PubMed Health⌕ Search

Biomedical subjects

D R Ciocca

Publications and source records attributed to D R Ciocca.

63 records · Page 4Linked to original sources

Endocrinologic milieu and susceptibility of the rat mammary gland to carcinogenesis.

The incidence of DMBA-induced mammary carcinomas in Sprague-Dawley rats depends upon their previous reproductive histories. Young virgin rats (YV) are highly susceptible to the carcinogen, while old virgin rats (OV) are less susceptible, and parous rats (P) are resistant. The authors performed endocrinologic studies in these three groups of rats in order to determine whether the different susceptibility to carcinogenesis, according to the reproductive history, is or is not related to the hormonal milieu. The pituitary, the ovaries, the adrenals, and the mammary glands were processed for light microscopy. Pituitary prolactin (PRL), follicle-stimulating hormone, and luteinizing hormone cells were immunostained by peroxidase-antiperoxidase and quantitated with an image analyzer. Radioimmunoassays of serum and pituitary PRL and serum estradiol were also done. The results showed no differences in the hormonal milieu of YV, OV, and P rats at the time of carcinogen treatment. Several changes were observed after DMBA administration, the most conspicuous being 1) hyperplasia of pituitary PRL cells, 2) high serum PRL levels, 3) nodular hyperplasia of the adrenal cortex, 4) high serum estradiol levels, and 5) lack of adrenal necrosis in P rats and some OV rats. These modifications did not correlate with the degree of susceptibility of YV, OV, and P rats to carcinogenesis, supporting the concept of the importance of the mammary gland differentiation at the moment of carcinogen administration. (Am J Pathol 1982, 109:47-56).

9,10-Dimethyl-1,2-benzanthracene↗

Immunohistochemical detection of an estrogen-regulated protein by monoclonal antibodies.

It has been shown previously that estradiol regulates the synthesis of a Mr 24,000 cytosol protein in MCF-7 human breast cancer cells. This protein is an attractive probe to study the mechanisms of estrogen regulation in human breast cancer. We have produced monoclonal antibodies against the Mr 24,000 protein which show immunocytochemical localization in the cytoplasm of MCF-7 cells grown as solid tumors in nude mice. They do not react with normal mouse tissue or with MDA-MB-231 cells, an estrogen receptor-negative cell line. Moreover, the monoclonal antibodies react against certain human breast tumor biopsy samples. These data suggest that the monoclonal antibodies obtained will be useful to detect the estrogen-regulated protein by immunohistochemistry.

Antibodies, Monoclonal↗

Scanning electron microscopy of the cleft of the rat pituitary.

Scanning electron microscopy of the lining of the pituitary cleft was carried out in normal, lactating, castrated, adrenalectomized, and cyproterone-treated adult rats. Four cell types could be differentiated in the posterior wall in control and experimental animals: (1) cells with a smooth surface, (2) cells with microvilli located at the cellular borders, (3) ciliated cells, and (4) cells with evenly distributed microvilli. The anterior wall showed mainly cells with few microvilli located at their margins, and clusters of ciliated cells. In normal, and more frequently in experimental animals, the anterior wall showed shriveled cells, and variously sized cavities. Colloid appeared either as a network of finely granular material or as compact bodies adhering to the epithelial surface. These observations suggest that a compact component of the colloid is derived at least in part from degraded cells.

Adrenalectomy↗

Immunomorphologic lymph node changes in rats bearing experimental breast tumors.

In this paper regional lymph nodes draining tumors and also nonregional lymph nodes have been studied at the light- and electron-microscopic levels. These nodes were obtained from rats bearing long-evolving autochthonous breast cancers. They were compared with a control group of the same age. A morphometric quantitative analysis was done to evaluate immunologically competent cell populations. In the experimental group there were no differences between regional and distal lymph nodes in the tumor challenge. However, when the experimental group was compared with the control group, differences appeared. The changes involved were diminution of the paracortical area with stimulation of plasma cells in the medullary cords. Ultrastructurally, in lymph nodes of the experimental group there were lymphoblasts in the paracortex and germinal centers, suggesting active lymphopoiesis. In addition, many plasma cells showed morphologic evidence of involution or other alterations. It is suggested that regional and distal lymph nodes have similar morphologic behavior when the tumor grows for a long period of time, a finding that contributes to our knowledge of the systemic implications of the lymphatic system.

Animals↗

Comparative light- and electron-microscopical study of the normal adenohypophysis in the human.

The pars distalis of 1 girl and of 3 sexually mature women was studied. The glands were dissected out and fixed within a period of 30 min following death; in the aldehyde fixative, each gland was systematically divided into ten pieces. Before fixation in osmium tetroxide, each piece was again divided into several blocks. At least 60 blocks were obtained from each gland. Semi-thin sections obtained from all the blocks were stained and studied under the light microscope. Ultrathin sections were obtained from selected blocks. Under the light microscope, 6 types of secretory cells and 2 types of non-secretory cells were characterized. At the ultrastructural level, 7 types of granulated cells and 2 types of non-granulated cells were distinguished. The range of the granule size for each type of sectetory cell was determined by applying a mathematical model and a computer program that corrected the size distribution curve in such a way that only the diameter of the equatorial sections of the granules, that is the real granule sizes, was recorded. By comparing the observations made in the ultrastructural study with those performed in adjacent semi-thin sections it was possible to correlate the cell types characterized ultrastructurally with those distinguished under the light microscope. In addition, the study of the semi-thin sections made it possible to quantitatively analyze the different cell types, while the ultrastructural characteristics suggested the probable functional role of each of these cell types.

