Article
Gastroenterology & Hepatology
Tessa Dieckman, Mette Schreurs, Ahmed Mahfouz, Yvonne Kooy-Winkelaar, Andra Neefjes-Borst, Gerd Bouma, Frits Koning
Summary: Novel high-dimensional single-cell technologies reveal substantial intertumoral and intratumoral heterogeneity in the aberrant cell population in RCDII. This heterogeneity may contribute to variability in refractory disease status among patients and their response to therapy, highlighting the need for personalized therapy in RCDII based on patient-specific immune profiles.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Titanilla Danko, Gabor Petovari, Regina Raffay, Daniel Sztankovics, Dorottya Moldvai, Eniko Vetlenyi, Ildiko Krencz, Andras Rokusz, Krisztina Sipos, Tamas Visnovitz, Judit Papay, Anna Sebestyen
Summary: This study provides a complex comparative analysis of 2D and 3D culturing systems, as well as breast cancer models using 3D bioprinting and xenografting. The results show that the 3D bioprinted tissue-mimetic scaffolds have the highest similarity to the less drug-sensitive xenograft models, and they also demonstrate the in situ tissue heterogeneity of human breast cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Jelmer Legebeke, Katie L. Horton, Claire L. Jackson, Janice Coles, Amanda Harris, Htoo A. Wai, John W. Holloway, Gabrielle Wheway, Diana Baralle, Jane S. Lucas
Summary: In this study, the differentiation and recapitulation of pseudostratified epithelium in air-liquid interface (ALI) cell culture were evaluated, showing its usefulness in researching respiratory health and disease. The transcriptomic changes of ALI-culture were compared to ex vivo nasal brushing samples, highlighting the need for co-cultures with immune cell representation to better reflect the physiological state. The study also revealed the timing of ALI-culture harvest for research studies needs to be carefully considered, as different time-points correspond to different gene expressions and cell functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Eline J. C. A. Kamp, Maikel P. Peppelenbosch, Michail Doukas, Joanne Verheij, Cyriel Y. Ponsioen, Ronald van Marion, Marco J. Bruno, Bas Groot Koerkamp, Winand N. M. Dinjens, Annemarie C. de Vries
Summary: This study found high intertumor and intratumor heterogeneity in PSC-CCA, including p53/p16 protein expression and TP53/CDKN2A genetic alterations. These tumors consist of multiple subclones with substantially different genetic makeup.
CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shuso Takeda, Masayo Hirao-Suzuki, Mitsuru Shindo, Hironori Aramaki
Summary: This study demonstrates that (-)-xanthatin is able to kill mammospheres of breast cancer CSCs, indicating a potential anti-proliferative mechanism.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kornphimol Kulthong, Guido J. E. J. Hooiveld, Loes Duivenvoorde, Ignacio Miro Estruch, Victor Marin, Meike van der Zande, Hans Bouwmeester
Summary: Dynamic culture conditions in gut-on-chip devices can mimic the in vivo intestinal environment and impact the gene expression of Caco-2 cells. The study shows that under dynamic culture conditions, gene expression patterns similar to those of the intestines in vivo were observed.
SCIENTIFIC REPORTS
(2021)
Review
Nutrition & Dietetics
Francesca Velotti, Roberta Bernini
Summary: Inflammaging refers to chronic low-grade inflammation caused by immune and non-immune cells stimulated by endogenous/self, misplaced or altered molecules, belonging to physiological aging. This inflammatory status is characterized by increased inflammation and decreased autophagy, and predisposes to age-related diseases. Phenolic compounds, particularly hydroxytyrosol (HTyr) found in extra-virgin olive oil, have antioxidant and anti-inflammatory properties that may counteract inflammaging and contribute to healthy aging.
