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M Krawczuk-Rybak

Publications and source records attributed to M Krawczuk-Rybak.

At least 19 recordsLinked to original sources
PubMed2006

Acute lymphoblastic leukaemia cells express CCR7 but not higher amounts of IL-10 after CD40 ligation.

OBJECTIVE: Production of cytokines that support T-cell activation and proliferation and migration to lymph nodes is one of the most important terms of cancer vaccine development. In previous studies we and others used CD40 ligation to obtain higher expression of co-stimulatory and adhesion molecules on leukaemic cells from children with acute lymphoblastic leukaemia (ALL). This time we assess the cytokine and chemokine gene expression profile in CD40-stimulated ALL cells. MATERIAL AND METHODS: Malignant cells from 25 children with BCP-ALL were stimulated (or not) with huCD40LT and rIL-4 for 96 h. Eleven different molecule, cytokine and chemokine mRNAs levels (CCR7, IL-23, TGF-beta-IP, IFN-gamma, IL-10, CD1a, CD40, CD54, CD80, CD83, CD86) were determined using the real-time PCR technique with TaqMan chemistry using ready-to-use low-density arrays for gene expression by Applied Biosystems. RESULTS: 1) Increases in mRNA levels for CD40, CD54 and CD80 after CD40L and IL-4 stimulation were observed, 2) CCR7 mRNA expression was higher after CD40 ligation than before the culture (p = 0.002), 3) IL-10 mRNA expression was higher after the culture with medium than before the culture (p = 0.01). CONCLUSIONS: The results show that leukaemia-derived dendritic cells obtained with CD40 ligation express CCR7 - chemokine is involved in migration to lymph nodes and does not produce higher amounts of IL-10, a potent immunosuppressive cytokine. Our preclinical findings could be used in the design of immunotherapy trials for the treatment of children with ALL.

CD40 Antigens↗
PubMed2006

Low expression of costimulatory molecules and mRNA for cytokines are important mechanisms of immunosuppression in acute lymphoblastic leukemia in children?

UNLABELLED: Mechanisms leading blasts of acute lymphoblastic leukemia to escape from immune surveillance are still unknown. Only few reports showed that ALL cells are inefficient antigen presenting cells. The aim of the study was to assess expression of critical costimulatory/adhesion molecules and mRNA for main pro- and anti-inflammatory cytokines in ALL cells. Children with B-cell precursor ALL (n=20) were prospectively enrolled into the study. Expression of costimulatory/adhesion molecules (CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II) was assessed by flow cytometry and mRNA for cytokines (IFN-gamma, IL-10, IL-4, TGF-beta) - with real-time PCR. RESULTS: 1) high expression was observed for HLA I and II class, moderate for CD40, CD83, CD86 and low or no expression for CD80, CD54, CD1a, CD11c and CD123; 2) we found expression of mRNA for IFN-gamma, IL-10, IL-4 and TGF-beta in blasts cells (but not in all specimens). We noted relatively lower expression of all assessed cytokines comparing to T-cells obtained from healthy donors but interestingly expression for IL-10 was higher in normal B-cells than in blast cells, and IFN-gamma and IL-4 were not found in normal B-cells. In summary we suggest that ALL-blasts present low expression of costimulatory/adhesion molecules and mRNA for cytokines and this probably contribute to the absence of host T- cells stimulation to immune response.

Antigens, CD↗
PubMed2005

In vitro sensitivity of leukemic cells to nucleoside derivatives in childhood acute leukemias: good activity in leukemic relapses.

Nucleoside analogues such as fludarabine and cladribine are used in therapy of indolent lymphomas and leukemias in adults, while cytarabine is used mainly in protocols for acute leukemias. Mechanisms of their activity is based on inhibition of enzymes involved in DNA, RNA and protein synthesis. The objective of the study was the analysis of in vitro cellular drug sensitivity in childhood acute lymphoblastic (ALL) and myeloid (AML) leukemia. Isolated leukemic cells obtained from 264 patients, including 152 initial ALL, 45 relapsed ALL, 54 initial AML and 13 relapsed AML were tested for cytotoxicity for fludarabine, cladribine, and cytarabine by the MTT assay. Drug concentration lethal to 50% of tested cells was regarded as a value of drug resistance. Three tested nucleoside analogues showed highest cytotoxicity against initial ALL samples. Samples of relapsed ALL and initial AML were more resistant than ALL de novo ones. Unexpectedly, no differences were observed between initial and relapsed AML samples for all tested drugs, what suggests that nucleoside analogues are active drugs in relapsed AML, which is commonly regarded as a resistant disease. All tested drugs presented significant cross-resistance in each of analyzed subgroups. In summary, tested nucleoside analogues presented relatively good activity against childhood leukemias at relapse stage.

