Metastatic large cell neuroendocrine lung cancer to the foramen magnum: A case report.

RATIONABLE: Large cell neuroendocrine carcinoma of the lung is rare, especially in the area of the foramen magnum. No previous studies have reported metastatic large cell neuroendocrine lung cancer to the foramen magnum. This paper will be the first time to report this special case. PATIENT CONCERNS: A case of a 37-year-old woman presented with headache that had developed 20 days previously. Imaging examination revealed a circular abnormal signal at the posterior margin of the foramen magnum. DIAGNOSES: The patient we report was diagnosed with a metastatic intracranial tumor. INTERVENTIONS: The patient underwent occipital craniotomy. Pathological results showed metastatic neuroendocrine carcinoma of the brain. Whole body PET-CT examination showed that fusiform soft tissue shadows could be seen near the hilum of the lower lobe of the left lung. OUTCOMES: The final bronchoscopy pathological results showed the large cell neuroendocrine carcinoma of the lung. The patient underwent further chemotherapy and radiotherapy in the oncology department. LESSONS: Diagnosis and treatment of large cell neuroendocrine carcinoma of the lung are difficult. The prognosis is poorer, and effective treatment is urgently needed.

Malignant transformation of bone marrow stromal cells induced by the brain glioma niche in rats.

Normal human embryonic stem cells (hESCs) can develop neoplastic cancer stem cell (CSC) properties after coculture with transformed hESCs in vitro. In the present study, the influence of the tumor microenvironment on malignant transformation of bone marrow stromal cells (BMSCs) was studied after allografting a mixture of enhanced green fluorescent protein (EGFP)-labeled BMSCs and C6 glioma cells into the rat brain to understand the influence of the cellular environment, especially the tumor environment, on the transformation of grafted BMSCs in the rat brain. We performed intracerebral transplantation in the rat brain using EGFP-labeled BMSCs coinjected with C6 tumor cells. After transplantation, the EGFP-labeled cells were isolated from the tumor using fluorescence-activated cell sorting, and the characteristics of the recovered cells were investigated. Glioma-specific biomarkers of the sorted cells and the biological characteristics of the tumors were analyzed. The BMSCs isolated from the cografts were transformed into glioma CSCs, as indicated by the marked expression of the glioma marker GFAP in glioma cells, and of Nestin and CD133 in neural stem cells and CSCs, as well as rapid cell growth, decreased level of the tumor suppressor gene p53, increased level of the oncogene murine double minute gene 2 (MDM2), and recapitulation of glioma tissues in the brain. These data suggest that BMSCs can be transformed into CSCs, which can be further directed toward glioma formation under certain conditions, supporting the notion that the tumor microenvironment is involved in transforming normal BMSCs into glial CSCs.

Temporal expression patterns of insulin-like growth factor binding protein-4 in the embryonic and postnatal rat brain.

BACKGROUND: IGFBP-4 has been considered as a factor involving in development of the central nervous system (CNS), but its role needs to be further clarified. In present study, the localization of IGFBP-4 expression in the embryonic forebrain, midbrain and hindbrain was determined using immunohistochemistry, and the levels of IGFBP-4 protein and mRNA were semi-quantified using RT-PCR and Western blot in the embryonic (forebrain, midbrain and hindbrain) and postnatal brain (cerebral cortex, cerebellum and midbrain). RESULTS: A clear immunoreactivity of IGFBP-4 covered almost the entire embryonic brain (forebrain, midbrain, hindbrain) from E10.5 to E18.5, except for the area near the ventricle from E14.5. The change of IGFBP-4 mRNA level was regularly from E10.5 to E18.5: its expression peaked at E13.5 and E14.5, followed by gradual decreasing from E15.5. The expression of IGFBP-4 protein was similar to that of mRNA in embryonic stage. After birth, the pattern of IGFBP-4 expression was shown to be rather divergent in different brain areas. In the cerebral cortex, the IGFBP-4 mRNA increased gradually after birth (P0), while the protein showed little changes from P0 to P28, but decreased significantly at P70. In the cerebellum, the IGFBP-4 mRNA decreased gradually from P0, reached the lowest level at P21, and then increased again. However, its protein level gradually increased from P0 to P70. In the midbrain, the IGFBP-4 mRNA first decreased and reached its lowest level at P28 before it increased, while the protein remained constant from P0 to P70. At P7, P14, P21, P28 and P70, the levels of IGFBP-4 mRNA in the cerebral cortex were significantly higher than that in the cerebellum or in the midbrain. Differently, the protein levels in the cerebellum were significantly higher than that either in the cerebral cortex or in the midbrain at P14, P21, P28 and P70. CONCLUSIONS: The temporal expression pattern of IGFBP-4 in the embryonic brain from E10.5 to E18.5 was consistent with the course of neurogenesis in the ventricular zone, suggesting an important role of IGFBP-4 in regulating differentiation of neural stem cells. A strikingly higher abundance of the IGFBP-4 protein observed in the cerebellum from P14 to P70 suggests that IGFBP-4 may participate in the maintenance of cerebellar plasticity.

