摘要:

Elastin and collagen are abundant fibrous molecules in the stroma. Tumor cells invading the stroma are in contact with fibers of both types much of the time. Both may serve as footholds for the traction required for movement. Elastin has an additional role. Elastin peptides are known to stimulate receptor signaling and chemotaxis, which could explain the morphometric changes (membrane and organelle polarization and cell volume shrinkage) that we have reported for certain tumor cell lines invading elastic lamina. Elastin and its peptides emerge as possible invasion enhancers for some tumor cells. In ongoing work we are screening human tumors that contact elastin (e.g., breast carcinomas) to see if the presence of elastin receptors correlates with early dissemination of metastatic tumor cells.

ISSN:1010-4283    

DOI:10.1159/000217829

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

To elucidate the inhibitory effect of prostaglandin E2 (PGE2) on the generation of recombinant interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) activity, we have examined the association between cellular 3′,5′-cyclic adenosine monophosphate (cAMP) and cytolytic activity of 3-day IL-2-cultured murine LAK cells, i.e. at late phase of IL-2 induction, in the presence and absence of PGE2. The results indicate that, at the late phase of IL-2 induction, LAK cells retain their responsiveness to PGE2 inhibition, and the inhibition can be partially suppressed by additional IL-2 in proportion to the decrease in the ratios of stimulated to basal cellular cAMP lev

ISSN:1010-4283    

DOI:10.1159/000217830

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In this study, the reactivity of three different monoclonal antibodies (MAbs) against the multiple-drug resistance (MDR)-related P-glycoprotein (P-170) were compared with each other using a collection of frozen and paraffin-embedded tumors, normal tissues and metastatic cells of malignant pleural and peritoneal effusions. The MAbs JSB-1, C 219 and 265/F4 were used in an indirect immunoperoxidase technique on frozen material. In addition, MAb C 219 was used on formalin-fixed, paraffin-embedded material from the same tumors, of which frozen sections were studied, and in a retrospective study C 219 was tested on paraffin blocks of the primary tumors that were responsible for the malignant effusions. The results show different staining patterns for all three MAbs to some extent. Results in frozen and paraffin sections obtained with MAb C 219 were comparable. MAb C 219 performs well both in frozen and formalin-fixed, paraffin-embedded material, making it a useful candidate for application in routine laboratory analysis. The retrospective analysis did not show consistency of P-170 expression in the same patients. This leads to the hypothesis that the actual status of P-170 expression in recurrent disease should be obtained before continuing or modifying chemotherapy. Clinical studies aimed at the correlation of immunohistochemistry with therapy response have to evaluate the relevance of P-170 expression in drug resistance of primary and metastatic tumors.

ISSN:1010-4283    

DOI:10.1159/000217831

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In the adult mouse, pancreatic islets contain four islet cell types: α, β, δ and pancreatic polypeptide cells that synthesize glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. The early progenitor cells to the pancreatic islets are multipotential and coactivate all the islet-specific genes from the time they first appear. As development proceeds, expression of islet-specific hormones becomes restricted to the pattern of expression characteristic of mature islet cells. The phenotype of mature islet cells, however, is not stable since different environmental stimuli can induce the reappearance of embryonal traits in mature β ce

ISSN:1010-4283    

DOI:10.1159/000217832

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Insight into the biogenesis of peptide hormones has grown explosively by elucidation of gene, mRNA and prohormone structures. In addition, information about prohormone processing enzymes is rapidly accumulating. Prohormones vary in size and organization from poly- to monoprotein structures. According to their structural organization and sequence homology, hormones are grouped in families. Prohormones are processed to bioactive peptides by multiple modifications during the transport from the endoplasmic reticulum to secretory granules. The modifications comprise different proteolytic cleavages and amino acid derivatizations. By constitutive secretion, the processing is less pronounced. The same prohormone may be expressed in several cell types that process the precursor in different ways. Awareness of cell-specific processing patterns is important for understanding the tumour synthesis of peptides and for appropriate diagnosis of peptide-producing tumours. These tumours comprise not only well-known neuroendocrine neoplasias. An increasing number of common carcinomas also expresses peptide hormone genes. However, the translation and post-translational processing in tumours are generally attenuated. Consequently, the expression is often functionally and clinically silent. A new diagnostic tool, processing-independent analysis (PIA), seems promising in quantitation of hormone gene expression at peptide level irrespective of the degree of processing. Studies of progastrin expression and processing in tumours illustrate the diagnostic superiority of PIA.

ISSN:1010-4283    

DOI:10.1159/000217833

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

We have established a model in which cellophane wrapping induces reiteration of the normal ontogeny of β-cell differentiation from ductal tissue. The secretion of insulin is physiologic and coordinated to the needs of the animal. Streptozotocin-induced diabetes in hamsters can be ‘cured’ at least half the time. There appears to be activation of growth factor(s) within the pancreas acting in an autocrine, paracrine or juxtacrine manner to induce ductal cell proliferation and differentiation into functioning β-cells. Given the results of our studies to date, it does not seem premature to envisage new approaches to the treatment of diabetes mellitus. Identification of the factory) which regulates islet cell proliferation and differentiation in our model may permit proto-undifferentiated cells and islets to be grown in culture. This concept could be extended to induce endocrine cell differentiation in vitro as well. Furthermore, islet cell growth factors could be used to provide ‘trophic support’ to islet transplants as a means of maintaining graft viability. There may also be greater scope for gene therapy when the growth factor(s) has been isolated, purified, sequenced a

ISSN:1010-4283    

DOI:10.1159/000217834

出版商:S. Karger AG    

年代:1993

数据来源: Karger