11 results on '"Raoul Charles Coombes"'
Search Results
2. Association between peri-operative angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers and acute kidney injury in major elective non-cardiac surgery: a multicentre, prospective cohort study
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Alvin Thomas, Rahul Bhome, Teo Lopez Bernal, Prashant Patel, Owen Thorpe, Conor Keogh, Raiyyan Aftab, Muhamed Farhan-Alanie, DEVENDER MITTAPALLI, Matthew Chan, Aditya Borakati, Roshni Bhudia, Christopher Graham, Vinci Naruka, Moritz Schramm, Michael Kerin, Nicholas Wroe, Samian Sulaiman, Michael Stoddart, James Fitzgerald, Matthew Hague, Shaikh Sanjid Seraj, Katie Dunleavy, Emily Greenan, Samira Bell, Robert Whitham, Hannah Charlotte Copley, Clementina Calabria, Daniel Ahern, Abdul-Rahman Gomaa, Joseph Yates, Fraser Peck, Chetan Khatri, Janet Martin, Martin Connor, Thomas Robert William Ward, Shyam Gokani, Thomas Pinkney, Luke McMenamin, Liam Cato, Sameera A, Edward Balai, Timothy Shao Ern Tan, Sogha Khawari, Siew Yim Loh, Jonathan Lund, Peter Coe, Stephen Robinson, Ledibabari Ngaage, STARSurg Collaborative, Joshua Burke, Melika Akhbari, P. Ronan O'Connell, James Glasbey, Roshan Joseph, Thomas Gardner, Jonathan Bannard-Smith, Catrin Morgan, Ewen Harrison, Paul Glen, Laurie Rigueros Springford, Chia Yew Kong, Claire Donohoe, Heather Davis, Richard Bogle, Tom Abbott, Elizabeth Wootton, Justine Davies, Mehnoor Khaliq, Viren Ahluwalia, Sam Myers, Alex Elizabeth Ward, Sivesh K Kamarajah, Joanna Osmanska, Raoul Charles Coombes, Oliver Warren, John Prowle, Harry VM Spiers, Kenneth A McLean, Thomas Ashdown, Katherine Bull, Paul Ridgway, Fortis Gaba, Hew David Torrance, Dalvir Bajwa, Emanuele Gammeri, Rebecca Spencer, Adam Gwozdz, Kirtan Patel, Jaspreet Kaur Seehra, Chung Shen Chean, and Fahad Mahmood
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Male ,medicine.medical_specialty ,Population ,Angiotensin-Converting Enzyme Inhibitors ,Comorbidity ,Drug Administration Schedule ,Perioperative Care ,03 medical and health sciences ,Angiotensin Receptor Antagonists ,0302 clinical medicine ,Postoperative Complications ,030202 anesthesiology ,Risk Factors ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,education ,Prospective cohort study ,Digestive System Surgical Procedures ,Aged ,Aged, 80 and over ,education.field_of_study ,Withholding Treatment ,biology ,business.industry ,Acute kidney injury ,Angiotensin-converting enzyme ,Perioperative ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,United Kingdom ,Anesthesiology and Pain Medicine ,Elective Surgical Procedures ,Propensity score matching ,biology.protein ,Female ,business ,Ireland - Abstract
The peri‐operative use of angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri‐operative period. This study aimed to investigate if withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers peri‐operatively reduces the risk of acute kidney injury following major non‐cardiac surgery. Patients undergoing elective major surgery on the gastrointestinal tract and/or the liver were eligible for inclusion in this prospective study. The primary outcome was the development of acute kidney injury within seven days of operation. Adjusted multi‐level models were used to account for centre‐level effects and propensity score matching was used to reduce the effects of selection bias between treatment groups. A total of 949 patients were included from 160 centres across the UK and Republic of Ireland. From this population, 573 (60.4%) patients had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers withheld during the peri‐operative period. One hundred and seventy‐five (18.4%) patients developed acute kidney injury; there was no difference in the incidence of acute kidney injury between patients who had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers continued or withheld (107 (18.7%) vs. 68 (18.1%), respectively; p = 0.914). Following propensity matching, withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers did not demonstrate a protective effect against the development of postoperative acute kidney injury (OR (95%CI) 0.89 (0.58–1.34); p = 0.567).