[Bone marrow stem cell-derived astrocytes are involved in glia limitans formation in rats after brain injury].

OBJECTIVE: To investigate the involvement of bone marrow stem cell-derived astrocytes (BMDSCs) in the formation of glia limitans after brain injury. METHODS: In a female SD rat model of brain injury, green fluorescence protein (GFP)-labeled BMDSCs from male SD rats were transplanted via the caudal vein 24 h after the injury. The rats were sacrificed at 2, 4 and 8 weeks after the transplantation, and immunohistochemistry for glial fibrillary acidic protein (GFAP) was performed to observe the astrocytes. The fluorescence emitted by GFP was observed to identify the presence of the bone marrow-derived stem cells, and the GFAP(+)/GFP(+) cells in the glia limitnas were detected under fluorescence microscopy. RESULTS The GFAP(+)/GFP(+) cells were found in the glia limitans between the brain lesion and normal brain tissue. CONCLUSION: Bone marrow stem cell-derived astrocytes is involved in glia limitans formation after brain injury, which can be of significance in brain injury recovery and implantation of engineered materials.

Establishment of an immortalized GABAergic neuronal progenitor cell line from embryonic ventral mesencephalon in the rat.

Effective cell replacement therapies for neurological disease require neuron-restricted precursors as grafted cells. The problem of obtaining sufficient grafts for transplantation can be resolved by creating an appropriate immortalized cell line. In the present study, a thermally controlled immortalized GABAergic neuronal progenitor cell line (RMNE6) was established from E13 rat ventral mesencephalon cells immortalized using the temperature-sensitive mutant of SV40 large T antigen (ts-TAg). RMNE6 cells proliferated rapidly and expressed a neuron-like phenotype at the permissive temperature (33 degrees C), but eventually stopped growing at the non-permissive temperature (39 degrees C). Expression of the neuronal markers PSA-NCAM, beta-tubulin III and MAP2 by RMNE6 cells was confirmed by RT-PCR or immunocytochemistry. Furthermore, these cells exhibited functional GABAergic neuron properties, as evidenced by the expression of glutamate decarboxylase (GAD) as well as the synthesis and release of the neurotransmitter GABA in a calcium-dependent manner. Moreover, RMNE6 cells spontaneously expressed and secreted several neurotrophic factors, such as NGF, BDNF, NT-3, NT-4/5, and GDNF. The cells survived well and kept expression of SV40 Tag, GAD65/67 and GABA in the striatum, at least 28 days after being transplanted in the rat brain. Tumorigenesis assays confirmed the safety of the immortalized cell line in vivo. Taken together, the results support the use of RMNE6 cells as an ideal cell model for transplantation research aimed at the treatment and prevention of neurodegenerative disease.

[Differentiation of bone marrow-derived stem cells in injured rat brain tissue].

OBJECTIVE: To investigate the differentiation of bone marrow-derived stem cells (BMDSCs) migrated from blood circulation and resided in the injured brain tissue. METHODS: Brain injury model was established by iridectomy in the right cerebral cortex of female SD rats. Twenty-four hours after brain injury, the female rats received the implantation of green fluorescence protein (GFP)-labeled BMDSCs from male SD rats and were sacrificed at 2, 4 and 8 weeks after the implantation. Fluorescent immunohistochemistry for CD11b and glial fibrillary acidic protein (GFAP) on the brain sections was used to detect the GFP-positive cells. RESULTS: One week after the transplantation of the GFP-labeled BMDSCs, 3.53% of the peripheral blood white cells were GFP-positive; at 4 weeks and 8 weeks, a significant number of GFP-positive cells were found at the injury sites, some of which expressed CD11b and others expressed GFAP. CONCLUSION: GFP-labeled BMDSCs can migrate to the injured brain tissue and differentiate into cells that express microglia- and astrocytes-specific antigens.

[Identification of bone marrow stromal cells and expression of tyrosine hydroxylase gene in them].

The study is to establish the method of isolation and identification of bone marrow stromal cells and to investigate the ability of bone marrow stromal cells to accept and express TH gene. Cells were isolated by a density gradient (lymphocytes separation) and identified by BrdU labeling and fluorescence-activated cell sorting (FACS) technology using CD11b, CD45 and CD90 antibodies. TH and lacZ gene were transfected to rBMSCs with an adeno-associated virus vector. The results showed that most tightly adherent cells in the primary culture were fibroblast-like and formed foci of two to four cells. The cells in the foci remained dormant for 2 to 4 days and then began to multiply rapidly. After several passages, the adherent cells became more uniformly spindle-shaped in appearance. BrdU, indicating that BMSCs replicate actively, labeled about 74.9% of cultured cells. Data from FACS showed that about 75% of isolated cells were CD90(+)/CD45(-)/CD11b(-), which is the marker of bone marrow stromal cells. The efficiency of TH gene transfection was about 75%. BMSCs could readily be genetically engineered and could be useful delivery targets of gene therapy for Parkinson's disease.