Bone Neoplasms ; immunology ; pathology ; Child ; Humans ; Osteosarcoma ; immunology ; pathology ; Rosette Formation

We describe a case of solitary myeloma showing cystic change filled with massive crystalline structures in a 54-year-old woman. A bone X-ray showed a solitary cystic osteolytic lesion in the right iliac bone. Serum and urine protein electrophoresis showed no demonstrable M-protein, and bone-marrow aspirates did not show any myeloma cells. Histologic examination of the tumor revealed aggregation of plasma cells with massive extracellular infiltration of the rhomboid-shaped crystalline structures. In immunoperoxidase staining, both these crystalline structures and the cytoplasms of the myeloma cells demonstrated a positive reaction for lambda light chain. By electron microscope, the large extracellular crystalline structures were observed, and we found unique rhomboid or rectangular-shaped crystalline structures in the cytoplasms of the myeloma cells.
Bone Neoplasms/immunology/*ultrastructure ; Crystallization ; Extracellular Space/immunology ; Female ; Humans ; Immunoglobulin lambda-Chains/ultrastructure ; Microscopy, Electron ; Middle Aged ; Plasmacytoma/immunology/*ultrastructure

Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Bone Neoplasms/immunology* ; Computational Biology/methods* ; Gene Expression Profiling/methods* ; Humans ; Osteosarcoma/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Tumor-Associated Macrophages/immunology*

Adolescent ; Adult ; Bone Marrow Transplantation ; immunology ; Bone Morphogenetic Proteins ; therapeutic use ; Bone Neoplasms ; therapy ; Combined Modality Therapy ; Extremities ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; therapy ; Transplantation, Autologous ; immunology ; Young Adult

OBJECTIVETo investigate the influence of (89)SrCl(2) (strontium-89 chloride) on immune functions in patients with simple bone metastases.

METHODSTwenty-five patients diagnosed as simple bone metastases with un-detectable primary tumors were treated with (89)SrCl(2). The CD4(+), CD8(+), CD4(+)/CD8(+) lymphocyte subsets were assessed before and after (89)SrCl(2) treatment. Twenty normal individuals served as controls.

RESULTSThe CD4(+), CD8(+) and CD4(+)/CD8(+) in the control group were (38.83 +/- 8.95)%, (32.19 +/- 8.51)% and 1.29 +/- 0.47, respectively. In patients, they were (31.12 +/- 8.12)%, (41.75 +/- 10.91)% and 0.84 +/- 0.22 before treatment, and (36.21 +/- 8.71)%, (35.08 +/- 10.14)% and 1.19 +/- 0.27 after treatment, respectively (P < 0.05). The patients were divided into treatment effective and non-effective groups by pain score. Before treatment, the immunologic parameters in the two groups had no significant differences (P > 0.05). After treatment, the frequencies of CD4(+) and CD8(+) subsets, CD4(+) to CD8(+) ratios and the number of metastatic foci in the effective group were (37.81 +/- 5.18)%, (33.17 +/- 6.38)%, 1.33 +/- 0.31 and 6.64 +/- 3.11, respectively, while in the treatment non-effective group, they were (32.09 +/- 5.72)%, (39.99 +/- 5.38)%, 0.82 +/- 0.22 and 9.87 +/- 3.46, respectively (P < 0.05).

CONCLUSIONThe immune functions in patients with simple bone metastases are inhibited. Treatment with (89)SrCl(2) may improve their immunity to certain extent. The degree of recovery in the treatment effective patients was better than that in the treatment non-effective cases.

Adult ; Aged ; Bone Neoplasms ; immunology ; radiotherapy ; secondary ; CD4-CD8 Ratio ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Unknown Primary ; immunology ; radiotherapy ; Strontium ; therapeutic use ; Strontium Radioisotopes ; therapeutic use ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo investigate the cytotoxic effect of γδ T cells from osteosarcoma patients against interferon-γ (IFN-γ)-treated osteosarcoma cells in vitro.

METHODSHuman γδ T cells were amplified by zoledronate from peripheral blood cells of osteosarcoma patients. The expression of Fas on the osteosarcoma cells were measured by flow cytometry and quantitative real-time PCR analysis before and after IFN-γ treatment. The cytotoxicity of γδ T cells against osteosarcoma cells was evaluated with LDH assay.

