Ofer Shpilberg

Tel Aviv Sourasky Medical Center, Tell Afif, Tel Aviv, Israel

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Publications (222)1154.15 Total impact

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    ABSTRACT: Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cell carrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) of the BCR-ABL kinase are the treatment of choice for CML patients. Imatinib was the first TKI used in clinical practice with excellent results. MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. Aberrant miRNA expression profiles have been shown to be characteristic of many cancers. Here, we demonstrate that miR-30e is expressed at low levels in CML cell lines and patient samples. Bioinformatics analysis reveals a putative target site for miR-30e in the 3'-untranslated region (UTR) of the ABL gene. In agreement, luciferase assay verified that miR-30e directly targets ABL. Enforced expression of miR-30e in K562 cells suppressed proliferation and induced apoptosis of these cells and sensitized them to imatinib treatment. These findings strongly suggest that miR-30e acts as a tumor suppressor by down regulating BCR-ABL expression. Up-regulation of miR-30e in CML cells may therefore have a therapeutic efficacy against this disease.
    Cancer letters. 10/2014;
  • Annals of Oncology 09/2014; 25 Suppl 3:iii83-iii92. · 7.38 Impact Factor
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    ABSTRACT: Background. Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism (VTE). We performed a meta-analysis of all randomized controlled trials (RCTs) which evaluated low molecular weight heparin (LMWH) as primary prophylaxis in ambulatory patients with solid malignancies. Methods. A comprehensive search was conducted until October 2013. Primary outcome was symptomatic VTE. Secondary outcomes were pulmonary embolism (PE), any VTE, deep vein thrombosis (DVT), mortality and adverse events. Results. Eleven trials met the inclusion criteria, and evaluated a total of 6942 patients. Primary prophylaxis with LMWH reduced symptomatic VTE (RR 0.46, 95% CI 0.32-0.67) and the rate of PE (RR 0.49, 95% CI 0.29-0.84). In the subgroup analysis of VTE in patients with lung and pancreatic cancers LMWH further reduced VTE [RR 0.42 (95% CI 0.25-0.71); RR 0.31 (95% CI 0.18-0.55), respectively]. Meta-analysis of six trials which reported survival outcomes revealed no statistically significant benefit for LMWH in one-year mortality rates (RR 0.93, 95% CI 0.83-1.04). There was no significant increase in major bleeding events (RR 1.28, 95% CI 0.84-1.95). Conclusions. LMWH reduces the incidence of symptomatic VTE and PE in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. The benefit is most apparent in pancreatic cancer and also lung cancer. VTE prophylaxis should be considered for these specific populations.
    Acta oncologica (Stockholm, Sweden) 08/2014; · 2.27 Impact Factor
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    ABSTRACT: We hypothesized that in patients with early post allogeneic transplantation toxicities, the omission of the 3rd dose of methotrexate with concomitant starting of MMF would favorably affect complications. We found a higher incidence of grade 2-4 acute GVHD in patients given two doses methotrexate and MMF (n=31) compared to those given three courses of methotrexate (n=70) (p=.004), while grade 3-4 was similar. Other transplantation outcomes, including overall regimen-related-toxicity, were comparable. We conclude that tailoring the GVHD prophylaxis regimen may decrease the early post transplantation complications, however this come at the extent of a higher incidence of non-severe acute GVHD.
    Leukemia research. 06/2014;
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    ABSTRACT: As interleukin (IL)-6 is considered important in the proliferation of early multiple myeloma (MM), we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab (S) to the VMP (bortezomib-melphalan-prednisone) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM. One hundred and six patients were randomized to receive 9 cycles of VMP or VMP+siltuximab (11 mg/kg every 3 weeks) followed by siltuximab maintenance. Baseline characteristics were well balanced except for IgA subtype and 17p deletions. With a CR rate of 27% on S+VMP and 22% on VMP, the study did not confirm its hypothesis that the addition of siltuximab would increase CR rate by at least 10%. Overall response rate was 88% on S+VMP and 80% on VMP and at least VGPR rates were 71% and 51% (P=0.0382), respectively. Median progression-free survival (17 months) and 1-year overall survival (88%) were identical in the two arms. Grade ≥3 adverse event incidence was 92% on S+VMP and 81% on VMP (P=0.09) with trends towards more hematologic events and infections on S+VMP. Maintenance therapy with siltuximab was well tolerated. In conclusion, the addition of siltuximab to VMP did not improve CR rate nor long-term outcomes. This study was registered at http://clinicaltrials.gov as NCT00911859.
