scholarly journals Clinical Candidates Targeting the ATR–CHK1–WEE1 Axis in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 795
Author(s):  
Lukas Gorecki ◽  
Martin Andrs ◽  
Jan Korabecny
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Current Status ◽  
Future Perspectives ◽  
Phase Ii Trials ◽  
Anticancer Treatment ◽  
Positive Outlook ◽  
Insight Into

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

scholarly journals Epigenetic Regulation of Apoptosis and Cell Cycle in Osteosarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Krithi Rao-Bindal ◽  
Eugenie S. Kleinerman
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Molecular Mechanisms ◽  
Genetic Mutations ◽  
Epigenetic Mechanisms ◽  
Epigenetic Alterations ◽  
Novel Therapeutic Strategies ◽  
Cycle Regulation ◽  
Insight Into

The role of genetic mutations in the development of osteosarcoma, such as alterations in p53 and Rb, is well understood. However, the significance of epigenetic mechanisms in the progression of osteosarcoma remains unclear and is increasingly being investigated. Recent evidence suggests that epigenetic alterations such as methylation and histone modifications of genes involved in cell cycle regulation and apoptosis may contribute to the pathogenesis of this tumor. Importantly, understanding the molecular mechanisms of regulation of these pathways may give insight into novel therapeutic strategies for patients with osteosarcoma. This paper serves to summarize the described epigenetic mechanisms in the tumorigenesis of osteosarcoma, specifically those pertaining to apoptosis and cell cycle regulation.

scholarly journals Use of artificial intelligence in imaging in rheumatology – current status and future perspectives

RMD Open ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. e001063 ◽  
Author(s):  
Berend Stoel
Keyword(s):  
Artificial Intelligence ◽  
Deep Learning ◽  
Basic Research ◽  
Current Status ◽  
Future Perspectives ◽  
Clinical Imaging ◽  
The World ◽  
Human Interpretation ◽  
The Impact ◽  
Insight Into

After decades of basic research with many setbacks, artificial intelligence (AI) has recently obtained significant breakthroughs, enabling computer programs to outperform human interpretation of medical images in very specific areas. After this shock wave that probably exceeds the impact of the first AI victory of defeating the world chess champion in 1997, some reflection may be appropriate on the consequences for clinical imaging in rheumatology. In this narrative review, a short explanation is given about the various AI techniques, including ‘deep learning’, and how these have been applied to rheumatological imaging, focussing on rheumatoid arthritis and systemic sclerosis as examples. By discussing the principle limitations of AI and deep learning, this review aims to give insight into possible future perspectives of AI applications in rheumatology.

MicroRNA-1225-5p acts as a tumor-suppressor in laryngeal cancer via targeting CDC14B

2019 ◽  
Vol 400 (2) ◽  
pp. 237-246 ◽  
Author(s):  
Peng Sun ◽  
Dan Zhang ◽  
Haiping Huang ◽  
Yafeng Yu ◽  
Zhendong Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Division ◽  
Cell Cycle Arrest ◽  
Molecular Mechanisms ◽  
Normal Tissues ◽  
Cycle Arrest ◽  
Enhanced Expression ◽  
Insight Into

Abstract This study aimed to investigate the role of miRNA-1225-5p (miR-1225) in laryngeal carcinoma (LC). We found that the expression of miR-1225 was suppressed in human LC samples, while CDC14B (cell division cycle 14B) expression was reinforced in comparison with surrounding normal tissues. We also demonstrated that enhanced expression of miR-1225 impaired the proliferation and survival of LC cells, and resulted in G1/S cell cycle arrest. In contrast, reduced expression of miR-1225 promoted cell survival. Moreover, miR-1225 resulted in G1/S cell cycle arrest and enhanced cell death. Further, miR-1225 targets CDC14B 3′-UTR and recovery of CDC14B expression counteracted the suppressive influence of miR-1225 on LC cells. Thus, these findings offer insight into the biological and molecular mechanisms behind the development of LC.

scholarly journals Tumor Lymphangiogenesis as a Potential Therapeutic Target

2012 ◽  
Vol 2012 ◽  
pp. 1-23 ◽  
Author(s):  
Tam Duong ◽  
Peter Koopman ◽  
Mathias Francois
Keyword(s):  
Lymph Node ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Regional Lymph Node ◽  
Lymphatic Vessels ◽  
Potential Therapeutic Target ◽  
Tumor Lymphangiogenesis

Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis.

