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1.
Nat Commun ; 9(1): 2433, 2018 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-29970895

RESUMEN

In modern human cultures where social hierarchies are ubiquitous, people typically signal their hierarchical position through consumption of positional goods-goods that convey one's social position, such as luxury products. Building on animal research and early correlational human studies linking the sex steroid hormone testosterone with hierarchical social interactions, we investigate the influence of testosterone on men's preferences for positional goods. Using a placebo-controlled experiment (N = 243) to measure individuals' desire for status brands and products, we find that administering testosterone increases men's preference for status brands, compared to brands of similar perceived quality but lower perceived status. Furthermore, testosterone increases positive attitudes toward positional goods when they are described as status-enhancing, but not when they are described as power-enhancing or high in quality. Our results provide novel causal evidence for the biological roots of men's preferences for status, bridging decades of animal behavioral studies with contemporary consumer research.


Asunto(s)
Comportamiento del Consumidor , Jerarquia Social , Masculinidad , Clase Social , Testosterona/fisiología , Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
2.
Neurol Sci ; 34 Suppl 1: S83-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23695052

RESUMEN

Oral contraceptive-induced menstrual migraine (OCMM) is a particularly severe form of migraine triggered by the cyclic hormone withdrawal. To review the efficacy of frovatriptan vs. other triptans, in the acute treatment of OCMM through a pooled analysis of three individual randomized Italian studies. With or without aura migraineurs were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, the subset of 35 of the 280 women of the intention-to-treat population taking combined oral contraceptives and experiencing a migraine attack during the withdrawal phase, were analyzed. The proportion of pain free and pain relief at 2 h were 25 and 51 % with frovatriptan and 28 and 48 % with comparators (p = NS). At 24 h, 71 and 83 % of frovatriptan-treated patients and 60 and 76 % of comparator-treated patients were pain free (p < 0.05 between treatments) and had pain relief (p = NS), respectively. Relapse at 24 and 48 h was significantly (p < 0.05) lower with frovatriptan (17 and 21 %) than with the comparators (27 and 31 %). Our results suggest that, due to its sustained antimigraine effect, frovatriptan may be particularly suitable for the management of OCMM than other triptans.


Asunto(s)
Carbazoles/uso terapéutico , Anticonceptivos Hormonales Orales/efectos adversos , Trastornos Migrañosos/tratamiento farmacológico , Síndrome Premenstrual/tratamiento farmacológico , Agonistas de Receptores de Serotonina/uso terapéutico , Triptaminas/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Menstruación , Trastornos Migrañosos/inducido químicamente , Estudios Multicéntricos como Asunto , Oxazolidinonas/uso terapéutico , Síndrome Premenstrual/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto , Triazoles/uso terapéutico
3.
Neurol Sci ; 34 Suppl 1: S87-91, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23695053

RESUMEN

Migraine might be associated with high blood pressure (BP), which can cause more severe and more difficult to treat forms of headache. To evaluate the efficacy of frovatriptan and other triptans in the acute treatment of migraine, in patients classified according to a history of arterial hypertension, enrolled in three randomized, double-blind, crossover, Italian studies. Migraineurs with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in 3 months with the first treatment, patients switched to the alternate treatment for the next 3 months. The present analysis assessed triptan efficacy in 60 subjects with a history of treated or untreated essential arterial hypertension (HT) and in 286 normotensive (NT) subjects. During the study, migraine attacks with aura were significantly more prevalent in HT subjects (21 vs. 13 % NT, p < 0.001). The proportion of pain free at 2 h did not significantly differ between HTs and NTs for either frovatriptan (25 vs. 26 %) or the comparators (33 vs. 32 %). Pain relief was achieved in significantly (p < 0.05) fewer episodes in HT subjects for both frovatriptan (41 vs. 52 % NT) and the comparators (48 vs. 58 %). Relapses at 48 h were similarly low in HTs and NTs with frovatriptan (29 vs. 31 %), while they were significantly (p < 0.05) larger in HTs (62 %) than in NTs (44 %) with comparators. No BP or heart rate increment was observed during the study in HT subjects. No difference in tolerability was reported between HTs and NTs. In conclusion, HT individuals tend to be less responsive than NT migraineurs to triptan therapy. However, frovatriptan, in contrast to other triptans, seems to have a sustained antimigraine effect in both HT and NT patients.


