Inhibition of SHH pathway mechanisms by arsenic trioxide in pediatric medulloblastomas: a comprehensive literature review.

Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment. Several new drugs aimed at SHH modulation are currently under development. This review focuses on the role of arsenic trioxide, a drug well established in clinical practice and probably an under-explored agent in medulloblastoma management, in the SHH pathway.

PLK1 expression and BI 2536 effects in childhood acute lymphoblastic leukemia.

BACKGROUND: Polo-like kinase 1 (PLK1) is a conserved kinase that mediates various mitotic events. Compelling data have repeatedly demonstrated its upregulation in different neoplasia, being frequently associated with poor prognosis. However, in childhood acute lymphoblastic leukemia (ALL), no studies have yet been conducted. PROCEDURE: PLK1 expression and association with biological features were evaluated in 65 consecutively diagnosed childhood ALL samples by quantitative real-time PCR. Moreover, the effects of a specific PLK1 inhibitor, BI 2536, was tested against a panel of nine ALL cell lines at nanomolar concentrations (10, 50, 100 nM). RESULTS: The mRNA expression of PLK1 showed great variability in pediatric ALL, but no difference was evidenced compared to normal bone marrow. Additionally, no association was found between PLK1 mRNA expression with any clinical or biological features. Alternatively, high mRNA expression of PLK1 was present in ALL cell lines. In vitro treatment with BI 2536 strongly diminished growth, while presenting significant reduction in colony formation capacity and increased apoptosis rates. Moreover, strong G2/M arrest was detected suggesting important impaired proliferation after treatment. CONCLUSIONS: PLK1 mRNA expression level is not associated with prognosis in childhood ALL; however, considering the great variability observed in the sample and the in vitro experiments presented herein, BI 2536 treatment might serve as a promising therapeutic to enhance the efficacy of conventional treatment modalities in some childhood ALL cases.

Osteosarcoma arising from osteochondroma of the tibia: case report and cytogenetic findings.

Osteochondroma is a cartilage capped benign tumor developing mainly at the juxta-epiphyseal region of long bones. The rate of malignant transformation, mainly into chondrosarcoma, is estimated to be less than 1-3%. Transformation into osteosarcoma is very rare and has been reported only thirteen times. There is little information on treatment and outcome. We report the case of a secondary osteosarcoma arising in the left tibia of a 23-year-old male, 10 years after the initial diagnosis of osteochondroma and after two partial resections. Malignant transformation occurred at the stalk and not at the cartilage cap, as would normally be expected. Chromosome banding analysis revealed the karyotype: 46,XY, t(3;13)(q21;q34) [2]/46,XY [18]. Records from additional cases will help determine the parameters that define these rare secondary bone lesions.

Tetraploidization in Wilms tumor in an infant.

Genetic instability is frequent in human cancer. Unscheduled tetraploidization can trigger cell transformation and tumorigenesis. We made a cytogenetic analysis by Giemsa-trypsin banding of a stage I, biphasic Wilms tumor diagnosed in a 10-month-old male. An evident karyotypic heterogeneity was found. Four different subclones of tumor cells were observed, with DNA content varying from diploid to near-tetraploid complements. The genetic events involved in the acquisition of aneuploidy in Wilms tumor remain unclear. We hypothesize that initial tetraploidization caused aberrant cell division, leading to abnormal chromosomal segregation, cell transformation and tumorigenesis.

ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma.

Over the last decade, the rho-associated kinases and several metastasis-associated microRNAs have emerged as important contributors of tumor invasion. However, despite prominence, our understanding of their involvement in the metastatic potential of Ewing Sarcoma (EWS) is incomplete. The expression profiles of ROCK1 or ROCK2 and miR-124-3p, miR-138-5p, miR-139-5p, miR-335-5p and miR-584-5p (all of which were previously predicted or validated to regulate these kinases) were evaluated through qRT-PCR and associated with clinical parameters. In vitro assays to evaluate colony formation and invasion/migration capacieties were performed on SK-ES-1 cells transfected with pre-miR mimics. ROCK1 expression was significantly reduced in EWS tissues, though there was no association with pathological parameters. miR-124-3p, miR-139-5p and miR-335-3p were also found significantly downregulated and positively correlated with ROCK1. Stratification indicated an association between lower levels of miR-139-5p and miR-584-5p with disease progression (p < 0.05), while reduced expression of the former and miR-124-3p were associated with reduced survival. In vitro miR-139-5p overexpression yielded inconsistent results: while mir-139-5p restoration significantly reduced invasion, the clonogenic capacity of cells was increased. Our study demonstrated that down-regulation of miR-124-3p, miR-139-5p and miR-584-5p are associated with disease progression in EWS and may serve as a risk assessment biomarkers though, as seen for mir-139-5p, their specific role remain to be elucidated for considering tailoring treatment options.

Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment.

BACKGROUND: Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP). OBJECTIVES: The objectives of this study were to observe the effect of budesonide on the expression of IL-1beta, TNF-alpha, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-alpha, GR-beta, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response. METHODS: Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR. RESULTS: There was a significant decrease in the expression of TNF-alpha (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1beta (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1beta (4.18 vs. 0.42; P<0.005) and GR-beta (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group. CONCLUSION: Topical budesonide reduced the expression of TNF-alpha, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1beta, ICAM-1 and nuclear factor (NF)-kappaB at diagnosis and higher expression of both IL-1beta and GR-beta after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1beta, ICAM-1 and NF-kappaB may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-beta in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease.

Cytogenetic findings in an epithelioid sarcoma with angiomatoid features. A case report.

Epithelioid sarcoma is a rare, aggressive soft tissue tumor of unknown histogenesis showing predominantly epithelioid cytomorphology. We conducted a conventional and molecular cytogenetic study of a 27-year-old male with epithelioid sarcoma with angiomatoid features. Cytogenetic analysis of epithelioid sarcoma metaphase spreads by GTG-banding revealed a diploid chromosome complement with structural and numerical aberrations. Comparative genomic hybridization analysis demonstrated the amplification of 3p24-pter, 4p15.2-p16 and 18q23, while chromosome losses involved 3p13-p14, 3q24-q26.1, 9q21, and 11q21. Fluorescence in situ hybridization assessment showed normal hybridization patterns for the C-MYC and CCND1 loci; CCND1 RNA overexpression was detected by real-time polymerase chain reaction analysis. Genetic evaluation of this rare condition may be useful in determining if epithelioid sarcoma is associated with a distinct genetic background.

Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma.

miRNAs have been identified as key regulators of almost all cellular processes, therefore, their dysregulation is involved with several diseases, including cancer. miRNAs specifically related to the metastastic cascade are called metastamiRs and can be involved with different steps of this process, including loss of adhesion. Osteosarcoma (OS) is the most common primary malignant pediatric bone tumor that often presents metastatic disease at diagnosis; therefore, a deeper study of adhesion-associated miRNAs could shed light on its pathophysiology. Online databases were used to select four miRNAs (miR-139; miR-181b; miR-584; miR-708) predicted or validated to target proteins related to adherent junctions and focal adhesion pathways, and their expression levels and possible associations with clinical features evaluated in primary OS samples. Our results showed downregulation of miR-139-5p and miR-708-5p in OS samples compared to non-neoplastic controls. Moreover, lower expression of miR-708-5p was associated with poor overall survival and higher expression of miR-181b-5p related to worst chemotherapy response (low HUVOS level). Based on these results, we selected miR-139-5p and miR-708-5p for further functional testing. Inducing the expression of miR-139-5p diminished the clonogenic capacity of the HOS cell line, while upregulation of miR-708-5p was related to a lower cellular adhesion. In summary, this work identified new signatures of microRNA dysregulation that may serve as useful prognostic markers in this aggressive pediatric bone tumor.

Expression of transcription factors NF-kappaB and AP-1 in nasal polyposis.

