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Plzeň, Czech Republic

Nemec P.,Masaryk University | Zemanova Z.,General University Hospital | Kuglik P.,Masaryk University | Michalova K.,General University Hospital | And 17 more authors.
Leukemia and Lymphoma | Year: 2012

The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11;14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and β 2-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with ≤ 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation. © 2012 Informa UK, Ltd. Source

Polivka J.,Charles University | Polivka J.,Faculty Hospital Plzen | Rohan V.,Faculty Hospital Plzen | Topolcan O.,Central Imunoanalytical Laboratory
Anticancer Research | Year: 2014

Oligodendrogliomas are uncommon tumors in neurooncology that represent about 5% of primary brain malignancies. Their high sensitivity to radiotherapy and chemotherapy was observed a long time ago. Nonetheless, the evidence-based proof of the significantly longer survival in patients with oligodendrogliomas treated with combined chemotherapy and radiotherapy in comparison to radiotherapy-alone did not exist. The long-term follow-up of two landmark phase III clinical trials: RTOG 9402 and EORTC 26951, recently demonstrated favorable effects of combined radiotherapy and chemotherapy (procarbazine, lomustine and vincristine) in patients with anaplastic oligodendrogliomas and anaplastic oligoastrocytomas carrying the chromosomal mutation of co-deletion of 1p/19q. There is also an increasing role of other molecular biomarkers, such as mutations in the metabolic enzyme isocitrate dehydrogenase 1/2, O6-methylguanine DNA methyltransferase gene promoter methylation, or glioma genome cytosine-phosphate-guanine islands methylator phenotype. The analysis of molecular genetics in oligodendrogliomas is now recommended as an important part of the management of these tumors and together with the novel chemotherapeutic regimens means a paradigm shift in current clinical practice in neurooncology. Source

Anghel R.,Institutul Oncologic Bucharest | Bachmann A.,University of Basel | Beksac M.,Ankara University | Brodowicz T.,Medical University of Vienna | And 10 more authors.
Wiener Klinische Wochenschrift | Year: 2013

Summary: Bisphosphonates have been a mainstay in the treatment of cancer-related bone disease and have greatly reduced the risk of skeletal complications. More recently, clinical studies suggested additional benefits of denosumab over zoledronic acid in the prevention of skeletal related events. Similar adverse event profiles have been reported for bisphosphonates and denosumab, with infrequent occurrences of osteonecrosis of the jaw with both agents, higher incidence of renal deterioration with zoledronic acid, and higher incidence of hypocalcaemia with denosumab. Based on current evidence, the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines do not recommend one drug class over the other in patients with metastatic bone disease. Denosumab, however, may present advantages over bisphosphonates in patients suffering from chronic renal insufficiency. Further research and growing clinical experience will refine the evidence based on which decisions in daily clinical practice can be taken. © 2013 Springer-Verlag Wien. Source

Suchy D.,Faculty Hospital Plzen | Dostalek M.,University of Rhode Island | Perinova I.,Faculty Hospital Ostrava | Brozmanova H.,Faculty Hospital Ostrava | And 3 more authors.
Biomedical Papers | Year: 2011

Background. Cyclosporine A (CsA) is an immunomodulatory agent used in standard immunosuppressive regimens in solid organ transplantations as well as in the treatment of autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus and psoriasis. Its immunosuppressive activity is primarily due to parent drug. However, following oral administration, absorption is incomplete and varies between individuals. Further, there is a dearth of pharmacokinetic data for CsA in autoimmune patients compared to transplant recipients. Aim. The goal of this study was to investigate the single-dose and steady state pharmacokinetics of CsA and two main primary metabolites, AM1 and AM4N, in patients with rheumatic/autoimmune diseases. Methods. Thirty-eight subjects, average age (years± SD) 46.8 (±11.6) years with rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, ankylosing spondylitis and undifferentiated SpA were included in an observational open study. The single dose pharmacokinetics (area under the concentration-time curve of CsA and its metabolites (AUC) and other PK parameters) were determined over a 24 h period following oral administration of 1.3 mg/kg oral CsA. Two CsA formulations-Neoral and the Czech generic substitute Consupren ®, were used. Pharmacokinetic analysis was performed on all 38 patients after administration of a single dose of CsA (1.34 mg/ kg/day). In 12 patients only, a second series of blood samples was taken to calculate monitored PK parameters under steady state conditions. Results. Pharmacokinetic assessment showed AUC 0-24 3009.66 ± 1449.78 ng/ml.h and C max 827.84 ± 425.84 after ad-ministration of a single dose of CSA, AUC 0-24 3698.50 ± 2147 ng/ml.h and C max 741 ± 493 ng/ml after repeated dose. The proportion of the AM1 metabolite (AUC 0-24) after a single dose of CsA corresponded to 40% of the parent compound and to approximately 35% of the parent compound in steady state conditions. The proportion of AM4N metabolite was low in both conditions and represented only 3 and 4.5% after a single dose and at steady state, respectively. Conclusion. The pharmacokinetic data (AUC CsA, C max) for the whole 24 h interval were similar to the published findings, mainly under steady state conditions. The AM1 (AUC 0-24) after a single dose of CsA and in steady state conditions represented about 40% of the parent drug. The ratio of AM4N metabolite was low in both conditions. © D. Suchy, M. Dostalek, I. Perinova, H. Brozmanova, M. Grundmann, V. Vyskocil, O. Mayer. Source

Vyskocil V.,Faculty Hospital Plzen | Pavelka T.,Faculty Hospital Plzen | Stajdlova K.,Charles University | Suchy D.,Charles University
BMC Musculoskeletal Disorders | Year: 2015

Background: Melorheostosis is quite a rare bone disease with still unclear ethiology. Although multifocal affection is highly debilitating with unfavorable prognosis, there is no clear consensus about therapeutical approach. There is still insufficient evidence in the literature for almost a century after the first description. Affected bone has a typical appearance of melting wax. Diagnosis is usually incidental with pain as a leading symptom. Diagnosis itself is relatively easy, routine X-ray examination is sufficient. Even though it could be easily overlooked and mistaken with other diseases. Melorheostosis is incurable, the therapy is mostly focused on maintaining patient quality of life. Presented case is unique in terms of extent of the affection (index finger, metacarp shaft, carpal bones, forearm, humerus and whole scapula) in combination with osteopoikilotic islands in other 3 regions (vertebrae, manubrium sterni and left collar bone). Currently there is only one such a case published in the literature (Campbell), but without osteopoikilotic islands. Case presentation: Melorheostosis was diagnosed in 26-year old female after injury as an incidental finding. This was quite surprising as the patient already suffered by limited movement in the upper limb and pain before the injury. Detailed examination were performed to confirm the diagnosis, no family history was found. Pharmacotherapy with bisphosphonates, non-steroidal antirheumatics and vasodilatans/rheologic drugs seemed to be effective to maintain the relatively good quality of patient life and good performance in daily routine. Questionable is further development of patient performance status and sustainability of conservative treatment in the long term follow up. Conclusion: Conservative treatment with bisphopshonates and COX-2 inhibitors in combination with naftidrofuryl can delay surgery solution. © 2015 Vyskocil et al. Source

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