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Biomedical subjects

Süreyya Savaşan

Publications and source records attributed to Süreyya Savaşan.

At least 19 recordsLinked to original sources

Vacuolated neuroblastoma cells mimicking FAB L(3) lymphoblasts in bone marrow aspirates.

Abundant cytoplasmic vacuolation of neuroblasts has been noted on bone marrow aspirate (BMA) smears of two patients with metastatic neuroblastoma. Occasional tumor cells were dispersed as individual cells as well as in clumps. These cells had basophilic cytoplasm and several nucleoli, reminiscent of L(3) lymphoblast morphology. Flow cytometric analysis of the bone marrow mononuclear cells and neuron-specific enolase staining of the bone marrow biopsy samples further distinguished the cells as neuroblasts. Cytoplasmic vacuolations of neuroblasts may be a feature of metastatic neuroblastoma cells in BMA smears.

Adrenal Gland Neoplasms↗

Altered in vitro immune response to hypoxia-treated normal peritoneal fibroblasts.

Hypoxia treatment of normal peritoneal fibroblasts results in alterations that are characteristic for fibroblasts obtained from postoperative peritoneal adhesion tissue. In this study, we have shown that hypoxia treatment enhances normal peritoneal fibroblast elimination by lymphokine-activated killer cells to the level of adhesion tissue fibroblasts, suggesting a pivotal role of hypoxia in the adhesion development.

Adaptation, Physiological↗

CD36 (thrombospondin receptor) expression in childhood acute megakaryoblastic leukemia: in vitro drug sensitivity and outcome.

The outcome for children with acute megakaryoblastic leukemia (AMKL) remains poor, except for cases associated with Down syndrome (DS). This study compared immunophenotypic and drug sensitivity patterns of childhood AMKL cases with or without DS. All DS-AMKL cases showed high expression of CD36 and were very sensitive to cytarabine and daunorubicin in vitro. In children without DS, high expression of CD36 on AMKL blasts identified a sub-group with immunophenotypic and drug sensitivity patterns similar to that of DS AMKL. Among non-DS AMKL patients, CD36-high cases had a superior outcome compared with CD36-negative cases. CD36 expression in acute myeloid leukemia cases other than AMKL was not associated with increased in vitro drug sensitivity. CD36 expression in AMKL may be an indicator of megakaryoblast maturation and chemotherapy sensitivity.

Adolescent↗

An enigmatic disease: childhood Langerhans cell histiocytosis in 2005.

Histiocytic proliferative diseases, although rare, constitute a challenge for pediatric pathologists and hematologists/oncologists because of difficulties in the identification of subtypes and the lack of established standard therapies, resulting in treatment failures, recurrences, or complications. Amongst the different types of such disorders, Langerhans cell histiocytosis (LCH) has been enigmatic to all involved, secondary to a long list of unresolved issues in pathogenesis and treatment. The fundamental dispute over its neoplastic vs. reactive nature remains unsettled. Unique features of LCH, including clonality, cases with spontaneous regression, frequent recurrences, and target tissue/organ tropism, have attracted significant interest. This article reviews the current understanding of LCH in the light of discoveries over the last few decades.

Child↗

Melatonin cytotoxicity in human leukemia cells: relation with its pro-oxidant effect.

Melatonin has a variety of functions in human physiology and is involved in a number of pathological events including neoplastic processes. The tissue protective actions of melatonin are attributed to its antioxidant activity though, under certain conditions, melatonin might also exert oxidant effects, particularly in cancer cells. This study evaluated the effects of 10(-5) and 10(-3) m concentrations of melatonin on human leukemia cells. Moderate cytotoxic effects of melatonin at 10(-3) m concentrations were observed in CMK, Jurkat and MOLT-4 cells which was associated with significant reactive oxygen species (ROS) generation. Melatonin treatment was not associated with significant cytotoxicity in HL-60 cells, although the generation of ROS was significantly increased. K562 and Daudi cells did not appear to be effected by melatonin treatment. Cellular membrane lipid peroxidation was not influenced by melatonin with the exception of CMK cells. Cell cycle kinetics were not affected in melatonin-treated samples, again with the exception of CMK cells which showed increased apoptosis. Melatonin, therefore, induces the production of ROS that may be associated with cytotoxicity depending on the concentration of melatonin in some leukemia cells and does not appear to stimulate leukemia cell growth. These pro-oxidant actions of melatonin may assist in limiting leukemic cell growth.

Apoptosis↗

Possible role of natural immune response against altered fibroblasts in the development of post-operative adhesions.

