Navarra S.V.,University of Santo Tomas of Philippines |
Guzman R.M.,SaludCoop Clinic |
Gallacher A.E.,Hospital Britanico Of Buenos Aires |
Hall S.,Emeritus Research Cabrini Hospital |
And 13 more authors.
The Lancet | Year: 2011
Background: Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Methods: Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new B organ domain score; and no worsening [<0.3 increase] in Physician's Global Assessment [PGA] score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00424476. Findings: 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 [51%], odds ratio 1.55 [95% CI 1.10-2.19]; p=0.0129) and 10 mg/kg (167 [58%], 1.83 [1.30-2.59]; p=0.0006) than with placebo (125 [44%]) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 [53%], 1.51 [1.07-2.14]; p=0.0189) and 10 mg/kg (169 [58%], 1.71 [1.21-2.41]; p=0.0024) than with placebo (132 [46%]). More patients given belimumab 1 mg/kg (226 [78%], 1.38 [0.93-2.04]; p=0.1064) and 10 mg/kg (236 [81%], 1.62 [1.09-2.42]; p=0.0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 [73%]). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 [79%], 1.68 [1.15-2.47]; p=0.0078) and 10 mg/kg (231 [80%], 1.74 [1.18-2.55]; p=0.0048) than with placebo (199 [69%]). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Interpretation: Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Funding: Human Genome Sciences and GlaxoSmithKline. © 2011 Elsevier Ltd.
PubMed | City Hospital No 9, Government Institution < > Uccc and State Institution < >
Type: Journal Article | Journal: Experimental oncology | Year: 2016
Genetic inborn along with acquired diseases arise due to the lesions in genome of multipotent hematopoietic stem cells. The aim was to study an influence of constitutional anomaly, Klinefelter syndrome, and additional structural rearrangements on the BCR-ABL tyrosine kinase inhibitor targeted therapy efficacy.We describe a 32-year-old male patient with chronic myeloid leukemia (CML) who was detected to have sex chromosomal abnormality during evaluation for Philadelphia chromosome.At diagnosis of CML, two clones were detected by standard cytogenetic investigation of bone marrow cells: 1) clone with translocation t(9;22)(q34;q11), with two sex X chromosomes and absence sex chromosome Y; 2) clone with t(9;22) and unbalanced t(Y;20)(q11;q13). Analysis of blast transformed lymphocytes from peripheral blood showed karyotype 47,XXY. Monitoring of targeted therapy with second generation inhibitor of BCR-ABL tyrosine kinase indicated a cytogenetic remission and absence of BCR-ABL1 fusion signals after 11 months.Absence of translocation t(9;22)(q34;q11) in blast transformed T-lymphocytes at diagnosis of CML evidences that this translocation may appear not only at the level of multipotent haemopoietic cell progenitors but also may have oligo lineage myeloid origin. Presence of additional structural chromosomal abnormality in the clone with t(9;22)(q34;q11) does not affect the efficacy of therapy with the use of second generation BCR-ABL tyrosine kinase inhibitor.
Gapeenko D.D.,State Institution |
Lavrenchuk H.I.,State Institution
Nuclear Physics and Atomic Energy | Year: 2014
Experimental study of the combined action of heavy metals and ionizing radiation on the viability of cells in culture was made. We established a significant toxic effect of copper and nickel in the proliferative and mitotic activity of cells in vitro. Under the combined effects of radiation and copper ions on cells we observed the morphological changes in morphologically-functional properties of cells that were determined by or radiation dose or by concentration of copper ions. While incubation of irradiated cells with nickel ions we observed sensitization of cells by nickel ions under the irradiation dose of 0.5 and 5.0 Gy, and the resistance of cells to exposure to sublethal dose of 10.0 Gy. © 2014, National Academy of Sciences of Ukraine. All rights reserved.
Sitko V.V.,State Institution < > |
Misharina J.A.,Bogomolets National Medical University |
Minchenko J.M.,State Institution < > |
Poluben L.O.,State Institution < > |
And 8 more authors.
Biopolymers and Cell | Year: 2015
Aim. Determination of deletion of the long arm of chromosome 13 in the patients with chronic lymphocytic leukemia, diffuse large B-cell lymphoma and multiple myeloma to provide prognostic assessments of Chronic Lymphoproliferative Neoplasms (CLPN) sub-variants progression, and early detection of therapy resistant cases and relapses of CLPN. Methods. Preparations of bone marrow cells from all patients (n = 115) with CLPN were studied. Fluorescence in situ hybridization was performed using commercial test Vysis LSI D13S319 (13q14.3) Spectrum Orange/ Vysis LSI 13q34 Spectrum Green FISH probe kit (Abbott Molecular, USA). Results. The molecular cytogenetic investigations have revealed deletions of 13q in 38 % of the patients with CLPN. We also present a clinical case where the deletion of 13q is detected along with other cytogenetic aberrations that significantly impair a disease prognosis. Conclusion. The analysis of deletions of the long arm of chromosome 13 is an important diagnostic and prognostic criterion, which assists to optimizes the treatment of the patients with CLPN. © 2015 V. V. Sitko et al.