Molecular mechanisms of G0/G1 cell-cycle arrest and apoptosis induced by terfenadine in human cancer cells

2003 ◽  
Vol 37 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Jean-Dean Liu ◽  
Ying-Jan Wang ◽  
Chien-Ho Chen ◽  
Cheng-Fei Yu ◽  
Li-Ching Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals Cyclin G2 promotes cell cycle arrest in breast cancer cells responding to fulvestrant and metformin and correlates with patient survival

Cell Cycle ◽  
2016 ◽  
Vol 15 (23) ◽  
pp. 3278-3295 ◽  
Author(s):  
Maike Zimmermann ◽  
Aruni P. S. Arachchige-Don ◽  
Michaela S. Donaldson ◽  
Tommaso Patriarchi ◽  
Mary C. Horne
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Patient Survival ◽  
Cycle Arrest ◽  
Cyclin G2

scholarly journals Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

Marine Drugs ◽  
2015 ◽  
Vol 13 (7) ◽  
pp. 4470-4491 ◽  
Author(s):  
Ulf Geisen ◽  
Marion Zenthoefer ◽  
Matthias Peipp ◽  
Jannik Kerber ◽  
Johannes Plenge ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Fucus Vesiculosus ◽  
Pancreatic Cancer Cells ◽  
Cell Cycle Inhibition

scholarly journals The Australian fruit Illawarra plum (Podocarpus elatusEndl., Podocarpaceae) inhibits telomerase, increases histone deacetylase activity and decreases proliferation of colon cancer cells

2012 ◽  
Vol 109 (12) ◽  
pp. 2117-2125 ◽  
Author(s):  
Erin L. Symonds ◽  
Izabela Konczak ◽  
Michael Fenech
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Molecular Mechanisms ◽  
Sirtuin 1 ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Class Iii ◽  
Ht 29

Fruit antioxidants have many health benefits including prevention of cancer development. The native Australian bush fruit Illawarra plum (Podocarpus elatusEndl., Podocarpaceae) has a high content of anthocyanin-rich phenolics, with an antioxidant capacity at levels higher than most fruits. In the present study the molecular mechanisms of the anti-proliferative activity of Illawarra plum on colorectal cancer cells were investigated. Non-tumorigenic young adult mouse colonic (YAMC) cells and tumorigenic human colonic (HT-29) cells were treated with a polyphenolic-rich Illawarra plum extract (0–1000 μg/ml). Illawarra plum had anti-proliferative properties in only the cancer cells, with growth suppressed in a dose- and time-dependent manner. Treatment of HT-29 cells with Illawarra plum extract (500 μg/ml; 24 h) was also associated with a 2-fold increase in apoptosis, and a cell cycle delay in the S phase (P< 0·01). Assessment of biomarkers for DNA damage revealed that plum treatment caused a 93 % down-regulation of telomerase activity (P< 0·001) and a decrease in telomere length (up to 75 %;P< 0·01). Treatment with Illawarra plum extract also induced morphological alterations to HT-29 cells that were suggestive of induction of autophagy, as the formation of cytoplasmic vacuoles was observed in many cells. This could be induced by the increased (6-fold) histone deacetylase (HDAC) activity (P< 0·001) and the trend for increased expression of the class III HDAC sirtuin 1. The present study has shown that Illawarra plum extract is able to reduce the proliferation of colon cancer cells by altering the cell cycle, increasing apoptosis and possibly inducing autophagy. The active ingredients in Illawarra plum may provide an alternative chemoprevention strategy to conventional chemotherapy.

scholarly journals Assessment of molecular mechanisms and potential biomarkers in bladder urothelial carcinoma

Acta Medica ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 8-15
Author(s):  
Ceren Sucularlı
Keyword(s):  
Cell Cycle ◽  
Urothelial Carcinoma ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Smooth Muscle Contraction ◽  
Receptor Interaction ◽  
Ppi Networks ◽  
Normal Bladder ◽  
Bladder Urothelial Carcinoma ◽  
Potential Biomarkers

Objective: Bladder cancer ranks 10th among the most common cancers worldwide, effecting mostly man than women. The aim of this study is to perform a detailed gene expression analysis of bladder urothelial carcinoma to reveal altered molecular mechanisms and to find potential biomarkers for this cancer. Materials and Methods: Bladder urothelial carcinoma RNA-seq data from TCGA and normal bladder samples from GTEx were analyzed by using GEPIA. Differentially expressed genes were annotated to GO-BP and KEGG pathway terms with DAVID and PPI networks were constructed by STRING. The association of upregulated cell cycle pathway proteins and patient survival was further investigated. Results: Upregulated genes mainly annotated to cell cycle, p53 signaling and oocyte meiosis and maturation pathways and cell cycle related GO-BP terms. Downregulated genes mostly annotated to adhesion, ECM-receptor interaction, vascular smooth muscle contraction and cardiomyopathy related KEGG pathways and muscle related GO-BP terms. The protein products of six cell cycle genes, which were upregulated in bladder urothelial carcinoma, showed significant association with patient survival. Conclusion: The results of this study showed altered molecular mechanisms and increased our understanding in bladder urothelial carcinoma, proposed potential prognostic biomarkers.  

Sign in / Sign up

Export Citation Format

Share Document