Publications
818 results found
Pinato DJ, Karamanakos G, Arizumi T, et al., 2014, Dynamic changes of the inflammation-based index predict mortality following chemoembolisation for hepatocellular carcinoma: a prospective study, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 40, Pages: 1270-1281, ISSN: 0269-2813
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- Citations: 27
Badreldin W, Krell J, Chowdhury S, et al., 2014, The efficacy of irinotecan, paclitaxel, and oxaliplatin (IPO) in relapsed germ cell tumors with high dose chemotherapy as consolidation- a non-cisplatin- based induction approach., BJU International, Vol: 117, Pages: 418-423, ISSN: 1464-4096
OBJECTIVES: To determine the outcome of an expanded cohort of patients with relapsed germ cell tumors (GCT) treated with a salvage chemotherapy regimen consisting of irinotecan, paclitaxel and oxaliplatin (IPO) and assess the role of IPO as an alternative to standard cisplatin-based chemotherapy regimens in this setting. PATIENTS AND METHODS: The results of 72 consecutive patients were reviewed retrospectively. IPO was used either as a second-line treatment (n=29), of which 20 patients subsequently received high-dose chemotherapy (HDCT), or third-line (n=43), of which 32 patients proceeded to HDCT. RESULTS: The 2-year PFS and 3-year OS rates for the whole cohort were 30.2% (95%CI 17.3-40.5%) and 33.4% (95%CI: 20.1-43.8 %) respectively. CR was achieved in 3%, m-ve PR in 41%, m+ve PR in 18%, SD in 17% and PD in 20%. In the second-line setting, the 2-year PFS rate was 43.5% (95%CI: 21.7-60.8%) and 3-year OS 49.1% (95%CI: 24.2-65.1%). In the third-line setting, the 2-year PFS rate was 21.0% (95%CI 9.5-35.4%) and the 3-year OS rate was 23.9% (95%CI 11.7-38.2).According to the current international prognostic factor study group criteria for first relapse for the high and very high risk group the 2 year PFS rates were 50% and 30% respectively. There were 2 treatment related deaths from IPO, and 4 from HDCT. Grade 3 or 4 toxicities included neutropenia (35%), thrombocytopenia (18%), infection (15%), diarrhea (11%) and lethargy (8%). CONCLUSIONS: IPO offers an effective, well-tolerated, non-nephrotoxic alternative to cisplatin-based salvage regimens for patients with relapsed GCT. It appears particularly useful in high risk patients and for those in whom cisplatin is ineffective or contra-indicated.
Stebbing J, Paz K, Schwartz GK, et al., 2014, Patient-derived xenografts for individualized care in advanced sarcoma (vol 120, pg 2006, 2014), CANCER, Vol: 120, Pages: 3588-3588, ISSN: 0008-543X
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- Citations: 1
Froeling FEM, Stebbing J, 2014, <i>Uncaria tomentosa</i>, the cat's whiskers or claws?, LANCET ONCOLOGY, Vol: 15, Pages: 1299-1300, ISSN: 1470-2045
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- Citations: 2
Alshaker H, Krell J, Frampton AE, et al., 2014, Leptin induces upregulation of sphingosine kinase 1 in oestrogen receptor-negative breast cancer via Src family kinase-mediated, janus kinase 2-independent pathway, Breast Cancer Research, Vol: 16, ISSN: 1465-542X
Introduction: Obesity is a known risk factor for breast cancer. Sphingosine kinase 1 (SK1) is an oncogenic lipidkinase that is overexpressed in breast tumours and linked with poor prognosis, however, its role in obesity-drivenbreast cancer was never elucidated.Methods: Human primary and secondary breast cancer tissues were analysed for SK1 and leptin receptorexpression using quantitative real-time polymerase chain reaction (qRT-PCR) assay. Leptin-induced signalling wasanalysed in human oestrogen receptor (ER)-positive and negative breast cancer cells using Western blotting,qRT-PCR and radiolabelling assays.Results: Our findings show for the first time that human primary breast tumours and associated lymph nodemetastases exhibit a strong correlation between SK1 and leptin receptor expression (Pearson R = 0.78 and R = 0.77,respectively, P <0.001). Both these genes are elevated in metastases of ER-negative patients and show a significantincrease in patients with higher body mass index (BMI). Leptin induces SK1 expression and activation in ER-negativebreast cancer cell lines MDAMB-231 and BT-549, but not in ER-positive cell lines. Pharmacological inhibition andgene knockdown showed that leptin-induced SK1 activity and expression are mediated by activation of extracellularsignal-regulated kinases 1/2 (ERK1/2) and Src family kinase (SFK) pathways, but not by the major pathwaysdownstream of leptin receptor (LEPR) - janus kinase 2 (JAK2) and signal transducer and activator of transcription 3(STAT3). Src-homology 2 domain-containing phosphatase 2 (SHP2) appeared to be key to SK1 activation, and mayfunction as an adaptor protein between SFKs and LEPR. Importantly, leptin-induced breast cancer cell proliferationwas abrogated by SK1-specific small interfering RNA (siRNA).Conclusions: Overall, our findings demonstrate a novel SFK/ERK1/2-mediated pathway that links leptin signallingand expression of oncogenic enzyme SK1 in breast tumours and suggest the potential significance