    Blood 05/2014; · 9.78 Impact Factor
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    ABSTRACT: This two-stage phase IB study investigated the pharmacokinetics and safety of subcutaneous (SC) versus intravenous (IV) administration of rituximab as maintenance therapy in follicular lymphoma. In stage 1 (dose finding), 124 patients who responded to rituximab induction were randomly assigned to SC rituximab (375 mg/m(2), 625 mg/m(2), or an additional group at 800 mg/m(2)) or IV rituximab (375 mg/m(2)). The objective was to determine an SC dose that would yield a rituximab serum trough concentration (Ctrough) in the same range as that of IV rituximab. In stage 2, 154 additional patients were randomly assigned (1:1) to SC rituximab (1,400 mg) or IV rituximab (375 mg/m(2)) given at 2- or 3-month intervals. The objective was to demonstrate noninferior rituximab Ctrough of SC rituximab relative to IV rituximab 375 mg/m(2). Stage 1 data predicted that a fixed dose of 1,400 mg SC rituximab would result in a serum Ctrough in the range of that of IV rituximab. Noninferiority (ie, meeting the prespecified 90% CI lower limit of 0.8) was then confirmed in stage 2, with geometric mean Ctrough SC:Ctrough IV ratios for the 2- and 3-month regimens of 1.24 (90% CI, 1.02 to 1.51) and 1.12 (90% CI, 0.86 to 1.45), respectively. Overall safety profiles were similar between formulations (in stage 2, 79% of patients experienced one or more adverse events in each group). Local administration-related reactions (mainly mild to moderate) occurred more frequently after SC administration. The fixed dose of 1,400 mg SC rituximab predicted by using stage 1 results was confirmed to have noninferior Ctrough levels relative to IV rituximab 375 mg/m(2) dosing during maintenance, with a comparable safety profile. Additional investigation will be required to determine whether the SC route of administration for rituximab provides equivalent efficacy compared with that of IV administration.
    Journal of Clinical Oncology 05/2014; · 18.04 Impact Factor
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    ABSTRACT: Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/µL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6–9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6–6.2), log-rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures. Am. J. Hematol. 89:243–248, 2014. © 2013 Wiley Periodicals, Inc.
    American Journal of Hematology 03/2014; 89(3). · 4.00 Impact Factor
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    ABSTRACT: Bone marrow (BM) trephine biopsy is a part of routine staging of patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The significance of lymphoid monoclonal population on flow cytometry (FC) of the BM aspirate in the presence of negative BM histology has not been clarified. In this study, we assessed the clinical role of positive FC in predicting outcome of patients with DLBCL and a negative BM histology. We retrospectively analysed 101 patients diagnosed with DLBCL at a single institution between years 1994-2003. Three groups of patients were compared: patients with histologic involvement of the BM (BM+), patients with no histologic involvement of the BM but with positive FC (BM-FC+) and patients with neither histologic or FC evidence of BM involvement (BM-FC-). The BM+ group included 13 patients (13%). The BM-FC+ group 16 patients (16%), and the BM-FC-included 72 patients (71%). Median age of the cohort was 67 years. Disease stage and International Prognostic Index score were significantly higher in the BM+ and BM-FC+ groups compared with the BM-FC- group. Median overall survival (OS) for the BM-FC-, BM-FC+ and BM + groups were 4.6, 2.2 and 0.9 years, respectively. Median progression free survival (PFS) for the BM-FC-, BM-FC+ and BM+ groups were 3.2, 1.4 and 0.6 years, respectively (p=0.01 for both analysis). In multivariable Cox regression models adjusting for age, sex, stage and International Prognostic Index, there was no significant differences in OS or PFS between the BM-FC+ and BM-FC- groups. In conclusion, positive FC in the setting of negative BM histology at diagnosis did not significantly affect OS or PFS. Copyright © 2014 John Wiley & Sons, Ltd.
