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JOURNAL ARTICLE
Julie George, Lukas Maas, Nima Abedpour, Maria Cartolano, Laura Kaiser, Rieke N Fischer, Andreas H Scheel, Jan-Philipp Weber, Martin Hellmich, Graziella Bosco, Caroline Volz, Christian Mueller, Ilona Dahmen, Felix John, Cleidson Padua Alves, Lisa Werr, Jens Peter Panse, Martin Kirschner, Walburga Engel-Riedel, Jessica Jürgens, Erich Stoelben, Michael Brockmann, Stefan Grau, Martin Sebastian, Jan A Stratmann, Jens Kern, Horst-Dieter Hummel, Balazs Hegedüs, Martin Schuler, Till Plönes, Clemens Aigner, Thomas Elter, Karin Toepelt, Yon-Dschun Ko, Sylke Kurz, Christian Grohé, Monika Serke, Katja Höpker, Lars Hagmeyer, Fabian Doerr, Khosro Hekmath, Judith Strapatsas, Karl-Otto Kambartel, Geothy Chakupurakal, Annette Busch, Franz-Georg Bauernfeind, Frank Griesinger, Anne Luers, Wiebke Dirks, Rainer Wiewrodt, Andrea Luecke, Ernst Rodermann, Andreas Diel, Volker Hagen, Kai Severin, Roland T Ullrich, Hans Christian Reinhardt, Alexander Quaas, Magdalena Bogus, Cornelius Courts, Peter Nürnberg, Kerstin Becker, Viktor Achter, Reinhard Büttner, Jürgen Wolf, Martin Peifer, Roman K Thomas
The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown1-3 . Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity...
March 13, 2024: Nature
#22
JOURNAL ARTICLE
Anne-Lise Gérard, Rachel S Owen, Antoine M Dujon, Benjamin Roche, Rodrigo Hamede, Frédéric Thomas, Beata Ujvari, Hannah V Siddle
Since the emergence of a transmissible cancer, devil facial tumour disease (DFT1), in the 1980s, wild Tasmanian devil populations have been in decline. In 2016, a second, independently evolved transmissible cancer (DFT2) was discovered raising concerns for survival of the host species. Here, we applied experimental and modelling frameworks to examine competition dynamics between the two transmissible cancers in vitro. Using representative cell lines for DFT1 and DFT2, we have found that in monoculture, DFT2 grows twice as fast as DFT1 but reaches lower maximum cell densities...
March 2024: Evolutionary Applications
#23
REVIEW
Pascal Meier, Arnaud J Legrand, Dieter Adam, John Silke
Most metastatic cancers remain incurable due to the emergence of apoptosis-resistant clones, fuelled by intratumour heterogeneity and tumour evolution. To improve treatment, therapies should not only kill cancer cells but also activate the immune system against the tumour to eliminate any residual cancer cells that survive treatment. While current cancer therapies rely heavily on apoptosis - a largely immunologically silent form of cell death - there is growing interest in harnessing immunogenic forms of cell death such as necroptosis...
March 7, 2024: Nature Reviews. Cancer
#24
JOURNAL ARTICLE
Simonne Griffith-Jones, Lucía Álvarez, Urbi Mukhopadhyay, Sarah Gharbi, Mandy Rettel, Michael Adams, Janosch Hennig, Sagar Bhogaraju
MAGEA4 is a cancer-testis antigen primarily expressed in the testes but aberrantly overexpressed in several cancers. MAGEA4 interacts with the RING ubiquitin ligase RAD18 and activates trans-lesion DNA synthesis (TLS), potentially favouring tumour evolution. Here, we employed NMR and AlphaFold2 (AF) to elucidate the interaction mode between RAD18 and MAGEA4, and reveal that the RAD6-binding domain (R6BD) of RAD18 occupies a groove in the C-terminal winged-helix subdomain of MAGEA4. We found that MAGEA4 partially displaces RAD6 from the RAD18 R6BD and inhibits degradative RAD18 autoubiquitination, which could be countered by a competing peptide of the RAD18 R6BD...
