Sub-THz nonresonant detection in AlGaN/GaN heterojunction FETs

Abstract. Un-cooled AlGaN/GaN-based heterojunction field-effect transistors (HFET) designed on sapphire (0001) substrates were considered as 140 GHz direct detection detectors without any specially attached antennas. The noise equivalent power (NEP) of these detectors was ~

THE RESULTS OF TREATMENT OF ACUTE MYELOID LEUKEMIA IN EVERYDAY CLINICAL PRACTICE

Aim: To assess efficacy of the “7 + 3” regimen in non-selective groups of patients with acute myeloid leukemia (AML).Materials and methods: We retrospectively assessed medical documentations (inand out-patient case histories) of 105 AML patients who were on treatment in MONIKI from January 2002 to December 2011, with evaluation of clinical and hematological characteristics of patients, remission rates depending on age, serum lactate dehydrogenase (LDH) levels and time from diagnosis to the start of treatment, as well as overall survival.Results: In total, the standard regimen “7 + 3” was effective in 58% of AML patients. Remission was achieved in 70.5% of 17 patients with normal LDH levels and in 50.9% of 53 patients with high LDH levels (р < 0,05). In the patients aged from 18 to 30 years, the remission rate was 81%, in those from 31 to 60 years, in 61%. In the elderly patients (from 60 years and older), remission was achieved in 29% of cases (р < 0.05 compared to each of two other age groups). Remission was associated with the time from diagnosis to the start of treatment, being 16.7% in those where this time period exceeded 10 days and 60.8% in those where this time was less than 10 days (р < 0.05). The median overall survival was 11 months in the total group, 15 months in the patients who achieved remission after 2 treatment cycles and 6 months in those who did not respond to treatment. Comparison of the 2 groups with different AML types did not reveal any difference in the treatment results: overall survival in М0–М2 was 11 months and in М4–М5 10 months. Conclusion: Treatment of AML patients with “7 + 3” regimen provides a good anti-tumor effect. Achievement of remission depends on patient age, time to the start of treatment and LDH levels. The results obtained in non-selective group of patients are comparable to those published on selected group of patients

LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib) and second line (nilotinib), overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse) or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival

Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

49 patients aged 28 to 81 years old (median age of 55 years old) with relapsed or refractory multiple myeloma (MM) were enrolled in the study. The relapse was diagnosed in 25 (51 %) patients, the refractory disease was determined in 24 (49 %) patients (including primary refractory disease in 14 (28.6 %) patients). The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %). Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP). The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR) in 1 (2 %) patient; very good partial response (VGPR) in 4 (8 %) patients; partial response (PR) in 26 (53 %) patients; minimal response (MR) in 2 (4 %) patients; stable disease (SD) in 8 (16.3 %) patients, and progressive disease (PD) in 8 (16.3 %) patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 %) patients. The objective response rate, including MR, was seen in 33 (67.1 %) patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management

