4.7 Article

MRI reveals the in vivo cellular and vascular response to BEZ235 in ovarian cancer xenografts with different PI3-kinase pathway activity

Journal

BRITISH JOURNAL OF CANCER
Volume 112, Issue 3, Pages 504-513

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.628

Keywords

-

Categories

Funding

  1. Norwegian Research Council [224788/F11]
  2. Norwegian Research School in Medical Imaging (MedIm)
  3. Dutch VSB fonds and Prins Bernhard cultuurfonds (Klok Korsmit Tacke fonds)
  4. Susan G. Komen for the Cure Career Catalyst Grant [KG090640]
  5. Norwegian Cancer Society
  6. Norwegian Breast Cancer Society [2209215-2011]
  7. Norwegian Cancer Society [171656-PR-2009-0270]
  8. Cancer Research Foundation at St Olav's University Hospital

Ask authors/readers for more resources

Background: The phosphoinositide-3 kinase (PI3K) pathway is an attractive therapeutic target. However, difficulty in predicting therapeutic response limits the clinical implementation of PI3K inhibitors. This study evaluates the utility of clinically relevant magnetic resonance imaging (MRI) biomarkers for noninvasively assessing the in vivo response to the dual PI3K/mTOR inhibitor BEZ235 in two ovarian cancer models with differential PI3K pathway activity. Methods: The PI3K signalling activity of TOV-21G and TOV-112D human ovarian cancer cells was investigated in vitro. Cellular and vascular response of the xenografts to BEZ235 treatment (65 mg kg(-1), 3 days) was assessed in vivo using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE)-MRI. Micro-computed tomography was performed to investigate changes in vascular morphology. Results: The TOV-21G cells showed higher PI3K signalling activity than TOV-112D cells in vitro and in vivo. Treated TOV-21G xenografts decreased in volume and DW-MRI revealed an increased water diffusivity that was not found in TOV-112D xenografts. Treatment-induced improvement in vascular functionality was detected with DCE-MRI in both models. Changes in vascular morphology were not found. Conclusions: Our results suggest that DW- and DCE-MRI can detect cellular and vascular response to PI3K/mTOR inhibition in vivo. However, only DW-MRI could discriminate between a strong and weak response to BEZ235.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Materials Science, Multidisciplinary

Polymerization as a Strategy to Improve Small Organic Matrices for Low-Molecular-Weight Compound Analytics with MALDI MS and MALDI MS Imaging

Kilian Horatz, Marco Giampa, Zhi Qiao, Siver A. Moestue, Franziska Lissel

Summary: MALDI MS and MSI are powerful analytical methods in medical and pathological research. Polymerizing SOMs into P(SOMs) mitigates background interferences, enhances vacuum stability, while maintaining the advantages of the original matrices.

ACS APPLIED POLYMER MATERIALS (2021)

Article Geriatrics & Gerontology

MRI-derived brain age as a biomarker of ageing in rats: validation using a healthy lifestyle intervention

Irene Brusini, Eilidh MacNicol, Eugene Kim, Orjan Smedby, Chunliang Wang, Eric Westman, Mattia Veronese, Federico Turkheimer, Diana Cash

Summary: The study suggests that interventions related to lifestyle factors can slow down brain aging in rodents, showing that long-term environmental enrichment and dietary restriction can lead to a slower increase in BrainAGE in rats. Higher BrainAGE at 5 months was found to be associated with increased mortality risk, highlighting the potential of BrainAGE as a predictor of age-related health outcomes.

NEUROBIOLOGY OF AGING (2022)

Article Mathematical & Computational Biology

Age-Specific Adult Rat Brain MRI Templates and Tissue Probability Maps

Eilidh MacNicol, Paul Wright, Eugene Kim, Irene Brusini, Oscar Esteban, Camilla Simmons, Federico E. Turkheimer, Diana Cash

Summary: Age-specific resources in human and rat MRI are important for mitigating processing biases and accurately estimating tissue volumes. This study found that by using age-specific rat brain templates and tissue probability maps, better estimations of gray matter volumes could be achieved. Furthermore, it was discovered that tissue volumes and proportions relative to total brain volume vary across adulthood in rats.

FRONTIERS IN NEUROINFORMATICS (2022)

Article Multidisciplinary Sciences

Relevance of sleep and associated structural changes in GBA1 mouse to human rapid eye movement behavior disorder

Cigdem Gelegen, Diana Cash, Katarina Ilic, Millie Sander, Eugene Kim, Camilla Simmons, Michel Bernanos, Joana Lama, Karen Randall, Jonathan T. Brown, Svjetlana Kalanj-Bognar, Samuel Cooke, K. Ray Chaudhuri, Clive Ballard, Paul Francis, Ivana Rosenzweig

SCIENTIFIC REPORTS (2022)

Review Neurosciences

Imaging Synaptic Density: The Next Holy Grail of Neuroscience?

