ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeThe nodular lymphocyte-predominant form of Hodgkin disease (LPHD) is a distinct clinicopathologic entity with a favorable prognosis. To see if children and adolescents could be spared the adverse sequelae of treatment, the authors adopted a policy of little or no treatment of localized LPHD in 1989.Patients and MethodsPresentation, pathology, and outcomes were reviewed for 15 consecutive children and adolescents with LPHD seen at a single institution since 1989. One patient was lost to follow-up and two patients were seen only once in consultation and treated elsewhere. These three cases were excluded, leaving twelve: nine males and three females, ranging in age at diagnosis from 2 to 17 years (median 11). Eleven of the 12 had stage I disease, and 1 had stage II. Six received no treatment following excisional biopsy, while five received a brief treatment with chemotherapy only. One was initially treated with involved field radiotherapy (IFRT) due to an initially imprecise histologic diagnosis of classic Hodgkin disease.ResultsAll patients are alive, without evidence of disease, for periods ranging from 2 to 13+ years after diagnosis (median 6 years). One patient recurred locally with LPHD 6 years after initial brief chemotherapy and was then treated with IFRT, achieving a prolonged second remission.ConclusionChildren and adolescents with localized LPHD have an excellent prognosis and may be safely approached either with a wait-and-see attitude of no initial therapy after initial adenectomy or with less aggressive treatments.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeMethotrexate is a major component of current treatment regimens for children with acute lymphocytic leukemia (ALL). Potential mechanisms of methotrexate resistance include impaired drug uptake, decreased drug retention, and dihydrofolate reductase (DHFR) amplification. The purpose of this study was to assess whether reduced folate carrier (RFC) and DHFR expression in untreated leukemic blasts correlated with outcome.MethodsQuantitative real-time RT-PCR was used to measure RFC and DHFR mRNA expression in leukemic blasts from 40 newly diagnosed patients with ALL obtained in a blinded fashion from Children's Cancer Group studies.ResultsLow RFC expression at diagnosis correlated significantly with an unfavorable event free survival. Surprisingly, low, not high, DHFR expression correlated significantly with an unfavorable event-free survival. Proliferative cell nuclear antigen (PCNA) expression demonstrated a weak inverse relationship between sample PCNA and DHFR or RFC expression, suggesting that DHFR and RFC expression may be markers for factors other than drug resistance.ConclusionsThese results suggest that impaired transport may be an important mechanism of intrinsic methotrexate resistance in ALL, and DHFR expression also may be an important prognostic factor in ALL. Additional studies are necessary to clarify the mechanism for the correlation of low DHFR expression with poor outcome.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeTreatment of acute myeloid leukemia (AML) is associated with substantial adverse effects, including neutropenia and infection.Viridansstreptococci (VS) are a primary cause of infection and pneumonia in patients with neutropenia. The authors determined the incidence, clinical features, and complications of VS sepsis in children receiving chemotherapy for AML.MethodsThe authors retrospectively reviewed the records of 172 patients treated on their institutional protocols AML91 (n = 95) and AML97 (n = 77) and identified 36 patients who had VS sepsis.ResultsThe 1-year cumulative incidence of VS sepsis was significantly higher in AML97 than in AML91. Patients with favorable cytogenetic features (ie, t(9;11), t(8;21), or inv(16)) had a significantly higher incidence of infection than did other patients. VS sepsis developed at various times after chemotherapy was initiated, and patients remained febrile for a median of 15 days. Twelve patients (33%) experienced hypotension, 10 (28%) acute respiratory distress syndrome, and 6 (17%) fungal infection. Twenty-three patients (64%) required intensive care, 21 (58%), oxygen therapy, and 7 (19%), vasopressor medications. One patient died of pulmonary aspergillosis after VS sepsis. The 3-year cumulative incidence of aspergillosis was higher in patients with VS sepsis than in those without.ConclusionsAlthough antibiotic therapy rapidly resolved VS sepsis, complications associated with this infection remained life-threatening in children receiving chemotherapy for AML.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeThe offer to return a summary of results to participants after the conclusion of clinical research has many potential benefits. The authors determined current practice and attitudes and needs of researchers in establishing programs to return results to research participants.MethodsAn Internet survey of all 236 principal investigators (PIs) of the Children's Oncology Group in May 2002 recorded PI and institutional demographics, current practice, and perceived barriers to and needs of PIs for the creation of research results programs.ResultsOne hundred fifty (63.8%) PIs responded. Few institutions (n = 5) had established, comprehensive programs to offer the return of results. PIs indicated that major impediments to the implementation of such programs are the preparation of lay summaries, time constraints, the task of contacting participants, and potential distress for the participants. PIs identified the following facilitators to the establishment of a program in their own institution: lay summaries, web site, preparation of an oncologist's summary, and financial credits. There was no clear consensus as to when the results should be shared: 30% indicated after the study was closed and 24% indicated at the time of publication of results. A substantial proportion of respondents opposed or strongly opposed the implementation of a universal offering of results to research participants.ConclusionsFew Children's Oncology Group institutions have programs that offer the return of results to research participants. Significant barriers and facilitators to this process have been identified.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeSarcomas express cyclooxygenase (COX)-2, an inducible enzyme with known tumor-promoting activity. COX-2 inhibition is efficacious against many cancer types but has not been tested for human sarcomas. Matrix metalloproteinase (MMP) inhibitors also possess antiproliferative activity. Because MMP inhibitor therapy induces COX-2 expression, the authors hypothesized that the combination of COX-2 and MMP inhibitors results in a synergistic antitumor effect.MethodsHuman osteosarcoma or rhabdomyosarcoma cells were injected into athymic mice. Tumor development and growth were measured following treatment with a COX-2 inhibitor (celecoxib), an MMP inhibitor (doxycycline), or both. The tumors were analyzed for necrosis, apoptosis, cyclooxygenase activity (PGE2production), and MMP-2 levels.ResultsWhen treatment was started prior to tumor cell implantation, doxycycline inhibited osteosarcoma tumor growth alone and in combination with celecoxib (30% and 33% reduction, respectively). An effect on osteosarcoma tumor implantation rates was noted in mice receiving doxycycline alone and in combination with celecoxib (12.5% and 6.25% reduction, respectively). Established osteosarcoma and rhabdomyosarcoma tumors were inhibited only by combination therapy (36% and 55%, respectively). A higher proportion of osteosarcoma tumors in the combination therapy group had more than 50% necrosis (3/7) when compared with control tumors (0/8). Antitumor effects did not correlate with PGE2levels, suggesting the observed interaction with doxycycline was due to previously described non-enzymatic effects of celecoxib.ConclusionsThe authors' preclinical data suggest that the combination of inexpensive, nontoxic, oral COX-2 and MMP inhibitors may be useful for the treatment of some types of solid tumors.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeThe precise changes in RNA and protein expression that accompany neuroblastoma differentiation remain unknown. The authors used microarray technologies to screen molecules associated with the differentiation of neuroblastoma (NB) cells induced by 13-cis retinoic acid.MethodsThe authors quantified the expression of 2,061 RNA transcripts related to oncogenesis and of 380 proteins expressed in SK-N-SH and CHP-134 NB cell lines in the presence or absence of 13-cis retinoic acid.ResultsHierarchical clustering captured gene expression altered during neuroblastoma differentiation induced by 13-cis retinoic acid. Several genes were further abstracted based onPvalues below 0.0017 or protein chips observed in both NB cell lines. The altered expressions of gene products revealed by both DNA and protein chips were in agreement. The expressions of N-myc, cyclin D3, and Wnt10B were downregulated, whereas those of retinoblastoma (RB) and related genes (p107, RB2/p130, p300/CBP, E2F-1, DP-1) as well as others were upregulated.ConclusionsThese results suggest that microarray technology can screen for genes that are important in neuroblastoma differentiation.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