Adolescent↗
PubMed2005

Variations of enzymatic activity and biotypes of the yeast like fungi strains isolated from cancer patients.

PURPOSE: Determination of the enzymatic activity and enzymatic biotypes variations of the yeast like fungi strains isolated from cancer patients with oral candidiasis during last 5 years. MATERIAL AND METHODS: We evaluated enzymatic activity of 92 Candida albicans strains isolated from oral ontocenosis from cancer patients with candidiasis symptoms in 1999 and 2003. The enzymatic activity of the strains tested was assessed by the API ZYM (bioMerieux) method. Biotypes of the strains were determined according to Williamson's or Kurnatowska's and Kurnatowski's classifications. RESULTS: In 1999 Candida albicans 17 of 19 tested isolates had hydrolytic activity hydrolases and 87% of strains were assigned according to Wiliamson's. Only 8.7% of strains were classified according to Kurnatowska's and Kurnatowski's, but 4.3% strains according to Krajewska-Kułak et al. In 2003, 18 of 19 strains had hydrolytic activity and 93.5% of strains were classified according to Wiliamson's, but 4.3% according to Kurnatowska's and Kurnatowski's and 2.2% according to Krajewska-Kułak et al. CONCLUSIONS: The results of present study indicate that most of tested strains were classified into Wiliamson's system. Our findings suggest that other Candida biotypes should be determined according to their different enzymatic activity and susceptibilities.

Candida albicans↗
PubMed2005

Relationship between insulin-like growth factors (IGF-I and IGF-II), IGF-binding proteins (IGFBP-3, IGFBP-2), leptin and anthropometric parameters (height, body mass index) during antileukaemic treatment in children.

PURPOSE: The aim of the study was to estimate the anthropometric parameters and their relationship to serum levels of IGF-I, IGF-II, IGFBP-3, IGFBP-2 and leptin before and during intensive antineoplastic treatment for acute lymphoblastic leukaemia in children. MATERIAL AND METHODS: In 46 children in median age 6.6 years (range from 1.6 to 16) we evaluated at the time of diagnosis, after protocol I and after intensive treatment, height, body mass index (BMI) and IGF-I, IGF-II, IGFBP-3, IGFBP-2 and leptin. RESULTS: Height SDS lowered in successive points of analysis whereas BMI SDS rose after protocol II. IGF-I SDS was low and similar at each point, IGF-II SDS and IGFBP-3 SDS values augmented progressively and IGFBP-2 SDS was significantly elevated before treatment and lowered (but not normalized) during the therapy. Leptin SDS was elevated, especially after protocol I. CONCLUSION: Leukaemia and its treatment affect directly growth factors, its binding proteins and leptin production leading to growth retardation and overweight.

Adolescent↗
PubMed2004

Association of collagen type I alpha1 gene polymorphism with bone density in survivors of childhood cancer--preliminary report.

A candidate gene, involved in the regulation of bone mass is the COLIA1 gene encoding type I collagen, the major protein of bone matrix. The disease per se, the age of its onset and treatment options might exert an impact on bone mineralization in survivors of childhood malignancy. We examined possible allelic influences of COLIA1 gene polymorphism on BMI, BMD spine and total body in 41 survivors (15 girls) of childhood cancer (the mean age 8.9 years). Genotype distribution was 33 (80.5%) SS and 8 (19.5%) Ss. There were no differences in SDS BMD and SDS BMI between patients with SS and Ss genotype. A tendency towards lower SDS values of BMD spine and BMI was observed (not significant). In conclusion, our preliminary observations suggest that COLIA1 genotype may affect bone accrual in a population treated for childhood cancer. Further investigations in a greater population are needed.

Adolescent↗
PubMed2004

Male gonadal function before and after chemotherapy in prepubertal boys.

UNLABELLED: We evaluated gonadal function in twenty prepubertal boys (6.87 +/- 3.84 years old) at diagnosis and 2.5 +/- 1.6 years after treatment for acute lymphoblastic leukaemia (ALL). We measured serum levels of inhibin B (RIA method), testosterone, FSH, LH (immunoenzymatic methods) and compared the results with controls (31 healthy boys in prepubertal stage). RESULTS: Serum inhibin B levels were lower at diagnosis (55.81 ng/ml +/- 33.74), comparing to respective values in the controls (105.89 ng/ml +/- 46.64), p<0.0002. The values of inhibin B slightly augmented after 2.5 +/- 1.6 years from chemotherapy (79.47 ng/ml +/- 47.39), p<0.06 but remained lower than those in the controls (p<0.07). We did not find any differences in FSH, LH or testosterone values, before and after chemotherapy, comparing to respective values in the controls. In conclusion, haematological malignancy and its treatment influence gonadal function before puberty with a possibility of recovery. During this period, inhibin B could be used as a sensitive indicator of testicular function.

