[Grapefruit juice interaction with cyclosporine in bone marrow transplantation]

Introduction: Recently Grapefruit juice is known to enhance the bioavailability of several clinically important drugs such as nifedipine, terfenadine, cyclosporine, ethinylestradiole, midazolam, and triazolam. Cyclosporine is an immunosuppressive agent that used in transplantation for preventation of chronic rejection. Grapefruit increase in C[max] and AUC of drug mediated by suppression of Cyp3A4 in small intestine wall

Methods: This study has been performed by twenty allogenic bone marrow transplant recipients at shariati hospital in Tehran with [Randomized Cross Over Placebo Controlled Study]. Subjects were co administrated oral cyclosporine and grapefruit juice as a controlled and water as a placebo, simultaneously and two hours later. Blood samples were collected at 3.5 and 11.5 hours following drug administration. Blood concentration analyzed by specific monoclonal radioimmunoassay [RIA] technique

Results: SPSS version 11 [2002] was used for data analysis. mean and standerd deviation of cyclosponie C. was [821 +/- 215] ng/ml immediately and 2 hours after using grapefruit, which shows%41 higher levels in compersion to drinking water as placebo [578 +/- 194] ng/ml [p<0/05], but C[min] blood concentration shows only%21 increase with grapefruit versus water as placebo [p>0/05] [319 +/- 173 in grapefrait verus 268 +/- 140 in water]. The averge systolic and diostolic blood pressare was decreased significanty in grapefruit group [p<0/05]

Conclusion: This study demonstrated that administration of grapefruit juice had increased the cyclosporine C[max] [%42] at Iranian bone marrow transplant recipients. Because grapefruit juice may be a safe and effective instrument to enhance absorption of many therapeutic agents, it is an appropriate means in terms of reducing dosing requirements of many Cyp3A4 substrates such as cyclosporine

[Cytotoxic effects of selective inhibitor 'Aurora Kinase B' on viability and metabolic features of human promyelocytic leukemia cell line]

A goal of modern cancer research is to reach targeted therapies with drugs having fewer side effects. AZD1152 is a highly specific inhibitor of Aurora Kinase B, which leads to the programmed cell death by different mechanisms. The aim of this study was to evaluate the effects of AZD1152 on viability and metabolic activity of NB4 cells [APL derived cell line]. The cells were treated with various concentrations of AZD1152. After 24, 48 and 72h treatments, the metabolic activity and viability of inhibitor-treated NB4 cells were assessed using MTT and trypan blue dye exclusion assays, respectively. Data were analyzed by applying student's t-test [Microsoft Excel]. At 25, 50 and 100 nM, AZD1152 reduced the metabolic activity by 9.2, 15.5 and 56.2% [after 24h], 10.3, 19.5 and 59.9% [after 48h], and 17.1, 28.4 and 64.8% [after 72h], respectively. Meanwhile, the percentage of viability was decreased to about 51, 45 and 40% [after 24h], 39, 36 and 30% [after 48h], and 34, 32 and 28% [after 72h], respectively. According to the results, AZD1152 has substantial efficacy on APL cell line and may be applied in some cases, e. g., for patients who have relapse or who become refractory to the conventional chemotherapy. Further studies are needed to show the molecular mechanisms regulating effects of this anti-cancer agent

[ detection Of micrometastases in peripheral blood and bone marrow of breast cancer patients using marker[MUC2] real time PCR]

Tumor dissemination via blood to distant organs is the main cause of death. Therefore, there is a critical need to set up sensitive methods for the early detection of circulating tumor cells[CTCs] and disseminated tumor cells[DTCs] in peripheral blood [PB] and bone marrow[BM] specimens of breast cancer patients. The aim of this research is to study the detection of micrometastasis using MUC2 in such patients. In this study, PB and BM samples were collected from 50 breast cancer patients after operation and before adjuvant therapy. Mucin 2 [MUC2] was used as a tumor marker and its transcript level in the sample patients was analyzed using gene specific, quantitative real-time PCR reaction with SYBR Green technology. Samples from 20 healthy individuals were used as negative controls. HPRT was used as a reference gene. MUC2 mRNA was detected in 8 [16%] of PB and BM samples. MUC2 mRNA was not detected in PB samples of healthy individuals. The relapse rate among MUC2-positive patients was higher than MUC2-negative patients; and it was statistically significant in BM [P<0.05]. This study shows that MUC2 can be a suitable marker for the detection of micrometastasis in breast cancer patients at early stages of cancer and that it may provide the basis for identifying women at risk of relapse

