scholarly journals EVI1 dysregulation: impact on biology and therapy of myeloid malignancies

2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Christine Birdwell ◽  
Warren Fiskus ◽  
Tapan M. Kadia ◽  
Courtney D. DiNardo ◽  
Christopher P. Mill ◽  
...  
Keyword(s):  
Integration Site ◽  
Therapeutic Interventions ◽  
Viral Integration ◽  
Common Site ◽  
Poor Clinical Outcome ◽  
Zinc Finger Transcription Factor ◽  
Myeloid Malignancies ◽  
Epithelial Cancers ◽  
New Knowledge ◽  
Novel Therapeutic

AbstractEcotropic viral integration site 1 (Evi1) was discovered in 1988 as a common site of ecotropic viral integration resulting in myeloid malignancies in mice. EVI1 is an oncogenic zinc-finger transcription factor whose overexpression contributes to disease progression and an aggressive phenotype, correlating with poor clinical outcome in myeloid malignancies. Despite progress in understanding the biology of EVI1 dysregulation, significant improvements in therapeutic outcome remain elusive. Here, we highlight advances in understanding EVI1 biology and discuss how this new knowledge informs development of novel therapeutic interventions. EVI1 is overexpression is correlated with poor outcome in some epithelial cancers. However, the focus of this review is the genetic lesions, biology, and current therapeutics of myeloid malignancies overexpressing EVI1.

scholarly journals Ecotropic viral integration site 1 regulates EGFR transcription in glioblastoma cells

2019 ◽  
Vol 145 (2) ◽  
pp. 223-231
Author(s):  
Asako Mizuguchi ◽  
Shinji Yamashita ◽  
Kiyotaka Yokogami ◽  
Kazuhiro Morishita ◽  
Hideo Takeshima
Keyword(s):  
Integration Site ◽  
Growth Factor Receptor ◽  
Viral Integration ◽  
Lower Grade ◽  
Glioma Tissue ◽  
Epithelial Cancers ◽  
Lower Grade Glioma ◽  
Reporter Assays ◽  
Epidermal Growth ◽  
The Relationship

Abstract Purpose Ecotropic viral integration site-1 (EVI1) is a transcription factor that contributes to the unfavorable prognosis of leukemia, some epithelial cancers, and glial tumors. However, the biological function of EVI1 in glioblastoma multiforme (GBM) remains unclear. Based on microarray experiments, EVI1 has been reported to regulate epidermal growth factor receptor (EGFR) transcription. Signal transduction via EGFR plays an essential role in glioblastoma. Therefore, we performed this study to clarify the importance of EVI1 in GBM by focusing on the regulatory mechanism between EVI1 and EGFR transcription. Methods We performed immunohistochemical staining and analyzed the EVI1-expression in glioma tissue. To determine the relationship between EVI1 and EGFR, we induced siRNA-mediated knockdown of EVI1 in GBM cell lines. To investigate the region that was essential for the EVI1 regulation of EGFR expression, we conducted promoter reporter assays. We performed WST-8 assay to investigate whether EVI1 affected on the proliferation of GBM cells or not. Results It was observed that 22% of GBM tissues had over 33% of tumor cells expressing EVI1, whereas no lower-grade glioma tissue had over 33% by immunohistochemistry. In A172 and YKG1 cells, the expression levels of EGFR and EVI1 correlated. Analysis of the EGFR promoter region revealed that the EGFR promoter (from − 377 to − 266 bp) was essential for the EVI regulation of EGFR expression. We showed that EVI1 influenced the proliferation of A172 and YKG1 cells. Conclusion This is the first study reporting the regulation of EGFR transcription by EVI1 in GBM cells.

scholarly journals Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1781
Author(s):  
Gustavo A. Arias-Pinilla ◽  
Helmout Modjtahedi
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Antibody Therapy ◽  
Therapeutic Targets ◽  
Poor Response ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Western World ◽  
Wide Range ◽  
Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

scholarly journals Novel therapeutic interventions towards improved management of septic arthritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jian Wang ◽  
Liucai Wang
Keyword(s):  
Antibiotic Therapy ◽  
Septic Arthritis ◽  
Clinical Success ◽  
Treatment Protocol ◽  
Current Treatment ◽  
Therapeutic Interventions ◽  
Medical Emergency ◽  
Success Rates ◽  
Joint Infections ◽  
Novel Therapeutic

