Overall Survival Rate Of Children Research Articles

Estimated Late Health Outcomes in Children Newly Diagnosed with Mature B-Cell Non-Hodgkin Lymphoma Treated with Contemporary LMB Chemotherapy Based upon Similarly Treated Participants in the Childhood Cancer Survivor Study (CCSS)

Introduction: Since the mid-1990’s, overall survival rates for children diagnosed with mature B-cell non-Hodgkin lymphoma (B-NHL) have exceeded 90%, due in large part to the widespread utilization of the LMB chemotherapy regimen. As a result, a population of survivors living beyond 5 years from diagnosis and treatment with this regimen is emerging, providing the first opportunity to study late-occurring and chronic health outcomes following contemporary B-NHL therapy. Methods: Late health outcomes and health status were self-reported among CCSS participants who were 5-year survivors of childhood B-NHL and whose treatment exposures were consistent with LMB-defined risk-groups (A - low; B - intermediate; and C - high risk). Combinations of individual chemotherapy agents (cyclophosphamide [CPM], vincristine, prednisone, doxorubicin [doxo], high-dose methotrexate [HD-MTX], cytarabine, and etoposide) and respective cumulative doses (for CPM, doxo, HD-MTX, and etoposide) were abstracted from medical records. Chronic health conditions occurring ≥5 years from cancer diagnosis were graded per the Common Terminology Criteria for Adverse Events (version 4.03). Decreased fertility was defined as failure to achieve or sire a pregnancy after ≥1 year of trying among survivors of childbearing age (15-44 years). Health status outcomes were obtained from validated questionnaires. Standardized mortality ratios (SMRs) were estimated. Cox and logistic regression models (adjusted for age, sex, and race) provided hazard (HR) and odds ratios (OR) and 95% confidence intervals (CI) of health conditions and status compared to a sibling comparison group (n=4,023). Results: We identified 94 B-NHL survivors (median age 10 [range 2-20] years at diagnosis, 24 [10-39] years at evaluation, 14 [7-26] years post diagnosis), for which pertinent LMB treatment exposures are included in Table 1. Compared to siblings, survivors were more likely to be male (79% vs. 48%, p<0.001), younger at evaluation (24.3 ± 6.1 vs. 26.7 ± 9.2 years, p<0.001), and non-white race (22% vs 13%, p=0.006). Thirty-five (37%) survivors had ≥1 chronic condition (grades 1-5); a 4-fold increased risk (HR 4.1, 95% CI: 2.9-5.8) compared to siblings (Group A HR 2.6, 95% CI 1.2-5.6, Group B HR 5.2, 95% CI 3.1-8.6, and Group C HR 4.2, 95% CI 2.4-7.6). The most frequently occurring conditions were obesity (24%) and decreased fertility (10%). Excluding these, Group B (HR 5.3, 95% CI 1.6-17.3) and Group C (HR 5.7, 95% CI 1.7-19.0) survivors remained at increased risk of having ≥1 chronic condition. Group A survivors showed a similar HR without statistical significance (HR 4.0, 95% CI 0.5-31.3). Three survivors died during study follow-up (SMR 6.5, 95% CI 1.3-19.0), only one died due to a non-cancer related cause of death. All Groups (A-C) were more likely than siblings to report impaired functional status (OR 11.2, 95% CI 3.5-35.6; 4.5, 95% CI 1.5-13.1; and 15.1, 95% CI 6.0-37.8, respectively). Groups B and C survivors were more likely to report poor mental health (OR 2.9, 95% CI 1.0-8.6 and 3.7, 95% CI 1.0-12.9, respectively), while Group B survivors were more likely to report poor general health (OR 5.1, 95% CI 2.2-11.9). No associations with activity limitations (p’s>0.1) or sociodemographic differences (educational level less than a college degree, p’s>0.1; household income less than $60,000/year, p’s>0.1) were identified in any Groups. Cancer-related pain and anxiety did not differ in Groups B or C compared to survivors in Group A (p=0.9 and 0.2, respectively). Conclusions: Despite excellent survival rates, children diagnosed with B-NHL and treated with contemporary LMB chemotherapy regimens are at risk for chronic health conditions and health status limitations by 14 years from diagnosis. Studies exploring the trajectory of these findings and the impact of early interventions are needed to inform future frontline treatment protocols. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pediatric-Based Versus Adult Treatment Protocols in Young Adults (18-40 years) with Standard Risk Acute Lymphoblastic Leukemia: The BC Cancer Agency Experience

