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5. Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma

Author

Liu, Daniel S.K., Puik, Jisce R., Patel, Bhavik Y., Venø, Morten T., Vahabi, Mahrou, Prado, Mireia Mato, Webber, Jason P., Rees, Eleanor, Upton, Flora M., Bennett, Kate, Blaker, Catherine, Immordino, Benoit, Comandatore, Annalisa, Morelli, Luca, Sivakumar, Shivan, Swijnenburg, Rutger-Jan, Besselink, Marc G., Jiao, Long R., Kazemier, Geert, Giovannetti, Elisa, Krell, Jonathan, and Frampton, Adam E.

Published
2024
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12. Cover

Author

Krell, Jonathan

Published
1994

19. Notes

Author

Krell, Jonathan

Published
1994

22. Index

Author

Krell, Jonathan

Published
1994

24. A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease

Author

Mato Prado, Mireia, Puik, Jisce R., Castellano, Leandro, López-Jiménez, Elena, Liu, Daniel S. K., Meijer, Laura L., Le Large, Tessa Y. S., Rees, Eleanor, Funel, Niccola, Sivakumar, Shivan, Pereira, Stephen P., Kazemier, Geert, Zonderhuis, Babs M., Erdmann, Joris I., Swijnenburg, Rutger-Jan, Frilling, Andrea, Jiao, Long R., Stebbing, Justin, Giovannetti, Elisa, Krell, Jonathan, and Frampton, Adam E.

Published
2023
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25. Recommendations for standardizing biopsy acquisition and histological assessment of immune checkpoint inhibitor-associated colitis

Author

Ma, Christopher, Pai, Rish K, Schaeffer, David F, Krell, Jonathan, Guizzetti, Leonardo, McFarlane, Stefanie C, MacDonald, John K, Choi, Won-Tak, Feakins, Roger M, Kirsch, Richard, Lauwers, Gregory Y, Pai, Reetesh K, Rosty, Christophe, Srivastava, Amitabh, Walsh, Joanna C, Feagan, Brian G, and Jairath, Vipul

Subjects
Biomedical and Clinical Sciences, Immunology, Digestive Diseases, Cancer, Clinical Research, Biopsy, Colitis, Colonoscopy, Humans, Immune Checkpoint Inhibitors, immunotherapy, programmed cell death 1 receptor, CTLA-4 Antigen, inflammation, neutrophil infiltration, Oncology and carcinogenesis
Abstract

Immune checkpoint inhibitor-associated colitis (ICIC) affects approximately 15% of cancer patients treated with immunotherapy. Although histological evaluation is potentially valuable for both the diagnosis of ICIC and evaluation of disease activity, use in clinical practice is heterogeneous. We aimed to develop expert recommendations to standardize histological assessment of disease activity in patients with ICIC. Using the modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methodology, an international panel of 11 pathologists rated the appropriateness of 99 statements on a 9-point Likert scale during two rounds of anonymous voting. Results were discussed between rounds using moderated videoconferences. There are currently no disease-specific instruments for assessing histological features of ICIC. The panel considered that colonoscopy with at least three biopsies per segment from a total of at least five segments, including both endoscopically normal and inflamed areas, was appropriate for tissue acquisition. They agreed that biopsies should be oriented such that the long axis of the colonic crypts is visualized and should be stained with hematoxylin and eosin. Histological items that the panel voted were appropriate to evaluate in ICIC included the degree of structural/architectural change, chronic inflammatory infiltrate, lamina propria and intraepithelial neutrophils, crypt abscesses and destruction, erosions/ulcerations, apoptosis, surface intraepithelial lymphocytosis, and subepithelial collagen thickness. The appropriateness of routine immunohistochemistry was uncertain. These expert recommendations will help standardize assessment of histological activity in patients with ICIC. The panel also identified the development and validation of an ICIC-specific histological index as a research priority.

Published
2022

26. A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer

Author

Han, Sileny N., Oza, Amit, Colombo, Nicoletta, Oaknin, Ana, Raspagliesi, Francesco, Wenham, Robert M., Braicu, Elena Ioana, Jewell, Andrea, Makker, Vicky, Krell, Jonathan, Alía, Eva María Guerra, Baurain, Jean-François, Su, Zhenqiang, Neuwirth, Rachel, Vincent, Sylvie, Sedarati, Farhad, Faller, Douglas V., and Scambia, Giovanni

Published
2023
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28. Spatial and temporal intra-tumoral heterogeneity in advanced HGSOC: Implications for surgical and clinical outcomes

