A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionfp3168u1p9qr9l62qqefgieopdnfcgq5): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 249

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated

Filename: models/Detail_model.php

Line Number: 71

Backtrace:

File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos

File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: 8192

Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated

Filename: helpers/my_audit_helper.php

Line Number: 8919

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace

File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "choices"

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 256

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 257

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 258

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 259

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Undefined array key "usage"

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Trying to access array offset on value of type null

Filename: controllers/Detail.php

Line Number: 260

Backtrace:

File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler

File: /var/www/html/index.php
Line: 316
Function: require_once

Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression. | LitMetric

Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression.

Gastroenterology

Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt am Main, Germany; German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany. Electronic address:

Published: February 2023

AI Article Synopsis

Article Abstract

Background & Aims: Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.

Methods: We examined the alterations in histone modifications in patient-derived colorectal cancer organoids. Patient-derived colorectal cancer organoids and mouse intestinal organoids were genetically manipulated for functional studies in patient-derived xenograft and orthotopic transplantation. Gene expression profiling, micrococcal nuclease assay, and chromatin immunoprecipitation were performed to understand epigenetic regulation of chromatin states and gene expression in patient-derived and mouse intestinal organoids.

Results: We found that reduced H4K20me3 levels occurred predominantly in right-sided patient-derived colorectal cancer organoids, which were associated with increased chromatin accessibility. Re-compaction of chromatin by methylstat, a histone demethylase inhibitor, resulted in reduced growth selectively in subcutaneously grown tumors derived from right-sided cancers. Using mouse intestinal organoids, we confirmed that Suv4-20h2-mediated H4K20me3 is required for maintaining heterochromatin compaction and to prevent R-loop formation. Cross-species comparison of Suv4-20h2-depleted murine organoids with right-sided colorectal cancer organoids revealed a large overlap of gene signatures involved in chromatin silencing, DNA methylation, and stemness/Wnt signaling.

Conclusions: Loss of Suv4-20h2-mediated H4K20me3 drives right-sided colorectal tumorigenesis through an epigenetically controlled mechanism of chromatin compaction. Our findings unravel a conceptually novel approach for subtype-specific therapy of this aggressive form of colorectal cancer.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9889219PMC
http://dx.doi.org/10.1053/j.gastro.2022.10.036DOI Listing

Publication Analysis

Top Keywords

colorectal cancer
24
cancer organoids
16
gene expression
12
patient-derived colorectal
12
mouse intestinal
12
chromatin compaction
8
drives right-sided
8
cancer
8
colorectal
8
intestinal organoids
8

Similar Publications

Colorectal cancer (CRC) is a significant contributor to cancer-related mortality, emphasizing the need for advanced biomarkers to guide treatment. As part of an international consortium, we previously categorized CRCs into four consensus molecular subtypes (CMS1-CMS4), showing promise for outcome prediction. To facilitate clinical integration of CMS classification in settings where formalin-fixed paraffin-embedded (FFPE) samples are routinely used, we developed NanoCMSer, a NanoString-based CMS classifier using 55 genes.

View Article and Find Full Text PDF

International consensus to define outcomes for trials of chemoradiotherapy for anal cancer (CORMAC-2): defining the outcomes from the CORMAC core outcome set.

EClinicalMedicine

December 2024

NIHR Manchester Biomedical Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.

Variation in outcomes definitions and reporting limit the utility of clinical trial results. The Core Outcome Research Measures in Anal Cancer (CORMAC) project developed a core outcome set (COS) for chemoradiotherapy trials for anal squamous cell carcinoma (ASCC) through an international healthcare professional and patient consensus process. The CORMAC-COS comprises 19 outcomes across 4 domains (disease activity, survival, toxicity, life impact).

View Article and Find Full Text PDF

The thyroid is a rare site for finding tumor metastases. Renal, colorectal, pulmonary, and mammary origin are the most frequent primary neoplasms. Clinical suspicion, early diagnosis, and active surveillance are important during follow-up.

View Article and Find Full Text PDF

Netrin-1, an essential extracellular protein, has gained significant attention due to its pivotal role in guiding axon and cell migration during embryonic development. The fundamental significance of netrin-1 in developmental biology is reflected in its high conservation across different species as a part of the netrin family. The bifunctional nature of netrin-1 demonstrates its functional versatility, as it can function as either a repellent or an attractant according to the context and the expressed receptors on the target cells including the deleted in colorectal cancer (DCC), the uncoordinated-5 (UNC5), DSCAM, Neogenin-1, Adenosine A2b and Draxin receptors.

View Article and Find Full Text PDF

Statin use after cancer diagnosis and survival among patients with cancer.

Cancer Causes Control

December 2024

Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, M4-C308, Seattle, WA, 98019, USA.

Purpose: The association between statin use and cancer survival has been investigated in previous studies with conflicting findings. This study aimed to assess the association between statin use following cancer diagnosis and survival in six common cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.

Methods: Individuals aged ≥ 66 years diagnosed with prostate cancer, colorectal cancer, lung cancer, bladder cancer, pancreatic cancer, or non-Hodgkin lymphoma (NHL) from 2008 through 2017 were identified.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!