Oncotarget
-
Cancer remains one of the major cause of death in the Western world. Although, it has been demonstrated that new therapies can improve the outcome of cancer patients, still many patients relapse after treatment. Therefore, there is a need to identify novel factors involved in cancer development and/or progression. ⋯ All metastatic tumors showed a decrease of NGAL expression when compared to matched primary lesions. According to these results, NGAL is a candidate marker for tumor growth in a fraction of solid tumors. Further investigations are required to elucidate the function of NGAL in tumor development and metastatic processes.
-
Multiple Myeloma (MM) is an incurable malignant plasma cell disorder. We have evaluated the counts of Multiple Myeloma Cells (MMCs) and normal plasma cells (N-PCs), seven days after high-dose melphalan (HDM) and autologous stem transplantation (ASCT). Two third of patients had detectable minimal residual disease (MRD+) (71.7 MMCs/µL) after induction treatment with dexamethasone and proteasome inhibitor. ⋯ Major difference between MRD- and MRD+ patients is that N-PC counts were increased 3 fold (P〈.05) by HDM+ASCT in MRD- patients, but were unaffected in MRD+ patients. Possible explanation could be that clearance of MMCs in MRD- patients makes more niches available for N-PCs. Thus, MMCs are not fully eradicated shortly after HDM, are bathed in high concentrations of MMC growth factors in an almost desert BM, are viable in short-term culture, which suggests providing additional therapies shortly after HDM to kill resistant MMCs before full repair of lesions.
-
Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of multiple over-expressed signaling proteins that promote growth and survival in cancer cells. Chronic lymphocytic leukaemia (CLL) is characterized by increased expression of several Hsp90 client proteins making it a potentially susceptible to Hsp90 inhibition. In this study we showed that the novel Hsp90 inhibitor NVP-AUY922-AG was cytotoxic to primary CLL cells in vitro (LD50=0.18μM±0.20). ⋯ In keeping with this hypothesis, the combination of NVP-AUY922-AG and fludarabine was highly synergistic (mean CI=0.110.06) and this synergy was enhanced in co-culture (mean CI=0.06±0.08). Furthermore, the combination maintained the decrease in MCL1, CFLAR and BIRC5 transcription suggesting that the ability of NVP-AUY922-AG to modulate expression of these genes may contribute to the efficacy of this drug under cytoprotective co-culture conditions and for its remarkable synergy with fludarabine. Taken together these findings indicate that Hsp90 inhibition is an attractive therapeutic strategy in CLL.
-
Squamous cell cancer of the head and neck (SCCHN) is the sixth leading cause for cancer deaths worldwide. Despite extense knowledge of risk factors and pathogenesis about 50 percent of all patients and essentially every patient with metastatic SCCHN eventually die from this disease. We analyzed the clinical data and performed immunohistochemistry for Epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurora-A) expression in 180 SCCHN patients. ⋯ Comparing pan-Aurora kinase and Aurora-A targeting hints towards a strong and clinically relevant biological effect mediated via Aurora kinase B. Taken together, our findings characterize a new poor risk group in SCCHN patients defined by elevated EGFR and Aurora-A protein expression. Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN.