Review
Gastroenterology & Hepatology
Azarakhsh Baghdadi, Sahar Mirpour, Maryam Ghadimi, Mina Motaghi, Bita Hazhirkarzar, Timothy M. Pawlik, Ihab R. Kamel
Summary: Colorectal cancer metastasis to the liver is common and often treated with surgical resection, although not all patients are eligible. Imaging plays a critical role in evaluating the characteristics and treatment of CRLM, with CT being the modality of choice for diagnosis and management.
JOURNAL OF GASTROINTESTINAL SURGERY
(2022)
Article
Biology
Mehmet S. Ozturk, Marta G. Montero, Ling Wang, Lucas M. Chaible, Martin Jechlinger, Robert Prevedel
Summary: Mehmet S. Ozturk et al. present an intravital mesoscopic fluorescence tomography (IFT) technique that is capable of tracking fluorescently labeled tumor cells inside living mice over several months. It demonstrates a promising new method for studying tumor growth dynamics in a quantitative and longitudinal fashion in-vivo.
COMMUNICATIONS BIOLOGY
(2021)
Review
Oncology
Drew Maclean, Maria Tsakok, Fergus Gleeson, David J. Breen, Robert Goldin, John Primrose, Adrian Harris, James Franklin
Summary: Colorectal liver metastases exhibit heterogenous histopathological and immunohistochemical phenotypes, impacting treatment responses and outcomes. Advanced imaging techniques like multiparametric MRI and functional imaging have the potential to provide clinically-actionable phenotypic characterisation. Advanced analysis techniques such as radiomics and machine learning play a growing role in linking imaging features to clinically relevant tumour phenotypes.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Sydney Relouw, George J. J. Dugbartey, Alp Sener
Summary: Bladder cancer requires the investigation of alternative therapies using animal models for thorough evaluation. Non-invasive techniques, such as bioluminescence imaging (BLI), micro-ultrasound imaging (MUI), magnetic resonance imaging (MRI), and positron emission tomography (PET), have been developed to visualize bladder cancer from outside the bladder. This paper reviews the use of these imaging techniques in an animal model where bladder cancer is developed within the bladder.
Article
Medicine, Research & Experimental
Ambre Giguelay, Evgenia Turtoi, Lakhdar Khelaf, Guillaume Tosato, Ikrame Dadi, Tommy Chastel, Marie-Alix Poul, Marine Pratlong, Stefan Nicolescu, Dany Severac, Antoine Adenis, Olivia Sgarbura-Popescu, Sebastien Carrere, Philippe Rouanet, Marc Ychou, Francois Quenet, Didier Pourqier, Pierre-Emmanuel Colombo, Andrei Turtoi, Jacques Colinge
Summary: This study confirms the heterogeneity of CRC-LM CAFs through single-cell transcriptomic analysis and proposes a model for recruiting different origins of CAFs to the liver in different liver malignancies. Additionally, the study finds that targeting LTBP2 with antibodies may help deplete ECM-remodeling CAFs in CRC-LMs.
Article
Pharmacology & Pharmacy
Jinbing Sun, Zhihua Lu, Wei Fu, Kuangyi Lu, Xiuwen Gu, Feng Xu, Jiamin Dai, Yang Yang, Jianlong Jiang
Summary: Exosomes derived from cancer cells, particularly those containing elevated levels of ADAM17, play a role in promoting the migratory ability of colorectal cancer cells by cleaving E-cadherin junctions. This finding suggests that exosomal ADAM17 may serve as a blood-based biomarker for colorectal cancer metastasis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Fang Liu, Zhen-Mei Song, Xiao-Di Wang, Shi-Yu Du, Na Peng, Jing-Rui Zhou, Ming-Gang Zhang
Summary: Colorectal cancer is one of the top three cancers in terms of incidence and mortality. Metastasis to the liver is a major cause of death. High HOTAIR/MALAT1 and low LOC285194 levels of lncRNA signature may serve as prognostic markers for liver metastasis and overall poor survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Wenhu Zhao, Shipeng Dai, Lei Yue, Fan Xu, Jian Gu, Xinzheng Dai, Xiaofeng Qian
Summary: Colorectal cancer is a common malignant tumor with the liver being the most common site of metastasis. Metastasis to the liver from colorectal cancer is a complex process involving various stages. This review discusses the characteristics of CRC cells and their interactions with liver cells and immune cells. It also explores current immunotherapy approaches and challenges, as well as potential therapeutic targets based on novel sequencing technologies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Andrew A. Gumbs, Eric Lorenz, Tzu-Jung Tsai, Lee Starker, Joe Flanagan, Andrea Benedetti Cacciaguerra, Ng Jing Yu, Melinda Bajul, Elie Chouillard, Roland Croner, Mohammad Abu Hilal
Summary: This study examined the short-term outcomes of minimally invasive liver resection for patients with colorectal liver metastases. The results suggest that laparoscopic and robotic approaches may have advantages over open hepatectomy in terms of blood loss, hospital stay, and morbidity rates.
