E2 ubiquitin-conjugating enzymes in cancer: Implications for immunotherapeutic interventions

Publication date: Available online 21 August 2019Source: Clinica Chimica ActaAuthor(s): Seyed Mohammad Hosseini, Isobel Okoye, Mitra Ghasemi Chaleshtari, Bita Hazhirkarzar, Javad Mohamadnejad, Gholamreza Azizi, Mohammad Hojjat-Farsangi, Hamed Mohammadi, Siamak Sandoghchian Shotorbani, Farhad Jadidi-NiaraghAbstractDespite the medical advances of the 21st century, the incidence of cancer continues to increase and the search for a universal cure remains a major health challenge. Our lack of understanding the complex pathophysiology of the tumor microenvironment has hindered the development and efficiency of anti-cancer therapeutic strategies. The tumor microenvironment, composed of multiple cellular and non-cellular components, enables tumor-promoting processes such as proliferation, angiogenesis, migration and invasion, metastasis, and drug resistance. The ubiquitin-mediated degradation system is involved in several physiologic processes including cell cycling, signal transduction, receptor downregulation, endocytosis and transcriptional regulation. Ubiquitination includes attachment of ubiquitin to target proteins via E1 (activating), E2 (conjugating) and E3 (ligating) enzymes. Several studies have shown that E2 enzymes are dysregulated in variety of cancers. Multiple investigations have demonstrated the involvement of E2s in various tumor-promoting processes including DNA repair, cell cycle progression, apoptosis and oncogenic signaling. E2 enzymes consist of 40 members that ...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research

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Source: MDDI - Category: Medical Devices Authors: Tags: Orthopedics Source Type: news
ConclusionsPeritoneal carcinomatosis of unknown primary site may be caused by an occult appendiceal adenocarcinoma. This error in diagnosis may lead to suboptimal treatment. Surgical exploration to visualize a normal appendix should occur prior to making a definitive diagnosis of peritoneal carcinomatosis of unknown primary site.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
Second interim analysis from the Phase 3 SPARTAN study reporting updated overall survival results in patients with non-metastatic castration-resistant prostate cancer treated with ERLEADA ® (apalutamide)Patient-reported outcomes from the Phase 3 TITAN study evaluating ERLEADA® in patients with metastatic castration-sensitive prostate cancer Interim analysis from the Phase 2 GALAHAD study evaluating niraparib in the treatment of patients with metastatic castration-resistant prostate cancer and biallelic DNA-repair gene defects, featured as late-breaking abstract
Source: Johnson and Johnson - Category: Pharmaceuticals Source Type: news
In conclusion, chromosome repair happens in two steps, including a last and hardly detectable one because of restoration of the chromosome integrity.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this issue of Molecular Cell, Kim et  al. (2019) identify small nucleolar RNAs (snoRNAs) as activators of poly(ADP-ribose) (PAR) synthesis, demonstrating that this snoRNA–PAR partnership promotes cancer cell growth independent of DNA repair pathways.
Source: Molecular Cell - Category: Cytology Authors: Tags: Preview Source Type: research
Publication date: Available online 17 September 2019Source: Mutation Research/Fundamental and Molecular Mechanisms of MutagenesisAuthor(s): Rebekah J. Hutcherson, Michael G. KempAbstractThe ATR protein kinase is known to protect cells from DNA damage induced during the replicative phase of the cell cycle. Small molecule ATR kinase inhibitors have therefore been developed to improve the effectiveness of DNA damage-based chemotherapy regimens aimed at killing rapidly proliferating tumor cells. However, whether ATR functions in a similar manner in non-replicating cells has not been examined and is important considering the fa...
Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - Category: Cytology Source Type: research
This study aimed to provide a better understanding of the altered molecular networks in BC from the gulf region. Herein, we compared the transcriptome of BC to adjacent normal tissue from six BC patients and identified 1,108 upregulated and 518 downregulated transcripts. A selected number of genes from the RNA-Seq analysis were subsequently validated using qRT-PCR. Differentially expressed (2.0-fold change, adj. p
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Ladányi A Abstract Genomic instability is a hallmark of cancer therefore of the metastatic disease as well. High tumor mutation burden is due to deficiencies of the DNA repair systems and leads to immunosensitivity due to generation of neoantigens. However, APOBEC activation of that system, though increases mutation rate, but causes immunoresistance. Deficient antigen presentation due to HLA class I defects is another major cause of immunoresistance. The contemporary immunotherapies may exploit gene amplification of PD-L1 but if the affected chromosome is damaged IFN activation can be lost, again causing i...
Source: Magyar Onkologia - Category: Cancer & Oncology Authors: Tags: Magy Onkol Source Type: research
Multiple myeloma (MM) is a malignancy characterized by accumulation of malignant plasma cells within the bone marrow (BM). MM is considered mostly without definitive treatment because of the inability of standard of care therapies to overcome drug-resistant relapse. Genotoxic agents are used in the treatment of MM and exploit the fact that DNA double-strand breaks are highly cytotoxic for cancer cells. However, their mutagenic effects are well-established and described. According to these effects, chemotherapy could cause harmful DNA damage associated with new driver genomic abnormalities providing selective advantage, dru...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract Recent advances in single-cell RNA sequencing (scRNA-seq) have endowed researchers with the ability to detect and analyze the transcriptomes of individual cancer cells. In the present study, 16,128 tumor cells from EGFR wild-type and EGFRvIII mutant cells were profiled by scRNA-seq. Analyses of scRNA-seq data from both U87MG and U87MG-EGFRvIII libraries revealed inherent heterogeneity in gene expression and biological processes. The cells stably expressing EGFRvIII showed enhanced transcriptional activities and a relatively homogeneous pattern, which manifested as less diverse distributions, gene expressi...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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