Biomedical subjects

Sophia Polychronopoulou

Publications and source records attributed to Sophia Polychronopoulou.

12 recordsLinked to original sources

PubMed2006

Melatonin and immunomodulation: connections and potential clinical applications.

Melatonin is the main hormone secreted by the pineal gland in the human brain. It has a strong impact on the sleep-wake cycle and is considered a general modulator of the human circadian rhythm. Apart from these well-established properties, melatonin possesses immunomodulatory, antioxidative and antiinflammatory properties. The potential ability of this hormone to act synergistically with several cytokines by enhancing their antitumoral activity and dramatically decreasing their adverse effects has placed melatonin among the new and promising agents in cancer immunotherapy. The use of the neurohormone alone or in combination with cytokines and traditional chemotherapeutic drugs is currently under vigorous investigation. Experimental and clinical trials have already depicted some of the immunomodulatory and antitumor effects of melatonin, delineating the need for further research in this field.

Animals↗

PubMed2006

Second and third malignant solid tumor in a girl with ovarian Sertoli-Leydig tumor.

We report a Sertoli-Leydig cell (SLC) tumor of the right ovary in a 10-year-old girl, which was dealt with surgical removal. Three months after resection, she presented with a new episode of acute abdomen because of an abdominal mass, which histologically was compatible with an undifferentiated embryonal rhabdomyosarcoma. Chemotherapy, according to SIOP-??? 89 protocol, was administered additionally to radiotherapy (3,960 cGy). Three years after completing treatment, the patient developed a painful swelling at her left upper arm. The diagnosis was Ewing sarcoma of the humerus, which was confirmed by identification of the typical 11; 22 translocation on cytogenetic and molecular analysis of the tumor tissue. The patient died 14 months from Ewing diagnosis due to progressive disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Transient and chronic neutropenias detected in children with different viral and bacterial infections.

AIM: The aim of the study was to identify the relationship of acquired neutropenias with infections in childhood and to assess their course, complications, short and long-term outcome. METHOD: During a two-year period, all children admitted to the pediatric ward with neutropenia were investigated for underlying infections with indices of infection, cultures of body fluids and serological tests. RESULTS: Sixty-seven previously healthy children, aged (median, 25-75%) 0.7 years (0.2-1.5), were identified with neutropenia (frequency: 2.0%). An infectious agent was identified in 34/67 cases (50.7%) (viral infection: n=24, bacterial: n=10). In 50/67 (74.6%) children, neutropenia recovered within 2 months (transient neutropenia, TN), while in 17/67 (25.4%) of them it persisted for more than two months. Two years after diagnosis 50/67 children (74.6%) accepted to be reassessed. Of these children, 8/50 (16%) remained neutropenic (neutropenic children, NC), while 42/50 had recovered completely. CONCLUSION: Neutropenia during childhood is usually transient, often following viral and common bacterial infections, does not present serious complications and in the majority, it resolves spontaneously. However, in a significant percentage of patients, neutropenia is discovered during the course of an infection, on a ground of a preceding chronic neutropenic status.

Adolescent↗

PubMed2006

Invasive Acremonium strictum infection in a bone marrow transplant recipient.

We describe an invasive Acremonium strictum infection in a 9-year-old debilitated bone marrow transplant recipient. Outcome was successful, despite resistance to the amphotericin B that was initially administered. A. strictum was isolated from bone and urine cultures. We summarize data on 15 opportunistic invasive infections caused by Acremonium in pediatric hosts reported thus far in the English language literature.

Acremonium↗

PubMed2005

Infections in a pediatric patient cohort with acute lymphoblastic leukemia during the entire course of treatment.

