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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progression to steroid insensitivity poses a major problem in therapy of breast cancer, but studies of the origin of steroid-insensitive cells have been few and have concentrated in any one system on the loss of response to only one steroid. Since both normal and tumour mammary cells have complex endocrine requirements, we wondered how different steroids might interact during loss of steroid sensitivity. Cloned cells from the androgen-responsive Shionogi 115 mouse mammary carcinoma respond in vitro to both androgens and glucocorticoids in terms of both cellular and molecular parameters but, following prolonged absence of any steroid, these cells become unresponsive. We show here that 2 steroids can interact to prevent the progression to steroid insensitivity since the S115 cells can be protected against any loss of response to either androgen or glucocorticoid with either steroid alone. Androgen protects against loss of glucocorticoid sensitivity and glucocorticoid protects against loss of androgen sensitivity. The clinical implications are discussed.
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PMID:Interaction of different steroid hormones during progression of tumour cells to steroid autonomy. 282 38

Principally, antiandrogens affect all androgen-dependent organs and functions as for instance accessory sexual glands, spermatogenesis, skin and skin appendages, libido and potency, male sexual differentiation, longitudinal bone growth and bone maturation. Pharmacologically, it is important to distinguish between the steroidal antiandrogens of the cyproterone acetate type and the nonsteroidal pure antiandrogens (flutamide, anandrone). For the clinical use of cyproterone acetate and similar antiandrogens in both men and women the three main properties are important: Cyproterone acetate is antiandrogenic, it is a quite potent progestogen and it is antigonadotrophic. Based on pharmacological and biochemical backgrounds cyproterone acetate is used in the following indications: Androgen mediated disorders of the skin such as acne, seborrhoea, hirsutism, alopecia, advanced prostatic carcinoma, precocious puberty and male hypersexuality. In order to avoid undesired systemic side effects local application of antiandrogens, e.g. of cyproterone acetate, has been tried several times. All these attempts have failed probably because insufficient concentration of the antiandrogen at the pilo sebaceous unit. 17 alpha-propylmesterolone is active when given topically (hamster ear model) and has no systemic antiandrogenic effects. This antiandrogen is highly lipophilic and does penetrate preferentially through the hair follicle as has been shown by autoradiography.
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PMID:Pharmacology of antiandrogens. 294 14

Androgen-dependent Shionogi carcinoma 115 (SC115) is an undifferentiated medullary carcinoma consisting of compact round cells. However, when host male DS mice were castrated 2 weeks after tumor transplantation, tumors composed of compact round cells, spindle-shaped cells and chondroid cells grew 4 weeks after castration. Compact round cells with desmosomes were arranged in solid nests and exhibited immunoreactivity for keratin protein. Spindle-shaped cells had prominent rough endoplasmic reticulum, and appeared to secrete collagen. Chondroid cells had the characteristics of chondrocytes. The light and electron microscopic features were highly suggestive of a transition from compact round cells to spindle-shaped cells, and from spindle-shaped cells to chondroid cells. The histology of this tumor thus suggests that SC115 cells are able to change into chondroid cells via spindle-shaped cells.
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PMID:Development of spindle-shaped cells and chondroid cells from androgen-dependent Shionogi carcinoma 115. A light and electron microscopic study. 306 8

The collagen production of androgen-responsive and -unresponsive Shionogi carcinoma 115 cells was investigated by culturing them in a medium with or without testosterone. Androgen-unresponsive cells were obtained by culturing a cloned androgen-responsive cell in a testosterone-free medium for 12 weeks. The collagen production of androgen-responsive cells slightly increased in the absence of testosterone, whereas testosterone did not affect the collagen production of androgen-unresponsive cells. Androgen-unresponsive cells produced 3-4 times more collagen than androgen-responsive cells. The major collagen produced by both androgen-responsive and - unresponsive cells migrated to the same position in sodium dodecylsulfate:polyacylamide gel electrophoresis. The present results indicate that the collagen production of androgen-responsive Shionogi carcinoma 115 cells increases with the loss of androgen responsiveness in culture.
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PMID:Increase in collagen production with loss of androgen responsiveness in cultured androgen-responsive Shionogi carcinoma 115 cells. 316 94

