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1.
J Pediatr Hematol Oncol ; 44(2): e532-e536, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34133374

ABSTRACT

A 15-year-old male presented with fatigue and weight loss for 1 month, petechiae and bruising for 2 weeks. He was diagnosed with concurrent new acute myeloid leukemia and coronavirus disease 2019. He was febrile and chest computed tomography scan showed ground glass opacities. Fever resolved after 4 days. Polymerase chain reaction test for coronavirus disease 2019 became negative after 2 days. Induction chemotherapy was initiated on day 8 and was complicated by multisystem inflammatory syndrome in children. The multisystem inflammatory syndrome in children was managed with symptomatic treatment and continued chemotherapy. Patient recovered and end of induction bone marrow showed remission of the leukemia.


Subject(s)
COVID-19/complications , Induction Chemotherapy/methods , Leukemia, Myeloid, Acute/complications , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/pathology , Adolescent , COVID-19/pathology , COVID-19/virology , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/virology , Male , Remission Induction , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , COVID-19 Drug Treatment
2.
J Pediatr Hematol Oncol ; 28(7): 412-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16825985

ABSTRACT

Alterations in apoptotic mechanisms favoring cell survival may be vital for modifying tumor behavior. Survivin, an inhibitor of apoptosis, and caspase 8, a proapoptotic enzyme, are key players in cellular apoptotic mechanisms. We investigated whether the levels of survivin and caspase 8 and the ratio between these 2 apoptotic factors correlate with tumor biology and predicts outcome in patients with neuroblastoma. Survivin and caspase 8 levels were quantified in 38 primary tumor specimens and analyzed individually and in relation to each other. High survivin expression and high survivin:caspase 8 ratios were associated with MYCN amplification, unfavorable histology, and high-risk group of disease (P<0.0008). High survivin mRNA levels were associated with worse overall survival (P=0.02) although the median follow up was only 22.6 months with a range of 1 day to 3.3 years. Low caspase 8 expression was associated with stage 4 disease, high-risk group, MYCN amplification, and unfavorable histology. Although the survivin:caspase 8 ratio was associated with these risk factors, the ratio did not improve the predictive value of survivin alone in this small series. Quantifying multiple apoptotic genes in neuroblastoma may supplement current risk stratification. Moreover, categorizing aberrant apoptotic gene expression in neuroblastoma may translate into novel therapeutic targets.


Subject(s)
Microtubule-Associated Proteins/genetics , Neoplasm Proteins/genetics , Neuroblastoma/genetics , RNA, Messenger/biosynthesis , Caspase 8 , Caspases/biosynthesis , Caspases/genetics , Cell Line, Tumor , Follow-Up Studies , Gene Amplification , Gene Expression Profiling , Humans , Inhibitor of Apoptosis Proteins , Microtubule-Associated Proteins/biosynthesis , N-Myc Proto-Oncogene Protein , Neoplasm Proteins/biosynthesis , Neuroblastoma/metabolism , Neuroblastoma/therapy , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Oncogene Proteins/biosynthesis , Oncogene Proteins/genetics , Proportional Hazards Models , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Risk Factors , Survival Rate , Survivin , Treatment Outcome
3.
J Pediatr Surg ; 40(5): e17-9, 2005 May.
Article in English | MEDLINE | ID: mdl-15937808

ABSTRACT

Two patients with hemangioendothelioma and elevated plasma vascular endothelial growth factor (VEGF) levels are presented. A reduction in the plasma VEGF level after therapeutic intervention correlated with a successful clinical response. Conversely, a stable plasma VEGF level correlated with therapeutic failure.


Subject(s)
Biomarkers, Tumor/blood , Hemangioendothelioma/blood , Liver Neoplasms/blood , Neoplasm Proteins/blood , Soft Tissue Neoplasms/blood , Vascular Endothelial Growth Factor A/blood , Hemangioendothelioma/congenital , Hemangioendothelioma/surgery , Hepatectomy , Hip Contracture/etiology , Hip Contracture/pathology , Humans , Infant , Liver Neoplasms/congenital , Liver Neoplasms/surgery , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local/drug therapy , Prednisolone/therapeutic use , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/surgery , Subcutaneous Tissue
4.
J Pediatr Hematol Oncol ; 27(1): 11-4, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15654272

ABSTRACT

Important in the homeostasis of normal tissues, apoptosis can be altered to favor cell survival within tumors. High expression of survivin, an inhibitor of apoptosis, and absence of caspase 8, a pro-apoptotic enzyme, independently correlate with poor outcomes in several tumor types. Favorable histology Wilms tumor has a remarkably high cure rate; as a result, the focus of therapy is now aimed at reducing treatment-related morbidity. With the goal of safely reducing therapy in select subgroups of patients, the authors investigated whether the levels of apoptotic factors in tumors could predict the risk for recurrence. Tumor apoptotic factor levels were surveyed in a case-control study from the National Wilms Tumor Study 5 (NWTS-5) and measured via quantitative real-time RT-PCR. Survivin and caspase 8 levels were surveyed in 92 primary tumor specimens and SMAC, Bid, and CD95 were surveyed in 24 specimens. All four pro-apoptotic factors studied (caspase 8, SMAC, Bid, and CD95) were analyzed individually and in relation to survivin expression. Although survivin mRNA was present at markedly greater levels than in normal kidney, none of the factors assayed independently or as a ratio was associated with stage of disease or risk for tumor recurrence in this group of tumors.


