24 results on '"Stebbing, Justin"'
Search Results
2. A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab.
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Esteva, Francisco J., Stebbing, Justin, Wood-Horrall, Rebecca N., Winkle, Peter J., Lee, Sung Young, and Lee, Sang Joon
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TRASTUZUMAB , *PHARMACOKINETICS , *MEDICATION safety , *CANCER treatment , *PHARMACODYNAMICS , *THERAPEUTICS , *BIOLOGICAL products , *DRUG monitoring , *IMMUNITY , *INTRAVENOUS therapy , *MONOCLONAL antibodies , *HEALTH outcome assessment , *RESEARCH funding , *STATISTICAL sampling , *RANDOMIZED controlled trials , *HUMAN research subjects , *BLIND experiment - Abstract
Purpose: Access to trastuzumab, a valuable anti-cancer treatment, can be limited by cost. The primary aim of this study was to evaluate and compare the PK profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference trastuzumab (Herceptin®) in healthy subjects. Secondary study aims included comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in these subjects.Methods: We performed a single-dose, randomised, double-blind, parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6 mg/kg, 90 min intravenous infusion) in 70 healthy adult males. Pharmacokinetics, safety and immunogenicity were evaluated up to 10 weeks post-dose. Primary endpoints were area under the serum concentration-time curve (AUC) from time 0 to infinity (AUCinf); AUC from time 0 to last quantifiable concentration (AUClast); and observed maximum serum concentration (Cmax). The pre-determined equivalence criterion was a 90% confidence interval of 80-125% for ratios of geometric least squares (LS) means.Results: Equivalence of CT-P6 and reference trastuzumab was demonstrated. Ratios (CT-P6/reference trastuzumab) of geometric LS means (90% confidence interval) were: AUCinf 99.05 (93.00, 105.51); AUClast 99.30 (92.85, 106.20); Cmax 96.58 (90.93, 102.59). Safety profiles were similar; treatment-emergent adverse events occurred in ten subjects (28.6%) in the CT-P6 group and 11 (31.4%) in the reference trastuzumab group. No serious adverse events or deaths occurred. No subjects tested positive for anti-drug antibodies.Conclusions: These data add to the totality of evidence required to demonstrate biosimilarity. A phase III study of CT-P6-in which equivalent neoadjuvant efficacy to reference trastuzumab has been demonstrated-is ongoing. [ABSTRACT FROM AUTHOR]- Published
- 2018
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3. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial.
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Stebbing, Justin, Baranau, Yauheni, Baryash, Valeriy, Manikhas, Alexey, Moiseyenko, Vladimir, Dzagnidze, Giorgi, Zhavrid, Edvard, Boliukh, Dmytro, Stroyakovskii, Daniil, Pikiel, Joanna, Eniu, Alexandru, Komov, Dmitry, Morar-Bolba, Gabriela, Li, Rubi K, Rusyn, Andriy, Lee, Sang Joon, Lee, Sung Young, and Esteva, Francisco J
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BREAST cancer treatment , *TRASTUZUMAB , *HER2 protein , *CLINICAL drug trials , *ADJUVANT treatment of cancer , *THERAPEUTICS , *BIOTHERAPY , *ADENOCARCINOMA , *ANTINEOPLASTIC agents , *BIOLOGICAL products , *BREAST tumors , *CELL receptors , *CLINICAL trials , *COMBINED modality therapy , *COMPARATIVE studies , *FLUOROURACIL , *HYDROCARBONS , *MASTECTOMY , *RESEARCH methodology , *MEDICAL cooperation , *NEUTROPENIA , *RESEARCH , *TUMOR classification , *EVALUATION research , *RANDOMIZED controlled trials , *BLIND experiment , *CYCLOPHOSPHAMIDE , *EPIRUBICIN - Abstract
Background: CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer.Methods: In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m2 on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m2], epirubicin [75 mg/m2], and cyclophosphamide [500 mg/m2]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting.Findings: Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%).Interpretation: CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer.Funding: Celltrion Inc. [ABSTRACT FROM AUTHOR]- Published
- 2017
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4. Brain metastases associated with germ cell tumors may be treated with chemotherapy alone.