Article
Oncology
Tatjana Geukens, Maxim De Schepper, Francois Richard, Marion Maetens, Karen Van Baelen, Amena Mahdami, Ha-Linh Nguyen, Edoardo Isnaldi, Sophia Leduc, Anirudh Pabba, Gitte Zels, Freya Mertens, Sara Vander Borght, Ann Smeets, Ines Nevelsteen, Kevin Punie, Patrick Neven, Hans Wildiers, Wouter van den Bogaert, Giuseppe Floris, Christine Desmedt
Summary: This study evaluated the inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer patients, finding that HER2-low and HER2-negative metastases coexisted in the same patients. This raises questions about the validity of HER2-low as a therapeutic marker.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Biochemical Research Methods
Samuel S. Hinman, Yuli Wang, Raehyun Kim, Nancy L. Allbritton
Summary: This protocol describes the fabrication of 3D collagen scaffolds used to culture human colonic crypts derived from primary intestinal epithelial cells. The methods include microfabrication and soft lithography protocols necessary to shape hydrogels to match in vivo crypt dimensions. The platform supports the formation of chemical gradients across the crypts, including growth and differentiation factors, inflammatory compounds, bile and food metabolites and bacterial products.
Article
Dermatology
Mimi R. Borrelli, Abra H. Shen, Michelle Griffin, Shamik Mascharak, Sandeep Adem, Nestor M. Diaz Deleon, Ledibabari Mildred Ngaage, Michael T. Longaker, Derrick C. Wan, Hermann Peter Lorenz
Summary: This study introduced a novel xenograft model utilizing full-thickness human neonatal foreskin to study human skin wound repair. Injection of antifibrotic FGF2 into wounded xenografts resulted in reduced fibrosis, indicating potential efficacy of topical therapies in wound repair.
ADVANCES IN WOUND CARE
(2022)
Article
Multidisciplinary Sciences
Diana Cadena Castaneda, Sonia Jangra, Marina Yurieva, Jan Martinek, Megan Callender, Matthew Coxe, Angela Choi, Juan Garcia-Bernalt Diego, Jianan Lin, Te-Chia Wu, Florentina Marches, Damien Chaussabel, Peter Yu, Andrew Salner, Gabrielle Aucello, Jonathan Koff, Briana Hudson, Sarah E. Church, Kara Gorman, Esperanza Anguiano, Adolfo Garcia-Sastre, Adam Williams, Michael Schotsaert, Karolina Palucka
Summary: The COVID-19 pandemic continues to present significant unfulfilled medical needs, particularly in understanding the early responses from airway epithelial cells. A study using human primary air-liquid interface cultures representing broncho-alveolar epithelia revealed the kinetics and dynamics of SARS-CoV-2 variants infection. The findings showed distinct temporal and spatial immune responses triggered by the virus.
Article
Multidisciplinary Sciences
Sahar J. Alothman, Keunsoo Kang, Xuefeng Liu, Ewa Krawczyk, Redha Azhar, Rong Hu, David Goerlitz, Bhaskar Kallakury, Priscilla A. Furth
Summary: This study explores the biology and transcriptomes of non-cancerous human mammary epithelial cells at risk for breast cancer development. The findings suggest that high-risk cells exhibit diverse behavioral and gene expression patterns, potentially indicating different risk profiles.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Tongde Wu, Joe A. Wrennall, Hong Dang, Deborah L. Baines, Robert Tarran
Summary: Primary human bronchial epithelial cultures (HBECs) are useful for studying airway physiology, disease, and drug development, but their expansion through passaging can affect their phenotype and gene expression, as well as their functional properties.
Article
Biochemistry & Molecular Biology
Andrea Zimmermann, Rene Hansel, Kilian Gemunden, Victoria Kegel-Hubner, Jonas Babel, Hendrik Blaker, Madlen Matz-Soja, Daniel Seehofer, Georg Damm
Summary: Liver macrophages play a central role in acute and chronic liver pathologies, with distinct characteristics in different disease states. Most liver tissues showed anti-inflammatory macrophages, while isolated macrophages exhibited a complex disease-dependent pattern.
Article
Genetics & Heredity
Hongju (Daisy) Chen, Bin Yi, Qiang Liu, Xia Xu, Lin Dai, Zhanshan (Sam) Ma
Summary: The study utilized DAR analysis to uncover the diversity scaling along the digestive tract and inter-individual heterogeneities of the human gut microbiome. Most digestive tract sites have different potential diversities, and individual microbiomes primarily differ in the composition of bacterial species.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Devika Ganesamoorthy, Alan James Robertson, Wenhan Chen, Michael B. Hall, Minh Duc Cao, Kaltin Ferguson, Sunil R. Lakhani, Katia Nones, Peter T. Simpson, Lachlan J. M. Coin
Summary: This study conducted deep sequencing analysis of plasma samples, revealing a higher fraction of unique somatic mutations in plasma samples that were not detected in matched tumour samples. Sequencing of di-nucleosome bound cfDNA fragments may increase recovery of tumour mutations from plasma.
