APC Promoter Methylation in Gastrointestinal Cancer

The adenomatous polyposis coli (APC) gene, known as tumor suppressor gene, has the two promoters 1A and 1B. Researches on APC have usually focused on its loss-of-function variants causing familial adenomatous polyposis. Hypermethylation, however, which is one of the key epigenetic alterations of the APC CpG sequence, is also associated with carcinogenesis in various cancers. Accumulating studies have successively explored the role of APC hypermethylation in gastrointestinal (GI) tumors, such as in esophageal, colorectal, gastric, pancreatic, and hepatic cancer. In sporadic colorectal cancer, the hypermethylation of CpG island in APC is even considered as one of the primary causative factors. In this review, we systematically summarized the distribution of APC gene methylation in various GI tumors, and attempted to provide an improved general understanding of DNA methylation in GI tumors. In addition, we included a robust overview of demethylating agents available for both basic and clinical researches. Finally, we elaborated our findings and perspectives on the overall situation of APC gene methylation in GI tumors, aiming to explore the potential research directions and clinical values.

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Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma

Cancers ◽

10.3390/cancers13164072 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4072

Author(s):

Maja T. Tomicic ◽

Mona Dawood ◽

Thomas Efferth

Keyword(s):

Dna Methylation ◽

Therapy Response ◽

Suppressor Gene ◽

Micro Rna ◽

Missense Mutations ◽

Epigenetic Alterations ◽

Loss Of Function ◽

Survival Prognosis ◽

P53 Signaling ◽

Micro Rnas

Colorectal cancer (CRC) belongs to the most common tumor types, and half of all CRC harbor missense mutations in the TP53 tumor suppressor gene. In addition to genetically caused loss of function of p53, epigenetic alterations (DNA methylation, histone modifications, micro-RNAs) contribute to CRC development. In this review, we focused on epigenetic alterations related to the entire p53 signaling pathway upstream and downstream of p53. Methylation of genes which activate p53 function has been reported, and methylation of APC and MGMT was associated with increased mutation rates of TP53. The micro-RNA 34a activates TP53 and was methylated in CRC. Proteins that regulate TP53 DNA methylation, mutations, and acetylation of TP53-related histones were methylated in CRC. P53 regulates the activity of numerous downstream proteins. Even if TP53 is not mutated, the function of wildtype p53 may be compromised if corresponding downstream genes are epigenetically inactivated. Thus, the role of p53 for CRC development, therapy response, and survival prognosis of patients may be much more eminent than previously estimated. Therefore, we propose that novel diagnostic devices measuring the entirety of genetic and epigenetic changes in the “p53 signalome” have the potential to improve the predictive and prognostic power in CRC diagnostics and management.

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Can resistant starch and/or aspirin prevent the development of coloi neoplasia? The Concerted Action Polyp Prevention (CAPP) 1 Study

Proceedings of The Nutrition Society ◽

10.1079/pns2002236 ◽

2003 ◽

Vol 62 (1) ◽

pp. 51-57 ◽

Cited By ~ 12

Author(s):

John C. Mathers ◽

Ian Mickleburgh ◽

Pam C. Chapman ◽

D. Tim Bishop ◽

John Burn

Keyword(s):

Resistant Starch ◽

Potato Starch ◽

Rectal Mucosa ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Early Event ◽

Adenomatous Polyposis ◽

Loss Of Function ◽

Concerted Action ◽

Apc Protein

Loss of function of the adenomatous polyposis coli (APC) tumour suppressor gene through truncating mutations or other means is an early event in most colo-rectal cancer (CRC). The AFC gene encodes a large multifunctional protein that plays key roles in several cellular processes, including the wnt signalling pathway where an intact APC protein is essential for down regulation of β-catenin. The APC protein also plays a role in regulation of cell proliferation, differentiation, apoptosis, cell-cell adhesion, cell migration and chromosomal stability during mitosis. Acquisition of a non-functional APC gene can occur by inheritance (in the disease familial adenomatous polyposis (FAP)) or by a sporadic event in a somatic cell. Whilst there is strong epidemiological evidence that variation in diet is a major determinant of variation in CRC incidence, conventional adenoma recurrence trials in sporadic cases of the disease have been relatively unsuccessful in identifying potentially protective food components. Since the genetic basis of CRC in FAP and in sporadic CRC is similar, intervention trials in FAP gene carriers provide an attractive strategy for investigation of potential chemo-preventive agents, since smaller numbers of subjects and shorter time frames are needed. The Concerted Action Polyp Prevention (CAPP) 1 Study is using a 2×2 factorial design to test the efficacy of resistant starch (30 g raw potato starch-Hylon VII (1:1, w/w)/d) and aspirin (600 mg/d) in suppressing colo-rectal adenoma formation in young subjects with FAP. Biopsies of macroscopically-normal rectal mucosa are also being collected for assay of putative biomarkers of CRC risk.

