Publications
297 results found
Freyer G, You B, Harvey R, et al., 2011, Validation of the predictive value of modeled hCG decline profiles in low-risk gestational trophoblastic neoplasia (GTN) treated with methotrexate (MTX)., JOURNAL OF CLINICAL ONCOLOGY, Vol: 29, ISSN: 0732-183X
Carmo CR, Lyons-Lewis J, Seckl MJ, et al., 2011, A Novel Requirement for Janus Kinases as Mediators of Drug Resistance Induced by Fibroblast Growth Factor-2 in Human Cancer Cells, PLOS ONE, Vol: 6, ISSN: 1932-6203
The development of resistance to chemotherapy is a major cause of cancer-related death. Elucidating the mechanisms of drug resistance should thus lead to novel therapeutic strategies. Fibroblast growth factor (FGF)-2 signaling induces the assembly of a multi-protein complex that provides tumor cells with the molecular machinery necessary for drug resistance. This complex, which involves protein kinase C (PKC) ε, v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) and p70 S6 kinase β (S6K2), enhances the selective translation of anti-apoptotic proteins such as B-cell leukaemia/lymphoma-2 (BCL-2) and inhibitors of apoptosis protein (IAP) family members and these are able to protect multiple cancer cell types from chemotherapy-induced cell death. The Janus kinases (JAKs) are most noted for their critical roles in mediating cytokine signaling and immune responses. Here, we show that JAKs have novel functions that support their consideration as new targets in therapies aimed at reducing drug resistance. As an example, we show that the Janus kinase TYK2 is phosphorylated downstream of FGF-2 signaling and required for the full phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Moreover, TYK2 is necessary for the induction of key anti-apoptotic proteins, such as BCL-2 and myeloid cell leukemia sequence (MCL) 1, and for the promotion of cell survival upon FGF-2. Silencing JAK1, JAK2 or TYK2 using RNA interference (RNAi) inhibits FGF2-mediated proliferation and results in the sensitization of tumor cells to chemotherapy-induced killing. These effects are independent of activation of signal transducer and activator of transcription (STAT) 1, STAT3 and STAT5A/B, the normal targets of JAK signaling. Instead, TYK2 associates with the other kinases previously implicated in FGF-2-mediated drug resistance. In light of these findings we hypothesize that TYK2 and other JAKs are important modulators of FGF-2-driven cell survival and that inhibitors of t
Costa-Pereira AP, Bonito NA, Seckl MJ, 2011, Dysregulation of janus kinases and signal transducers and activators of transcription in cancer, AMERICAN JOURNAL OF CANCER RESEARCH, Vol: 1, Pages: 806-816, ISSN: 2156-6976
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- Citations: 18
White S, Harvey R, Mitchell H, et al., 2011, Characterisation of transient benign hCG elevations in women following chemotherapy for GTT, JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 31, Pages: 169-172, ISSN: 0144-3615
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- Citations: 1
Turner NC, Seckl MJ, 2010, A Therapeutic Target for Smoking-Associated Lung Cancer, SCIENCE TRANSLATIONAL MEDICINE, Vol: 2, ISSN: 1946-6234
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- Citations: 17
Alifrangis C, Seckl MJ, 2010, Genetics of gestational trophoblastic neoplasia: an update for the clinician, FUTURE ONCOLOGY, Vol: 6, Pages: 1915-1923, ISSN: 1479-6694
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- Citations: 9
do Carmo CR, Lyons-Lewis J, Seckl MJ, et al., 2010, A novel requirement for the Janus kinase TYK2 as a mediator of drug resistance induced by fibroblast growth factor-2 in cancer cells, 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Research, Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: 74-74, ISSN: 1043-4666
Gately KA, Dhillon T, Mauri F, et al., 2010, OVEREXPRESSION OF MTOR A NOVEL MARKER FOR POOR SURVIVAL IN EARLY STAGE NSCLC: A VALIDATION STUDY, 35th European-Society-for-Medical-Oncology (ESMO) Congress, Publisher: OXFORD UNIV PRESS, Pages: 71-72, ISSN: 0923-7534
Seckl MJ, Sebire NJ, Berkowitz RS, 2010, Gestational trophoblastic disease, LANCET, Vol: 376, Pages: 717-729, ISSN: 0140-6736
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- Citations: 563
Harvey RA, Mitchell HDC, Stenman U-H, et al., 2010, Differences in Total Human Chorionic Gonadotropin Immunoassay Analytical Specificity and Ability to Measure Human Chorionic Gonadotropin in Gestational Trophoblastic Disease and Germ Cell Tumors, JOURNAL OF REPRODUCTIVE MEDICINE, Vol: 55, Pages: 285-295, ISSN: 0024-7758
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- Citations: 28
Savage P, Williams J, Wong S-L, et al., 2010, The Demographics of Molar Pregnancies in England and Wales from 2000-2009, JOURNAL OF REPRODUCTIVE MEDICINE, Vol: 55, Pages: 341-345, ISSN: 0024-7758
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- Citations: 49
Rakha S, Bayliss C, Sanderson F, et al., 2010, Pituitary hCG production and cerebral tuberculosis mimicking disease progression during chemotherapy for an advanced ovarian germ cell tumour, BMC CANCER, Vol: 10, ISSN: 1471-2407