IntroductionIn recent decades, overall survival rates for children with acute lymphoblastic leukemia (ALL) have improved dramatically. Unfortunately, older patients have not experienced the same benefit. Recent years have seen investigation into the use of pediatric protocols for younger adults with ALL. Increased toxicity has often limited use to patients 40 years or younger.The Leukemia/Bone Marrow Transplant Program of BC is the referral center for adults with ALL in British Columbia. Approximately 20 patients are newly diagnosed with ALL each year. Until 2008, an adult protocol (known as ALL 89-1) was used in patients over 18 years. Since 2008, pediatric-based chemotherapy has been offered to patients 40 years or younger.We analyzed whether this change altered complete remission (CR), relapse and survival rates. We assessed whether the more intense protocol increased toxicity.MethodsA retrospective analysis was performed on patients treated for ALL on a pediatric-based protocol. These protocols (ALL 08-01 and ALL 13-01) were modifications of the Donna Farber Cancer Institute 01-175 protocol. The format included induction with high dose methotrexate, followed by central nervous system (CNS) therapy including cranial irradiation. A single cycle of etoposide and high-dose cytarabine was given. Consolidation and continuation cycles included doxorubicin, asparaginase, vincristine and dexamethasone. Patients were included if they were aged 18-40 years and had standard risk, Philadelphia chromosome negative ALL.Between February 2008 and November 2014, 25 eligible patients were identified. These were compared with the 23 consecutive standard risk patients most recently treated with ALL 89-1. They had been diagnosed between February 2003 and July 2008.Exclusion criteria were age greater than 40 and non-standard risk ALL.Demographic and clinical data were collected on all patients from the Leukemia Program databases.Overall survival (OS) was calculated from time of diagnosis until death. Event free survival (EFS) was calculated from diagnosis until death, induction failure or relapse. Estimation of OS and EFS was performed using the Kaplan-Meier method. Patient characteristics were compared using Chi-squared test or Fisher's exact test.Ethics approval was obtained from the University of British Columbia ethics board.ResultsThe median age of the combined patient group was 24.5 years. There were no statistically significant differences pre-treatment between groups. Combined median follow up was 28.7 monthsAll 25 patients receiving a pediatric protocol achieved a CR, compared to 19 of 22 with the adult protocol. Despite the more intense chemotherapy dosing regimen in the pediatric protocol, there was no increase in hospitalizations, invasive fungal infections or deaths from treatment toxicity (Table 1). There was a trend towards increased thrombotic events in the pediatric-treated group, at 32% versus 9%. These included deep vein thrombosis in 4 patients, pulmonary emboli in 2, and cerebral sinus thrombosis in 2.Relapse occurred in 24% of the pediatric-treated patients and 45% of the adult-treated ones (p=0.215). Allogeneic stem cell transplantation was performed in 4 patients in the former group and 7 in the latter. Nine of these were carried out in CR2 or later, with two patients going into transplant with active disease. Overall survival following transplant was 44%.Two year event free survival was significantly improved in the group treated on the pediatric protocol (Figure 1), at 79% versus 36% (p=0.011). There was a trend towards improved overall survival in this small cohort, at 83% versus 49% (Figure 2).ConclusionsA pediatric-based ALL treatment protocol was tolerated in patients up to the age of 40 years. In our centre, this is associated with an increase in EFS, and a trend towards increased OS, even considering the small cohort. We await with interest the results of larger studies investigating the ideal upfront therapy for young patients with ALL.Table 1ResultsAll Patients N=47Adult N=22Pediatric N=25PNumber%Number%Number%CR after induction44 of 479419 of 228625 of 25100.095Severe infection20 of 47439 of 224111 of 2544.831Thrombosis10 of 47212 of 2298 of 2532.079Pancreatitis2 of 4740 of 2202 of 258.491Toxicity deaths3 of 4762 of 2291 of 254.593Relapse16 of 473410 of 22456 of 2524.215AlloHSCT11 of 47237 of 22324 of 2516.303 [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Improved outcome for children and adolescent with acute lymphoblastic leukemia in the first decade of the 21st century: Areport from the Slovak Republic.