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MicroRNA Promoter Methylation in Colorectal Cancer

Basic & Clinical Cancer Research ◽

10.18502/bccr.v11i3.5720 ◽

2021 ◽

Author(s):

Masoud Asefi ◽

Nayebali Rezvani ◽

Mohammad Hasan Soheilifar ◽

Massoud Saidijam ◽

Ali Mahdavinezhad

Keyword(s):

Colorectal Cancer ◽

Promoter Methylation ◽

Cpg Island ◽

Gene Promoter ◽

Epigenetic Alterations ◽

Genetic Changes ◽

Microrna Gene ◽

Cancer Types ◽

Cpg Island Methylation

Colorectal cancer (CRC) is one of the most common cancers worldwide. The beginning and progression of the disease are thought to be determined by combinations of epigenetic and genetic changes that trigger multistep programs of carcinogenesis. In colorectal cancer, epigenetic alterations, in particular promoter CpG island methylation, occur more commonly than genetic mutations. Hyper-methylation contributes to carcinogenesis via inducing transcriptional silencing or down-regulation of tumor suppressor genes. DNA methylation alteration has a high potential for minimally invasive biomarker identification. Genome analysis has confirmed that microRNA expression is deregulated in most cancer types through several mechanisms, including failings in the microRNA biogenesis machinery. Moreover, microRNAs can be dysregulated by abnormal CpG methylation in cancer. Since it is believed that epigenetic changes occur in the early stages of the disease, these changes can be used for the early detection of cancer. In this review, we intend to study the role of microRNA gene promoter methylation in colorectal cancer.

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Depletion ofDNMT3ASuppressed Cell Proliferation and RestoredPTENin Hepatocellular Carcinoma Cell

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/737535 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 28

Author(s):

Zhujiang Zhao ◽

Qingxiang Wu ◽

Jian Cheng ◽

Xuemei Qiu ◽

Jianqiong Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Tumor Suppressor ◽

Cpg Island ◽

Cpg Islands ◽

Promoter Hypermethylation ◽

Suppressor Gene ◽

Dna Methyltransferases ◽

Cpg Island Methylation

Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed thatDNMT1andDNMT3Bplay an important role in CpG island methylation in tumorigenesis. Little is known about the role ofDNMT3Ain this process, especially in hepatocellular carcinoma (HCC). In the present study, increasedDNMT3Aexpression in 3 out of 6 HCC cell lines and 16/25 (64%) HCC tissues implied thatDNMT3Ais involved in hepatocellular carcinogenesis. Depletion ofDNMT3Ain HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%). Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153) of them contain CpG islands in their5′region. 13 of them includingPTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation ofPTENpromoter was observed inDNMT3A-depleted cells implying that DNMT3A silencedPTENvia DNA methylation. These results provide insights into the mechanisms ofDNMT3Ato regulate TSGs by an epigenetic approach in HCC.

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R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability

10.21203/rs.3.rs-337351/v1 ◽

2021 ◽

Author(s):

Petra Beli ◽

Thorsten Mosler ◽

Francesca Conte ◽

Ivan Mikicic ◽

Nastasja Kreim ◽

...

Keyword(s):

Notch Signaling ◽

Genomic Instability ◽

Cpg Island ◽

Gene Promoters ◽

Loss Of Function ◽

Dead Box ◽

Dna Strand ◽

Nucleic Acid Structures ◽

Template Dna

Abstract Transcription can pose a threat to genomic stability through the formation of R-loops that obstruct the progression of replication forks. R-loops are three-stranded nucleic acid structures formed by an RNA-DNA hybrid with a displaced non-template DNA strand. We developed RDProx to identify proteins that regulate R-loops in human cells. RDProx relies on the expression of the hybrid-binding domain (HBD) of Ribonuclease H1 (RNaseH1) fused to the ascorbate peroxidase (APEX2) and permits mapping of the R-loop proximal proteome using quantitative mass spectrometry. We implicate different cellular proteins in R-loop regulation and identify a role of the tumor suppressor DEAD box protein 41 (DDX41) in opposing R-loop-dependent genomic instability. Depletion of DDX41 resulted in replication stress, double strand breaks and inflammatory signaling. DDX41 opposes the accumulation of R-loops by unwinding RNA-DNA hybrids at gene promoters and its loss leads to upregulation of TGFβ and NOTCH signaling genes. Germline loss-of-function mutations in DDX41 lead to predisposition to acute myeloid leukemia (AML) in adulthood. We propose that accumulation of R-loops at CpG island promoters, altered TGFβ and NOTCH signaling, and inflammatory response contribute to the development of familial AML with mutated DDX41.