INCREASE OF DRUG RESISTANCE OF ACUTE MYELOID LEUKEMIA CELLS IN MULTICELLULAR AGGREGATES IN VITRO

Background: Therapeutic efficiency in treatment of acute myeloid leukemia (AML) ranges from 20 to 45%. One of the causes of the latter is a drug resistance acquired by leukemic cells under the influence of treatment with antitumor medicines. More important cause is a development of the primary resistance of myeloid leukemic cells to induction of cellular death associated with elemental microenvironment within the bone marrow. Studying primary resistance is very important, and first of all, to prevent development of drug resistance of leukemic cells and, correspondingly, to increase the efficiency of medicamental therapy. Aim: To study the mechanisms of primary resistance of AML cells to induction of cellular death. Materials and methods: Human AML cells of THP-1 line and mononuclear cells of the bone marrow were used in the study of patients with diagnosed AML. Multicellular aggregates were formed during cell cultivating on the 1.5% agarose. To cut off intercellular adhesion, the cells were cultivated in the medium with methylcellulose (0.9%). The viability of the cells was assessed by reduction of Alamar Blue indicator. Results: Within multicellular aggregates, about 75±5% of THP-1 cells were resistant to the activity of recombinant protein izTRAIL, 70±5% – to etoposide, and 40±7% – to sorafenib. Cutting off intercellular contacts decreased the resistance to them. Within multicellular aggregates of primary mononuclear cells, 45±5% of cells were resistant to sorafenib, 57±4% – to etoposide, and all cells were resistant to izTRAIL. Cutting off intracellular adhesion reduced the resistance to sorafenib and etoposide but not to izTRAIL. Conclusion: In multicellular aggregates, AML cells of THP-1 line and mononuclear cells of the bone marrow showed increased resistance to activity of recombinant protein izTRAIL, etoposide, and sorafenib. Diminishing intracellular adhesion in the medium including methylcellulose decreases cellular resistance to cytotoxic agents

Efficiency of lenalidomide, bortezomib and prednisone (RVP) in patients with newly diagnosed multiple myeloma

Objective: to study the efficacy and safety of the antitumor RVP program (lenalidomide, bortezomib, prednisone) as a first-line therapy in patients with multiple myeloma (MM). Materials and methods. A prospective study involved 39 patients with MM (15 women, 24 men), median age 61 years (30–76 years). All patients had Durie–Salmon stage III disease. According to the paraprotein isotype variant, 19 patients (48.7 %) had Gk myeloma, 8 (20.5 %) had Gλ, 4 (10.2 %) – Ak, 1 – Aλ, 1 – Dk, 1 – paraproteinemia Bens-Jones k and 1 – Bens-Jones λ, 2 – Dλ, and 2 patients – nonsecreting MM. The average level of plasma cells in the bone marrow was 31.7 % (0.8–80.0 %). In 14 (35.8 %) patients there were plasmacytomas of various localization (spine, cranial bones, clavicle, pleura). Nine (23.0 %) patients had renal failure, requiring the start of renal replacement therapy. The average Karnovsky index in the study group was 50 %. All patients received RVP therapy (lenalidomide 25 mg in 1–14 days, bortezomib 1.3 mg subcutaneously in 1, 4, 8, 11 days, prednisolone 60 mg/m2; the interval between courses was 42 days) as the first line therapy. Evaluation of therapy efficacy, characterized by overall survival, objective response rates (the number of complete, very good partial and partial remissions) was performed after 6 treatment courses. Results. The median follow-up was 15 months; the median of overall survival was not achieved. Objective antitumor response achieved in 29 (74.3 %) patients, including complete remissions in 3 (7.6 %), very good partial remissions – in 7 (17.9 %), partial remissions – in 19 (48.7 %) patients. In 2 out of 9 patients who received renal replacement therapy, independence from dialysis therapy was achieved. Cases of III–IV stage hematological and non-hematological toxicity in the study were not noted. Conclusion. The antitumor RVP program showed high efficacy and safety as a first-line therapy in a non-selective group of patients, including those with a complicated MM course

Treatment efficacy of chronic myeloid leukemia with imatinib in clinical practice

Imatinib (IM) treatment efficacy in 116 chronic myeloid leukemia (CML) patients in different studies was analyzed. Patient group was non‑selective with prospective enrollment. The study was based on real‑time patient’s register allows to treatment quality control due to clinical results. Cytogenetic response (CO), hematological data, and overall survival (OS) were used as criteria for the therapy efficacy. After 12 month of treatment in 46.4 % of CML patients in early chronic phase complete CO (CCO) was obtained, in 33.3 % — in the late chronic phase, and in 13.3 % — in accelerated phase. Deficit of daily imatinib dose and intervals in treatment schedule were made a negative influence on CO quality. The median of OS was 120 months.</p

