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Biomedical subjects

K Höffken

Publications and source records attributed to K Höffken.

At least 127 records · Page 7Linked to original sources

Human placental conditioned medium reverses apparent commitment to differentiation of human promyelocytic leukemia cells (HL60).

Using a system of sequential daughter cell transfers in semisolid medium, we have analyzed self-renewal and differentiation of human promyelocytic leukemia cells (HL60) in presence of all-trans retinoic acid and human placental conditioned medium (HPCM). We find that retinoic acid induces coordinated losses of self-renewal potential which are followed by phenotypic differentiation. The latter occurs as an all-or-none event and is reversible in the presence of HPCM. Thus, HL60 cells that apparently had terminally differentiated (as estimated by the ability to reduce nitroblue tetrazolium [NBT]) can lose their differentiation marker and reenter the proliferative pool.

Cell Differentiation↗

T lymphocyte-mediated graft--antigraft reactivity during graft-versus-host reaction in vitro.

Spleen organ cultures were prepared from lethally irradiated mice that had been injected with allogeneic bone marrow, with or without lymph node cells. These cultures were used in the analysis of graft-versus-host reactions (GVHR) in vitro. It was found that donor-derived T lymphocytes, which had been grown in an allogeneic spleen, prevented hemopoietic progenitor cells (colony-forming cells, CFC) of the recipient from differentiating in agar cultures. Furthermore, these lymphocytes were found to inhibit growth and differentiation of CFCs of the same donor. This graft-antigraft reactivity was not abolished by monoclonal anti-Thy-1 plus complement (C'), in contrast to the conventional GVHR. This indicates that the graft-versus-graft reaction depends on "de novo" generation of mature T lymphocyte effector cells from transplanted graft precursors.

Animals↗

Immunogenicity of cellular and acellular antigen preparations from a methylcholanthrene-induced mouse sarcoma.

Inbred mice were immunized with various cellular and subcellular preparations from a syngeneic, methylcholanthrene-induced sarcoma to induce transplantation immunity against a subsequent challenge of viable cells from the same tumor. Only with conventional immunization procedures using radiation-attenuated tumor cells or viable tumor cells in admixture with bacillus Calmette-Guérin was transplantation immunity obtained. Neither native soluble tumor extracts prepared using several extraction methods, nor cross-linked preparations of these extracts gave rise to transplantation immunity. With few exceptions, however, the immunizing preparations resulted in the production of tumor-specific humoral antibody. The manner in which tumor antigens are presented to the host as well as the experimental system (animal strain; tumor) used appear to play an important role in the development of transplantation immunity against tumors.

Animals↗

[Results of cytostatic therapy with cyclophosphamide, vincristine, adriamycin and DTIC (CYVADIC) in localized and metastasized osteosarcoma. A retrospective analysis].

From December 1973 to november 1978, 31 patients with osteosarcoma were treated with combination chemotherapy consisting of cyclophosphamide, vincristine, adriamycin and DTIC. 11 out of 19 patients with localized osteosarcoma are alive with no evidence of disease, 14+ to 40+ months after initiation of adjuvant postoperative chemotherapy. The probability of relapse-free survival for this group was calculated as 62% at 2 years and 48% at 3 years. Considering the 15 patients with osteosarcoma of the limbs relapse-free survival will be 79% at 2 years and 62% at 3 years. In 10 of 11 patients with no relapse the primary tumor has been located in the metaphysis of the proximal tibia or the distal femur. All patients with osteosarcoma of the trunk have died from metastases. Most of the 12 patients with metastasizing osteosarcoma died within one year after onset of chemotherapy. In none of these patients a complete remission could be achieved. For patients receiving adjuvant chemotherapy results are comparable with those reported by other investigators. In patients with disseminated osteosarcoma alternative chemotherapy regimens including adriamycin, cis-dichloro-diammine-platinum and ifosfamide may prove superior. In a pilot-study using vincristine-adriamycin-DDP or ifosfamide-DDP response to chemotherapy was noted in 4 out of 7 patients with two continuing complete remissions for 13+ and 5 1/2+ months, respectively.

Adolescent↗

[Combined chemotherapy and radiotherapy of localized and metastasizing Ewing's sarcoma (author's transl)].

Between 1973 and 1978 combined radiotherapy and chemotherapy were given to 22 patients with histologically proven Ewing's sarcoma. The combined chemotherapy consisted of cyclophosphamide, vincristin, adriamycin, as well as dacarbazine in some cases. The neoplasm was a localized one at the beginning of treatment in 14 of the 22. These patients received high-voltage radiotherapy to the primary focus at a focal dose between 42 and 55 Gray (4200-5500 rad), followed by chemotherapy. After 6--8 treatment cycles, adriamycin was replaced by methotrexate. Nine of the 14 patients survived without recurrence for 12 to over 59 months. Eight patients had extensive metastases at the beginning of treatment: they at first received only chemotherapy, followed by radiotherapy or operation, as indicated. Full clinical remission was achieved in five of them: in three this remission has now lasted for more than 18, 40 and 44 months, respectively. These results indicate that (1) additional chemotherapy improves the prognosis of localized Ewing's sarcoma, and (2) even in far-progressed cases the combination of chemotherapy and radiotherapy can achieve lasting remission, which may in fact be a true cure.

Adolescent↗

Quantitation of immune complexes by nephelometry.

Laser nephelometry was used to quantitate immune complexes and IgG aggregates in native sera. Sensitivity limits and calibration curves were in good agreement with the C1q binding assay frequently used for measuring immune complexes. Distinction between sera containing lipids or immune complexes was achieved by polyethylene glycol precipitation. Although not superior to other methods for quantitating immune complexes, the nephelometric assay may prove useful as a screening test and has the potential of an antigen-specific immune complex assay.

Animals↗

Activity of syngeneic complement for revealing antibody-induced cytotoxicity against a rat hepatoma.

The cytotoxicity of tumour-bearer serum against a transplanted aminoazodye-induced rat hepatoma was revealed using normal rat serum as the source of complement as assessed using a short-term 51Cr release test. The tumour-bearing rat was not deficient in a functional complement system and direct cytolysis against hepatoma cells was demonstrated following admixture of tumour cells and serum with no additional complement. No tumour growth was observed in animals receiving subcutaneous transfer of cells treated with tumour-bearer serum, although when heat-inactivated (56 C for 60 min) or normal sera were used, there was no modification of tumour development. The present findings indicate that the tumour-bearing animal contains both antibodies and complement sufficient for tumour lysis, although the full contribution of serum-mediated cytotoxicity in imposing immunological constraints upon tumour growth remains to be elucidated.

Animals↗

Circulating immune complexes in rats bearing chemically induced tumours. II. Characterization of sera from different stages of tumour growth.

Sera from rats bearing intraperitoneal implants of an aminoazo dye-induced hepatoma were fractionated by Sephadex G200 and DEAE-cellulose ion exchange column chromatography. Isolated fractions were examined for their capacity to bind [125I]C1q as a measure of immune complex levels, and for their ability to bind soluble tumour-specific antigen as well as to react with antigens expressed at the surface of viable hepatoma cells. Elevated levels of circulating immune complexes in unfractionated serum were directly detectable during early tumour development although, following serum fractionation, immune complexes were identified at both early and late stages of tumour growth. The present findings suggest that the detection of immune complexes in unfractionated samples of late tumour-bearer serum using a C1q-binding assay is masked by the increasing production of tumour-specific antibodies and by a shift from complement fixing to non-complement-fixing tumour-specific antibodies.

Animals↗