Maria Elisa Serrano, Eugene Kim, Marija M. Petrinovic, Federico Turkheimer, Diana Cash

Summary: The brain is a complex organ composed of billions of neurons and trillions of synapses. Proper regulation of synaptic density is crucial for normal brain development, and abnormalities in synapses have been associated with various neurological and psychiatric disorders. Several methods, including PET and MRI, are being developed to measure synaptic density, but further research is needed to address their limitations before they can be used clinically.

FRONTIERS IN NEUROSCIENCE (2022)

Article Biophysics

Tissue optimization strategies for high-quality ex vivo diffusion imaging

Rachel L. C. Barrett, Diana Cash, Camilla Simmons, Eugene Kim, Tobias C. Wood, Richard Stones, Anthony C. Vernon, Marco Catani, Flavio Dell'Acqua

Summary: In this study, an optimization strategy for ex vivo diffusion imaging was developed to improve image quality and signal-to-noise ratio (SNR). The strategy successfully enabled the acquisition of high-resolution diffusion data with improved SNR efficiency and allowed for faster acquisitions in preclinical experiments.

NMR IN BIOMEDICINE (2023)

Article Psychiatry

Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes

Amanda Kiemes, Maria Elisa Serrano Navacerrada, Eugene Kim, Karen Randall, Camilla Simmons, Loreto Rojo Gonzalez, Marija-Magdalena Petrinovic, David J. Lythgoe, Diana Rotaru, Davide Di Censo, Lydiane Hirschler, Emmanuel L. Barbier, Anthony C. Vernon, James M. Stone, Cathy Davies, Diana Cash, Gemma Modinos

Summary: This study found that specific disruption of cortical inhibitory interneurons in mice can reproduce some of the neuroimaging findings in patients with psychosis, linking inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.

SCHIZOPHRENIA BULLETIN (2023)

Article Biology

Individual behavioral trajectories shape whole-brain connectivity in mice

Jadna Bogado Lopes, Anna N. Senko, Klaas Bahnsen, Daniel Geisler, Eugene Kim, Michel Bernanos, Diana Cash, Stefan Ehrlich, Anthony C. Vernon, Gerd Kempermann

Summary: By continuously tracking the behavioral activity of mice in an enriched environment for 3 months and using ex vivo structural magnetic resonance imaging, it was found that behavioral activity can shape the connectivity of the mouse brain. Furthermore, there are differences in brain structural covariance between mice with different behavioral trajectories.

ELIFE (2023)

Article Cell Biology

Opposite and dynamic regulation of the interferon response in metastatic and non-metastatic breast cancer

Apsana Lamsal, Sonja Benedikte Andersen, Ida Johansson, Marina Vietri, Ansooya Avinash Bokil, Natalie Jayne Kurganovs, Felicia Rylander, Geir Bjorkoy, Kristine Pettersen, Miriam S. S. Giambelluca

Summary: Solid tumors rely on suppressed local immune reactions in the tumor microenvironment, and the formation of immunosuppressive tumor microenvironments is still not fully understood. This study found that the type I interferon response is dampened in tumors with metastatic ability, and decreased expression of IFN-I-related genes predicts poor prognosis in breast cancer patients.

CELL COMMUNICATION AND SIGNALING (2023)

Article Biochemistry & Molecular Biology

Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure

Matthew R. Bruce, Amalie C. M. Couch, Simone Grant, Janna McLellan, Katherine Ku, Christina Chang, Angelica Bachman, Matthew Matson, Robert F. Berman, Richard J. Maddock, Douglas Rowland, Eugene Kim, Matthew D. Ponzini, Danielle Harvey, Sandra L. Taylor, Anthony C. Vernon, Melissa D. Bauman, Judy van de Water

Summary: Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Maternal autoantibodies (aAbs) may disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. Rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites, reminiscent of findings observed in clinical ASD.

