Article
Multidisciplinary Sciences
Shunli Fu, Lili Chang, Shujun Liu, Tong Gao, Xiao Sang, Zipeng Zhang, Weiwei Mu, Xiaoqing Liu, Shuang Liang, Han Yang, Huizhen Yang, Qingping Ma, Yongjun Liu, Na Zhang
Summary: The authors developed a pH and photothermal therapy targeted nanoparticle that simultaneously targeted tumours and lymph nodes, leading to mobilization of anti-tumour cytotoxic T cells and NK cells and a synergistic therapeutic effect with immune checkpoint blockade. Targeting the immunosuppressive microenvironment of tumours is a critical strategy in immunotherapy and this study highlights the important role of the tumour lymph node immune microenvironment. Combining lymph node targeting with immune checkpoint blockade significantly enhances the effectiveness of T and NK cells and suppresses tumour growth.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Yansong Xu, Yi Chen, Chenyan Long, Huage Zhong, Fangfang Liang, Ling-xu Huang, Chuanyi Wei, Shaolong Lu, Weizhong Tang
Summary: Preoperative CEA level, grading, and PNI were identified as independent risk factors for LNM in colon cancer. The nomogram constructed in this study demonstrated good consistency and calibration capabilities for predicting LNM risk in both the training and validation sets.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Xu Guan, Pu Cheng, Ran Wei, Jiangtao Li, Shuai Jiao, Zhixun Zhao, Haipeng Chen, Zheng Liu, Zheng Jiang, Zhaoxu Zheng, Shuangmei Zou, Xishan Wang
Summary: Enlarged TDLN in non-metastatic CRC exhibits an activated anti-tumour immune profile and is associated with favorable survival outcomes. The presence of numerous immune-activating pathways and higher numbers of CD3+ and CD8+ T cells in L-TDLN suggests its potential as a prognostic indicator.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Ning Liao, Cheukfai Li, Li Cao, Yanhua Chen, Chongyang Ren, Xiaoqing Chen, Hsiaopei Mok, Lingzhu Wen, Kai Li, Yulei Wang, Yuchen Zhang, Yingzi Li, Jiaoyi Lv, Fangrong Cao, Yuting Luo, Hongrui Li, Wendy Wu, Charles M. Balch, Armando E. Giuliano
Summary: This study examined the host-tumor interaction in breast cancer nodal metastases at a single cell level. It found that the sentinel lymph node serves as the initial meeting site for tumor infiltration and immune response, with some T lymphocytes exhibiting anti-tumor activity and others in an exhausted state.
Article
Oncology
Inge van den Berg, Marcel Smid, Robert R. J. Coebergh van den Braak, Carolien H. M. van Deurzen, Vanja de Weerd, John A. Foekens, Jan N. M. IJzermans, John W. M. Martens, Saskia M. Wilting
Summary: Circular RNAs (circRNAs) play an important role in tumor progression of colon cancer (CC) and have potential clinical value as biomarkers for diagnosis, prognosis, and treatment. A large cohort study identified a diverse catalog of circRNAs in stage I/II colon tumors and found that high circRNA diversity was associated with favorable disease-free survival (DFS). Specific circRNAs were also associated with MSI and CMS, highlighting their potential utility for prognostic stratification in patients with early-stage colon cancer.
Review
Oncology
Isobelle Wall, Victoire Boulat, Aekta Shah, Kim R. M. Blenman, Yin Wu, Elena Alberts, Dinis Pedro Calado, Roberto Salgado, Anita Grigoriadis
Summary: The tumor microenvironment (TME), lymph nodes (LNs), and peripheral blood form the interconnected immune sites in breast cancer. Understanding the dynamic interaction between these immune sites is crucial for improving anti-cancer responses and therapeutic outcomes in breast cancer patients.
Article
Urology & Nephrology
Frederik Wessels, Max Schmitt, Eva Krieghoff-Henning, Tanja Jutzi, Thomas S. Worst, Frank Waldbillig, Manuel Neuberger, Roman C. Maron, Matthias Steeg, Timo Gaiser, Achim Hekler, Jochen S. Utikal, Christof Von Kalle, Stefan Froehling, Maurice S. Michel, Philipp Nuhn, Titus J. Brinker
Summary: A new digital biomarker based on CNN analysis of primary tumor tissue was developed for predicting lymph node metastasis in prostate cancer patients. With 10 trained models, an average AUROC of 0.68 and balanced accuracy of 61.37% was achieved. The CNN probability score and lymphovascular invasion were identified as independent predictors for LNM.