RESULTSIFN-γ significantly enhanced the susceptibility of the osteosarcoma cell lines HOS and U2OS to the cytotoxicity of γDelta; T cells from osteosarcoma patients (P<0.01). IFN-γ obviously up-regulated the expression of Fas in HOS and U2OS cells (P<0.01). Anti-FasL mAb failed to inhibit the cytotoxicity of γδ T cells in untreated osteosarcoma targets (P>0.05), but significantly impaired γδ T cell cytotoxicity in IFN-γ pre-treated osteosarcoma targets (P<0.01).

CONCLUSIONIFN-γ can enhance the cytotoxic effect of human γδ T cells from osteosarcoma patients against osteosarcoma cells in vitro.

Bone Neoplasms ; metabolism ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Humans ; Interferon-gamma ; pharmacology ; Osteosarcoma ; immunology ; metabolism ; Receptors, Antigen, T-Cell, gamma-delta ; immunology ; T-Lymphocytes, Cytotoxic ; cytology ; drug effects ; immunology ; fas Receptor ; metabolism

The purpose of study was to investigate the impact of killer immunoglobulin-like receptor (KIR) and its ligand on haploidentical bone marrow transplantation. 74 cases were analyzed for the distribution frequencies and characteristics of KIR and its ligand as well as the impact of KIR ligand for the haploidentical bone marrow transplantation in terms of the overall survival, disease-free survival (DFS), GVHD and relapse. The results showed that among the 19 KIR genotypes currently nominated KIR2DL1, KIR2DL4 and KIR3DL2-3 could be detected in all the cases. Other high frequency genotypes included KIR3DP1 (98.6%), KIR2DP1 (98.6%), KIR3DL1 (97.3%) and KIR2DL3 (97.3%). Inhibitory receptor genotypes were 1.37-fold of activating receptor genotypes. KIR2DL1, KIR3DL2, KIR3DL3 and KIR2DL4 were found in all haplotypes and at least one genotype of KIR2DL2 and/or KIR2DL3 existed in all haplotypes. Among the 14 genotypes found in the test, the HLA-Cw7 was the most popular (37.8%) and the group 2 (HLA-Cw1, 3, 7, 8, 13, 14) recognized by KIR2DL2/2DL3 counted for 43.2%. The incompatibility of KIR for 32 cases of haploidentical BMT was 43.8%, of which 9/14 were KIR2DL incompatible, 5/14 were KIR2DL2 or KIR3DL1 incompatible. Among the 46 cases of haploidentical BMT, 29 cases were HLA-Cw matched and 14 cases were mismatched. The completed mismatch ratio of HLA-Cw was 30.4% and the match ratio was 63.4%. The survival rate was higher for the 14 cases of KIR genotype compatible group than the 13 cases of KIR genotype incompatible group (p = 0.032). The disease-free survival was significantly higher for the 17 cases of mismatched KIR ligands (HLA-Cw) group than the matched group (p = 0.024). The survival rate was higher in GVHD group than that in non-GVHD group when the KIR ligand was missing. The acute and severe GVHD was related to the existence of activating receptor of KIR2DS1/2DS2. The incompatibility group was accompanied with frequent acute and severe GVHD and less relapse and vice versa for the compatibility group. One patient died after BMT among the 14 mismatched KIR ligand group suffering from myelogenous leukemia while 4 patients out of 12 patients died in the matched group. It is concluded that the haploidentical BMT is characterized by mismatch between donor and recipient and its immunological reactions also features by the incompatibility of KIR genotype and missing ligand. The missing ligand for the donor KIR has strong effect on the outcome of BMT and it means a lot to analyze the KIR genotype and its ligand for the selection of best donor and prognostic evaluation in haploidentical BMT.
Adolescent ; Adult ; Bone Marrow Transplantation ; immunology ; Child ; Child, Preschool ; Female ; Genotype ; Graft vs Host Disease ; immunology ; HLA-C Antigens ; genetics ; immunology ; Haplotypes ; genetics ; immunology ; Hematologic Neoplasms ; therapy ; Histocompatibility ; genetics ; immunology ; Humans ; Ligands ; Male ; Middle Aged ; Receptors, KIR ; genetics ; immunology ; Young Adult

OBJECTIVETo investigate whether whole tumor cell vaccination strategies in combination with bone marrow transplantation (BMT) can stimulate graft-versus-tumor effect (GVT).

