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Tumour cell implantation

Julia Ketteler, Andrej Panic, Henning Reis, Alina Wittka, Patrick Maier, Carsten Herskind, Ernesto Yagüe, Verena Jendrossek, Diana Klein
Tumour resistance to chemo- and radiotherapy, as well as molecularly targeted therapies, limits the effectiveness of current cancer treatments. We previously reported that the radiation response of human prostate tumours is critically regulated by CAV1 expression in stromal fibroblasts and that loss of stromal CAV1 expression in advanced tumour stages may contribute to tumour radiotherapy resistance. Here we investigated whether fibroblast secreted anti-apoptotic proteins could induce radiation resistance of prostate cancer cells in a CAV1-dependent manner and identified TRIAP1 (TP53 Regulated Inhibitor of Apoptosis 1) as a resistance-promoting CAV1-dependent factor...
March 12, 2019: Journal of Clinical Medicine
Minxun Lu, Jie Wang, Fan Tang, Li Min, Yong Zhou, Wenli Zhang, Chongqi Tu
BACKGROUND: Subchondral bone is commonly affected in cases of giant cell tumour (GCT) of the proximal tibia. Numerous studies have stated that retaining a sufficient subchondral bone layer could decrease the possibilities of postoperative degenerative changes and mechanical failure of the knee joint. However, the most commonly used methods of cement packing only or cement packing combined bone grafting have some limitations regarding the protection of subchondral bone after surgery. Our paper describes our attempt to reconstruct a tumorous defect associated with the subchondral area in the proximal tibia with a three-dimensional (3D)-printed porous implant combined with bone grafting and our evaluation of the short-term outcomes...
February 28, 2019: BMC Surgery
Jonathan P Evans, Boleslaw K Winiarski, Paul A Sutton, Lorenzo Ressel, Carrie A Duckworth, D Mark Pritchard, Daniel H Palmer, Christopher E Goldring, Neil R Kitteringham
Improving outcomes in colorectal cancer requires more accurate in vivo modelling of the disease in humans, allowing more reliable pre-clinical assessment of potential therapies. Novel imaging techniques are necessary to improve the longitudinal assessment of disease burden in these models, reducing the number of animals required for translational studies. This report describes the development of an immune-competent syngeneic orthotopic murine model of colorectal cancer, utilising caecal implantation of CT26 cells stably transfected with the luciferase gene into immune-competent BALB/c mice, allowing serial bioluminescent imaging of cancer progression...
February 13, 2019: Laboratory Animals
Chloé Maignien, Pietro Santulli, Sandrine Chouzenoux, Iñaki Gonzalez-Foruria, Louis Marcellin, Ludivine Doridot, Mohammed Jeljeli, Philippe Grange, Fernando M Reis, Charles Chapron, Frédéric Batteux
STUDY QUESTION: Is endometriosis associated with aberrant sialylation patterns and what is the potential impact of such anomalies on cell migratory properties? SUMMARY ANSWER: The reduced α-2,6 sialylation patterns in the peritoneal fluid of endometriosis-affected women and in stromal and epithelial cells from endometriotic lesions could be associated with enhanced cell migration. WHAT IS KNOWN ALREADY: Endometriosis is considered to be a benign disease although, like cancer, it has the characteristic of being an invasive disease with cells that have an enhanced capacity to migrate...
March 1, 2019: Human Reproduction
Mingxia Lu, Claire E Henry, Haiwang Lai, Yee Yee Khine, Caroline E Ford, Martina H Stenzel
INTRODUCTION: Ovarian cancer is often diagnosed at a late stage, when disease has spread to extra-pelvic regions such as the omentum. There are limited treatment options available for women with extensive disease and tumours often relapse after current chemotherapy regimens. Therefore, novel drugs should be investigated for the treatment of ovarian cancer. A 3D organotypic model of ovarian cancer can provide a specific platform for the evaluation of nano-drugs. Using patient derived primary cells, the 3D model mimics the ovarian metastatic microenvironment allowing efficient and reproducible testing of many nanoparticles...