Article
Surgery
C. Jin, Y. Jiang, H. Yu, W. Wang, B. Li, C. Chen, Q. Yuan, Y. Hu, Y. Xu, Z. Zhou, G. Li, R. Li
Summary: A deep learning system was developed for predicting LNMs in gastric cancer based on preoperative CT images, showing excellent accuracy, sensitivity, and specificity in an external validation cohort for 11 nodal stations. The imaging models outperformed clinicopathological variables for predicting LNMs, with features related to intratumoral heterogeneity and the invasive front being most useful for prediction.
BRITISH JOURNAL OF SURGERY
(2021)
Editorial Material
Oncology
Hilda L. Chan, Xiang H. -F. Zhang
Summary: According to an article in Cell, lymph node metastases can suppress the immune system and promote further cancer spread, which has also been confirmed in patients as described in a letter in this issue of Cancer Cell. This suggests that the lymph node actively creates a cancer-permissive environment and could be a potential target for immune system manipulation.
Article
Medicine, General & Internal
Paul-Andrei Stefan, Adrian Cote, Csaba Csutak, Roxana-Adelina Lupean, Andrei Lebovici, Carmen Mihaela Mihu, Lavinia Manuela Lenghel, Marius Emil Puscas, Andrei Roman, Diana Feier
Summary: The conventional MRI evaluation and staging of cervical cancer are subject to subjective evaluations, but texture analysis can offer a superior non-invasive characterization of lymph node status and improve the accuracy of staging cervical cancers.
Review
Oncology
Mathieu Struys, Wim Ceelen
Summary: The incidence of locoregional, potentially preventable lymph node recurrence after surgery for colon cancer is low and is not affected by the extent of lymphadenectomy.
Article
Medicine, General & Internal
Bo Chen, Guochun Zhang, Jianguo Lai, Weikai Xiao, Xuerui Li, Cheukfai Li, Hsiaopei Mok, Kai Li, Yulei Wang, Li Cao, Minghan Jia, Chongyang Ren, Lingzhu Wen, Guangnan Wei, Jiali Lin, Yingzi Li, Yuchen Zhang, Xiaoqing Chen, Xueying Wu, Henghui Zhang, Min Li, Jing Liu, Charles M. Balch, Ning Liao
Summary: This study revealed significant differences in molecular and immune profiles between single lymph node metastases and multiple lymph node metastases in breast cancer patients. Single lymph node metastases were associated with more aggressive tumor characteristics and more favorable immune characteristics compared to multiple lymph node metastases.
Article
Oncology
Yu Xin Xu, Ying Huang, Xiao Jie Wang, Dao Xiong Ye, Pan Chi
Summary: The study suggests that lymph node metastasis in station 206 is not an independent prognostic factor for transverse colon cancer, but it can serve as a predictive factor for disease-free survival (DFS). Only patients with T1-3, N+ and high risk should consider dissecting the lymph nodes in station 206.
Article
Gastroenterology & Hepatology
Hironori Fukuoka, Yosuke Fukunaga, Toshiya Nagasaki, Takashi Akiyoshi, Tsuyoshi Konishi, Satoshi Nagayama, Masashi Ueno
Summary: This study analyzed the patterns of lymph node metastasis in transverse colon cancer and reported the short- and long-term outcomes of different treatment procedures. The results showed differences in lymph node metastasis frequency and pathological vascular invasion rate among different surgical approaches. 5-year overall survival rates and relapse-free survival rates also varied for right hemicolectomy, transverse colectomy, and left hemicolectomy. The only independent prognostic factor for relapse-free survival was lymph node metastasis.
DISEASES OF THE COLON & RECTUM
(2022)
Article
Oncology
Cornelis M. de Mooij, Thiemo J. A. van Nijnatten, Briete Goorts, Loes F. S. Kooreman, Isabel W. M. Raymakers, Silke P. L. van Meijl, Maaike de Boer, Kristien B. M. I. Keymeulen, Joachim E. Wildberger, Felix M. Mottaghy, Marc B. I. Lobbes, Marjolein L. Smidt
Summary: This study investigated the feasibility of sequential hybrid [18F]FDG PET/MRI in predicting the treatment response in breast cancer patients undergoing neoadjuvant chemo(targeted) therapy. The qualitative or quantitative evaluation of PET/MRI after therapy was found to be unreliable in predicting the response of the primary tumor and axillary lymph nodes. However, combining the relative decrease in PET and MR imaging variables halfway through therapy improved the diagnostic accuracy, especially for predicting the response of axillary lymph nodes. These findings suggest that sequential hybrid [18F]FDG PET/MRI may have complementary value in the early prediction of treatment response in breast cancer.