Article
Oncology
Daniele Lavacchi, Giandomenico Roviello, Elisa Giommoni, Lorenzo Dreoni, Silvia Derio, Marco Brugia, Amedeo Amedei, Serena Pillozzi, Lorenzo Antonuzzo
Summary: The addition of aflibercept to FOLFIRI has shown to enhance survival in mCRC patients who have progressed after standard oxaliplatin-based regimens. A retrospective study on real-world clinical practice found that aflibercept-FOLFIRI is a feasible second-line treatment, with PFS in first-line therapy >12 months being the key predictive marker for improved survival.
Article
Oncology
Eva Lukacova, Tatiana Burjanivova, Petar Podlesniy, Marian Grendar, Eva Turyova, Ivana Kasubova, Ludovit Laca, Peter Mikolajcik, Eva Kudelova, Andrea Vanochova, Juraj Miklusica, Sandra Mersakova, Zora Lasabova
Summary: A sensitive droplet digital PCR (ddPCR) assay was developed to evaluate the diagnostic potential of GRIA4 hypermethylation in colorectal cancer (CRC) patients. The study found that GRIA4 methylation was significantly increased in tumor tissues and showed promising diagnostic ability. Furthermore, high levels of GRIA4 hypermethylation were also observed in the blood samples of patients with metastatic CRC, suggesting its potential for non-invasive early detection.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Hao Wang, Xuemin Li, Ran Peng, Yuxia Wang, Junjie Wang
Summary: SABR plays a crucial role in the multidisciplinary treatment of CRLM by causing an immunological change in the tumor microenvironment and potentially increasing the abscopal response rate of out-field lesions. The synergy of SABR and immunotherapy targets different steps of the immune-mediated response and may lead to a higher response rate by inducing cell death within and beyond the tumor sites.
SEMINARS IN CANCER BIOLOGY
(2021)
Review
Cell Biology
Dian R. Arifin, Kenneth W. Witwer, Jeff W. M. Bulte
Summary: Extracellular vesicles (EVs) are mediators of intercellular signalling and play a key role in normal and pathological cellular processes. Non-invasive imaging methods allow for a better understanding of their biodistribution and pharmacokinetics, advancing their clinical applications.
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Article
Medicine, Research & Experimental
Kai-Li Zhang, Wen-Wei Zhu, Sheng-Hao Wang, Chao Gao, Jun-Jie Pan, Zun-Guo Du, Lu Lu, Hu-Liang Jia, Qiong-Zhu Dong, Jin-Hong Chen, Ming Lu, Lun-Xiu Qin
Summary: This study identified a specific cholesterol metabolic pathway in colorectal cancer liver metastasis involving the activation of SREBP2-dependent cholesterol biosynthesis, which is essential for the growth and colonization of metastatic CRC cells in the liver. Targeting this pathway could be a promising treatment for CRC liver metastasis.
Review
Oncology
Qian Ding, Xiangxu Kong, Weilong Zhong, Wentian Liu
Summary: Colorectal cancer is a common and serious disease globally. Fecal examination is a simple and non-invasive method for clinical examination, and it is widely used for large-scale population screening. In recent years, with the advancements in molecular biology, researchers have focused on discovering new fecal biomarkers for early screening and diagnosis of colorectal cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Remya Valsalakumari, Sunil Kumar Yadava, Marzena Szwed, Abhilash D. Pandya, Gunhild Mari Maelandsmo, Maria Lyngaas Torgersen, Tore-Geir Iversen, Tore Skotland, Kirsten Sandvig, Jyotsnendu Giri
Summary: The study found that LNCs-PTX were taken up by MDA-MB-468 cells more effectively than the other two cell lines. Additionally, the cytotoxicity of LNCs-PTX on cells was primarily attributed to endocytosis mechanisms involving Cdc42/GRAF-dependent endocytosis and macropinocytosis.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Endocrinology & Metabolism
Caroline E. Nunes-Xavier, Wanja Kildal, Andreas Kleppe, Havard E. Danielsen, Hakon Waehre, Roberto Llarena, Gunhild M. Maelandsmo, Oystein Fodstad, Rafael Pulido, Jose I. Lopez
Summary: This study identified distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer, with B7-H3 potentially serving as a significant therapeutic target.
