Article
Biochemistry & Molecular Biology
Huawei Zeng, Bryan D. Safratowich, Wen-Hsing Cheng, Andrew D. Magnuson, Matthew J. Picklo
Summary: High-fat diet-induced obesity is a risk factor for colon cancer. A study found that mice fed a high-fat diet exhibited different fecal metabolomic profiles after AOM treatment. Accumulation of specific fecal lipid species may alter the overall metabolism during colon tumorigenesis.
Article
Food Science & Technology
Yuko Murase Hetrick, Meseret Fesseha, Mee Young Hong
Summary: This study showed that watermelon powder and L-arginine supplementation can reduce the risk of colorectal cancer by upregulating gene expression of cell cycle regulators, leading to decreased proliferation and inhibition of aberrant crypt foci formation in all anatomical regions of the colon.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Nutrition & Dietetics
Luane Aparecida do Amaral, Taina da Silva Fleming de Almeida, Gabriel Henrique Oliveira de Souza, Adrivanio Baranoski, Rafael Souza Maris, Felipe Francisco Bittencourt Junior, Bruna Paola Murino Rafacho, Antonio Carlos Duenhas Monreal, Candida Aparecida Leite Kassuya, Andreia Conceicao Milan Brochado Antoniolli-Silva, Elisvania Freitas dos Santos, Rodrigo Juliano Oliveira
Summary: The study aimed to formulate a natural fiber-rich food product (NFRFP) for colorectal cancer prevention and evaluate its safety and effects in a preclinical model. Results showed that NFRFP exhibited a chemopreventive effect and reduced the incidence of aberrant crypts in the colon.
Article
Medicine, General & Internal
Marek Kowalczyk, Lukasz Klepacki, Ewa Zielinski, Waldemar Kurpiewski, Krzysztof Zinkiewicz, Lukasz Dysko, Wieslaw Pesta
Summary: Smoking has a significant influence on the occurrence of precursors and advanced colorectal cancer. Smokers have a greater number of ACFs in the rectum, with the most common type being hyperplastic ACF. As age increases, the likelihood of developing ACFs and colon polyps is higher in smokers than non-smokers.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Fa-An Chao, Srisathiyanarayanan Dharmaiah, Troy Taylor, Simon Messing, William Gillette, Dominic Esposito, Dwight Nissley, Frank McCormick, R. Andrew Byrd, Dhirendra K. Simanshu, Gabriel Cornilescu
Summary: This article investigates the influence of conformational dynamics of RAS proteins on their interactions with downstream effectors and explains and predicts the altered binding affinities of different mutants.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Zhongtang Yu, Xiaoqiang He, Ruiliu Wang, Xinxin Xu, Zhang Zhang, Ke Ding, Zhi-Min Zhang, Yi Tan, Zhengqiu Li
Summary: Due to their unique pharmaceutical properties, targeted covalent inhibitors (TCIs) have emerged as a powerful method for cancer treatment. The K-Ras mutant, which is prevalent in multiple cancers, has been confirmed as a crucial drug target. However, no covalent inhibitors targeting K-Ras(G12D) have been developed yet. We present the first compound capable of engaging both K-Ras(G12D) and K-Ras(G12C) mutants, offering a novel pathway for the development of dual covalent inhibitors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Food Science & Technology
Mariana Araujo Vieira do Carmo, Marina Fidelis, Pollyanna Francielli de Oliveira, Lais Quellen Feitoza, Marcos Jose Marques, Eric Batista Ferreira, Won Young Oh, Fereidoon Shahidi, Jarkko Hellstrom, Leonardo Augusto Almeida, Romulo Dias Novaes, Daniel Granato, Luciana Azevedo
Summary: The study demonstrated that Jabuticaba seed extract (LJE) may provide chemopreventive protection against colon cancer development by reducing inflammation and increasing proapoptotic pathways.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Food Science & Technology
Weerachai Chantana, Rentong Hu, Songphon Buddhasiri, Parameth Thiennimitr, Payungsak Tantipaiboonwong, Teera Chewonarin
Summary: This study investigated the chemoprotective action of perilla frutescens (PF) seed residue crude ethanolic extract (PCE) on the promotion stage of colon carcinogenesis and cell culture models. The results showed that PCE reduced the number of aberrant crypt foci (ACF) and decreased pro-inflammatory cytokines. PCE could also modulate inflammation in macrophage cells and suppress cancer cell proliferation induced by inflammation.
