A5069044650- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- PARP inhibition in cancer therapy
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Cancer Treatment and Pharmacology
- Information and Cyber Security
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- Gastrointestinal motility and disorders
- Economic and Financial Impacts of Cancer
- Elder Abuse and Neglect
- Digital Mental Health Interventions
- Childhood Cancer Survivors' Quality of Life
- Vascular Tumors and Angiosarcomas
- Photography and Visual Culture
- Clinical Nutrition and Gastroenterology
- Toxin Mechanisms and Immunotoxins
- Pharmaceutical studies and practices
- Cancer-related Molecular Pathways
- Renal cell carcinoma treatment
- BRCA gene mutations in cancer
- Chronic Myeloid Leukemia Treatments
- Information Systems Theories and Implementation
Federation University
2019-2024
Covance (United Kingdom)
2019-2021
AstraZeneca (United Kingdom)
2011-2015
AstraZeneca (Spain)
2015
AstraZeneca (Brazil)
2012-2015
York St John University
2011
East Cheshire NHS Trust
2011
This study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of first-in-class dual mammalian target rapamycin complex (mTORC)1/mTORC2 inhibitor, AZD8055. Patients with advanced solid malignancies or lymphomas were recruited into this phase I, open-label, dose-escalation AZD8055 starting at 10 mg twice-daily oral dosing (BID). Forty-nine patients received Dose-limiting toxicities reported 40 (n=1), 90 (n=1) 120 (n=3) BID; all grade 3 rises in transaminases, reversible...
Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) is essential in cellular processing of DNA damage via the base excision repair pathway (BER). The PARP inhibition can be directly cytotoxic to tumour cells and augments anti-tumour effects DNA-damaging agents. This study evaluated optimally tolerated dose olaparib (4-(3--4-fluorophenyl) methyl-1(2H)-one; AZD2281, KU0059436), a potent inhibitor, with dacarbazine assessed safety, toxicity, clinical pharmacokinetics efficacy combination...
AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown in vitro and vivo efficacy across range of preclinical human cancer models.A rolling six-dose escalation was performed to define an MTD (part A), at further cohort patients treated characterize toxicities perform pre- posttreatment biopsies B). administered orally twice day continuously. Flow cytometry, ELISA, immunohistochemistry were used quantify pharmacodynamic biomarkers. Pharmacokinetic analysis carried out by mass...
Abstract The Australian healthcare sector is a complex mix of government departments, associations, providers, professionals, and consumers. Cybersecurity attacks, which have recently increased, challenge the in many ways; however, best approaches for to manage threat are unclear. This study will report on semi-structured focus group conducted with five representatives from computer security sectors. An analysis this transcript yielded four themes: 1) securing landscape; 2) financial...
Intestinal absorption characteristics of eleven beta-adrenoceptor antagonists were measured by monitoring their disappearance from in-situ intestinal loops in the anaesthetized rat. All have basic pKa values around 9.5 (with exception sotalol) but show a wide range lipophilic character (octanol-water log P -0.79 to 3.65). The results two types behaviour, indicating different mechanisms for 'hydrophilic' and 'lipophilic' antagonists. four most hydrophilic molecules (sotalol, atenolol, nadolol...
As a prelude to combination studies aimed at resistance reversal, this dose-escalation/dose-expansion study investigated the selective Src kinase inhibitor saracatinib (AZD0530) in with carboplatin and/or paclitaxel. Patients advanced solid tumours received once-daily oral tablets either AUC 5 every 3 weeks (q3w), paclitaxel 175 mg m−2 q3w, 80 1 week (q1w), or plus q3w. The primary endpoint was safety/tolerability. A total of 116 patients 125 (N=20), (N=44), 225 (N=40), 250 (N=9), 300 (N=3)....
3004 Background: AZD2014 is a potent, dual mTORC1/mTORC2 inhibitor with clear activity in vivo and vitro experimental models. Methods: This 2-part study consisted of "rolling six" dose escalation (Part A) expansion B) phases. Part A: 3–6 pts per cohort received an oral solution BD starting at 50 mg. A further 6 were treated below the MTD to changes pharmacodynamic (PD) biomarkers. B: additional dosed MTD, including group ER+/PR+ or HER2+ patients breast cancer. Primary endpoint: safety...