Benhaim L, Zhang W, Wakatsuki T, et al., 2014, Genetic variants of kinase suppressors of Ras (KSR1) to predict survival in patients with ER alpha-positive advanced breast cancer, Pharmacogenomics Journal, Vol: 15, Pages: 235-240, ISSN: 1473-1150
In patients with breast cancer (BC), deregulation of estrogen receptor (ERα) activity may account for most resistance to endocrine therapies. Our previous study used a whole-human kinome siRNA screen to identify functional actors in ERα modulation and showed the implication of proteins kinase suppressors of ras (KSR1). From those findings we evaluated the clinical impact of KSR1 variants in patients with ERα+ BC treated with TAM. DNA was obtained from 222 patients with advanced ERα+ BC treated with TAM who had undergone surgery from 1981 to 2003. We selected three potentially functional relevant KSR1 polymorphisms; two within the 3’UTR (rs224190, rs1075952) and one in the coding exon 7 (rs2293180). The primary end points were overall survival (OS) and disease-free survival (DFS). After a 6.4-year median follow-up, patients carrying the rs2241906 TT genotype showed shorter DFS (2.1 vs 7.1 years, P=0.005) and OS (2.6 vs 8.4 years P=0.002) than those with the TC or TT genotypes. Those associations remained significant in the multivariable analysis adjusting age, lymph node status, LMTK3 and IGFR variants and HER2 status. The polymorphisms rs2241906 and rs1075952 were in linkage disequilibrium. No association was shown between rs2293180 and survival. Among the actors of ERα signaling, KSR1 rs2241906 variants may predict survival in patients with advanced ERα+ BC treated with adjuvant TAM.
Zhang H, Stebbing J, Xu Y, et al., 2014, Global mapping of tyrosine kinase signalling in breast cancer by combined use of RNAi and SILAC quantitative proteomics, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Magturo S, Giamas G, Mallick S, et al., 2014, Evaluation of LMTK3 expression and tumor phenotype in estrogen-dependent colorectal cancer, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Mazarakis NK, Smith S, Vraka A, et al., 2014, The expression of lemur tyrosine kinase-3 in high grade pediatric tumors, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Britton D, Zen Y, Selzer S, et al., 2014, Quantification of pancreatic cancer proteome & phosphorylome: Indicates molecular events likely contributing to cancer & activation status of drug targets, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Nunes JFG, Zhang H, Stebbing J, et al., 2014, SILAC-BASED ANALYSIS REVEALS A UNIQUE PHOSPHOPROTEOMIC-SIGNATURE OF HER2-RESISTANT BREAST CANCER CELLS, ANTICANCER RESEARCH, Vol: 34, Pages: 5900-5900, ISSN: 0250-7005
Xu Y, Zhang H, Vorgias C, et al., 2014, POSITIONING LMTK3 ON THE MAP OF ONCOGENIC SIGNALING CASCADES AND ELUCIDATING ITS ROLE IN INVASION AND METASTASIS IN BREAST CANCER, ANTICANCER RESEARCH, Vol: 34, Pages: 5923-5924, ISSN: 0250-7005
Ottaviani S, de Giorgio A, Harding V, et al., 2014, Noncoding RNAs and the control of hormonal signaling via nuclear receptor regulation, JOURNAL OF MOLECULAR ENDOCRINOLOGY, Vol: 53, Pages: R61-R70, ISSN: 0952-5041
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- Citations: 8
Sagoo MS, Harbour JW, Stebbing J, et al., 2014, Combined PKC and MEK inhibition for treating metastatic uveal melanoma, ONCOGENE, Vol: 33, Pages: 4722-4723, ISSN: 0950-9232
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- Citations: 23
Miller H, Castellano L, Frampton A, et al., 2014, 1158PROLE OF MICRORNA AS BIOMARKERS IN SMALL BOWEL NEUROENDOCRINE TUMOURS., Ann Oncol, Vol: 25
Hills A, Stebbing J, 2014, Electrotherapy: enlightening modern medicine, LANCET ONCOLOGY, Vol: 15, Pages: 1060-1061, ISSN: 1470-2045
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- Citations: 2
Krell J, Stebbing J, 2014, Stage-Stratified Approach to AIDS-Related Kaposi's Sarcoma: Implications for Resource-Limited Environments Reply, JOURNAL OF CLINICAL ONCOLOGY, Vol: 32, Pages: 2514-U162, ISSN: 0732-183X