Article
Oncology
Oren Yakovian, Julia Sajman, Rand Arafeh, Yair Neve-Oz, Michal Alon, Yardena Samuels, Eilon Sherman
Summary: The study reveals the nanoscale organization and signal coupling of NRas and BRAF in melanoma cells, showing that mutant NRas exhibits more pronounced self-clustering and increased association with BRAF. The findings suggest a new regulatory mechanism for NRas signaling and potential therapeutic targets for MEK inhibitors in melanoma.
Article
Pathology
Sara Gomes Espirito Santo, Tereza Cristina Da Silva, Bruno Cogliati, Luis Fernando Barbisan, Guilherme Ribeiro Romualdo
Summary: Colorectal cancer is a leading cause of cancer-related deaths globally and is characterized by preneoplastic aberrant crypt foci (ACF) as an early manifestation. The role of Panx1 protein, which forms hemichannels, in colon carcinogenesis has not been explored. This study found that Panx1 knockout increased genotoxicity, oxidative stress, and apoptosis in the colon. Moreover, Panx1 knockout led to an increase in ACF development. Overall, these findings suggest a protective role of Panx1 in preventing the development of preneoplastic ACF during chemically induced colon carcinogenesis.
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
(2023)
Article
Cell Biology
Rui Tang, Emily G. G. Shuldiner, Marcus Kelly, Christopher W. W. Murray, Jess D. D. Hebert, Laura Andrejka, Min K. K. Tsai, Nicholas W. W. Hughes, Mitchell I. I. Parker, Hongchen Cai, Yao-Cheng Li, Geoffrey M. M. Wahl, Roland L. L. Dunbrack, Peter K. K. Jackson, Dmitri A. A. Petrov, Monte M. M. Winslow
Summary: Using CRISPR/Cas9 technology, Tang et al. show that HRAS and NRAS suppress the growth of KRAS-driven lung cancer by inhibiting KRAS-KRAS interactions and reducing downstream ERK signaling. The study highlights the specific suppressive role of RAS paralogues in KRAS-driven lung cancer, as compared to BRAF-driven lung cancer.
NATURE CELL BIOLOGY
(2023)
Review
Oncology
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: This study examines driver mutations in cancer and questions whether activating mutations or signal strength play a larger role in tumor development. It suggests that signal strength, rather than the initial mutation, determines cell fate. Factors such as homeostatic mechanisms, additional mutations, and the expression levels of certain genes and regulators can impact signaling strength. Signal levels vary across cell types, states, and time windows due to chromatin structure. The study highlights the importance of determining signaling thresholds and predicting signal strength for improving patient outcomes.
Article
Biochemistry & Molecular Biology
Grigori Y. Rychkov, Zeeshan Shaukat, Chiao Xin Lim, Rashid Hussain, Ben J. Roberts, Claudia M. Bonardi, Guido Rubboli, Brandon F. Meaney, Robyn Whitney, Rikke S. Moller, Michael G. Ricos, Leanne M. Dibbens
Summary: The effects of various KCNT1 mutations on the severity of neurological disorders were investigated, and a positive correlation was found between the severity of the disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Qinheng Zheng, D. Matthew Peacock, Kevan M. Shokat
Summary: This paper reports a long-awaited small molecule drug candidate for the treatment of pancreatic cancer, targeting the oncogenic KRAS (G12D) mutant, which is currently incurable.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hongling Zhou, Youfang Gan, Yuanyuan Li, Xiaoqian Chen, Yuyang Guo, Rui Wang
Summary: Protein degradation is an effective strategy to modulate protein functions and cellular signaling pathways. A chemically catalyzed PROTAC approach was developed to induce the degradation of RAS protein through post-translational prenyl modification. This method successfully degraded RAS protein in multiple cancer cell lines, expanding the PROTAC toolsets for studying disease-relevant protein targets.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Meeting Abstract
Oncology
Mei Mei Chan, Jean M. Winter, Susanne Kartin Pedersen, Amitesh Chandra Roy, David I. Watson, Damian Hussey, Graeme P. Young, Erin L. Symonds
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Jean M. Winter, Lorraine Sheehan-Hennessy, Susanne Kartin Pedersen, Graeme P. Young, Erin L. Symonds
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Erin L. Symonds, Susanne K. Pedersen, Bernita Yeo, Hiba Al Naji, Susan E. Byrne, Amitesh Roy, Graeme P. Young
Summary: This study assessed the use of BCAT1 and IKZF1 methylation levels to quantify circulating tumor DNA (ctDNA) in colorectal cancer patients. The results showed that ctDNA levels were correlated with disease progression, tumor diameter, and volume. After treatment, ctDNA levels decreased and the presence of ctDNA was associated with disease progression.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Susanne K. Pedersen, Benjamin L. Musher, Lawrence C. LaPointe, Melissa K. Tuck, Erin L. Symonds, Naima Loayza, Graeme P. Young
Summary: Establishing an upper reference limit for the methylated BCAT1 and IKZF1 blood assay improved specificity for detecting CRC recurrence without compromising sensitivity. The BCAT1/IKZF1 test was more sensitive than CEA for identifying recurrences amenable to surgery with curative intent.