March 6, 2024: EMBO Journal
#25
REVIEW
Siwen Xie, Thomas Charles Wood, Prokar Dasgupta, Abdullatif Aydin
Laparoscopic surgery is extensively utilized to treat a range of gynaecological conditions and pathologies. The advantages of laparoscopic surgery include the minimalization of blood loss and scarring, improved recovery times, and shorter hospital admissions. However, robotic technologies have had an increasing presence within gynaecological laparoscopic surgery in recent decades. This literature review therefore aims to discuss laparoscopy from 3 perspectives. First, the evolution of laparoscopy is reviewed with a focus on its origins, its transition from a diagnostic to an operative tool, and its role in present-day gynaecology...
March 6, 2024: Surgical Innovation
#26
JOURNAL ARTICLE
Mousumi Banerjee, Yarrarapu Siva Naga Sravani, Shorya Vardhan Azad, Pradeep Venkatesh
No abstract text is available yet for this article.
February 27, 2024: BMJ Case Reports
#27
JOURNAL ARTICLE
Yaron Ben-Ami, Joe M Pitt-Francis, Philip K Maini, Helen M Byrne
Interstitial fluid flow is a feature of many solid tumours. In vitro experiments have shown that such fluid flow can direct tumour cell movement upstream or downstream depending on the balance between the competing mechanisms of tensotaxis (cell migration up stress gradients) and autologous chemotaxis (downstream cell movement in response to flow-induced gradients of self-secreted chemoattractants). In this work we develop a probabilistic-continuum, two-phase model for cell migration in response to interstitial flow...
February 26, 2024: Biophysical Journal
#28
JOURNAL ARTICLE
Peter Y F Zeng, Stephenie D Prokopec, Stephen Y Lai, Nicole Pinto, Michelle A Chan-Seng-Yue, Roderick Clifton-Bligh, Michelle D Williams, Christopher J Howlett, Paul Plantinga, Matthew J Cecchini, Alfred K Lam, Iram Siddiqui, Jianxin Wang, Ren X Sun, John D Watson, Reju Korah, Tobias Carling, Nishant Agrawal, Nicole Cipriani, Douglas Ball, Barry Nelkin, Lisa M Rooper, Justin A Bishop, Cathie Garnis, Ken Berean, Norman G Nicolson, Paul Weinberger, Ying C Henderson, Christopher M Lalansingh, Mao Tian, Takafumi N Yamaguchi, Julie Livingstone, Adriana Salcedo, Krupal Patel, Frederick Vizeacoumar, Alessandro Datti, Liu Xi, Yuri E Nikiforov, Robert Smallridge, John A Copland, Laura A Marlow, Martin D Hyrcza, Leigh Delbridge, Stan Sidhu, Mark Sywak, Bruce Robinson, Kevin Fung, Farhad Ghasemi, Keith Kwan, S Danielle MacNeil, Adrian Mendez, David A Palma, Mohammed I Khan, Mushfiq Shaikh, Kara M Ruicci, Bret Wehrli, Eric Winquist, John Yoo, Joe S Mymryk, James W Rocco, David Wheeler, Steve Scherer, Thomas J Giordano, John W Barrett, William C Faquin, Anthony J Gill, Gary Clayman, Paul C Boutros, Anthony C Nichols
Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes...
February 26, 2024: Cell Reports
#29
JOURNAL ARTICLE
Xiang Huang, Jianhan Huang, Xiaoyu Zhou, Chao Zhang, Xinghua Ding, Peter Jih Cheng Wong, Yang Wang, Rong Zhang
AIMS: Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. METHODS AND RESULTS: In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%)...
February 26, 2024: Histopathology
#30
REVIEW
Xiaowei Yan, Paul Mischel, Howard Chang
Extrachromosomal DNA (ecDNA) has recently been recognized as a major contributor to cancer pathogenesis that is identified in most cancer types and is associated with poor outcomes. When it was discovered over 60 years ago, ecDNA was considered to be rare, and its impact on tumour biology was not well understood. The application of modern imaging and computational techniques has yielded powerful new insights into the importance of ecDNA in cancer. The non-chromosomal inheritance of ecDNA during cell division results in high oncogene copy number, intra-tumoural genetic heterogeneity and rapid tumour evolution that contributes to treatment resistance and shorter patient survival...