Article
Oncology
Malcolm Lim, Tam H. Nguyen, Colleen Niland, Lynne E. Reid, Parmjit S. Jat, Jodi M. Saunus, Sunil R. Lakhani
Summary: This study investigated the relationship between brain metastases and drug treatment in HER2+ breast cancer patients. The results showed that brain metastases from breast, ovarian, lung, and kidney cancers have higher levels of HER2-HER3 dimers compared to other primary tumor types. However, traditional HER2-targeted therapies, such as pertuzumab, have limited inhibitory effects on HER2-HER3 dimerization in the presence of excess neuregulin, which may explain the occurrence of brain metastases.
Article
Oncology
Kekoolani S. Visan, Richard J. Lobb, Shu Wen Wen, Justin Bedo, Luize G. Lima, Sophie Krumeich, Carlos Palma, Kaltin Ferguson, Ben Green, Colleen Niland, Nicole Cloonan, Peter T. Simpson, Amy E. McCart Reed, Sarah J. Everitt, Michael P. MacManus, Gunter Hartel, Carlos Salomon, Sunil R. Lakhani, David Fielding, Andreas Moeller
Summary: Lung cancer is a leading cause of cancer-related death worldwide and has low survival rates due to lack of early detection. A study on a lung cancer biomarker based on a simple blood test shows promising advantages for diagnostic assessment. The study identifies a specific micro-RNA, miR-3182, as a potential biomarker for lung cancer diagnosis that can be detected in the blood.
Review
Cell Biology
Benjamin Yongcheng Tan, Stephen B. Fox, Sunil R. Lakhani, Puay Hoon Tan
Summary: Grading of breast phyllodes tumors (PTs) varies due to differences in weighting of grading criteria by pathologists. Key diagnostic criteria include increased stromal cellularity, stromal overgrowth, increased stromal mitoses, stromal atypia, stromal fronding, irregular tumor borders, and/or lesional heterogeneity. Clinical and radiological findings, as well as age, also play important roles in determining the diagnosis.
Review
Cell Biology
A. Sokolova, K. J. Johnstone, A. E. McCart Reed, P. T. Simpson, S. R. Lakhani
Summary: Hereditary factors, including pathogenic variants in genes such as BRCA1, BRCA2, ATM, CHEK2, etc., play a significant role in breast cancer risk. Polygenic risk, which results from carrying multiple low-penetrance breast cancer susceptibility alleles, also contributes to the risk. This review provides an overview of established breast cancer susceptibility genes, breast cancer predisposition syndromes, and discusses the implications of molecular testing and therapy in hereditary breast cancer.
Article
Cell Biology
Nur Diyana Md Nasir, Valerie C. Y. Koh, Ian A. Cree, Blanca I. I. Ruiz, Javier Del Aguila, Subasri Armon, Stephen B. Fox, Sunil R. Lakhani, Puay Hoon Tan
Summary: In this study, an evidence gap map (EGM) was developed based on the literature cited in the PT chapter of the breast WCT. The EGM revealed a lack of high-level evidence citations and an uneven distribution of references. Future work is needed to bridge evidence gaps and broaden citations.
Article
Oncology
David I. Fielding, Andrew J. Dalley, Mahendra Singh, Lakshmy Nandakumar, Vanessa Lakis, Haarika Chittoory, David Fairbairn, Ann-Marie Patch, Stephen H. Kazakoff, Kaltin Ferguson, Farzad Bashirzadeh, Michael Bint, Carl Pahoff, Jung Hwa Son, Alan Hodgson, Sowmya Sharma, Nicola Waddell, Sunil R. Lakhani, Gunter Hartel, Katia Nones, Peter T. Simpson
Summary: Microscopy of Diff-Quik smears can predict DNA yield and be used for molecular diagnostics. This method can be a better alternative to traditional cell block testing.
