فهرست مطالب

  • Volume:10 Issue: 1, 2020
  • تاریخ انتشار: 1398/11/02
  • تعداد عناوین: 8
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  • Morteza Mousavi, Hasanzadeh, Arefeh Adelnia, Golrokh Farokhmehr, Sarvenaz Mehrabi, Siam Zahedi, Aigin Eghbali, Aziz Eghbali* Pages 1-9
    Background

    Nausea and vomiting are the common side-effects of chemotherapy in children with malignancy. In this study, the effectiveness of vitamin B6 in reducing the chemo-induced nausea and vomiting (CINV) in children was tested.

    Material and methods

    A triple-blind clinical trials was performed on 100 children with malignancy referring to the pediatric clinic of Amir Kabir Hospital, Arak, Iran. Besides the infusion of granisetron (3mg/3ml) half an hour before each chemotherapy cycle, an intravenous dose of vitamin B6 (100 mg for children from 2 to 5 years old, 200 mg for children from 5 to 10 years old, and 300 mg for children older than 10) was given 6 hours before the first chemotherapy cycle and placebo was injected (2-5 years old: 100 mg, 5-10 years old: 200 mg, age≥ 10 years old: 300mg) 6 hours before the second cycle. Then the severity of nausea and the frequency of vomiting episodes in each cycle were recorded to be compared. 

    Results

    The mean age of children was 7.98 ± 3.133 years old. The most common and rare malignancy were acute lymphocytic leukemia (ALL) (46%) and ependymoma (0.5%), respectively. Vincristin was the most commonly used chemotherapy agent (28%). A positive correlation between the severity of nausea(R=0.313, P-value=0.0016) and frequency of vomiting with age was found (R=0.319, P-value=0.0012). However, no noticeable association was observed between N/V and gender (P-value.0.05). There was a considerable correlation between the frequency of vomiting and different tumor types in this study (P-value=0.0006).In comparison with placebo, Vitamin B6 significantly reduced the severity of nausea (P = 0.0001) as well as the frequency of vomiting (P-value = 0.0005). It was also more effective in ALL compared to rhabdomyosarcoma (P-value=0.001).

    Conclusion

    This study suggested that vitamin B6 can be considered as an appropriate alternative to treat CINV in children with malignancy.

    Keywords: Chemotherapy, Children, Vitamin B6, Vomiting
  • Soheila Zareifar, Anahita Sanaei Dashti, Tayebe Masoomzade, Mojtaba Anvarinejad, Omid Reza Zekavat, Mohammad Reza Bordbar, Nader Cohan, Sezaneh Haghpanah* Pages 10-16
    Background

    Febrile neutropenia is still one of the most important complications of treatment in cancer patients. These patients become prone to infection and consequently higher mortality and morbidity. This study aimed to determine the accuracy of serum procalcitonin (PCT) level in the detection of infection in pediatric cancer patients complicated with febrile neutropenia.

    Materials and Methods

    In this cross-sectional study, all pediatric patients affected by cancer and febrile neutropenia following chemotherapy (n=107) were investigated from August 2014 to August 2015. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum levels of PCT, as well as blood and urine culture, were evaluated in all patients.

    Results

    The mean age of the patients was 78 ± 55 months (3 - 214 months), and in terms of gender, 53 patients (49.5%) were male. Overall, 25 patients (23.4%) and 13 patients (12%) showed positive blood and urine culture, respectively. The area under the curve (AUC) receiver operating characteristic (ROC) curve was illustrated to determine how much PCT can couldpredict infection.(AUC =0.74, 95% CI: 0.61-0.87, P<0.001). Considering the cut-off of serum PCT levels as 0.70ng/mL, sensitivity, specificity, and positive and negative predictive valueof PCT were 0.76, 0.744, 0.475, and 0.91, respectively. In addition, PCT showed significant correlations with CRP (rs=0.415, P<0.001) and ESR (rs =0.262, P=0.009).

    Conclusion

    According to the findings of this study, serum PCT levels can be used as a diagnostic test with acceptable sensitivity and specificity and high negative predictive value, but the low positive predictive value in the evaluation of infections in patients affected by cancer and complicated with fever and neutropenia.

    Keywords: Fever, Malignancy, Neutropenia, Pediatric, Procalcitonin
  • Mehdi Allahbakhshian Farsani, Esmaeil Shahabi Satlsar*, Alireza Mohseni, Mohammad Mosleh, Mahdieh Mehrpouri, Mahnaz Agaeipour, Mohammad Hossein Mohammadi, Roohollah Gholampour, Farzaneh Jadali Pages 17-27
    Background

    Hematogones are normal B-cell precursor which can be seen in different physiological and pathological conditions. Due to variation in B-cell acute lymphoblastic leukemia (B-ALL) blasts immunophenotyping and interference of hematogones in minimal residual disease (MRD) assessment, precise discrimination of hematogones is very crucial.  The purpose of this study was to evaluate the expression pattern of surface markers in hematogones and compare them with lymphoblasts.