Cherednyk Y.O.,State Institution < > |
Anopryenko O.V.,NASU Institute of Molecular Biology and Genetics |
Gorovenko N.G.,P L Shupik National Medical Academy Of Post Graduate Education |
Feschenko Y.I.,State Institution < >
Biopolymers and Cell | Year: 2013
Aim. Based on the method of single-nucleotide polymorphism (SNP) determination with hairpin primers to perform a differential identification in clinical material of M. tuberculosis (Mtb) strains, which belong to the 1st or 2/3 principal genotypic groups (PGG), with the aim of shortening the terms of tuberculosis diagnosing and early detection of most clinically and epidemiologically-significant strains. Methods. PCR with the SNP-specific hairpin primers to group-specific SNP katG463, and statistical analysis of clinical/epidemiological categories of the patients were used for study of sputum clinical samples from patients with pulmonary tuberculosis living in Kyiv. Results. PCR system of differential group-specific detection of Mtb in clinical samples using hairpin primers to SNP katG463 effectively detected Mtb in 47.8 % of samples of which 57.6%were strains of the PGG-1 and 42.4%- PGG-2/3. The association between belonging to the PGG-1 and resistance to isoniazid (OR [95 % CI], 5.417 [1.196-24.522] P = 0.0283) and to any of the first-line drugs (rifampicin/isoniazid) (OR [95 % CI], 7.00 [1.493-32.82] P = 0.014) was revealed. Conclusions. SNP-analysis with the hairpin SNP-specific primers to locus katG463 of Mtb strains group member ship in clinical material allows effective detection of epidemiologically important PGG-1 strains. © Institute of Molecular Biology and Genetics, NAS of Ukraine, 2013.
Popov V.E.,State Institution |
Il'Icheva N.S.,State Institution |
Stepina I.A.,State Institution |
Maslova K.M.,State Institution
Radiochemistry | Year: 2011
It is suggested to describe the dependence of K d -1 of 137Cs on the potassium ion concentration for clinoptilolite and illite with a quasi-Langmuir equation in which the maximal radiocesium interception potential relative to potassium, RIP(K) max, is used instead of the maximal sorption capacity of the sorbent. For describing the dependence of the selective sorption of 137Cs on the concentration of ammonium ions, an approximation equation consisting of two normalized quasi-Langmuir equations is suggested, with one equation describing the 137Cs sorption on low-affinity sorption centers for concentrations exceeding 3 mM and the other equation describing the sorption on high-affinity centers for ammonium concentrations of up to 3 mM. © 2011 Pleiades Publishing, Ltd.
PubMed | State Institution
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
15529 Background: Gastric cancer patients (pts) have a high risk of peritoneal recurrence due to disseminated tumor cells after surgery. The trifunctional antibody catumaxomab (anti-EpCAM anti-CD3) administered locally into the peritoneal cavity aims at residual tumor cells while activating a complex anti-tumor immune reaction.A total of 55 gastric cancer pts (T2b/T3/T4, N, M0) were randomized during surgical D2 procedure to surgery alone or catumaxomab administered as one intraoperative intraperitoneal (ip) and 4 postoperative ip infusions with ascending doses on day 7, 10, 13 and 16. Primary objectives were safety, tolerability and feasibility.All 55 pts (27 surgery alone, 28 catumaxomab) were included in the safety analysis. The target antigen EpCAM was confirmed in 100 % of pts. 78 % (22/28) of the patients treated with catumaxomab received all 5 infusions. 40 % of the treatment-emergent adverse events (TEAEs) occurred directly after the intraoperative administration. TEAEs (CTC-grade 3) occurred in 22 patients (control arm: 10 patients). The most frequently TEAEs in the catumaxomab group were anemia, pyrexia, SIRS and abdominal pain. All related serious TEAEs resolved until end of treatment except for nephropathy (one patient), which resolved with minor sequelae. No trend of an accumulation of severe adverse reactions or complications (e.g. wound healing) occurred compared to the surgery only group.Adjuvant treatment of ip administration of catumaxomab is safe and well-tolerable in pts after curative resection, the safety results reflecting catumaxomabs mode of action (cytokine release related symptoms). This offers a new chance to avoid intraabdominal tumor recurrence. First clinically relevant efficacy data will be obtained after the 1- and 2-year follow-up period. [Table: see text].