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Hardt, Anna, Krell, Jonathan, Wilson, Peter D., Harding, Victoria, Chowdhury, Simon, Mazhar, Danish, Berney, Dan, Stebbing, Justin, and Shamash, Jonathan
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BRAIN metastasis ,GERM cell tumors ,CANCER chemotherapy ,KAPLAN-Meier estimator ,METHOTREXATE ,RADIOTHERAPY ,THERAPEUTICS - Abstract
BACKGROUND The management of brain metastases in patients with germ cell tumors remains controversial. The authors assessed the outcome in this patient group after the introduction of GAMEC chemotherapy (14-day cisplatin, high-dose methotrexate, etoposide, and actinomycin-D with filgrastim support) and cessation of the routine use of cranial irradiation. METHODS Data were recorded prospectively from 39 patients with germ cell tumors and concurrent brain metastases who received treatment before and after the advent of GAMEC after they relapsed on conventional cisplatin-based chemotherapy. Neurosurgery was offered to selected patients. Radiotherapy generally was used only as a salvage therapy after chemotherapy failure. The primary outcome measure was overall survival and was depicted using a Kaplan-Meier plot. RESULTS The 3-year overall survival rates were 38% for the whole cohort, 69% for those who presented with brain metastases at diagnosis (group 1), and 21% and 0% for those who developed metastases after initial chemotherapy (group 2) and while receiving chemotherapy (group 3), respectively. For the whole cohort, the median overall survival was 10.6 months (range, 5.5 months to not evaluable); and, for groups 1, 2, and 3 individually, the overall survival was not yet reached (range, from 7.4 months to not evaluable), 6.2 months (range, 2.1-15.3 months), and 2.7 months (range, from 0.6 months to not evaluable), respectively. The 3-year survival rate for those who received GAMEC chemotherapy was 56% compared with 27% for those who received chemotherapy pre-GAMEC. CONCLUSIONS The prognosis for patients with germ cell tumors and brain metastases seems less bleak than previously thought. It is possible to achieve long-term survival with chemotherapy alone. Cancer 2014;120:1639-1646. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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5. Castrate-resistant prostate cancer: the future of antiandrogens.
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Pchejetski, Dmitri, Alshaker, Heba, and Stebbing, Justin
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PROSTATE cancer treatment ,ANTIANDROGENS ,ETHNICITY ,RADIOTHERAPY ,HORMONE therapy ,TUMOR suppressor genes ,THERAPEUTICS - Abstract
Several promising new treatment options for men with castrate-resistant prostate cancer have become available recently. The authors look at developments in this rapidly progressing area. Copyright © 2014 John Wiley & Sons [ABSTRACT FROM AUTHOR]
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- 2014
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6. The Emergence of Baricitinib: A Story of Tortoises Versus Hares.
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Lenz, Heinz-Josef, Richardson, Peter, and Stebbing, Justin
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COVID-19 ,COMBINATION drug therapy ,SARS-CoV-2 ,JANUS kinases ,CYTOKINE release syndrome ,ANTIRHEUMATIC agents ,NEUROTRANSMITTER uptake inhibitors ,HYDROXYCHLOROQUINE ,THERAPEUTICS - Abstract
In the article, the authors discuss the emergence of baricitinib as a treatment for coronavirus disease 2019 (COVID-19). Topics include the approved use of baricitinib as treatment of moderate to severe rheumatoid arthritis (RA), how artificial intelligence algorithms projected the effectiveness of the drug in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of cells, and the use of baricitinib and hydroxychloroquine to treat COVID-19.
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- 2021
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7. An overview of drug development for metastatic breast cancer.