Subject(s)
Apoptosis/physiology , Biomarkers, Tumor/analysis , Kidney Neoplasms/metabolism , Wilms Tumor/metabolism , BH3 Interacting Domain Death Agonist Protein , Carrier Proteins/metabolism , Case-Control Studies , Caspase 8 , Caspases/metabolism , Gene Expression , Inhibitor of Apoptosis Proteins , Kidney Neoplasms/pathology , Microtubule-Associated Proteins/metabolism , Mitochondrial Proteins/metabolism , Neoplasm Proteins , Prognosis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Survivin , Wilms Tumor/pathology , fas Receptor/metabolism
5.
Transfusion ; 44(3): 373-81, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14996194

ABSTRACT

BACKGROUND: Pediatric emergency RBC transfusions are often infused rapidly through 22-gauge (ga) or smaller needles or catheters using hand-held syringes. Data relating needle size, unit age, and infusion rate are needed to assess the risk of hemolysis and hyperkalemia in this setting. STUDY DESIGN AND METHODS: Multiple simulated transfusions were performed during storage of RBC units. Aliquots from five units were rapidly passed through needles (18, 20, 22-25 ga) using a hand-held syringe. Resulting plasma Hb and K+ concentrations were measured. Free Hb levels were used as a measure of needle-associated hemolysis (NAH). RESULTS: Passage through 18-ga and 20-ga needles caused no hemolysis, but rapid passage through 23-ga, 24-ga, and 25-ga did. RBCs stored less than 7 days showed significant K+ release with 23- to 25-ga needles. The greatest needle-associated K+ release was 10 mEq per L, on Day 5. Due to high K+ concentrations resulting from spontaneous efflux, K+ release from NAH was not detectable after 2 or more weeks of storage. CONCLUSIONS: Rapidly transfusing RBCs using hand-held syringes through 23-ga or smaller needles can cause hemolysis. In RBCs stored 2 weeks or more, NAH does not measurably increase K+ concentrations above that present from storage-related efflux. During rapid transfusions, RBC storage time is the primary risk factor for transfusion-associated hyperkalemia.


Subject(s)
Blood Transfusion/instrumentation , Hyperkalemia/etiology , Needles , Syringes , Blood Preservation , Hemoglobins , Hemolysis , Humans , Hyperkalemia/epidemiology , In Vitro Techniques , Potassium/metabolism , Risk Factors
6.
Cancer Res ; 63(2): 394-9, 2003 Jan 15.
Article in English | MEDLINE | ID: mdl-12543793

ABSTRACT

Granulocyte macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cells form the basis of many immunotherapeutic strategies. We tested whether combining this approach with T-helper 1 (Th-1)-like immunostimulatory CpG oligodeoxynucleotides (CpG ODNs) would improve therapeutic efficacy in an established model of murine neuroblastoma. The weakly immunogenic Neuro-2a cell line was used in syngeneic A/J mice. CpG 1826 was tested for its antitumor effect alone and as an adjuvant to Neuro-2a cells retrovirally transduced to express murine GM-CSF (GM/Neuro-2a). Three days after wild-type (WT) tumor cell inoculation, mice in different groups were s.c. vaccinated in the opposite leg with combinations of WT neuro2a, irradiated (15 Gy) WT or GM/Neuro-2a transfectants with or without CpG 1826 (200 micro g). To test for the induction of memory responses, mice that rejected their tumor were rechallenged with WT Neuro-2a (1 x 10(6)) 7 weeks after vaccination. All of the mice in the control (unvaccinated) group died within 3 weeks after Neuro-2a inoculation. Most of the vaccinated groups had only minimal-to-modest antitumor responses, and the mice succumbed to tumor. Tumor growth was remarkably inhibited in the group of mice that received irradiated GM/Neuro-2a plus CpG and four (50%) of eight mice in this group survived tumor free. Tumor-free mice were resistant to further WT tumor cell challenge, indicating a memory response. Mechanistic studies showed that CpG alone induced a favorable Th-1-like cytokine immune response and vaccine-induced tumor cell killing was dependent on both CD4 and CD8 T cells that killed tumor cell targets by apoptosis. These results demonstrate that CpG ODNs enhanced the antitumor effect of irradiated GM-CSF secreting Neuro-2a cells. This vaccine strategy elicits a potent tumor antigen-specific immune response against established murine neuroblastoma and generates systemic neuroblastoma-specific immunity.


Subject(s)
Cancer Vaccines/pharmacology , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Immunotherapy, Active/methods , Neuroblastoma/therapy , Oligonucleotides/pharmacology , Animals , Apoptosis/immunology , CD3 Complex/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/genetics , Cancer Vaccines/immunology , CpG Islands/genetics , Female , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Lymphocyte Activation/immunology , Mice , Mice, Inbred A , Neuroblastoma/genetics , Neuroblastoma/immunology , Neuroblastoma/metabolism , Oligonucleotides/genetics , Oligonucleotides/immunology , Th1 Cells/immunology , Transfection
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