PROBLEM: Post-operative adhesion tissue fibroblasts (ATF) differ from normal peritoneal fibroblasts (NPF). Natural immune response participates in the elimination of altered cells. In this study, we investigated NPF and ATF expression patterns of immune response-related markers, and lymphokine-activated killer (LAK) cell-mediated fibroblast elimination in vitro. METHOD OF STUDY: Primary cell cultures of both NPF and ATF obtained from the same four patients were used in the experiments. The expression of CD54, CD40 and CD120b, and allogeneic LAK cell-mediated ATF and NPF elimination were studied by flow cytometry. RESULTS: Average expression of CD54 in ATF was greater by 12.3-fold compared with NPF (P = 0.021), with ratios of 2.4 and 1.9-fold for CD40 (P < 0.001) and CD120b (P = 0.013), respectively. Average LAK cell-mediated fibroblast killing was 1.8 +/- 0.8-fold greater in ATF over NPF (P = 0.008). Furthermore, LAK cell-mediated fibroblast elimination correlated significantly with the increased CD40, CD54 and CD120b expression (R > 0.956; P < 0.05 for each). CONCLUSIONS: These results demonstrate that ATF are more susceptible to lymphocyte-mediated elimination than NPF and the development of adhesions despite this could be explained by either impaired or overwhelmed autologous natural immune response against reactive fibroblasts.

CD40 Antigens↗

Combinational IL-2/IL-15 induction does not further enhance IL-15-induced lymphokine-activated killer cell cytotoxicity against human leukemia/lymphoma cells.

In vitro comparisons of induction of perforin (PFP), granzyme B (GRB), production of cytokines, and cell-mediated cytotoxicity by interleukin-2 (IL-2), interleukin-15 (IL-15), or combinational IL-2/IL-15-induced lymphokine-activated killer cells were studied in this study. Whereas IL-2-induction was associated with a decrease in cultured cell population over a 7-day period, IL-15 alone or in combination with IL-2 resulted in significant increase including cytotoxic T lymphocytes and subsets of CD56+ lymphocytes, particularly cytokine-induced killer and cytolytic natural killer-T lymphocytes. The overall PFP, GRB, and tumor necrosis factor-alpha expression in different subtypes were also significantly higher with IL-15 alone or in combination with IL-2 induction with resultant superior cytotoxicity compared to IL-2 treatment. There was no significant advantage of addition of IL-2 over IL-15 induction. These results offer further information on the cytotoxic potency of these cytokines and their mechanisms of action implicating potential use of IL-15 as part of cytokine adoptive immunotherapy.

Adolescent↗

Pediatric EBV-positive T-cell/histiocyte-rich large B-cell lymphoma with clonal cells in the bone marrow without overt involvement.

T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL) is a variant of large B-cell lymphoma only rarely encountered in children. Here we report the case of an 8-year-old African American boy with Epstein-Barr virus (EBV)-positive TCHRLBCL who initially presented with right submandibular, anterior cervical and supraclavicular lymphadenopathy. Cytogenetic analysis of the lymph node revealed a near-triploid karyotype with complex chromosomal aberrations. Although morphologically the bone marrow was normal, the same cytogenetically abnormal clone was detected. The patient responded to chemotherapy with CHOP (doxorubicin, cyclophosphamide, vincristine and prednisone) therapy, with disappearance of the abnormal clone from the bone marrow. The patient remains in remission 26 months after the initial diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

Evaluation of cytotoxicity by flow cytometric drug sensitivity assay in childhood T-cell acute lymphoblastic leukemia.

Risk-based treatment strategies have improved outcome in childhood B-precursor acute lymphoblastic leukemia, and in vitro drug sensitivity assessment using methyl-thiazol-tetrazolium (MTT) assay has been shown to be an independent prognostic marker. To date, such strategies in childhood T-cell acute lymphoblastic leukemia (T-ALL) have proved elusive, and in vitro drug sensitivity testing has had limited success in T-ALL due to poor T-cell lymphoblast survival in vitro. We have developed the flow cytometric drug sensitivity assay (FCDSA) to evaluate in vitro drug sensitivity. We studied 68 cases of childhood T-ALL for cytarabine (Ara-C) and daunorubicin sensitivity by FCDSA and compared the results with those obtained by MTT assay. Spontaneous apoptosis was correlated with cytotoxicity rates for both drugs by FCDSA, but not with the results obtained by MTT assay. Daunorubicin sensitivity had a positive correlation with Ara-C in individual cases by FCDSA; but not by MTT assay. Studies repeated on stored samples had comparable results for both drugs by FCDSA (P<0.01), but not for Ara-C by MTT assay. Comparison of T-ALL sensitivity with acute myeloid leukemia (AML) cases revealed a unique pattern difference. Median cytotoxicity (expressed in arbitrary units) for Ara-C was 8 (0-47) and 27 (0-81), and daunorubicine cytotoxicity for T-ALL and AML samples was 79 (5-100) and 34 (0-98), respectively. Although age or white blood cell count at diagnosis was not associated with any particular drug response pattern, CD13 expression on T-lymphoblasts was associated with in vitro resistance. FCDSA is a reliable, practical and reproducible method that can be integrated into studies of drug-target cell interactions in T-ALL.