It is currently thought that approximately 1% of children with Down syndrome will develop a “premalignant” syndrome known as transient myeloproliferative disorder (TMD). Prospective, population-based studies of the incidence of TMD in Down syndrome infants is lacking. Although most cases of TMD resolve by 1 year of age, data suggest that 10% to 20% of Down syndrome patients with TMD develop AML-M7 (megakaryoblastic leukemia). To identify the true incidence of TMD in the Down syndrome population, a sensitive, rapid, and cost-effective method of quantifying circulating megakaryoblasts in large numbers of patients was needed. In this pilot study, the authors tested the hypothesis that there are fewer than 1% megakaryoblasts of nucleated cells circulating in the blood of normosomic infants. Four-antigen flow cytometry was used to establish the percentage of megakaryoblasts present in each of 100 cord blood samples collected blindly from “normosomic” live births. There was a mean percentage of 0.017% megakaryoblasts in 100 cord blood samples from normosomic infants. Flow cytometry proved to be a sensitive, rapid, and reproducible method for the quantification of megakaryoblasts. Less than 1% of circulating nucleated cells in the blood of newborn infants are megakaryoblasts, providing a comparison population for the authors' larger proposed incidence study.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

PurposeTo retrospectively review the authors' institutional experience with arthroscopic synovectomy in young patients with hemophilia.Patients and MethodsPatients with moderate or severe hemophilia seen in the authors' center were eligible to undergo synovectomy if they developed subacute or chronic synovitis that did not improve with prophylactic factor replacement. A single orthopedic surgeon performed all procedures. Each patient received aggressive physical rehabilitation and regular factor replacement for 6 weeks following surgery. Outcome data regarding the frequency of bleeding and range of motion were evaluated.ResultsTwenty-eight arthroscopic synovectomies (11 knees, 12 ankles, 5 elbows) were performed on 26 joints in 20 hemophilia patients between November 1992 and May 2002. There were no intraoperative complications. One patient developed hemarthrosis 1 week postoperatively and another had a soft tissue hematoma at the incision site. Two patients required a second procedure on the same joint because of trauma that occurred 2 months following surgery. Follow-up data were available on 26 joints during the first year after the procedure. The frequency of hemarthrosis diminished significantly in that first year and was maintained for up to 5 years in all but three joints. Seventy-six percent of evaluable patients (19/25) had stable or improved joint function at their most recent comprehensive clinic visit. Patients whose range of motion worsened were older and required more than one procedure.ConclusionsArthroscopic synovectomy significantly reduces hemorrhage into the index joint and allows for stabilization of joint range of motion. This procedure should be considered in young hemophilia patients with chronic synovitis.

ISSN:1077-4114    

出版商:OVID    

年代:2003

数据来源: OVID