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Biomedical subjects

J Rak

Publications and source records attributed to J Rak.

At least 73 records · Page 4Linked to original sources
PubMed1995

The 92-kDa gelatinase B is expressed by advanced stage melanoma cells: suppression by somatic cell hybridization with early stage melanoma cells.

The production and local release of various proteolytic enzymes, either by tumor cells or tumor-associated stromal cells, is thought to facilitate the malignant behavior of solid tumors. Human cutaneous melanoma offers an excellent clinical model to study the possible contribution of such proteases to solid tumor progression because melanoma goes through a series of well defined stages in its pathogenesis; moreover, permanent cell lines have been established from these various stages. As a first step to analyzing the gelatinolytic enzymes in melanoma pathology, we examined cell lines derived from early stage primary melanomas in which patients were cured of their disease and compared the results to those obtained with cell lines established from advanced stage primary lesions or metastases (i.e., from patients who eventually succumbed to the disease). We found that 80% of cell lines examined from early stage lesions constitutively produced only the 72-kDa gelatinase A but never the 92-kDa gelatinase B. In contrast, the majority of advanced stage cell lines examined produced both the 72-kDa gelatinase A and the 92-kDa gelatinase B. Advanced stage cell lines that did not constitutively produce the 92-kDa gelatinase B could be induced to do so with transforming growth factor beta, interleukin 1 beta or 12-O-tetradecanoyl-phorbol-13-acetate. In total, 0 of 5 early stage cell lines constitutively expressed the 92-kDa gelatinase B, and only 2 of 5 could be induced to produce this activity. In contrast, all advanced stage cell lines that were evaluated either constitutively or inducibly produced the 92-kDa gelatinase B. To analyze the mechanism by which 92-kDa gelatinase B production is switched on in the advanced stage melanoma cell lines, somatic cell hybrids were constructed using an advanced stage melanoma cell line as one partner and either one of two early stage cell lines as the other. Constitutive production of the 92-kDa gelatinase B in such hybrids was lost and could not be induced in such hybrids. Coculture of the early and advanced stage cell lines failed to recapitulate what was seen after somatic hybridization, and zymographic analysis of lysates from hybrid cell lines demonstrated no 92-kDa gelatinase B activity. Reverse transcription-PCR analysis demonstrated that the loss of 92-kDa gelatinase B production occurred at the level of steady-state mRNA for the enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Oncogenes as inducers of tumor angiogenesis.

Dominantly acting transforming oncogenes are generally considered to contribute to tumor development and progression by their direct effects on tumor cell proliferation and differentiation. However, the growth of solid tumors beyond 1-2 mm in diameter requires the induction and maintenance of a tumor blood vessel supply, which is attributed in large part to the production of angiogenesis promoting growth factors by tumor cells. The mechanisms which govern the expression of angiogenesis growth factors in tumor cells are largely unknown, but dominantly acting oncogenes may have a much greater impact than hitherto realized. An example of this is the induction of expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) by mutant H- or K-ras oncogenes, as well as v-src and v-raf, in transformed fibroblasts or epithelial cells. Besides VEGF/VPF, mutant ras genes are known to upregulate the expression of a variety of other growth factors thought to have direct or indirect stimulating effects on angiogenesis, e.g. TGF-beta and TGF-alpha. This effect may be mediated through the ras-raf-MAP kinase signal transduction pathway, resulting in activation of transcription factors such as AP1, which can then bind to relevant sites in the promoter regions of genes encoding angiogenesis growth factors. In principle, similar events could take place after activation or overexpression of many other oncogenes, especially those which can mediate their function through ras-dependent signal transduction pathways. The regulatory effect of oncogenes on mediators of angiogenesis has some potentially important therapeutic consequences. For example, it strengthens the rationale of pharmacologically targeting oncogene products, such as mutant RAS proteins, as an anti-tumor therapeutic strategy. Such drugs may attack the source of one or more angiogenic growth factors and by doing so, function, at least in part, as anti-angiogenic agents in vivo.

Genes, Tumor Suppressor↗
PubMed1995

Massive programmed cell death in intestinal epithelial cells induced by three-dimensional growth conditions: suppression by mutant c-H-ras oncogene expression.