Review
Public, Environmental & Occupational Health
H. K. Sekhon Inderjit Singh, N. Lal, A. Majeed, N. Pawa
Summary: This systematic review aims to clarify the impact of ethnicity on colorectal cancer screening uptake and identify barriers to understanding. The results show inconsistent screening uptake behavior among different ethnic minority groups. Further international collaboration and action are needed to address and improve screening inequity.
PERSPECTIVES IN PUBLIC HEALTH
(2023)
Article
Gastroenterology & Hepatology
Edward J. Jarman, Marta Horcas-Lopez, Scott H. Waddell, Stephanie MacMaster, Konstantinos Gournopanos, Daniel Y. H. Soong, Kamila Musialik, Panagiota Tsokkou, Minn-E Ng, William A. Cambridge, David H. Wilson, Michael H. Kagey, Walter Newman, Jeffrey W. Pollard, Luke Boulter
Summary: This study reveals the immune regulatory role of DKK1 in iCCA, showing that its overexpression leads to recruitment of immune suppressive macrophages and an increase in regulatory T cells. Inhibiting DKK1 can effectively reduce tumor growth in iCCA, and these findings are validated in human patient tissue.
LIVER INTERNATIONAL
(2023)
Article
Immunology
Eric Jou, Noe Rodriguez-Rodriguez, Ana-Carolina F. Ferreira, Helen E. Jolin, Paula A. Clark, Kovilen Sawmynaden, Michelle Ko, Jane E. Murphy, Jonathan Mannion, Christopher Ward, David J. Matthews, Simon J. A. Buczacki, Andrew N. J. McKenzie
Summary: Intestinal IL-25-activated ILC2s create a cancer-permissive microenvironment, associated with reduced survival and increased MDSCs in colorectal cancer patients. Ablation of IL-25 signaling reduces tumors and extends lifespan, while therapeutic antibody blockade enhances antitumor immunity.
SCIENCE IMMUNOLOGY
(2022)
Review
Oncology
Constantinos Simillis, Beth Taylor, Ayesha Ahmad, Nikhil Lal, Thalia Afxentiou, Michael P. Powar, Elizabeth C. Smyth, Nicola S. Fearnhead, James Wheeler, Richard J. Davies
Summary: This study compared long-term survival outcomes of patients of different BMI categories after colorectal cancer surgery, showing that patients with BMI < 18.5 or BMI > 35 had worse long-term survival, while patients with BMI 25-30 may improve survival in a subgroup of colon cancer patients.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Teresa Brevini, Mailis Maes, Gwilym J. Webb, Binu John, Claudia D. Fuchs, Gustav Buescher, Lu Wang, Chelsea Griffiths, Marnie L. Brown, William E. Scott, Pehuen Pereyra-Gerber, William T. H. Gelson, Stephanie Brown, Scott Dillon, Daniele Muraro, Jo Sharp, Megan Neary, Helen Box, Lee Tatham, James Stewart, Paul Curley, Henry Pertinez, Sally Forrest, Petra Mlcochova, Sagar S. Varankar, Mahnaz Darvish-Damavandi, Victoria L. Mulcahy, Rhoda E. Kuc, Thomas L. Williams, James A. Heslop, Davide Rossetti, Olivia C. Tysoe, Vasileios Galanakis, Marta Vila-Gonzalez, Thomas W. M. Crozier, Johannes Bargehr, Sanjay Sinha, Sara S. Upponi, Corrina Fear, Lisa Swift, Kourosh Saeb-Parsy, Susan E. Davies, Axel Wester, Hannes Hagstrom, Espen Melum, Darran Clements, Peter Humphreys, Jo Herriott, Edyta Kijak, Helen Cox, Chloe Bramwell, Anthony Valentijn, Christopher J. R. Illingworth, Bassam Dahman, Dustin R. Bastaich, Raphaella D. Ferreira, Thomas Marjot, Eleanor Barnes, Andrew M. Moon, Alfred S. Barritt, Ravindra K. Gupta, Stephen Baker, Anthony P. Davenport, Gareth Corbett, Vassilis G. Gorgoulis, Simon J. A. Buczacki, Joo-Hyeon Lee, Nicholas J. Matheson, Michael Trauner, Andrew J. Fisher, Paul Gibbs, Andrew J. Butler, Christopher J. E. Watson, George F. Mells, Gordon Dougan, Andrew Owen, Ansgar W. Lohse, Ludovic Vallier, Fotios Sampaziotis
Summary: Modulating the expression of angiotensin-converting enzyme 2 (ACE2) through farnesoid X receptor (FXR) can reduce susceptibility to SARS-CoV-2 infection, as shown in various tissues and organoids in vitro, in vivo, and ex vivo. The use of z-guggulsterone and ursodeoxycholic acid (UDCA) can downregulate ACE2 and decrease viral infection, including in the nasal epithelium. Clinical data also indicate positive outcomes with UDCA treatment in SARS-CoV-2 infection. These findings suggest that targeting the FXR-ACE2 pathway could be a potential strategy for preventing COVID-19.