    Material and Methods

    In this applied study, flow cytometric analysis was performed using Coulter FC-500 and MXP software in 4-color combination and 6 different tubes. In this study, 85 patients diagnosed with acute lymphoblastic leukemia were evaluated. Out of these patients, 45 were boys and 40 were girls. Patients aged from 1 to 15 years old. In addition, 27 bone marrow samples from other patients aged 4 to 18 years were included in this investigation. These samples had been obtained for other diagnostic purposes, such as immune thrombocytopenic purpura and juvenile idiopathic arthritis.

    Results

    During flow cytometric analysis, hematogones showed expressions of CD19, CD20, CD22, CD10, CD45, CD81, CD123, CD9, CD34 (partial expression), and tdt (partial expression). In these patients, hematgones were negative for CD66c expression. Lymphoblastic cells were positive for CD19, CD20 (in some cases), CD22, CD10, CD45, CD81, CD123, CD58, CD9, CD66c, CD34 (in most cases), and TDT. CD81 mean fluorescence intensity (MFI) in hematogones was higher than that in lymphoblasts. (112.5 (30-251) vs. 17.5 (5-30); P<0.0001)

    Conclusion

    According to findings of this study, it seems that the use of CD81, CD58, CD123, CD66c, CD9, and CD81 MFI in combination with B-Cells associated markers can be very effective in differentiating hematogone from lymphoblast.

    Keywords: B-ALL, Hematogone, Lymphoblast, MRD
  • Tohid Rostamian, Fatemeh Pourrajab, Seyedhossein Hekmatimoghaddam* Pages 28-37
    Background

    6-thioguanine (6-TG) is one of the thiopurine drugs with successful use in oncology, especially for acute lymphoblastic leukemia (ALL). 6-TG is proposed to act as an epigenetic drug affecting DNA methylation. The aim of this study was to clarify the effect of 6-TG on the proliferation, viability and expression of genes coding for the enzymes DNA methyltransferase 3A and DNA methyltransferase 3B (DNMTs) as well as histone deacetylase 3 (HDAC3) in the human B cell-ALL cell line Nalm6.

    Materials and Methods

    In this experimental study, Nalm6 cells and also normal peripheral blood mononuclear cells (PBMCs) were grown in RPMI 1640 medium containing 10% fetal bovine serum. They were then treated with 6-TG at their exponential growth phase. Cell viability was monitored using the Cell Counting Kit-8 assay with an enzyme-linked immunosorbent assay (ELISA) reader. The expressions of the above-mentioned 3 genes were quantified using real-time PCR.

    Results

    6-TG could inhibit the proliferation of Nalm6 cells and decrease their viability. In Nalm6 cells, as compared to normal PBMCs, 6-TG significantly decreased HDAC3 (p = 0.008) as well as DNMT3B (p = 0.003) gene expressions, but increased the expression of DNMT3A gene (p = 0.02) after normalization to GAPDH, as the housekeeping gene.

    Conclusion

    These findings suggested that the altered expression of DNMT3A, DNMT3B and HDAC3 genes was responsible for at least part of the antitumoral properties of 6-TG, providing an insight into mechanism of its action as an epigenetic drug.

    Keywords: DNA methyltransferase, Histone deacetylase, Leukemia, Thioguanine, Thiopurine
  • Edris Sharif Rahmani, Majid Fathi, Mohammad Foad Abazari, Hojat Hhahraki, Vahid Ziaee, Hamzeh Rahimi, Arshad Hoseini* Pages 38-48
    Background

    Hemophagocytic lymphohistiocytosis (HLH) is an immune system disorder characterized by uncontrolled hyper-inflammation owing to hypercytokinemia from the activated but ineffective cytotoxic cells. Establishing a correct diagnosis for HLH patients due to the similarity of this disease with other conditions like malignant lymphoma and leukemia and similarity among its two forms is difficult and not always a successful procedure. Besides, the molecular characterization of HLH due to the locus and allelic heterogeneity is a challenging issue.

    Materials and Methods

    In this experimental study, whole exome sequencing (WES) was used for mutation detection in a four-member Iranian family with children suffering from signs and symptoms of HLH disease. Data analysis was performed by using a multi-step in-house WES approach on Linux OS.

