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1.  Partial Response at Completion of Bortezomib-Thalidomide-Dexamethasone (VTd) Induction Regimen Upfront in Multiple Myeloma Does Not Preclude Response to VTd in Consolidation 
Journal of Cancer  2014;5(3):248-252.
The impact of consolidation on response rates and PFS has recently been demonstrated after induction and autotransplantation upfront in Multiple Myeloma (MM). We further showed that patients in ≥VGPR following the intensification procedure benefited most from consolidation. Question remains as to the benefit of consolidation for patients in PR at completion of induction - feature of partial resistance to the induction regimen.
We collected data from 54 newly diagnosed MM treated with VTd-auto-VTd regimen that reached only PR at completion of the induction procedure.
Overall, 37 patients (68%) improved depth of response (≥VGPR) at completion of consolidation, including 35% that reached CR and 38% solely related to consolidation. Of patients that remained on PR or improved depth of response after ASCT, 26% and 38% further responded to consolidation, respectively. With a median follow-up of 36 months, improved depth of response translated into lower relapse rate compared with patients remaining in PR, 19% vs. 36%. This difference was more striking in patients that reached CR vs. others, 8% and 38%, respectively (p=0.039). The median TTP was prolonged in patients that improved depth of response after consolidation (p=0.012), with a 3-year TTP of 87% vs. 18% otherwise. In multivariate analysis, lack of improved depth of response to consolidation independently predicted shorten median TTP [OR=4.4, 95%CI=1-21; p=0.039], with elevated LDH and beta2m, and adverse FISH.
This study shows that VTd consolidation should be recommended to patients solely on PR at completion of induction with VTd, feature of lower sensitivity to VTd.
doi:10.7150/jca.8541
PMCID: PMC3963082  PMID: 24665349
Consolidation; Partial response; Multiple Myeloma.
2.  A Prospective Study of Bone Marrow Hematopoietic and Mesenchymal Stem Cells in Type 1 Gaucher Disease Patients 
PLoS ONE  2013;8(7):e69293.
Gaucher disease (GD) is an autosomal recessive disorder characterized by lysosomal glucocerebrosidase (GBA) deficiency leading to hematological and skeletal manifestations. Mechanisms underlying these symptoms have not yet been elucidated. In vivo, bone marrow (BM) mesenchymal stem cells (MSCs) have important role in the regulation of bone mass and in the support of hematopoiesis, thus representing potential candidate that could contribute to the disease. GBA deficiency may also directly impair hematopoietic stem/progenitors cells (HSPCs) intrinsic function and induce hematological defect. In order to evaluate the role of BM stem cells in GD pathophysiology, we prospectively analyzed BM-MSCs and HSPCs properties in a series of 10 patients with type 1 GD. GBA activity was decreased in all tested cell subtypes. GD-MSCs had an impaired growth potential, morphological and cell cycle abnormalities, decreased capacities to differentiate into osteoblasts. Moreover, GD-MSCs secreted soluble factors that stimulated osteoclasts resorbing activities. In vitro and in vivo primitive and mature hematopoiesis were similar between patients and controls. However, GD-MSCs had a lower hematopoietic supportive capacity than those from healthy donors. These data suggest that BM microenvironment is altered in GD and that MSCs are key components of the manifestations observed in GD.
doi:10.1371/journal.pone.0069293
PMCID: PMC3723887  PMID: 23935976
3.  Vasculitic emergencies in the intensive care unit: a special focus on cryoglobulinemic vasculitis 
Vasculitis is characterized by the infiltration of vessel walls by inflammatory leukocytes with reactive damage and subsequent loss of vessel integrity. The clinical course of systemic vasculitis may be punctuated by acute life-threatening manifestations that require intensive care unit (ICU) admission. Furthermore, the diagnosis may be established in the ICU after admission for a severe inaugural symptom, mostly acute respiratory failure. Among the systemic vasculitides, cryoglobulinemic vasculitis (CV) has been rarely studied in an ICU setting. Severe CV-related complications may involve the kidneys, lungs, heart, gut, and/or central nervous system. The diagnosis of CV in the ICU may be delayed or completely unrecognized. A high level of suspicion is critical to obtain a timely and accurate diagnosis and to initiate appropriate treatment. We describe severe acute manifestations of CV based on six selected patients admitted to our ICU. That all six patients survived suggests the benefit of prompt ICU admission of patients with severe CV.
doi:10.1186/2110-5820-2-31
PMCID: PMC3488028  PMID: 22812447
Cryoglobulinemia; Cryoglobulinemic vasculitis; Acute respiratory failure; Acute kidney injury; Vasculitis; Systemic disease
5.  Neuropilin-1 Is Involved in Human T-Cell Lymphotropic Virus Type 1 Entry 
Journal of Virology  2006;80(14):6844-6854.
Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral synapse and enters target cells via interaction with the glucose transporter GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and VEGF-A165 and a member of the immune synapse, is also a physical and functional partner of HTLV-1 envelope (Env) proteins. HTLV-1 Env and NRP1 complexes are formed in cotransfected cells, and endogenous NRP1 contributes to the binding of HTLV-1 Env to target cells. NRP1 overexpression increases HTLV-1 Env-dependent syncytium formation. Moreover, overexpression of NRP1 increases both HTLV-1 and HTLV-2 Env-dependent infection, whereas down-regulation of endogenous NRP1 has the opposite effect. Finally, overexpressed GLUT1, NRP1, and Env form ternary complexes in transfected cells, and endogenous NRP1 and GLUT1 colocalize in membrane junctions formed between uninfected and HTLV-1-infected T cells. These data show that NRP1 is involved in HTLV-1 and HTLV-2 entry, suggesting that the HTLV receptor has a multicomponent nature.
doi:10.1128/JVI.02719-05
PMCID: PMC1489069  PMID: 16809290

Results 1-5 (5)