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1.  Six cases of aggressive natural killer-cell leukemia in a Chinese population 
Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy that is particularly common among the Asian population. In the current study, we retrospectively evaluated six Chinese ANKL patients, including five males and one female, with a median age of 42 years (range 22 to 50 years). A number of unusual pathogenic manifestations were found in these ANKL patients, such as isolated extraocular muscle involvement, and hemophagocytic syndrome (HPS) with acute renal failure and multiple cavity effusion. Four of the patients died between two and six months after the diagnosis; however, there were two ANKL cases whose clinical behavior differed from the typical clinical course. One survived for over 30 months after splenectomy and chemotherapy treatment, and another ANKL case derived from chronic lymphoproliferative disorders of NK-cells (CLPD-NK) was treated with allogeneic bone marrow transplant (allo-BMT) and survived over 18 months. In conclusion, four cases experienced an aggressive clinical course whereas two demonstrated an indolent manifestation of their disease. New therapeutic regimens including allo-BMT should be optimized in order to improve outcomes of this disease.
PMCID: PMC4097262  PMID: 25031771
Aggressive NK-cell leukemia; lymphoproliferative disorders of NK-cells; hemophagocytic syndrome; retrospective study
2.  Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation 
Dysregulated microRNA (miRNA) expression contributes to cancer cell proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple myeloma (MM) development and progression. Argonaute 2 (AGO2) protein, a core component of the RNA-induced silencing complex (RISC), can directly bind to miRNAs and mediate target messenger RNA (mRNA) degradation. A previous study showed that AGO2 knockdown suppressed human umbilical vein endothelial cell (HUVEC) growth and tube formation. However, the roles and molecular mechanisms of AGO2-induced myeloma angiogenesis are not yet fully understood. The aim of this study was to characterize these roles and effects and their associated mechanisms.
Supernatants from AGO2-overexpressing MM lines induced HUVEC migration and accelerated tube formation. Conversely, supernatants from AGO2-knockdown MM lines suppressed HUVEC cell migration and tube formation. Moreover, a chick chorioallantoic membrane (CAM) assay was used to demonstrate that AGO2 could drive neovessel formation in MM lines in vivo. Using an miRNA microarray, we observed that 25 miRNAs were upregulated and 7 were downregulated in response to AGO2. Most let-7 family members and 2 miR-17/92 cluster members (miR-17a and miR-92-1), all known pro-angiogenic miRNAs, were positively regulated by AGO2 whereas anti-angiogenic miRNAs such as miR-145 and miR-361 were negatively regulated by AGO2.
We conclude that AGO2 can drive neovessel formation in vitro and in vivo by dysregulating the expression of some angiogenic miRNAs. The pro-angiogenic miRNAs of the let-7 family and the miR-17/92 cluster, along with the anti-angiogenic miRNA miR-145, play crucial roles in AGO2-mediated angiogenesis by targeting angiogenesis-related genes.
PMCID: PMC4108130  PMID: 24886719
Argonaute 2; microRNA; let-7 family; miR-17/92 cluster; miR-145; Myeloma; Angiogenesis
3.  Gambogic acid induces mitochondria-dependent apoptosis by modulation of Bcl-2 and Bax in mantle cell lymphoma JeKo-1 cells 
To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro.
The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apoptosis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting.
GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo-1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bcl-2 and Bax without cell cycle arresting.
GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle.
PMCID: PMC3626980  PMID: 23592899
Gambogic acid; JeKo-1 cells; cell cycle arrest, apoptosis; membrane potential of mitochondria; caspase-3; caspase-8; caspase-9; Bax; Bcl-2
4.  Correction: High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation as a First-Line Therapy for High-Risk Primary Breast Cancer: A Meta-Analysis 
PLoS ONE  2012;7(11):10.1371/annotation/928a7cff-1ae7-4ce5-908c-f765ea53663f.
PMCID: PMC3553191
5.  High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation as a First-Line Therapy for High-Risk Primary Breast Cancer: A Meta-Analysis 
PLoS ONE  2012;7(3):e33388.
Background and Objectives
Several trials have generated conflicting results about the results of high-dose chemotherapy followed by autologous stem cell transplantation (HDCT) for primary breast cancer. This meta-analysis summarizes the available evidence from all suitable studies.
Design and Methods
Prospective, randomized trials with HDCT as a first-line therapy for primary breast cancer were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival and overall survival); secondary endpoints included treatment-related mortality (TRM) and second (non-breast) cancers. We used a median age of 47, a PR positive rate of 50% and a premenopausal rate of 70% as cutoff values to complete the subgroup analyses, which were pre-planned according to the prepared protocol.
Fourteen trials with 5747 patients were eligible for the meta-analysis. Compared with non-HDCT, non-significant second (non-breast) cancers (RR = 1.28; 95% CI = 0.82–1.98) and higher TRM (RR = 3.42; 95% CI = 1.32–8.86) were associated with HDCT for primary breast cancer. A significant DFS benefit of HDCT was documented (HR = 0.89; 95% CI = 0.79–0.99). No difference in OS (overall survival) was found when the studies were pooled (HR = 0.91; 95% CI = 0.82–1.00, p = 0.062). In subgroup analysis, age and hormone receptor status had a significant interaction with prolonged DFS and OS.
HDCT has a benefit on DFS and OS compared to SDC in some special patients with high-risk primary breast cancer.
PMCID: PMC3299795  PMID: 22428041

Results 1-5 (5)