    Result

    In this study, a homozygous nucleotide substitution mutation (c.551G>A:p.W184*) was detected in exon number six of the UNC13D gene. W184* drives to a premature stop codon, so produce a truncated protein. This mutation inherited from parents to a four-month female infant with an autosomal recessive pattern. Parents were carrying out the heterozygous form of W184* without any symptoms. The patient showed clinical signs such as fever, diarrhea, hepatosplenomegaly, high level of ferritin, and a positive family history of HLH disease. W184* has a damaging effect on cytotoxic T lymphocytes, and natural killer cells. These two types of immune system cells without a healthy product of the UNC13D gene will be unable to discharge toxic granules into the synaptic space, so the inflammation in the immune response does not disappear.

    Conclusion

    According to this study, WES can be a reliable, fast, and cost-effective approach for the molecular characterization of HLH patients. Plus, WES specific data analysis platform introduced by this study potentially offers a high-speed analysis step. This cost-free platform doesn't require online data submission.

    Keywords: Hemophagocytic Lymphohistiocytosis, Sequencing, UNC13D
  • Robab Naghibzadeh, Narges Obeidi*, Alireza Farsinejd, Gholamreza Khamisipour, Masoud Tohid Far Pages 49-56
    Background

    Due to the estrogen participation in modulating the proliferation and commitment of stem cells and the effects of miR-21 and miR-155 expression on reduced proliferation and colony formation of acute myeloid leukemia (AML), the aim of the present study was to evaluate the effect of estradiol on expression of miR-21 and miR-155 in the NB4 cell line, as an acute promyelocytic leukemia (APL).

    Materials and Methods

    In the present experiment, NB4 cells were treated with different quantities of estradiol (5, 25, 50, 75, 100, 150, 200, 250 μg/ml) and vehicle control for 24 and 48 hours. Viability, apoptosis, and cellular proliferation were estimated by trypan blue exclusion, flow cytometry, and MTT assays, respectively. The level of miR-155 and miR-21 expression was studied using absolute quantitative real-time PCR.

    Results

    Results showed that estradiol in the effective dose (200 μg/ml) led to decreased cellular viability (in a dose dependent manner, P = 0.004) and apoptosis of NB4 cells. In addition, the expressions of miR-155 and miR-21 were significantly and dose-dependently decreased (p<0.05).

    Conclusion

    Estradiol at the effective dose caused apoptosis in NB4 cell line. This substance can be used as a drug for the treatment of APL. However, further assessments are needed to support the effectiveness of estradiol in the treatment of APL.

    Keywords: cute Myeloid Leukemia (AML), Estradiol, MiR-155, MiR-21
  • Mozhgan Hashemieh* Pages 57-68

    Improved survival among transfusion dependent thalassemia patients in recent years has led to the manifestation of morbidities such as renal dysfunction. Renal injury is still an underestimated complication in β thalassemia major patients. Chronic anemia, iron overload due to repeated transfusion, and specific iron chelators are the main factors in pathogenesis of renal dysfunction in β thalassemia. Early identification of this morbidity allows us to delay the progression of kidney damage and therefore reduce renal impairment. In recent decades , novel biomarkers for early recognition of renal dysfunction have been studied in thalassemic patients, such as cystatin C, beta 2 microglobulin , alpha 1 microglobulin, N-acetyl beta-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocaline (NGAL) , kidney injury molecule 1 (KIM-1) , liver type fatty acid binding protein (L-FABP), and retinol binding protein (RBP). In this review, renal aspects of thalassemia with focus on novel biomarkers were discussed.

    Keywords: : β thalassemia, Biomarkers, Renal Insufficiency
  • Kourosh Goudarzipour, Ahmad Mohammadi, Reza Taherian, Mehran Arabahmadi*, Behdad Behnam, Niloofar Ayoobi Yazdi Pages 69-73

    Acute lymphocytic leukemia (ALL) is one of the frequent malignancies in pediatrics and involves bone marrow and extramedullary sites. Proptosis as extramedullary involvement of leukemia usually present in acute and chronic myeloid leukemia. It is extremely rare for ALL to present initially as proptosis.Here, a-21-month-old boy was presented with proptosis without any associated symptoms except lymphadenopathy. He was referred with the impression of malignancy from an ophthalmologist. After bone marrow biopsy which showed 33% blast cells, all positive for CD10, CD19, and CD79, the diagnosis of pre-B cell ALL was finally made. His symptoms were improved completely 16 days after starting standard protocol for ALL.Afterone-year follow-up, he was free of any symptoms.According to this initial presentation of ALL and no typical associated symptoms, it is important to make rapid diagnosis and start the treatment in the childhood.

    Keywords: Acute lymphoblastic leukemia, Proptosis, Childhood