Our aim was to analyze event-free (EFS) and overall survival (OS) among children and adolescents with acute lymphoblastic leukemia (ALL) treated with International BFM Intercontinental trial (ALL IC 2002) therapy in the Slovak Republic. In total, 280 children and adolescent age 1 to 18 years were treated with ALL IC BFM 2002 based therapy from 2002 to 2012, which was divided into two periods. During 2002-2007, when patients were actively enrolled in the ALL IC-BFM 2002 trial, and during 2008-2012 when the trial was closed and patients were treated with the same therapy without randomization. Five-year EFS and OS rates were 79% (+/- 2.6%) and 86% (+/- 2.1%), respectively, similar to results obtained in the ALL-BFM 95 trial, which was the basis for ALL IC BFM 2002 therapy. The EFS (p<0.012) and OS (p<0.003) were significantly better than the prior Slovak experience in 1997-2001. Survival is improved in standard and intermediate risk groups, including those age 1 to 6 years, and older; with B-cell or T-cell immunophenotype, and is also excellent for those with good early response. The rate of death in induction, cumulative incidence of death in complete remission and of relapse decreased. However, outcome was suboptimal for patients in the high risk group. Current EFS and OS rates for children and adolescents with ALL in the Slovak Republic resembled those obtained in Western Europe as aresult of clinical trial participation, and clinical experience acquired with intensive BFM type treatment.

Abstract B25: A human-mouse xenograft model to evaluate therapies and study the role of TSLP-induced signals in Ph-like ALL

Abstract While the overall survival rate for children with B cell precursor acute lymphoblastic leukemia (B-ALL) is high, a subset of children with this disease are at high risk for relapse and death. Genome-wide analysis has shown that gene expression profiles in these high-risk B-ALLs is similar to that of Philadelphia chromosome–positive ALL and these are designated Ph-like ALL. Approximately half of Ph-like ALL are characterized by genetic defects resulting in overexpression of CRLF2. CRLF2, together with the IL-7Rα, forms a receptor complex that is activated by the cytokine, TSLP. The JAK-STAT5 pathway is phosphorylated downstream of this receptor complex activation. The activating JAK mutations found in some CRLF2 B-ALL have led to speculation that TSLP stimulation is not a factor in CRLF B-ALL. In preliminary studies to address this question we evaluated the effect of TSLP on a CRLF2 B-ALL cell lines with JAK defects and which have been reported to exhibit constitutive JAK-STAT5 activation. Our data show that TSLP increases STAT5 phosphorylation in these cell lines and also in primary CRLF2 B-ALL cells. Our next step was to evaluate the role of TSLP-CRLF2 interactions in vivo in the human-mouse xenograft model. However, mouse TSLP is different from most other cytokines produced in the xenograft in that it is species-specific and does not activate the human TSLP receptor complex that includes CRLF2. Thus, traditional xenograft models do not provide the TSLP-CRLF2 interactions that we believe to be a major factor in CRLF2 B-ALL. To overcome this obstacle we engineered immune-deficient NOD/SCID IL-2Rγ null (NSG) mice to express human TSLP (hTSLP+ mice) as well as control mice that lack the TSLP cytokine (hTSLP– mice). ELISA assays show serum hTSLP levels in the hTSLP+ mice that approximate the normal range in human serum. We used this hTSLP+/- xenograft model system to study the in vivo effects of TSLP on mice transplanted with a CRLF2 B-ALL. We used this hTSLP+/– xenograft model system to evaluate the in vivo effects of TSLP on survival and proliferation of transplanted CRLF2 B-ALL cells harboring a JAK defect (MUTZ5 cell line). Mice were euthanized at 5 weeks and BM was harvested. Evaluation of BM disease by flow cytometry showed that the percentage of viable human leukemia cells in hTSLP+ mice was twice that observed in hTSLP– mice. Evaluation of cell cycle progression in human CRLF2 B-ALL cells isolated from xenograft BM showed that the percentage of cycling cells in hTSLP+ mice was 2.5 fold higher than in hTSLP– mice. When primary Ph-like ALL cells were transplanted to produce hTSLP+/– xenografts, the viable pre-B ALL cells present in the BM of hTSLP+ mice showed higher expression levels of the TSLPR components (CRLF2 and IL-7Rα) than those in the hTSLP- mice. These data provide evidence that the TSLP produced in this model is active and that it impacts primary pre-B ALL cells. Preliminary data obtained from this model suggests that TSLP provides a signal that promotes in vivo survival of CRLF2 B-ALL cells and that it may play a role in selection of leukemia clones during in vivo leukemogenesis. Microarray analysis comparing gene expression in primary CRLF2 B-ALL cells isolated from hTSLP+ and hTSLP– xenograft mice identified 565 that genes are differentially regulated (&amp;gt; 2 fold up or downregulated; p&amp;lt;.05). Ingenuity Pathway Analysis is currently underway to identify the signaling pathways that are regulated by hTSLP in CRLF2 B-ALL in vivo in the hTSLP+/– xenograft model. The identification of genes downstream of TSLP-CRLF2 signaling has the potential of providing drug targets for combination therapy to effectively treat Ph-like B-ALL. The hTSLP+/– xenograft model provides an important tool for evaluating the in vivo efficacy of these and other drugs to treat CRLF2 B-ALL. Citation Format: Ruijun Su, Francis L. Olivia, Shannalee R. Martinez, Ineavely Baez, Terry Ann Milford, Terrence Bennett, Ross Fisher, Christopher L. Morris, Sinisa Dovat, Kimberly J. Payne. A human-mouse xenograft model to evaluate therapies and study the role of TSLP-induced signals in Ph-like ALL. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr B25.

