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RISS 인기검색어
- 검색키워드
- 저자 : Pennell, Nathan A. (검색결과 3 건)
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Cho, Byoung Chul,Dy, Grace K.,Govindan, Ramaswamy,Kim, Dong-Wan,Pennell, Nathan A.,Zalcman, Gerard,Besse, Benjamin,Kim, Joo-Hang,Koca, Goekben,Rajagopalan, Prabhu,Langer, Simon,Ocker, Matthias,Nogai, Elsevier 2018 Lung cancer Vol.123 No.-
<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>This phase Ib/II study evaluated safety, pharmacokinetics, maximum tolerated dose (MTD), and efficacy of the pan-cyclin-dependent kinase inhibitor roniciclib with cisplatin-etoposide (CIS-ETOP) or carboplatin-etoposide (CARBO-ETOP) in patients with extensive-disease small-cell lung cancer (ED-SCLC).</P> <P><B>Patients and methods</B></P> <P>In this open-label, non-randomized study, patients with previously untreated ED-SCLC received roniciclib twice daily (BID) in a 3 days on/4 days off schedule. Cisplatin 75 mg/m<SUP>2</SUP> or carboplatin (AUC5) dose was administered on day 1, and etoposide 100 mg/m<SUP>2</SUP> on days 1–3, of 21-day cycles. Phase Ib used a dose-escalation design to define the MTD for phase II. Pharmacokinetics were assessed.</P> <P><B>Results</B></P> <P>Forty-three patients received treatment (roniciclib 2.5 mg BID [+ CARBO-ETOP, n = 4; + CIS-ETOP, n = 3] and roniciclib 5 mg BID [+ CARBO-ETOP, n = 24; + CIS-ETOP, n = 12]). The MTD of roniciclib was 5 mg BID with CARBO-ETOP or CIS-ETOP. Common adverse events were nausea (90.7%) and vomiting (69.8%). Roniciclib was readily absorbed following oral administration at the MTD (median t<SUB>max</SUB> 0.5–1 h), with a 30–40% reduction in exposure when co-administered with CARBO-ETOP or CIS-ETOP; administration of roniciclib had no effect on etoposide or platinum pharmacokinetics. The response rate was 81.4% (35/43) overall and 86.1% (31/36) in the pooled roniciclib 5 mg BID population (all partial responses).</P> <P><B>Conclusion</B></P> <P>Roniciclib co-administered with chemotherapy in patients with ED-SCLC demonstrated tolerability, acceptable pharmacokinetics, and promising efficacy. An observed safety signal in a related phase II study resulted in discontinuation of the present study and termination of further roniciclib development.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Phase Ib/II study of ED-SCLC patients treated with roniciclib plus chemotherapy. </LI> <LI> Combination was well tolerated and readily absorbed across all dose combinations. </LI> <LI> No clinically relevant PK interactions were observed upon concomitant treatment. </LI> <LI> Promising efficacy of roniciclib plus chemotherapy, despite low patient numbers. </LI> <LI> Unfavorable benefit/risk balance from another study led to study termination. </LI> </UL> </P>
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Invasive and Non-Invasive Imaging for Ischaemia with No Obstructive Coronary Artery Disease
Ming-Yen Ng,Hok Shing Tang,Lucas Chun Wah Fong,Victor Chan,Roxy Senior,Dudley John Pennell 아시아심장혈관영상의학회 2021 Cardiovascular Imaging Asia Vol.5 No.3
Ischaemia with no obstructive coronary artery disease (INOCA) affects up to 50% of patients referred for coronary angiography for suspected angina. Although originally thought to be benign, recent data shows that patients with INOCA have an adverse prognosis. There are challenges in identifying and managing the underlying cause, which is most often attributed to coronary microvascular disease or coronary vasospasm. This review will cover the clinical relevance and prognosis of INOCA as well as the invasive and non-invasive imaging techniques available to identify the underlying aetiology. Upcoming technological advancements will also be discussed.
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High-resolution metabolomics of occupational exposure to trichloroethylene
Walker, Douglas I,Uppal, Karan,Zhang, Luoping,Vermeulen, Roel,Smith, Martyn,Hu, Wei,Purdue, Mark P,Tang, Xiaojiang,Reiss, Boris,Kim, Sungkyoon,Li, Laiyu,Huang, Hanlin,Pennell, Kurt D,Jones, Dean P,Rot Oxford University Press 2016 International journal of epidemiology Vol.45 No.5
<P><B>Background:</B> Occupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin’s lymphoma and kidney and liver cancer; however, TCE’s mode of action for development of these diseases in humans is not well understood.</P><P><B>Methods:</B> Non-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppm<SUB>a</SUB>)] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population.</P><P><B>Results:</B> Metabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (<I>β</I> = 0.13, <I>P</I>-value = 3.6 × 10<SUP>−5</SUP>), glutamine (<I>β</I> = 0.08, <I>P</I>-value = 0.0013), cystine (<I>β</I> = 0.75, <I>P</I>-value = 0.0022), methylthioadenosine (<I>β</I> = −1.6, <I>P</I>-value = 0.0043), taurine (<I>β</I> = −2.4, <I>P</I>-value = 0.0011) and chenodeoxycholic acid (<I>β</I> = −1.3, <I>P</I>-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations.</P><P><B>Conclusions:</B> High-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology.</P>
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