Article
Multidisciplinary Sciences
Lisa Svartdal Normann, Miriam Ragle Aure, Suvi-Katri Leivonen, Mads Haugland Haugen, Vesa Hongisto, Vessela N. Kristensen, Gunhild Mari Maelandsmo, Kristine Kleivi Sahlberg
Summary: HER2-positive breast cancer patients that do not respond to targeted treatment have a poor prognosis. Through a high-throughput screen, it was found that certain miRNA mimics can sensitize HER2+ breast cancer cells to targeted therapy, with miR-101-5p showing a correlation with better prognosis in patients. This suggests the potential of combining targeted drugs with miRNAs to improve current treatments for HER2+ breast cancers.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Vegar Johansen Dagenborg, Serena Elizabeth Marshall, Krzysztof Grzyb, Asmund Avdem Fretland, Marius Lund-Iversen, Gunhild Mari Maelandsmo, Anne Hansen Ree, Bjorn Edwin, Sheraz Yaqub, Kjersti Flatmark
Summary: The study found a significant accumulation of T-cells in the IM regions of both pCRC and CLM, with lower densities in the IT regions. The correlation between T-cell densities in pCRC and matched CLM was poor for all regions and subtypes. The ratios of TH : CTL and Treg : TH were different between pCRC and CLM, indicating a potential immune suppressive microenvironment in both types of tumors.
FRONTIERS IN ONCOLOGY
(2021)
Article
Mathematical & Computational Biology
Sigurdur Trausti Karvelsson, Qiong Wang, Bylgja Hilmarsdottir, Arnar Sigurdsson, Siver Andreas Moestue, Gunhild Mari Maelandsmo, Skarphedinn Halldorsson, Steinn Gudmundsson, Ottar Rolfsson
Summary: Proteomic data provides more accurate predictions of metabolic fluxes compared to transcriptomic data when describing breast epithelial metabolism in the context of EMT. The altered cholesterol metabolism and increased dependency on argininosuccinate lyase (ASL) following EMT predicted by proteomic GSMMs were confirmed through drug assays and siRNA knockdown experiments. The iBreast2886 metabolic reconstruction model can be utilized to interpret high throughput clinical data and identify subtype-specific vulnerabilities in breast cancer patients.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2021)
Meeting Abstract
Oncology
C. E. Nunes-Xavier, M. Emaldi, T. Oyjord, G. Larrinaga, P. Errarte, J. C. Angulo, R. Llarena, G. M. Maelandsmo, O. Fodstad, R. Pulido, J. I. Lopez
ANNALS OF ONCOLOGY
(2021)
Article
Oncology
Henrik A. Svendsen, Torstein R. Meling, Vigdis Nygaard, Stein Waagene, Hege Russnes, Siri Juell, Siril G. Rogne, Jens Pahnke, Eirik Helseth, Oystein Fodstad, Gunhild M. Maelandsmo
Summary: This study established animal models of brain metastases by injecting human melanoma cell lines intracardially in mice, showing that cerebellar metastases had longer survival time and were more likely to form in mice compared to cerebral metastases. The models provide new opportunities for studying factors involved in determining tissue specificity of brain metastasis.
Article
Chemistry, Multidisciplinary
Tripti Tamhane, Robin W. Njenga, Roberta E. Burden, Heiko Bueth, Gunhild M. Maelandsmo, Mads H. Haugen, Christopher J. Scott, Klaudia Brix
Summary: The study reveals increased levels of cathepsin B in adenocarcinoma tissue compared to normal colon, and its localization in the nucleus of mucosal cells and colorectal carcinoma cells. A distinct 40kDa form of cathepsin B was detected in HCT116 cells, suggesting a specific form lacking a signal peptide and part of the propeptide. Further research is needed to determine which form/s of cathepsin B may be sorted to the nuclei of colorectal carcinoma cells and if redundant regulation of related cathepsin expression occurs.