Article
Oncology
Jean M. Winter, Lorraine Sheehan-Hennessy, Beibei Yao, Susanne K. Pedersen, Molla M. Wassie, Michael Eaton, Michael Chong, Graeme P. Young, Erin L. Symonds
Summary: Detection of circulating DNA methylated in BCAT1 and IKZF1 is sensitive and specific for colorectal cancer, but not effective for breast or prostate cancer.
Review
Oncology
Natalie Lim, Martha Hickey, Graeme P. Young, Finlay A. Macrae, Christabel Kelly
Summary: There is limited evidence to support screening for endometrial and ovarian cancer in Lynch syndrome. Data on mortality reduction are not available. Further randomized trials comparing targeted screening methods are needed. Risk reducing surgery remains the most reliable way to reduce endometrial and ovarian cancer risk in Lynch syndrome.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2022)
Article
Gastroenterology & Hepatology
Molla M. Wassie, Graeme P. Young, Charles Cock, Peter Bampton, Jean M. Winter, Kalindra Simpson, Hariti Saluja, Anthony Chuang, Robert J. Fraser, Erin L. Symonds
Summary: Delayed surveillance colonoscopy may increase the risk of advanced neoplasia, particularly in individuals with prior advanced adenoma diagnosis, older age, and nonparticipation in interval FIT testing. However, colonoscopy delay does not seem to increase the risk in individuals with negative interval FIT results.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Oncology
Susanne K. Pedersen, Erin L. Symonds, Amitesh C. Roy, Kathryn J. Cornthwaite, Lawrence C. LaPointe, Graeme P. Young
Summary: This study found that detection of methylated BCAT1 and IKZF1 after curative-intent treatment for colorectal cancer is significantly associated with an increased risk of recurrence and poorer recurrence-free survival. Patients with detectable methylated BCAT1 and IKZF1 may require personalized surveillance for better management.
Article
Gastroenterology & Hepatology
Molla M. Wassie, Graeme P. Young, Jean M. Winter, Charles Cock, Peter Bampton, Mahadya Rahman, Richard Heddle, Robert Fraser, Rosie Meng, Erin L. Symonds
Summary: Multiple rounds of negative FIT are associated with a reduced risk of advanced neoplasia in above-average-risk individuals undergoing surveillance colonoscopy.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Medical Laboratory Technology
Geraldine Laven-Law, Dawn Bastin, Robert J. L. Fraser, Charles Cock, Graeme P. Young, Jean M. Winter, Erin L. Symonds
Summary: This study aimed to determine the impact of high temperature on OC-Sensor FIT hemoglobin concentration and found that incubation at temperatures of 30 to 35 degrees Celsius reduced FIT hemoglobin concentration after more than 4 days. During mail transit, the maximum FIT temperature was on average 6.4 degrees Celsius above the maximum ambient temperature, but exposure to temperatures above 30 degrees Celsius was less than 24 hours. Data from a screening program showed no association between FIT hemoglobin concentration and maximum ambient temperatures.