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- 2018
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3. Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer
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Yoko Omoto, Jan-Åke Gustafsson, Bo Huang, Raoul Charles Coombes, Aleksandra Filipovic, Margaret Warner, Hiroko Yamashita, Tatsuya Toyama, and Hirotaka Iwase
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Adult ,Oncology ,medicine.medical_specialty ,Estrogen receptor ,Breast Neoplasms ,Epithelium ,Breast cancer ,Internal medicine ,medicine ,Estrogen Receptor beta ,Humans ,Neoplasm Invasiveness ,Breast ,skin and connective tissue diseases ,neoplasms ,Estrogen receptor beta ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Multidisciplinary ,business.industry ,Carcinoma, Ductal, Breast ,Estrogen Receptor alpha ,Cancer ,Middle Aged ,Biological Sciences ,Hyperplasia ,medicine.disease ,body regions ,Carcinoma, Lobular ,Ki-67 Antigen ,Invasive lobular carcinoma ,Cancer research ,Female ,business ,Estrogen receptor alpha ,hormones, hormone substitutes, and hormone antagonists ,Tamoxifen ,medicine.drug - Abstract
The role of estrogen receptor (ER) α as a target in treatment of breast cancer is clear, but those of ERβ1 and ERβ2 in the breast remain unclear. We have examined expression of all three receptors in surgically excised breast samples from two archives: (i): 187 invasive ductal breast cancer from a Japanese study; and (ii) 20 lobular and 24 ductal cancers from the Imperial College. Samples contained normal areas, areas of hyperplasia, and in situ and invasive cancer. In the normal areas, ERα was expressed in not more than 10% of epithelium, whereas approximately 80% of epithelial cells expressed ERβ. We found that whereas ductal cancer is a highly proliferative, ERα-positive, ERβ-negative disease, lobular cancer expresses both ERα and ERβ but with very few Ki67-positive cells. ERβ2 was expressed in 32% of the ductal cancers, of which 83% were postmenopausal. In all ERβ2-positive cancers the interductal space was filled with dense collagen, and cell nuclei expressed hypoxia-inducible factor 1α. ERβ2 expression was not confined to malignant cells but was strong in stromal, immune, and endothelial cells. In most of the high-grade invasive ductal cancers neither ERα nor ERβ was expressed, but in the high-grade lobular cancer ERβ was lost and ERα and Ki67 expression were abundant. The data show a clear difference in ER expression between lobular and ductal breast cancer and suggest (i) that tamoxifen may be more effective in late than in early lobular cancer and (ii) a potential role for ERβ agonists in preventing in situ ductal cancers from becoming invasive.
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- 2014
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4. Effects of radiotherapy and surgery in early breast cancer: an overview of the randomized trials
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Raoul Charles Coombes, Judith Bliss, Abe, O, Abe, R, Asaishi, K, Enomoto, K, Hattori, T, Iino, Y, Kikuchi, K, Koyama, H, Sawa, K, Uchino, J, Yoshida, M, Vandevelde, A, Vermorken, J, Foroglou, P, Giokas, G, Lissaios, B, Harvey, V, Holdaway, T, Kay, R, Mason, B, Forbes, J, Focan, C, Lobelle, J, Peek, U, and Oates, G
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Humans ,Breast Neoplasms ,Female ,General Medicine ,Neoplasm Recurrence, Local ,Combined Modality Therapy ,Survival Analysis ,Randomized Controlled Trials as Topic - Abstract
Background Randomized trials of radiotherapy and surgery for early breast cancer may have been too small to detect differences in long-term survival and recurrence reliably. We therefore performed a systematic overview (meta-analysis) of the results of such trials. Methods Information was sought on each subject from investigators who conducted trials that began before 1985 and that compared local therapies for early breast cancer. Data on mortality were available from 36 trials comparing radiotherapy plus surgery with the same type of surgery alone, 10 comparing more-extensive surgery with less-extensive surgery, and 18 comparing more-extensive surgery with less-extensive surgery plus radiotherapy. Information on mortality