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https://www.readbyqxmd.com/read/30536898/preclinical-evaluation-of-the-first-intravenous-small-molecule-mdm2-antagonist-alone-and-in-combination-with-temozolomide-in-neuroblastoma
#1
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
https://www.readbyqxmd.com/read/30532556/the-anticancer-activity-of-genistein-is-increased-in-estrogen-receptor-beta-1-positive-breast-cancer-cells
#2
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
https://www.readbyqxmd.com/read/30505696/the-diagnostic-conundrum-of-chronic-ectopic-pregnancy-a-case-report
#3
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
https://www.readbyqxmd.com/read/30498230/pre-and-post-operative-anti-pd-l1-plus-anti-angiogenic-therapies-in-mouse-breast-or-renal-cancer-models-of-micro-or-macro-metastatic-disease
#4
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)...
November 30, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/30455614/association-between-inflammatory-bowel-disease-and-uveal-melanoma-case-report-of-two-young-adults-and-a-literature-review
#5
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
https://www.readbyqxmd.com/read/30427531/ex-vivo-culture-of-cells-derived-from-circulating-tumour-cell-xenograft-to-support-small-cell-lung-cancer-research-and-experimental-therapeutics
#6
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
https://www.readbyqxmd.com/read/30348128/recombinant-papp-a-resistant-insulin-like-growth-factor-binding-protein-4-dbp4-inhibits-angiogenesis-and-metastasis-in-a-murine-model-of-breast-cancer
#7
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
https://www.readbyqxmd.com/read/30345474/breast-implant-associated-anaplastic-large-cell-lymphoma
#8
REVIEW
P Rastogi, A K Deva, H Miles Prince
PURPOSE OF REVIEW: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognised malignancy of T lymphocytes exclusively associated with textured breast implants. This review aims to evaluate existing theories regarding the epidemiology, pathogenesis, clinical evaluation and management of the disease. RECENT FINDINGS: The true incidence of BIA-ALCL is difficult to define. Prevailing pathogenic theories recognise the interplay between textured implants, Gram-negative bacteria, host genetics (e...
October 22, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/30291675/adenosine-deaminase-inhibition-suppresses-progression-of-4t1-murine-breast-cancer-by-adenosine-receptor-dependent-mechanisms
#9
Barbara Kutryb-Zajac, Patrycja Koszalka, Paulina Mierzejewska, Alicja Bulinska, Magdalena A Zabielska, Karolina Brodzik, Aleksandra Skrzypkowska, Lukasz Zelazek, Iwona Pelikant-Malecka, Ewa M Slominska, Ryszard T Smolenski
The activity of a cell-surface ecto-adenosine deaminase (eADA) is markedly increased in the endothelial activation and vascular inflammation leading to decreased adenosine concentration and alterations in adenosine signalling. Depending on the specific pathway activated, extracellular purines mediate host cell response or regulate growth and cytotoxicity on tumour cells. The aim of this study was to test the effects of adenosine deaminase inhibition by 2'deoxycoformycin (dCF) on the breast cancer development...
December 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/30266933/clonal-dynamics-in-osteosarcoma-defined-by-rgb-marking
#10
Stefano Gambera, Ander Abarrategi, Fernando González-Camacho, Álvaro Morales-Molina, Josep Roma, Arantzazu Alfranca, Javier García-Castro
Osteosarcoma is a type of bone tumour characterized by considerable levels of phenotypic heterogeneity, aneuploidy, and a high mutational rate. The life expectancy of osteosarcoma patients has not changed during the last three decades and thus much remains to be learned about the disease biology. Here, we employ a RGB-based single-cell tracking system to study the clonal dynamics occurring in a de novo-induced murine osteosarcoma model. We show that osteosarcoma cells present initial polyclonal dynamics, followed by clonal dominance associated with adaptation to the microenvironment...
