Anti-tumour effects of elatol, a marine derivative compound obtained from red algae Laurencia microcladia

Objectives This paper aims to evaluate the anti‐tumour properties of elatol, a compound (sesquiterpene) isolated from algae Laurencia microcladia. Methods In‐vitro and in‐vivo anti‐tumour properties of elatol were investigated using: MTT assays to assess the cytotoxic effects; flow cytometry analysis to examine the cell cycle and apoptosis; Western blot analysis for determination of the expression of cell cycle and apoptosis proteins; and study of in‐vivo tumour growth in mice (C57Bl6 mice bearing B16F10 cells). Key findings Elatol exhibited a cytotoxic effect, at least in part, by inducing cell cycle arrest in the G₁ and the sub‐G₁ phases, leading cells to apoptosis. Western blot analysis demonstrated that elatol reduced the expression of cyclin‐D1, cyclin‐E, cyclin‐dependent kinase (cdk)2 and cdk4. A decrease in bcl‐xl and an increase in bak, caspase‐9 and p53 expression was also observed. In the in‐vivo experiment, treatment with elatol was able to reduce tumour growth in C57Bl6 mice. Conclusions Elatol promotes a delay in the cell cycle, probably in the G₁/S transition, activating the apoptotic process and this could be responsible, at least in part, for the in‐vivo effects observed. Taken together, the in‐vitro and in‐vivo experiments suggested that elatol has anti‐tumour properties. Further studies should be conducted to clarify the mechanism of action.     

Hormone und Karzinogenese beim Mammakarzinom

Background

Epidemiological studies have shown that the pathogenesis of breast cancer is multifactorial. Since women have a lifetime risk of 10?% to develop breast cancer, it is one of the most important female malignancies.

The significance of estrogen exposure

The hypothesis that endogenous or exogenous estrogen influences the genesis of breast cancer was first formulated in the late 1890s. The use of hormone replacement therapy is one of the most controversially discussed topics in gynecology. The present article provides a short overview of the principles of hormone replacement therapy in order to then focus on the carcinogenesis of breast cancer more closely, and discusses the particular relevance of the Women’s Health Initiative (WHI) study, despite limitations in the study design.

The role of prolactin

The influence of high serum prolactin on the development of breast cancer needs to be evaluated in further studies.     

The effect of scene articulation on transparent layer constancy

In this article, we examine the influence of scene articulation on transparent layer constancy. We argue that the term articulation may be understood as an aspect of the more general concept naturalness of a stimulus that relates to the degree of enrichment compared with a minimal stimulus and to the extent to which a stimulus contains regularities that are typically found in natural scenes. We conducted two matching experiments, in which we used strongly reduced scenes and operationalized articulation by the number of background reflectances (numerosity). The results of the first experiment show that higher numerosity actually leads to an increase in transparent layer constancy when reflectances are randomly drawn from a fixed population. However, this advantage disappears if the spatial mean and the variation of the subset colors are controlled as in our second experiment. Furthermore, our results suggest that the mechanism underlying transparent layer constancy leads to a rather stable compromise between two matching criteria, namely, proximal identity and constant filter properties according to our perceptual model. For filters with an additive component, which appear more or less hazy, we observed improved recovered filter properties and correspondingly higher degrees of transparent layer constancy, suggesting an additional mechanism in this type of filter.     

Zur Kenntniss der Ursache der secundären Veränderungen beim musculären Schiefhalse

Ohne Zusammenfassung     

Hysterie und Epilepsie

Ohne ZusammenfassungNach einem in der Sitzung der Berliner Gesellschaft für Psychiatrie und Nervenheilkunde vom 9. März 1903 gehaltenen Vortrage.     

In vivo induction of terminal differentiation of malignant myelopoietic progenitor cells by CSF-inducing biological response modifiers

We have investigated the mechanisms by which colony-stimulating factor (CSF)-inducing biological response modifiers (BRM) may have beneficial effects on tumor-bearing hosts undergoing anti-tumor therapy. First, we have documented that treatment of mice with the chemically defined BRM maleic anhydride divinyl ether copolymer (MVE-2), which induces CSF secretion by macrophages (M phi) and bone marrow cells (BMC), significantly increased growth and differentiation of normal myelopoietic cells and counteracted the myelosuppressive effects of cyclophosphamide (CY). Second, we established that MVE-2 may exert CSF- mediated antitumor effects on certain leukemic tumor cells. Serum from mice pretreated in vivo with MVE-2, which contained CSF, induced terminal differentiation of cloned tumor cells from the CSF responsive WEHI-3B D+ subline in vitro, but not from the WEHI-3B D- subline, which is unresponsive to CSF. In vivo experiments showed that treatment of mice bearing the WEHI-3B D+ tumor first with CY and three days later with the CSF inducer MVE-2, significantly increased their survival time and rendered 20% to 50% of the tumor-bearing mice disease free. No such effects were obtained in mice bearing the WEHI-3B D- tumor. Thus, the induction of CSF or other differentiation factors by some BRMs may result in therapeutic effects against certain leukemias based on at least two distinct mechanisms: In addition to their restorative effects on normal bone marrow functions, CSF-inducing BRMs may also prevent further leukemogenesis by induction of terminal differentiation of leukemic cells.     

Identification of fragments of proximal and distal tubular cells in the urine of patients under cytostatic treatment by immunoelectron microscopy with monoclonal antibodies

In an attempt to identify the origin of cellular fragments released in the urine of patients treated with potentially nephrotoxic drugs such as cytostatics, two monoclonal antibodies were applied: monoclonal antibody PM II 9 C2, directed against an antigen in distal tubular cells; and monoclonal antibody PM II 39 H11 specific for an antigen in proximal tubular cells. The specificities of both monoclonal antibodies were elaborated in the indirect as well as in the direct immunofluorescence technique. Both antibodies were then used to identify cellular fragments obtained from the urine of patients treated with cytostatic drugs by ultracentrifugation. By application of the indirect immunogold method, it was shown that material of proximal as well as distal tubular origin was shed by the damaged cells. Whereas the proximal tubular antigenic epitope recognized by PM II 39 H11 was always found in large irregular complexes of debris-containing vesicles, the distal tubular antigenic epitope recognized by PM II 9 C2 was always found associated with filament-like regular structures. This is the first report in which excretion of components of distal tubular cells is demonstrated as a consequence of the nephrotoxic side effects of cytostatic treatment. With the help of monoclonal antibodies, it has now become possible to identify and to investigate the damage inflicted on the distal part of the tubule system in addition to the well-documented proximal tubular damage.     

Kidney-derived urinary antigens assayed with monoclonal antibodies for the detection of renal damage

For the quantitation of kidney-derived Urinary Antigens (UA) monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron were applied in sandwich ELISA. Antigen excretion was measured in the urine of healthy individuals, patients suffering from various diseases, kidney transplant recipients, and healthy volunteers receiving therapeutic doses of antibiotic drugs. In healthy individuals, in patients with diseases primarily affecting the glomerulus, and in inactive phases of chronic diseases antigen excretion was low. Toxic drug effects enhanced antigenuria. Excretion of some or all of the antigens always indicated tubular alterations. The tests thus provide information on location and extent of acute primary tubular damage.