    Hematological Oncology 01/2014; · 2.04 Impact Factor
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    ABSTRACT: Tumor relapse in scar tissue is uncommon in cancer patients. Likewise, extramedullary plasmacytoma (EMP) relapse in scar tissue in the setting of multiple myeloma (MM) has been rarely reported. We report a series of 3 patients whose disease progressed as EMP at the site of a wound from previous invasive procedures. All 3 patients were treated for the relapsed disease with different treatment modalities, but failed to respond adequately and died several months after relapse. At original MM diagnosis, all had advanced-stage disease. They were treated with novel agents with or without autologous hematopoietic stem cell transplantation and achieved either a complete or very good partial response. We suggest that these treatments, which have become the standard of care in MM, may permit a predominance of myeloma subclones which are independent of the bone marrow microenvironment. These myeloma subclones then gain a survival advantage in the active scar-tissue niche, allowing for their uncontrolled proliferation. This case series might represent an underreported phenomenon and therefore may indicate an emerging and difficult-to-treat disease in the era of targeted therapies in MM. Physicians treating MM should be aware of this phenomenon, especially when referring their patients for invasive procedures. © 2014 S. Karger AG, Basel.
    Acta Haematologica 01/2014; 132(1):39-44. · 0.89 Impact Factor
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    ABSTRACT: Total therapy 3 is an intensified protocol for multiple myeloma (MM). The “real life” outcomes of this protocol were seldom reported. Data was obtained for 81 patients (newly diagnosed, n = 49; progressive MM, n = 32), most of which had high risk parameters. Overall response rate following (V)DT-PACE was 96% and 75% for the newly diagnosed and progressive groups, respectively. Median progression-free survival was 42.5 and 9 months, respectively. The 2 year overall survival was 88% and 40%, respectively. Treatment with (V)DT-PACE achieves high response rate among patients with high-risk disease, which can be translated into long-term remission only for newly diagnosed patients.
    Leukemia Research. 01/2014;
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    ABSTRACT: Repeated imaging with positron emission tomography-computed tomography (PET-CT) is associated with cumulative exposure to substantial doses of radiation. Furthermore, PET-CT is an expensive and limited resource in many institutions. We conducted a retrospective analysis to evaluate whether limited PET-CT focused on the initially involved field of view (FOV) at diagnosis, corresponding to an above- or below-the-diaphragm scan, is sufficient for follow-up of patients with Hodgkin (HL) and aggressive non-Hodgkin lymphoma (NHL). One hundred thirty-one examinations of 44 patients with early-stage (I-II) HL (n = 27) and aggressive NHL (n = 17) who had PET-CT performed as part of their initial staging and at follow-up were analyzed. Regardless of the extent of response to treatment, there was no single case in which the disease progressed outside of the initially involved FOV (0/44, 95% CI 0-0.08). This was true even in cases of disease progression, including in the setting of relapse. Our findings suggest that limited PET-CT analysis of the initially involved FOV in patients with early-stage curable lymphoma may be satisfactory for response assessment. © 2013 S. Karger AG, Basel.
    Acta Haematologica 12/2013; 131(4):239-244. · 0.89 Impact Factor
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    ABSTRACT: We report the development of hypothermia in a patient with Hodgkin lymphoma which resolved with chemotherapy administration. A review of the literature revealed 16 previous reports of hypothermia in patients with Hodgkin lymphoma. Overall prognosis seems to be unfavorable. To the best of our knowledge this is the first report of hypothermia in a patient with Hodgkin lymphoma transforming from chronic lymphocytic leukemia (Richter's syndrome). A possible pathophysiology could be paraneoplastic autonomic neuropathy. Physicians should be aware that Hodgkin lymphoma can present with hypothermia and should carefully monitor newly diagnosed patients with advanced disease for this complication. Likewise, patients with Hodgkin lymphoma who develop hypothermia should be screened for signs of autonomic neuropathy. © 2013 S. Karger AG, Basel.
