Biomedical subjects

Q Dan

Publications and source records attributed to Q Dan.

5 recordsLinked to original sources

PubMed2001

Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer.

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.

Animals↗

PubMed2001

Non-immunogenic murine hepatocellular carcinoma Hepa1-6 cells expressing the membrane form of macrophage colony stimulating factor are rejected in vivo and lead to CD8+ T-cell immunity against the parental tumor.

Hepatocellular carcinoma is a lethal disease and methods that develop effective cellular-based immunotherapy are needed. We retrovirally transduced non-immunogenic mouse Hepa1-6 hepatoma cells with the gene encoding the membrane form of macrophage colony stimulating factor (mM-CSF). Excess recombinant M-CSF and phagocytosis-inhibiting chemicals blocked macrophage-mediated killing of cloned mM-CSF transfected Hepa1-6 hepatoma cells. Macrophages derived from Hck(-/-)Fgr(-/-) and Lyn(-/-) triple knockout mice, which are incapable of performing phagocytosis, failed to kill the mM-CSF transduced cells. The mM-CSF transfected tumor clones failed to grow when injected into C57BL/6 or C57L/J mice. Splenocytes from these vaccinated mice displayed cytotoxicity against parental Hepa1-6 cells, but not against B16 and CT-26 tumor cells in vitro. Mice that rejected the mM-CSF transfected Hepa1-6 tumor subsequently rejected parental Hepa1-6 cells but not the B16 melanoma cells when rechallenged. Elimination of the CD8+ effector cells by an anti-CD8 antibody and complement treatment prevented the adoptive transfer of anti-Hepa1-6-specific immunity into naive animals. Thus, mM-CSF provides a method of generating effective anti-tumor immune responses by macrophages and cytotoxic T cells against the parental Hepa1-6 cells. Our work suggests that mM-CSF transduced hepatoma cells could be used as a tumor vaccine to stimulate immune responses against hepatocellular carcinoma.

Animals↗

PubMed2001

Dexamethasone increases the expression of membrane macrophage colony stimulating factor from retrovirally transduced tumor cells expressing macrophage colony stimulating factor.

Many different tumor cell types (breast, ovarian, glioma, liver and colon) were retrovirally transduced with the human macrophage colony stimulating factor (M-CSF) gene (either the membrane associated form [mM-CSF] or the secreted form [sM-CSF]). These cells were tested for their ability to display increased amounts of mM-CSF in response to dexamethasone. M-CSF-transfected tumor cells expressed additional mM-CSF in response to 18-72 h incubations with 3-15 microg/ml dexamethasone, while non-transfected parental cells were unaffected by this treatment. Increased mM-CSF protein expression on the M-CSF transduced cells was observed by flow cytometry and Western blotting using M-CSF specific antibodies. Northern blot analysis revealed an increase in the mM-CSF specific transcripts within the dexamethasone-treated mM-CSF transduced cells, but this was not seen within the non-transfected tumor cells that were treated with dexamethasone. ICAM-1 expression was unaffected by dexamethasone treatment, indicating that this response is mM-CSF specific. All trans-retinal and 1,25-dihydroxy vitamin D3 compounds that have been reported to induce M-CSF expression failed to increase mM-CSF. When dexamethasone-treated mM-CSF transfected clones were used as target cells for macrophage-mediated cytotoxicity assays, an increased killing with the dexamethasone-treated cells was seen. The macrophage-mediated cytotoxicity of these mM-CSF expressing tumor cells was blocked with excess recombinant M-CSF by saturating M-CSF receptors on the macrophage that is required for this form of tumor cell killing. This work suggests the possibility that dexamethasone may prove useful for vaccination purposes using mM-CSF retrovirally transfected tumor cells.

Animals↗

PubMed1995

[DNA polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster in coronary artery disease].

Two polymorphic sites of the apolipoprotein AI (ApoAI) gene, PstI and SstI, were examined in a sample of 43 unrelated Chinese patients with coronary artery disease (CAD) and 60 unrelated healthy individuals. Allele frequencies were compared between patients and controls and their impact on lipid and oxygen free radicals metabolism were also studied. The frequencies of the uncommon P2 and S2 alleles in CAD cases were found as 0.14 and 0.22 respectively, which were significantly higher than 0.05 and 0.13 in controls. The more the number of vessel disease in CAD cases, the higher the frequencies of S2 alleles which were the highest in the group of 3 vessel diseases. Some serum lipid and oxygen free radicals levels differed between CAD cases of different genotypes. These data suggest that genetic variation in P2 and S2 alleles of APOAI gene may contribute to the development and extent of CAD in Chinese subjects.

Alleles↗

PubMedDate not supplied

Certainty factor theory and its implementation in a medical expert system shell.

In this article some topics related to the MYCIN-model for uncertainty handling are discussed. First, it is pointed out that one of the problems identified by Adams should be considered as evidence supporting the point of view that the probabilistic interpretations of measures of belief and measures of disbelief given by Shortliffe are inappropriate. In this context some results achieved by Heckerman are reviewed, and it is shown that similar problems can be identified in the interpretation given by him. It is also pointed out that Heckerman's argument that the original probabilistic interpretation of certainty factors implies non-commutative evidence-updating is not correct. Then, in the context of the result achieved by Horvitz and Heckerman, in which it was proven that there is an isomorphic mapping from the evidence combination scheme for the likelihood ratio to the evidence combination function in EMYCIN and its successors, it is pointed out that the evidence combination scheme for the likelihood ratio suffers from a great restriction on its applicability in expert systems. Subsequently, some short remarks are made with respect to the complaint that sometimes the MYCIN model cannot work as well as expected. Lastly implementation of the certainty factor mechanism in a HIS-oriented expert system shell with some substantial changes is described.

Databases, Factual↗