APPLIED SCIENCES-BASEL
(2021)
Article
Multidisciplinary Sciences
Marta Nyakas, Karianne Giller Fleten, Mads Haugland Haugen, Nikolai Engedal, Christina Sveen, Inger Nina Farstad, Vivi Ann Florenes, Lina Prasmickaite, Gunhild Mari Maelandsmo, Kotryna Seip
Summary: This study investigated the therapeutic potential of combining an AXL inhibitor (AXLi) and a clinically relevant BRAF inhibitor (BRAFi) for the treatment of metastatic melanoma. The results showed that AXL was expressed in the majority of melanoma lymph node metastases. In vitro experiments demonstrated that the combination of AXLi and BRAFi resulted in the largest reduction in cell viability. Moreover, pre-clinical studies using AXL(high) melanoma models showed a therapeutic benefit of adding AXLi to the BRAF-targeted therapy. Mechanistic insights revealed that AXLi potentiated BRAFi-induced apoptosis, stimulated ferroptosis, and inhibited autophagy. Overall, this study suggests that combining AXLi with standard therapy could improve the therapeutic outcome in metastatic melanoma.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Caroline E. Nunes-Xavier, Janire Mingo, Maite Emaldi, Karine Flem-Karlsen, Gunhild M. Maelandsmo, Oystein Fodstad, Roberto Llarena, Jose I. Lopez, Rafael Pulido
Summary: This study revealed heterogeneous expression of PDH complex components in PCa tumors, with PDH complex components being related to AR signaling and PDK2 expression associated with poor PCa prognosis. These findings highlight the potential of targeting PDH complex components for intervention in PCa.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Croi E. Buckley, Xiaofei Yin, Sebastian Meltzer, Anne Hansen Ree, Kathrine Roe Redalen, Lorraine Brennan, Jacintha O'Sullivan, Niamh Lynam-Lennon
Summary: Resistance to neoadjuvant chemoradiation therapy in rectal cancer is a challenge, and there is a need to identify its underlying mechanisms and develop predictive biomarkers and novel treatment strategies. This study identified an in vitro model of radioresistant rectal cancer and found significant alterations in multiple molecular pathways, including cell cycle, DNA repair, and oxidative phosphorylation-related genes. Metabolomic profiling of pre-treatment serum samples from rectal cancer patients identified metabolites significantly associated with treatment response and overall survival. This study highlights metabolic reprogramming as a role in radioresistance of rectal cancer and suggests altered metabolites as potential circulating predictive markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Tonje Bjornetro, Paula A. A. Bousquet, Kathrine Roe Redalen, Anne-Marie Siebke Troseid, Torben Luders, Espen Stang, Adriana M. M. Sanabria, Christin Johansen, Anniken Jorlo Fuglestad, Christian Kersten, Sebastian Meltzer, Anne Hansen Ree
Summary: Recent studies have found that the entire mitochondrial genome can be secreted in extracellular vesicles (EVs), but the biological characteristics of this cell-free mitochondrial DNA (mtDNA) are not well understood. In this study, the mtDNA derived from plasma EVs of colorectal cancer patients was compared to that of whole blood, peripheral blood mononuclear cells, and tumor tissue. The results showed that EV mtDNA had more variants and low-level heteroplasmy compared to whole blood mtDNA. The EV mtDNA variants were mainly located in the coding regions and had a higher proportion of missense mutations compared to whole blood and tumor tissue.
Article
Radiology, Nuclear Medicine & Medical Imaging
Tengzhi Liu, Maria Aanesland Dahle, Mathilde Hirsum Lystad, Laure Marignol, Morten Karlsen, Kathrine Roe Redalen
Summary: This study investigated Cu-64(II)-elesclomol ([Cu-64][Cu(ES)]) as a novel therapeutic agent for hypoxic tumors. The therapeutic and diagnostic potential of [Cu-64][Cu(ES)] was compared to established Cu-64 radiopharmaceuticals [Cu-64]CuCl2 and [diacetyl-bis(N4-methylthiosemicarbazone) [Cu-64][Cu(ATSM)]. The results showed that [Cu-64][Cu(ES)] had better therapeutic effects and could detect tumor hypoxia using positron emission tomography (PET).
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Oncology
Vigdis Nygaard, Anne Hansen Ree, Vegar Johansen Dagenborg, Anne-Lise Borresen-Dale, Bjorn Edwin, Asmund Avdem Fretland, Krzysztof Grzyb, Mads H. Haugen, Gunhild M. Maelandsmo, Kjersti Flatmark
Summary: A mesenchymal subgroup with an immunosuppressive phenotype, characterized by high expression of immune checkpoints HAVCR2/TIM-3 and VISTA, as well as the M2 macrophage marker CD163, was identified in colorectal cancer liver metastases. These findings suggest potential novel opportunities for immune-based therapy approaches in microsatellite stable colorectal cancer.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Margherita Ambrosini, Marzia Del Re, Paolo Manca, Andrew Hendifar, Alexander Drilon, Guilherme Harada, Anne Hansen Ree, Samuel Klempner, Gunhild Mari Maelandsmo, Kjersti Flatmark, Hege G. Russnes, James M. Cleary, Harshabad Singh, Elisa Sottotetti, Antonia Martinetti, Giovanni Randon, Andrea Sartore-Bianchi, Iolanda Capone, Massimo Milione, Maria Di Bartolomeo, Filippo Pietrantonio
Summary: This study collected data from patients with GI cancers and ALK rearrangements, showing remarkable responses and clinical benefit with ALK inhibitors. Despite the low frequency, ALK rearrangements play an important role in personalized treatment for GI cancers.
JCO PRECISION ONCOLOGY
(2022)