Autophagy in Cisplatin Nephrotoxicity during Cancer Therapy

Cisplatin is a widely used chemotherapeutic agent but its clinical use is often limited by nephrotoxicity. Autophagy is a lysosomal degradation pathway that removes protein aggregates and damaged or dysfunctional cellular organelles for maintaining cell homeostasis. Upon cisplatin exposure, autophagy is rapidly activated in renal tubule cells to protect against acute cisplatin nephrotoxicity. Mechanistically, the protective effect is mainly related to the clearance of damaged mitochondria via mitophagy. The role and regulation of autophagy in chronic kidney problems after cisplatin treatment are currently unclear, despite the significance of research in this area. In cancers, autophagy may prevent tumorigenesis, but autophagy may reduce the efficacy of chemotherapy by protecting cancer cells. Future research should focus on developing drugs that enhance the anti-tumor effects of cisplatin while protecting kidneys during cisplatin chemotherapy.

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Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy

Current Pharmaceutical Design ◽

10.2174/1381612822666161026162347 ◽

2017 ◽

Vol 23 (3) ◽

pp. 454-466 ◽

Cited By ~ 16

Author(s):

Daniele R. Nogueira-Librelotto ◽

Cristiane F. Codevilla ◽

Ammad Farooqi ◽

Clarice M. B. Rolim

Keyword(s):

Drug Delivery ◽

Cancer Therapy ◽

Tumor Cells ◽

Therapeutic Benefit ◽

Active Targeting ◽

Future Research ◽

Passive Targeting ◽

The Right ◽

Review Current ◽

Target Effects

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research.

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SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways

The Journal of Cell Biology ◽

10.1083/jcb.201111121 ◽

2012 ◽

Vol 197 (2) ◽

pp. 219-230 ◽

Cited By ~ 114

Author(s):

Florian Steinberg ◽

Kate J. Heesom ◽

Mark D. Bass ◽

Peter J. Cullen

Keyword(s):

Isotope Labeling ◽

Degradation Pathway ◽

Lysosomal Degradation ◽

Sorting Nexins ◽

Retromer Complex ◽

Proteomic Approach ◽

Cytoplasmic Tails ◽

Npxy Motif ◽

Global Identification ◽

Insight Into

The FERM-like domain–containing sorting nexins of the SNX17/SNX27/SNX31 family have been proposed to mediate retrieval of transmembrane proteins from the lysosomal pathway. In this paper, we describe a stable isotope labeling with amino acids in culture–based quantitative proteomic approach that allows an unbiased, global identification of transmembrane cargoes that are rescued from lysosomal degradation by SNX17. This screen revealed that several integrins required SNX17 for their stability, as depletion of SNX17 led to a loss of β1 and β5 integrins and associated a subunits from HeLa cells as a result of increased lysosomal degradation. SNX17 bound to the membrane distal NPXY motif in β integrin cytoplasmic tails, thereby preventing lysosomal degradation of β integrins and their associated a subunits. Furthermore, SNX17-dependent retrieval of integrins did not depend on the retromer complex. Consistent with an effect on integrin recycling, depletion of SNX17 also caused alterations in cell migration. Our data provide mechanistic insight into the retrieval of internalized integrins from the lysosomal degradation pathway, a prerequisite for subsequent recycling of these matrix receptors.

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Therapeutic concentrations of cyclosporine A, but not FK506, increase P-glycoprotein expression in endothelial and renal tubule cells

Kidney International ◽

10.1046/j.1523-1755.1998.00095.x ◽

1998 ◽

Vol 54 (4) ◽

pp. 1139-1149 ◽

Cited By ~ 54

Author(s):

Ingeborg A. Hauser ◽

Michael Koziolek ◽

Ulrich Hopfer ◽

Frank Thévenod

Keyword(s):

Cyclosporine A ◽

Renal Tubule ◽

P Glycoprotein ◽

Tubule Cells

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Intraoral radiation stents—Primer for clinical use in head and neck cancer therapy

Head & Neck ◽

10.1002/hed.26848 ◽

2021 ◽

Author(s):

Annu Singh ◽

Evan B. Rosen ◽

Joseph D. Randazzo ◽

Cherry L. Estilo ◽

Daphna Y. Gelblum ◽

...

Keyword(s):

Head And Neck Cancer ◽

Cancer Therapy ◽

Head And Neck ◽

Neck Cancer ◽

Clinical Use

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Apoptosis Antagonizing Transcription Factor Protects Renal Tubule Cells against Oxidative Damage and Apoptosis Induced by Ischemia-Reperfusion

Journal of the American Society of Nephrology ◽

10.1681/asn.2006040311 ◽

2006 ◽

Vol 17 (12) ◽

pp. 3336-3346 ◽

Cited By ~ 35

Author(s):

Jun Xie ◽

Qing Guo

Keyword(s):

Transcription Factor ◽

Oxidative Damage ◽

Renal Tubule ◽

Ischemia Reperfusion ◽

Tubule Cells

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N-Acetyl Galactosamine Targeting: Paving the Way for Clinical Application of Nucleotide Medicines in Cardiovascular Diseases

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316290 ◽

2021 ◽

Author(s):

Erik A.L. Biessen ◽

Theo J.C. Van Berkel

Keyword(s):

