فهرست مطالب

Iranian Journal of Pediatric Hematology and Oncology
Volume:11 Issue: 1, Winter 2021

  • تاریخ انتشار: 1399/10/20
  • تعداد عناوین: 8
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  • Masumeh Sanaei, Fraidoon Kavoosi* Pages 1-10
    Background

    Aberrant DNA methylation of the promoter region is one of the most epigenetic changes in numerous cancers. DNA methyltransferase inhibitors (DNMTIs) can revert DNA hypermethylation in tumor suppressor genes (TSGs). The present study was designed to investigate the effect of 5-fluoro-2′-deoxycytidine (FdCyd) on p16INK4a, p14ARF, p15INK4b, and DNA methyltransferase 1, 3a, and 3b genes expression, apoptosis induction, cell growth inhibition in pancreatic cancer AsPC-1 and hepatocellular carcinoma LCL-PI 11 cell lines.

    Materials and Methods

    The cells were treated with FdCyd at different periods. Then, the MTT assay, cell apoptosis assay, and qRT-PCR were done to determine cell viability, cell apoptosis, and the relative gene expression level respectively.

    Results

    The FdCyd decreased DNA methyltransferase 1, 3a, and 3b and increased p16INK4a, p14ARF, and p15INK4b genes expression significantly (P<0.001). Besides, LCL-PI 11 cell was more sensitive to FdCyd in comparison to AsPC-1 cell. FdCyd induced significant cell growth inhibition with a dose- and time-dependent manner (P<0.001). The IC50 value of FdCyd was obtained with approximately 1μM. Further, FdCyd induced cell apoptosis significantly as a time-dependent manner. The number of apoptotic cells was significantly increased in all groups. The percentage of apoptotic cells after 24 and 48 h were 13.86 and 29.6 % in AsPC-1 and 21.04 and 41.52 % in LCL-PI 11 cell line respectively (P<0.001).

    Conclusion

    The FdCyd can reactivate the p16INK4a, p14ARF, and p15INK4b through inhibition of DNA methyltransferase 1, 3a, and 3b gene expression.

    Keywords: : 5-fluoro-2′-deoxycytidine, Genes, Neoplasm, Onco-Suppressor
  • Win-Yu Aung*, Thae Nu Htwe, Myat Thandar, Ohn Mar Pages 11-17
    Background

    Thalassemia constitutes a major public health problem causing a significant burden on children and their families. Zinc deficiency plays an important role in many thalassemia-related complications like growth retardation, hypogonadism and delayed puberty which are frequently noted in adolescent age. Although zinc is supplemented to thalassemic patients visiting Day Care Center, Yangon Children Hospital (YCH), Myanmar, a report concerning serum zinc level of these patients is still lacking. This study, therefore, aimed to assess serum zinc status in thalassemic adolescents attending Day Care Center, YCH.

    Materials and Methods

    This hospital-based cross-sectional study was conducted on 99 thalassemic adolescents. Mean age of diagnosis was 5.1±2.1 years. Non-fasting serum zinc concentration was determined by atomic absorption spectrophotometry. According to National Health and Nutrition Examination Survey data, zinc deficiency was defined as serum zinc concentration < 66 μg/dL (female) and < 70 μg/dL (male).

    Results

    Serum zinc concentration (μg/dL) was 57.35 (47.30-80.14) (median, interquartile range) with maximum, 195.05 and minimum, 28.83. Zinc deficiency was observed in 69.7% (69 out of 99; 35 males and 34 females) of the patients. The associations of zinc deficiency with gender, phenotype and the use of chelator were non-significant (P>0.05).

    Conclusion

    In spite of zinc supplementation, nearly 70% of the thalassemic adolescents showed zinc deficiency. Zinc deficiency in these adolescents might not be related to gender, phenotypes or the use of chelator. Poor compliance to take zinc supplementation and/or irregular blood transfusion could partly be attributable to zinc deficiency in these adolescents. Providing health education on the importance of regular intake of adequate zinc is advisable and periodic evaluation of zinc levels is recommended for thalassemic adolescents.

    Keywords: Adolescents, Thalassemia, Zinc
  • Shahin Koohmanaee, Bahram Dabandi, Adel Baghersalimi, Roghayeh Zare, Mohammad Aghaeizadeh Zoroufi, Seyyedeh Golnaz Mirmonsef, Afagh Hassanzadeh Rad, Arian Akhavan, Kioomars Golshekan, Farzaneh Moamer, Abdolreza Medghalchi, Setila Dlili* Pages 18-23
    Background

    Osteoporosis is one of the main causes of morbidity in patients with thalassemia major. Osteoprotegerin (OPG) is secreted by osteoblasts and osteogenic stromal stem cells and protects the skeleton from excessive bone reabsorption. In this study, the authors aimed to assess the relationship between OPG with osteoporosis and osteopenia in patients with thalassemia major.

