Medical Oncology
http://hdl.handle.net/10541/56774
Medical Oncology2024-03-16T00:03:17ZRandomised phase II study of amrubicin as single agent or in combination with cisplatin versus cisplatin etoposide as first-line treatment in patients with extensive stage small cell lung cancer - EORTC 08062.
http://hdl.handle.net/10541/232872
Randomised phase II study of amrubicin as single agent or in combination with cisplatin versus cisplatin etoposide as first-line treatment in patients with extensive stage small cell lung cancer - EORTC 08062.
O'Brien, M E R; Konopa, K; Lorigan, Paul C; Bosquee, L; Marshall, E; Bustin, F; Margerit, S; Fink, C; Stigt, J A; Dingemans, A; Hasan, B; Van Meerbeeck, J; Baas, P
The EORTC 08062 phase II randomised trial investigated the activity and safety of single agent amrubicin, cisplatin combined with amrubicin, and cisplatin combined with etoposide as first line treatment in extensive disease (ED) small cell lung cancer (SCLC).
2011-10-01T00:00:00ZSecond cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study.
http://hdl.handle.net/10541/232851
Second cancer risk after chemotherapy for Hodgkin's lymphoma: a collaborative British cohort study.
Swerdlow, A J; Higgins, C D; Smith, P; Cunningham, D; Hancock, B W; Horwich, A; Hoskin, P J; Lister, T A; Radford, John A; Rohatiner, A Z S; Linch, D C
We investigated the long-term risk of second primary malignancy after chemotherapy for Hodgkin's lymphoma (HL) in a much larger cohort than any yet published, to our knowledge.
2011-11-01T00:00:00ZA phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors.
http://hdl.handle.net/10541/230943
A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors.
Jonker, D J; Rosen, L S; Sawyer, M B; de Braud, F; Wilding, G; Sweeney, C J; Jayson, Gordon C; McArthur, G A; Rustin, G; Goss, G; Kantor, J; Velasquez, L; Syed, S; Mokliatchouk, O; Feltquate, D M; Kollia, G; Nuyten, D S A; Galbraith, S
This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors.
2011-06-01T00:00:00ZCancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors.
http://hdl.handle.net/10541/230938
Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors.
Martinez-Outschoorn, U E; Lin, Z; Trimmer, C; Flomenberg, N; Wang, C; Pavlides, S; Pestell, R G; Howell, Anthony; Sotgia, F; Lisanti, M P
Previously, we proposed that cancer cells behave as metabolic parasites, as they use targeted oxidative stress as a "weapon" to extract recycled nutrients from adjacent stromal cells. Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis, and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the "reverse Warburg effect." To further test the validity of this hypothesis, here we used an in vitro MCF7-fibroblast co-culture system, and quantitatively measured a variety of metabolic parameters by FACS analysis (analogous to laser-capture micro-dissection). Mitochondrial activity, glucose uptake, and ROS production were measured with highly-sensitive fluorescent probes (MitoTracker, NBD-2-deoxy-glucose, and DCF-DA). Interestingly, using this approach, we directly show that cancer cells initially secrete hydrogen peroxide that then triggers oxidative stress in neighboring fibroblasts. Thus, oxidative stress is contagious (spreads like a virus) and is propagated laterally and vectorially from cancer cells to adjacent fibroblasts. Experimentally, we show that oxidative stress in cancer-associated fibroblasts quantitatively reduces mitochondrial activity, and increases glucose uptake, as the fibroblasts become more dependent on aerobic glycolysis. Conversely, co-cultured cancer cells show significant increases in mitochondrial activity, and corresponding reductions in both glucose uptake and GLUT1 expression. Pre-treatment of co-cultures with extracellular catalase (an anti-oxidant enzyme that detoxifies hydrogen peroxide) blocks the onset of oxidative stress, and potently induces the death of cancer cells, likely via starvation. Given that cancer-associated fibroblasts show the largest increases in glucose uptake, we suggest that PET imaging of human tumors, with Fluoro-2-deoxy-D-glucose (F-2-DG), may be specifically detecting the tumor stroma, rather than epithelial cancer cells.
2011-08-01T00:00:00Z