Apoptosis↗

Severe neutropenia and thrombocytopenia following cardiac transplantation in a child.

Hematological complications have been occasionally described after cardiac transplantation. We are reporting a 5-yr-old child who developed sequential severe neutropenia and thrombocytopenia following cardiac transplantation while on tacrolimus-based immune suppression therapy. There was no improvement in blood counts following a change in immune suppression to cyclosporine A. The neutropenia was associated with a maturation arrest in the bone marrow. The occurrence of thrombocytopenia coincided with rising anti-herpes virus 6 IgG titers suggesting a possible contributory role. Neutropenia resolved following treatment with rituximab, and the thrombocytopenia responded to Dapsone therapy eventually. This case points out the potential multifactorial pathogenesis of cytopenias following cardiac transplantation with differing response to various immune suppressive therapies.

Antibodies, Viral↗

Successful bone marrow transplantation for life threatening xanthogranuloma disseminatum in neurofibromatosis type-1.

A 2-yr and 9-month-old female patient with neurofibromatosis type-1 presented with hepatomegaly, anemia, thrombocytopenia, and croupy cough and diagnosed with xanthogranuloma disseminatum (XD). She failed chemotherapy consisting of steroids, 6-mercaptopurine and methotrexate. A partial response to HLH-94 therapy that included etoposide and cyclosporine A was initially observed. However, she continued to have significant organ dysfunction without further improvement at 6 months of therapy. She then received matched unrelated donor bone marrow transplantation (BMT) following carmustine, etoposide, cytarabine and melphelan conditioning with complete resolution of symptoms. BMT is an option in therapy-resistant, life threatening XD cases.

Bone Marrow Transplantation↗

Acute megakaryoblastic leukemia with t(17;22)(q21;q13) and liver dysfunction.

The t(1;22)(p13;q13) is associated with acute megakaryoblastic leukemia (AMKL) seen mostly in young infants and known to have a poor prognosis. A 5-year-old child had prolonged prothrombin and partial thromboplastin times, low albumin, and decreased vitamin K-dependent coagulation factors and factor V activities at the time of AMKL diagnosis. All of these factors normalized following chemotherapy when remission was achieved. Cytogenetic analysis revealed a female karyotype with a balanced t(17;22)(q21;q13). Here, we present an AMKL pediatric case with a novel translocation and significant hepatocellular dysfunction that resolved with chemotherapy. The t(17;22) (q21;q13) may represent a variant of t(1;22)(p13;q13).

Antineoplastic Combined Chemotherapy Protocols↗

Cell-mediated cytotoxicity evaluation using monoclonal antibody staining for target or effector cells with annexinV/propidium iodide colabeling by fluorosphere-adjusted counts on three-color flow cytometry.

BACKGROUND: In addition to (51)chromium release assay, flow cytometric methods have been described to assess in vitro cell-mediated cytotoxicity. In this report, we describe a new flow cytometric approach for determination of in vitro cell-mediated cytotoxicity utilizing three-color flow cytometric assay. METHODS: This method is based on monoclonal antibody staining of either effector or target cells to evaluate cytotoxicity with increased accuracy by utilizing fluorospheres for calibration. The basic strategy involves labeling effector or target cells with a specific fluorescent-conjugated monoclonal antibody, in addition to staining with annexinV-FITC and propidium iodide to identify apoptotic/dead cells. The effector and target cell populations as well as conjugates were clearly and easily identified by this approach. RESULTS: We obtained significant correlation between cytotoxicity calculated by this technique and (51)chromium release assay results. The integration of fluorospheres allowed us to determine the absolute number of events reflective of the cumulative cell death rather than a cross-sectional, percentage-based cytotoxicity assessment in the target cell population at the time of analysis. CONCLUSIONS: This method provides additional advantages to other methods and enables the study of target cell fate in more detail, as well as providing a potential contribution to understanding the mechanisms of cell elimination.

Annexin A5↗