BACKGROUND: The treatment and prognosis of nasal polyposis (NP) may be influenced by transcription factors, but their expression is poorly understood. OBJECTIVE: To determine the expression of transcription factors [(nuclear factor-kappaB) NF-kappaB and (activator protein) AP-1], cytokines [IL-1beta, TNF-alpha and (granulocytes and macrophage colony-stimulating factor) GM-CSF], growth factor (b-FGF), chemokine (eotaxin-2) and adhesion molecule (ICAM-1) in NP in comparison with nasal mucosa controls. Methods Cross-sectional study. Twenty biopsies of nasal polyps were compared with eight middle turbinate biopsies. p65, c-Fos, IL-1beta, TNF-alpha, ICAM-1, b-FGF, eotaxin-2 and GM-CSF were analysed through RQ-PCR, and p65 and c-Fos were also analysed through Western blotting. RESULTS: NF-kappaB expression was increased in patients with NP when compared with control mucosa (P<0.05), whereas AP-1 expression did not differ significantly between groups. Expressions of IL-1beta, eotaxin-2 and b-FGF were also increased in patients with NP compared with controls (P<0.05). CONCLUSIONS: The transcription factor NF-kappaB is more expressed in NP than in control mucosa. This is important in NP because NF-kappaB can induce the transcription of cytokines, chemokines and adhesion molecules, which play an important role in the inflammatory process. Moreover, transcription factors influence the response to corticosteroids, which are the basis of NP treatment. Transcription factor AP-1 does not seem to have a significant role in the pathological process.

Differential expression of E-cadherin gene in human neuroepithelial tumors.

Cadherins are cell-to-cell adhesion molecules that play an important role in the establishment of adherent-type junctions by mediating calcium-dependent cellular interactions. The CDH1 gene encodes the transmembrane glycoprotein E-cadherin which is important in maintaining homophilic cell-cell adhesion in epithelial tissues. E-cadherin interacts with catenin proteins to maintain tissue architecture. Structural defects or loss of expression of E-cadherin have been reported as a common feature in several human cancer types. This study aimed to evaluate the expression of E-cadherin and their correlation with clinical features in microdissected brain tumor samples from 81 patients, divided into 62 astrocytic tumors grades I to IV and 19 medulloblastomas, and from 5 white matter non-neoplasic brain tissue samples. E-cadherin (CDH1) gene expression was analyzed by quantitative real-time polymerase chain reaction. Mann-Whitney, Kruskal-Wallis, Kaplan-Meir, and log-rank tests were performed for statistical analyses. We observed a decrease in expression among pathological grades of neuroepithelial tumors. Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than did neuroepithelial tumors. Expression of E-cadherin gene was higher in astrocytic than embryonal tumors (P = 0.0168). Low-grade malignancy astrocytomas (grades I-II) showed higher CDH1 expression than did high-grade malignancy astrocytomas (grades III-IV) and medulloblastomas (P < 0.0001). Non-neoplasic brain tissue showed a higher expression level of CDH1 gene than grade I malignancy astrocytomas, considered as benign tumors (P = 0.0473). These results suggest that a decrease in E-cadherin gene expression level in high-grade neuroepithelial tumors may be a hallmark of malignancy in dedifferentiated tumors and that it may be possibly correlated with their progression and dissemination.

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia.

Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of

Analysis of ETV6/RUNX1 fusions for evaluating the late effects of cancer therapy in ALL (acute lymphoblastic leukemia) cured patients.

Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in childhood. The improvements of therapies have increased the number of long-term survivors. However, an increased incidence of secondary neoplasias has been observed in this cohort. Our purpose was to evaluate the late effects of cancer therapy in cured patients previously treated for ALL, considering previous reports on the occurrence of gene fusions as putative markers of chromosomal instability. Twelve ALL patients (aged 5 to 16 years) and twelve healthy subjects (aged 18 to 22 years) were studied for the presence of ETV6/RUNX1 (TEL/AML1) translocations, which were detected by FISH (fluorescence in situ hybridization). The blood samples were collected months or years after completion of the therapy, and the frequencies of gene fusions in lymphocytes were compared with those obtained retrospectively for bone marrow samples at the time of diagnosis, and also for the control group. It was demonstrated that ETV6/RUNX1 gene fusion was a frequent event (0.59-1.84/100 cells) in peripheral blood lymphocytes from normal individuals and the ALL patients who underwent chemotherapy showed significantly (P = 0.0043) increased frequencies (0.62-3.96/100 cells) of the rearrangement when compared with the control groups (patients at diagnosis and healthy subjects). However, a significant difference was not found between the groups of patients at diagnosis and healthy subjects, when the two patients who were positive for the rearrangement were excluded. Therefore, increased frequencies of ETV6/RUNX1 fusions in ALL cured patients indicate the influence of previous exposure to anti-cancer drugs, and they may represent an important genetic marker for estimating the risk of relapse, or development of secondary neoplasias.