This study aimed to explore the cybersecurity landscape identify indexes that may be relevant health industry. While healthcare sector poses security concerns regarding patients' records, in has not been given much consideration.
3096 Background: AZD8055 is a dual mTORC1/mTORC2 inhibitor with properties that prevent the feedback activation of AKT seen rapalogues. This first-in-man study to determine safety, PK and preliminary efficacy two oral formulations in patients advanced solid tumours (NCT00731263). Another inhibitor, AZD2014, currently being tested clinic. Methods: In an open-label, ascending dose study, cohorts 3 or 6 received single followed 1 week later by continuous, twice-daily dosing. Starting at 10 mg,...
3048 Background: We previously reported the comparative bioavailability of capsule (CAP) formulation olaparib and more convenient new tablet (TAB) (Molife et al ASCO 2010). subsequently performed two separate dose expansions (DE1 DE2) to explore safety efficacy TAB (NCT00777582). Methods: Patients with breast or ovarian cancer BRCA1/2 mutations, ECOG PS 0–2 adequate organ function were randomized receive: DE1: 200 400 CAP; DE2: 300 TAB, CAP (all mg BID). Endpoints included safety,...
3051 Background: We previously reported the comparative bioavailability of olaparib tablet (TAB) up to 200 mg BID, with initial capsule formulation; gmean AUC 0–T following BID TAB was ~20% lower than 400 (CAP; Molife et al ASCO 2010). Olaparib had an acceptable tolerability profile suggesting further dose escalation might be justified. Methods: Study NCT00777582 amended include a dose-escalation phase, define maximum tolerated (MTD) and safety TAB, 2 expansion phases compare efficacy doses...
We investigated savolitinib pharmacokinetics (PK) when administered alone or in combination with rifampicin, itraconazole famotidine, and midazolam PK without healthy males.Savolitinib was evaluated before/after: rifampicin (600 mg once daily [QD] for 5 days); (200 QD a single dose of famotidine (40 QD) 2 hours before savolitinib. Midazolam before/after (1 QD). Each study enrolled 20, 16, 16 14 volunteers, respectively. Plasma samples were collected to determine the effect on PK.The...
Abstract Background: AZD8055 is a dual mTORC1/mTORC2 inhibitor with properties that prevent the feedback activation of AKT seen rapalogues. This first-in-man study to determine safety, PK and preliminary efficacy two oral formulations in patients (pts) advanced solid tumors (NCT00731263). Methods: In an open-label, ascending dose study, cohorts 3 or 6 pts received single followed 1 week later by continuous, twice-daily dosing. Starting at 10 mg, each subsequent cohort increased until...
Abstract Background: Preclinical and clinical (BOLERO 2) data suggest that pts with ER+ breast cancer become less sensitive to hormonal therapy over time greater dependency on the mTOR pathway. AZD2014 is a selective dual mTORC1 mTORC2 inhibitor may offer additional benefit vs inhibitors through suppression of AKT via mTORC2. demonstrate continuous or intermittent dosing schedules are equally effective in model latter achieve improved tolerability pts. This Ph I trial assesses safety,...
Abstract Background: Preclinical data suggest that patients with ER+ Breast Cancer become less sensitive to hormonal therapy by upregulation of the mTOR pathway. BOLERO-2 demonstrated combination an allosteric inhibitor and aromatase improves progression-free survival in postmenopausal women hormone resistant advanced breast cancer (NEJM 2012; 366:520-529). AZD2014 is a selective dual mTORC1 mTORC2 whilst fulvestrant estrogen receptor antagonist approved for treatment disease progression...
<p>Supplementary Data - materials and methods</p>
<div>Abstract<p><b>Purpose:</b> AZD2014 is a novel, oral, m-TORC 1/2 inhibitor that has shown <i>in vitro</i> and vivo</i> efficacy across range of preclinical human cancer models.</p><p><b>Experimental Design:</b> A rolling six-dose escalation was performed to define an MTD (part A), at further cohort patients treated characterize toxicities perform pre- posttreatment biopsies B). administered orally twice day continuously....