Ovarian epithelial carcinoma originates from the surface mesothelium. It is controversial whether these tumors possess steroidogenic enzymes, similar to malignancies of other ovarian cell types. This study reports aromatase enzymatic activity for three epithelial cell lines, OV1225, OV166, and 2774, established from patients with ovarian adenocarcinoma. Aneuploidy of the cells was demonstrated by flow cytometric DNA analyses which showed OV1225 tetraploid, OV166 near diploid, and 2774 triploid. Estrogen synthesis was confirmed by measurement of estradiol (6 to 11 pg/10(7) cells/24 h) by radioimmunoassay in extracts of conditioned medium. To directly assay aromatase enzymatic activity, intact cells were incubated with tritiated testosterone. Medium was extracted with organic solvent after addition of trace 14C-labeled 17 beta-estradiol and 14C-labeled estrone. Androgen was separated from estrogen by celite column chromatography. Estrogen was further purified by silica gel thin-layer chromatography and derivatization of separate products to acetates. Purity of compounds was confirmed by consistency of the 3H:14C ratio of acetylated product versus that of product recrystallized with authentic standard. Conversion of testosterone to estradiol proceeded with apparent Michaelis-Menten kinetics. The apparent Km was 4 microM, 15 microM, and 59 microM, and the Vmax was 20 pmol/h/mg of cell protein, 52 pmol/h/mg of cell protein, and 152 pmol/h/mg of cell protein for 2774, OV166, and OV1225, respectively. We conclude that at least a portion of ovarian adenocarcinoma possesses sufficient aromatase activity to convert ovarian stromal androgen to estrogen.
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PMID:Aromatization of testosterone by epithelial tumor cells cultured from patients with ovarian carcinoma. 318 66

The relative success with which the response of breast cancer to endocrine therapy can be predicted by assay of female sex steroid receptors has led to attempts to use measurement of androgen receptors in neoplastic prostate tissue for predicting the success of anti-androgen therapy in prostate cancer. Hitherto hopes have not been fulfilled. Androgen receptors are present in almost all prostate samples, but with inhomogeneous distribution. No relationship was found between androgen receptor levels in needle aspirate and prognosis in prostatic carcinoma. Receptors for oestrogen, progestin and prolactin were also studied for identification of possible prognostic indicators. Progestin receptors appear to be present in prostatic tissue. Lack of consensus regarding prostatic oestrogen and prolactin receptors is due partly to their low (if any) concentrations and partly to differing methodology and interpretation of results. Oestrogen, progestin and prolactin receptors seem to lack prognostic significance in prostatic cancer. These findings and the high initial response rate of prostatic carcinoma to endocrine therapy indicate that further studies should focus on elucidating how such tumours become hormone-independent.
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PMID:Hormone receptors in human prostate cancer. 328 96

Androgen withdrawal rarely if ever results in a cure of prostatic carcinoma. Thus, if the object of therapy is to cure rather than palliate, it is necessary for us to alter our strategem so as to trick the prostatic cancer cells into dying while sparing the host. Data has been presented that suggest that tumor cell heterogeneity and the preexistence of populations of cells resistant to androgen withdrawal are responsible for the failure of hormonal therapy. Additionally, the use of androgen withdrawal as a single mode of therapy may actually induce a more rapid emergence of cells resistant to chemotherapeutic intervention by increasing the genetic instability of the tumor population. Assuming that a tumor is composed of a heterogeneous population of cells and the institution of unimodal therapy will exert a destabilizing influence on the tumor, the logical therapy for disseminated disease would be multimodal therapy. Animal models suggest that the most effective therapy for disseminated disease would be a combination of androgen withdrawal and cytotoxic chemotherapy instituted as early as possible when the number of cells capable of division, stem cells, is at minimum. Whether or not early, sequential withdrawal, repletion, withdrawal of hormones to synchronize the tumor cell cycle and increase the growth fraction of the tumor will have any beneficial effects remains to be determined. This form of androgen priming should be safer than in patients with hormonally refractive disease since LHRH initially stimulates testosterone production without any significant irreversible sequelae. Although the above therapeutic logarithms may prove to have no therapeutic advantage over androgen withdrawal alone, it certainly seems a good starting point for a change in our therapeutic concepts. Only by adopting new approaches based upon what we know about tumor biology can we hope to impact on the current dismal prognosis.
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PMID:Management of primary stage D prostatic cancer. 330 94

