Gole L.,National University of Singapore |
Lin A.,National Cancer Institute of Singapore |
Chua C.,National University of Singapore |
Chng W.J.,National Cancer Institute of Singapore
Cancer Genetics | Year: 2014
The International Myeloma Working Group recommends that fluorescence in situ hybridization (FISH) be performed on specifically identified plasma cells (PC). This is because chromosomal abnormalities are not frequently detected by traditional karyotyping due to the low proliferative rate of PC in multiple myeloma (MM). Conventional FISH enhances the sensitivity but lacks the specificity, as it does not distinguish PC from other hematopoetic cells. To fulfill this recommendation, PC need to be selected either by flow cytometry or immunomagnetic bead-based PC sorting or by concomitant labeling of the cytoplasmic immunoglobulin light chain, which allows for unambiguous identification. These techniques require expertise, time, and funding and are not easily incorporated into the routine workflow of the cytogenetic laboratory. We have modified and refined the technique using fixed cell pellets to achieve nicely separated and easily identifiable PC. With immunostaining and subsequent FISH (i.e., cytoplasmic immunoglobulin FISH, cIg-FISH), this technique can be easily incorporated into every cytogenetic laboratory. Twenty samples from patients with MM were subjected to routine FISH, cIg-FISH, and chromosomal karyotyping and the results were compared. Three FISH probes, which enabled detection of the t(4;14), t(14;16) and deletion of TP53, were used to validate this modified technique successfully. © 2014 Elsevier Inc.
Ji X.-D.,CAS Shanghai Institutes for Biological Sciences |
Li G.,CAS Shanghai Institutes for Biological Sciences |
Feng Y.-X.,CAS Shanghai Institutes for Biological Sciences |
Zhao J.-S.,CAS Shanghai Institutes for Biological Sciences |
And 10 more authors.
Cancer Research | Year: 2011
Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attention. Until now, research on EphB3 function in cancer is limited to focusing on tumor suppression by EphB receptors in colorectal cancer. However, its function in other types of cancer remains poorly investigated. In this study, we explored the function of EphB3 in non-small-cell lung cancer (NSCLC). We found that the expression of EphB3 was significantly upregulated in clinical samples and cell lines, and the expression level correlated with the patient pathologic characteristics, including tumor size, differentiation, and metastasis. Overexpression of EphB3 in NSCLC cell lines accelerated cell growth and migration and promoted tumorigenicity in xenografts in a kinase-independent manner. In contrast, down-regulation of EphB3 inhibited cell proliferation and migration and suppressed in vivo tumor growth and metastasis. Furthermore, we showed that silencing of EphB3 inhibited cell growth by reducing DNA synthesis and caspase-8-mediated apoptosis and suppressed cell migration by increasing accumulation of focal adhesion formation. Taken together, our findings suggest that EphB3 provides critical support to the development and progression of NSCLC by stimulating cell growth, migration, and survival, thereby implicating EphB3 as a potential therapeutic target in NSCLC. ©2011 AACR.
PubMed | National University Hospital and National Cancer Institute of Singapore
Type: | Journal: Transfusion | Year: 2016
Despite advances in surgical techniques for spinal metastases, there is often substantial blood loss, resulting in patients requiring blood transfusion during the perioperative period. Allogeneic blood transfusion (ABT) has been the main replenishment method for lost blood. However, the impact of ABT on cancer-related outcomes has been controversial in various studies. We aimed to evaluate the influence of perioperative ABT on disease progression and survival in patients undergoing metastatic spinal tumor surgery (MSTS).We conducted a retrospective study that included 247 patients who underwent MSTS at a single tertiary institution between 2005 and 2014. The impact of using perioperative ABT (either exposure to or quantities of transfusion) on disease progression and survival was assessed using Cox regression analyses while adjusting for potential confounding variables.Of 247 patients, 133 (54%) received ABT. The overall median number of blood units transfused was 2 (range, 0-10 units). Neither blood transfusion exposure nor quantities of transfusion were associated with overall survival (hazard ratio [HR], 1.15 [p=0.35] and 1.10 [p=0.11], respectively) and progression-free survival (HR, 0.87 [p=0.18] and 0.98 [p=0.11], respectively). The factors that influenced overall survival were primary tumor type and preoperative Eastern Cooperative Oncology Group performance status, whereas primary tumor type was the only factor that had an impact on progression-free survival.This is the first study providing evidence that disease progression and survival in patients who undergo MSTS are less likely to be influenced by perioperative ABT. The worst oncologic outcomes are more likely to be caused by the clinical circumstances necessitating blood transfusion, but not transfusion itself. However, because ABT can have a propensity toward developing postoperative infections, including surgical site infection, the use of patient blood management interventions would be worthwhile rather than relying solely on ABTs for these patients, if and whenever possible.
