Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.
Humans ; Autoantibodies/isolation & purification* ; Female ; Breast Neoplasms/immunology* ; Ovarian Neoplasms/immunology*

Adult ; Female ; Humans ; Limbic Encephalitis ; etiology ; Ovarian Neoplasms ; complications ; Paraneoplastic Syndromes, Nervous System ; etiology ; Receptors, N-Methyl-D-Aspartate ; immunology ; Seizures ; etiology ; Teratoma ; complications

Acupuncture Therapy ; Edema ; etiology ; immunology ; therapy ; Female ; Humans ; Lower Extremity ; pathology ; Middle Aged ; Ovarian Neoplasms ; surgery ; Postoperative Complications ; etiology ; therapy

Primary retroperitoneal mucinous cystadenoma is an extremely uncommon tumor, even though mucinous cystadenoma often develops in the ovary and less frequently in the pancreas. A 21-year-old female was admitted to our hospital due to severe abdominal pain. A well-demarcated, oval shaped cystic tumor at the retropancreatic area with displacement of the pancreas and surrounding major vessels was observed on CT and MRI. Exploratory laparotomy was performed, and complete excision of the entire cyst was performed without complication. The pathologic finding was consistent with primary retropancreatic mucinous cystadenoma. To the best of our knowledge, this report is the first to describe a case of retropancreatic mucinous cystadenoma arising from the retropancreatic area in Korea.
Antibodies/metabolism ; Cystadenoma, Mucinous/*diagnosis/pathology/surgery ; Female ; Humans ; Magnetic Resonance Imaging ; Mucin 5AC/immunology ; Mucin-2/immunology ; Ovarian Neoplasms/*diagnosis/pathology/surgery ; Retroperitoneal Neoplasms/*diagnosis/pathology/surgery ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo analyze the drift of T cell receptor (TCR) Vα and Vβ gene family CDR3 spectratype in response to ovarian carcinoma cells mediated by an anti-human ovarian carcinoma/CD3 bispecific single-chain antibody (BHL-1), and explore the mechanism of the bispecific single-chain antibody-mediated T cell immune response.

METHODSImmunoscopic spectratyping technique was used to analyze the TCR repertoire diversity (CDR3 spectratype distribution) of the T cells from 6 healthy donors before and after stimulation of the cells with human ovarian carcinoma in the presence of BHL-1. The predominant usage of TCR α and Vβ chain CDR3 was analyzed after the stimulation, and sequence analysis was performed for the CDR3 region of the monoclonal T cells.

RESULTSThe spectratypes of Vα and Vβ gene family TCR CDR3 region showed a Gaussian distribution before stimulation of the T cells from the 6 donors. After stimulation of the T cells, CDR3 spectratype drift occurred in the T cells, and some TCR Vα and Vβ families showed an anomalous and oligoclonal expansion. Different CDR3 sequences of the Vα and Vβ gene family TCR were found in the monoclonal T cells stimulated with BHL-1.

CONCLUSIONCDR3 spectratype drift occurs in TCR α and Vβ chains of T cells after stimulation with human ovarian carcinoma cells and BHL-1, indicating that the predominant usage of TCR Vα and Vβ families is associated with the specific T cell immune response mediated by BHL-1.

Antibodies, Bispecific ; immunology ; Cell Line ; Cell Line, Tumor ; Complementarity Determining Regions ; immunology ; Female ; Humans ; Monocytes ; immunology ; Ovarian Neoplasms ; immunology ; Receptors, Antigen, T-Cell, alpha-beta ; immunology ; Single-Chain Antibodies ; immunology

OBJECTIVETo examine the in vivo anti-metastatic effect of enhanced expression of CD40L cDNA in murine ovarian cancer OVHM cells (CD40L-OVHM) injected into the spleen on liver metastasis in mice.

