Vol 2-1 Mini Review

Epigenetic aberration at enhancer regions in gastric cancer

Atsushi Okabe1, Atsushi Kaneda1*

1Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

Cancer arises through the accumulation of genetic and epigenetic alterations. Comprehensive analyses of human cancer epigenomes over the past decade have revealed that chromatin and epigenetic aberrations induced by genetic, metabolic, and environmental stimuli play important roles in tumor initiation as well as progression. Among these aberrations, DNA hypermethylation at promoter regions is one of the major mechanisms to silence tumor suppressor genes in cancer, and has been studied in detail. For gastric cancer, for example, we and other groups have conducted genome-wide DNA methylation analyses, and classified gastric cancer into several DNA methylation epigenotypes. Gastric cancer with Epstein-Barr virus (EBV) infection exhibits the most extensive hypermethylation phenotype among all the human malignancies, and EBV infection itself is shown to cause aberrant DNA methylation induction. EBV infection also alters histone modifications, not only at promoter regions but also at enhancer regions. Epigenetic alteration at enhancers causes aberrant regulation of cancer-related genes together with epigenetic alteration at promoters, and it is known to contribute to tumorigenesis. We here review epigenetic aberration at enhancer regions in gastric cancer.

DOI: 10.29245/2578-2967/2018/1.1120 View / Download Pdf View Full Text
Vol 2-1 Mini Review

The ability of long non-coding RNA IGFBP4-1 to modulate Cellular Metabolism is a potential breakthrough in Lung Cancer Therapy

Soham Datta1,2, Binyao Yang2, Jiachun Lu1,2 *

1The State Key Lab of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou, 510120, China.

2The School of Public Health, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou, 510182, China

Lung cancer being one of the leading causes of cancer-related deaths around the world has significantly added to the global burden of disease. Late diagnosis, unavailability of definitive treatment and an unclear pathophysiological mechanism behind the role of various genes expressed in lung cancer make it a challenge that needs new techniques and better understanding of the underlying pathology and role of genetics. Long non coding RNAs, once considered insignificant, are now being elucidated to have major roles to play in the regulation and development of carcinogenesis. In this review, the ability of a lncRNA, lncRNA IGFBP4-1 to modulate cellular metabolic processes, eventually affecting lung cancer progression and consequently being a potential biomarker for lung cancer diagnosis has been discussed.

DOI: 10.29245/2578-2967/2018/1.1116 View / Download Pdf View Full Text
Vol 2-1 Mini Review

Effector and Regulatory CD4+ T helper lineages in cancer

Estefanía Nova-Lamperti1,2*, Marco Fraga1, Marco Romano3, Giovanna Lombardi3#

1Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, 4070386. Concepcion, Chile

2PreveGen Laboratory, Chacabuco 556, Concepcion, Chile

3MRC Centre for Transplantation, School of Immunology & Microbial Sciences, King’s College London, Guy’s Hospital, SE1 9RT. London, United Kingdom

Regulatory CD4+T-cells have been recently classified as regulatory T helper (Th)-like cells according to the expression of specific transcription factors, cytokines and chemokine receptors that mirror effector Th lineages. In our report: “An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment” we found that Th2-like Tregs were increased in the tumour microenvironment in comparison with Th1-like, Th17-like and Th1/Th17-like Tregs. In addition, despite similar expression of CCR4 between all Tregs subtypes, Th2-like Tregs migrated more toward CCL17 and CCL22, and expressed higher levels of CCR8 than the other Th-like Tregs. Other studies have characterised human tissue-infiltrating Tregs and demonstrated that CCR8 is the main chemokine receptor differentially expressed in Tregs isolated from malignant tissues in comparison with healthy tissues. Given that CCR8 is a marker of Th2 lineages it is possible that Th2-like Tregs and CCR8+ Tregs are the same population of cells involved in tumour progression. However, whether they are recruited or differentiated in situ by the tumour microenvironment is still unknown. In this mini review, we describe the role of the different Th subsets in health and cancer and we present the different hypotheses about the presence of Th2-like Tregs in the tumorigenic environments.

DOI: 10.29245/2578-2967/2018/1.1119 View / Download Pdf View Full Text
Vol 2-1 Mini Review

Novel Platforms of Multiplexed Immunofluorescence for Study of Paraffin Tumor Tissues

Edwin Roger Parra

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

Multiplexed immunofluorescence (IF) methods to detect simultaneously different molecules are revolutionizing immunohistochemistry (IHC) in the last years. These new technologies can be valuable for tumor examination in formalin-fixed paraffin-embedded (FFPE) specimens, and for improved new treatment discoveries and translational cancer studies. The aim of this mini-review is to highlight the recent methodologies that using multiplexed IF to study simultaneous proteins identification in FFPE tumor tissues to clinical research and potential translational analysis. Multiplexed IF methods, which permit the identification of up to 4 proteins at the same time, have been increased in the last years the abilities of study cells by cells and their spatial distribution in several tumor tissues. Although, most of the old platforms are not more used after the powerful multiplex IHC methods are continue growing, the basis of these old methodologies have helped to improve the new technologies. Associated with image analysis software’s these technologies can be improved to performance high throughput assay to study these specimens. Each multiplexed IF technique, detailed herein, is associated with important advantages in cancer study as well as translational research studies.

DOI: 10.29245/2578-2967/2018/1.1122 View / Download Pdf View Full Text
Vol 2-1 Mini Review

The anti-apoptotic protein MCL1, a novel target of lung cancer therapy

Wataru Nakajima and Nobuyuki Tanaka*

Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Japan

Evasion of apoptosis is one of the typical hallmarks of cancer and a major mechanism for cancer development, tumor growth, and acquisition of resistance to chemotherapy. The anti-apoptotic Bcl-2 protein family, particularly MCL1 and BCL-XL, play an important role in acquisition of apoptosis evasion. MCL1 is a highly unstable protein that is constantly degraded by the ubiquitin-proteasome system. An increase in MCL1 protein has been reported in many cancers, including lung cancer, through high mRNA expression or impairment of its degradation systems. To date, much evidence has shown that MCL1 is important for cancer cell survival and drug resistance in lung cancers. In this review, we discuss the role and mechanism of high MCL1 expression in lung cancer.

DOI: 10.29245/2578-2967/2018/1.1123 View / Download Pdf View Full Text