September 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/30232071/custom-3d-printed-finger-proximal-phalanx-as-salvage-of-limb-function-after-aggressive-recurrence-of-giant-cell-tumour
#11
Giovanni Beltrami
Giant cell tumours (GCT) of the finger phalanges are extremely rare but have a high rate of recurrence. This report details the case of a GCT of the proximal phalanx of the fourth finger in a 64-year-old man. The patient was initially subjected to systemic neoadjuvant denosumab treatment, and subsequent aggressive curettage, sparing of the articular joints, local cryotherapy and autologous intercalary fibular bone graft. Finger function after surgery was considered satisfactory, despite limited proximal interphalangeal (PIP) joint motion...
September 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/30228780/delta-like-ligand-4-in-hepatocellular-carcinoma-intrinsically-promotes-tumour-growth-and-suppresses-hepatitis-b-virus-replication
#12
Areerat Kunanopparat, Jiraphorn Issara-Amphorn, Asada Leelahavanichkul, Anapat Sanpavat, Suthiluk Patumraj, Pisit Tangkijvanich, Tanapat Palaga, Nattiya Hirankarn
AIM: To investigate the role of Delta-like ligand 4 (DLL4) on tumour growth in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) in vivo . METHODS: We suppressed DLL4 expression in an HBV expressing HCC cell line, HepG2.2.15 and analysed the growth ability of cells as subcutaneous tumours in nude mice. The expression of tumour angiogenesis regulators, VEGF-A and VEGF-R2 in tumour xenografts were examined by western blotting. The tumour proliferation and neovasculature were examined by immunohistochemistry...
September 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/30215546/pre-clinical-imaging-for-establishment-and-comparison-of-orthotopic-non-small-cell-lung-carcinoma-in-search-for-models-reflecting-clinical-scenarios
#13
Rozina Aktar, Antje Dietrich, Falk Tillner, Shady Kotb, Steffen Löck, Henning Willers, Michael Baumann, Mechthild Krause, Rebecca Bütof
Objective Clinically relevant animal models of non-small cell lung carcinoma (NSCLC) are required for the validation of novel treatments. We compared two different orthotopic transplantation techniques as well as imaging modalities to identify suitable mouse models mimicking clinical scenarios. Methods We used three genomically diverse NSCLC cell lines [National Cancer Institute (NCI)-H1703 adenosquamous cell carcinoma, NCI-H23 adenocarcinoma and A549 adenocarcinoma) for implanting tumour cells either as spheroids or cell suspension into lung parenchyma...
September 14, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/30170559/targeting-the-notch1-oncogene-by-mir-139-5p-inhibits-glioma-metastasis-and-epithelial-mesenchymal-transition-emt
#14
Jianlong Li, Qingbin Li, Lin Lin, Rui Wang, Lingchao Chen, Wenzhong Du, Chuanlu Jiang, Ruiyan Li
BACKGROUND: Glioma metastasis, invasion, epithelial-mesenchymal transition (EMT) and chemoresistance indicate poor prognosis. Accumulating evidence reveals that Notch1 is an important factor in tumour progression. However, the role of Notch1 in glioma EMT and associated microRNAs (miRNAs) with the Notch pathway remain controversial. METHODS: Utilizing cBioPortal database to examine the gene signature of NOTCH1 (encoding Notch1), CDH2 (encoding N-cadherin) and SNAI1 (encoding Snail-1) in disease-free survival (DFS) and overall survival (OS)...
August 31, 2018: BMC Neurology
https://www.readbyqxmd.com/read/30150428/characterisation-of-a-mouse-model-of-breast-cancer-with-metabolic-syndrome
#15
Linda A Buss, Anishah Mandani, Elisabeth Phillips, Nicola J A Scott, Margaret J Currie, Gabi U Dachs
BACKGROUND/AIM: Patients with breast cancer and metabolic syndrome have poorer outcomes. We aimed to develop and characterise an apolipoprotein E-null/aromatase knockout (ApoE-/- /ArKO) mouse model of breast cancer with metabolic syndrome to aid research of the mechanisms behind poor prognosis. MATERIALS AND METHODS: Wild-type, ApoE-/- and ApoE-/- /ArKO mice were orthotopically implanted with EO771 murine breast cancer cells. Tumour growth was monitored and tumours investigated for pathological features such as cancer-associated adipocytes, hypoxia and cancer cell proliferation...