METHODSOVHM cells were inoculated into the spleen of 6 to 8 week-old female B6C3F1 (C57BL/6N x C3H/He) mice. The established liver metastasis was identified by histopathology (HE staining). OVHM cells, DNA-pMKITneo-OVHM cells or CD40L-OVHM cells were inoculated into the spleen of female B6C3F1 mice and the expressions of CD11c in splenic cells were detected by flow cytometry. The specific cytotoxicity of splenic cells was detected by MTT assay, and the serum cytokines of IFN-gamma, TNF-alpha, IL-12, IL-4 and IL-10 of the mice were measured by enzyme linked immunoabsorbent assay. The liver metastases and the survival time of the mice were also recorded.

RESULTSThe mouse models with liver metastasis by injecting tumor cells into the spleen of mice were established. The expression of CD11c and the specific killing rate in CD40L-OVHM cells group was significantly higher than that in the OVHM cells group and DNA-pMKITneo-OVHM cells group. The expressions of IFN-gamma, TNF-alpha and IL-12 in the CD40L-OVHM cells group were much more increased than OVHM cells group and DNA-pMKITneo-OVHM cells group, but the expressions of IL-4 and IL-10 in the CD40L-OVHM cells group were decreased significantly (p < 0.05). The average weights of livers and spleens of mice in CD40L-OVHM cells group were significantly lower than those of DNA-pMKITneo-OVHM cells group and OVHM cells group. The survival time of mice in CD40L-OVHM cells group was also significantly longer than that in the OVHM cells group and DNA-pMKITneo-OVHM cells group (P < 0.05).

CONCLUSIONThe data directly demonstrate that the expression of CD40L in ovarian cancer cells (CD40L-OVHM) can enhance the proliferation and differentiation of dendritic cells in the spleen and induce specific cytotoxic effect of T cells in the spleen, and may regulate the immune function of peripheral blood cells and the immune balance between Th1 cells and Th2 cells, which maybe the possible mechanism induced by CD40L in mice inhibiting the development of liver metastasis.

Animals ; CD11c Antigen ; metabolism ; CD40 Ligand ; genetics ; metabolism ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; DNA, Complementary ; genetics ; Dendritic Cells ; cytology ; Female ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; metabolism ; Liver Neoplasms ; pathology ; secondary ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Ovarian Neoplasms ; metabolism ; pathology ; Spleen ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Necrosis Factor-alpha ; metabolism

Female ; Genes, p53 ; immunology ; Humans ; Ovarian Neoplasms ; genetics ; pathology ; Ovary ; pathology ; Proto-Oncogene Proteins ; immunology ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Proto-Oncogenes ; immunology ; Sertoli-Leydig Cell Tumor ; genetics ; pathology ; ras Proteins ; immunology ; metabolism

BACKGROUNDWe have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B11, which mimics an ovarian carcinoma associated antigen OC166 - 9 and whose corresponding monoclonal antibody is COC166 - 9 (Ab1). In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment (scFv)/human granulocyte macrophage colony-stimulating factor (hGM-CSF) and 6B11scFv in BALB/c mice.

METHODSThe fusion protein 6B11scFv/hGM-CSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-CSF. BALB/c mice were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively.

RESULTSThe fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F (ab) 2' and was also biologically active as measured by proliferation of human GM-CSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and 6B11ScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11scFv/hGM-CSF compared with the 6B11scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week.

CONCLUSIONThe fusion protein 6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11scFv/hGM-CSF for active immunotherapy of ovarian cancer.

Animals ; Antibodies, Anti-Idiotypic ; immunology ; Antibodies, Neoplasm ; blood ; Cancer Vaccines ; immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Immunization ; Immunoglobulin Fragments ; immunology ; Mice ; Mice, Inbred BALB C ; Ovarian Neoplasms ; immunology ; Recombinant Fusion Proteins ; immunology

OBJECTIVETo observe the functional changes of dendritic cells (DCs) infected in vitro by 3 recombinant adenoviruses encoding Her2/neu extracellular first-receptor domain (Her2-ECDs), full-length extracellular domain (Her2-ECD), and extracellular and transmembrane domain (Her2-TM) proteins (rAdHer2-ECDs, rAdHer2-ECD and rAdHer2-TM, respectively).