The transplantable, hormone-dependent, human prostatic carcinoma PC-82 was used as an in vivo model for monitoring the proliferative fraction of tumor cells under the influence of androgen withdrawal and resubstitution. The number of cycling cells was assessed by means of an immunoperoxidase method and monoclonal antibody Ki-67. The number of Ki-67-positive tumor cells dropped from an average of 17% in androgen-supplemented, tumor-bearing female BALB/c mice to approximately 1.0% within 10 days after removal of the testosterone (T) implant. A similar effect was noted after castration of tumor-bearing male BALB/c mice. Androgen resubstitution after a 10-day period of T deprivation resulted in a rise in the tumor cell proliferation index to 20% within 4 days. The same pattern of response to androgen depletion and resubstitution also was found when the number of cycling cells in S phase was assessed by the 5-bromo-2'-deoxyuridine incorporation technique. Administration of supraphysiologic doses of T in intact male mice did not lead to an increase in the number of Ki-67-stained nuclei. Androgen manipulation did not influence the immunohistochemically assessed expression of prostatic acid phosphatase and prostate-specific antigen. The rapid effect of hormone deprivation and resubstitution in the tumor cell proliferation fraction suggests that monoclonal antibody Ki-67 can be used for monitoring the short-term effects of hormonal treatment of prostatic cancer.
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PMID:Determination of the proliferative fraction of a transplantable, hormone-dependent, human prostatic carcinoma (PC-82) by monoclonal antibody Ki-67: potential application for hormone therapy monitoring. 332 Apr 49

Androgen-responsive (SC-3) and -unresponsive (SC-4) cloned cell lines in culture were established from an androgen-responsive mouse mammary tumor, Shionogi carcinoma 115. By using a serum-free medium [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], characteristics of androgen-induced and autonomous growth factors (GFs) were examined. Serum-free conditioned medium (CM) obtained from testosterone-stimulated (+T) SC-3 cells had remarkable growth-stimulatory effects on both SC-3 and SC-4 cells. To examine the molecular characteristics of GF, CM(+T) from SC-3 was fractioned by heparin-Sepharose affinity chromatography; two peaks, eluted at 0.5 M (GF-low) and 1.1 M NaCl (GF-high) were identified. GF-high had the ability to stimulate growth with a morphological change of both SC-3 and SC-4 cells; the GF-high was not found in CM from T-unstimulated (-T) SC-3 or CM from SC-4. GF-low stimulated the growth without the morphological change of only SC-4 cells; the GF-low was also present in CM(-T) from SC-3 and CM from SC-4. The present findings demonstrate that T-induced autocrine GF-high secreted from SC-3 cells can also stimulate the growth of progressed unresponsive SC-4 cells in a paracrine mechanism and that autonomous GF-low secreted from both SC-3 and SC-4 cells can stimulate the growth of only SC-4 cells.
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PMID:Growth-stimulatory effect of androgen-induced autocrine growth factor(s) secreted from Shionogi carcinoma 115 cells on androgen-unresponsive cancer cells in a paracrine mechanism. 340 25

This paper is the first part of a series of three describing a number of observations made on the PC-82 human prostatic carcinoma, xenografted into nude mice. The previously described androgen-dependence, one of the main properties of this tumor, has been the subject of subsequent studies. The impact of hormonal manipulation on the growth of the tumor and on plasma and tissue concentrations of androgens is discussed in this first part of the series. The great variability of plasma testosterone (T) levels in intact male mice (range: 1-90 nmol/liter) has been levelled out by the use of T-containing Silastic implants, resulting in levels ranging from 18 to 35 nmol/liter. Moreover, this route of administration also facilitated hormonal manipulation of tumor bearing mice. Androgen withdrawal from male mice with growing PC-82 tumors caused 80% tumor regression at ten weeks after androgen deprivation; the decline of the tumor volume followed a biphasic course. Delayed androgen substitution in castrated male mice grafted with PC-82 30 days before resulted in growth of the tumor tissue. This indicates that cells do not die and keep the capability to respond to androgens. It was concluded that the growth of the PC-82 tumor is not compatible with plasma T levels lower than 1 nmol/liter. Variable concentrations of endogenous T and dihydrotestosterone (DHT) were detected in total homogenates of PC-82 tumor tissue. Androgen withdrawal from T-implanted, tumor-bearing female mice caused a rapid reduction (90% within one day) of the tissue-T and a slower decline (up to 90% within seven to ten days) of tissue-DHT concentrations.
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PMID:Transplantable human prostatic carcinoma (PC-82) in athymic nude mice: I. Hormone dependence and the concentration of androgens in plasma and tumor tissue. 367 Nov 91


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