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MATERIAL HANDLING MACHINES AND SYSTEMS – UMI-TWINN PROJECT CONTRIBUTION

Advanced Logistic Systems - Theory and Practice ◽

10.32971/als.2019.001 ◽

2019 ◽

Vol 12 (1) ◽

pp. 7-20

Author(s):

Péter Telek ◽

Béla Illés ◽

Christian Landschützer ◽

Fabian Schenk ◽

Flavien Massi

Keyword(s):

Material Handling ◽

Digital Data ◽

Flow Process ◽

Research Directions ◽

Scientific Excellence ◽

Research Activities ◽

New Research ◽

Eu Project ◽

The University

Nowadays, the Industry 4.0 concept affects every area of the industrial, economic, social and personal sectors. The most significant changings are the automation and the digitalization. This is also true for the material handling processes, where the handling systems use more and more automated machines; planning, operation and optimization of different logistic processes are based on many digital data collected from the material flow process. However, new methods and devices require new solutions which define new research directions. In this paper we describe the state of the art of the material handling researches and draw the role of the UMi-TWINN partner institutes in these fields. As a result of this H2020 EU project, scientific excellence of the University of Miskolc can be increased and new research activities will be started.

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The Role of Physical Exercise and Diet in management of Medoroga (STHAULYA) Reference Novel Coronavirus Covid 19

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3793 ◽

2021 ◽

Vol 11 (SPL1) ◽

pp. 1585-1592

Author(s):

Roshna Sukhdeoji Bhutada

Keyword(s):

Vitamin D ◽

Vitamin C ◽

Physical Movement ◽

Work From Home ◽

Causative Factors ◽

Exercise Routine ◽

Novel Coronavirus ◽

Day By Day ◽

General Wellbeing

Nowadays, due to Covid-19 pandemic circumstance, numerous individuals are Staying from home. Understudy is additionally concern with the online class from home, because of which all physical movement of all individual has been stopped. Medoroga is one of the dominating metabolic problems and driving reason for mortality. Numerous patients with Covid infection 2019 (COVID-19) have identified with the metabolic disorder during the lockdown. The general wellbeing proposes (Work from Home, requests, gyms, terminations of garden and wellness focuses) to forestall Covid-19 spread can possibly decrease day by day physical movement. Ideas of Agni, Prakriti, strategy for victualing ought to be given equivalent consideration while choosing ones dietary and exercise routine to turn away/control Medoroga (STHAULYA). Organizing of diet is generally important to support insusceptibility. According to numerous investigates to give valuable pabulum which contains Zinc, Vitamin C, Vitamin D and invulnerability. It is practically equivalent to Medoroga referenced in Ayurveda compositions. Strick likeness outwardly inspected in both customary arrangement of medication and Ayurveda while portraying its causative components, outcomes and preventive part of exercise and diet in its administration. Striking is outwardly analyzed in both Traditional arrangements of medication and Ayurveda depicting its causative factors, and preventive capacity of movement and diet in its pandemic Covid-19.

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The Role of hCDC4 as a Tumor Suppressor Gene in Genomic Instability Underlying Prostate Cancer

10.21236/ada463404 ◽

2006 ◽

Author(s):

Audrey Van Drogen ◽

Charles H. Spruck

Keyword(s):

Prostate Cancer ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Genomic Instability ◽

Suppressor Gene

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Interpersonal Psychotherapy for the Treatment of Eating Disorders

The Oxford Handbook of Eating Disorders ◽

10.1093/oxfordhb/9780195373622.013.0020 ◽

2010 ◽

pp. 347-372 ◽

Cited By ~ 1

Author(s):

Marian Tanofsky-Kraff ◽

Denise E. Wilfley

Keyword(s):

Anorexia Nervosa ◽

Clinical Care ◽

Interpersonal Psychotherapy ◽

Future Research ◽

Cognitive Behavior ◽

Research Directions ◽

Routine Clinical Care ◽

Interpersonal Factors ◽

Future Research Directions

Interpersonal psychotherapy (IPT) is a focused, time-limited treatment that targets interpersonal problem(s) associated with the onset and/or maintenance of EDs. IPT is supported by substantial empirical evidence documenting the role of interpersonal factors in the onset and maintenance of EDs. IPT is a viable alternative to cognitive behavior therapy for the treatment of bulimia nervosa and binge eating disorder. The effectiveness of IPT for the treatment of anorexia nervosa requires further investigation. The utility of IPT for the prevention of obesity is currently being explored. Future research directions include enhancing the delivery of IPT for EDs, increasing the availability of IPT in routine clinical care settings, exploring IPT adolescent and parent–child adaptations, and developing IPT for the prevention of eating and weight-related problems that may promote full-syndrome EDs or obesity.

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