AbstractSeptic arthritis (SA) represents a medical emergency that needs immediate diagnosis and urgent treatment. Despite aggressive treatment and rapid diagnosis of the causative agent, the mortality and lifelong disability, associated with septic arthritis remain high as close to 11%. Moreover, with the rise in drug resistance, the rates of failure of conventional antibiotic therapy have also increased. Among the etiological agents frequently isolated from cases of septic arthritis, Staphylococcus aureus emerges as a dominating pathogen, and to worsen, the rise in methicillin-resistant S. aureus (MRSA) isolates in bone and joint infections is worrisome. MRSA associated cases of septic arthritis exhibit higher mortality, longer hospital stay, and higher treatment failure with poorer clinical outcomes as compared to cases caused by the sensitive strain i.e methicillin-sensitive S. aureus (MSSA).In addition to this, equal or even greater damage is imposed by the exacerbated immune response mounted by the patient’s body in a futile attempt to eradicate the bacteria. The antibiotic therapy may not be sufficient enough to control the progression of damage to the joint involved thus, adding to higher mortality and disability rates despite the prompt and timely start of treatment. This situation implies that efforts and focus towards studying/understanding new strategies for improved management of sepsis arthritis is prudent and worth exploring.The review article aims to give a complete insight into the new therapeutic approaches studied by workers lately in this field. To the best of our knowledge studies highlighting the novel therapeutic strategies against septic arthritis are limited in the literature, although articles on pathogenic mechanism and choice of antibiotics for therapy, current treatment algorithms followed have been discussed by workers in the past. The present study presents and discusses the new alternative approaches, their mechanism of action, proof of concept, and work done so far towards their clinical success. This will surely help to enlighten the researchers with comprehensive knowledge of the new interventions that can be used as an adjunct therapy along with conventional treatment protocol for improved success rates.

scholarly journals Mitochondrial Function, Biology, and Role in Disease

2016 ◽  
Vol 118 (12) ◽  
pp. 1960-1991 ◽  
Author(s):  
Elizabeth Murphy ◽  
Hossein Ardehali ◽  
Robert S. Balaban ◽  
Fabio DiLisa ◽  
Gerald W. Dorn ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Mitochondrial Function ◽  
The United States ◽  
Therapeutic Interventions ◽  
Therapeutic Approaches ◽  
Mitochondrial Defects ◽  
Exciting Time ◽  
Insight Into ◽  
Novel Therapeutic

Cardiovascular disease is a major leading cause of morbidity and mortality in the United States and elsewhere. Alterations in mitochondrial function are increasingly being recognized as a contributing factor in myocardial infarction and in patients presenting with cardiomyopathy. Recent understanding of the complex interaction of the mitochondria in regulating metabolism and cell death can provide novel insight and therapeutic targets. The purpose of this statement is to better define the potential role of mitochondria in the genesis of cardiovascular disease such as ischemia and heart failure. To accomplish this, we will define the key mitochondrial processes that play a role in cardiovascular disease that are potential targets for novel therapeutic interventions. This is an exciting time in mitochondrial research. The past decade has provided novel insight into the role of mitochondria function and their importance in complex diseases. This statement will define the key roles that mitochondria play in cardiovascular physiology and disease and provide insight into how mitochondrial defects can contribute to cardiovascular disease; it will also discuss potential biomarkers of mitochondrial disease and suggest potential novel therapeutic approaches.

scholarly journals Methodology and software to detect viral integration site hot-spots

2011 ◽  
Vol 12 (1) ◽  
Author(s):  
Angela P Presson ◽  
Namshin Kim ◽  
Yan Xiaofei ◽  
Irvin SY Chen ◽  
Sanggu Kim
Keyword(s):  
Hot Spots ◽  
Integration Site ◽  
Viral Integration
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