GOALS: To assess the type, frequency, severity, and outcome of all infectious episodes in a pediatric patient cohort with acute lymphoblastic leukemia (ALL) from a single institution during the entire length of leukemia treatment. PATIENTS AND METHODS: Eighty-six patients were treated according to a modified ALL Berlin-Frankfurt-Munster protocol. Retrospective analysis of all types of infections according to the treatment phase and the degree of neutropenia is presented. RESULTS: A total of 610 infectious episodes were recorded. Most infections were documented during maintenance (57%), followed by the induction phase (20.3%). During maintenance, 347 episodes were encountered, with nonspecific viral upper respiratory tract infections (URIs) being the commonest diagnosis (40.0%). Additionally, 38 of 58 total specific viral infections occurred during maintenance: 16 herpes simplex, 7 varicella, 10 herpes zoster infections [varicella-zoster virus (VZV), 45%]. The majority of bacteremia and fever of unknown origin occurred during induction (20%). The number of Gram-negative bacteremia was 50% of the total (26 of 52). The majority of the infections (59.5%) occurred without neutropenia [absolute neutrophil count (ANC) >1,000 microl(-1)]. Fewer infections (9.3%) were recorded with concurrent very severe neutropenia (ANC <100 microl(-1)), although 38.5% of positive blood cultures were documented with severe neutropenia. No infection-related fatality occurred. CONCLUSIONS: Most of the severe infections occurred during induction. Gram-positive bacteremia and Gram-negative bacteremia were almost equal. URIs were the commonest infections during the entire treatment and during maintenance. Specific viral infections represented a smaller percentage of the total (VZV was the commonest pathogen). Infectious complications represented a significant morbidity factor, but notably, mortality was negligible.

Acute Disease↗

PubMed2005

Hypermethylation of CpG islands in the promoter region of the p15INK4B gene in childhood acute leukaemia.

It has been reported that the cyclin-dependent kinase inhibitor (CDKI) gene p15INK4B is frequently inactivated by genetic alterations and may be responsible for various malignant tumours. Another way of inactivation of this CDKI is by hypermethylation of 5'CpG islands in the promoter region of the p15INK4B gene and this inactivation seems to be a frequent event in various haematological malignancies. In the present study, we investigated the methylation status of the p151NK4B gene to clarify its role in the pathogenesis of childhood acute myeloid (AML) and acute lymphoblastic leukaemia (ALL). The study included 23 cases of B-cell origin ALL, 13 cases of T-cell origin ALL, 32 cases of AML, and 10 apparently healthy controls. Hypermethylation was studied by methylation-specific polymerase chain reaction. Hypermethylation of the p15INK4B gene was more frequent in cases with T-cell origin ALL (46.2%), but similar among children with B-cell origin ALL (13.0%) and AML (18.8%). Hypermethylation of p15INK4B may be involved in the pathogenesis of T-cell origin ALL, but not in that of AML or B-cell origin ALL.

Child↗

PubMed2004

Telomere length and telomerase activity: variations with advancing age and potential role in childhood malignancies.

Telomeres, representing the chromosome nucleoprotein tails, shorten during each cell division due to the inability of conventional DNA polymerases to completely replicate the chromosome termini. When telomeres become critically short, cells are directed to exit from the cell division cycle (replicative senescence). Telomerase is a reverse transcriptase that synthesizes telomeric sequences, thereby prolonging the lifespan of cells. Telomere length and telomerase activity expression vary significantly in different normal somatic tissues and age groups. In many childhood malignancies (ie, acute leukemias and solid tumors), telomere length and telomerase activity of the malignant cell population may be correlated with the disease outcome and thus may be promising tools in evaluating prognosis and monitoring treatment progress. Finally, telomerase inhibition by using several strategies (ie, antisense oligonucleotides) represents a potentially valuable target for antitumor therapy in the near future.

Cell Survival↗

PubMed2004

Osteosarcoma as a second tumor after treatment for primary non-Hodgkin's lymphoma in a child with ataxia-telangiectasia: presentation of a case and review of possible pathogenetic mechanisms.

Patients with ataxia-telangiectasia (A-T) and cancer are exposed to additional toxicity due to their underlying inability to repair chemotherapy-induced DNA damage. The authors report the development of osteosarcoma as a second neoplasia in a child with A-T who was treated, without being irradiated, for non-Hodgkin's lymphoma as a primary malignancy. This is the first report of osteosarcoma associated with A-T. The authors postulate that the mechanisms of carcinogenesis are common and independent of the different histopathology categories of these two neoplasias, and the underlying "canvas" of the A-T mutated gene was further triggered by chemotherapy, leading to the development of a second malignancy.

