So far treatment of advanced neuroblastoma is still difficult, due to its high malignancy. Currently comprehensive therapies, including high-dose multi-drug chemotherapy, surgery, stem cell transplantation, radiation, biological therapy and immune therapy as well as target therapy dominant the treatment of this disease, and we hereby introduce the latest development of treatment protocols for this disease.
Acute myeloid leukemia (AML) is a rare type of childhood acute leukemia, which has a worse prognosis than childhood acute lymphoblastic leukemia. Over the past decade, significant progress has been made in the treatment of childhood AML and the 5-year event-free survival rate may be as high as 70% in developed countries. This survival improvement is largely attributable to risk-stratified treatments, therapies tailored to individual patients based on the biological characteristics of the disease, and continuously improving supportive care. An accurate diagnosis is the prerequisite for risk stratification, prognostic evaluation and therapeutic decision making. How to reduce early mortality and thus improve overall survival, how to implement appropriate supportive treatment to reduce treatment-associated complications, and how to reduce treatment-related mortality are the key to the improvement of therapies for childhood acute myeloid leukemia.
Objective To study the treatment and outcome of childhood endodermal sinus tumor. Methods The clinical data of twelve children with endodermal sinus tumor between April 2000 and July 2013 were reviewed. The basic demographics, stages of the lesion and the treatment outcome were analyzed. Of the twelve patients, seven were boys and five were girls. The age of the disease onset was between 1 and 3.3 years, except one in 11 years. Two patients were in Brodeur Stage Ⅰ, four in Stage Ⅱ, two in Stage Ⅲ, and four in Stage Ⅳ. One patient underwent surgery alone, one underwent surgery plus a combination therapy with vincristine, actinomycin and cyclophosphamide (VAC), and the other ten were treated by surgery with the use of cisplatin, etoposide and bleomycin (PEB) before or after the operation. Results Eleven patients were successfully followed up and ten were alive. The length of survival was 4.5 to 66 months in the 10 patients. In the 10 patients treated with PEB before or after surgery, 8 achieved complete remission, one achieved partial remission and one was not followed up. The major complications associated with the PEB regimen included myelosuppression and gastrointestinal upset symptoms and no late toxicity was observed. Conclusions Preoperative or postoperative administration of PEB may be an effective and safe management modality for childhood endodermal sinus tumor. Nevertheless, further validation is warranted in prospective studies involving a larger sample size.
Objective Matrine, a major ingredient of sophora, has an anti-tumor activity, capable of suppressing the proliferation and metastasis and promoting apoptosis or differentiation of tumor cells. This study was designed to investigate the effects of matrine on survival and apoptosis of nephroblastoma cell line SK-NEP-1, reduction of drugresistance of cisplatin and the mechanism(s) underlying these effects. Methods SK-NEP-1 cells were treated with matrine and cisplatin at various doses (0.5, 1.0 and 1.5 mg/mL), either each alone or in combination. The viability in treated SK-NEP-1 cells was assessed by MTT colorimetric assay, apoptosis by flow cytometry, and PDCD4 mRNA abundance by RT-PCR. Results As compared with the non-treatment control, matrine and cisplation, regardless of combination and dosage, significantly reduced the viability (P<0.01), induced apoptosis (P<0.01), and increased PDCD4 mRNA abundance (P<0.01), in SK-NEP-1 cells. The above effects of matrine and cisplation were dose-dependent when they were used alone, and were more pronounced when they were used in combination (P<0.05). Conclusions Matrine can significantly induce apoptosis and inhibit growth of SK-NEP-1 cells in a dose-dependent manner, thus increasing the chemotherapeutic sensibility of cisplatin. The observed effects of matrine may be a result of increased PDCD4 expressi on.