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Stebbing, Justin and Ellis, Paul
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PROTEIN-tyrosine kinase inhibitors , *ANTINEOPLASTIC agents , *BIOMARKERS , *BREAST tumors , *CANCER chemotherapy , *CANCER relapse , *CELL receptors , *COST effectiveness , *DRUG resistance in cancer cells , *GENE expression , *HEALTH care teams , *METASTASIS , *ONCOGENES , *DRUG development , *VASCULAR endothelial growth factors , *EARLY detection of cancer , *THERAPEUTICS - Abstract
The prevalence of breast cancer is increasing as more women are living with the disease. Outcomes have improved as a result of progress in all major aspects of multidisciplinary care. These include surgery, radiotherapy, hormonal therapy, chemotherapy and newer targeted drugs. Two aspects merit particular attention here. First, there is an understanding now that cancer is a heterogenous disease and a 'one-size-fits-all' approach is becoming redundant, albeit slowly. Second, basic science and an appreciation of cellular molecular targets in those different types of breast cancer is being translated into the clinic and has led to the development of exciting new drugs for both triple negative and HER2-positive relapsed disease. An improved understanding of endocrine resistance remains an unmet need in drug development and here, it appears worthwhile to adopt less conventional approaches. Better trial design with a focus on biomarkers should lower barriers to regulatory approval as well as increase cost effectiveness. [ABSTRACT FROM AUTHOR]
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- 2012
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8. Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer.
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Giamas, Georgios, Filipović, Aleksandra, Jacob, Jimmy, Messier, Walter, Hua Zhang, Dongyun Yang, Wu Zhang, Shifa, Belul Assefa, Photiou, Andrew, Tralau-Stewart, Cathy, Castellano, Leandro, Green, Andrew R., Coombes, R. Charles, Ellis, Ian O., Ali, Simak, Lenz, Heinz-Josef, and Stebbing, Justin
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THERAPEUTICS ,BREAST cancer treatment ,PROTEIN kinases ,PHOSPHORYLATION ,HORMONE therapy ,GENETIC polymorphisms - Abstract
Therapies targeting estrogen receptor α (ERα, encoded by ESR1) have transformed the treatment of breast cancer. However, large numbers of women relapse, highlighting the need for the discovery of new regulatory targets modulating ERα pathways. An siRNA screen identified kinases whose silencing alters the estrogen response including those previously implicated in regulating ERα activity (such as mitogen-activated protein kinase and AKT). Among the most potent regulators was lemur tyrosine kinase-3 (LMTK3), for which a role has not previously been assigned. In contrast to other modulators of ERα activity, LMTK3 seems to have been subject to Darwinian positive selection, a noteworthy result given the unique susceptibility of humans to ERα
+ breast cancer. LMTK3 acts by decreasing the activity of protein kinase C (PKC) and the phosphorylation of AKT (Ser473), thereby increasing binding of forkhead box O3 (FOXO3) to the ESR1 promoter. LMTK3 phosphorylated ERα, protecting it from proteasomal degradation in vitro. Silencing of LMTK3 reduced tumor volume in an orthotopic mouse model and abrogated proliferation of ERα+ but not ERα− cells, indicative of its role in ERα activity. In human cancers, LMTK3 abundance and intronic polymorphisms were significantly associated with disease-free and overall survival and predicted response to endocrine therapies. These findings yield insights into the natural history of breast cancer in humans and reveal LMTK3 as a new therapeutic target. [ABSTRACT FROM AUTHOR]- Published
- 2011
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9. A Validated Prognostic Index Predicting Response to Dexamethasone and Diethylstilbestrol in Castrate-Resistant Prostate Cancer.
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Shamash, Jonathan, Stebbing, Justin, Sweeney, Chris, Sonpavde, Guru, Harland, Steve, Dawkins, Guy, Brock, Cathryn, Abelman, Walter, Wilson, Peter, Sanitt, Adam, Oliver, Tim, and Powles, Thomas
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PROSTATE cancer treatment , *DEXAMETHASONE , *DIETHYLSTILBESTROL , *PROSTATE-specific antigen , *HORMONE therapy , *CANCER prognosis , *THERAPEUTICS - Abstract
The article discusses a study on the prognostic significance of a combined dexamethasone and diethylstilbestrol (DS) therapy by measuring the prostate-specific antigen (PSA) level before and after a month of DS therapy. An assessment of the prognostic patients factors was done 30 days after the start of DS therapy. The study indicates that the prognostic index developed showed the possibility of identifying patients with castrate-resistant prostate cancer (CRPC) who had a good prognosis within a month of DS therapy.