September 2018: In Vivo
https://www.readbyqxmd.com/read/30097997/therapeutic-implications-of-how-tnf-links-apolipoprotein-e-phosphorylated-tau-%C3%AE-synuclein-amyloid-%C3%AE-and-insulin-resistance-in-neurodegenerative-diseases
#16
REVIEW
I A Clark, B Vissel
While cytokines such as TNF have long been recognized as essential to normal cerebral physiology, the implications of their chronic excessive production within the brain are now also increasingly appreciated. Syndromes as diverse as malaria and lead poisoning, as well as non-infectious neurodegenerative diseases, illustrate this. These cytokines also orchestrate changes in tau, α-synuclein, amyloid-β levels and degree of insulin resistance in most neurodegenerative states. New data on the effects of salbutamol, an indirect anti-TNF agent, on α-synuclein and Parkinson's disease, APOE4 and tau add considerably to the rationale of the anti-TNF approach to understanding, and treating, these diseases...
October 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/30065265/s100p-enhances-the-motility-and-invasion-of-human-trophoblast-cell-lines
#17
Maral E A Tabrizi, Tara L Lancaster, Thamir M Ismail, Athina Georgiadou, Ankana Ganguly, Jayna J Mistry, Keqing Wang, Philip S Rudland, Shakil Ahmad, Stephane R Gross
S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein's role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi...
July 31, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30064148/-multiple-myeloma-current-standards-in-surgical-treatment
#18
Michael Kehrer, Sebastian Koob, Andreas Kehrer, Dieter Christian Wirtz, Jan Schmolders
BACKGROUND: Multiple myeloma is a haematological blood cancer in elderly patients, in which neoplastic cell populations cause osteolytic destruction in the bone skeleton. More than 50% of all patients sustain pathological fractures during the course of their disease. Of all malignant lesions of the spine, multiple myeloma is the most frequent spinal tumour and accounts for approximately 15% of all cases. 8 - 10% of the patients develop neurological deficits. In addition to systemic antineoplastic therapy, surgical treatment is often required in order to reconstruct and stabilise bone defects associated with multiple myeloma, as well as to address tumour-related complications...
July 31, 2018: Zeitschrift Für Orthopädie und Unfallchirurgie
https://www.readbyqxmd.com/read/29959879/gambogic-acid-inhibits-melanoma-through-regulation-of-mir-199a-3p-zeb1-signalling
#19
Lili Liang, Zhixin Zhang, Xiaowei Qin, Ying Gao, Peng Zhao, Jing Liu, Weihui Zeng
Malignant melanoma is an aggressive form of cancer which is highly resistant to chemotherapy. We have previously found that gambogic acid (GA), a kind of polyprenylated xanthone, exhibits an antitumour role in melanoma. The study was designed to investigate novel mechanisms of the antitumour effect of GA in melanoma cells and implanted nude mice. Gambogic acid significantly decreased cell viability, increased apoptosis and reduced migration and invasion in A375 cells. In addition, cisplatin-induced cytotoxicity in both A375 and A375/CDDP cells was increased by GA...
June 30, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29953980/repression-of-wt1-mediated-lef1-transcription-by-mangiferin-governs-%C3%AE-catenin-independent-wnt-signalling-inactivation-in-hepatocellular-carcinoma
#20
Hor-Yue Tan, Ning Wang, Sha Li, Ming Hong, Wei Guo, Kwan Man, Chien-Shan Cheng, Zhen Chen, Yibin Feng
BACKGROUND/AIMS: The development of hepatocellular carcinoma (HCC) is a complex process which involves deregulation of multiple signalling pathways. The hyper-activation of Wnt signalling promotes sustained expansion, invasion, and neovascularization of HCC. Mangiferin, a natural small molecule present in Mangifera indica L. has been shown to inactivate β-catenin, which is an indispensable regulator in Wnt pathway. Our study aimed to determine whether mangiferin has any inhibitory effect on HCC and examine how it modulates Wnt signalling...
2018: Cellular Physiology and Biochemistry
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