Iranian Journal of Pediatric Hematology and Oncology
Volume:10 Issue: 4, Autumn 2020

Given that Hodgkin’s lymphoma (HL) accounts for 5%–6% of pediatric malignancies, we investigated the clinical characteristics and survival of pediatric patients with HL in our center.

In this cross sectional and retrospective study, the medical charts of all patients under the age of 18 diagnosed with HL from 2006 to 2016 at Shahid Sadoughi Hospital Yazd, Iran, were retrieved. Data were analyzed by SPSS (version 18) using K square and T-Test. Survival was analyzed using Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression method.

This study included 34 patients. In terms of gender, there were 20 boys and 14 girls in this study. The mean age of the patients was 10.42 years. The most common subtype of HL was mixed cellularity. Regarding disease stage, 55.9% of the patients were in stage I. All subtypes except for nodular sclerosis were more common in boys. The mean survival of patients in this study was 151.68 months. At the end of the study, there was just one death. The 5-year survival of patients was 100% and the 10-year survival was 94%. There was no significant relationship between survival and sex, histologic subtype, or the stage of the disease.

The results of the current study showed that majority of our patients had been diagnosed in a low stage and we achieved the best results for 5- and 10- year- overall survival through applied treatment.

Acute kidney injury (AKI) is defined as a failure in renal function leading to insufficiency of fluid and electrolyte homeostasis. Thus, sensitive biomarkers of renal tubular injury are needed to detect AKI earlier. In this study, urinary beta 2-microglobulin (β2-MG) and urinary N-acetyl-β-D-glucosaminidase (NAG) were evaluated for AKI prognosis/diagnosis in pediatric patients suffering different cancers prescribed with Ifosfamide, Ifosfamide plus Carboplatin, and Ifosfamide plus Cisplatin.

In this prospective study done in Isfahan, Iran, urinary β2-MG, urinary NAG, blood urea nitrogen (BUN), and serum and urinary creatinine (Cr) were measured in 40 pediatric cancer patients less than 16 years old in three age groups during 61 courses of chemotherapy on day 0, three and six after the treatment.

Using ANOVA and t-test, the mean levels of urinary β2-MG (p= 0.001), urinary β2-MG/Cr (p= 0.003) and urinary NAG/Cr (p= 0.001), before and on day six of the treatment were statistically significant (p< 0.05). Also, the mean levels of BUN (p= 0.01), urinary β2-MG (p= 0.001), β2-MG/Cr (p= 0.001) and NAG/Cr (p= 0.004) based on the gender groups, the mean levels of urinary NAG (p=0.001), NAG/Cr (p= 0.001) and β2-MG/Cr (p= 0.008) based on three age groups, and the mean levels of serum Cr (p= 0.047), urinary β2-MG (p= 0.005), β2-MG/Cr (p= 0.032) and NAG/Cr (p= 0.032) based on the Ifosfamide dosage were statistically significant during the time of the treatment.

Urinary β2-MG, urinary β2-MG/Cr, and urinary NAG/Cr are more significant biomarkers than serum Cr in earlier diagnosis and treatment of AKI in cancer patients. However, urinary NAG should be further studied to prove its reliability for AKI prognosis/diagnosis. It is suggested that urinary NAG can be used along with other renal biomarkers such as urinary β2-MG, kidney injury molecule-1(KIM-1), or interleukin-18 (IL-18) for AKI prognosis/diagnosis.

Creating a new berberine liposome with high encapsulation efficiency and slow release formulation in the treatment of cancer is a new issue. Therefore, the aim of current study was to develop slow release berberine-containing nanoliposome for delivery to bone cancer cells Saos2.

In this experimental study, after synthesis nanoliposomal formulation, physical parameters, including size, zeta potential, and drug loading, in liposome were assessed using different techniques. Saos2 cell line was incubated in micro-plates containing Dulbeccochr('39')s Modified Eaglechr('39')s medium (DMEM) and FBS at 37˚C and 5% CO2. Cytotoxicity of nanoliposome was assessed using MTT assay. The release of drug from nanoliposome was assessed by dialysis method. P< 0.05 was assumed significant.

The size of drug-free nanoliposome and drug nanoliposome (berberine-nanoliposome) was 112.1 and 114.9 nm, respectively. The zeta potential of drug-free nanoliposome and drug- nanoliposome was –16.1 and –1.9 mv, respectively. There was no significant difference between control and drug-free nanoliposome groups regarding viability (p>0.05). The viability of cells in different concentration of nanoliposome containing berberines in Saos2 cell line was significantly higher than that in free berberines (p<0.05). The release of berberine at temperature 37 º C and pH 7.4 showed that approximately 47% of the drug was released in the first 12 hours of study and then the slow release of drug was continued. IC50 value of free berberine and berberine containing nanoliposome was 137.3 and 52.2 µg / ml, respectively.