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Objective To study the expression of ecotropic viral integration site (EVI1) gene in childhood acute myeloid leukemia (AML) and the clinical features of EVI1-positive children with AML. Methods The clinical data of EVI1-positive children with AML were collected and analyzed. RT-PCR and real-time quantitative PCR were used for qualitative and quantitative analysis of expression of EVI1. Flow cytometry (FCM) was used for determining the immunophenotypes of bone marrow cells. Multiparameter FCM was used for monitoring minimal residual disease. The karyotypes were determined. Results Of 241 children with AML, 33 (13.7%) were positive for EVI1 expression. There were no significant differences in age at first visit as well as the white blood cell count, hemoglobin level, and platelet count in peripheral blood between EVI1-positive and EVI1-negative children with AML (P>0.05), but EVI1-positive children had a significantly increased proportion of females compared with EVI1-negative children (P<0.05). The change in EVI1 expression was not synchronous with clinical remission and the change of MRD: some children had clinical remission or negative conversion of MRD before negative conversion of EVI1, while some had negative conversion of EVI1 before clinical remission or while MRD showed positive. EVI1 gene was usually co-expressed with other fusion genes. CD33 (100%), CD38 (88%), and HLADR (76%) were highly expressed in EVI1-positive children with AML. Abnormal chromosome structure or number was found in 15 patients. Compared with EVI1-negative children, EVI1-positive children had significantly lower complete remission rates after the first course of treatment (P<0.05). Conclusions EVI1-positive children with AML have a poor short-term prognosis. In the development of AML, the activation of EVI1 gene is not isolated, but the result of interactions with other genes or chromosome abnormalities, and the mechanism of activation and its function need further study.
Objective To investigate the effect of small interfering RNA (siRNA) silencing Apollon gene combined with tetramethylpyrazine (TMP) on the proliferation and apoptosis of human chronic myeloid leukemia cell line K562. Methods K562 cells were divided into blank control, negative control, and RNA interference (RNAi) group. For the RNAi group, the pGPHI-GFP-Neo-Apollon eukaryotic expression vector based on the best Apollon siRNA fragments screened out in previous experiments was constructed; the blank control group received no treatment, and the negative control group was transfected with negative plasmid vector. The mRNA and protein expression of Apollon was measured by RT-PCR and cell immunofluorescence, respectively. Additionally, TMP (320 μg/mL) was applied to set TMP, TMP+negative control, and TMP+RNAi groups. The cell viability and apoptosis rate were determined by MTT assay and flow cytometry, respectively. Results The constructed vector was stably expressed in K562 cells. The RNAi group had significantly lower mRNA and protein expression of Apollon than the blank control group and negative control (P<0.05). The RNAi group had significantly increased proliferation inhibition rate and apoptosis rate, as compared with the blank contorl group (P<0.05). The TMP+RNAi group had significantly increased proliferation inhibition rate and apoptosis rate, as compared with the RNAi, and TMP groups (P<0.05). Conclusions Apollon siRNA can significantly inhibit the proliferation and promote the apoptosis of K562 cells, and the addition of TMP can further increase the proliferation inhibition rate and apoptosis rate, suggesting that siRNA technology combined with drugs has a significant potential value in the treatment of leukemia.
Objective To investigate the effect of Huangqi injection on the short-term prognosis in childhood with acute lymphoblastic leukemia (ALL). Methods A retrospective analysis was performed on the clinical data of 105 children newly diagnosed with ALL between January 2009 and December 2012. These children were randomly divided into treatment group (18 low-risk cases, 7 medium-risk cases, and 24 high-risk cases) and control group (21 low-risk cases, 7 medium-risk cases, 28 high-risk cases). Both groups were given remission induction therapy based on the levels of risk. Throughout the remission induction therapy, the treatment group also received Huangqi injection (0.5-1.0 mL/kg per day) by intravenous infusion, while the control group was given 0.9% sodium chloride injection instead. The two groups were compared in terms of distribution of prognostic factors and complete remission (CR) rate after remission induction therapy, as well as the incidence of minimal residual disease (MDR) (≥ 10-4 and < 10-4) among all patients in the two groups on day 19 of remission induction therapy and among B-ALL patients in the two groups when achieving a CR at the end of remission induction therapy. Results Of the 105 children with ALL, 99 had B-ALL, and 6 had T-ALL. There were no significant differences in the distribution of prognostic factors between the two groups (P>0.05). The overall CR rate of 105 patients was 79%; there was no significant difference in CR rate between the treatment and control groups (82% vs 77%; P>0.05); also, no significant differences were found between the two groups in the CR rates among high-, medium-, and low-risk cases (P>0.05). On day 19 of remission induction therapy, the incidence of MRD ≥10-4 in the treatment group was significantly lower than that in the control group (69% vs 95%; P<0.05); among 80 children with B-ALL who achieved a CR (43 cases in the control group and 37 cases in the treatment group), the incidence of MRD ≥10-4 was significantly lower in the treatment group than in the control group (27% vs 58%; P<0.05); in both circumstances above, the high-and low-risk cases in the treatment group had a significantly lower incidence of MRD ≥10-4 than the control group (P<0.05). Conclusions Huangqi injection combined with chemotherapy has an enhanced anti-tumor effect and can improve the short-term prognosis and clinical outcome in children with ALL.