Immune Responses ◽

Targeted Delivery ◽

Antisense Oligonucleotides ◽

Sugar Metabolism ◽

Innate Immune ◽

Future Research ◽

Clinical Use ◽

Innate Immune Responses ◽

Chemically Modified ◽

Intrinsic Capacity

While the promise of oligonucleotide therapeutics, such as (chemically modified) ASO (antisense oligonucleotides) and short interfering RNAs, is undisputed from their introduction onwards, their unfavorable pharmacokinetics and intrinsic capacity to mobilize innate immune responses, were limiting widespread clinical use. However, these major setbacks have been tackled by breakthroughs in chemistry, stability and delivery. When aiming an intervention hepatic targets, such as lipid and sugar metabolism, coagulation, not to mention cancer and virus infection, introduction of N-acetylgalactosamine aided targeting technology has advanced the field profoundly and by now a dozen of N-acetylgalactosamine therapeutics for these indications have been approved for clinical use or have progressed to clinical trial stage 2 to 3 testing. This technology, in combination with major advances in oligonucleotide stability allows safe and durable intervention in targets that were previously deemed undruggable, such as Lp(a) and PCSK9, at high efficacy and specificity, often with as little as 2 doses per year. Their successful use even the most visionary would not have predicted 2 decades ago. Here, we will review the evolution of N-acetylgalactosamine technology. We shall outline their fundamental design principles and merits, and their application for the delivery of oligonucleotide therapeutics to the liver. Finally, we will discuss the perspectives of N-acetylgalactosamine technology and propose directions for future research in receptor targeted delivery of these gene medicines.

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Gender Role Conflict Scale for Adolescents

Boyhood Studies ◽

10.3149/thy.0102.191 ◽

2007 ◽

Vol 1 (2) ◽

pp. 191-204 ◽

Cited By ~ 2

Author(s):

Chris Blazina ◽

Maribel A. Cordova ◽

Stewart Pisecco ◽

Anna G. Settle

Keyword(s):

Gender Role ◽

Role Conflict ◽

Gender Role Conflict ◽

Concurrent Validity ◽

Future Research ◽

Clinical Use ◽

Male Role ◽

Masculinity Ideology ◽

Conflict Scale

This study investigated the Gender Role Conflict Scale-Adolescent Version (GRCS-A) and its relationship with the Gender Role Conflict Scale (GRCS), the measure from which it was adapted. Significant correlations between the adult and adolescent versions provided support for the concurrent validity of the GRCS-A. Further analyses revealed that two other measures of male masculinity, the Adolescent Masculinity Ideology in Relationships Scale (AMIRS) and Male Role Attitudes Scale (MRAS), are also significantly related to the GRCS-A. Implications for future research and clinical use are discussed.

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Autophagy gene-dependent intracellular immunity triggered by interferon-γ

10.1101/2021.05.10.443539 ◽

2021 ◽

Author(s):

Michael R McAllaster ◽

Jaya Bhushan ◽

Dale R Balce ◽

Anthony Orvedahl ◽

Arnold Park ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Interferon Γ ◽

Degradation Pathway ◽

Lysosomal Degradation ◽

Cellular Processes ◽

Binding Domains ◽

New Genes ◽

Autophagy Gene ◽

Atg Genes ◽

Dependent Processes

Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of Norovirus and Toxoplasma gondii replication. Herein we identified new genes that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. IFNγ-induced inhibition of norovirus replication required Wipi2b and Atg9a, but not Becn1 (encoding Beclin1), Atg14, or Sqstm1. The phosphatidylinositol-3-phosphate and ATG16L1 binding domains of WIPI2B were required for IFNγ-induced inhibition of norovirus replication. Both WIPI2 and SQSTM1 were required for IFN?-induced inhibition of Toxoplasma gondii replication in HeLa cells. These studies further delineate the mechanisms of a programmable form of cytokine-induced intracellular immunity that relies on an expanding cassette of essential ATG genes to restrict the growth of phylogenetically diverse pathogens.

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Biomarkers in Posttraumatic Stress Disorder: Overview and Implications for Future Research

Disease Markers ◽

10.1155/2013/835876 ◽

2013 ◽

Vol 35 ◽

pp. 43-54 ◽

Cited By ~ 56

Author(s):

Ulrike Schmidt ◽

Sebastian F. Kaltwasser ◽

Carsten T. Wotjak

Keyword(s):

Posttraumatic Stress Disorder ◽

Sexual Abuse ◽

Anxiety Disorder ◽

Posttraumatic Stress ◽

Stress Disorder ◽

Future Research ◽

Clinical Use ◽

Current State ◽

Life Threatening ◽

State Of Research

PTSD can develop in the aftermath of traumatic incidents like combat, sexual abuse, or life threatening accidents. Unfortunately, there are still no biomarkers for this debilitating anxiety disorder in clinical use. Anyhow, there are numerous studies describing potential PTSD biomarkers, some of which might progress to the point of practical use in the future. Here, we outline and comment on some of the most prominent findings on potential imaging, psychological, endocrine, and molecular PTSD biomarkers and classify them into risk, disease, and therapy markers. Since for most of these potential PTSD markers a causal role in PTSD has been demonstrated or at least postulated, this review also gives an overview on the current state of research on PTSD pathobiology.

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