CD10 and CD19 fluorescence intensity of B-cell precursors in normal and leukemic bone marrow. Clinical characterization of CD10(+strong) and CD10(+weak) common acute lymphoblastic leukemia.

In order to assess the age-related changes in CD10 and CD19 fluorescence intensity (FI) the present study analyzed by flow cytometry 56 sternal biopsies from 'normal' infants, children and adults undergoing cardiac surgery. The CD10(+weak) subset was predominant in all age groups, representing approximately 50% of the bone marrow (BM) lymphoid cells in children younger than 4 years. Both CD10+ subsets significantly decreased with age but their ratio did not differ significantly. Moreover, the intensity of CD10 and CD19 fluorescence in the strong and weak subsets did not vary with age. The CD19 intensity was significantly higher in CD10(+weak) than in CD10(+strong) cells. In addition, we classified as CD10(+weak) or CD10(+strong) the leukemic cells from BM aspirates of 117 patients with common acute lymphoblastic leukemia (cALL) (78 children and 39 adults). A higher frequency of cases expressing the CD19+ CD10(+strong) phenotype was observed both in children and adults. Children of the CD10(+weak) group tended to be older than those of the CD10(+strong) group (median = 7 vs. 4 years, P = 0.07), and presented a significantly higher frequency of splenomegaly (93.7 vs. 55%, P = 0.04), which was massive in about 60% of these cases. Among adults, a significantly higher frequency of cases expressing the CD10(+weak) phenotype was observed in females. No other clinical or biological difference was detected between the two groups either for children or adults. Concerning the treatment outcome, we did not observe significant differences in complete remission rate (CRR) or in disease free survival (DFS) among the 32 children and 28 adults analyzed. Finally, we compared the CD10 and CD19 intensity in normal and leukemic BM. Overexpression of either or both antigens in leukemic cells was observed in 42.4% of the cALL cases. In these cases, using cut off values of 110 afu for the CD10 FI and of 100 afu for the CD19 FI, the detection of leukemic cells was possible at levels of 0.2% based on CD10 analysis, of 0.6% based on CD19, and 0.02% when both antigens were overexpressed. In conclusion, we demonstrated that the heterogeneity of CD10 and CD19 fluorescence intensity is of no clinical relevance in cALL, although its study may be helpful for the diagnosis and the detection of minimal residual disease.

Cytogenetic study of a case of childhood erythroleukemia.

We report a case of childhood erythroleukemia diagnosed by French-American-British Cooperative group (FAB) and by cytogenetic analysis of bone marrow cells. The following major chromosome anomalies were detected: hyperdiploidy with a modal number of 49, three markers consisting of translocations between chromosomes 3, 9, 20, and 15, deletion of the long arm of chromosome 16 (q22----qter), and karyotype instability. These changes were compared with others reported in the literature and discussed in terms of their importance for diagnostic confirmation.

Translocation (1;5)(q32;q35) in CD30+ anaplastic large cell non-Hodgkin lymphona of childhood. A case report.

The authors studied cytogenetically a case of CD30+ anaplastic large cell non-Hodgkin lymphoma previously diagnosed as malignant histiocytosis and detected a translocation involving chromosomes 1 and 5, t(1;5)(q32:q35). After comparing their findings with those from reports in the literature, they comment about the importance of breakpoint q35 on chromosome 5 and point out the importance of associating morphologic, immunoperoxidase, and cytogenetic findings to confirm the diagnosis of this tumor.

Lack of evidence for mutations or deletions in the CDKN2A/p16 and CDKN2B/p15 genes of Brazilian neuroblastoma patients.

