St Bartholomew's Hospital

About: St Bartholomew's Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 11054 authors who have published 13229 publications receiving 501102 citations. The organization is also known as: St. Bartholomew's Hospital & The Royal Hospital of St Bartholomew.

Diagnosis of acute promyelocytic leukaemia by RT‐PCR: detection of PML‐RARA and RARA‐PML fusion transcripts

Abstract: Acute promyelocytic leukaemia (APL; AML M3) is identified by a unique t(15;17) translocation which fuses the PML gene to the retinoic acid receptor alpha gene (RARA). Reverse transcription coupled with the polymerase chain reaction (RT-PCR) has been used to develop a diagnostic test for APL based on the PML-RARA fusion message. Separate PCR assays were designed to amplify either PML-RARA (15q+ derived) or RARA-PML (17q- derived) chimaeric transcripts. PML-RARA transcripts were detected in every case from a series of 18 APL patients with cytogenetically confirmed t(15;17) translocations, whereas RARA-PML messages were detected in only 67% (12/18) of these patients. This suggests that it is the 15q+ derivative which mediates leukaemogenesis. Furthermore the PCR approach (or Southern analysis) may be used to identify in which of the alternative PML introns the breakpoint occurs; 52% of cases (15/29 patients) utilize a 5' PML intron and 48% the 3' intron (14/29 cases). Neither the choice of PML intron nor the expression of the 17q- derivative could be correlated with the microgranular variant of APL (M3V), overall survival rate, age, sex or presence of coagulopathy. Finally, the fusion message is undetectable in five remission samples. This indicates a possible use for RT-PCR in monitoring remission patients for evidence of relapse.

A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma.

Abstract: Bagnara, D., Kaufman, M.S., Calissano, C., Marsilio, S., Patten, P.E., Simone, R., Chum, P., Yan, X.J., Allen, S.L., Kolitz, J.E., Baskar, S., Rader, C., Mellstedt, H., Rabbani, H., Lee, A., Gregersen, P.K., Rai, K.R. & Chiorazzi, N. (2011) A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease. Blood, 117, 5463–5472. Brachtl, G., Sahakyan, K., Denk, U., Girbl, T., Alinger, B., Hofbauer, S.W., Neureiter, D., Hofbauer, J.P., Egle, A., Greil, R. & Hartmann, T.N. (2011) Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. PLoS ONE, 6, e23758. Burger, J.A., Ghia, P., Rosenwald, A. & CaligarisCappio, F. (2009) The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood, 114, 3367–3375. Hallaert, D.Y., Jaspers, A., van Noesel, C.J., van Oers, M.H., Kater, A.P. & Eldering, E. (2008) c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches. Blood, 112, 5141–5149. Hamilton, E., Pearce, L., Morgan, L., Robinson, S., Ware, V., Brennan, P., Thomas, N.S., Yallop, D., Devereux, S., Fegan, C., Buggins, A.G. & Pepper, C. (2012) Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells. British Journal of Haematology, 158, 589–599. Herishanu, Y., Perez-Galan, P., Liu, D., Biancotto, A., Pittaluga, S., Vire, B., Gibellini, F., Njuguna, N., Lee, E., Stennett, L., Raghavachari, N., Liu, P., McCoy, J.P., Raffeld, M., Stetler-Stevenson, M., Yuan, C., Sherry, R., Arthur, D.C., Maric, I., White, T., Marti, G.E., Munson, P., Wilson, W. H. & Wiestner, A. (2011) The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood, 117, 563–574. Hofbauer, J.P., Heyder, C., Denk, U., Kocher, T., Holler, C., Trapin, D., Asslaber, D., Tinhofer, I., Greil, R. & Egle, A. (2011) Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL. Leukemia, 25, 1452–1458. Messmer, B.T., Messmer, D., Allen, S.L., Kolitz, J. E., Kudalkar, P., Cesar, D., Murphy, E.J., Koduru, P., Ferrarini, M., Zupo, S., Cutrona, G., Damle, R.N., Wasil, T., Rai, K.R., Hellerstein, M.K. & Chiorazzi, N. (2005) In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest, 115, 755–764. Patten, P.E., Buggins, A.G., Richards, J., Wotherspoon, A., Salisbury, J., Mufti, G.J., Hamblin, T. J. & Devereux, S. (2008) CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment. Blood, 111, 5173–5181. Plander, M., Seegers, S., Ugocsai, P., DiermeierDaucher, S., Ivanyi, J., Schmitz, G., Hofstadter, F., Schwarz, S., Orso, E., Knuchel, R. & Brockhoff, G. (2009) Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles. Leukemia, 23, 2118–2128.

Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening

Abstract: Purpose Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. Patients and Methods In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. Results After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P .0027) higher than that for a single-threshold rule (0.869). Conclusion Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.