Abstract B21: A human-mouse xenograft model to evaluate therapies and study the role of TSLP-induced signals in Ph-like ALL

Abstract While the overall survival rate for children with B cell precursor acute lymphoblastic leukemia (B-ALL) is high, a subset of children with this disease are at high risk for relapse and death. Genome-wide analysis has shown that gene expression profiles in these high-risk B-ALLs is similar to that of Philadelphia chromosome–positive ALL and these are designated Ph-like ALL. Approximately half of Ph-like ALL are characterized by genetic defects resulting in overexpression of CRLF2. CRLF2, together with the IL-7Rα, forms a receptor complex that is activated by the cytokine, TSLP. The JAK-STAT5 pathway is phosphorylated downstream of this receptor complex activation. The activating JAK mutations found in some CRLF2 B-ALL have led to speculation that TSLP stimulation is not a factor in CRLF B-ALL. In preliminary studies to address this question we evaluated the effect of TSLP on a CRLF2 B-ALL cell lines with JAK defects and which have been reported to exhibit constitutive JAK-STAT5 activation. Our data show that TSLP increases STAT5 phosphorylation in these cell lines and also in primary CRLF2 B-ALL cells. Our next step was to evaluate the role of TSLP-CRLF2 interactions in vivo in the human-mouse xenograft model. However, mouse TSLP is different from most other cytokines produced in the xenograft in that it is species-specific and does not activate the human TSLP receptor complex that includes CRLF2. Thus, traditional xenograft models do not provide the TSLP-CRLF2 interactions that we believe to be a major factor in CRLF2 B-ALL. To overcome this obstacle we engineered immune-deficient NOD/SCID IL-2Rγ null (NSG) mice to express human TSLP (hTSLP+ mice) as well as control mice that lack the TSLP cytokine (hTSLP– mice). ELISA assays show serum hTSLP levels in the hTSLP+ mice that approximate the normal range in human serum. We used this hTSLP+/- xenograft model system to study the in vivo effects of TSLP on mice transplanted with Ph-like B-ALL. First, we used the hTSLP+/– xenograft model system to evaluate the in vivo effects of TSLP on survival and proliferation of transplanted CRLF2 B-ALL cells harboring a JAK defect (MUTZ5 cell line). Mice were euthanized at 5 weeks and BM was harvested. Evaluation of BM disease by flow cytometry showed that the percentage of viable human leukemia cells in hTSLP+ mice was twice that observed in hTSLP– mice. Evaluation of cell cycle progression in human CRLF2 B-ALL cells isolated from xenograft BM showed that the percentage of cycling cells in hTSLP+ mice was 2.5 fold higher than in hTSLP– mice. When primary Ph-like ALL cells were transplanted to produce hTSLP+/– xenografts, the viable pre-B ALL cells present in the BM of hTSLP+ mice showed higher expression levels of the TSLPR components (CRLF2 and IL-7Rα) than those in the hTSLP- mice. These data provide evidence that the TSLP produced in this model is active and that it impacts primary pre-B ALL cells. Preliminary data obtained from this model suggests that TSLP provides a signal that promotes in vivo survival of CRLF2 B-ALL cells and that it may play a role in selection of leukemia clones during in vivo leukemogenesis. Microarray analysis comparing gene expression in primary CRLF2 B-ALL cells isolated from hTSLP+ and hTSLP– xenograft mice identified 565 that genes are differentially regulated (&amp;gt; 2 fold up or downregulated; p&amp;lt;.05). Ingenuity Pathway Analysis is currently underway to identify the signaling pathways that are regulated by hTSLP in CRLF2 B-ALL in vivo in the hTSLP+/– xenograft model. The identification of genes downstream of TSLP-CRLF2 signaling has the potential of providing drug targets for combination therapy to effectively treat Ph-like B-ALL. The hTSLP+/– xenograft model will provide an important tool for evaluating the in vivo efficacy of these and other drugs to treat CRLF2 B-ALL. Citation Format: Olivia Francis, Ruijun Su, Shannalee Martinez, Ineavely Baez, Terry-Ann Milford, Terrence Bennett, Ross Fisher, Christopher L. Morris, Sinisa Dovat, Kimberly J. Payne. A human-mouse xenograft model to evaluate therapies and study the role of TSLP-induced signals in Ph-like ALL. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B21.

