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Biomedical subjects

W Budzyński

Publications and source records attributed to W Budzyński.

At least 19 recordsLinked to original sources

Cytotoxicity and proliferation of splenocytes and lymph node cells from adjuvant-treated nude mice. Studies of natural and in vitro activation.

The cytotoxicity of NK cells and lymphocytes derived from nonadherent splenocytes (SPL) and regional lymph node cells (LNC) from complete Freund's adjuvant (CFA)-treated athymic nude young (4-6 weeks) and aged (over 1 year) BALB/c nu/nu mice in vitro activated with rIL-2, anti-CD3 mAb or PPD was analyzed and compared to SPL and LNC from age-matched euthymic BALB/c mice. The high natural cytotoxicity to YAC-1 target cells of SPL or LNC could be augmented by 48 h stimulation in vitro with rIL-2, especially when derived from young nude BALB/c mice. The increase in cytotoxic activity was accompanied by increased proliferative activity of both SPL and LNC, which showed statistically significant differences between the rates of stimulation of cells from the young and aged groups. Anti-CD3 mAb strongly activated the cytotoxicity of BALB/c euthymic donor effector cells against P-815 target cells, corresponding to a very high proliferative activity of these cells, but anti-CD3 mAb did not lead to activation of effector cells from nude donors. FACS analyses of antigenic markers similarly showed an increased number of T cells in LNC from aged BALB/c nude donors, which, however, never reached the levels of those of euthymic animals.

Aging↗

Activity of natural killer (NK) cells in the course of experimental trichinellosis in mice.

B6C3F1 mice were infected with 200 or 500 larvae of Trichinella spiralis per mouse and pulmonary NK cell-mediated clearance of semisyngeneic tumour cells was determined in vivo on days 10, 20, 30, and 60 after the infection. Cytotoxic activity of NK cells in the lungs was substantially elevated on days 20 and 30 after challenge with both "doses" of the parasite. At the same time large granular lymphocytes (LGLs) as well as cells expressing surface asialo-GM1 molecules were isolated in elevated numbers from spleens of the infected as opposed to the normal mice. Expression of other markers of differentiation, such as THy 1, CD4, and CD8 was also enhanced on splenocytes isolated from the infected mice on day 30 but not 20 after administration of the larvae. The present results indicate that NK cell-mediated activity in vivo is stimulated above the baseline level during migration and early muscle phases of the infection with T. spiralis in mice. The possible impact of this effect upon the course of trichinellosis as well as upon the growth of tumours in the infected host is discussed.

Animals↗

Antitumor activity of optical isomers of cyclophosphamide, ifosfamide and trofosfamide as compared to clinically used racemates.

The relationship between enantiomeric homogeneity of three oxazaphosphorine drugs: cyclophosphamide, ifosfamide and trofosfamide and their antitumor activity was evaluated by standard screening tests against four in vivo transplantable tumor models: L 1210 and P 388 lymphoid leukemias, Lewis lung carcinoma and 16/C line of mouse mammary adenocarcinoma. It was shown that the stereodifferentiation of anti-tumor effect of enantiomers was not outstanding although quite consistently in favour of levorotatory forms. The only exception was seen for cyclophosphamide enantiomers tested against leukemias where R/+/form was more effective than S/-/or racemate.

Animals↗

Comparative studies on biological activity of /+/R and /-/S enantiomers of cyclophosphamide and ifosfamide. I. Antitumour effect of cyclophosphamide and ifosfamide enantiomers.

The differences in antitumour effect of /+/R and /-/S enantiomers of both cyclophosphamide and ifosfamide were detected. In the case of ifosfamide in all five tested tumour models (Leukemia L1210, P388, Lewis lung carcinoma, 16/C mammary adenocarcinoma and B16 melanoma) the /-/S form exerted not only higher antitumour effects than /+/R form, but revealed higher therapeutic indices as well. The same appeared to be true for /-/S enantiomer of cyclophosphamide in three models of solid tumours. In L1210 and P-388 ascitic leukemia models /+/R and /-/S cyclophosphamide exerted the same antitumour effect.

Animals↗

LL2 cell line derived from transplantable murine Lewis lung carcinoma--maintenance in vitro and growth characteristics.

LL2 is a new in vitro cell line derived from Lewis lung carcinoma passaged routinely in C57BL mice. It has been in continuous culture for more than 1 year and has survived 72 subcultivations. The cells grow in semi-suspension culture being loosely connected with a culture vessel's surface. The cell line is hypotetraploid, with modal chromosome number 72. Tumorigenicity and metastasibility of the cells are retained but lowered as compared with original in vivo tumor line. The LL2 cell line is being used in studies on phenotypic characteristics (markers) related to its pattern of growth.

