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Biomedical subjects

L Olsson

Publications and source records attributed to L Olsson.

At least 19 recordsLinked to original sources

Tumor-associated antigen 43-9F is of prognostic value in squamous cell carcinoma of the lung. A retrospective immunohistochemical study.

BACKGROUND: Squamous cell lung carcinoma (SLC), the most frequent type of lung cancer, generally is treated surgically and its prognosis is poor. The only current clinically useful prognostic criterion is lymph node staging (TNM classification). Expression of a novel tumor-associated carbohydrate epitope Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3 Gal beta 1-4Glc identified by the 43-9F monoclonal antibody (MoAb) is associated with the growth pattern of SLC cell lines in athymic mice and in vitro. This implies that the 43-9F epitope may be related to tumor progression in patients with SLC and that, as such, it could be of prognostic value. METHODS: Primary tumor specimens from 231 patients with lung carcinoma (130 with SLC, 64 with adenocarcinoma, 10 with small cell carcinoma, 16 with large cell carcinoma, and 11 with adenosquamous carcinoma) were examined by immunohistochemical studies on formalin-fixed, paraffin-embedded tissue samples for immunoreactivity with an MoAb to the 43-9F antigen. Univariate and step-wise Cox regression analyses were used to compare survival time by histopathologic diagnosis, smoker status, TNM classification, and type of surgical treatment. RESULTS AND CONCLUSIONS: Patients with 43-9F epitope-positive SLC tumors had a significantly (P less than 0.01) better prognosis than patients with epitope-negative tumors. In contrast, no association was seen between 43-9F epitope expression and survival time for patients with lung adenocarcinomas. Further, the prognostic value of 43-9F expression in SLC was found to be superior to the N-classification with the added advantage that it requires access only to primary tumor tissue and thus is available before therapy.

Adult

Immobilization of pyranose oxidase (Phanerochaete chrysosporium): characterization of the enzymic properties.

Immobilization of pyranose oxidase (E.C.1.1.3.10) from Phanerochaete chrysosporium is described. The enzyme was bound to a glass-beaded support according to the glutardialdehyde, diazo, and carbodiimide methods with activity yields of 10%-23.3%. Characterization of the enzyme immobilized with the glutardialdehyde showed enhanced operational, storage, and temperature stability. The temperature optimum remained unchanged, but the pH optimum was slightly altered. Kinetic properties and the relative substrate specificities for glucose and xylose showed certain differences.

Agaricales

Natural polyclonality of spontaneous AKR leukemia and its consequences for so-called specific immunotherapy.

Young female AKR mice made leukemic by iv inoculation of 10(3) spontaneous AKR thymoma cells were treated with repeated injections of irradiated cells from the same tumor. Treatment began 1 day after injection of the viable cells. The cytotoxicity of sera and lymphoid cells from healthy mice immunized with lymphoma cells from either treated or nontreated mice with leukemia grafts revealed that the tumor cells could be subdivided into four distinct antigenic types. One type (clone A) accounted for about 97% of the lymphoma cells in each mouse with spontaneous leukemia, whereas the remaining 3% were subdivided into three other distinct antigenic types (clones B, C, and D). Lymphoma cells from treated mice with grafted leukemia were never clone A type but either clone B, C, or D type. Repeated sc injections of 10(7) irradiated cells from spontaneous AKR thymomas induced from 15 to 34% cure in mice with grafts of leukemia cells. Treatment with only clone A induced about 32% cure, whereas treatment with clone B, C, or D had no beneficial effect. Treatment with 10(7) cells each of clone A plus clone B gave 33% cure; clone A plus clone B plus clone C, 45%; and all four clones cured 92% of the mice with leukemia grafts. The efficiency of immunotherapy may be influenced by the natural clonality of the tumor to be treated.

Animals

Immunoadjuvant treatment of primary grafted and spontaneous AKR-leukemia. I. Treatment efficiency correlated to autoimmune reactivity.

Young AKR mice grafted i.v. with 10(1) or 10(3) cells from spontaneous AKR thymomas were treated with repeated i.v. injections of BCG or subcutaneous injections of irradiated AKR thymoma cells. BCG often cured mice from graft leukemia, whereas the effect of irradiated thymoma cells was less effective. Mice that did not develop graft-leukemia after graft of 10(1) leukemia cells and BCG treatment showed a spontaneous leukemia in 30% of the cases later. Ninety percent of nongrafted mice developed spontaneous leukemia whether BCG-treated or not. General immune reactivity as assessed in individual mice by T and B lymphocyte mitogen tests as well as the hemolytic plaque-forming cell assay had no clear correlation to the effects of immune adjuvants in respect to survival. In contrast, occurrence of self-directed immune reactions were clearly correlated to survival and cure of grafted and BCG-treated mice as revealed by assays both in vitro and in vivo. However, 13 to 25% of the mice apparently cured of leukemia developed a wasting-like syndrome that sometimes terminated in death. The immplications of self-directed immune reactions as mediators of the anti-neoplastic effects of immunoadjuvants.