Abstract B80: NK therapy for pediatric brain tumors of the posterior fossa

Abstract Brain tumors are the second most common childhood malignancies and the leading cause of childhood cancer mortality. Medulloblastomas (MBs) account for approximately 20% of pediatric brain tumors. They develop in the cerebellum and frequently metastasize. Current treatment has increased overall survival to 70-80%, however the prognosis for patients with recurrent disease, metastases or diagnosis at &amp;lt;3 years old is still poor. Atypical teratoid/rhabdoid tumors (ATRTs) represent yet another pediatric brain malignancy with poor prognosis. ATRTs generally occur in children &amp;lt;3 years old and the overall survival rate for children &amp;lt;3 is only 17%. In addition, therapy related toxicities including impaired neurological development and function are a critical problem associated with the treatment of both diseases. Thus, there is an urgent need to discover new therapies for these tumors. Immunotherapy is an alternative to traditional therapies that may circumvent the potential toxicities associated with chemotherapy and radiation. Many therapeutics that harness the power of the immune system to combat cancer rely on the presence of tumor associated antigens (TAAs) and/or antigen processing and class I human leukocyte antigen (HLA I) expression. However, the identification of well-defined TAAs for MB or ATRT has remained elusive and neuronal tissues have very low HLA I expression. Therefore an agent that does not require the presence of TAAs, such as natural killer (NK) cells, might be useful for the treatment of these diseases. The current barriers to clinical application of NK therapy for brain tumors are both quantitative and qualitative. We have overcome the former problem by developing a platform technology wherein large numbers of NK cells can be generated ex vivo through co-culture of peripheral blood mononuclear cells with artificial antigen presenting cells expressing membrane-bound IL-21 (mbIL21). This method results in an average 48,000-fold expansion of donor NK cells from a small volume of blood. The qualitative barriers of NK lifespan, persistence and cytolytic activity have also been addressed by our approach. We demonstrate significantly increased life-span characterized by continued ex vivo proliferation for at least 6 weeks using mbIL21 as compared to only 3 weeks of ex vivo proliferation with IL-15. Furthermore, these NK cells have the ability to persist for up to 3 weeks post-infusion in the murine brain as determined by fluorescence imaging. These cells also express high levels of immune stimulatory and anti-tumor cytokines Ifnγ and TNFα following activation. Finally we demonstrate NK cytolytic activity in vitro against a panel of primary and established ATRT and MB cells and in vivo following locoregional delivery in a mouse orthotopic model of MB. Successful tumor infiltration of mbIL21 expanded NK cells was demonstrated by immunohistochemistry. Our data provide the first pre-clinical evidence supporting the use of mbIL21 expanded NK cells to target pediatric brain tumors. Based on this data our group has begun the first pediatric phase I clinical trial to assess the safety and efficacy of locoregional delivery of mbIL21 expanded NK cells for the treatment of posterior fossa brain tumors. Citation Format: William Benjamin Brugmann, Alvaro Laureano, Cecele Denman, Harjeet Singh, Helen Huls, Zaky Wafik, David Sandberg, Soumen Khatua, Dean Lee, Laurence Cooper, Vidya Gopalakrishnan. NK therapy for pediatric brain tumors of the posterior fossa. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B80.

