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Biomedical subjects

Jan Styczynski

Publications and source records attributed to Jan Styczynski.

12 recordsLinked to original sources
PubMed2006

Alternative medicine remedies might stimulate viability of leukemic cells.

OBJECTIVE: Ex vivo activity of three products of alternative therapy against leukemic and normal cells was analyzed. MATERIAL AND METHODS: Extracts of Viscum album, Uncaria tomentosa, and Croton lechleri were used for the study. Leukemic cells of 53 children with acute leukemias and four cell lines, Jurkat, CCRF-CEM, HL-60, and K-562 were tested for sensitivity to alternative medicine remedies by the MTT assay, cell-cycle analysis and annexin-V binding assay. RESULTS: Leukemic cells showed high resistance to tested three compounds of alternative medicine in all performed assays. Additionally, tested remedies stimulated survival of leukemic cells in 45%, 96%, and 83% cases, respectively; while no effect was observed in normal lymphocytes. In combination studies, Viscum album extract did not increase prednisolone and cytarabine cytotoxicity in leukemic cells. CONCLUSION: We conclude that some alternative medicine remedies might stimulate the viability of childhood leukemic cells.

Adolescent↗
PubMed2006

Ex vivo activity of thalidomide in childhood acute leukemia.

Thalidomide is a drug with anti-angiogenic, anti-inflammatory, immunomodulatory and anti-cancer properties that were found to inhibit the production of TNF-alpha in vitro, stimulate reactive oxygen species production, and inhibit VEGFR in acute leukemias. Ex vivo activity of thalidomide as a single agent and in combination with prednisolone or cytarabine in childhood acute leukemias was analyzed. Forty samples of childhood acute lymphoblastic leukemia (ALL) and 13 acute myeloid leukemia (AML) were tested for cytotoxicity by the MTT assay and cell cycle phases by flow cytometry. Control studies were performed on 9 samples of normal lymphocytes and 4 cell lines. A weak anti-leukemic activity of thalidomide against childhood leukemic samples was observed. However, in the presence of thalidomide, cytotoxicity of prednisolone or cytarabine, increased 3.3-fold and 2.7-fold, respectively, in childhood ALL but was not changed in AML. Thalidomide increased apoptosis in lymphoblasts, and modulated cell cycle arrest caused by prednisolone but not cytarabine in childhood acute lymphoblastic leukemia samples. Thalidomide potentiated ex vivo sensitivity of childhood ALL cells to prednisolone and cytarabine, while no sensitization effect was observed in AML cells.

Angiogenesis Inhibitors↗
PubMed2006

Ex vivo modulation of response to prednisolone in childhood acute lymphoblastic leukaemia.

We hypothesised that the intensity of mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukaemia might be decreased by concurrent ex vivo use of compounds with specific blocking or activating properties at different steps of the glucocorticoid intracellular pathway. The following modifiers were used: ciclosporin A, rifampicin, doxycycline, meta-iodobenzylguanidine, buthionine sulfoximine, ethacrinic acid, pentoxifylline, indomethacin, rotenone, forskolin, olomoucin, 5-aza-2'-deoxycytidine, 3-aminobenzamide, O(6)-benzylguanidine and nitroprusside sodium. All modulators sensitised lymphoblasts and potentiated prednisolone cytotoxicity in most cases indicating that various compounds, which can influence the antileukaemic effect of prednisolone during anticancer therapy, might modulate some mechanisms of glucocorticoid resistance.

Antineoplastic Agents, Hormonal↗
PubMed2005

Calcified fibromatosis of the neck in 4-year old girl: rapid growth, rapid therapy.

Fibromatosis is a rare soft tissue disease typical for infants and characterized by fibroblastic proliferation, which may appear similar to fibrosarcoma. An unusual case of 4-year old girl presenting large tumor of the neck with massive calcification is described. The growth of the tumor was rapid and mediastinal involvement was observed. The final diagnosis showed benign nature of tumor with microscopic features of fibromatosis calcificans. After surgical resection of neck tumor, residual mass persisted both in the neck and in the mediastinum in 6 years of follow-up without signs of progression.

Calcinosis↗
PubMed2004

Ex vivo drug resistance in childhood acute myeloid leukemia on relapse is not higher than at first diagnosis.

