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Their study, published Dec.
14 in the journal Cell, describes the discovery of single-cell transcriptomic and imaging profiles of the two most common colorectal polyps in humans: traditional adenomas and serrated polyps
.
They determined that adenomas are caused by the expansion of stem cells driven by activation of WNT signaling, which contributes to cancer development, while serrated polyps develop into cancer through a different process called gastric metaplasia
"Metaplastic cellular plasticity is now recognized as a key pathway in cancer initiation, and Vanderbilt University researchers have demonstrated Pioneering contribution
.
" "We have now provided evidence of this process and its downstream consequences in one of the largest single-cell transcriptomic studies of human participants by a single center to date
The researchers conducted a comprehensive analysis of 128 datasets from 62 tumor tissue samples
.
They performed single-cell RNA sequencing, multiplex immunofluorescence, and multiplex immunohistochemistry on samples collected from different gender, ethnicity, and age groups
The cells of the serrated polyp had neither WNT pathway activation nor stem cell markers
.
In addition, the researchers observed that these cells had highly expressed genes not normally found in the colon, leading them to hypothesize that metaplasia plays an important role in the carcinogenesis of serrated polyps
"We propose a new paradigm in which damage to the proximal colon, possibly from the microbiota, initiates a metaplastic cascade that may ultimately select survival/proliferation pathways," the researchers wrote in their paper.
Such as mutations that activate BRAF
.
"
Vanderbilt University graduate students Bob Chen and Cherie' Scurrah, Ph.
D.
, are co-first authors of the paper
.
The study also provided several other findings with clinical implications
.
For example, sessile serrated lesions are difficult to identify, and studies have shown that biomarkers can confirm their diagnosis
"The findings in our atlas lay the groundwork for new strategies to block cancer progression, including better surveillance protocols, chemoprevention, and prebiotic and prebiotic therapies," said corresponding author Martha Shrubsole, Ph.
D.
, research professor in the Division of Epidemiology
.
The Vanderbilt research was supported by the National Cancer Institute Cancer Moon Shot's Human Tumor Atlas Network as well as the National Cancer Institute, the U.
S.
Department of Defense's Congressional Directed Medical Research Program, Cancer Research UK, Jensen, and Nicholas Dr.
Tierney Gastrointestinal Cancer Memorial Fund
.
"Only through the close collaboration of a multidisciplinary team, combining input from Vanderbilt University Basic Sciences, Vanderbilt University Medical Center Center for Epithelial Biology, Vanderbilt Center for Epidemiology and Vanderbilt-Ingram The expertise of the cancer center makes this massive effort possible
.
” Robert Coffey, Jr.
Vanderbilt authors contributed to other research include Elliott McKinley, Ellen Simmons, Marisol, Ramirez-Solano, Shannon, Nicholas Markham, Cody Black, Paige Vega, Andrea Rolong Hyeyon, Kim Quanhu Sheng, Yuan Zhou, Austin Southard-Smith Yanwen Xu, James Ro, Angela Jones, Frank Revetta, Lynn Berry, Niitsu President, Hiroaki Nakanishi, Mirazul Islam, Jeremy Goettel, Wei Zheng, Kay Washington, Qiuyin Cai, James Goldenring, Jeffrey Franklin, Timothy Su, Won Jae Huh, Simon Vandekar, Joseph Roland and Qi Liu
Journal Reference :
Bob Chen, Cherie’ R.