Animals↗

Changes in natural killer cells activity in mice bearing subcutaneously implanted Lewis lung carcinoma.

Natural killer (NK) cytotoxic activity was measured against the standard target cell line YAC-1 in a four-hour chromium release assay. Effector cells were taken from spleen and bone marrow of BDF1 mice inoculated 3, 7, 14 or 21 days earlier with 2 X 10(6) Lewis lung carcinoma (LL) cells. The peak of cytotoxic activity both in spleen and bone marrow appeared in mice 3 days after tumor inoculation. There were no differences in cytotoxic effect between tumor bearing and normal mice on day 7. The significant decrease was observed in tumor bearing mice on day 14 and 21. However, at that time the spleen cellularity increased 2.7 and 3.8 times, respectively suggesting a possible dilution effect of NK cells in mice with splenomegaly. Bone marrow cellularity remained unchanged as compared to control. The possible mechanisms of decrease in NK cytotoxic activity and its implications for progression of tumor growth are considered.

Animals↗

Studies on antitumor and myelotoxic effect of Ledakrin and its selected analogues.

Ledakrin (Nitracrine) and its three analogues (C-846, C-857, C-1006) selected in primary in vitro and in vivo screening systems have been tested for antitumor activity in Lewis lung carcinoma, B16 melanoma of 16/C mammary adenocarcinoma bearing mice. Their effect on mouse bone marrow stem cells has also been evaluated by means of CFU-S technique. None of the tested compounds, including Ledakrin, revealed anti-tumor activity. Their bone marrow toxicity was minimal and comparable with that of Bleomycin.

Aminoacridines↗

Lewis lung carcinoma in mice as an experimental therapy model. I. The growth kinetics and the effect of tumor on host.

Some biologic characteristics of Lewis lung carcinoma (LL) which are relevant for the experimental protocols both for the single drug and combined treatment were examined. The studies included the influence of route and size of inoculum of the median survival time (MST) of tumor bearing nice, the growth kinetics of primary tumor and time of metastases appearance. In addition the effect of tumor growth on some host parameters as hematopoietic stem cells activity and on the spleen weights was tested.

Animals↗

Lewis lung carcinoma in mice as an experimental therapy model. II. The effect of BCNU, cyclophosphamide and/or surgery treatment on early and advanced tumor in mice.

The effect of BCNU, Cyclophosphamide (CY) and surgery treatment was studied in mice inoculated s.c. with LL cells. With BCNU given in a single 40 mg/kg dose 24V h after s.c. implantation of 2 X 10(6) tumor cells only increase in life span (ILS) was observed while with CY given in a dose 300 mg/kg at the same time it was possible to cure the tumor-bearing mice. However, if the drugs were administered on day 8 when the average tumor mass was about 548 mg and the micrometastases in the lung were detectable, only an increase in life span could be achieved. The combination of surgery and CY in advanced tumor bearing mice resulted again in the high percentage of cures.

Animals↗

Studies on antitumor effect of corynebacterium parvum and pustulan on Lewis lung carcinoma in mice.

Antitumor effect of two biological adjuvants and their supported mechanism was studied in mice inoculated s.c. with Lewis lung carcinoma (LL) cells. The studies included in vivo tests: median survival time (MST) evaluation, tumor weight inhibition (TWI) and splenohepatomegaly measurements. The nonspecific in vitro cytostatic effect of peritoneal adherent cells stimulated with adjuvants was measured by inhibition of 3H thymidine incorporation into tumor cells. In in vivo studies the reproducible 20-30% of TWI was achieved in groups treated with both drugs, while no significant increase in MST was observed. Corynebacterium parvum activated peritoneal adherent cells caused 80% DNA synthesis inhibition of tumor cells while Pustulan activated peritoneal cells showed very low (26%) cytostatic effect.

Adjuvants, Immunologic↗

Effect of cyclophosphamide on mouse bone marrow and leukemic stem cells.

The colony forming unit assay was introduced in our laboratory for studies in vivo on the differential effect of new antitumor agents on normal bone marrow and tumor cells, the normal (NCFU) and leukemic (LCFU). To verify the technique the effect of Cyclophosphamide (CY) on the total number and the number of stem cells in bone marrow was examined. Different sensitivity of the mouse normal as compared with leukemic stem cells (leukemia P-388) was shown.

Animals↗