Author

Cunnea, Paula, Curry, Edward W., Christie, Elizabeth L., Nixon, Katherine, Kwok, Chun Hei, Pandey, Ahwan, Wulandari, Ratri, Thol, Kerstin, Ploski, Jennifer, Morera-Albert, Cristina, McQuaid, Stephen, Lozano-Kuehne, Jingky, Clark, James J., Krell, Jonathan, Stronach, Euan A., McNeish, Iain A., Bowtell, David D.L., and Fotopoulou, Christina

Published
2023
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30. The Hammersmith Score optimises patient selection and predicts for overall survival in early-phase cancer trial participants independent of tumour burden

Author

Korolewicz, James Alexander, primary, Scheiner, Bernhard, additional, Fulgenzi, Claudia A.M., additional, D'Alessio, Antonio, additional, Cortellini, Alessio, additional, Pascual, Chynna, additional, Mehan, Aman, additional, Partridge, Sarah, additional, Gujral, Dorothy M., additional, Mohammed, Waleed, additional, Mohammed, Oreoluwa, additional, Grzesiak, Aneta, additional, Booker, Lauren, additional, Cleator, Susan, additional, Pokrovska, Tzveta, additional, Saleem, Waqar, additional, Rackie, James, additional, Needham, Yasmine, additional, Krell, Jonathan, additional, McNeish, Iain, additional, Tookman, Laura, additional, Park, Won-Ho Edward, additional, Asif, Muzamil, additional, Evans, Joanne S., additional, and Pinato, David J., additional

Published
2024
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37. The genomic trajectory of ovarian high‐grade serous carcinoma can be observed in STIC lesions.

Author

Cheng, Zhao, Ennis, Darren P, Lu, Bingxin, Mirza, Hasan B, Sokota, Chishimba, Kaur, Baljeet, Singh, Naveena, Le Saux, Olivia, Russo, Giorgia, Giannone, Gaia, Tookman, Laura A, Krell, Jonathan, Barnes, Chris, McDermott, Jackie, and McNeish, Iain A

Subjects
FALLOPIAN tubes, PERITONEUM, OVARIAN tumors, PLOIDY, OVARIES
Abstract

Ovarian high‐grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early‐ and late‐stage HGSC and found higher ploidy in late‐stage (median 3.1) than early‐stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole‐genome duplication (WGD) observed in late‐stage disease were determined early in the evolution of HGSC, we analysed archival formalin‐fixed paraffin‐embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser‐capture microdissected and sequenced using shallow whole‐genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next‐generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Published
2024
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38. The genomic trajectory of ovarian high grade serous carcinoma is determined in STIC lesions

Author

Cheng, Zhao, primary, Ennis, Darren P, additional, Lu, Bingxin, additional, Mirza, Hasan B, additional, Sokota, Chishimba, additional, Kaur, Baljeet, additional, Singh, Naveena, additional, Le Saux, Olivia, additional, Russo, Giorgia, additional, Giannone, Gaia, additional, Tookman, Laura A, additional, Krell, Jonathan, additional, McDermott, Jacqueline, additional, Barnes, Chris, additional, and McNeish, Iain A, additional

Published
2024
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39. Abstract PR-004: The evolution of ovarian high grade serous carcinoma from STIC lesions

Author

Cheng, Zhao, primary, Ennis, Darren P., additional, Lu, Bingxin, additional, Mirza, Hasan, additional, Sokota, Chishimba, additional, Kaur, Baljeet, additional, Singh, Naveena, additional, Le Saux, Olivia, additional, Giannone, Gaia, additional, Tookman, Laura, additional, Krell, Jonathan, additional, McDermott, Jacqueline, additional, Barnes, Chris, additional, and McNeish, Iain A., additional

Published
2024
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41. Abstract B114: Effect of spatial and temporal inter-tumoral heterogeneity on homologous recombination deficiency scores in high grade serous ovarian cancer

Author

Christie, Elizabeth L., primary, Lorentzen, Marc, additional, Liu, Maiqi, additional, Burdett, Nikki, additional, Curry, Edward, additional, Kwok, Chun Hei, additional, Pandey, Ahwan, additional, Nixon, Katherine, additional, Ploski, Jennifer, additional, Clark, James J., additional, McNeish, Iain, additional, Bowtell, David D.L., additional, Krell, Jonathan, additional, Fotopoulou, Christina, additional, and Cunnea, Paula, additional

Published
2024
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42. Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial

Author

Morgan, Robert D, McNeish, Iain A, Cook, Adrian D, James, Elizabeth C, Lord, Rosemary, Dark, Graham, Glasspool, Rosalind M, Krell, Jonathan, Parkinson, Christine, Poole, Christopher J, Hall, Marcia, Gallardo-Rincón, Dolores, Lockley, Michelle, Essapen, Sharadah, Summers, Jeff, Anand, Anjana, Zachariah, Abel, Williams, Sarah, Jones, Rachel, Scatchard, Kate, Walther, Axel, Kim, Jae-Weon, Sundar, Sudha, Jayson, Gordon C, Ledermann, Jonathan A, and Clamp, Andrew R