Neuroblastoma, the most common extracranial tumor in childhood, has a wide spectrum of clinical and biological features. The loss of heterozygosity within the 9p21 region has been reported as a prognostic factor. Two tumor suppressor genes located in this region, the CDKN2B/p15 and CDKN2A/p16 (cyclin-dependent kinase inhibitors 2B and 2A, respectively) genes, play a critical role in cell cycle progression and are considered to be targets for tumor inactivation. We analyzed CDKN2B/p15 and CDKN2A/p16 gene alterations in 11 patients, who ranged in age from 4 months to 13 years (male/female ratio was 1.2:1). The most frequent stage of the tumor was stage IV (50%), followed by stages II and III (20%) and stage I (10%). The samples were submitted to the multiplex PCR technique for homozygous deletion analysis and to single-strand conformation polymorphism and nucleotide sequencing for mutation analysis. All exons of both genes were analyzed, but no deletion was detected. One sample exhibited shift mobility specific for exon 2 in the CDKN2B/p15 gene, not confirmed by DNA sequencing. Homozygous deletions and mutations are not involved in the inactivation mechanism of the CDKN2B/p15 and CDKN2A/p16 genes in neuroblastoma; however, these two abnormalities do not exclude other inactivation pathways. Recent evidence has shown that the expression of these genes is altered in this disease. Therefore, other mechanisms of inactivation, such as methylation of promoter region and unproperly function of proteins, may be considered in order to estimate the real contribution of these genes to neuroblastoma genesis or disease progression.

Nutritional assessment and serum zinc and copper concentration in leukemic children.

CONTEXT: Malnutrition in childhood cancer is commonly a serious problem. Changes in blood zinc and copper have also been found in malignant diseases. OBJECTIVE: To describe the protein-energy nutritional status and serum zinc and copper of children with newly diagnosed leukemia. DESIGN: Cross-sectional study. SETTING: University referral center. PARTICIPANTS: 23 children with newly diagnosed acute lymphocytic leukemia (ALL) or acute non-lymphocytic leukemia (ANLL) between the ages of 1 and 10 years. The control subjects were 31 healthy school children of similar age from local schools. MAIN MEASURES: Anthropometric measurements of height/age and weight/height, food intake and serum levels of zinc and copper. RESULTS: Almost the entire group of children were eutrophic. Zinc and copper intake were below the recommended values. Serum zinc levels were significantly lower and serum copper levels were significantly higher in the leukemic group when compared to normal children. CONCLUSION: At the time of diagnosis the children suffering from leukemia were not overtly malnourished but blood analysis showed alterations in concentrations of the trace elements zinc and copper.

Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction.

CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH) for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%). There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%), presence of CALLA+ (81.2% versus 80%) or risk group (62.5% versus 60%). Disease-free survival was similar in both groups, with no significant difference (p: 0.7695). CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

Analysis of the p53 gene by PCR-SSCP in ten cases of Wilms' tumor.

CONTEXT: Mutations of the p53 tumor suppressor gene are the most frequent alterations observed in human neoplasias affecting adults. In pediatric oncology, however, they have seldom been identified. Wilms' tumor is a renal neoplasia commonly occurring in children and is associated with mutations of the WT1 gene. The correlation between Wilms' tumor and alterations of the p53 gene has not been well established, with a low frequency of mutations having been reported in this type of tumor. Mutation may be associated with advanced stage disease and unfavorable histology. OBJECTIVE: To screen for mutations of the p53 gene by the PCR-SSCP method and DNA sequencing in cases of Wilms' tumor sug-gestive of mutation. DESIGN: Case Report. CASE REPORT: Evaluations of exons 5-9 of the p53 gene in DNA samples extracted by PCR-SSCP from 10 Wilms' tumors in children at different stages, and DNA sequencing. Changes in SSCP analy-sis were observed in exon 8 in two samples. The probable muta-tions were not confirmed by DNA sequencing. The absence of point mutations in p53 gene observed in the 10 samples of Wilms' tumor studied agrees with literature data, with DNA sequencing being of fundamental importance for the confirmation of possible mutations.

[Zinc in protein-calorie malnutrition. I. Concentration in serum of children with the clinical types, kwashiorkor and marasmic kwashiorkor]. / Zinco na desnutrição protéico-calórica. I. Concentração no soro de crianças com os tipos clínicos kwashiorkor e kwashiorkor-marasmático.

Zinc concentration was measured in the serum of 10 children with protein-energy malnutrition (eight with clinical signs of kwashiorkor, and two with marasmic-kwashiorkor) on the first, 15th and 30th day after admission. The zinc levels were significantly lower for these patients on the first day than those observed for children with good nutritional status. No significant increase in zinc concentration occurred in the serum of these patients during initial period of recovery of nutritional status. The possibility of zinc supplementation for malnourished children during recovery is discussed.