Adult Survivors of Childhood Cancer: The Medical and Psychosocial Late Effects of Cancer Treatment and the Impact on Sexual and Reproductive Health

There are over 13 million cancer survivors in the United States, which constitutes 3-4% of the U.S. population. According to the Surveillance Epidemiology and End Results program (SEER) data the 5-year overall survival rate for children diagnosed with cancer between ages 0-19 is 83.1%, and 2/3 of childhood cancer survivors will experience at least one late effect of treatment. To provide a brief overview of the medical and psychosocial effects of cancer treatments in survivors of childhood cancer with a focus on sexual and reproductive health issues in this population. The development of a manuscript from a presentation at the Annual Society of Sexual Medicine meeting. An overview of long-term and late effects of treatment experienced by young adult cancer survivors was presented. This manuscript is based on a presentation that reviewed the medical and psychosocial literature, consensus statements of professional groups, and clinical observations. Cancer and cancer treatments have both direct and indirect effects of physiological, psychological, and interpersonal factors that can negatively impact the health and well-being of cancer survivors including sexual and reproductive function and satisfaction. Cancer, its management, and the resulting late effects must be explored and understood by providers caring for childhood cancer survivors so that educational, psychological, pharmacologic, as well as preventive interventions can be implemented with this population.

Children's Oncology Group L991 final study report: Establishing an important benchmark for assessing late effects of trimodality care of pediatric patients treated for high grade gliomas.

As advances are made in children’s cancer care, there will be growing numbers of adult survivors of pediatric cancer. In the United States, the number of adult survivors of pediatric cancers is approaching 300,000 (1). According to the National Cancer Institute’s Surveillance Epidemiology and End Result’s Cancer Statistics Review 1975-2008, the 5 year overall survival rate for children with brain tumors has risen from 58.8 % in 1975-1977 to 75% from 2001-2007 (2). With improved survivorship from childhood cancers, researchers have generated an abundance of literature pertaining to quality of life. A PubMed literature search with the terms “childhood cancer survivors quality of life” yields 420 citations. Studies focus on late effects in nearly every organ system, secondary malignancies, fertility, productivity, socioeconomic impact, and numerous other effects.

S100A4 antisense oligodeoxynucleotide suppresses invasive potential of neuroblastoma cells

Background S100A4 gene product has been implicated in tumor invasion and metastasis. The overall survival rate of children with neuroblastoma remains poor because of disease dissemination at the time of diagnosis. The purpose of this study was to investigate the effect and mechanism of S100A4 on invasion and metastasis of neuroblastoma. Methods A 20-mer phosphorothioate antisense oligodeoxynucleotide (asODN) targeted against the S100A4 mRNA was transfected into the human neuroblastoma cell line LA-N-6 by Lipofectamine 2000. The expressions of S100A4 and MMP-2 mRNAs were quantified by the reverse transcription polymerase chain reaction. The capability of migration and invasion of LA-N-6 cells were evaluated by the transwell chamber assay. Results The S100A4 mRNA and the MMP-2 mRNA levels in asODN-treated cells were decreased by 35.6% and 25.5%, respectively, compared with those in nontreated cells. The numbers of migrating and invading LA-N-6 cells were both significantly lower in the asODN-treated groups than those in the nontreated groups ( 9.33 ± 4.73 vs 20.67 ± 2.89 and 2.33 ± 1.15 vs 9.00 ± 2.65, respectively; both P = .03 ). Conclusions The S100A4 asODN significantly reduced the S100A4 mRNA levels and the motility and invasive ability of neuroblastoma cells, with concomitant decrease of the MMP-2 mRNA levels. Thus, S100A4 may exert its effect on invasion and metastasis of neuroblastoma cells by stimulating the motility of tumor cells as well as influencing the expression of MMP-2.

Philosophy of treatment and the role of chemotherapy in paediatric soft tissue sarcomas

Although overall survival rates for children with soft tissue sarcoma have improved, progress for some sub-groups of patients has been less encouraging than might be expected. Priorities for the future include the better identification of patients who can be cured with minimal therapy and better treatment for those who have a poor outcome with current therapy. Improved understanding of the biology of this group of tumours may provide opportunities to utilise some of the more recently designed novel forms of therapy aimed at molecular targets. Although considerable amounts of valuable clinical data have been acquired through clinical trials in patients with RMS, further efforts to systematically explore therapy in children with non-RMS soft tissue sarcoma are now required and there are opportunities for adult-paediatric collaboration in designing new approaches to therapy.

Low grade astrocytomas in the West of Scotland 1987–96: treatment, outcome, and cognitive functioning

BACKGROUNDLow grade astrocytomas are among the most common central nervous system tumours in children.AIMSTo identify risk factors for the development of persistent intellectual handicap.METHODSThe notes of 30 children with histologically...

Optimizing antimetabolite-based chemotherapy for the treatment of childhood acute lymphoblastic leukaemia.

Optimizing antimetabolite-based chemotherapy for the treatment of childhood acute lymphoblastic leukaemia.