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- 2010
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10. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma
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Stebbing, Justin, Powles, Thomas, McPherson, Kirsty, Shamash, Jonathan, Wells, Paula, Sheaff, Michael T., Slater, Sarah, Rudd, Robin M., Fennell, Dean, and Steele, Jeremy P.C.
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DRUG efficacy , *VINORELBINE , *MESOTHELIOMA , *CANCER chemotherapy , *CANCER relapse , *DRUG dosage , *HEALTH outcome assessment , *THERAPEUTICS - Abstract
Summary: Malignant pleural mesothelioma (MPM) is a rapidly progressive invariably lethal tumor. Treatment options remain limited and the outcome in relapsed disease is poor warranting new therapeutic options. Following our previous experience in the first-line setting, we conducted a phase 2 open-label non-comparative study to assess the safety and efficacy of weekly vinorelbine chemotherapy, each cycle consisting of 30mg/m2 for 6 weeks, in patients with previous exposure to chemotherapy. In 63 individuals with relapsed MPM who had not received previous vinorelbine, we observed an objective response rate of 16% and an overall survival of 9.6 months (95% confidence interval 7.3–11.8 months). The main grade III/IV toxicity observed was neutropenia and toxicity was similar to weekly vinorelbine when used in the first-line setting. Weekly vinorelbine appeared to have a reasonable response rate with an acceptable toxicity profile in the second-line treatment of MPM. Its use should be prospectively evaluated in a randomised trial in the first or second-line therapy of MPM. [Copyright &y& Elsevier]
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- 2009
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11. Kaposi's sarcoma as a model for cancer immunotherapy
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Stebbing, Justin, Bower, Mark, and Srivastava, Pramod
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IMMUNE system , *CANCER treatment , *THERAPEUTICS , *SPONTANEOUS cancer regression , *TUMOR antigens - Abstract
Physicians have, for over a century, attempted to harness the potential therapeutic power of the immune system to treat patients with cancer. The discovery that cancer regression can be achieved by immune rejection of tumour antigens theoretically allows the eradication of neoplastic cells without toxicity to normal tissues. An understanding of the mode of presentation of tumour antigens, including those complexed to heat shock proteins by major histocompatibility complex (MHC) class I and class II molecules, and their recognition by CD8+ and CD4+ T cells, respectively, has further delineated the potential cancer rejection pathways involved. This also enables the sustained induction and expansion of specific anti-tumour T cells with cytolytic activity. [Copyright &y& Elsevier]
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- 2004
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12. HIV and AIDS in the People's Republic of China: a collaborative review.
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Portsmouth, Simon, Stebbing, Justin, Xu Keyi, Zhang Jianping, and Pi Guohua
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AIDS ,HIV infections ,ANTIRETROVIRAL agents ,CHLOROQUINE ,HERBAL medicine ,THERAPEUTICS - Abstract
The number of individuals diagnosed with HIV in China has risen dramatically in the last two years coincident with increased awareness and an attitude change within government. UNAIDS has suggested that China could have 10 million HIV infected people by 2010. However, antiretroviral treatments and HIV testing are not yet widely available and infected individuals often live in remote areas. It is unlikely that cheaper, locally produced, generic antiretroviral formulations will be available in China in the near future. Consequently, alternative strategies to manage HIV infection are being considered including the use of hydroxyurea, chloroquine and traditional Chinese herbal medicines. It is recognized in China that prevention and educational strategies will need to be at the forefront of approaches to control this epidemic. [ABSTRACT FROM AUTHOR]
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- 2003
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13. The Evolution of Coreceptor Tropism in HIV-infected Patients Interrupting Suppressive Antiretroviral Therapy.
