Search PubMed⌕ Search

Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

477 records · Page 27Linked to original sources
PubMedDate not supplied

Ex vivo assays to evaluate the role of protein kinase C in tumor cells of patients with breast cancer.

New anti-cancer strategies have been developed with respect to proteinkinase C (PKC) as a potential target for therapeutic intervention in patients with advanced breast cancer. Using cell lines, most of the preliminary data are encouraging but insufficient information is available concerning clinical breast cancer cells. Thus, we decided to clarify the involvement of PKC in clinical breast carcinoma cells. We isolated viable tumor cells from fluids or tissue burden of eleven patients with advanced breast cancer. Performance of short term cultures supplemented with commonly used antineoplastics mimicked the clinical situation. We determined the ex vivo chemosensitivity pattern of each cell population. Additionally, we analysed total PKC activity and quantified the PKC-isoform eta. All assays showed a heterogeneous highly variable distribution of the data investigated. No tendency could be observed regarding the influence of the therapeutics on PKC activity, PKC-eta expression or chemoresistance, respectively. Moreover, changes in neither PKC-eta expression, PKC activity nor chemoresistance induced by a particular drug in an individual tumor necessarily predicted the same reaction in another tumor to this agent. Therefore, we concluded that more explorative data concerning this topic are required prior to the development of a clinically useful therapy regimen with PKC as the major target.

Antineoplastic Agents↗
PubMedDate not supplied

Early macrophage and cytokine response during the growth of immunogenic and non-immunogenic murine tumors.

Very little data exist on the mechanisms of innate immunity during the first days after syngeneic tumor inoculation. Nonspecific macrophage reaction precedes the development of specific immune response and is important for further tumor growth and stroma formation. We investigated two lymphoma cell lines of the same origin, differing in immunogenicity: non-immunogenic parental strain P388 and its highly immunogenic subline P388/adria. Early systemic inflammatory response resulted in the enhancement of nitric oxide (NO) and superoxide production by peritoneal macrophages which was at a maximum on the first day after s.c. tumor inoculation and was observed in mice bearing either of these tumors independently of immunogenicity. It was followed by a transient elevation of the serum levels of pro-inflammatory cytokines: TNF-alpha IL-6. In order to evaluate the role of inflammatory response, vaccinations with lethally irradiated lymphoma cells were performed. After two weekly injections, the mice were challenged s.c. with live tumor cells of the same subline. Effective vaccination with P388/adria lymphoma cells induced retardation of tumor growth in parallel with down-regulation of peritoneal macrophage activity and abrogation of serum cytokine release. Non-effective immunization with P388 cells influenced neither tumor growth nor macrophage functions and cytokine level. Thus, a positive correlation was found between down-regulation of the inflammatory response and inhibition of tumor growth. We suppose that, in efficiently immunized mice, special mechanisms exist which are responsible for down-regulation of the inflammatory reaction. Macrophage products may facilitate tumor cell survival by preventing apoptosis or participate in the activation of tumor neoangiogenesis. Suppression of these activities may serve as an important tool for the inhibition of tumor growth at the early stages of malignant transformation.

Animals↗
PubMedDate not supplied

An observational study of sun and heat protection during Canada Day outdoor celebration, 2003.

Attendance at summer outdoor mass gatherings may lead to heat- and sun-related illness. The purposes of this study were: (1) to estimate the proportion of people in attendance at the 2003 Canada Day celebration in the National Capital Region who used sun and heat protective items; (2) to identify factors associated with the utilization of these protective items; and (3) to provide research data to public outdoor event organizers when developing evidence-based plans for safer events. A naturalistic observational cross-sectional method was used to gather information at the 2003 Canada Day celebration in the National Capital Region on attendees' demographics, the sun and heat protective items they used and the protective resources available at the event sites. Of the 398 observed attendees, the proportion using any one of the protective items ranged from 3 percent (an open umbrella) to 51.5 percent (sunglasses). Females were more likely to use protective items more than males, and adults more likely than children. Planners of public outdoor events should consider the factors that influence the utilization of sun and heat protective behaviours and the environmental modifications that would allow participants to make safe choices.

Adolescent↗
PubMedDate not supplied

In vivo characterization of immunogenicity of a mitoxantrone-resistant murine P388 leukemia.

The Mitoxantrone-resistant murine leukemia P388/Mitox, expressing the multidrug-resistant phenotype, has a higher immunogenicity than the parent sensitive P388. This could be shown in vivo by immunization with lethally-irradiated tumor cells. If the P388/Mitox was used for immunization before subsequent challenge with viable tumor cells of the same line, this resulted in a partial rejection of tumors and production of a substantial number of tumor-free survivors. For an effective immunization at least two primings s.c., i.v. or i.p. with at least 10(6) irradiated cells were necessary. This protected the recipient mice from a challenge of up to 10(8) viable cells over a period of at least 75 days. Treatment of BDF1 mice with the T-cell suppressor Cyclosporin A prevents immunization. In nude mice no immunization effect could be obtained. It was possible to transfer immunity adoptively with spleen cells from mice, which were treated with irradiated tumor cells of the P388/Mitox line. Treatment of tumor-bearing mice with IL-2 resulted in a prolongation of survival both when it was administered prophylactically before transplantation of P388/Mitox and at an advanced stage (day 7-11). Also the alkyl-phosphocholine hexadecylphosphocholine was significantly effective in the resistant but not in the parent P388 leukemia. The data presented demonstrate that by development of a multidrug-resistance, concomitantly a xenogenization must have taken place which leads to a recognition of cells by immune mechanisms. In our model, T-lymphocytes and NK-/LAK-cells probably play a role in the immunologically conditioned rejection of tumor cells of the P388/Mitox leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Involvement of macrophages and cytokines into rejection mechanism of the drug-resistant and immunogenic murine lymphoma P388/adria.

Macrophages and their products may exert either inhibitory or stimulatory effects on malignant cells,thus preventing or supporting tumor growth, however, the mechanisms of this interaction are not fully understood. It was the aim of the present study to elucidate the role of macrophage activation during the growth and rejection of highly immunogenic murine leukemia P388/adria cell line which was made resistant by suboptimal treatment of mice with adriablastin during the serial passaging of parental P388 cells. The functional activity of peritoneal macrophages and the serum level of cytokines IL-1 beta, IL-6 and TNF-alpha were studied in different groups of mice. Mice from group 1 (control) received saline. Mice from group 2 (tumor bearers) with fast subcutaneous (s.c) 100% tumor growth were compared with animals from group 3 that had been twice previously immunized with lethally irradiated P388/adria cells and later inoculated with viable tumor cells. Tumors grew in only 25% of group 3 animals with a significant delay. The activity of peritoneal macrophages was studied by NO2- production and the NBT-test. Both tests revealed the early high systemic activation of macrophages in group 2. This coincided with the elevation of serum TNF-alpha and IL-6 levels. This effect was not dependent on whether alive or lethally irradiated tumor cells were inoculated. The NO2- production by peritoneal macrophages correlated well with the dynamics of serum cytokine levels while the NBT-test did not. Studies on group 3 showed total abrogation of early macrophage and cytokine reactions. The production of inhibitory factors by macrophages in previously immunized mice is suggested. The fact that the early activation of macrophages and increase of serum levels of proinflammatory cytokines occurred in animals with fast growing tumors, which was decreased or absent in animals with tumor delay or rejections, allows us to suppose that this reaction plays more a supporting than a protecting role for tumor growth.

Animals↗