Antineoplastic Agents↗
PubMed2004

mRNA for chosen pro- and anti-inflammatory cytokines in T-lymphocytes in paediatric leukemias and lymphomas--a preliminary report.

We assessed mRNA for chosen pro- and anti-inflammatory cytokines in T-lymphocytes of peripheral blood in paediatric patients with leukemias and lymphomas. Levels of four different cytokine mRNAs (IFN-gamma, IL-10, IL-4, TGF-beta) were determined by the real-time PCR technique. In the whole examined group, at the time of diagnosis, we noted lower amounts of mRNA for TGF-beta1, comparing to respective values in the control patients. In the ALL group, we observed the following: 1) at the time of diagnosis: lower amounts of mRNA for IL-4 and for TGF-beta1, comparing to respective values in the control group; 2) lower amounts of mRNA for IL-10 after remission induction, comparing to the time of diagnosis. In our opinion, "immunedysregulation" in lymphoproliferative diseases in children is not caused by IFN-gamma deficiency. The deficit of anti-inflammatory cytokines, i.e., IL-4, TGF-beta, with higher amounts of IL-10, suggests their role in cancer development.

CD4-Positive T-Lymphocytes↗
PubMed1999

[Usefulness of antioxidant vitamin supplementation in children and adolescents with newly diagnosed diabetes mellitus type I].

BACKGROUND: Diabetes type I is caused by immune-mediated destruction of the b-cells. During the immune response macrophages release free oxygen radicals and cytokines which damage DNA. Ascorbic acid, b-carotene, a-tocopherol and nicotinamide act as antioxidants (free radical scavengers). OBJECTIVES: Comparative analysis of diabetes mellitus clinical course in the first year after diagnosis with and without antioxidative vitamin supplementation. MATERIAL AND METHODS: 40 children and adolescents with newly-diagnosed diabetes type I treated with: group A (n=13) n insulin + diet, group B (n=14) n additional vitamins A+E, C, group C (n=13) n additional vitamins A+E, C, PP. RESULTS: The remission was observed in n=13 (92.8%) children in group B, in n=6 (46.1%) in group C and only in 2 (15.4%) in group A after 3-4 months. After 6-7 months the remission was obtained in 10 patients (71.5%) in group B, in 6 (46.1%) - in group C and in 4 (30.8%) - in group A. After one year observation 6 (42.5%) patients in group B had remission, 4 (30.7%) in group C and 2 (15.4%) - in group A. Daily insulin demand was similar after diagnosis, after 3-4 months it was more reduced in group B (x - 0.28 u./kg/d, SD n 0.23) vs. x - 0.40 u./kg/d SD n 0.24 (group C) and vs., x - 0.5 u./kg/d - (group A). The insulin demand was augmented in the following months but all the time it was lower in the group supplemented by vitamins A, E, C. The glycaemic control and the values of lipids, thiobarbituric and reactive substances, group-SH of glutathione and vitamin C were similar in analysed groups in simultaneous periods. CONCLUSIONS: Supplementation with antioxidant vitamins in newly diagnosed diabetes mellitus type I leads to more frequent remissions and reduced insulin demand, particularly in the first months of diabetes duration.

English Abstract↗
PubMed1999

[The prevalence of autoimmunological diseases in families of children with type I diabetes].

BACKGROUND: type I diabetes mellitus is considered as an autoimmune disease and is often associated with other diseases of that etiology. The genetic susceptibility to autoimmune disorders causes type I diabetes to occur more frequently in relatives of the diabetic patients. OBJECTIVE: To evaluate the prevalence of type I diabetes and other autoimmune diseases in families of the children with type I diabetes. MATERIAL AND METHODS: The prevalence of type I diabetes mellitus and other autoimmune endocrinopathies was evaluated in I, II and III degree relatives of 155 children with type I diabetes mellitus and 90 control children. RESULTS: It was observed that: 1) diabetes mellitus occurred more often in relatives of diabetic children (in 22 families - 14.2%) in comparison with the control group (in 2 families - 2.2%); 2) other autoimmune diseases occurred frequently in families of diabetic children and they affected 2 or more members of one family more often than in the control group (18 families vs 4); 3) rheumatoid arthritis occurred more frequently in families of diabetic children. CONCLUSIONS: The familial prevalence of type I diabetes mellitus and the tendency to more frequent prevalence of other autoimmune diseases in families of diabetic children was confirmed.

English Abstract↗
PubMed1992

[Lipid metabolism in children and adolescents with insulin dependent diabetes. II. Evaluation of changes in lipoprotein A-I in children and adolescents with insulin dependent diabetes].