According to these findings, IC50 value of free berberine was 2.67 times more than berberine containing nanoliposome, indicating that nanoliposome containing berberine had more inhibition on growth of cancer cells than free berberine. In addition, the drug release was slow exposing the drug to the tumor for longer time at a lower dose and fewer injections, increasing the effect of the drug on cancer cells.

Due to the increase in cancer and side effects of common therapies, researchers are looking for treatments with the least side effects, which is why medicinal plants have become so important. Adiantum capillus-veneris L. plant commonly called southern maidenhair fern, and also named as “Pare-siavashan” in medical and pharmaceutical textbooks of Iranian Traditional Medicine, contains triterpenoid compounds that have anti-tumor properties. It is a perennial fern with narrow stems and small leaves that grows in hot and humid places. This study aims to make biocompatible nanosystems carrying Adiantum capillus-veneris extract with an appropriate loading rate and to compare the anti-tumor properties of the extract-carrying system with its free state.

After Extracting by Soxhlet, the resulting extract was loaded in the nano-niosome system by thin-film method and was subjected to physical, chemical, and cellular characterization.

The results of this study showed that the loading rate of Adiantum capillus-veneris extract in niosomic formulation is 50.74% and the resulting particles are spherical with a size of 325.7nm and anionic. No chemical interactions were found between niosome and extract and the resulting system was chemically stable.

Based on acquired results, the designed system has acceptable anti-cancer properties on MCF7 cell line. It is notable that the cell survival rate was about 19 %.

Iron extra load is an anticipated and lethal consequence of chronic blood transfusion in major beta-thalassemia patients; therefore it is necessary to use an efficient iron chelator drug to stimulate the evacuation of the surplus iron from the body. This trial was performed to compare myocardial and hepatic magnetic resonance imaging T2 (MRI T2*) results of beta-thalassemia patients treated by Deferasirox or combination of Deferoxamine and Deferiprone.

In this clinical trial, 44 patients who were on combination therapy with Deferiprone and Deferoxamine and complied with the inclusion criteria were randomized to either case (Deferasirox) or control (combined therapy) groups. Twenty-two patients in the case group received Deferasirox. For 22 patients in the control group, prior treatment with Deferiprone and Deferoxamine was continued. Myocardial and hepatic MRI T2* results were assessed before and after the study. Moreover, serum ferritin level (SFL) was evaluated every 3 months.

SFL at the start of the study did not differ significantly in two groups (2158.1± 1012.2 μg/L in the control group vs. 2145.5±1121.4 μg/L in the case group) (P=0.08). SFL at the end of the study did not differ significantly in two groups (2204.4±1143.5 μg/L in the control group vs. 2347.2±1236.6 μg/L in the case group), either (P=0.12). In each group, myocardial and hepatic MRI T2 at the start and at the end of the trial did not differ significantly (P>0.1).

Myocardial and hepatic MRI T2*results were better in the control (combination therapy) group than those in the case (Deferasirox) group. Major beta-thalassemia patients replied to combined treatment better than Deferasirox.

Patients with thalassemia major require frequent blood transfusions. Blood transfusion can lead to the adverse reactions. Reporting and evaluating the transfusion reactions are among the goals of implementing the hemovigilance system to improve blood recipients’ safety. This study aimed to compare the transfusion reactions in the thalassemia patients before and after implementation of the hemovigilance system in the Shahid Sadoughi Hospital in Yazd (Iran).

  In this historical cohort study conducted in 2018, the data of 87 patients with thalassemia major including age, sex, the total number of blood transfusions before and after the implementation of hemovigilance system, information about the occurrence of blood transfusion reactions, type, and severity of each reaction were recorded in the questionnaire. Paired-Samples T-test and Chi-Square test were used for data analysis.

The mean age of the participants was equal to 19.69±8.41 years old and 52% of them were male. The age of onset of transfusion was 14.3±16.62 months with a range of 2 - 96 months. The relative frequency of transfusion reactions in the thalassemia patients was 0.74% and 0.81%, respectively before and after implementation of the hemovigilance system. Allergic (54%) and non-hemolytic febrile reactions (23%) were the most frequent transfusion reactions. Severe and life-threatening reactions were reported more frequently after implementation of the hemovigilance system compared to pre-implementation (p=0.007). Totally, 8% of the reactions were hemolytic reactions and 7.5% of the patients had unexpected alloantibodies identified after implementation of the hemovigilance system.