    Materials and Methods

    In this analytic cross-sectional study, 37 patients aged 8-18 years, with thalassemia major were enrolled. Biochemical markers including hemoglobin, ferritin, calcium, phosphorus levels, and MRI T2* heart and liver were assessed. A bone mineral densitometry (BMD) was performed as well. Statistical analysis was performed by the independent T-test and Chi-Square test using the SPSS 20. The Multiple linear regression analysis was used to investigate the association between the BMD Z-score and OPG by the effect modification.

    Results

    The mean age of patients was 14.86±3.72 years. Normal bone density, osteopenia, and osteoporosis were noted in 2 (5.4%), 21 (56.8%), and 14 (37.08%) patients, respectively. The number of girls (P=0.042), mean age (P=0.045), and MRI T2* heart (P=0.033) in patients with osteopenia was significantly higher than patients with osteoporosis. The BMD Z-score was not significantly associated with OPG regarding the total number of participants, whereas in patients with osteoporosis, this association was significant (P=0.001). In all effect modified models, BMD remained statistically non-significant except for body mass index modification (P=0.046).

    Conclusion

    Based on the results, it seems that further complicated studies are needed to be performed on this issue.

    Keywords: Beta-Thalassemia, Child, Osteoprotegerin
  • Teny Tjitra Sari*, Dewi Wulandari, Astrid Indrafebrina Sugianto Pages 24-29
    Background

    Zinc depletion decreases monocyte functions and survival while excessive amount of zinc inhibits monocyte activation. Monocytes shift from conducting intercellular communication to becoming innate immune function as a response. This study aims to examine the influence of zinc status on the monocyte phagocytosis in patients with major beta-thalassemia.

    Materials and Methods

    This study was a randomized-placebo-controlled trial. The patients were randomly assigned into either the zinc-treated group using zinc gluconate 50mg daily or the placebo group. Analysis is based on the 12-weeks observation of the complete blood count, plasma zinc level, and phagocytosis level of monocytes. The phagocytic activity of monocytes was measured using atomic absorption spectroscopy (AAS) or x-ray fluorescence (XRF). The comparisons of the data within each group were analyzed using Mann-Whitney test.

    Results

    The results indicated no significant differences in patients’ characteristics; the level of plasma zinc at week 12 in the zinc-treated group (67.41+14.4) was significantly higher than the placebo group (54.37+9.38) (p=0.047). The phagocytosis levels of monocyte at week 12 in zinc-treated group (8.70+4.61) were higher than the placebo groups (8.23+4.22) (p=0.002). The ferritin level of zinc-treated group was higher than placebo group (p=0.084), while high level of ferritin is associated with higher level of monocyte phagocytic activity, the result is statistically significant (p=0.002). The results also showed that higher level of plasma zinc insignificantly correlates with lower phagocytic activity of the monocytes (p=0.059).

    Conclusion

    The immune mechanisms in response to zinc-deficient environment underlying the shifting between adaptive to innate immune response involves multiple molecular components of the immune system and have been attributed to specific features of -thalassemia, in which overall immune activity is decreased even though the phagocytic activity of monocytes is increased.

    Keywords: Major beta thalassemia, Monocytes, Phagocytosis, Zinc
  • Reihaneh Mortazavi Ardestani, Masoud Ardestani* Pages 30-40
    Background

    Iron overload is caused early progression of atherosclerosis in beta thalassemia patients due to regular repeated blood transfusion. MRI T2* is a gold standard non-invasive method for detecting hepatic and cardiac iron overload. The aim of this study was the comparison of carotid intima media thickness (CIMT) in the patients and healthy control groups with Doppler ultrasound for early diagnosis of atherogenesis. Another purpose was to assess the relationship between CIMT and iron overload among patients.

    Materials and methods

    This cross-sectional study was performed on twenty patients referred to the Sarvar clinic and twenty age- and sex-matched control group. The CIMT was measured with Color Doppler ultrasound in both groups. Then, MRI T2* results, demographic, and therapeutic information were extracted from their documents.

    Results

    CIMT was insignificantly higher in the patients compared to the control group. For example, it was 0.49 ± 0.05 vs. 0.45 ± 0.03 (p = 0.009) for the right common carotid artery (RCCA) and 0.48 ± 0.06 vs. 0.46 ± 0.04 (p = 0.17) for the left common carotid artery (LCCA). There was no strong relationship between CIMT and age (p = 0.09 for RCCA, p = 0.00 for LCCA), sex, chelation type (for example, p = 0.51 for RCCA with Desferal and p = 0.91 for LCCA with Desferal), age at diagnosis, age at the beginning on transfusion (p = 0.49 for RCCA, p = 0.20 for LCCA), age at the start of chelator (p = 0.74 for RCCA, p = 0.78 for LCCA), and hepatic and cardiac iron overload.