February 6, 2019: Biomaterials Science
A Saam Youshani, Samuel Rowlston, Claire O'Leary, Gabriella Forte, Helen Parker, Aiyin Liao, Brian Telfer, Kaye Williams, Ian D Kamaly-Asl, Brian W Bigger
BACKGROUND: Chimeric mouse models generated via adoptive bone marrow transfer are the foundation for immune cell tracking in neuroinflammation. Chimeras that exhibit low chimerism levels, blood-brain barrier disruption and pro-inflammatory effects prior to the progression of the pathological phenotype, make it difficult to distinguish the role of immune cells in neuroinflammatory conditions. Head-shielded irradiation overcomes many of the issues described and replaces the recipient bone marrow system with donor haematopoietic cells expressing a reporter gene or different pan-leukocyte antigen, whilst leaving the blood-brain barrier intact...
February 5, 2019: Journal of Neuroinflammation
Evgeniya N Burgovа, Yana I Khristidis, Aleksandr V Kurkov, Vasak D Mikoyan, Anatoly B Shekhter, Leila V Adamyan, Peter S Timashev, Anatoly F Vanin
The possibility that binuclear dinitrosyl iron complexes with glutathione and cysteine (DNIC-GSН and B-DNIC-Cys) have a strong cytotoxic effect on the growth of endometrioid tumours (EMT) in rats with surgically induced experimental endometriosis established in our previous studies has been supported with experimental data. The increase in the DNIC-GSН or B-DNIC-Cys dose from 10 (in our previous studies) to 20 μmol/kg (after i/p administration to experimental rats) fully suppressed the growth of uterine tissues implanted onto the inner surface of the abdominal wall...
February 1, 2019: Cell Biochemistry and Biophysics
Jun-Wen Shi, Ting-Ting Zhang, Wei Liu, Jie Yang, Xiao-Lin Lin, Jun-Shuang Jia, Hong-Fen Shen, Sheng-Chun Wang, Jing Li, Wen-Tao Zhao, Wei-Wang Gu, Yan Sun, Dong Xiao
Unexpectedly, we found that c-Myc-expressing porcine embryonic fibroblasts (PEFs) subcutaneously implanted into nude mice formed cartilage-like tissues in vivo, while previous studies revealed the direct conversion of mouse and human somatic cells into chondrocytes by the combined use of several defined factors, including c-Myc, which prompted us to explore whether PEFs can be reprogrammed to become pig induced chondrocyte-like cells (piCLCs) via ectopic expression of c-Myc alone. In this study, c-Myc-expressing PEFs, designated piCLCs, which exhibited a significantly enhanced proliferation ability in vitro, displayed a chondrogenic phenotypes in vitro, as shown by the cell morphology, toluidine blue staining, alcian blue staining and chondrocyte marker gene expression...
2019: Cell Death Discovery
Xinxia Zhu, Kevin G Burfeind, Katherine A Michaelis, Theodore P Braun, Brennan Olson, Katherine R Pelz, Terry K Morgan, Daniel L Marks
BACKGROUND: Up to 80% of pancreatic cancer patients suffer from cachexia, a devastating condition that exacerbates underlying disease, reduces quality of life, and increases treatment complications and mortality. Tumour-induced inflammation is linked to this multifactorial wasting syndrome, but mechanisms and effective treatments remain elusive. Myeloid differentiation factor (MyD88), a key component of the innate immune system, plays a pivotal role in directing the inflammatory response to various insults...
January 21, 2019: Journal of Cachexia, Sarcopenia and Muscle
R Ghermandi, V Pipola, S Colangeli, P Parchi, L Andreani, R Capanna, A Gasbarrini
The use of pedicle screws in low bone quality patients implicates risks of secondary implant loosening for grip lack. In fact, the result is a reduced mechanical stability at bone-screw interface and consequently an increased chance of pullout and hardware failure. Augmentation techniques have been described for many years and fenestrated screws that allow cement injection is one of them. This is a retrospective observational study of patients treated at our department with polymethylmethacrylate- (PMMA) augmented fenestrated screws...