CLINICAL CHEMISTRY
(2023)
Article
Oncology
Norma B. Bulamu, Gang Chen, Ellen Mcgrane, Charles Cock, Graeme P. Young, Erin L. Symonds
Summary: This study compares the sensitivity and discriminant validity of generic and cancer-specific measures for assessing health-related quality of life (HRQoL) for individuals undergoing diagnostic or surveillance colonoscopy for colorectal cancer. The results show that patients undergoing colonoscopy for symptoms have lower HRQoL compared to surveillance or positive FOBT. The cancer-specific QLU-C10D was found to be more sensitive and capable of distinguishing between patients undergoing colonoscopy for different indications.
CANCER CAUSES & CONTROL
(2023)
Article
Gastroenterology & Hepatology
Robert S. Bresalier, Carlo Senore, Graeme P. Young, James Allison, Robert Benamouzig, Sally Benton, Patrick M. M. Bossuyt, Luis Caro, Beatriz Carvalho, Han-Mo Chiu, Veerle M. H. Coupe, Willemijn de Klaver, Clasine Maria de Klerk, Evelien Dekker, Sunil Dolwani, Callum G. Fraser, William Grady, Lydia Guittet, Samir Gupta, Stephen P. Halloran, Ulrike Haug, Geir Hoff, Steven Itzkowitz, Tim Kortlever, Anastasios Koulaouzidis, Uri Ladabaum, Beatrice Lauby-Secretan, Marcis Leja, Bernard Levin, Theodore Robert Levin, Finlay Macrae, Gerrit A. Meijer, Joshua Melson, Colm O'Morain, Susan Parry, Linda Rabeneck, David F. Ransohoff, Roque Saenz, Hiroshi Saito, Silvia Sanduleanu-Dascalescu, Robert E. Schoen, Kevin Selby, Harminder Singh, Robert J. C. Steele, Joseph J. Y. Sung, Erin Leigh Symonds, Sidney J. Winawer
Summary: New non-invasive tests for colorectal cancer (CRC) are emerging, making it challenging to conduct trials with mortality reduction as the main goal. A formal consensus approach involving experts resulted in the revision of previously established principles and the emergence of twelve new principles. The effectiveness of a new test can be evaluated by comparing it with an established non-invasive test, with the faecal immunochemical test considered as the appropriate comparator. Flexible adjustment of the new test's positivity threshold is desirable to meet different screening goals and requirements. A four-phased approach is proposed for the evaluation of new tests, including small studies, prospective estimation of accuracy, evaluation in screening populations, and monitoring for missed lesions.
Article
Gastroenterology & Hepatology
Jean M. Winter, Kathryn J. Cornthwaite, Graeme P. Young, Carlene Wilson, Gang Chen, Richard Woodman, Michelle Coats, Robert Fraser, Charles Cock, Peter Bampton, Erin L. Symonds
Summary: The purpose of this study is to determine the safety, cost-effectiveness, and patient acceptance of extending colonoscopy surveillance intervals using the fecal immunochemical test (FIT) for individuals at elevated risk of colorectal cancer (CRC). Participants with a low FIT result will be randomized to either continue surveillance colonoscopy as scheduled or delay it by 1 or 2 years. The primary endpoint is the incidence of advanced neoplasia.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2023)
Letter
Urology & Nephrology
Richard Le Leu, Paul N. Bennett, Kathryn Dansie, Lisa Shanahan, Anna Chur-Hansen, Kathryn L. Collins, Anne L. J. Burke, Fiona Donnelly, Emily Duncanson, Anthony Meade, Stephen McDonald, Shilpanjali Jesudason
JOURNAL OF NEPHROLOGY
(2023)
Article
Nursing
Emily Duncanson, Richard K. Le Leu, Anna Chur-Hansen, Tahlia Masotti, Kathryn L. Collins, Anne L. J. Burke, Luke P. Macauley, Stephen Mcdonald, Shilpanjali Jesudason
Summary: This study aims to identify the key knowledge, skills and attitudes of nephrology nurses working with patients with needle-related distress. Two overarching themes were identified: Flexibility in Practice and Care, and Responsibility of Nephrology Nursing, which are relevant to all nephrology nurses. Additionally, the study found that nurses desire additional education regarding strategies to improve patient experience and nurse confidence and skill in cannulation.
JOURNAL OF RENAL CARE
(2023)