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- Citations: 2
Rupniewska E, Watling D, Mauri FA, et al., 2010, Src family kinases in lung cancer, 21st Meeting of the European-Association-for-Cancer-Research, Publisher: Elsevier, Pages: 95-95, ISSN: 1878-1217
Seckl MJ, Savage PM, Hancock BW, et al., 2010, "Hyperglycosylated hCG in the management of quiescent and chemorefractory gestational trophoblastic diseases", GYNECOLOGIC ONCOLOGY, Vol: 117, Pages: 505-506, ISSN: 0090-8258
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- Citations: 4
Wojtalla A, Fischer B, Mauri FA, et al., 2010, Targeting phosphoinositide 3-kinase signalling in small cell lung cancer, 21st Meeting of the European-Association-for-Cancer-Research, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 92-92, ISSN: 1359-6349
Goh ETH, Pardo OE, Michael N, et al., 2010, Involvement of Heterogeneous Ribonucleoprotein F in the Regulation of Cell Proliferation via the Mammalian Target of Rapamycin/S6 Kinase 2 Pathway, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 285, Pages: 17065-17076
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- Citations: 42
Sebire NJ, Seckl MJ, 2010, Immunohistochemical Staining for Diagnosis and Prognostic Assessment of Hydatidiform Moles <i>Current Evidence and Future Directions</i>, 15th World Congress on Gestational Trophoblastic Diseases, Publisher: SCI PRINTERS & PUBL INC, Pages: 236-246, ISSN: 0024-7758
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- Citations: 11
Dhillon T, Seckl M, Mauri F, et al., 2010, OVER-EXPRESSION OF THE MAMMALIAN TARGET OF RAPAMYCIN (MTOR): A NOVEL BIOMARKER FOR POOR SURVIVAL IN RESECTED EARLY STAGE NON-SMALL CELL LUNG CANCER, JOURNAL OF THORACIC ONCOLOGY, Vol: 5, Pages: S70-S70, ISSN: 1556-0864
McGrath S, Short D, Harvey R, et al., 2010, The management and outcome of women with post-hydatidiform mole 'low-risk' gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l<SUP>-1</SUP>, BRITISH JOURNAL OF CANCER, Vol: 102, Pages: 810-814, ISSN: 0007-0920
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- Citations: 62
Dhillon T, Mauri FA, Bellezza G, et al., 2010, Overexpression of the Mammalian Target of Rapamycin <i>A Novel Biomarker for Poor Survival in Resected Early Stage Non-small Cell Lung Cancer</i>, JOURNAL OF THORACIC ONCOLOGY, Vol: 5, Pages: 314-319, ISSN: 1556-0864
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- Citations: 42
Murphy SM, Khan U, Alifrangis C, et al., 2010, Anti-MA2 associated paraneoplastic myelo-radiculopathy, United Kingdom Neuromuscular Translational Research Conference 2010, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: S20-S20, ISSN: 0960-8966
Pardo OE, Latigo J, Jeffery RE, et al., 2009, The Fibroblast Growth Factor Receptor Inhibitor PD173074 Blocks Small Cell Lung Cancer Growth <i>In vitro</i> and <i>In vivo</i>, CANCER RESEARCH, Vol: 69, Pages: 8645-8651, ISSN: 0008-5472
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- Citations: 138
do Carmo CR, Seckl MJ, Costa-Pereira AP, 2009, A role for janus kinases in chemoresistance, Tri-Society Annual Conference of the International-Cytokine-Society/International-Society-of-Interferon-and-Cytokine-Research/Society-of-Leukocyte-Biology, Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Pages: 126-126, ISSN: 1043-4666
Seckl M, Pardo OE, Lara R, et al., 2009, RNAi library screen reveals RSK1 as a key regulator of lung cancer metastasis, JOURNAL OF THORACIC ONCOLOGY, Vol: 4, Pages: S559-S560, ISSN: 1556-0864
Seckl MJ, Pardo OE, Aboagye EO, et al., 2009, The FGF receptor (FGFR) inhibitor PD0173074 blocks SCLC growth in vitro and in vivo, JOURNAL OF THORACIC ONCOLOGY, Vol: 4, Pages: S385-S385, ISSN: 1556-0864
Wang CM, Dixon PH, Decordova S, et al., 2009, Identification of 13 novel <i>NLRP7</i> mutations in 20 families with recurrent hydatidiform mole; missense mutations cluster in the leucine-rich region, JOURNAL OF MEDICAL GENETICS, Vol: 46, Pages: 569-575, ISSN: 0022-2593
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- Citations: 110
Sebire NJ, Lindsay I, Fisher RA, et al., 2009, Intraplacental choriocarcinoma: Experience from a tertiary referral center and relationship with infantile choriocarcinoma, FETAL AND PEDIATRIC PATHOLOGY, Vol: 24, Pages: 21-29, ISSN: 1551-3815
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- Citations: 39
Schmid P, Nagai Y, Agarwal R, et al., 2009, Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study, LANCET, Vol: 374, Pages: 48-55, ISSN: 0140-6736
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- Citations: 157
Newsom-Davis T, Poulter D, Gray R, et al., 2009, Case report: Malignant teratoma of the uterine corpus, BMC CANCER, Vol: 9, ISSN: 1471-2407
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- Citations: 18
Kerkmeijer LG, Thomas CM, Harvey R, et al., 2009, External validation of serum hCG cutoff levels for prediction of resistance to single-agent chemotherapy in patients with persistent trophoblastic disease, BRITISH JOURNAL OF CANCER, Vol: 100, Pages: 979-984, ISSN: 0007-0920
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- Citations: 14
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