    Acta Haematologica 12/2013; 131(4):227-230. · 0.89 Impact Factor
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    ABSTRACT: Concern about extramedullary relapse (EMR) despite favorable response in the bone marrow has been raised with the use of imatinib for treatment of chronic myeloid leukemia (CML). In the present study we show an increase in adhesion, migration and invasion capabilities of the CML cell line K562 following imatinib administration. Imatinib induced upregulation of Pyk2 mRNA and protein levels. Pyk2 inhibition resulted in a reduction of K562 cells' adhesion and migration subsequent to imatinib treatment. This effect was similar to that shown by us previously with all trans retinoic acid (ATRA) in the acute promyelocytic leukemia (APL) cell line NB4. Our data pinpoint Pyk2 as a shared key mediator of targeted-therapy induced adhesion and migration and may implicate that targeting Pyk2 may serve as an effective therapeutic strategy to reduce EMR in APL and CML.
    Leukemia research 10/2013; · 2.36 Impact Factor
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    ABSTRACT: We assessed the performance of PET/CT for diagnosis and management of infections in high-risk hematological cancer patients with persistent febrile neutropenia in a prospective study. (18)F-FDG PET/CT with contrast-enhanced CT was performed on day 5-7 of persistent fever. Between 2008 and 2011, 91 PET/CT examinations were performed for different episodes in 79 patients, resulting in 117 diagnoses. The sensitivity of the PET/CT was 79.8% (71/89) compared to 51.7% (46/89) with chest/sinus CT alone. Specificities were 32.14% (9/28) vs. 42.85% (12/28), respectively. PET/CT resulted in a change from the pre-test diagnosis in 63/91 (69%) of episodes and in modification of patients' management in 46/91 (55%). PET/CT was beneficial in diagnosing abdominal infections. PET/CT has a potential role in the diagnostic evaluation of patients with persistent febrile neutropenia.
    Leukemia research 07/2013; · 2.36 Impact Factor
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    ABSTRACT: Anthracycline-containing regimens (ACR) are the most prevalent regimens in the management of patients with advanced follicular lymphoma (FL). However, there is no proof that they are superior to non-anthracycline-containing regimens (non-ACR). To compare the efficacy of ACRs to other chemotherapy regimens, in the treatment of FL. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), MEDLINE (January 1966 to April 2013), smaller databases, relevant conference proceedings (2004 to 2012) and the National Medical Library (April 2013). We included randomized controlled trials (RCTs) comparing ACR with non-ACR for adult patients with FL. We excluded trials in which immunotherapy, radiotherapy alone or stem-cell transplantation were used in one arm alone. Our primary outcome was overall survival (OS). Secondary outcomes included disease control, as measured by progression-free survival (PFS) or remission duration (RD). Two review authors assessed the quality of trials and extracted data. We contacted study authors for additional information. We analyzed trials separately according to resemblance of the chemotherapeutic regimens in study arms, other than the addition of anthracyclines ('same' versus 'different' chemotherapy). Hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the fixed-effect model. Eight RCTs, conducted between 1974 and 2011, and involving 2636 patients were included in this meta-analysis. All trials included therapy-naive patients. Rituximab was used in one trial only. Follow-up was between three and five years in most trials (range three to 18 years). All trials were published in peer-reviewed journals.Five trials compared similar chemotherapeutic regimens, except for the anthracycline. In three studies reporting overall survival specifically in FL patients, there was no statistically significant difference between ACR and non-ACR arms (HR 0.99; 95% CI 0.77 to 1.29; I(2) = 0%). ACR significantly improved disease control (HR 0.65; 95% CI 0.52 to 0.81; four trials). Progression or relapse at three years were reduced (RR 0.73; 95% CI 0.63 to 0.85). Anthracyclines did not significantly increase rates of complete response (RR 1.05; 95% CI 0.94 to 1.18) or overall response (RR 1.06; 95% CI 1.00 to 1.12), but heterogeneity was substantial.Overall, ACR were more often associated with cytopenias, but not with serious infections or death related to chemotherapy. Cardiotoxicity, albeit rare, was associated with anthracycline use (RR 4.55; 95% CI 0.92 to 22.49; four trials).Three trials added anthracycline to one arm of two different regimens. None showed benefit to ACR regarding OS, yet there was a trend in favor of anthracyclines for disease control. Results were heterogeneous.We judged the overall quality of these trials as moderate as all are unblinded, some are outdated and are not uniform in outcome definitions. The use of anthracyclines in patients with FL has no demonstrable benefit on overall survival, although it may have been mitigated by the more intense regimens given in the control arms of three of five trials. ACR improved disease control, as measured by PFS and RD with an increased risk for side effects, notably cardiotoxicity. The current evidence on the added value of ACR in the management of FL is limited. Further studies involving immunotherapy during induction and maintenance may change conclusion.
