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Biomedical subjects

K Y Tsang

Publications and source records attributed to K Y Tsang.

12 recordsLinked to original sources

Human recombinant interleukin-6 enhances antibody-dependent cellular cytotoxicity of human tumor cells mediated by human peripheral blood mononuclear cells.

The effects of human recombinant interleukin-6 (hrIL-6) on antibody-dependent cellular cytotoxicity (ADCC) activity mediated by human peripheral blood mononuclear cells (PMNC) were investigated. Human PMNC were preincubated for 24 h with various concentrations of hrIL-6 and were used as effector cells in a 4-h 51Cr-release assay. The ability of hrIL-6 to augment ADCC was measured using anti-colorectal carcinoma mAbs D612, 17.1A and 31.1 (each directed against a distinct tumor antigen) and using three human colorectal carcinoma cell lines, LS-174T, WiDr and HT-29, as targets. A significant increase in ADCC activity was observed after PMNC were preincubated in 100-400 U/ml but not in lower concentrations of hrIL-6. Variations in activities of PMNC among donors were observed. Non-specific mAb showed no effect in augmenting ADCC activity. hrIL-6 treatment did not augment non-specific (non-mAb-mediated) cytotoxicity. The enhancement of ADCC activity was blocked by the addition of an antibody against hrIL-6 but not by an antibody to the IL-2 receptor (capable of blocking the induction of lymphokine-activated killer cell cytotoxicity by IL-2), suggesting that hrIL-6 augmentation of ADCC activity may not be mediated through IL-2. These results demonstrate that hrIL-6 augments ADCC activity of human PMNC using mAbs to human tumor antigens and human tumor cells as targets, suggesting a potential role for IL-6 in combination with anti-cancer antibodies for cancer immunotherapy.

Adult

Circulating immune complexes in human osteosarcoma.

Sera from 8 patients with osteosarcoma and 64 normal individuals were examined by C1q and Raji cell radioimmunoassays for the presence of circulating immune complexes. Of the 8 patients with osteosarcoma, 6 had elevated levels of immune complexes in their sera. The elevated levels of immune complexes were demonstrated by both the C1q radioimmunoassay and the Raji cell radioimmunoassay. The amount of immune complexes was quantitated by Raji cell radioimmunoassay; the mean plus or minus the standard error of the amount of aggregated human IgG equivalent per milliliter of serum was 80.12+/-72.64 micrograms for patients with osteosarcoma and 23.07+/-6.2 micrograms for normal individuals. The blocking effect of sera from patients with osteosarcoma on lymphocyte cytotoxicity against cultured osteosarcoma cells (TE-85) was examined. The result indicated that sera with elevated amounts of immune complexes also had increased levels of blocking activity. Sera were fractionated to separate immune complexes from gamma-globulins. No free tumor-specific antibody could be detected in fractionated gamma-globulin fractions from 2 patients with osteosarcoma. The sera of these patients had high amounts of immune complexes and high blocking activities.

Antibodies, Neoplasm

A model for human osteosarcoma in hamsters.

An animal model for human osteosarcoma was established in newborn Syrian golden hamsters by injecting productively infected TE-85 cells (cultured human osteosarcoma cells) adjacent to the femur. Tumors were palpable 10 to 15 days following cell injection and enlarged progresively until the animal died (mean survival time was 36 days). The tumor take was 100% and all animals developed pulmonary metastases. Osteoid and bone were identified in sections of the tumor by light and electron microscopy. Invasion of the marrow spaces and adjacent skeletal muscle by the malignant osteoblasts, anaplastic sarcoma cells and multinucleated giant cells was frequently observed. The tumor was transplantable. TE-85 cell surface antigens were demonstrable by immunofluorescence on the surface of the cells of the induced tumors. The present tumor model had unique immunologic characteristics in that no antibodies were demonstrable in the sera of the tumored animals.

Animals

Placenta-like alkaline phosphatases from human osteosarcoma cells.

Hormone-induced alkaline phosphatases in human osteosarcoma cells (LM) were extracted and purified. Characterization of the purified enzyme showed two distinct isoenzymes. One isoenzyme was heat labile, was homoarginine inhibited, and had the electrophoretic migration of alkaline phosphatase of human osseous origin. Immunodiffusion showed that this isoenzyme reacted positively only against anti-bone alkaline phosphatase antibodies. The second isoenzyme was heat stable, was inhibited by phenylalanie, and had the same electrophoretic migration as did alkaline phosphatase extracted from mature normal human placenta. This second isoenzyme had the same antigenicity as did the normal placental enzyme. Like the D-variant placental phenotype, this second isoenzyme was inhibited by L-leucine and ethylenediaminetetraacetic acid.