METHODSThe expressions of the target proteins were detected with Western blotting. The level of both interleukin (IL)-12 in the supernatant of in vitro cultured DCs infected with recombined adenoviruses and interferon gamma (IFN-gamma) in the supernatant of the lymphocyte populations co-cultured with DCs were determined by enzyme-linked immunosorbent assay (ELISA). The capacity of the DCs to stimulate allogeneic T lymphocyte proliferation was assessed by mixed lymphocyte reaction, and the activity of cellular toxic T lymphocytes (CTL) were investigated by MTT assay.

RESULTSHer2-ECDs, ECD and TM proteins were detected in the transfected DCs. Compared with the untransfected DCs, more abundant IL-12 production was detected in the supernatant of the DCs 5 days after transfection, but the IL-12 level showed no significant difference between the DCs infected with the 3 recombinant adenoviruses. IFN-gamma production increased gradually with passage of the time following DC-stimulated lymphocyte proliferation irrespective of infection of the DCs, and only the DCs infected with rAdHer2-TM seemed to result in significant difference in DC-mediated allogeneic T lymphocyte proliferation. The killing of breast cancer cell line with Her2 overexpression was more efficient with infected DCs priming autologous T lymphocyte to generate CTL than with uninfected DCs and those modified by SK-OV-3 cell fragment. CTL activity induced by rAdHer2-TM-infected DCs was the strongest, and breast cancer cell-killing activity was more efficient against cell line with Her2/neu-overexpression.

CONCLUSIONThe DCs infected with the recombinant adenovirus encoding Her2/neu extracellular and transmembrane domains show enhanced anti-tumor effect and induce Her2/neu-specific CTL activity.

Adenoviridae ; genetics ; Blotting, Western ; Breast Neoplasms ; genetics ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; immunology ; Coculture Techniques ; Cytotoxicity, Immunologic ; immunology ; Dendritic Cells ; cytology ; immunology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins ; genetics ; metabolism ; Female ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocytes ; cytology ; immunology ; Membrane Proteins ; genetics ; metabolism ; Ovarian Neoplasms ; genetics ; immunology ; pathology ; Receptor, ErbB-2 ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Transfection

OBJECTIVETo investigate the impact of human peritoneal mesothelial cells (HPMC) on angiogenesis factor expression and secretion of ovarian carcinoma cell line SKOV3.

METHODSThe conditioned medium with HPMC was tested by ELISA for tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-1beta). Millicell was used to co-culture HPMC and ovarian carcinoma cell line SKOV3 in the presence or absence of neutralizing antibody against TNF-alpha or IL-1beta. RT-PCR was used to detect vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene expression in SKOV3 cells. VEGF and bFGF protein levels in the SKOV3 conditioned medium were assessed by ELISA.

RESULTSConditioned medium with HPMC contained both TNF-alpha and IL-1beta. SKOV3 co-cultured with HPMC expressed higher levels of VEGF and bFGF mRNA and secreted at increased levels of both VEGF and bFGF, in comparison with those in SKOV3 cells cultured alone (P < 0.01). Addition of neutralizing antibody against TNF-alpha or IL-1beta during co-cultures resulted in decrease in mRNA expression and secretion of VEGF and bFGF in SKOV3 cells. When both antibodies were administered during co-culture, additive decrease was observed.

CONCLUSIONHPMC can act in a paracrine fashion to stimulate ovarian tumor cells to produce and secret at increased levels of VEGF and bFGF through TNF-alpha and IL-1beta, and contribute to angiogenesis and peritoneal metastasis of ovarian cancer.

Antibodies ; pharmacology ; Cell Line, Tumor ; Cells, Cultured ; Coculture Techniques ; Culture Media, Conditioned ; metabolism ; Cystadenocarcinoma, Serous ; genetics ; metabolism ; pathology ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; secretion ; Female ; Fibroblast Growth Factor 2 ; genetics ; secretion ; Gene Expression ; drug effects ; Humans ; Interleukin-1beta ; immunology ; secretion ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; Peritoneal Cavity ; cytology ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; immunology ; secretion ; Vascular Endothelial Growth Factor A ; genetics ; secretion