November 2018: Journal of Biological Regulators and Homeostatic Agents
Amy L Wilson, Kirsty L Wilson, Maree Bilandzic, Laura R Moffitt, Ming Makanji, Mark D Gorrell, Martin K Oehler, Adam Rainczuk, Andrew N Stephens, Magdalena Plebanski
Ovarian cancers (OCs) are the most lethal gynaecological malignancy, with high levels of relapse and acquired chemo-resistance. Whilst the tumour⁻immune nexus controls both cancer progression and regression, the lack of an appropriate system to accurately model tumour stage and immune status has hampered the validation of clinically relevant immunotherapies and therapeutic vaccines to date. To address this need, we stably integrated the near-infrared phytochrome iRFP720 at the ROSA26 genomic locus of ID8 mouse OC cells...
December 31, 2018: Cancers
Ruba Al-Abdulla, Elisa Lozano, Rocio I R Macias, Maria J Monte, Oscar Briz, Colm J O'Rourke, Maria A Serrano, Jesus M Banales, Matias A Avila, Maria L Martinez-Chantar, Andreas Geier, Jesper B Andersen, Jose J G Marin
BACKGROUND AND PURPOSE: In hepatocellular carcinoma (HCC), the expression of the human organic cation transporter-1 (hOCT1, gene SLC22A1) is reduced. The molecular bases of this phenotypic characteristic and the relationship with the poor response of HCC to sorafenib were investigated. EXPERIMENTAL APPROACH AND KEY RESULTS: hOCT1 over-expression in human hepatoma cells (HuH7 and HepG2) enhanced sorafenib, but not regorafenib, uptake in a quinine sensitive manner. The analysis of HCC transcriptomes (TCGA, n=366) showed reduced hOCT1 mRNA, which was inversely correlated with SLC22A1 promoter methylation...
December 28, 2018: British Journal of Pharmacology
Pallavi Singh, Sagnik Sen, Mousumi Banerjee, Rachna Meel
Orbital cellulitis is the most common subset of orbital inflammatory disease. We describe a patient with necrotic choroidal melanoma who presented with orbital cellulitis. MRI revealed a mass lesion suggesting intraocular melanoma with no extrascleral extension. There was no metastasis on positron emission tomography-CT scan. Enucleation with orbital implant was performed. Histopathological analysis of the specimen revealed intraocular necrotic melanoma with very few recognisable melanoma cells. The necrotic subtype is more commonly associated with extrascleral extension, distant metastasis and poorer prognosis than other melanoma types...
December 9, 2018: BMJ Case Reports
Lindi Chen, Fabio Pastorino, Philip Berry, Jennifer Bonner, Calum Kirk, Katrina M Wood, Huw D Thomas, Yan Zhao, Antonio Daga, Gareth J Veal, John Lunec, David R Newell, Mirco Ponzoni, Deborah A Tweddle
High-risk neuroblastoma, a predominantly TP53 wild-type (wt) tumour, is incurable in >50% patients supporting the use of MDM2 antagonists as novel therapeutics. Idasanutlin (RG7388) shows in vitro synergy with chemotherapies used to treat neuroblastoma. This is the first study to evaluate the in vivo efficacy of the intravenous idasanutlin prodrug, RO6839921 (RG7775), both alone and in combination with temozolomide in TP53 wt orthotopic neuroblastoma models. Detection of active idasanutlin using liquid chromatography-mass spectrometry and p53 pathway activation by ELISA assays and Western analysis showed peak plasma levels 1h post-treatment with maximal p53 pathway activation 3-6h post-treatment...