MOLECULAR PSYCHIATRY (2023)

Article Neurosciences

A consensus protocol for functional connectivity analysis in the rat brain

Joanes Grandjean, Gabriel Desrosiers-Gregoire, Cynthia Anckaerts, Diego Angeles-Valdez, Fadi Ayad, David A. Barriere, Ines Blockx, Aleksandra Bortel, Margaret Broadwater, Beatriz M. Cardoso, Marina Celestine, Jorge E. Chavez-Negrete, Sangcheon Choi, Emma Christiaen, Perrin Clavijo, Luis Colon-Perez, Samuel Cramer, Tolomeo Daniele, Elaine Dempsey, Yujian Diao, Arno Doelemeyer, David Dopfel, Lenka Dvorakova, Claudia Falfan-Melgoza, Francisca F. Fernandes, Caitlin F. Fowler, Antonio Fuentes-Ibanez, Clement Garin, Eveline Gelderman, Carla E. M. Golden, Chao C. G. Guo, Marloes J. A. G. Henckens, Lauren A. Hennessy, Peter Herman, Nita Hofwijks, Corey Horien, Tudor M. Ionescu, Jolyon Jones, Johannes Kaesser, Eugene Kim, Henriette Lambers, Alberto Lazari, Sung-Ho Lee, Amanda Lillywhite, Yikang Liu, Yanyan Y. Liu, Alejandra Lopez-Castro, Xavier Lopez-Gil, Zilu Ma, Eilidh MacNicol, Dan Madularu, Francesca Mandino, Sabina Marciano, Matthew J. McAuslan, Patrick McCunn, Alison McIntosh, Xianzong Meng, Lisa Meyer-Baese, Stephan Missault, Federico Moro, Daphne M. P. Naessens, Laura J. Nava-Gomez, Hiroi Nonaka, Juan J. Ortiz, Jaakko Paasonen, Lore M. Peeters, Mickael Pereira, Pablo D. Perez, Marjory Pompilus, Malcolm Prior, Rustam Rakhmatullin, Henning M. Reimann, Jonathan Reinwald, Rodrigo Triana Del Rio, Alejandro Rivera-Olvera, Daniel Ruiz-Perez, Gabriele Russo, Tobias J. Rutten, Rie Ryoke, Markus Sack, Piergiorgio Salvan, Basavaraju G. Sanganahalli, Aileen Schroeter, Bhedita J. Seewoo, Erwan Selingue, Aline Seuwen, Bowen Shi, Nikoloz Sirmpilatze, Joanna A. Smith, Corrie Smith, Filip Sobczak, Petteri J. Stenroos, Milou Straathof, Sandra Strobelt, Akira Sumiyoshi, Kengo Takahashi, Maria E. Torres-Garcia, Raul Tudela, Monica van den Berg, Kajo van der Marel, Aran T. B. van Hout, Roberta Vertullo, Benjamin Vidal, Roel M. Vrooman, Victora X. Wang, Isabel Wank, David J. G. Watson, Ting Yin, Yongzhi Zhang, Stefan Zurbruegg, Sophie Achard, Sarael Alcauter, Dorothee P. Auer, Emmanuel L. Barbier, Juergen Baudewig, Christian F. Beckmann, Nicolau Beckmann, Guillaume J. P. C. Becq, Erwin L. A. Blezer, Radu Bolbos, Susann Boretius, Sandrine Bouvard, Eike Budinger, Joseph D. Buxbaum, Diana Cash, Victoria Chapman, Kai-Hsiang Chuang, Luisa Ciobanu, Bram F. Coolen, Jeffrey W. Dalley, Marc Dhenain, Rick M. Dijkhuizen, Oscar Esteban, Cornelius Faber, Marcelo Febo, Kirk W. Feindel, Gianluigi Forloni, Jeremie Fouquet, Eduardo A. Garza-Villarreal, Natalia Gass, Jeffrey C. Glennon, Alessandro Gozzi, Olli Grohn, Andrew Harkin, Arend Heerschap, Xavier Helluy, Kristina Herfert, Arnd Heuser, Judith R. Homberg, Danielle J. Houwing, Fahmeed Hyder, Giovanna Diletta Ielacqua, Ileana O. Jelescu, Heidi Johansen-Berg, Gen Kaneko, Ryuta Kawashima, Shella D. Keilholz, Georgios A. Keliris, Clare Kelly, Christian Kerskens, Jibran Y. Khokhar, Peter C. Kind, Jean-Baptiste Langlois, Jason P. Lerch, Monica A. Lopez-Hidalgo, Denise Manahan-Vaughan, Fabien Marchand, Rogier B. Mars, Gerardo Marsella, Edoardo Micotti, Emma Munoz-Moreno, Jamie Near, Thoralf Niendorf, Willem M. Otte, Patricia Pais-Roldan, Wen-Ju Pan, Roberto A. Prado-Alcala, Gina L. Quirarte, Jennifer Rodger, Tim Rosenow, Cassandra Sampaio-Baptista, Alexander Sartorius, Stephen J. Sawiak, Tom W. J. Scheenen, Noam Shemesh, Yen-Yu Ian Shih, Amir Shmuel, Guadalupe Soria, Ron Stoop, Garth J. Thompson, Sally M. Till, Nick Todd, Annemie van der Linden, Annette van der Toorn, Geralda A. F. van Tilborg, Christian Vanhove, Andor Veltien, Marleen Verhoye, Lydia Wachsmuth, Wolfgang Weber-Fahr, Patricia Wenk, Xin Yu, Valerio Zerbi, Nanyin Zhang, Baogui B. Zhang, Luc Zimmer, Gabriel A. Devenyi, M. Mallar Chakravarty, Andreas Hess