Objective To investigate the effects of Huangqi injection on the infection factors in children with acute lymphoblastic leukemia (ALL) during remission induction chemotherapy. Methods Ninety-one children with ALL were divided into treatment (n=47) and control groups (n=44) by a randomized double-blind method. During remission induction chemotherapy, the treatment group was given Huangqi injection (0.5 mL/kg·d) for 35 days, while an equal volume of normal saline was used instead in the control group; the other supportive care was the same for the two groups. After remission induction chemotherapy, the incidence of infection, duration of infection, white blood cell and neutrophil counts, site of infection, and positive rate of pathogenic bacteria in secretion were compared between the two groups. Results Four cases in the treatment group dropped out of the study due to allergic reaction. After remission induction chemotherapy, compared with the control group, the treatment group had a significantly lower incidence of infection (P<0.05), a shorter duration of infection at any site (P<0.05), a higher neutrophil count after chemotherapy (P<0.05), and lower incidence rates of respiratory tract infection, urinary tract infection, blood infection, and skin and soft tissue infections (P<0.05). Gram-negative bacteria were the main pathogens. Among the infected children, the positive rate of pathogenic bacteria in secretion was significantly lower in the treatment group than in the control group (P<0.05). Conclusions Huangqi injection may reduce bone marrow suppression caused by chemotherapy drugs and increase neutrophil count during remission induction chemotherapy to reduce the incidence and duration of infection in children with ALL.
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The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a long-term curative effect. However, L-asp is associated with high incidence of adverse reactions. This has prompted the development of pegylated asparaginase (PEG-asp), which has undergone extensive testing. Apparently, PEG-asp has a prolonged half-life with a better tolerance profile while retaining the antileukemic effect. In this review, we attempt to outline the history of clinical application of L-asp, the pharmacological and clinical potential of various preparations of L-asp, the development of PEG-asp, and the clinical application and adverse events of PEG-asp. The literatures reviewed in this article is collected through online search of the major databases both in English and Chinese.
Objective This study aimed to evaluate the diagnostic value of a 24-hour esophageal combined multichannel intraluminal impedance pH (24 h our MⅡ-pH) monitoring in children with gastroesophageal reflux (GER) disease and recurrent pneumonia. Methods A total of 17 cases with a suspected diagnosis of GER disease children with unexplained recurrent pneumonia underwent a 24-hour MⅡ-pH monitoring to analysis of the nature and characteristics of reflux. Results In the 17 cases of GER disease with recurrent pneumonia, 11 (65%) were confirmed positively by a 24-hours of MⅡ-pH monitoring. A total of 853 reflux cycle were detected, of which 65.3% were acid refluxes predominantly occurring within 2 hours after meal, and 71.6% were mixed refluxes. Refluxes occurred most frequently in the supine position, followed by the lateral position and the prone position. Distal reflux was the predominant form of reflux. According to the Biox-Ochoa classification, 73% of cases (8/11) were severe GER. Conclusions MII-pH monitoring may effectively characterize refluxate properties and thereby increase the detection rate of GER disease.
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Tuberculosis (TB) is a chronic infectious disease that seriously harms human health and wellbeing. Given its atypical clinical manifestations, TB is hard to be diagnosed in clinical settings; to date no highly sensitive screening approaches are available. Due to the emergence of multidrug-resistant strains of TB (MDR-TB) and limited options for medications in children, the treatment of TB is even more challenging in pediatric patients. This paper aims to comprehensively review the literature on the recent advances in the research on the epidemiology and clinical manifestations of TB, on TB diagnostic approaches (e.g., tuberculin skin test, imaging studies, and laboratory tests), and on TB treatment in children.