Deregulation of molecular pathways controlling cell survival and death, including programmed cell death, are thought to be important factors in tumor formation, disease progression, and response to therapy. Studies devoted to analyzing the role of programmed cell death in cancer have been carried out primarily using conventional monolayer cell culture systems. However the majority of cancers grow as three-dimensional solid tumors. Because gene expression, and possibly function, can be significantly altered under such conditions, we decided to analyze the control and characteristics of cell death using a compatible three-dimensional tissue culture system (multicellular spheroids) and compare the results obtained to those using two-dimensional monolayer cell culture. To do so we selected for study an immortalized, but nontumorigenic line of rat intestinal epithelial cells, called IEC-18, and several tumorigenic variants of IEC-18 obtained by transfection with a mutant (activated) c-H-ras oncogene. The rationale for choosing these cell lines was based in part on the fact that intestinal epithelial cells grow in vivo in a monolayer-like manner and form solid tumors only after sustaining certain genetic mutations, including those involving the ras gene family. We found that the IEC-18 cells, which grow readily and survive in monolayer cell culture, undergo massive cell death within 48-72 h when cultured as multicellular spheroids on a nonadhesive surface. This process was accompanied by a number of features associated with programmed cell death including chromatin condensation (Hoechst 33258 staining) apoptotic morphology, DNA degradation, and a virtual complete loss of colony forming (clonogenic) ability in the absence of apparent membrane damage as well as accumulation of lipid containing vacuoles in the cytoplasm. Moreover, enforced over-expression of a transfected bcl-2 gene could prevent this cell death process from taking place. In marked contrast, three different stably transfected ras clones of IEC-18 survived when grown as multicellular spheroids. In addition, an IEC cell line (called clone 25) carrying its mutant transfected ras under a glucocorticoid inducible promoter survived in three-dimensional culture only when the cells were exposed to dexamethasone. If exposure to dexamethasone was delayed for as long as 48 h the cells nevertheless survived, whereas the cells became irreversibly committed to programmed cell death (PCD) if exposed to dexamethasone after 72 h. These results suggest that intestinal epithelial cells may be programmed to activate a PCD pathway upon detachment from a physiologic two-dimensional monolayer configuration, and that this process of adhesion regulated programmed cell death (ARPCD) can be substantially suppressed by expression of a mutant ras oncogene.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

[Theory and practice within the framework of pharmaceutical education].

The present paper deals with the problems of the graduate study of pharmacy with regard to the relationship of theoretical and practical teaching. The situation in Slovakia is discussed and compared with the present-day states in some countries of Western Europe.

Education, Pharmacy, Graduate↗
PubMed1995

[Drug forms for drug delivery into the gastrointestinal tract].

Most drugs introduced into the GIT are absorbed into the stomach and/or the small intestine according to their chemical character. Some drugs (their number is on the increase) require targeted supply to a certain site in the GIT if their biological activity is to be manifested and made use of. Fulfilling this condition, which concerns primarily peptides and proteins, requires adjustments of dosage forms. Much effort is put forth to shift absorption into the large intestine (colon), which is advantageous from the viewpoint of circadian biorhythms.

Biological Availability↗
PubMed1992

[Investigations of the ototoxicity of dicortinef (ear drops)].

The authors investigated the ototoxic influence of Dicortinef in laboratory animals. Their examinations were performed on 15 guinea pigs (weighing 210-380 g.) after application of this medicine to the fenestra rotunda. The harmful effect of Dicortinef was expressed by the characteristic fall in the microphonic potential (PM) and potential of the acoustic nerve (AP).

Animals↗
PubMed1992

[The role of sclerotherapy in the treatment of esophageal varices in children].

The authors presented the actual views and their own results of using sclerotherapy in children with oesophageal varices. Oesophageal varices exist almost every time as a most dangerous complication in patients with portal hypertension. Acute haemorrhage caries a high mortality and the extremely important priority is control of bleeding as soon as possible. Traditional conservative methods of treatment often do not improve long-term survival and portal systematic shunt is rarely possible in patients under the age of 10. Because of it sclerotherapy may be proposed as a treatment of choice for children with oesophageal varices.

Adolescent↗
PubMed1990

[Histological and electron microscopic examinations of laryngeal papilloma in children and adults].

The authors present the results of histologic and electron microscopic investigations of larynx papillomas in 11 children and 8 adults. Comparative estimation showed the characteristic changes for clinical and morphological division of papilloma into adult-type and juvenile one. Detailed morphological analysis in adult-type papilloma either with dysplastic changes or with hyperkeratosis was performed.

Adolescent↗
PubMed1989

[The problem of diagnosing tumors of the nose and paranasal sinuses].

A case of incorrect diagnosis of extensive nasal cavity, maxillary sinus and nasopharynx neoplasm was presented. The imitation of tumor symptoms was due by long lying in nasal cavity foreign body, inflammation of maxillary sinus and adenoiditis. The author underline that over hasty neoplasm diagnosis always exerts an unjustified and destructive psychologic influence on patient and his family.

Diagnosis, Differential↗
PubMed1989

Transplantable mouse 16/c mammary adenocarcinoma as a model in experimental cancer therapy. II. Modification of tumor-host interactions by therapeutic procedures.

The influence of therapeutic procedures on tumor--host interactions was analysed using 16/c mouse mammary adenocarcinoma model system. After partial removal of tumor burden the growth enhancement of remnant tumor mass was observed. Pretreatment of the host either with cyclophosphmide or X-rays resulted in enhancement of experimental metastasis formation. Unexpectedly, such a procedure caused the growth delay of the primary subcutaneous tumor. The possible mechanisms of observed phenomena are discussed.

Adenocarcinoma↗
PubMed1989

Transplantable mouse mammary adenocarcinoma 16/c as a model in experimental cancer therapy. III. Sensitivity to antitumor drugs.

On the basis of biological characteristics of murine transplantable mammary adenocarcinoma 16/c, experimental conditions optimal for chemotherapeutic experiments were defined. Sensitivity of primary tumor and lung metastases to the treatment with drugs used in breast cancer therapy: cyclophosphamide, 5-fluorouracil and adriamycin was confirmed. These drugs were significantly more effective in combination than when administered as monotherapy. Antimetastatic but not antitumor effect of 5-fluorouracil could be potentiated by using albumin microspheres as a carrier. Usefulness of the tumor model system in experimental chemotherapy is discussed.

Adenocarcinoma↗