was available for 28,405 women (97.4 percent of the 29,175 women in the trials). Results The addition of radiotherapy to surgery resulted in a rate of local recurrence that was three times lower than the rate with surgery alone, but there was no significant difference in 10-year survival; among a total of 17,273 women enrolled in such trials, mortality was 40.3 percent with radiotherapy and 41.4 percent without radiotherapy (P = 0.3). Radiotherapy was associated with a reduced risk of death due to breast cancer (odds ratio, 0.94; 95 percent confidence interval, 0.88 to 1.00; P = 0.03), which indicates that, after 10 years, there would be about 0 to 5 fewer deaths due to breast cancer per 100 women. However, there was an increased risk of death from other causes (odds ratio, 1.24; 95 percent confidence interval, 1.09 to 1.42; P = 0.002). This, together with the age-specific death rates, implies, after 10 years, a few extra deaths not due to breast cancer per 100 older women or per 1000 younger women. During the first decade or two after diagnosis, the excess in the rate of such deaths that was associated with radiotherapy was much greater among women who were over 60 years of age at randomization (15.3 percent vs. 11.1 percent [339 vs. 249 deaths]) than among those under 50 (2.5 percent vs. 2.0 percent [62 vs. 49 deaths]). Breast-conserving surgery involved some risk of recurrence in the remaining tissue, but no significant differences in overall survival at 10 years were found in the studies of mastectomy versus breast-conserving surgery plus radiotherapy (4891 women), more-extensive surgery versus less-extensive surgery (4818 women), or axillary clearance versus radiotherapy as adjuncts to mastectomy (4370 women). Conclusions Some of the local therapies for breast cancer had substantially different effects on the rates of local recurrence — such as the reduced recurrence with the addition of radiotherapy to surgery — but there were no definite differences in overall survival at 10 years.
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- 2016
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5. The Biodistribution and Radiation Dosimetry of the Arg-Gly-Asp Peptide 18F-AH111585 in Healthy Volunteers
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Raoul Charles Coombes, Eric O. Aboagye, Brian McParland, Mandeep Khela, Terence J. Spinks, Safiye Osman, Laura M. Kenny, Matthew P. Miller, Pamela S. Cohen, and Ai-Min Hui
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Male ,Biodistribution ,Pyridines ,Glycine ,Peptide ,Urine ,Arginine ,Radiation Dosage ,Effective dose (radiation) ,Excretion ,In vivo ,Humans ,Medicine ,Dosimetry ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Radiometry ,Aged ,Whole blood ,chemistry.chemical_classification ,Aspartic Acid ,business.industry ,Middle Aged ,chemistry ,Positron-Emission Tomography ,Azetidines ,Female ,Radiopharmaceuticals ,Peptides ,business ,Nuclear medicine - Abstract
We report the safety, biodistribution, and internal radiation dosimetry of a new PET tracer, (18)F-AH111585, a peptide with a high affinity for the alpha(v)beta(3) integrin receptor involved in angiogenesis.PET scans of 8 healthy volunteers were acquired at time points up to 4 h after a bolus injection of (18)F-AH111585. (18)F activity in whole blood and plasma and excreted urine were measured up to 4 h after injection. In vivo (18)F activities in up to 12 source regions were determined from quantitative analysis of the images. The cumulated activities subsequently calculated were then used to determine the internal radiation dosimetry, including the effective dose.Injection of (18)F-AH111585 was well tolerated in all subjects, with no serious or drug-related adverse events reported. The main route of (18)F excretion was renal (37%), and the 3 highest initial uptakes were by liver (15%); combined walls of the small, upper large, and lower large intestines (11%); and kidneys (9%). The 3 highest absorbed doses were received by the urinary bladder wall (124 microGy/MBq), kidneys (102 microGy/MBq), and cardiac wall (59 microGy/MBq). The effective dose was 26 microGy/MBq.(18)F-AH111585 is a safe PET tracer with a dosimetry profile comparable to other common (18)F PET tracers.