Gueller S.,Goethe University Frankfurt |
Gueller S.,Cedars Sinai Medical Center |
Goodridge H.S.,Cedars Sinai Medical Center |
Niebuhr B.,University of Hamburg |
And 7 more authors.
Journal of Leukocyte Biology | Year: 2010
The M-CSFR (c-Fms) participates in proliferation, differentiation, and survival of macrophages and is involved in the regulation of distinct macrophage functions. Interaction with the ligand M-CSF results in phosphorylation of tyrosine residues on c-Fms, thereby creating binding sites for molecules containing SH2 domains. Lnk is a SH2 domain adaptor protein that negatively regulates hematopoietic cytokine receptors. Here, we show that Lnk binds to c-Fms. Biological and functional effects of this interaction were examined in macrophages from Lnk-deficient (KO) and WT mice. Clonogenic assays demonstrated an elevated number of M-CFUs in the bone marrow of Lnk KO mice. Furthermore, the M-CSF-induced phosphorylation of Akt in Lnk KO macrophages was increased and prolonged, whereas phosphorylation of Erk was diminished. Zymosan-stimulated production of ROS was increased dramatically in a M-CSF-dependent manner in Lnk KO macrophages. Lastly, Lnk inhibited M-CSF-induced migration of macrophages. In summary, we show that Lnk binds to c-Fms and can blunt M-CSF stimulation. Modulation of levels of Lnk in macrophages may provide a unique therapeutic approach to increase innate host defenses. © Society for Leukocyte Biology.
Chen W.,University of the Free State |
Chen W.,Cedars Sinai Medical Center |
Leiter A.,Cedars Sinai Medical Center |
Dong Y.,Cedars Sinai Medical Center |
And 4 more authors.
International Journal of Oncology | Year: 2010
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer with a substantial risk of metastasis which causes clinical treatment failure. This study investigated the anti-CSCC effects of a triterpenoid compound, Cucurbitacin B (CuB). Dose-response studies showed that CuB inhibited 50% growth (ED 50) of the CSCC cell lines (SRB1, SRB12, SCC13, COLO16) in liquid culture at 4×10 -7 -10 -5 M. Soft-agar assays demonstrated that nearly all of the CSCC clonogenic cells were inhibited at 10 -7 M CuB. FACS analysis found that the compound (10 -7 M, 48 h) caused G2/M arrest. The CSCC cells underwent profound morphologic changes within 60 min after exposure to CuB (10 -7 M), rounding up and losing their pseudopodia. CuB (10 -7 M) caused prominent multinucleation of the cells after they were pulse-exposed (24 h) to the drug, washed and cultured in normal medium for an additional 24 h. The drug (10 -8-10 -6 M, 3-24 h) decreased levels of CDC2 and cyclin B1 in SRB1 and SRB12 cell lines as seen by Western blot analysis. Migration of SRB1 and SRB12 cells was inhibited by 10 -7 M CuB. Interestingly, CuB synergistically potentiated the anti-proliferative effect of cisplatin in CSCC. In summary, CuB has a prominent anti-proliferative activity on CSCC cells. In vivo studies and clinical trials of this drug should be pursued in CSCC.
Koeffler H.P.,Cedars Sinai Medical Center |
Koeffler H.P.,National Cancer Institute of Singapore
Best Practice and Research: Clinical Haematology | Year: 2010
Differentiation therapy with all-trans retinoic acid has been a very successful therapeutic strategy in acute promyelocytic leukemia (APL), but the value of differentiation therapy in acute myeloid leukemia (AML) remains to be determined. A number of current treatments, such as tyrosine kinase inhibitors, cytokines, and epigenetic agents, induce differentiation of leukemic cells to some extent, but differentiation is not the main goal of these treatments. Forcing expression of certain transcription factors, such as C/EBP, has also been useful in inducing differentiation in cell lines and in murine models, but an effective way to force expression of these genes in humans is yet to be discovered. © 2010 Elsevier Ltd. All rights reserved.