Ataxia Telangiectasia↗

PubMed2004

Ineffective erythropoiesis underlies the clinical heterogeneity of congenital dyserythropoietic anemia type II (CDA II).

BACKGROUND: Congenital dyserythropoietic anemia type II (CDA II) is an autosomal recessive disease, and is the most common CDA. The qualitative and quantitative defects of erythropoiesis in CDA II, as estimated by the hematological and biochemical parameters at the time of diagnosis, may not reflect the heterogeneity of the disease course of each patient. METHODS: Three pediatric patients with CDA II are herein presented, having an heterogeneous clinical course. In addition to bone marrow morphology, Ham test and SDS-PAGE of erythrocyte membrane protein, the present study also examined erythroid marrow activity, by measuring serum Erythropoietin (Epo), soluble Transferrin Receptors (sTfR) concentrations and Reticulocyte Production Index (RPI). RESULTS: All patients demonstrated the same pattern of ineffective erythropoiesis, having increased Epo (350-389 IU/L), sTfR concentrations (6.2-7.8 mg/L) and low RPI values (0.8-1.3). Erythron expansion was expressed by RPI values nearly twofold higher than normal values in parallel to raised sTfR and high Epo production. Despite the same degree of ineffective erythropoiesis seen in all patients, the severity of the clinical course was diverse in terms of frequency and clinical relevance of transfusion needs. CONCLUSION: An analysis of the parameters expressing ineffective erythropoiesis in CDA II can provide a better understanding of the degree of dyserythropoiesis, however it is not useful for predicting the clinical course of disease in patients, because the underlying genetic heterogeneity of this disorder remains obscure.

Anemia, Dyserythropoietic, Congenital↗

PubMed2004

Telomere length variation and telomerase activity expression in patients with congenital and acquired aplastic anemia.

Telomeres represent the nucleoprotein tails of chromosomes that get shortened with each cell division. When the telomere length reaches a critical point, cell senescence and death occur. Telomerase is a reverse transcriptase that counteracts telomere loss by adding telomeric sequences. In patients with acquired aplastic anemia, the mean telomere length (TRF) of peripheral blood leukocytes is generally short when compared to normal controls, without it being clear whether a relationship between TRF and disease severity exists. Additionally, increased telomerase activity (TA) is found in the bone marrow mononuclear cell population (MNCs) of aplastic anemia patients, especially in the chronic form of the disease. Fanconi anemia (FA) patients generally demonstrate increased TA and short telomeres in peripheral blood MNCs, a fact attributed to the high turnover of hematopoietic progenitor cells in combination with direct breakages at telomeric sequences. Furthermore, a strong correlation has been shown between TRF and the severity of aplastic anemia, but not with FA evolution towards myelodysplastic syndrome or acute myeloblastic leukemia. In respect of dyskeratosis congenita (DC), a disease of either X-linked or autosomal dominant/recessive inheritance which is characterized by premature ageing of highly regenerative tissues, studies have been carried out in order to elucidate whether the X-linked DC is caused by a defect in ribosomal RNA processing and/or telomere maintenance. Finally, the direct genetic link established between DC pathogenesis and short telomeres may lead to the development of new therapeutic protocols for diseases characterized by short telomere length and subsequent genomic instability.

Anemia, Aplastic↗

PubMed2004

Decrease of CD4+ and B-lymphocyte populations is not associated with severe infectious complications in children with acute lymphoblastic leukemia during maintenance.