December 11, 2018: International Journal of Cancer. Journal International du Cancer
Hua Jiang, Jingjing Fan, Lin Cheng, Pan Hu, Renbin Liu
Background: Most breast cancers are estrogen dependent and were sensitive to endocrine therapy, and genistein (GEN) shows strong affinity with human oestrogen receptor beta (ERβ). Purpose: The present study aimed to investigate the anticancer activity of GEN in breast cancer cell lines that constitutively expressing ERβ1 in vitro and in vivo. Methods: MCF-7/ERβ1 and MDA-MB-231/ERβ1 cell sub-lines were established through lentiviral infection...
2018: OncoTargets and Therapy
Danielle O'Neill, Rachel Pounds, Josefa Vella, Kavita Singh, Jason Yap
Chronic ectopic pregnancy (CEP) is a rare condition caused by implantation of trophoblastic tissue in the fallopian tube, which causes protracted tissue destruction at the site of attachment. The process of minor rupture and bleeding results in chronic inflammation, giving rise to a haematocele which often resembles a pelvic mass. Unlike ectopic pregnancy, the level of serum human chorionic gonadotropin (hCG) in patients with CEP is usually low or undetectable as chorionic villi are generally sparse. Therefore, CEP often poses a specific diagnostic challenge for clinicians, as both biochemical markers and imaging modalities are unreliable in its diagnosis...
October 2018: Case Reports in Women's Health
Florence T H Wu, Ping Xu, Annabelle Chow, Shan Man, Janna Krüger, Kabir A Khan, Marta Paez-Ribes, Elizabeth Pham, Robert S Kerbel
BACKGROUND: There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. METHODS: This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively)...
January 2019: British Journal of Cancer
Salvatore Cozzi, Andrea Slocker Escarpa, Daniel Lorenzo Parra, Dina Najjari Jamal, Josep Maria Caminal Mitjana, Josep Maria Piulats R, Ferran Guedea Edo, Cristina Gutierrez Miguelez
Introduction: Uveal melanoma is a rare tumour caused by genetic factors and alterations in the immune response. Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disorder characterized by an inappropriate or excessive immune response. The two main types of IBD are Crohn's disease (CD) and ulcerative colitis (UC). A diagnosis of IBD and the use of immunosuppressive drugs are both independently associated with an increased risk of developing skin melanoma. The association between IBD and uveal melanoma (UM) has not been previously described...
January 2019: Reports of Practical Oncology and Radiotherapy
Alice Lallo, Sakshi Gulati, Maximilian W Schenk, Garima Khandelwal, Ulrika Warpman Berglund, Ioannis S Pateras, Christopher P E Chester, Therese M Pham, Christina Kalderen, Kristopher K Frese, Vassilis G Gorgoulis, Crispin Miller, Fiona Blackhall, Thomas Helleday, Caroline Dive
BACKGROUND AND PURPOSE: Small cell lung cancer (SCLC) is an aggressive disease with median survival of < 2 years. Tumour biopsies for research are scarce, especially from extensive-stage patients, with repeat sampling at disease progression rarely performed. We overcame this limitation for relevant preclinical models by developing SCLC circulating tumour cell derived explants (CDX) which mimic the donor tumour pathology and chemotherapy response. To facilitate compound screening and identification of clinically relevant biomarkers, we developed short term ex vivo cultures of CDX tumour cells...
November 14, 2018: British Journal of Pharmacology
Y E Smith, S Toomey, S Napoletano, G Kirwan, C Schadow, A J Chubb, J H Mikkelsen, C Oxvig, J H Harmey
BACKGROUND: The Insulin-like growth factor (IGF) pathway plays a role in tumour development and progression. In vivo, IGF1 activity is regulated by the IGF binding proteins (IGFBPs). IGFBP4 inhibits the activity of IGF1 but proteolytic cleavage by pregnancy-associated plasma protein-A (PAPP-A) releases active IGF1. A modified IGFBP4, dBP4, which was resistant to PAPP-A cleavage but retained IGF1 binding capacity, was engineered, expressed in Human Embryonic Kidney (HEK) 293 cells and purified...
October 22, 2018: BMC Cancer
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