The levels of lipoprotein A-I (LP A-I) containing apolipoprotein A-I (apo A-I) and devoid of apolipoprotein A-II (apo A-II) have been determined in a group of 86 children and adolescents with insulin-dependent diabetes of age between 1.3 and 22 years. The duration of diabetes in the studied group ranged between 0.25 and 15 years. The patients studied were further divided into subgroups taking into account the duration of diabetes as well as the occurrence of complications of diabetes, obesity and predisposition to early development of atherosclerosis in family history. The analysis of the results took into account the relations between the levels of LP A-I and other parameters of lipid metabolism like cholesterol, triglycerides, HDL-cholesterol, apo A-I and apo A-II concentrations as well as the effectiveness of metabolic control of diabetes. LP A-I concentration was the lowest in group of children with diabetes lasting up to one year. This parameter was correlated positively with the levels of HDL-cholesterol and apo A-I, and negatively with HbA1c. It was not related to the coexisting complications, obesity or predisposition to atherosclerosis in family history. The above results indicate that the state of metabolic control of diabetes significantly influences the level of LP A-I. Considering the importance of LP A-I in preventing atherosclerosis it should be stressed that a decrease in its level during the period of prolonged hypoglycemia constitutes still another risk factor for development of atherosclerosis in diabetic children and adolescents.

Adolescent↗
PubMed1992

[Lipid metabolism in patients with insulin dependent diabetes. III. Effect of metabolic control of diabetes on the concentration of some blood serum lipid constituents in patients with insulin dependent diabetes].

The levels of the following blood serum lipid constituents: total cholesterol, triglycerides, phospholipids, HDL-cholesterol, lipoprotein fractions, as well as apolipoproteins AI, AII and B, have been determined in patients with insulin-dependent diabetes lasting from 3 months to 15 years in relation to the degree of metabolic control characterized by the levels of fructosamine and glycosylated hemoglobin HbA1c. The group of patients having the level of HbA1c exceeding 10% was characterized by significantly higher levels of cholesterol, triglycerides and Apo-B, and lower content of alpha-lipoprotein as compared to the group with HbA1c level beneath 10%. When fructosamine concentration was considered as an index of metabolic control of diabetes, it was found that the levels of cholesterol, phospholipids and apolipoproteins apo-A and apo-AI are highest in the group with the poor metabolic control and differ significantly from the respective values found in patients with mediocre and good metabolic control. Considering biological role of the individual lipids and lipoproteins, it should be stressed that the proper control of glycaemia is important for preventing the development of atherosclerosis in patients with insulin-dependent diabetes.

Adolescent↗
PubMed1992

[Lipid metabolism in patients with insulin dependent diabetes. IV. Effect of sex, age, excess body weight, duration of diabetes, insulin dosage and family history on lipid metabolism in patients with insulin dependent diabetes].

The levels of the following blood serum lipid constituents: total cholesterol, triglycerides, phospholipids, HDL-cholesterol, apolipoproteins AI, AII and B, and lipoprotein fractions have been determined in patients with insulin-dependent diabetes in relation to sex, age, duration of diabetes, coexistence of obesity, insulin dosage and history of genetic predispositions. The age of the patients was between 1.3 and 22 years and the duration of the disease ranged between 3 months and 15 years. The analysis of the results revealed that sex, age, daily insulin dose and the known genetic predispositions have no influence on the values of the parameters of lipid metabolism. However, an increase in the levels of cholesterol, HDL-cholesterol, triglycerides and apolipoproteins AI and B was observed along with the progressing duration of the disease. An increase in the levels of cholesterol, apolipoprotein B and beta-lipoprotein, and a decrease in the level of alpha-lipoprotein have been found in diabetic children with coexisting obesity. The above analysis indicates that besides metabolic control of diabetes its duration and accompanying obesity may negatively influence the course of the disease contributing to the precocious development of atherosclerosis.

Adolescent↗
PubMed1991

[State of lipid metabolism in children and adolescents with insulin-dependent diabetes. I. Evaluation of lipoprotein (A) behavior in children and adolescents with insulin-dependent diabetes].

The level of lipoprotein Lp(a), one of the risk factors of atherosclerosis, was determined in 91 children and adolescents of age ranging from 3.3 to 22 years suffering from insulin-dependent diabetes. The changes in Lp(a) were analyzed in relation to the group of patients, the duration of diabetes, possible genetic factors, other factors predisposing to early onset of atherosclerosis, and occurrence of obesity in the analyzed group. The relation between the level of Lp(a) and other parameters of lipid metabolism (total cholesterol, triglycerides, phospholipids, HDL-cholesterol and apolipoprotein B) as well as a degree of metabolic normalization of diabetes (as assessed by the determination of glycosylated hemoglobin and fructosamine) was studied in addition. No relation between Lp(a) and the factors mentioned above, with exception of glycosylated hemoglobin and fructosamine concentrations, could be demonstrated. The elevated level of Lp(a) in children and adolescents during the period of poor metabolic control of diabetes may constitute an additional risk factor for early onset of atherogenic changes.

Adolescent↗