The suppression of lymphopoiesis and immune competence during the maintenance phase in children with acute lymphoblastic leukemia (ALL) and the occurrence of infectious complications remain an unexplored area. In this study we assessed lymphocyte subpopulation disturbances during maintenance for childhood ALL along with the incidence, type, and severity of infections that occur during that period in the absence of neutropenia. Twenty-eight children (13 boys, 15 girls) with ALL aged 3-14 years (median 7 years) and treated according to the ALL-BFM 90/95 protocol were studied during maintenance for ALL. Complete white blood cell (WBC) counts and peripheral blood lymphocyte (PBL) analyses were performed. Major lymphocyte subsets (CD19+, CD3+CD4+, CD3-CD8+, CD3-CD16+CD56+, CD45RA-, CD45RO+) and markers of T-cell activation (CD25, CD38, CD69, HLA-DR) were analyzed with flow cytometry. Serum immunoglobulin G (IgG), IgA, and IgM levels were measured by a nephelometric assay. All infectious episodes during the study period were recorded in detail. Additionally, 41 age-matched immunocompetent children were used as controls. Absolute WBC counts (median, 3627/microL) and PBL counts (median, 1206/microL) were significantly below the age-adjusted control values (7400/microL and 2673/microL, respectively; P < .0001). B-lymphocyte, total CD4+, and memory CD4+ (CD4+CD45RO+) subsets were also significantly decreased (33/microL versus 377/microL [P < .0001], 531/microL versus 1045/microL [P < .01], and 80/microL versus 299/microL [P < .001], respectively). Significantly lower immunoglobulin levels were found in all patients. Twenty-two of the 28 patients presented with 74 episodes of a variety o minor infections (mostly respiratory viral [39], skin [7], and gastrointestinal [3]), none demanding prolonged hospital treat ment. Our findings demonstrate a profound immunosuppression throughout maintenance therapy in children with ALL tha has no major clinical impact in terms of increased incidence or severity of systemic infections.

Adolescent↗

PubMedDate not supplied

Nasopharyngeal carcinoma in childhood and adolescence: a single institution's experience with treatment modalities during the last 15 years.

Pediatric nasopharyngeal carcinoma (NPC) represents a locally advanced undifferentiated tumor with widely varying epidemiological features and with a high cure rate when combined modality treatment is provided. Both local and systemic treatment is necessary, and additional treatment with biologic modifiers seems promising. In this study, clinical experience and therapeutic results of 10 children with newly diagnosed NPC, treated in a single pediatric hematology/oncology institution in Athens over a period of 15 years, are analyzed. Results from Greece on NPC in young patients are reported for the first time. Ten patients (6 male, 4 female) 7-14 years old (median = 12.5) with a nasopharyngeal tumor were retrospectively evaluated. Disease extent was staged according to the TNM system. EBV-DNA, EBERs, and LMP-1 from paraffin-embedded tissues were studied in 8 patients. All patients received both local and systemic treatment. All cases were classified as type WHO-3. The presence of EBV-DNA and expression of EBER 1-2 mRNAs was demonstrated in the 8 tumors examined, while LMP-1 protein was expressed in 4/8 of the studied cases. Disease stage was III in 4 and IV in 6 patients. Time from the onset of symptoms to diagnosis ranged from 4 to 24 weeks (mean 8 weeks). All patients received preradiation chemotherapy and radiotherapy, and 5/10 received postradiation chemotherapy due to either resistant or advanced disease. In 9/10 patients, complete locoregional control was achieved. In addition to chemotherapy and radiotherapy the latest patient of this series was treated with recombinant IFN-beta (10(5) IU/Kg i.v. 3 times a week) for 6 months and at 18 months remains in continuous complete remission. One patient was lost to follow-up 3 years after cessation of treatment while remaining in complete remission. Of the remaining 9 patients, 7 are alive for a median follow-up of 54 months (range 18-186); 5/7 are free of disease, and 2/7 are with disease but stable. The median time for first relapse was 17 months. The data confirm the good results of combined chemo-radiotherapy treatment for high-risk NPC in young patients. The documented EBV latency underlying this tumor, which possibly critically mediates its pathogenesis, justifies the use of biological modifiers with antiviral and immunoregulatory activity, like the IFNs, which may offer better therapeutic results in the future.

Adolescent↗