Article
Genetics & Heredity
Yichen Wang, Philip S. Robinson, Tim H. H. Coorens, Luiza Moore, Henry Lee-Six, Ayesha Noorani, Mathijs A. Sanders, Hyunchul Jung, Riku Katainen, Robert Heuschkel, Roxanne Brunton-Sim, Robyn Weston, Debbie Read, Beverley Nobbs, Rebecca C. Fitzgerald, Kourosh Saeb-Parsy, Inigo Martincorena, Peter J. Campbell, Simon Rushbrook, Matthias Zilbauer, Simon James Alexander Buczacki, Michael R. Stratton
Summary: APOBEC mutational signatures SBS2 and SBS13 are commonly present in various human cancer types, but the stimulus, timing, and responsible APOBEC enzymes are not fully understood. Whole-genome sequencing of 342 microdissected normal epithelial crypts from the small intestines of 39 individuals revealed that SBS2/SBS13 mutations occurred in 17% of crypts, which is more frequent than in most other normal tissues. The study suggests that the high levels of SBS2/SBS13 in the small intestine are a result of APOBEC1 fulfilling its physiological function of editing APOB mRNA. Overall, APOBEC enzymes are a common contributor to the mutational burden in small intestine tissue.
Article
Biochemical Research Methods
Dedrick Kok Hong Chan, Scott David Collins, Simon James Alexander Buczacki
Summary: In this study, a multi-guide RNA CRISPR-Cas9 gene-editing protocol is described that enables efficient complete gene knockout in adult human colonic organoids. The protocol also details crucial steps for maximizing gene-editing efficacy through tissue harvesting and validating gene knockout using immunofluorescent staining of the organoids against the target protein.
Article
Gastroenterology & Hepatology
Dimitrios A. Koutoukidis, Susan A. Jebb, Claire Foster, Pete Wheatstone, Alison Horne, T. Martyn Hill, Amy Taylor, Alba Realpe, Felix Achana, Simon J. A. Buczacki
Summary: The aim of this trial is to assess the feasibility of intentional weight loss before colorectal cancer surgery and determine whether to proceed with a definitive trial.
COLORECTAL DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Aik Seng Ng, Dedrick Kok Hong Chan
Summary: Advances in sequencing have revealed a highly diverse landscape of mutational signatures and somatic driver mutations in normal tissues. Different normal tissues have varying mutation rates, with the liver having 11 mutations per cell per year and the bladder having 1879 mutations per cell per year. Understanding the relationship between normal tissue somatic mutations and tumor initiation remains limited. This study describes the mutational signatures and somatic driver mutations in different organs, highlighting unique characteristics and seeking commonalities to develop a unified theory on the role of these mutations in tumor initiation.
Article
Cell Biology
Dedrick Kok Hong Chan, Amit Mandal, Svenja Hester, Zhanru Yu, Geoff Stuart Higgins, Benedikt Mathias Kessler, Roman Fischer, Simon James Alexander Buczacki
Summary: This study found that FBXW7 gene mutation in colorectal cancer cells leads to DNA damage in neighboring wildtype cells. The study also discovered that FBXW7 mutant cells induce DNA damage through the secretion of AKAP8 protein. These findings highlight the importance of understanding the local effects of cancer driver mutations between subclonal populations.
CELL DEATH DISCOVERY
(2023)