CANCER CYTOPATHOLOGY
(2023)
Article
Cell Biology
Heather Thorne, Lisa Devereux, Jason Li, Kathryn Alsop, Liz Christie, Courtney T. van Geelen, Nikki Burdett, Kathleen Pishas, Noel Woodford, Jodie Leditschke, Mohamed H. M. A. Izzath, Kate Strachan, Gregory Young, Rufaro D. Jaravaza, Mohammed S. Madadin, Melanie Archer, Joanna Glengarry, Linda Iles, Ajith Rathnaweera, Clare Hampson, Khamis Almazrooei, Michael Burke, Pradeep Bandara, David Ranson, Essa Saeedi, Orla McNally, Linda Mileshkin, Anne Hamilton, Sumitra Ananda, George Au-Yeung, Yoland Antill, Shahneen Sandhu, Peter Savas, Prudence A. Francis, Stephen Luen, Sherene Loi, Ross Jennens, Clare Scott, Kate Moodie, Margaret Cummings, Andrew Reid, Amy McCart Reed, David Bowtell, Sunil R. Lakhani, Stephen Fox
Summary: This study aims to examine the metastatic patterns of breast, ovarian, and prostate cancer in germline BRCA1/2 mutation carriers and non-carriers through a rapid autopsy program. It found significant differences in the patterns of metastases in breast and ovarian cancer between BRCA1/2 carriers and non-carriers, while no significant differences were observed in prostate cancer. The findings have implications for clinical diagnostic imaging in monitoring metastases.
Review
Oncology
Isobel P. Taylor, J. Alejandro Lopez
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a common and difficult-to-treat cancer. Surgical resection and chemotherapy are the standard treatments, but the clinical outcomes are still poor. This paper reviews the clinical trials of conditionally-replicative adenoviruses in pancreatic cancer, providing a summary of the current literature and future prospects of this therapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Janelle L. Hancock, Murugan Kalimutho, Jasmin Straube, Malcolm Lim, Irma Gresshoff, Jodi M. Saunus, Jason S. Lee, Sunil R. Lakhani, Kaylene J. Simpson, Ashley I. Bush, Robin L. Anderson, Kum Kum Khanna
Summary: This study found that loss of the COMMD3 gene promotes aggressive behavior in breast cancer cells and is associated with a lower survival rate. Further experiments showed that COMMD3 is involved in copper signaling and functions by regulating the expression of the Na+/K+-ATPase subunit ATP1B1.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Maina Bitar, Isela Sarahi Rivera, Isabela Almeida, Wei Shi, Kaltin Ferguson, Jonathan Beesley, Sunil R. Lakhani, Stacey L. Edwards, Juliet D. French
Summary: Single-cell RNAseq has revealed the expression of thousands of long noncoding RNAs (lncRNAs) in human mammary epithelial cells, providing new insights into breast cell subpopulations. Clustering cells based on lncRNA expression can better discern basal subpopulations compared to annotated gene expression. Tissue-specific annotation of lncRNAs is necessary for accurate expression analysis. Breast-specific lncRNAs can serve as potential biomarkers and therapeutic targets for breast cancer subtypes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Andrew Causer, Xiao Tan, Xuehan Lu, Philip Moseley, Siok M. Teoh, Natalie Molotkov, Margaret McGrath, Taehyun Kim, Peter T. Simpson, Christopher Perry, Ian H. Frazer, Benedict Panizza, Rahul Ladwa, Quan Nguyen, Jazmina L. Gonzalez-Cruz
Summary: In this study, advanced integrative spatial proteogenomic analysis was used to investigate the role of spatial determinants in cancer therapy outcomes. The researchers found that spatial transcriptomics successfully detected tumor cells and allowed for the investigation of phenotypic traits. Additionally, spatial proteomic imaging resolved the profiling of tumor infiltrating immune cells. The study also discovered clinically relevant alternative medicines based on their interaction with their matching ligand-receptor. Importantly, the researchers found that new tumors were not the product of immune checkpoint inhibitor (ICI) resistance but rather of a dose reduction due to complications.
NPJ PRECISION ONCOLOGY
(2023)