cancer Types ◽  
Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

scholarly journals Noncoding RNAs

2014 ◽  
Vol 121 (2) ◽  
pp. 409-417 ◽  
Author(s):  
Brianna Marie Lutz ◽  
Alex Bekker ◽  
Yuan-Xiang Tao
Keyword(s):  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Antisense Rna ◽  
Dorsal Root ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Current Evidence ◽  
Noxious Stimuli ◽  
Chronic Pain Conditions ◽  
Novel Therapeutic Strategies

Abstract Chronic pain, a common clinical symptom, is often treated inadequately or ineffectively in part due to the incomplete understanding of molecular mechanisms that initiate and maintain this disorder. Newly identified noncoding RNAs govern gene expression. Recent studies have shown that peripheral noxious stimuli drive expressional changes in noncoding RNAs and that these changes are associated with pain hypersensitivity under chronic pain conditions. This review first presents current evidence for the peripheral inflammation/nerve injury–induced change in the expression of two types of noncoding RNAs, microRNAs, and Kcna2 antisense RNA, in pain-related regions, particularly in the dorsal root ganglion. The authors then discuss how peripheral noxious stimuli induce such changes. The authors finally explore potential mechanisms of how expressional changes in dorsal root ganglion microRNAs and Kcna2 antisense RNA contribute to the development and maintenance of chronic pain. An understanding of these mechanisms may propose novel therapeutic strategies for preventing and/or treating chronic pain.

scholarly journals Respiratory Homeostasis and Exploitation of the Immune System for Lung Cancer Vaccines

2009 ◽  
Vol 05 (01) ◽  
pp. 40
Author(s):  
Adam Yagui-Beltrán ◽  
Lisa M Coussens ◽  
David M Jablons ◽  
◽  
◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Vaccines ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Lung Carcinogenesis ◽  
Respiratory Homeostasis ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Lung cancer is the leading cause of all cancer deaths in the US. The international scientific and clinical community has made significant advances toward understanding specific molecular mechanisms underlying lung carcinogenesis; however, despite these insights and advances in surgery and chemoradiotherapy, the prognosis for non-small-cell lung cancer (NSCLC) remains poor. Nonetheless, significant effort is being focused on advancing translational research evaluating the efficacy of novel targeted therapeutic strategies for lung cancer. Illustrative examples of this include antagonists of the epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib, and a diverse assortment of anti-angiogenic compounds targeting growth factors and/or their receptors that regulate tumorassociated angiogenic programs. In addition, with the increased awareness of the significant role chronically activated leukocytes play as potentiators of solid-tumor development, the role of innate and adaptive immune cells as regulators of lung carcinogenesis is being examined. While some of these studies are examining how novel therapeutic strategies may enhance the efficacy of lung cancer vaccines, others are evaluating the intrinsic characteristics of the immune response to lung cancer in order to identify rate-limiting molecular and/or cellular programs to target with novel anticancer therapeutics. In this article, we explore important aspects of the immune system and its role in regulating normal respiratory homeostasis compared with the immune response accompanying development of lung cancer. These hallmarks are then discussed in the context of recent efforts to develop lung cancer vaccines, where we have highlighted important concepts that must be taken into consideration for future development of novel therapeutic strategies and clinical trials assessing their efficacy.

scholarly journals Prospects for NK Cell Therapy of Sarcoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3719
Author(s):  
Mieszko Lachota ◽  
Marianna Vincenti ◽  
Magdalena Winiarska ◽  
Kjetil Boye ◽  
Radosław Zagożdżon ◽  
...  
Keyword(s):  
Nk Cells ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Current Treatment ◽  
Lymphoid Cells ◽  
Current Evidence ◽  
Treatment Regimens ◽  
Novel Therapeutic Strategies

Natural killer (NK) cells are innate lymphoid cells with potent antitumor activity. One of the most NK cell cytotoxicity-sensitive tumor types is sarcoma, an aggressive mesenchyme-derived neoplasm. While a combination of radical surgery and radio- and chemotherapy can successfully control local disease, patients with advanced sarcomas remain refractory to current treatment regimens, calling for novel therapeutic strategies. There is accumulating evidence for NK cell-mediated immunosurveillance of sarcoma cells during all stages of the disease, highlighting the potential of using NK cells as a therapeutic tool. However, sarcomas display multiple immunoevasion mechanisms that can suppress NK cell function leading to an uncontrolled tumor outgrowth. Here, we review the current evidence for NK cells’ role in immune surveillance of sarcoma during disease initiation, promotion, progression, and metastasis, as well as the molecular mechanisms behind sarcoma-mediated NK cell suppression. Further, we apply this basic understanding of NK–sarcoma crosstalk in order to identify and summarize the most promising candidates for NK cell-based sarcoma immunotherapy.