Alkaline Phosphatase

Effect of xenogeneic immune RNA on normal human lymphocytes against human osteosarcoma cells in vitro.

New Zealand White rabbits were immunized with whole-cell suspensions of TE-85 cells (from a human osteosarcoma) maintained in tissue culture. RNA was extracted from the lymphoid tissues of the immunized animals. Normal human peripheral blood lymphocytes were pretreated with both the whole-cell immune RNA (IRNA) and the Sephadex column-eluted fractions of the whole-cell IRNA. Significant stimulation of the cytotoxic effect of the lymphocytes was observed following whole-cell IRNA pretreatment and pretreatment with peak III fractions eluted from the column. This increase in inhibition was observed whether the target cells were TE-85 (the immunizing cells), L.M. and M.Mc. (two unrelated osteosarcoma primary cell cultures), or TE-85-M-MSV cells (a cell line capable of producing a human osteosarcoma in immunosuppressed hamsters). No inhibition was observed when cells from other types of human tumors were used as target cells. The results suggested that the transferred immunity was directed against tumor-specific osteosarcoma antigens.

Antigens, Neoplasm

Activation of Epstein-Barr virus in hybrid cells.

Human-primate hybrid cell lines were established by fusion of African green monkey kidney cells (VERO) with lymphoblastoid cells from patients with infectious mononucleosis (IM)(IMK101) and from Burkitt's lymphoma culture (HR1K). Both Epstein-Barr virus (EBV)-specific antigens and EBV particle-containing cells increased in the hybrid lines (IMK1-1/VERO,HR1K/VERO). Treatment of the hybrids with 5-bromodeoxyuridine induced more antigen-positive and more virus-containing cells. EBV could be activated from IM lymphoblastoid cells by fusion of the lymphoblastoid cells with the VERO cells. The increase of viral antigens and virus particles may have been due to the cellular interaction between VERO cells and the lymphoblastoid cells or to a possible derepressor supplied by the VERO component of the hybrid. Virus derived from the HR1K cell line was replicated in the human-primate hybrid, but further investigation may be necessary to determine if it was identical to the EBV derived from the human cell line.

Animals

An animal model for human osteosarcoma.

Osteosarcomas formed in antilymphocyte serum (ALS)-treated hamsters when 2x10(6) TE-85 human osteosarcoma cells (maintained in tissue culture) infected with M-MSV (RD-114) virus were injected adjacent to the femur or the scapula; undifferentiated sarcomas formed when 1 x 10(6) cells were injected subcutaneously. Tumors were palpable 10 to 14 days after the cells were injected and grew progressively until the animals died (mean survival time was 30 days). All animals had pulmonary metastases. Neither the subcutaneous sarcomas nor the metastases contained bone or osteoid; however, the osteosarcomas adjacent ot the femur and scapula contained collagen, osteoid and calcified bone when observed by light and electron microscopy. These results indicate that the TE-85-M-MSV cell-ALS hamster system is an animal model for the study of osteosarcomas of human cell origin.

Animals

Isolation and partial purification of plasma membrane-associated antigens from human osteosarcoma (TE-85) cells in tissue culture.

The plasma membrane of a cloned line of TE-85 (human osteosarcoma) cells subcultured for the last 4 years was isolated. The isolation was by hypotonic swelling, cell homogenization, and discontinuous sucrose gradient ultracentrifugation for 16 hr. Tumor-specific water-soluble antigens were identified by limited papain digestion of the isolated plasma membrane. Fractionation by diethylamino-ethyl anion-exchange column chromatography yielded antigenic fractions that inhibited the reaction of immune serum (from an unrelated patient with osteosarcoma) with the plasma membrane of TE-85 cells in tissue culture by indirect immunofluorescence test. Microimmunodiffusion confirmed the specificity of the isolated antigen against the sera of other patients with osteosarcoma. The definition of the antigen fraction may permit evaluation of antigen-antibody interaction in tumor immunity.

Antigen-Antibody Complex