METHODSTwenty-six BALB/c mice were randomly divided into 3 groups: BMT group (group A, n = 10), BMT + vaccination group (group B, n = 10), control group (group C, n = 6). (BALB/c × C57BL/6) F1 mice [CB6F1, H-2K(b/d)] were used as donors. BALB/c mice of group C were only inoculated with Renca cell (2.6 × 10(6)). Mice of group A and B were conditioned with 8 Gy irradiation, followed by infusion by bone marrow cell of CB6F1 mice on day 1, then inoculated with Renca cell (2.6 × 10(6)) on day 8. All mice of group B were immunized subcutaneous on the back with 5 × 10(5) irradiated Renca tumor cells on day 9 and day 16. All mice of group C were inoculated with Renca cell (2.6 × 10(6)) on day 8. In group A and B, all mice were analyzed by fluorescence activated cell sorter (FACS) on day 14, and 28 day after BMT. Mice were killed on day 32 after inoculation with tumor cell and collected blood sample. All tumors were taken out to be weighed and then fixed in 10% buffered formalin, embedded in paraffin, and cut into 5 µm slices. The slices were stained with HE and examined by TdT mediated-dUTP nick end labeling (TUNEL). Liver, skin, intestine, and spleen were biopsied for histopathological examination.

RESULTSThe results of chimera showed that engraftments of group A, B were full donor chimerism, and the chimerism of those remained above 90% and preserved even after 28 days. The tumor weight, tumor volume increment in the group B was lower than group A and C (P < 0.05). The tumor suppressing rates of the group A and B were 54%, 60% respectively. The area ratio of tumor necrosis and apoptosis index (AI) of the tumor in the group B were higher than group A and C (P < 0.05). Graft-versus-host disease was not observed in each group.

CONCLUSIONThe mechanism of GVT after haploidentical allogeneic bone marrow transplantation with tumor vaccination may be the promotion of tumor necrosis and apoptosis.

Animals ; Bone Marrow Transplantation ; immunology ; Cancer Vaccines ; immunology ; Carcinoma, Renal Cell ; immunology ; therapy ; Cells, Cultured ; Disease Models, Animal ; Graft vs Tumor Effect ; immunology ; Kidney Neoplasms ; immunology ; therapy ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Transplantation Chimera ; immunology

To explore the dynamic change of CD34(+) cell expressing adhesion molecules in bone marrow and peripheral blood during mobilization with combination of chemotherapy and G-CSF and its clinical significance, mononuclear cells of bone marrow and peripheral blood from malignant hematopathy cases before and after mobilization with G-CSF were labeled by CD45-CY-Chrome, PE conjugated anti-CD34, and FITC conjugated anti-CD44, anti-CD49d, anti-CD62L and anti-CXCR4. For three-color fluorescence analysis by flow cytometry was performed on a FACScalibur. Also the relationship between the number of subpopulations in different expressions of adhesion molecules infused and the time of recovery in different blood cells after transplantation was evaluated. Results showed that a significantly lower expression of CD44(+) and CD49d(+) on CD34(+) cells in bone marrow after mobilization compared to that before mobilization, whereas great higher expression of CD44(+), CD49d(+), anti-CD62L(+) and lower of anti-CXCR4(+) in peripheral blood were observed after mobilization. No significant relations were found between expression of different adhesion molecules on CD34(+) cells infused and the time of reconstitution in blood cells after transplantation. It was concluded that this mobilizing regimen could downregulate the expressions of CD44, CD49d, CD62L, and anti-CXCR4 on CD34(+) cells in bone marrow, it may related to mobilization of CD34(+) cells from marrow to blood, and homing of blood CD34(+) cells into marrow.
Adolescent ; Adult ; Antigens, CD34 ; immunology ; Bone Marrow Cells ; immunology ; metabolism ; Cell Adhesion Molecules ; biosynthesis ; blood ; Female ; Flow Cytometry ; methods ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematologic Neoplasms ; immunology ; metabolism ; therapy ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Hodgkin Disease ; immunology ; metabolism ; therapy ; Humans ; Hyaluronan Receptors ; biosynthesis ; Integrin alpha4 ; biosynthesis ; L-Selectin ; biosynthesis ; Leukocytes, Mononuclear ; immunology ; metabolism ; Lymphoma, Non-Hodgkin ; immunology ; metabolism ; therapy ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; metabolism ; therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; metabolism ; therapy

Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases. Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells. Here, we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion. Finally, we offer pre-clinical evidence that this receptor is a viable target for therapy.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Bone Marrow ; enzymology ; pathology ; Bone Neoplasms ; prevention & control ; secondary ; Enzyme Activation ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptor, Platelet-Derived Growth Factor alpha ; antagonists & inhibitors ; genetics ; immunology ; metabolism ; Signal Transduction ; Transcriptional Activation