Dec 1, 2016
XPO1 inhibitor combination therapy with bortezomib or carfilzomib induces nuclear localization of IκBα and overcomes acquired proteasome inhibitor resistance in human multiple myeloma
J. G. Turner, T. Kashyap, J. L. Dawson, J. Gomez, A. A. Bauer, S. Grant, Y. Dai, K. H. Shain, M. Meads, Y. Landesman, D. M. Sullivan , Oncotarget , DOI: 10.18632/oncotarget.12969
Acquired proteasome-inhibitor (PI) resistance is a major obstacle in the treatment of multiple myeloma (MM). We investigated whether the clinical XPO1-inhibitor selinexor, when combined with bortezomib or carfilzomib, could overcome acquired resistance in MM. PI-resistant myeloma cell lines both in vitro and in vivo and refractory myeloma patient biopsies were...
Nov 29, 2016
Chemokine Levels in the Penile Coronal Sulcus Correlate with HIV-1 Acquisition and Are Reduced by Male Circumcision in Rakai, Uganda
J. L. Prodger, R. H. Gray, B. Shannon, K. Shahabi, X. Kong, K. Grabowski, G. Kigozi, F. Nalugoda, D. Serwadda, M. J. Wawer, S. J. Reynolds, C. M. Liu, A. A. R. Tobian, R. Kaul , PLoS pathogens , DOI: 10.1371/journal.ppat.1006025
Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology...
Nov 18, 2016
Infrequent mismatch repair protein loss in gallbladder cancer patients in Japan
H. Yoshida, K. Shimada, N. Hiraoka , Virchows Archiv , DOI: 10.1007/s00428-016-2043-5
Gallbladder cancer (GBC) represents a rare malignancy worldwide. Its prognosis is poor, and in Chile and East Asia, including Japan and China, a relative increase in the incidence of GBC has been observed . The development of new therapies is required for the treatment of this aggressive and intractable type...
Nov 17, 2016
Generation of metastatic melanoma specific antibodies by affinity purification
B. Schütz, A. Koppensteiner, D. Schörghofer, K. Kinslechner, G. Timelthaler, R. Eferl, M. Hengstschläger, A. Missbichler, H. Hundsberger & M. Mikula , Scientific Reports , doi:10.1038/srep37253
Melanoma is the most aggressive type of skin cancer and one of the most frequent tumours in young adults. Identification of primary tumours prone to develop metastasis is of paramount importance for further patient stratification. However, till today, no markers exist that are routinely used to predict melanoma progression. To...
Nov 17, 2016
Activity-Based Protein Profiling Shows Heterogeneous Signaling Adaptations to BRAF Inhibition
R. Sharma, I. Fedorenko, P. T. Spence, V. K. Sondak, K. S. M. Smalley, J. M. Koomen , Journal of Proteome Research , DOI: 10.1021/acs.jproteome.6b00613
Patients with BRAF V600E mutant melanoma are typically treated with targeted BRAF kinase inhibitors, such as vemurafenib and dabrafenib. Although these drugs are initially effective, they are not curative. Most of the focus to date has been upon genetic mechanisms of acquired resistance; therefore, we must better understand the global...