    Cochrane database of systematic reviews (Online) 07/2013; 7:CD008909. · 5.70 Impact Factor
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    ABSTRACT: Managing the patient's immune system after haematopoietic cell transplantation (HCT) is a challenge, mainly in the unstable period immediately after the transplant. Currently there is no standardized non-invasive diagnostic tool for the evaluation of immunological complications such as graft-versus-host disease (GVHD) and for managing the cellular immune function of the transplant recipient. The ImmuKnow assay for cellular immune function monitoring has been incorporated successfully into the clinical follow-up routine of solid organ transplant recipients. This study aims to explore the relevance and potential contribution of immune monitoring using the assay in the setting of HCT. We found that ImmuKnow-level measurement can distinguish between states of immune function quiescence and between events of acute GVHD. ImmuKnow levels were significantly higher in patients going through GVHD than the levels measured for the same patients during immunological stability. Moreover, we demonstrate a patient case where longitudinal monitoring using the ImmuKnow assay provided a trustworthy depiction of the patient's cellular immune function post-HCT. In conclusion, we provide evidence for the potential contribution of the ImmuKnow assay for longitudinal individualized cellular immune function monitoring of patients following HCT. Further studies are necessary in order to establish the optimal practice for utilizing the assay for this purpose.
    Clinical & Experimental Immunology 06/2013; 172(3):475-82. · 3.41 Impact Factor
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    ABSTRACT: OBJECTIVES: We aimed to examine whether C-reactive protein (CRP) elevation precedes the clinical signs and symptoms of infection among patients undergoing allogeneic hematopoietic cell transplantation (HCT). METHODS: Prospective cohort of patients undergoing allogeneic HCT in whom daily blood samples for CRP were taken. In a nested case-control study, cases were defined as patients with clinically-significant bloodstream infection (BSI). Controls were defined as afebrile patients without infection, matched by age, time after transplantation and GVHD status. We calculated the mean difference (MD) between CRP 1 day before clinical suspicion of infection (day -1) and days -2 and -3 (deltaM1M2 and delta M1M3, respectively) and compared cases vs. controls. RESULTS: From January 2010 to April 2012 we identified 46 cases of BSIs. The difference between the mean delta M1M3 and delta M1M2 in cases and controls were significantly higher in patients with BSI compared to controls (MD=5.9, 95% CI 3.5-8.3, p<.001 and MD=4.2 mg/dL, 95% CI 2.2-6.2, p<.001, respectively). In the overall cohort, sensitivity, specificity, positive and negative predictive values of a daily delta value >4 mg/dL were 52%, 98%, 66% and 98%, respectively. CONCLUSIONS: A daily increase of CRP blood levels of >4 mg/dL in afebrile HCT recipients should trigger an evaluation for infection.
