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Biomedical subjects

M Peterlik

Publications and source records attributed to M Peterlik.

119 records · Page 7Linked to original sources

Inhibitory effect of amylin on basal and parathyroid hormone-stimulated bone resorption in cultured neonatal mouse calvaria.

Amylin is a secretory product of pancreatic beta-cells which shares major sequence homology with calcitonin gene-related peptide. In neonatal mouse calvaria maintained in organ culture for 72 h, amylin inhibited basal (i.e., unstimulated) resorption in medium concentrations above 2.5 x 10(-9) M. In addition, amylin (> or = 1.0 x 10(-7) M) in a calcitonin-like fashion transiently inhibited bone resorption induced by 1.0 x 10(-8) M PTH ("escape phenomenon"). Pretreatment of calvarial bones with amylin (1.0 x 10(-8) - 1.0 x 10(-6) M) for 72 h attenuated the subsequent response to 1.0 x 10(-8) M PTH. Changes in location and appearance of osteoclasts in amylin-treated bones, as visualized by light microscopy, suggest that amylin inhibits bone resorption by causing a loss of specialized contact zones to the mineralized matrix in resorbing osteoclasts, and in addition, by preventing retraction of osteoblasts from the mineralized surface which impedes attachment of osteoclasts thereon.

Amyloid↗

25-Hydroxyvitamin D(3)-1alpha-hydroxylase and vitamin D receptor gene expression in human colonic mucosa is elevated during early cancerogenesis.

Human colorectal cancer cells not only express the nuclear vitamin D receptor (VDR) but are also endowed with 25-hydroxy-vitamin D(3)-1alpha-hydroxylase activity and therefore are able to produce the specific ligand for the VDR, the hormonally active steroid 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)). In the present study we show by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) as well as by Western blotting and immunohistochemical methods, that in human large intestinal carcinomas expression of the genes encoding the 25-(OH)D(3)-1alpha-hydroxylase as well as the VDR increases in parallel with ongoing dedifferentiation in the early phase of cancerogenesis, whereas in poorly differentiated late stage carcinomas only low levels of the respective mRNAs can be detected. This indicates that, through up-regulation of this intrinsic 1alpha,25(OH)(2)D(3)/VDR system which mediates the anti-mitotic effects of the steroid hormone, colorectal cancer cells are apparently able to increase their potential for an autocrine counter-regulatory response to neoplastic cell growth, particularly in the early stages of malignancy.

Adenocarcinoma↗

Aging, neuroendocrine function, and osteoporosis.

Osteoporosis may occur in both women and men. Osteoporosis is defined as age-related involutional bone loss that exceeds that observed in the normal population of the same age and sex. The hallmark of the disease is a reduction in mineralized bone matrix. Osteoporosis is a multifactorial disease and can be considered the result of impaired coordination of bone remodeling ("resorption/formation coupling"). This review describes the role of systemic hormones and local acting mediators, including neuropeptides and neurotransmitters, in the control of bone turnover. Furthermore the significance of age-related (neuro)endocrine dysfunction for bone remodeling and consequently for development of osteoporosis is discussed.

Aging↗

Interspecies comparative pathology of colorectal neoplasms: relevance for treatment.

Comparative pathology may serve as a practical tool for therapy by comparison of normal and abnormal structures of the digestive tract in animals and men. A better understanding of colon cancer as the most common solid neoplasm after lung cancer in the industrialized world is sought. In the so-called developed nations and in animals colon cancer is less frequent. The pathogenesis of colon cancer involves environmental and genetic factors. Several types of colorectal cancer can be discerned and the species distribution ranges from invertebrates to man. Colorectal neoplastic progression is species-specific. An intraspecies-specific comparison of large bowel cancer is also valuable. Alteration of signal transduction pathways and somatic mutations of oncogenes are described, as well as the occurrence, research and current treatment. Metastasis of neoplasms of the colon and of the rectum can be studied by intraspecies-specific comparison. Sections of this review deal with vitamin D and cancer and close with present therapies for colorectal cancer.

Animals↗

Vitamin D receptor and cytokeratin expression may be progression indicators in human colon cancer.

Epidemiological data suggest the protective role of vitamin D against the development of colorectal carcinoma in man. This could be due to the anti-mitogenic effect of the steroid hormone on human colon carcinoma cells which is mediated by a specific nuclear vitamin D receptor (VDR). Western blot analysis showed that VDR expression increases during the transition from normal mucosa to polyps and later to pT3 tumors. In later stages, however, VDR is dramatically reduced. Cytokeratin 20, which was monitored as a differentiation marker, decreases in parallel with advancing proliferation and disappears from "normal" mucosa adjacent to later stage carcinoma. Interestingly, VDR density was conspicuously higher in all tumors tested when compared to adjacent "normal" tissue. This suggest that, up to a certain degree of dedifferentiation, malignant colonocytes can upregulate the VDR, probably as a counteractive measure in response to tumor cell growth, but that this ability is finally lost in highly undifferentiated carcinoma cells.

Cell Division↗