Relapsed pediatric patients with acute myeloid leukemia (AML) have a poor clinical prognosis. The aim of this study was the analysis of the ex vivo drug resistance profile on relapse in childhood AML in comparison to newly diagnosed AML. The results of 98 pediatric AML samples tested by the MTT assay were analyzed. Eighteen samples (18%) were excluded from the further analysis due to spontaneous apoptosis of blasts in 4-days culture, low percentage of myeloblasts in the sample either in the beginning or at the end of the assay, infection, or formation of clots in the sample. Finally, ex vivo drug resistance of 20 relapsed samples were compared with that of 60 de novo AML, including 9 matched pairs. Up to 18 drugs were tested for each patient. No significant differences between drug resistance at diagnosis and at relapse in AML was found, neither for the whole groups of patients, nor for matched pairs only. Possibly, relatively good sensitivity of myeloblasts on relapse was found against melphalan, thiotepa, 4-HOO-ifosfamide, and cladribine. In summary, cellular drug resistance in childhood AML at relapse is not higher than at first diagnosis. These observations suggest that other, than cellular drug resistance, factors play a key role in therapy failure of relapsed childhood AML.

Acute Disease↗
PubMed2002

Ex vivo drug resistance profile in childhood acute myelogenous leukemia: no drug is more effective in comparison to acute lymphoblastic leukemia.

Therapy results in childhood acute myelogenous leukemia (AML) differ from those of acute lymphoblastic leukemia (ALL). Cellular drug resistance might be one of the reasons of therapy failure in AML. The aim of the study was the analysis of ex vivo drug resistance profile in childhood initial and relapsed AML in comparison to initial ALL. Fifty-three AML samples were tested for chemosensitivity and results were compared with those of 106 initial ALL samples. Ex vivo drug resistance was tested by means of the MTT assay. Up to 29 cytotoxic drugs were tested for each patient. When compared to de nova ALL samples, myeloblasts from initial AML samples were significantly more resistant to most tested drugs, except cytarabine, mercaptopurine and thioguanine. Relapsed AML samples, in relation to initial AML samples, showed comparable sensitivity to cytarabine, idarubicin, fludarabine and cladribine. Patients, who have died due to refractory or relapsing disease, were already on first diagnosis 2-fold more resistant to cytarabine, 6.4-fold more resistant to cisplatin and 3-fold more resistant to carboplatin, when compared to those who stay in remission. Resistance to prednisolone was observed in 85% initial and all relapsed AML samples, in comparison to 33% of ALL samples. Resistance to cytarabine occurred in 2.1% of ALL and 12% of AML cases while a patient with Down syndrome presented the most sensitive drug resistance profile. In conclusion this study shows that no drug was found which, on average, was more effective in AML than in ALL samples. The sensitivity of myeloblasts to platinum derivatives might have prognostic value.

Carboplatin↗
PubMed2002

In vitro drug resistance profiles of adult acute lymphoblastic leukemia: possible explanation for difference in outcome to similar therapeutic regimens.

Age has important prognostic impact in acute lymphoblastic leukemia (ALL). Adults with ALL have a worse prognosis compared to children. This may be due to different, unfavorable biology, poor treatment tolerance, drug resistance, higher expression of drug resistance related proteins. The lymphoblasts from adult ALL show an increased in vitro resistance to cytotoxic drugs, including prednisolone, dexamethasone, cytosine arabinoside, daunorubicin, L-asparaginase and methotrexate. Glucocorticoid resistance may be a fundamental difference between children, adolescents and adults with ALL, which may underlie different biological aspects and also explain the difference in prognosis. It seems that in vitro resistance to prednisolone with respect to the age might be a continuous variable in ALL patients, except infants. The greater the age, the higher the in vitro resistance to prednisolone. This may be due to induction of various defense mechanisms, such as an activation of P-glycoprotein, which develops throughout the life and protect the human against xenobiotics. Among a number of various drug resistance mechanisms, only several weak differences between adults and children with ALL have been reported including higher P-glycoprotein expression, lower methotrexate polyglutamate accumulation and possibly more often p53 gene mutations in adults. Intrinsic resistance, induction of drug resistance proteins expression during chemotherapy and co-existence of various mechanisms are common phenomena in adult ALL. It seems that age itself, more than drug resistance profile, reflects factors which have direct effect on chemotherapy response in adult ALL.

Adult↗
PubMedDate not supplied

In vitro activity of glufosfamide in childhood acute leukemia.