Expression of MRP1 gene in acute leukemia / Expressão do gene MRP1 em leucemias agudas

CONTEXT AND OBJECTIVE: Overexpression of the multidrug resistance-associated protein 1 (MRP1) gene has been linked with resistance to chemotherapy in vitro, but little is known about its clinical impact on acute leukemia patients. Our aim was to investigate the possible association between MRP1 gene expression level and clinical outcomes among Iranian leukemia patients. DESIGN AND SETTING: This was an analytical cross-sectional study on patients referred to the Hematology, Oncology and Stem Cell Research Center, Sharyatee Public Hospital, whose diagnosis was acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL). All molecular work was performed at NIGEB (public institution). METHODS: To correlate with prognostic markers and the clinical outcome of acute leukemia, MRP1 gene expression was assessed in 35 AML cases and 17 ALL cases, using the quantitative real-time polymerase chain reaction and comparing this to the chemotherapy response type. RESULTS: Mean expression in AML patients in complete remission (0.032 ± 0.031) was significantly lower than in relapsed cases (0.422 ± 0.297). In contrast, no significant difference in MRP1 mRNA level was observed between complete remission and relapsed ALL patients. There was a difference in MRP1 expression between patients with unfavorable and favorable cytogenetic prognosis (0.670 ± 0.074 and 0.028 ± 0.013, respectively). MRP1 expression in M5 was significantly higher (p-value = 0.001) than in other subtypes. CONCLUSIONS: The findings suggest that high MRP1 expression was associated with poor clinical outcome and was correlated with the M5 subtype and poor cytogenetic subgroups among AML patients but not among ALL patients.

CONTEXTO E OBJETIVO: A superexpressão do gene de resistência a múltiplas drogas associado à proteína 1 (MRP1) tem sido ligada à resistência à quimioterapia in vitro, porém pouco é conhecido sobre seu impacto clínico nos pacientes com leucemia aguda. Nosso objetivo foi investigar a possível associação entre a expressão do gene MRP1 e os desfechos clínicos em pacientes iranianos com leucemia. DESENHO E LOCAL: Este foi um estudo analítico transversal em pacientes encaminhados ao Centro de Pesquisa em Hematologia, Oncologia e Células Tronco do Hospital Público de Sharyatee, com diagnóstico de leucemia mielóide aguda (LMA) ou leucemia linfoblástica aguda (LLA). Todo trabalho molecular foi realizado no NIGEB (instituição pública). MÉTODOS: Para correlação de marcadores prognósticos e desfechos clínicos da leucemia aguda, a expressão do MRP1 foi avaliada em 35 casos de LMA e 17 de LLA, usando a reação da cadeia de polimerase quantitativa em tempo real, e comparando este dado ao tipo de resposta à quimioterapia. RESULTADOS: A média da expressão em pacientes com LMA em remissão completa (0,032 ± 0,031) foi significativamente menor que aquela dos casos recidivantes (0,422 ± 0,297). Por outro lado, não foram observadas diferenças significativas nos níveis de mRNA para MRP1 entre os casos de LLA com remissão completa e os casos recidivantes. Houve uma diferença na expressão de MRP1 entre pacientes com prognóstico citogenético não-favorável e favorável (0,670 ± 0,074 e 0,028 ± 0,013, respectivamente). A expressão de MRP1 em M5 foi significativamente maior (valor de p = 0,001) do que em outros subtipos. CONCLUSÕES: Os achados sugerem que a alta expressão de MRP1 se associou com o pior desfecho clínico, estando correlacionada com o subtipo M5 e os subgrupos citogenéticos menos favoráveis para os pacientes com LMA, mas não para pacientes com LLA.