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.

Molecular mechanisms controlling human adipose tissue development: insights from monogenic lipodystrophies

2010 ◽  
Vol 12 ◽  
Author(s):  
Justin J. Rochford
Keyword(s):  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Single Gene ◽  
Human Adipose Tissue ◽  
Therapeutic Strategies ◽  
Fat Tissue ◽  
Tissue Development ◽  
Adipose Tissue Development ◽  
Novel Therapeutic Strategies ◽  
And Function

Appropriately functioning adipose tissue is essential for human health, a fact most clearly illustrated by individuals with lipodystrophy, who have impaired adipose development and often suffer severe metabolic disease as a result. Humans with obesity display a similar array of metabolic problems. This reflects failures in fat tissue function in obesity, which results in consequences similar to those seen when insufficient adipose tissue is present. Thus a better understanding of the molecules that regulate the development of fat tissue is likely to aid the generation of novel therapeutic strategies for the treatment of all disorders of altered fat mass. Single gene disruptions causing lipodystrophy can give unique insights into the importance of the proteins they encode in human adipose tissue development. Moreover, the mechanisms via which they cause lipodystrophy can reveal new molecules and pathways important for adipose tissue development and function as well as confirming the importance of molecules identified from studies of cellular and animal models.

scholarly journals Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

2022 ◽  
Vol 9 ◽  
Author(s):  
Fangyu Zhou ◽  
Xin Wang ◽  
Lingjun Wang ◽  
Xin Sun ◽  
Guiqin Tan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Treg Cells ◽  
Current Treatment ◽  
Therapeutic Strategies ◽  
Vital Role ◽  
Graves Disease ◽  
Cellular Immunology ◽  
Organ Specific ◽  
Novel Therapeutic Strategies

Graves’ disease (GD) is a well-known organ-specific autoimmune disease characterized by hyperthyroidism, goiter, and exophthalmos. The incidence of GD is approximately 2.0–3.0% in China and 0.5–2.0% in Western countries. Due to the complex pathogenesis and etiology of GD, current treatment methods have great side effects that seriously endanger human health. Therefore, it is particularly important to understand the pathogenesis of GD. Various studies have shown that genetics, epigenetics, cellular immunology, and gut microbiota are all involved in the development of GD. Genetically, CD25 gene and VDR gene polymorphisms are involved in the development of GD by increasing the ratio of Th17/Treg cells. Epigenetically, miR-23a-3p and lncRNA-MEG3 lead to Th17/Treg imbalance and participate in the progression of GD. Moreover, commensal microbe deletion can disrupt Th17/Treg balance and participate in the occurrence of GD. The imbalance of Th17/Treg cells induced by genetics, epigenetics, and gut microbiota plays a vital role in the pathogenesis of GD. Therefore, this article reviews the role of genetics, epigenetics, cellular immunology, and gut microbiota in the pathogenic mechanism of GD. This may lead to the development of novel therapeutic strategies and providing promising therapeutic targets.

scholarly journals The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight

2021 ◽  
Vol 10 ◽  
Author(s):  
Tongyue Zhang ◽  
Danfei Liu ◽  
Yijun Wang ◽  
Mengyu Sun ◽  
Limin Xia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gastrointestinal Stromal Tumors ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Strategies ◽  
Stromal Tumors ◽  
Advanced Tumor ◽  
Novel Therapeutic Strategies ◽  
Ets Factors

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Although therapeutic strategies have recently advanced, tumor metastasis and drug resistance continue to pose challenges in the treatment of HCC. Therefore, new molecular targets are needed to develop novel therapeutic strategies for this cancer. E-twenty-six (ETS) transcription family has been implicated in human malignancies pathogenesis and progression, including leukemia, Ewing sarcoma, gastrointestinal stromal tumors. Recently, increasing studies have expanded its great potential as functional players in other cancers, including HCC. This review focuses primarily on the key functions and molecular mechanisms of ETS factors in HCC. Elucidating these molecular details may provide novel potential therapeutic strategies for cancers.

Sign in / Sign up

Export Citation Format

Share Document