Summary: Task-free functional connectivity in animal models is an important tool for studying connectivity phenomena. However, the lack of standardized protocols and analysis methods hampers result comparison and integration. In this study, the authors developed a standardized protocol, called StandardRat, for rat functional magnetic resonance imaging (fMRI) acquisition and analysis, which enhances the detection of functional connectivity patterns and promotes cooperation in neuroscience research.

NATURE NEUROSCIENCE (2023)

Article Immunology

Mapping acute neuroinflammation in vivo with diffusion-MRI in rats given a systemic lipopolysaccharide challenge

Eugene Kim, Ines Carreira Figueiredo, Camilla Simmons, Karen Randall, Loreto Rojo Gonzalez, Tobias Wood, Brigida Ranieri, Paula Sureda-Gibert, Oliver Howes, Carmine Pariante, N. I. M. A. NIMA Consortium, Ofer Pasternak, Flavio Dell'Acqua, Federico Turkheimer, Diana Cash

Summary: It has been found that neuroinflammation is crucial in various neurological and psychiatric disorders. Recent studies have shown that diffusion MRI (dMRI) can detect changes in microglial density and morphology related to neuroinflammation, but these studies were mostly conducted ex vivo or in extreme animal models. In this study, the utility of established dMRI methods to detect neuroinflammation in a clinically relevant animal model of sickness behavior was investigated. The results demonstrated that diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) indicated widespread increases in diffusivity in the brains of rats with a lipopolysaccharide challenge. These findings confirm the sensitivity of dMRI to neuroinflammatory processes and contribute to the development of a noninvasive indicator of neuroinflammation for early diagnosis and treatment monitoring in neurological and psychiatric diseases.

BRAIN BEHAVIOR AND IMMUNITY (2023)

Article Chemistry, Inorganic & Nuclear

Radiometal-Labeled Photoactivatable Pt(IV) Anticancer Complex for Theranostic Phototherapy

Cinzia Imberti, Jamie Lok, James P. C. Coverdale, Oliver W. L. Carter, Millie E. Fry, Miles L. Postings, Jana Kim, George Firth, Philip J. Blower, Peter J. Sadler

Summary: A novel photoactivatable Pt(IV) diazido anticancer agent with a pendant deferoxamine (DFO) siderophore for radiometal chelation was synthesized, and its in vivo behavior was studied using radionuclide imaging. The results showed that the Pt-succ-DFO complex had photoactivation properties and photocytotoxicity in cancer cells. PET imaging in healthy mice exhibited a promising biodistribution profile, suggesting the potential of this agent for clinical development. This research provides important insights into the development of light-activated agents.

INORGANIC CHEMISTRY (2023)

Article Oncology

Discovery of a new marker to identify myeloid cells associated with metastatic breast tumours

Ansooya A. Bokil, Mathieu Le Boulvais Borkja, Camilla Wolowczyk, Apsana Lamsal, Wenche S. Prestvik, Unni Nonstad, Kristine Pettersen, Sonja B. Andersen, Anna M. Bofin, Geir Bjorkoy, Sjoerd Hak, Miriam S. Giambelluca

Summary: This study identified a unique expression pattern of arginase 1 (ARG1) in myeloid cells, which is correlated with the metastatic capacity of breast cancer. The presence of ARG1-positive cells in human breast cancer biopsies is strongly associated with high-grade proliferating tumors, poor prognosis, and low survival.

CANCER CELL INTERNATIONAL (2023)

Meeting Abstract Obstetrics & Gynecology

Discriminatory value of steroid hormones on polycystic ovary syndrome in women with infertility and obesity

Z. Wang, A. Van der Veen, H. Groen, A. E. P. Cantineau, A. Van Oers, J. M. Hawley, B. G. Keevil, H. J. R. Van Faassen, I. P. Kema, A. Hoek

HUMAN REPRODUCTION (2022)

No Data Available