Glufosfamide is a new agent for cancer chemotherapy. The objective of the study was the comparison of the in vitro drug resistance profile of glufosfamide with other oxazaphosphorines in 106 samples of childhood acute leukemia by means of the MTT assay. The following drugs were tested: glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide, mafosfamide cyclohexylamine salt, prednisolone, vincristine, L-asparaginase, daunorubicin and cytarabine. In the group of initial Acute Lymphoblastic Leukemia (ALL) samples, equivalent cytotoxicity values for glufosfamide, 4-HOO-ifosfamide, 4-HOO-cyclophosphamide and mafosfamide were 5.95, 9.92, 4.60 and 3.90 microg/ml, respectively. In comparison to initial ALL samples, the relative resistance for glufosfamide and 4-HOO-ifosfamide in relapsed ALL samples were 1.9 (p=0.049) and 1.3 (ns), and in initial Acute Myeloblastic Leukemia (AML) samples, respectively, 31 (p<0.001) and 5 (p=0.001). All oxazaphosphorines showed highly significant cross-resistance. In conclusion, in vitro activity of glufosfamide is comparable to ifosfamide. Glufosfamide shows high activity against lymphoblasts both on diagnosis and on relapse, however it cannot circumvent resistance to other oxazaphosphorines.

Adolescent↗
PubMedDate not supplied

Cytotoxicity of cortivazol in childhood acute lymphoblastic leukemia.

BACKGROUND: Glucocorticoids are the most important group of drugs used in the treatment of childhood acute lymphoblastic leukemia (ALL), however, resistance to this group remains the main obstacle in curing the disease. One of the possibilities to circumvent glucocorticoid resistance is the use of new compounds, such as cortivazol (CVZ), which has two binding sites for the glucocorticoid receptor. AIM: Analysis of ex vivo sensitivity to cortivazol and other glucocorticoids in childhood acute lymphoblastic leukemia, as well as the relationship to anticancer therapy outcome. PATIENTS AND METHODS: Leukemic samples from 60 children with ALL were tested by the M7T assay for glucocorticoid resistance. Cell cycle before and after ex vivo glucocorticoid treatment was analyzed by flow cytometry. RESULTS: Although all tested glucocorticoids presented significant cross-resistance, CVZ showed high antileukemic activity. The equivalent activity of CVZ was 165-fold higher than prednisolone, 7.ZS5-fold higher than dexamethasone and 2.8-fold higher than betamethasone. CVZ showed relatively better cytotoxicity than other glucocorticoids in prednisolone-poor-responders. CVZ, like other glucocorticoids, caused cell cycle arrest in the GI-phase, and increased the percentage of apoptotic cells to a greater extent than other glucocorticoids. The results of antileukemic therapy were strongly related to the ex vivo resistance to all tested glucocorticoids. CONCLUSION: Cortivazol has potent antileukemic activity in childhood ALL. Its activity is related to cell cycle arrest and induction of apoptosis.

Adolescent↗
PubMedDate not supplied

Activity of bortezomib in glioblastoma.

BACKGROUND: Chemotherapy is the commonly accepted standard therapy for most types of brain tumor, especially in medulloblastoma, primitive neuroectodermal tumor and astrocytoma. However, no efficient therapy has been established to date for glioblastoma multiforme. The aim of the present study was to analyze the activity of bortezomib in glioblastoma cell lines in comparison with that in a pediatric acute lymphoblastic leukemia cell line. MATERIALS AND METHODS: Glioblastoma multiforme T98G, glioblastoma-astrocytoma U373M and T-lineage acute lymphoblastic leukemia CCRF-CEM cell lines were used. Proteasome inhibitor, bortezomib and 14 other anticancer drugs were tested using the MTT assay. RESULTS: Compared to the acute lymphoblastic cell line, both glioblastoma cell lines showed relatively good sensitivity to bortezomib, as well as to cisplatin, carboplatin, etoposide and actinomycin-D. The lines showed intermediate sensitivity to thiotepa and daunorubicin, but were highly resistant to first-line drugs used in the therapy of acute lymphoblastic leukemia, such as prednisolone, L-asparaginase, vincristine, doxorubicin and cytarabine. Bortezomib, which is not a substrate for PGP and MRP1, did not show cross resistance to drugs transported by these proteins. CONCLUSION: Our results support the necessity for further research on the role of bortezomib in the therapy of glioblastoma.

Antineoplastic Agents↗