THE EFFECT OF MULTIDRUG RESISTANCE GENE EXPRESSION ON THE CLINICAL COURSE OF MULTIPLE MYELOMA

Background: Implementation of a proteasome inhibitor bortezomib into treatment of multiple myeloma has helped to improve survival of patients with this malignancy that is characterized by continuous relapsing course as a clinical manifestation of multidrug resistance (MDR). Previous studies have resulted in contradictory data on the effects of various MDR genes expression on efficacy of bortezomib. Aim: To evaluate an impact of MDR1, MRP1, LRP, BCRP gene mRNA expression responsible for the development of MDR in bone marrow aspirates from patients with newly diagnosed multiple myeloma before bortezomib-containing therapy on the clinical course of the disease, response to treatment and overall survival. Materials and methods: MDR gene expression was assessed in a  group of 15  patients with newly diagnosed multiple myeloma Durie-Salmon stage  III before initiation of a bortezomib-based chemotherapeutic regimen. The assessment was done in bone marrow mononuclear cell fraction containing plasmocytes. MDR gene expression was measured by reverse transcription polymerase chain reaction test. Results: MDR gene expression was found in all patients with newly diagnosed multiple myeloma before initiation of cytostatic therapy: MDR1 was expressed in 14 (93%) of patients, MRP1 and LRP  – in 11 (73%), BCRP  – in 15  (100%). There was no difference between patient subgroups with high and low MDR gene expression in their clinical parameters, such as hemoglobin level, erythrocyte counts, total calcium, creatinine, total protein, lactate dehydrogenase, and albumin. At diagnosis of multiple myeloma, only absolute levels of paraprotein were significantly lower in patients with high MDR1 gene expression (31.52±3 vs  44.27±3.62  g/L, p&lt;0.05). After 6  cycles of induction, there was a  significant decrease of paraprotein levels in the group with low MDR1 gene expression (from 44.3±3.6 to 16.8±5.2 g/L, p&lt;0.05). Overall survival was negatively associated with high LRP gene expression only (median of overall survival in patients with high LRP gene expression was 17 months and in those with low expression – 62 months, р&lt;0.05). Conclusion: High expression of MDR genes in patients with newly diagnosed multiple myeloma is not associated with clinical characteristics of the disease but may deteriorate the immediate response to bortezomib-based regimens and overall survival

The efficacy of therapy with rituximab (R-CHOP) in patients with diffuse large cells lymphoma

<p>This study aimed to evaluate treatment results in patients with diffuse large cell lymphoma (DBL CL) received R-CHOP program (as 1 st and<br />2 nd line therapy), including cases with complications. We observed 77 DBLCL patients (50 primary and 27 received other chemotherapy programs, in relapse, progression or treatment resistance phase). The median age is 54.1 years (21–79 years). 33 patients (43 %) had a high risk for unfavorable disease course according to IPI. Complications associated with development of severe compression syndromes, which required the appropriate surgical intervention, w as diagnosed in 45 (58.4 %) patients. From 50 primary patients received R-C HOP as the f irst line therapy objective treatment response was registered in 47 (94.0 %). Complete response was registered in 43 (86.0 %). The proportion of patients in whom response was maintained for 6 months w as 72.0 % in group with maintenance therapy and 28.0 % in group without it. These results were achieved when induction period density was 0.9. The last parameter is the ratio of the courses number to their time in mon ths. The density of standard induction R-C HOP-21 is 1.4. From 27 relapse or refractory patients received R-C HOP as the second line therapy objective<br />treatment response was registered in 85.1 % of patients. Induction period density w as 1.03. The proportion of patients in whom response was maintained for 6 months was 74.0 %. Three classes serum Ig concentrations analysis before and after induction period in 16 pati ents showed normal values. With the median (Me) follow-up time in all patients over 24 months 3-years survival w as 93 % and Me w as not achieved. 3-years survival was 100 % in primary patients and 80 % in patients with previously treatment, and Me is also not achieved.</p