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Waters, Laura J., Scourfield, Andrew T., Marcano, Marie, Gazzard, Brian G., Bower, Mark, Nelson, Mark, and Stebbing, Justin
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TROPISMS ,HIV-positive persons ,HIV infections ,THERAPEUTICS ,ANTIRETROVIRAL agents ,RNA ,HIGHLY active antiretroviral therapy ,COMBINATION drug therapy - Abstract
CCR5 antagonists may provide a well-tolerated switch option for patients experiencing tolerability or toxicity of their antiretroviral regimen. We analyzed stored samples from patients undergoing planned treatment interruptions for reasons other than virological failure, in order to analyze tropism evolution during fully suppressive antiretroviral therapy (ART). Two of 37 patients showed evidence of switching. Tropism switching after suppressive ART was uncommon in this cohort. Pretreatment human immunodeficiency virus (HIV) RNA tropism testing may help guide the switch to CCR5 antagonists in patients with undetectable HIV RNA. [ABSTRACT FROM AUTHOR]
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- 2011
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14. Clinical outcome in resistant HIV-2 infection treated with raltegravir and maraviroc
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Armstrong-James, Darius, Stebbing, Justin, Scourfield, Andrew, Smit, Erasmus, Ferns, Bridget, Pillay, Deenan, and Nelson, Mark
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DRUG resistance , *THERAPEUTICS , *HIV infections , *HEALTH outcome assessment , *HIV-positive persons , *ANTIRETROVIRAL agents , *GENOTYPE-environment interaction - Abstract
Abstract: Therapy for infection with HIV-2 remains limited. We report an HIV-2-infected patient in whom genotyping demonstrated PI, NRTI and NNRTI resistance, with a subsequent response to raltegravir- and maraviroc-based therapy. Further studies are required to assess the clinical efficacy of maraviroc in HIV-2 infection. [Copyright &y& Elsevier]
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- 2010
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15. New therapies for hepatitis infection.
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Stebbing, Justin, Powles, Tom, and Bower, Mark
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HEPATITIS treatment ,THERAPEUTICS ,HEPATITIS B virus ,HEPATITIS C virus ,MOLECULES - Abstract
The article focuses on new therapies for hepatitis infection. Current therapies for hepatitis B virus including lamivudine, tenofovir and adefovir are said to be more advanced than those for hepatitis C virus (HCV). However, new classes of molecules promise to improve outcome for HCV by providing complete viral eradication with a reduced treatment duration from 1 year to 3 months.
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- 2006
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16. Artemisia: a divine dart against cancer?
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Pinato, David J and Stebbing, Justin
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CANCER treatment , *MALARIA treatment , *ARTEMISIA , *MEDICAL emergencies , *DRUG resistance , *DRUG development , *THERAPEUTICS - Published
- 2015
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17. Black cohosh, hot flushes, and breast cancer.
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Merchant, Shairoz and Stebbing, Justin
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BUGBANE , *HOT flashes , *BREAST cancer treatment , *PREMATURE menopause , *CANCER chemotherapy , *THERAPEUTICS - Published
- 2015
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18. Liquorice: a treatment for all sorts?
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Harding, Victoria and Stebbing, Justin
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LICORICE (Plant) , *ANTINEOPLASTIC agents , *GASTROINTESTINAL diseases , *ANTI-inflammatory agents , *THERAPEUTICS , *ANIMALS , *GLYCYRRHIZA , *HERBAL medicine , *MEDICINAL plants , *RISK assessment , *PLANT roots , *EVIDENCE-based medicine , *PLANT extracts ,THERAPEUTIC use of plant extracts - Published
- 2017
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19. Turmeric: a spice for life?
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Balachandran, Kirsty and Stebbing, Justin
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CURCUMIN , *AYURVEDIC medicine , *CANCER chemotherapy , *DRUG side effects , *BREAST cancer treatment , *THERAPEUTICS - Published
- 2016
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20. Baricitinib for COVID-19: a suitable treatment? - Authors' reply.
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Richardson, Peter J, Corbellino, Mario, and Stebbing, Justin
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COVID-19 , *SARS disease , *MIDDLE East respiratory syndrome , *COVID-19 pandemic , *THERAPEUTICS , *BARICITINIB - Published
- 2020
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21. Combining luteinising hormone releasing hormone agonists and aromatase inhibitors in breast cancer
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Krell, Jonathan, Ewart, Edwina K., and Stebbing, Justin
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ANTINEOPLASTIC agents , *GOSERELIN , *AROMATASE inhibitors , *ESTROGEN antagonists , *BREAST tumors , *METASTASIS , *THERAPEUTICS - Published
- 2010
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22. Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours.