April 2024: Nature Reviews. Cancer
#31
Eszter Lakatos, Vinaya Gunasri, Luis Zapata, Jacob Househam, Timon Heide, Nicholas Trahearn, Ottilie Swinyard, Luis Cisneros, Claire Lynn, Maximilian Mossner, Chris Kimberley, Inmaculada Spiteri, George D Cresswell, Gerard Llibre-Palomar, Miriam Mitchison, Carlo C Maley, Marnix Jansen, Manuel Rodriguez-Justo, John Bridgewater, Ann-Marie Baker, Andrea Sottoriva, Trevor A Graham
Immune system control is a major hurdle that cancer evolution must circumvent. The relative timing and evolutionary dynamics of subclones that have escaped immune control remain incompletely characterized, and how immune-mediated selection shapes the epigenome has received little attention. Here, we infer the genome- and epigenome-driven evolutionary dynamics of tumour-immune coevolution within primary colorectal cancers (CRCs). We utilise our existing CRC multi-region multi-omic dataset that we supplement with high-resolution spatially-resolved neoantigen sequencing data and highly multiplexed imaging of the tumour microenvironment (TME)...
February 14, 2024: bioRxiv
#32
JOURNAL ARTICLE
Amit Deshpande, Jan Brants, Christine Wasylyk, Onno van Hooij, Gerald W Verhaegh, Peter Maas, Jack A Schalken, Bohdan Wasylyk
Tubulin tyrosine ligase 12 (TTLL12) is a promising target for therapeutic intervention since it has been implicated in tumour progression, the innate immune response to viral infection, ciliogenesis and abnormal cell division. It is the most mysterious of a fourteen-member TTL/TTLL family, since, although it is the topmost conserved in evolution, it does not have predicted enzymatic activities. TTLL12 seems to act as a pseudo-enzyme that modulates various processes indirectly. Given the need to target its functions, we initially set out to identify a property of TTLL12 that could be used to develop a reliable high-throughput screening assay...
2024: PloS One
#33
REVIEW
Ricardo Roque, Ilda Patrícia Ribeiro, Margarida Figueiredo-Dias, Charlie Gourley, Isabel Marques Carreira
Circulating tumour DNA (ctDNA) facilitates longitudinal study of the tumour genome, which, unlike tumour tissue biopsies, globally reflects intratumor and intermetastatis heterogeneity. Despite its costs, next-generation sequencing (NGS) has revolutionised the study of ctDNA, ensuring a more comprehensive and multimodal approach, increasing data collection, and introducing new variables that can be correlated with clinical outcomes. Current NGS strategies can comprise a tumour-informed set of genes or the entire genome and detect a tumour fraction as low as 10-5 ...
January 31, 2024: Biology
#34
REVIEW
Jianhua Zou, Yu Zhang, Yuanbo Pan, Zhengwei Mao, Xiaoyuan Chen
Neoantigens play a pivotal role in the field of tumour therapy, encompassing the stimulation of anti-tumour immune response and the enhancement of tumour targeting capability. Nonetheless, numerous factors directly influence the effectiveness of neoantigens in bolstering anti-tumour immune responses, including neoantigen quantity and specificity, uptake rates by antigen-presenting cells (APCs), residence duration within the tumour microenvironment (TME), and their ability to facilitate the maturation of APCs for immune response activation...
February 21, 2024: Chemical Society Reviews
#35
JOURNAL ARTICLE
Srinivasa Rao, Clare Verrill, Lucia Cerundolo, Nasullah Khalid Alham, Zeynep Kaya, Miriam O'Hanlon, Alicia Hayes, Adam Lambert, Martha James, Iain D C Tullis, Jane Niederer, Shelagh Lovell, Altan Omer, Francisco Lopez, Tom Leslie, Francesca Buffa, Richard J Bryant, Alastair D Lamb, Boris Vojnovic, David C Wedge, Ian G Mills, Dan J Woodcock, Ian Tomlinson, Freddie C Hamdy
BACKGROUND: Extension of prostate cancer beyond the primary site by local invasion or nodal metastasis is associated with poor prognosis. Despite significant research on tumour evolution in prostate cancer metastasis, the emergence and evolution of cancer clones at this early stage of expansion and spread are poorly understood. We aimed to delineate the routes of evolution and cancer spread within the prostate and to seminal vesicles and lymph nodes, linking these to histological features that are used in diagnostic risk stratification...