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- 2008
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6. miR-106b similar to 25 cluster regulates multidrug resistance in an ABC transporter-independent manner via downregulation of EP300
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Yuan Zhou, Kaiyong Li, Raoul Charles Coombes, Raquel Cuella, Hui Shi, Muhammad Asaduzzaman, Ernesto Yagüe, Yunhui Hu, and Selina Raguz
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0301 basic medicine ,Cancer Research ,ATP-binding cassette transporter ,chemistry.chemical_compound ,paclitaxel ,INDUCED SENESCENCE ,0302 clinical medicine ,Transduction, Genetic ,Breast ,RNA, Neoplasm ,Tumor Stem Cell Assay ,Cell Line, Transformed ,Etoposide ,P-glycoprotein ,biology ,apoptosis ,GLYCOPROTEIN ,BREAST-CANCER CELLS ,General Medicine ,Transfection ,Cell cycle ,Cadherins ,EPITHELIAL-MESENCHYMAL TRANSITION ,Drug Resistance, Multiple ,Neoplasm Proteins ,Phenotype ,Paclitaxel ,Oncology ,Multigene Family ,030220 oncology & carcinogenesis ,Life Sciences & Biomedicine ,STEM-CELLS ,EXPRESSION ,Down-Regulation ,Antineoplastic Agents ,03 medical and health sciences ,breast cancer ,TOPOISOMERASE-II ,Downregulation and upregulation ,E-CADHERIN ,Humans ,DRUG-RESISTANCE ,Science & Technology ,Epithelial Cells ,Multiple drug resistance ,MicroRNAs ,030104 developmental biology ,chemistry ,Doxorubicin ,Drug Resistance, Neoplasm ,Gamma Rays ,Apoptosis ,Immunology ,Cancer research ,biology.protein ,ATP-Binding Cassette Transporters ,Colchicine ,E1A-Associated p300 Protein ,1112 Oncology And Carcinogenesis - Abstract
MicroRNA (miR)-106b~25 cluster regulates bypass of doxorubicin and γ-radiation induced senescence by downregulation of the E-cadherin transcriptional activator EP300. We asked whether upregulation of miR-106~25 cluster generates cells with a truly multidrug resistant (MDR) phenotype and whether this is due to upregulation of the ATP-binding cassette (ABC) transporter P-glycoprotein. We used minimally transformed mammary epithelial breast cancer cells (MTMECs) in which the miR-106b~25 cluster was experimentally upregulated by lentiviral transfection or in which hairpins targeting either EP300 or E-cadherin mRNAs have been expressed with lentiviruses. We find that overexpression of miR-106b~25 cluster led to the generation of MDR MTMECs (resistant to etoposide, colchicine and paclitaxel). Paclitaxel resistance was also studied after experimental downregulation of EP300 or E-cadherin. However none of these cells overexpressed P-glycoprotein or where able to efflux a fluorescent derivative of paclitaxel, making this phenotype drug-transporter independent. Paclitaxel treatment in MTMECs led to an increase in early apoptotic cells (Annexin V-positive), activation of caspase-9 and increase in the proportion of cells at the G2/M phase of the cell cycle. However, MTMEC overexpressing miR-106b~25 cluster, or with EP300 or E-cadherin downregulated, showed less activation of apoptosis, caspase-9 and caspase-3/-7 activities. Thus, miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.