    The Journal of infection 05/2013; · 4.13 Impact Factor
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    ABSTRACT: Despite the large local donor registries, for some Israeli patients an HLA-matched unrelated donor cannot be identified within a favorable time period. This study aims to retrospectively analyze donor search processes in our transplantation center in order to provide a basis to enhance the efficacy of these procedures. We analyzed 121 donor searches performed in the last five years in our center and investigated various parameters characterizing these searches. For over 80% of patients, a donor matched at least at 9/10 alleles was identified, mostly from the local donor registries. The probability of finding a 10/10 HLA-matched donor in a local registry for patients of the Arab minority was significantly lower than patients of Jewish origin (25% versus 64%, respectively; p<0.05). Furthermore, we found that identifying a fully matched donor for an adult patient is significantly more probable than for a pediatric patient (66% versus 43%, respectively; p<0.05). These data indicate of dissimilarities between HLA profiles of the older versus the younger patients, which influence their probability to find a suitable donor. In conclusion, in spite of the large size of local donor registries, they do not optimally reflect the immunogenetic profiles of patients of ethnic minorities and of pediatric patients.
    Human immunology 04/2013; · 2.55 Impact Factor
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    ABSTRACT: Since the introduction of all-trans-retinoic acid (ATRA) treatment for acute promyelocytic leukemia (APL) there has been increasing concern about extramedullary disease (EMD) progression despite favorable response in the bone marrow. We postulated that ATRA treatment enhances migration and adhesion abilities possibly enabling APL cells to inhabit extramedullary sites. We revealed an increase in adhesion, migration and invasion capabilities of NB4 cells following ATRA treatment. ATRA induced upregulation of Pyk2 mRNA, protein and phosphorylation levels and enhanced Pyk2 interaction with paxillin and vinculin. Pyk2 inhibition resulted in a reduction of NB4 cell adhesion and migration following ATRA treatment. These results indicate that in vitro Pyk2 might function to regulate cell adhesion and motility following ATRA treatment and its upregulated expression may contribute to EMD development in APL patients.
    Leukemia research 04/2013; · 2.36 Impact Factor
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    ABSTRACT: PURPOSE: Identify subgroups of relapsed/refractory follicular lymphoma patients deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase 3 LYM-3001 study. EXPERIMENTAL DESIGN: 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary endpoint was PFS; this pre-specified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for four proteins and eight genes. RESULTS: In initial pair-wise analyses, using individual SNP genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair (PSMB1 P11A G allele, low CD68 expression [≤50 CD68-positive cells], population frequency: 43.6%), median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next anti-lymphoma therapy longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. CONCLUSIONS: Patients with PSMB1 P11A (G allele) and low CD68 expression appeared to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab.
    Clinical Cancer Research 04/2013; · 7.84 Impact Factor

Publication Stats

4k Citations
1,154.15 Total Impact Points


  • 2014
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 2001–2014
    • Rabin Medical Center
      • Department of Cardiology
      Tell Afif, Tel Aviv, Israel
    • Technion - Israel Institute of Technology
      H̱efa, Haifa District, Israel
  • 1990–2014
    • Tel Aviv University
      • • Felsenstein Medical Research Center
      • • Faculty of Medicine
      • • Department of Internal Medicine
      Tell Afif, Tel Aviv, Israel
  • 2003–2013
    • Ben-Gurion University of the Negev
      • Faculty of Health Sciences
      Be'er Sheva`, Southern District, Israel
  • 2011
    • Athens State University
      Athens, Alabama, United States
    • Universitair Ziekenhuis Leuven
      Louvain, Flanders, Belgium
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2010
    • Hospital Universitario de Salamanca
      Helmantica, Castille and León, Spain
  • 2009
    • Alexandra Regional General Hospital
      Athínai, Attica, Greece
  • 2008–2009
    • Meir Medical Center
      Kafr Saba, Central District, Israel
  • 2002–2009
    • Soroka Medical Center
      • Department of Pathology
      Be'er Sheva`, Southern District, Israel
    • Johns Hopkins University
      • Department of Dermatology
      Baltimore, MD, United States
  • 1995–2002
    • Hadassah Medical Center
      • • Department of Paediatrics
      • • Department of Hematology
      Yerushalayim, Jerusalem District, Israel
  • 1989–2002
    • Sheba Medical Center
      • • Department of Pathology
      • • Cancer Research Center
      Gan, Tel Aviv, Israel
  • 1997–2001
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, PA, United States