Adjuvants, Immunologic

Immune reactions with cytotoxic activity to "self" in natural surveillance of aberrant cells.

Cytotoxic autoreactive lymphoid cells have been demonstrated to be a normal immunologic component in both normal and tumor-bearing organisms. The cells have a high antineoplastic potential. They are cytotoxic in vitro to non-immunogenic tumor cells, and a high in vivo activity of such cells may be positively correlated to in vivo regression of tumors. It is suggested that the cytotoxic activity of cytotoxic autoreactive cells reflects a natural mechanism to removal of all types of aberrant cells of which malignant cells are only a subset. It is further deduced that such mechanisms must be independent of cell surface neoantigens, and that cytotoxic autoreactive mechanisms with high probability therefore also are efficient against spontaneous malignant tumors.

Animals

Specificity of the inhibition of DNA synthesis by extracts from cloned normal, sarcoma-virus-transformed and revertant 3T3 cells.

Extracts containing tissue-specific DNA-inhibitory activity were prepared from normal FL (Swiss) and BALBc3T3 cells, from these cells transformed with sarcoma virus and from revertants cloned from the transformed cell lines. By testing all extracts on all cell lines we found that (1) production of and susceptibility to the inhibitors were decreased in transformed BALB/c cells (2) specificity varied with expression of the transforming genome, as an extract from a given cell line inhibited the growth of its cell of origin, e.g. revertant, more than normal or transformed cells, and (3) there was also a DNA-synthesis stimulator.

Animals

Effect of tissue specific mitotic inhibitors on survival time of spontaneous and virus-induced murine leukaemia and influence on myocardial degeneration.

Treatment of adult AKR mice with tissue-specific mitotic inhibitor mol. wt. 1,000--20,000 extracted from the AKR thymus significantly delayed the onset of spontaneous thymus leukaemia, whereas extracts of other organs were without effect. A slight prolongation of survival time was found with spleen extract when administered to BALB/c mice infected with Rauscher virus, which causes leukaemia starting in the spleen. Thymus extracts of MW 100,000--300,000 caused myocardial degeneration in some leukaemic and nonleukaemic mice.

Animals

Pharmacologic factors and manipulation of immunity systemic adjuvants in cancer therapy.

Because of the experimental and clinical studies which have been extensively conducted with bacillus Calmette-Guérin (BCG) as a systemic adjuvant in cancer immunotherapy, we have analyzed the main factors and conditions which determine its beneficial action and have underlined some of these (eg, the dose factor which controls the amplification of suppressor cells which is probably responsible for failures and even the possible tumor-enhancing effect of immunotherapy). Knowing those factors and conditions, we have been able to establish a systematic immunopharmacologic study of systemic immunity adjuvants, which has resulted in the discovery of agents whose actions are more rapid than that of BCG on one or a few populations of cells involved in immunity and which, unlike BCG, do not induce suppressor cell amplification. This amplification may explain the difference in the results obtained with this mycobacterium in various clinical immunotherapy trials in which it was applied differently. It is proposed to combine these mono- or pauc-functional adjuvants in order to try to obtain all of the beneficial effects of BCG without the amplification of suppressor cells.

Adjuvants, Immunologic

Experimental induction of tumor growth control by immune adjuvants: current status and some theories to be explored.

Immune adjuvants have been shown to induce tumor growth control in many experimental tumor-host models. The beneficial effect depends on tumor size and type and dose of the adjuvants in question, but few experimental data elucidate, which immunological mechanisms--if any--that are directly involved in the tumor destructive processes induced by immuno-adjuvants. The importance of non-specific tumor immunity is discussed with emphasize on the importance of immuno-competent cells that react non-specifically, and that may include "self-directed" cells. Non-immunological mechanisms are proposed also to be of importance, underlining the possible role of the phenomenon of spontaneous reversion of malignant cells to a non-malignant state. It is finally stressed that both immunologic and non-immunologic properties of immunoadjuvant induced tumor growth control must be analysed before therapy with immunoadjuvants can be optimally applicated in the cancer patient.

Adjuvants, Immunologic