February 19, 2024: Genome Medicine
#36
JOURNAL ARTICLE
Xiaoyu Wang, Adrianne L Jenner, Robert Salomone, David J Warne, Christopher Drovandi
Agent-based models (ABMs) are readily used to capture the stochasticity in tumour evolution; however, these models are often challenging to validate with experimental measurements due to model complexity. The Voronoi cell-based model (VCBM) is an off-lattice agent-based model that captures individual cell shapes using a Voronoi tessellation and mimics the evolution of cancer cell proliferation and movement. Evidence suggests tumours can exhibit biphasic growth in vivo. To account for this phenomena, we extend the VCBM to capture the existence of two distinct growth phases...
February 15, 2024: Journal of Mathematical Biology
#37
JOURNAL ARTICLE
Rana Fetit, Alistair McLaren, Mark White, Megan L Mills, John Falconer, Xabier Cortes-Lavaud, Kathryn Gilroy, Tamsin Rm Lannagan, Rachel A Ridgway, Colin Nixon, Varushka Naiker, Renee Njunge, Cassie J Clarke, Declan Whyte, Kristina Kirschner, Rene Jackstadt, Jim C Norman, Leo M Carlin, Andrew D Campbell, Owen J Sansom, Colin W Steele
Neutrophils are a highly heterogenous cellular population. However, a thorough examination of the different transcriptional neutrophil states between health and malignancy, has not been performed. We utilised single-cell RNA-sequencing of human and murine datasets, both publicly available and independently generated, to identify neutrophil transcriptomic subtypes and developmental lineages in health and malignancy. Datasets of lung, breast and colorectal cancer (CRC) were integrated to establish and validate neutrophil gene-signatures...
February 15, 2024: Cancer Res Commun
#38
JOURNAL ARTICLE
Valentin Yuste, Ester Sanz, Isabel Negredo
Vulvar cancers are usually diagnosed at an advanced stage and require wide surgical resections in the form of vulvectomy. Immediate vulvar reconstruction can potentially reduce the reoperation rate and postoperative complications. With this objective, we introduced a protocol for immediate vulvar reconstruction. This study, five years after its introduction, assesses the impact of this intervention on the postoperative evolution of vulvectomy patients. In January 2017 we introduced a protocol for immediate vulvar reconstruction that considered four criteria of high risk for postoperative dehiscence...
February 1, 2024: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
#39
JOURNAL ARTICLE
Giorgia Ciavolella, Nathalie Ferrand, Michéle Sabbah, Benoît Perthame, Roberto Natalini
One of the most crucial and lethal characteristics of solid tumors is represented by the increased ability of cancer cells to migrate and invade other organs during the so-called metastatic spread. This is allowed thanks to the production of matrix metalloproteinases (MMPs), enzymes capable of degrading a type of collagen abundant in the basal membrane separating the epithelial tissue from the connective one. In this work, we employ a synergistic experimental and mathematical modelling approach to explore the invasion process of tumor cells...
February 12, 2024: Bulletin of Mathematical Biology
#40
JOURNAL ARTICLE
Julie Garcia, Jay Daniels, Yujin Lee, Iowis Zhu, Kathleen Cheng, Qing Liu, Daniel Goodman, Cassandra Burnett, Calvin Law, Chloë Thienpont, Josef Alavi, Camillia Azimi, Garrett Montgomery, Kole T Roybal, Jaehyuk Choi
Adoptive T cell therapies have produced exceptional responses in a subset of patients with cancer. However, therapeutic efficacy can be hindered by poor T cell persistence and function1 . In human T cell cancers, evolution of the disease positively selects for mutations that improve fitness of T cells in challenging situations analogous to those faced by therapeutic T cells. Therefore, we reasoned that these mutations could be co-opted to improve T cell therapies. Here we systematically screened the effects of 71 mutations from T cell neoplasms on T cell signalling, cytokine production and in vivo persistence in tumours...
February 7, 2024: Nature
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