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- 2015
7. International study on inter-reader variability for circulating tumor cells in breast cancer
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Edith A. Perez, Madeline Repollet, Leonardus Wendelinus Mathias Marie Terstappen, Elin Borgen, Brigitte Rack, Craig Miller, Stefan Sleijfer, Maria Cristina Cassatella, Laura Zorzino, Ulrich Andergassen, Martine Piccart, Klaus Pantel, Françoise Rothé, Wolfgang Janni, Tanja Fehm, Jaco Kraan, Silvia Bessi, Angelo Di Leo, Dimitris Mavroudis, Ghizlane Rouas, Michael B. Campion, Monica M. Reinholz, Raoul Charles Coombes, Eleni Politaki, Stella Apostolaki, Michail Ignatiadis, Maria Teresa Sandri, Claudia Aura, Bjørn Naume, Stefan Michiels, Isabelle Vaucher, Rachel E. Payne, Ingrid Teufel, Martta Pestrin, François-Clément Bidard, Jessica Metallo, Christos Sotiriou, Bianca Mostert, Jean-Yves Pierga, Sabine Riethdorf, Mustapha Khazour, Jose Jimenez, Medical Oncology, Faculty of Science and Technology, Medical Cell Biophysics, and Cancer Research UK
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Oncology ,CA15-3 ,International Cooperation ,Breast Neoplasms -- blood -- metabolism -- pathology ,Neoplastic Cells, Circulating -- metabolism -- pathology ,Cell Count ,Medical Oncology -- instrumentation -- standards ,Medical Oncology ,DISEASE ,Circulating tumor cell ,Receptor, ErbB-2 -- metabolism ,Stage (cooking) ,Neoplasm Metastasis ,skin and connective tissue diseases ,Medicine(all) ,Laboratories -- standards ,IR-91687 ,CHEMOTHERAPY ,Reference Standards ,Neoplastic Cells, Circulating ,SURVIVAL ,METIS-304906 ,TRIAL ,Female ,Life Sciences & Biomedicine ,Research Article ,EXPRESSION ,Receptor, erbB-2 ,medicine.medical_specialty ,CA 15-3 ,Breast Neoplasms ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Oncology & Carcinogenesis ,Reference standards ,neoplasms ,Science & Technology ,Her2 expression ,business.industry ,Médecine pathologie humaine ,Reproducibility of Results ,ONCOLOGY ,medicine.disease ,Cell Count -- instrumentation -- standards ,Cancérologie ,HER-2 ,Laboratories ,business ,Nuclear medicine ,1112 Oncology And Carcinogenesis ,Kappa - Abstract
Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch(R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2014
8. Human Estrogen Receptor β Binds DNA in a Manner Similar to and Dimerizes with Estrogen Receptor α
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Raoul Charles Coombes, Jacqueline Taylor, Paul E. Pace, Simak Ali, and S Suntharalingam
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medicine.drug_class ,Estrogen receptor ,Biology ,Ligands ,Polymerase Chain Reaction ,Biochemistry ,chemistry.chemical_compound ,Estrogen-related receptor alpha ,medicine ,Animals ,Estrogen Receptor beta ,Humans ,Cloning, Molecular ,Receptor ,Fulvestrant ,Molecular Biology ,Estrogen receptor beta ,Estradiol ,Estrogen Antagonists ,Estrogen Receptor alpha ,Temperature ,DNA ,Cell Biology ,DNA-binding domain ,Molecular biology ,Tamoxifen ,Receptors, Estrogen ,chemistry ,Estrogen ,COS Cells ,Dimerization ,Estrogen receptor alpha ,hormones, hormone substitutes, and hormone antagonists - Abstract
The cloning of a novel estrogen receptor beta (denoted ERbeta) has recently been described (Kuiper, G. G. J. M., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J-A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5925-5930 and Mosselman, S., Polman, J. , and Dijkema, R. (1996) FEBS Lett. 392, 49-53). ERbeta is highly homologous to the "classical" estrogen receptor alpha (here referred to as ERalpha), has been shown to bind estrogens with an affinity similar to that of ERalpha, and activates expression of reporter genes containing estrogen response elements in an estrogen-dependent manner. Here we describe functional studies comparing the DNA binding abilities of human ERalpha and beta in gel shift assays. We show that DNA binding by ERalpha and beta are similarly affected by elevated temperature in the absence of ligand or in the presence of 17beta-estradiol and the partial estrogen agonist 4-hydroxy-tamoxifen. In the absence of ligand, DNA binding by ERalpha and beta is rapidly lost at 37 degrees C, while in the presence of 17beta-estradiol and 4-hydroxy-tamoxifen, the loss in DNA binding at elevated temperature is much more gradual. We show that the loss in DNA binding is not due to degradation of the receptor proteins. However, while the complete antagonist ICI 182, 780 does not "protect" human ERalpha (hERalpha) from loss of DNA binding at elevated temperature in vitro, it does appear to protect human ERbeta (hERbeta), suggestive of differences in the way ICI 182, 780 acts on hERalpha and beta. We further report that ERalpha and beta can dimerize with each other, the DNA binding domain of hERalpha being sufficient for dimerization with hERbeta. Cell and promoter-specific transcription activation by ERalpha has been shown to be dependent on the differential action of the N- and C-terminal transcription activation functions AF-1 and AF-2, respectively. The existence of a second estrogen receptor gene and the dimerization of ERalpha and beta add greater levels of complexity to transcription activation in response to estrogens.
