Chest wall resection effective for recurrent mesothelioma

Salvage chest wall resection could lengthen survival in patients with isolated chest wall recurrence of malignant pleural mesothelioma, research indicates.

via Med Wire News

Erlotinib ‘dose-to-rash’ strategy effective in advanced NSCLC

Erlotinib as first-line therapy in patients with advanced non-small-cell lung cancer is equivalent to chemotherapy with regard to overall survival, an “all-comers” phase II trial has shown.

via Med Wire News

Establishment of a bortezomib-resistant Chinese human multiple myeloma cell line: MMLAL

Background: A new human myeloma cell line, MMLAL, was established from the myelomatous pleural effusion of a 73-year-old Chinese patient suffering from symptomatic International stage III IgG/lambda myeloma. After a brief period of complete remission, he developed aggressive systemic relapse complicated by malignant pleural effusion with exclusive plasma cell infiltration. His disease remained chemo-refractory, and died six months after relapse. Methods: Purified mononuclear cells from the pleural effusion of the patient were cultured in the presence of IL-6. Continually growing cells were characterized by morphological, immunophenotypic, cytogenetic, fluorescence in situ hybridization (FISH) and TP53 mutation analyses. Cell proliferation was measured and compared with other myeloma cell lines by cell counting at day 3, 6, 9, and 12. Drug resistance against bortezomib, a proteasome inhibitor approved as a frontline chemotherapy for eligible myeloma patients, was evaluated and compared with other myeloma cell lines by MTT assay. Results: Immunophenotypic analysis of the myeloma cells confirmed strong expression of plasma cell markers CD38 and CD138 but not T-cell or natural killer-cell marker CD56. Cytogenetic analysis of the myeloma cells showed a hypodiploid composite karyotype including loss of chromosome 13 and 17 or deletion of the short arm of chromosome 17, i.e. del(17p), in the form of isochromosome 17q10. FISH confirmed a hypodiploid karyotype with TP53 deletion but absence of t(4;14). Sequencing analysis of the TP53 gene indicated absence of mutation. Cell counting revealed that the maximum viable cell density was about 2.5 X 106 cells/ml. Upon bortezomib treatment, MTT assay reported an IC50 of 72.17nM, suggesting a strong bortezomib resistance. Conclusion: A hypodiploid with loss of chromosome 13 and loss or del(17p) human myeloma cell line, MMLAL, was established from the pleural effusion of a Chinese myeloma patient.

via Cancer Cell International

Cetuximab fails in second-line combination for recurrent NSCLC

Results from a phase III trial indicate that cetuximab should not be given alongside chemotherapy in patients with recurrent non-small-cell lung cancer after platinum-based therapy.

via Med Wire News

Low sodium levels linked to poor targeted therapy outcomes in RCC

Low serum sodium levels in patients receiving targeted therapy for metastatic renal cell carcinoma (mRCC) may signal a poor outcome, study findings indicate.

via Med Wire News

Early tumor shrinkage predicts targeted therapy efficacy in RCC

Early tumor shrinkage in patients with metastatic renal cell carcinoma following vascular endothelial growth factor-targeted therapy may herald good long-term survival, research shows.

via Med Wire News

Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines

Background: MET is a receptor tyrosine kinase that is activated by the ligand HGF and this pathway promotes cell survival, migration, and motility. In accordance with its oncogenic role, MET is constitutively active, mutated, or over-expressed in many cancers. Corollary to its impact, inhibition of MET kinase activity causes reduction of the downstream signaling and demise of cells. In myeloma, a B-cell plasma malignancy, MET is neither mutated nor over-expressed, however, HGF is increased in plasma or serum obtained from myeloma patients and this was associated with poor prognosis. The small-molecule, amuvatinib, inhibits MET receptor tyrosine kinase. Based on this background, we hypothesized that targeting the HGF/MET signaling pathway is a rational approach to myeloma therapy and that myeloma cells would be sensitive to amuvatinib. Methods: Expression of MET and HGF mRNAs in normal versus malignant plasma cells was compared during disease progression. Cell death and growth as well as MET signaling pathway were assessed in amuvatinib treated primary myeloma cells and cell lines. Results: There was a progressive increase in the transcript levels of HGF (but not MET) from normal plasma cells to refractory malignant plasma cells. Amuvatinib readily inhibited MET phosphorylation in primary CD138+ cells from myeloma patients and in concordance, increased cell death. A 48-hr amuvatinib treatment in high HGF-expressing myeloma cell line, U266, resulted in growth inhibition. Levels of cytotoxicity were time-dependent; at 24, 48, and 72 h, amuvatinib (25 muM) resulted in 28%, 40%, and 55% cell death. Consistent with these data, there was an amuvatinib-mediated decrease in MET phosphorylation in the cell line. Amuvatinib at concentrations of 5, 10, or 25 muM readily inhibited HGF-dependent MET, AKT, ERK and GSK-3-beta phosphorylation. MET-mediated effects were not observed in myeloma cell line that has low MET and/or HGF expression. Conclusions: These data suggest that at the cellular level MET/HGF pathway inclines with myeloma disease progression. Amuvatinib, a small molecule MET kinase inhibitor, is effective in inducing growth inhibition and cell death in myeloma cell lines as well as primary malignant plasma cells. These cytostatic and cytotoxic effects were associated with an impact on MET/HGF pathway.

via Journal of Hematology & Oncology