Cytoplasmic Granules↗

The pituitary cleft of the rat: an electron microscopic study.

The epithelium of the pituitary cleft and its colloid have been studied at the ultrastructural level in normal, adrenalectomized, castrated, dehydrated and lactating adult rats. Both control and experimental animals showed cells in different stages of degradation inside the cleft and mixed with the colloid. These exfoliated cells seems to have originated from the cleft's epithelium of the adjacent granular cells. In adrenalectomized and castrated rats the rostral epithelium of the cleft had large intercellular spaces that in some instances appeared to open directly into the cleft. Occasionally, the adenohypophysial canaliculi of the adrenalectomized rats were also seen connecting with the cleft. In lactating and castrated animals dark cells appeared more frequently in the rostral and caudal epithelium of the cleft. The results obtained suggest that the colloids is originated at least in part by involuted pituitary cells. There is also evidence that the follicular cavities of the Pars distalis and the cleft are continuous structures.

Adrenalectomy↗

Ultrastructure of the human pharyngeal hypophysis.

Four types of secretory cells have been distinguished in the human pharyngeal hypophysis. Type I cells contain granules of about 70-90 nm in diameter; type II cells are the most numerous and are loaded with granules ranging in size between 100 and 200 nm. In type III cells the size of the granules ranges between 150 and 250 nm in diameter. Type IV cells contain the largest secretory granules (250-400 nm). In addition, there is a type of cell lacking secretory granules and which has been regarded as interstitial cell (type V). The different cell types are arranged in clusters which, in turn, are surrounded by numerous blood capillaries. A few nerve fibres have been observed within the gland. These fibres make synaptoid contacts with type II cells. The ultrastructural analysis of the human phayngeal hypophysis strongly suggests that this formation is an endocrine gland with distinct characteristics and with a functional role probably different from that of the sellar hypophysis.

Blood Vessels↗

Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques.

Three hundred and one primary breast cancers from patients with tumor infiltrated lymph nodes were analyzed for the presence of HER-2/neu oncoprotein by two procedures: Western blot (WB) and immunohistochemistry (IHC). Overexpression of this protein was found by WB in 16.6% of the tumors, and by IHC in 16.3%. Concordance between the two methods was found in 95% of tumors (286/301). In 7 cases we found HER-2/neu by IHC but not by WB, while the opposite was found in the remaining 8 patients. This discrepancy was found mainly in samples with HER-2/neu values just above the cut points and were therefore close to the sensitivity limits of the procedures used here. This study helps to define the parameters that should be considered to evaluate the immunostaining for HER-2/neu as positive (i.e., membrane staining, IHC score of 2 or more). The results obtained by both techniques were correlated with several currently used prognostic factors. Higher HER-2/neu protein expression was found in tumors lacking estrogen or progesterone receptors, in tumors with high S-phase fraction and in patients with more than 3 positive lymph nodes. In contrast, no relationship was found between overexpression of this protein and tumor size, ploidy, or age of the patient. Patients with elevated HER-2/neu expression showed a significantly worse overall survival by both methods, IHC (p = 0.05) and WB (p = 0.001). In conclusion, there is very high agreement between IHC and WB when measuring expression of HER-2/neu and both techniques showed prognostic significance.

Biomarkers, Tumor↗

Effects of short-term tamoxifen administration in patients with invasive cervical carcinoma.

Cervical cancer is not considered a hormone-responsive tumor in spite of the presence of estrogen receptors (ER) and progesterone receptors (PgR) in some of them. Endocrine treatments have not achieved clinical responses, however, tamoxifen has been reported to induce PgR and to inhibit cell growth of many cervical carcinoma cell lines. In this study we investigated whether tamoxifen administration affects the histopathological characteristics of cervical cancer and the expression of ER, PgR, HER-2/neu and p53 protein. Nineteen patients with invasive cervical cancer free of previous treatments were studied. The triphenylethylene antiestrogen tamoxifen was given orally during 10 days (20 or 40 mg/day). Pre- and post-tamoxifen biopsies were evaluated using slides stained with hematoxylin and eosin and immunostained (ER, PgR, HER-2/neu, p53, PCNA, keratin, heat shock protein 27,000 daltons). Estrogen receptors were present in 37% and PgR in 16% of the biopsies from untreated patients. Only one case that was PgR-negative before tamoxifen administration showed weak PgR-positivity following antiestrogen administration. No obvious changes were observed in ER, HER-2/neu and p53 proteins. A statistically significant decrease in the number of mitotic figures was obtained in 16% (3/19) of the post-tamoxifen biopsies and two of them showed higher differentiation. The results showed that tamoxifen did not induce changes in estrogen-regulated proteins in cervical cancer. However, the data showed that certain cervical carcinomas had changes in their proliferation and differentiation levels following tamoxifen administration. These findings suggest that tamoxifen may affect some cervical cancer tissues by a hormone-independent mechanism(s).

Administration, Oral↗