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- 1997
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9. The miR-106b~25 cluster promotes bypass of doxorubicin-induced senescence and increase in motility and invasion by targeting the E-cadherin transcriptional activator EP300
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Ernesto Yagüe, Raoul Charles Coombes, Parmjit S. Jat, Yunhui Hu, D Xiong, Yuan Zhou, Selina Raguz, Ylenia Lombardo, M Yang, and Kaiyong Li
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cancer stem cells ,Biochemistry & Molecular Biology ,TUMOR-CELLS ,Motility ,Breast Neoplasms ,Biology ,CISPLATIN RESISTANCE ,Transfection ,OVARIAN-CANCER ,Cancer stem cell ,Cell Movement ,Cell Line, Tumor ,microRNA ,Humans ,TERMINAL PROLIFERATION ARREST ,MULTIDRUG-RESISTANCE ,Molecular Biology ,11 Medical and Health Sciences ,Cellular Senescence ,Skin ,doxorubicin-induced senescence ,EP300 ,DRUG-RESISTANCE ,MESENCHYMAL TRANSITION ,Original Paper ,Science & Technology ,Cadherin ,EMT ,E-cadherin ,BREAST-CANCER CELLS ,Cell Biology ,06 Biological Sciences ,Fibroblasts ,Cadherins ,Phenotype ,Cell biology ,PROSTATE-CANCER ,MicroRNAs ,Cell Aging ,Doxorubicin ,Drug Resistance, Neoplasm ,Female ,Stem cell ,Cell aging ,Life Sciences & Biomedicine ,STEM-CELLS ,E1A-Associated p300 Protein - Abstract
Resistance to chemotherapeutic treatment, which is indirectly responsible for many cancer deaths, is normally associated with an aggressive phenotype including increased cell motility and acquisition of invasive properties. Here we describe how breast cancer cells overcome doxorubicin-induced senescence and become drug resistant by overexpression of the microRNA (miR)-106b~25 cluster. Although all three miRs in the cluster contribute to the generation of doxorubicin resistance, miR-25 is the major contributor to this phenotype. All three miRs in this cluster target EP300, a transcriptional activator of E-cadherin, resulting in cells acquiring a phenotype characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT), including an increase in both cell motility and invasion, as well as the ability to proliferate after treatment with doxorubicin. These findings provide a novel drug resistance/EMT regulatory pathway controlled by the miR-106b~25 cluster by targeting a transcriptional activator of E-cadherin.
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- 2013
10. Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer
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W. Heller, H. D. Sinnett, A. Fayaz, Raoul Charles Coombes, Danish Mazhar, R. Phillips, C. Palmieri, Charles Lowdell, S. Shousha, and R. Ward
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Breast Neoplasms ,Docetaxel ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Breast-conserving surgery ,Humans ,Neoadjuvant therapy ,Aged ,Epirubicin ,Retrospective Studies ,Chemotherapy ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,Female ,Taxoids ,Fluorouracil ,business ,Mastectomy ,medicine.drug - Abstract
The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.
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- 2006
11. Operation manual for control of selection, production, preclinical toxicology and phase I trials of endocrine agents for patients with cancer
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Raoul Charles Coombes
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Cancer Research ,Hormone Antagonists ,Oncology ,Clinical Protocols ,Drug Evaluation ,Humans ,Antineoplastic Agents ,Hormones ,Research Article - Published
- 1989
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