Documentation and reporting of the transfusion reactions after implementation of the hemovigilance system have resulted in reporting of more severe reactions and determination of the clinically significant alloantibodies. Therefore, prevention of the subsequent reactions and increasing the safety of the blood transfusion for the thalassemia patients could be provided, emphasizing the continuation of the system.

Transcription factors (TFs) play a key role in the development, therapy, and relapse of B-cell malignancies, such as B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Given the essential function of Forkhead box protein P1 (FOXP1) transcription factor in the early development of B-cells, this study was designed to evaluate FOXP1 gene expression levels in pediatric BCP-ALL patients and NALM6 cell-line.

This case-control study was done on the NALM6 cell-line and bone marrow specimens of 23 pediatric BCP-ALL patients (median age: 7.5 years; range: 2.0 – 15.0 years) at different clinical stages including new diagnosis, 15th day after the treatment, and relapse. Also, 10 healthy children were included as the control group. FOXP1 gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation analysis was performed between the FOXP1 gene expression and patients’ demographic and laboratory characteristics.

The results showed that FOXP1 gene expression was significantly downregulated in the NALM-6 cell-line (median=0.05, P<0.001) and patients at new diagnosis (median=0.06, p<0.0001), and relapse (median=0.001, p<0.0001) phases, compared to the control group (median=0.08). FOXP1 gene expression on the 15th day of the treatment was significantly higher than its level at the new diagnosis stage (p<0.001). Moreover, FOXP1 gene was significantly downregulated in the relapse phase compared to the new diagnosis. Patients whose number of bone marrow blasts on the 15th day of the treatment was below 5% had higher FOXP1 gene expression at the diagnosis phase (Spearman’s correlation, P<0.05, r=-0.485) and higher ratio of diagnosis/day 15 (p<0.001, Mann-Whitney U test).

FOXP1 levels could be a potential biomarker of therapy response in remission induction therapy for pediatric BCP-ALL patients.

The basic unit of chromatin is a nucleosome included an octamer of the four core histones and 147 base pairs of DNA. Posttranslational histones modifications affect chromatin structure resulting in gene expression changes. CpG islands hypermethylation within the gene promoter regions and the deacetylation of histone proteins are the most common epigenetic modifications. The aberrant patterns of methylation localized in normally unmethylated CPG islands mediate chromatin compaction resulting in gene silencing and cancer induction. The current review article aimed to assess and analyze the available literature on the tumor suppressor genes (TSGs) hypermethylation in hepatocellular carcinoma (HCC). For this review article, the suitable studies were obtained by searching PubMed, SCOPUS, NCBI, and Ovid database from 1995 up to September 2018 with the MeSH terms combined with free terms.  A total 1483 Items were identified in SCOPUS (n = 459), PubMed (n = 832), Ovid (n = 118), and other reference sources (n = 74). After the assessment, 73 manuscripts were included in the current study. In total, 13 genes were found to have the most effect on HCC. Therefore, we selected them to evaluate as candidate genes in this cancer. TSGs can affect cell cycle during various stages of the cycle an at the cell cycle checkpoints. The hypermethylation of these genes results in chromatin compaction and TSGs silencing which induces HCC.

Kikuchi Fujimoto Disease (KFD), also known as necrotic histiocystic lymphadenitis, is a condition with unknown etiology. Probably, infectious, viral, and also autoimmune etiologies, especially lupus erythematosus, contribute to this disorder. The common signs are lymphadenopathy along with fever and leukopenia. Our case was a13-year-old boy with fever of unknown origin. He underwent ordinary fever of unknow origin (FUO) investigations and the only positive finding on his examination was lymphadenopathic fever of posterior cervical chain. The results of primary tests and also cultures of blood and urine samples did not have any specific contribution to diagnosis of infectious causes. Besides, bone marrow aspiration and biopsy led to the exclusion of chances of lymphoma or other malignancies. Finally, diagnosis of KFD was confirmed by the use of dissection of cervical lymph nodes and also via immunohistochemical tests and simultaneous positive antinuclear antibody (ANA). Hence, the patient was put on suitable medical treatment for lupus. Given the rare demonstrations of this case, i.e., the male sex and fever of unknown origin, and also the positive ANA despite clear clinical symptoms of lupus, this case was presented to provide both proper education and make a faster and more appropriate diagnosis.