Humans ; Tumor-Associated Macrophages/pathology* ; Neuroblastoma/pathology*

Central Nervous System Neoplasms ; secondary ; Humans ; Neoplasm Metastasis ; Neuroblastoma ; pathology

Adolescent ; Bone Marrow ; pathology ; Female ; Humans ; Leukemia ; diagnosis ; Neuroblastoma ; diagnosis

Bone Marrow Neoplasms/pathology* ; Bone Neoplasms/pathology* ; Humans ; Neoplasm Metastasis ; Neuroblastoma/pathology*

We used retroviral-mediated gene transfer of the human interleukin (IL)-2 gene into murine neuroblastoma cells to investigate whether locally-secreted IL-2 is able to influence the generation of anti-tumor immune responses. Supernatant obtained from cultures of approximately 1 x 10(6) IL-2 gene-transduced, G-418 selected neuro-2a cells was assayed for human IL-2 production by ELISA kit. First, to estimate whether the local secretion of IL-2 from the genetically-modified tumor cells would affect their tumorigenicity in vivo, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice and tumor growth was measured weekly. And to estimate whether IL-2 transfected neuroblastoma cells protect mice from tumor development after wild-type tumor cell challenge, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice. Seven days after IL-2 gene-transfected neuroblastoma cell injection, unmodified neuro-2a cells were s.c. injected into the contralateral site of A/J mice and tumor growth was measured weekly. Finally, to estimate IL-2 effect on pre-established large tumor burdens, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice with established tumor and its growth was measured weekly. The IL-2 gene-transduced neuro-2a clones secreted 120.25-177.3 IU of IL-2 per ml per 10(6) cells during 24 hr. None of the mice injected with IL-2-secreting neuro-2a cells developed tumors within 6 weeks, while all of the mice injected with wild-type neuro-2a cells developed tumors. Immunization of mice with IL-2 gene-transfected, irradiated neuro-2a cells protected these animals against a subsequent challenge with wild-type tumor cells. Finally, the size of large neuroblastomas decreased after IL-2-secreting neuro-2a cell injection into mice. Local secretion of IL-2 gene-transduced tumor cells abrogates their tumorigenicity and induces protective immunity and may inhibit the growth of neuroblastoma.
Animal ; Antibody Formation ; Gene Transfer Techniques* ; Human ; Immunization/methods ; Interleukin-2/therapeutic use ; Interleukin-2/genetics* ; Mice ; Neoplasm Transplantation ; Neuroblastoma/therapy ; Neuroblastoma/prevention & control ; Neuroblastoma/pathology ; Neuroblastoma/genetics* ; Retroviridae/genetics* ; Tumor Cells, Cultured

Apoptosis ; Calcineurin ; metabolism ; Chymotrypsin ; metabolism ; Humans ; Lysosomes ; enzymology ; Mitochondria ; metabolism ; pathology ; Mitochondrial Dynamics ; Neuroblastoma ; metabolism ; pathology

OBJECTIVETo evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic (DAergic) neurons for Parkinson's disease (PD) research and to determine the effect of differentiation on this cell model.

DATA SOURCESThe data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals (Pubmed 1973 to 2009).

STUDY SELECTIONAfter searching the literature, 60 articles were selected to address this review.

RESULTSThe SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-beta-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium (MPP(+)) uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons.

CONCLUSIONSDifferentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxicity and neuroprotection and are thus more relevant to experimental PD research.

Cell Differentiation ; physiology ; Cell Line, Tumor ; Dopamine ; metabolism ; Humans ; Neuroblastoma ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Parkinson Disease ; metabolism ; pathology

Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.
Adolescent ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Human ; Korea ; Male ; Myeloablative Agonists/therapeutic use ; Neuroblastoma/mortality ; Neuroblastoma/pathology ; Neuroblastoma/therapy* ; Retrospective Studies ; Stem Cell Transplantation* ; Survival Rate ; Transplantation Conditioning ; Transplantation, Autologous ; Treatment Outcome

We present an autopsy case of a two-day-old female infant with a very unusual combination of neuroblastoma in situ in both adrenals and microcephaly. This baby was born to a 28-year-old mother after 38 weeks of gestation, and died of respiratory difficulty 2 days later. At autopsy, the baby weighted 1,840gm, and the brain was extraordinarily small with a weight of 125gm. The gyral pattern was simplified and irregular. Microscopically massive migration defects, pachygyria, micropolygyria, leptomeningeal glioneuronal islands, small corticospinal tract and heterotopic Purkinje cells in the cerebellum were found. In addition, there were medullary nodules in both adrenals. They measured 0.7 x 0.4cm and 0.7 x 0.3cm, respectively. These nodules showed the typical histological features of undifferentiated neuroblastoma. The tumor nodules were confined to the medullary portion and did not extend to the cortex or contiguous structures meeting the criteria of neuroblastoma in situ. Based on these unusual and seemingly unrelated sets of findings, it is suggested that the histogenesis of neuroblastoma in situ could be a part of the generalized dysontogenic process.
Adrenal Gland Neoplasms/complications/*congenital/pathology ; Adult ; Carcinoma in Situ/complications/*congenital/pathology ; Female ; Humans ; Infant, Newborn ; *Microcephaly/complications/pathology ; Neuroblastoma/complications/*congenital/pathology ; Pregnancy

A case of abdominal Burkitt's lymphoma diagnosed through aspiration cytology is described. This 9-year-old boy presented with abdominal pain and distention for three months accompanied by fever and night sweat during the last month. An abdominal sonography and CT scan showed hepatosplenomegaly and an intrahepatic mass with celiac lymph node enlargement, ascites, and pleural fluid. A peripheral blood smear showed a few blast cells. Aspiration of the abdominal mass revealed very cellular aspirates consisting of diffusely scattered small monotonous round cells. The cells had little cytoplasm, along with round nuclei that showed clear-cut nuclear membrane, coarse chromatin pattern, and multiple small prominent nucleoli. Differential diagnoses considered were small round cell sarcomas such as malignant lymphoma, neuroblastoma, Ewing's sarcoma, and rhabdomyosarcoma. Of these, malignant lymphoma of the small noncleaved cell type was most consistent with the results of several studies including immunohistochemical staining, peripheral blood smear, and bone marrow biopsy. The cells were positive for leukocyte common antigen (LCA) and showed finely vacuolated basophilic cytoplasm in both the peripheral blood smear and bone marrow biopsy, characteristic of Burkitt's lymphoma cells.
Biopsy, Needle ; Burkitt Lymphoma/*diagnosis/pathology/radionuclide imaging ; Child ; Diagnosis, Differential ; Humans ; Male ; Neuroblastoma/*diagnosis/pathology ; Rhabdomyosarcoma/*diagnosis/pathology ; Sarcoma, Ewing/*diagnosis/pathology ; Tomography, X-Ray Computed