scholarly journals PDS5A and PDS5B in Cohesin Function and Human Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 5868
Author(s):  
Nenggang Zhang ◽  
Luiza E. Coutinho ◽  
Debananda Pati
Keyword(s):  
Therapeutic Strategies ◽  
Molecular Characteristics ◽  
Cohesin Complex ◽  
Repair Gene ◽  
Associate Protein ◽  
Cellular Processes ◽  
Damage Repair ◽  
Chromatid Cohesion ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Precocious dissociation of sisters 5 (PDS5) is an associate protein of cohesin that is conserved from yeast to humans. It acts as a regulator of the cohesin complex and plays important roles in various cellular processes, such as sister chromatid cohesion, DNA damage repair, gene transcription, and DNA replication. Vertebrates have two paralogs of PDS5, PDS5A and PDS5B, which have redundant and unique roles in regulating cohesin functions. Herein, we discuss the molecular characteristics and functions of PDS5, as well as the effects of its mutations in the development of diseases and their relevance for novel therapeutic strategies.

scholarly journals TMOD-29. ESTABLISHMENT OF PATIENT-DERIVED XENOGRAFTS FROM RARE PRIMARY BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii234-ii234
Author(s):  
Noriyuki Kijima ◽  
Yoshikazu Nakajima ◽  
Daisuke Kanematsu ◽  
Tomoko Shofuda ◽  
Yuichiro Higuchi ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Translational Research ◽  
Single Cells ◽  
Molecular Classification ◽  
Therapeutic Strategies ◽  
Molecular Characteristics ◽  
Preclinical Development ◽  
Primary Brain Tumors ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Abstract Patient derived xenografts are essential tools for translational research and preclinical development of novel therapeutic strategies of primary brain tumors. Recent advances in genomics of primary brain tumors revealed molecular classification of primary brain tumors, thus establishment of patient derived xenografts from each subtype of primary brain tumors is urgently needed. However, currently available patient derived xenografts are limited and are from specific subtype of primary brain tumors such as glioblastoma IDH wild type. In this study, we aim to establish patient derived xenografts from primary brain tumors with various molecular characteristics, especially rare primary brain tumors. We got primary brain tumor tissues from patients, dissociated those tissue into single cells, and orthotopically injected those cells into NOD/Shi-scid IL2Rγ KO mouse. We successfully established rare patient-derived xenografts from atypical teratoid rhabdoid tumor and CNS Ewing sarcoma family tumor with CIC alteration, which is recently described as new entity of primitive neuroectodermal tumors of the CNS. We also analyzed histopathological characteristics of these xenografts and found that each xenograft well recapitulated histopathological features of original patients’ resected tumors. These xenografts have advantages for translational research and preclinical development of novel therapeutic strategies for rare primary brain tumors. In addition, further efforts are needed to establish other types of rare primary brain tumors.

PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDLCholesterol

2018 ◽  
Vol 19 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Yan Wang ◽  
Zhao-Peng Liu
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Maximum Tolerated Dose ◽  
Therapeutic Strategies ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Safety Issues ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-offunction mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors have been under investigation, and much progress has been made in clinical trials, especially for monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and adnectins, and the related safety issues.

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 Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management

2021 ◽  
Vol 139 ◽  
pp. 111708
Author(s):  
Pushkar Singh Rawat ◽  
Aiswarya Jaiswal ◽  
Amit Khurana ◽  
Jasvinder Singh Bhatti ◽  
Umashanker Navik
Keyword(s):  
Molecular Mechanism ◽  
Therapeutic Strategies ◽  
Effective Management ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

scholarly journals Short-Term Reproducibility of MUC5AC Measurement in Human Tear Fluid

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 57
Author(s):  
Ashley M. Woodward ◽  
Michelle Senchyna ◽  
Pablo Argüeso
Keyword(s):  
Statistical Difference ◽  
Tear Film ◽  
Therapeutic Strategies ◽  
Individual Variability ◽  
Tear Fluid ◽  
Individual Data ◽  
Short Term ◽  
Coefficients Of Variation ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

The assessment of tear fluid components is a common and valuable approach to understanding ocular surface disease and testing the efficacy of novel therapeutic strategies. However, the interpretation and utility of the findings can be limited by changes in the composition of the tear film, particularly in studies requiring repetitive patient sampling. Here, tear samples were collected twice within a one-hour interval to evaluate the short-term reproducibility of an immunoassay aimed to measure the amount of MUC5AC mucin. We found no statistical difference in total protein or MUC5AC content between the two consecutive collections of tear fluid, although the inter-individual variability in each group was high, with coefficients of variation exceeding 30% and 50%, respectively. Scatterplots showed a significant correlation in both protein and MUC5AC following collection within a one-hour interval. These data indicate that, regardless of the high inter-individual variability, repeated collection of tear fluid within an hour interval produces reproducible intra-individual data in terms of MUC5AC mucin content, and suggest that the normal mucin composition of the tear fluid can be re-established within an hour of the initial collection.

scholarly journals Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Nastassja Terraneo ◽  
Francis Jacob ◽  
Anna Dubrovska ◽  
Jürgen Grünberg
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Strategies ◽  
Ovarian Cancer Stem Cells ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic
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