Annels NE, Simpson GR, Denyer M, et al., 2014, Spontaneous antibodies against Engrailed-2 (EN2) protein in patients with prostate cancer, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 177, Pages: 428-438, ISSN: 0009-9104
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- Citations: 3
Bower M, Stebbing J, 2014, Exploiting interleukin 6 in multicentric Castleman's disease, LANCET ONCOLOGY, Vol: 15, Pages: 910-912, ISSN: 1470-2045
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- Citations: 11
Roca-Alonso L, Castellano L, Mills A, et al., 2014, Myocardial miR-30 down-regulation caused by doxorubicin alters the beta-adrenergic system and mitochondrial death pathways, CARDIOVASCULAR RESEARCH, Vol: 103, ISSN: 0008-6363
de Giorgio A, Castellano L, Krell J, et al., 2014, Crosstalk-induced loss of miR-126 promotes angiogenesis, ONCOGENE, Vol: 33, Pages: 3634-3635, ISSN: 0950-9232
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- Citations: 11
Xu Y, Zhang H, Lit LC, et al., 2014, The Kinase LMTK3 Promotes Invasion in Breast Cancer Through GRB2-Mediated Induction of Integrin β<sub>1</sub>, SCIENCE SIGNALING, Vol: 7, ISSN: 1945-0877
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- Citations: 31
Stebbing J, Paz K, Schwartz GK, et al., 2014, Patient-Derived Xenografts for Individualized Care in Advanced Sarcoma, CANCER, Vol: 120, Pages: 2006-2015, ISSN: 0008-543X
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- Citations: 125
Krell J, Frampton AE, Mirnezami R, et al., 2014, Growth Arrest-Specific Transcript 5 Associated snoRNA Levels Are Related to p53 Expression and DNA Damage in Colorectal Cancer, PLOS One, Vol: 9, ISSN: 1932-6203
Background: The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts anumber of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes and cancer.Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into thepotential role of this locus in cell survival and oncogenesis both in vivo and in vitro.Methods: We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assessthe relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignanthuman colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damageresponse.Results: GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancercell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNAexpression in colorectal tissue.Conclusions: In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they havean important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome.We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA)-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used asendogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experimentscan lead to inaccurate results.
Hardt A, Krell J, Wilson PD, et al., 2014, Brain Metastases Associated With Germ Cell Tumors May Be Treated With Chemotherapy Alone, CANCER, Vol: 120, Pages: 1639-1646, ISSN: 0008-543X
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- Citations: 15
Bevan R, Nickerson C, Patnick J, et al., 2014, BOWELSCOPE: EARLY RESULTS FROM THE PILOT SITES, GUT, Vol: 63, Pages: A145-A145, ISSN: 0017-5749
Bevan R, Nickerson C, Blanks R, et al., 2014, VARIATION IN ADENOMA DETECTION RATE IN BOWELSCOPE SCREENING, GUT, Vol: 63, Pages: A146-A146, ISSN: 0017-5749
Stebbing J, 2014, Cancer: Where were we, where are we, where are we going., Med Leg J, Vol: 82, Pages: 57-66
Cancer diagnosis, medicine, prevention and care is changing - all for the better. As opposed to the "old days" of luck, trial and error and toxicity, we are now entering a new dawn due to advances in genomics and our understanding of biology. Personalised medicine or PM (aspects of which may also be referred to as precision medicine) is a medical model that proposes the customisation of healthcare - with medical decisions, practices, and/or products being tailored to the individual patient. This talk examines how this has evolved in the field of oncology, to maximise benefits to our patients and minimise toxicity, being able to predict in advance who our therapies will work for.
Bevan R, Patnick J, Loke R, et al., 2014, DELIVERY OF BOWELSCOPE SCREENING - EXPERIENCE FROM THE PILOT SITES, GUT, Vol: 63, Pages: A147-A148, ISSN: 0017-5749
Gall TMH, Jacob J, Frampton AE, et al., 2014, Reduced dissemination of circulating tumor cells with no-touch isolation surgical technique in patients with pancreatic cancer, JAMA Surgery, Vol: 149, Pages: 482-485, ISSN: 2168-6254
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