    Conclusion

    Preventive and curative methods should be planned to cease its progression. Furthermore, early initiation of chelator drugs with better efficacy and compliance may reverse the hepatotoxic and adverse myocardial effects of excessive iron.

    Keywords: Beta thalassemia major, Carotid intima media thickness, Iron overload, Magnetic Resonance Imaging
  • Mojgan Shaiegan, Ali Ghasemi, Maryam Zadsar*, Jahangir Ahmadi, Shahram Samiee, Tahereh Madani Pages 41-50
    Background

    Human platelet antigens (HPAs) are part of platelet GP complexes have the potential to contribute to the autoantibody production. Moreover, these antigens demonstrate different patterns of distribution on different ethnic groups and variation in some types of diseases. This study was objected to determine the incidence of HPA-1 to -5 and -15 polymorphisms in the Iranians suffering from primary Immune thrombocytopenic purpura (ITP). 

    Materials and Methods

    In this case-control investigation, 30 patients by definite primary ITP were randomly selected and enrolled in the study. HPA genotyping was performed implicating by the Single Specific Primer PCR (SSP-PCR). For the control group, data of recently published gene polymorphism among Iranian Blood donors were deployed for comparison. 

    Results

    The incidence of HPA-1 to -5 and -15 polymorphisms in the Iranian patients with primary ITP was found to be: HPA-1a/1a: 0.933, HPA-1a/1b: 0.067, HPA-2a/2a: 0.133, HPA-2a/2b: 0.867, HPA-3a/3a: 0.2, HPA-3a/3b: 0.533, HPA-3b/3b: 0.267, HPA-4a/4a: 1, HPA-5a/5a: 0.967, HPA-5a/5b: 0.330, HPA-15a/15a: 0.166, HPA-15a/15b: 0.667 & HPA-15b/15b: 0.167.  

    Conclusion

    This study provides special new data on the distribution of HPA allele among the Iranians ITP patients.Furthermore, it might useful toccharacterize understanding more presizely about ITP and HPA distribution. However, further studies concerning platelet immunology are needed to do help on best practice on management of immune diseases triggered by platelet antibodies.

    Keywords: Antigens, Blood Platelets, Human Platelet, Purpura, Thrombocytopenic
  • Mozhgan Hashemieh, Kourosh Sheibani* Pages 51-63

    Cardiac disease is the main cause of death in both forms of thalassemia; thalassemia major (TM) and thalassemia intermedia (TI). Pulmonary hypertension (PH) is one of the cardiopulmonary morbidities with high mortality that, if not treated, may trigger right-sided heart failure and premature death. PH is defined as a mean pulmonary artery pressure of ≥25 mmHg at rest or ≥30 mmHg during exercise. The prevalence of PH is known to be higher in TI than in TM. Moreover, the pathophysiology of PH in thalassemia appears to be sophisticated and complex. Risk factors for occurrence of PH consists of non-transfusion dependent thalassemia (NTDT), sub-optimally transfused transfusion dependent thalassemia (TDT), splenectomy, thrombocytosis, anemia, NRBC ≥ 300 × 106, iron accumulation, history of thrombosis and older age. Other parameters which aggravate the risk of PH include hemolysis, oxidative stress, hypoxemia, alteration of erythrocyte membrane, decline of nitric oxide biological availability, arginine abnormal regulation and arginase excess. The screening method for PH is Doppler echocardiography but the gold standard for detection of PH is right heart catheterization (RHC). Current medical therapeutic options in PH comprise hydroxyurea, L- Carnitine, sildenafil, calcium channel antagonists, endothelin 1-receptor blockers and prostacyclin agonists. The only curative surgical method for the refractory and severe cases of PH is pulmonary endarterectomy. In this article, the etiology, pathophysiology, diagnostic methods and novel therapies of thalassemia associated PH are discussed.

    Keywords: Cardiac, Pulmonary hypertension, Thalassemia
  • Sanaz Mehrabani*, Hassan Mahmoodi Nesheli Pages 64-69

    Lymphoma which has a wide range of manifestations is the third malignancy in pediatrics. Nearly, 50% of patients have extranodal involvement. Pancreas can be affected secondarily more than primarily. A 10-year-old boy with recurrent abdominal pain in the epigastric region for six weeks was referred to Amirkola Childrenchr('39')s Hospital, affiliated to Babol University of medical sciences (north of Iran). The patient was icteric with elevated levels of amylase and lipase. A hypoechoic mass near the head of the pancreas was detected by ultrasound examination. Pathology of stomach polyps revealed small blue round-cell tumor compatible with a lymphoma. In children with acute pancreatitis symptoms and palpable abdominal mass, the non-Hodgkin lymphomas (NHL) should be considered as an important, though rare possible cause.

    Keywords: B cell lymphoma, Child, Pancreatitis