Published
2021
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45. PR055/#936 Influence of spatial tumour heterogeneity on homologous recombination deficiency scores for high grade serous ovarian cancer patients

Author

Fotopoulou, Christina, primary, Christie, Elizabeth, additional, Lorentzen, Marc, additional, Liu, Maiqi, additional, Curry, Edward, additional, Kwok, Chun Hei, additional, Nixon, Katherine, additional, Ploski, Jennifer, additional, Clark, James, additional, Mcneish, Iain, additional, Krell, Jonathan, additional, and Cunnea, Paula, additional

Published
2023
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46. Diversity of thought: public perceptions of genetic testing across ethnic groups in the UK

Author

Harris, Benjamin H. L., primary, McCabe, Caitlin, additional, Shafique, Hana, additional, Lammy, Simon, additional, Tookman, Laura, additional, Flanagan, James, additional, Miron-Barroso, Sofia, additional, Lythgoe, Mark, additional, Clark, James, additional, Walsh, Jason L., additional, Di Giovannantonio, Matteo, additional, and Krell, Jonathan, additional

Published
2023
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48. The complex network of p53-regulated small non-coding RNAs and their gene targets in cancer

Author

Krell, Jonathan, Stebbing, Justin, and Castellano, Leandro

Subjects
610
Abstract

DNA damage transactivates TP53-regulated surveillance mechanisms that are crucial in maintaining cellular integrity and suppressing tumorigenesis. TP53 mediates this directly by transcriptionally modulating gene and microRNA (miRNA) expression and by regulating miRNA biogenesis through interaction with the DROSHA complex. However, the regulative mechanism of miRNA-AGO2 loading and the global change in AGO2 binding to its gene targets in response to DNA damage have not been investigated yet. In addition, the role of other non-coding RNAs, such as snoRNAs, in the TP53-mediated response to DNA damage has not yet been defined. Here we identify a novel group of TP53-regulated miRNAs and show that DNA damage induces and reduces the loading of a subset of miRNAs, including the let-7 family members onto AGO2, in a TP53-dependent manner and that this previously undescribed process is most likely the result of TP53 binding to AGO2. These findings indicate that TP53 control of AGO2 loading is a new mechanism of miRNA regulation in carcinogenesis. Using AGO2 RIP-Seq and PAR-CLIP we also show that TP53 modulates the reduction, induction and remodelling of AGO2 binding to the 3'UTR of different mRNA targets at specific RNA motifs. Furthermore, we determine on a transcriptome-wide level the miRNA-mRNA interaction networks involved in the response to DNA damage both in the presence or absence of TP53. We also show that those miRNAs whose cellular abundance or differential loading onto AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits that fine tune gene expression levels in response to DNA damage to permit DNA repair or the initiation of programmed cell death. Finally, we demonstrate a relationship between TP53 and the GAS5-derived snoRNAs both in cancer cell lines and human tissue samples which implies that this class of non-coding RNAs might also be involved in coordinating the TP53-mediated response. These findings provide a novel insight into the complexities surrounding the role of non-coding RNAs in the TP53 response to DNA damage and their relevance to carcinogenesis.

Published
2015
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49. The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper

Author

Cristofanilli, Massimo, Pierga, Jean-Yves, Reuben, James, Rademaker, Alfred, Davis, Andrew A., Peeters, Dieter J., Fehm, Tanja, Nolé, Franco, Gisbert-Criado, Rafael, Mavroudis, Dimitrios, Grisanti, Salvatore, Giuliano, Mario, Garcia-Saenz, Jose A., Stebbing, Justin, Caldas, Carlos, Gazzaniga, Paola, Manso, Luis, Zamarchi, Rita, de Lascoiti, Angela Fernandez, De Mattos-Arruda, Leticia, Ignatiadis, Michail, Cabel, Luc, van Laere, Steven J., Meier-Stiegen, Franziska, Sandri, Maria-Teresa, Vidal-Martinez, Jose, Politaki, Eleni, Consoli, Francesca, Generali, Daniele, Cappelletti, Maria Rosa, Diaz-Rubio, Eduardo, Krell, Jonathan, Dawson, Sarah-Jane, Raimondi, Cristina, Rutten, Annemie, Janni, Wolfgang, Munzone, Elisabetta, Carañana, Vicente, Agelaki, Sofia, Almici, Camillo, Dirix, Luc, Solomayer, Erich-Franz, Zorzino, Laura, Darrigues, Lauren, Reis-Filho, Jorge S., Gerratana, Lorenzo, Michiels, Stefan, Bidard, François-Clément, and Pantel, Klaus

Published
2019
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