- Author
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Centelles, Miguel N., Wright, Michael, So, Po-Wah, Amrahli, Maral, Xu, Xiao Yun, Stebbing, Justin, Miller, Andrew D., Gedroyc, Wladyslaw, and Thanou, Maya
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TOPOTECAN , *THERMOTHERAPY , *ULTRASONIC imaging , *DRUG delivery systems , *TUMOR treatment , *TREATMENT effectiveness , *THERAPEUTICS - Abstract
Image guided drug delivery using imageable thermosensitive liposomes (iTSLs) and high intensity focused ultrasound (FUS or HIFU) has attracted interest as a novel and non-invasive route to targeted delivery of anti-cancer therapeutics. FUS-induced hyperthermia is used as an externally applied “trigger” for the release of a drug cargo from within thermosensitive drug carriers. It is suggested that sub-ablative hyperthermia significantly modifies the permeability of tumour vasculature and enhances nanoparticle uptake. Here we describe the preparation and use of magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF) labelled thermosensitive liposomes for imaging and tracking of biodistribution and drug release in a murine cancer model. We prepared iTSLs to encapsulate topotecan (Hycamtin®), a chemotherapeutic agent which when released in tumours can be monitored by an increase in its intrinsic drug fluorescence. FUS was applied using feedback via subcutaneously placed fine-wire thermocouples to maintain and monitor hyperthermic temperatures. iTSL accumulation was detected within tumours using NIRF imaging immediately after liposome administration. Mild FUS-induced hyperthermia (3 min at 42 °C, 30 min post i.v. administration) greatly enhanced iTSLs uptake. A co-localised enhancement of topotecan fluorescence emission was also observed immediately after application of FUS indicating rapid triggered drug release. The phenomena of increased iTSL accumulation and concomitant topotecan release appeared to be amplified by a second mild hyperthermia treatment applied one hour after the first. MRI in vivo also confirmed enhanced iTSLs uptake due to the FUS treatments. Our imaging results indicate the effects of hyperthermia on the uptake of carriers and drug. FUS-induced hyperthermia combined with real time imaging could be used as a tool for tumour targeted drug delivery. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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23. Strategies in functional proteomics: Unveiling the pathways to precision oncology.
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Favicchio, Rosy, Thepaut, Chloe, Zhang, Hua, Arends, Richard, Stebbing, Justin, and Giamas, Georgios
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ONCOLOGY research , *DRUG development , *PROTEOMICS , *HEALTH outcome assessment , *BIOMARKERS , *ANTINEOPLASTIC agents , *PROTEIN metabolism , *ANIMAL experimentation , *CELLULAR signal transduction , *DRUG therapy , *DATABASES , *DRUG design , *METABOLISM , *MOLECULAR diagnosis , *PROTEINS , *RESEARCH funding , *TUMORS , *BIOINFORMATICS , *PREDICTIVE tests , *PATIENT selection - Abstract
Personalised strategies in cancer care are required to overcome the therapeutic challenges posed by variability between patients and disease subsets. To this end, enhanced precision tools must be developed to describe the molecular drivers of malignant proliferation. Such tools must also identify druggable targets and biomarkers in order to provide essential information regarding drug development and therapeutic outcome. Here we discuss how proteomics-based approaches provide a set of viable methodologies capable of delivering quantitative information throughout the main stages of personalised oncology and a ratiometric platform that delivers systems-wide methods for drug evaluation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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24. The Nucleoside Backbone Affects Durability of Efavirenz- or Nevirapine-Based Highly Active Antiretroviral Therapy in Antiretroviral-Naive Individuals.
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Annan, Naa Torshie, Nelson, Mark, Mandalia, Sundhiya, Bower, Mark, Gazzard, Brian G., and Stebbing, Justin
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HIGHLY active antiretroviral therapy , *NUCLEOSIDES , *REVERSE transcriptase , *DRUG efficacy , *THERAPEUTICS , *HIV infections - Abstract
The article presents a study which examines the effectiveness of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimes among antiretroviral-naive patients who are undergoing highly active antiretroviral therapy (HAART). The study analyzed the data of 994 antiretroviral-naive patients who were taking efavirenz and nevirapine with dual-nucleoside analogue backbones. It reveals no significant differences between efavirenz and nevirapine on the success and failure of the treatment.
- Published
- 2009
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