Asunto(s)
Carbazoles/uso terapéutico , Hipertensión/complicaciones , Trastornos Migrañosos/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Agonistas de Receptores de Serotonina/uso terapéutico , Triptaminas/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Humanos , Trastornos Migrañosos/etiología , Oxazolidinonas/uso terapéutico , Triazoles/uso terapéutico
4.
Allergy Asthma Proc ; 30 Suppl 1: S37-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19679004

RESUMEN

In childhood, recurrent airway infections are the most common cause for medical visits and hospitalizations. Their economic impact is considerable and their treatment accounts for a substantial quota of the health care budget. Despite documented efficacy and safety, ribosomal bacterial vaccine and membrane fraction use is still limited by being prevalently considered for prevention rather than treatment. The objective of this study was to analyze the economic benefit achieved with ribosomal immunotherapy. A review was performed of available literature data on economic parameters. Pharmacoeconomic studies published during the past few years showed how the use of ribosome component immune modulator is capable of reducing expenditure associated with treatment of recurrent respiratory infection and allows achievement of substantial savings in terms of cost, time, and loss of productivity. The initial cost of prevention in patients suffering from chronic respiratory infections is offset by a subsequent saving arising from less recurrence of disease. Direct management costs such as therapy courses, medical visits, medical exams, hospitalizations, etc., and indirect costs such as absence from school and work are not routinely considered by primary care physicians.


Asunto(s)
Antígenos Bacterianos/economía , Costo de Enfermedad , Costos de la Atención en Salud , Factores Inmunológicos/economía , Infecciones del Sistema Respiratorio/economía , Antígenos Bacterianos/uso terapéutico , Análisis Costo-Beneficio , Humanos , Factores Inmunológicos/uso terapéutico , Infecciones del Sistema Respiratorio/prevención & control , Prevención Secundaria
5.
Percept Mot Skills ; 91(2): 391-401, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11065298

RESUMEN

This study investigated in 40 young university women the possible relationships between levels of testosterone and specific measures of overall self-confidence and self-confidence in approaching mathematics. Correlations of -.43 and -.49 with each measure of self-confidence, respectively, and level of testosterone were found in the portion of the sample displaying normal ovulatory function. There was no correlation (r=.02) between the measures of mathematics and overall self-confidence. 19 women did not display normal ovulatory function. The only significant result for the full sample was a significant correlation of -.73 between scores on the Bem Sex Role Inventory Masculinity and overall self-confidence. The reasons for the high anovulatory percentage are not clear, nor are the associations which anovulation might have with either hormonal levels or the personality characteristics in question.


Asunto(s)
Identidad de Género , Matemática , Solución de Problemas/fisiología , Saliva/metabolismo , Autoimagen , Estereotipo , Testosterona/metabolismo , Adolescente , Adulto , Anovulación/fisiopatología , Anovulación/psicología , Femenino , Humanos , Estudiantes/psicología
6.
Proc Soc Exp Biol Med ; 217(3): 369-78, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9492350

RESUMEN

In this study we report on the content and bioactivity of plant (phyto) estrogens and progestins in various foods, herbs, and spices, before and after human consumption. Over 150 herbs traditionally used by herbalists for treating a variety of health problems were extracted and tested for their relative capacity to compete with estradiol and progesterone binding to intracellular receptors for progesterone (PR) and estradiol (ER) in intact human breast cancer cells. The six highest ER-binding herbs that are commonly consumed were soy, licorice, red clover, thyme, tumeric, hops, and verbena. The six highest PR-binding herbs and spices commonly consumed were oregano, verbena, tumeric, thyme, red clover and damiana. Some of the herbs and spices found to contain high phytoestrogens and phytoprogestins were further tested for bioactivity based on their ability to regulate cell growth rate in ER (+) and ER (-) breast cancer cell lines and to induce or inhibit the synthesis of alkaline phosphatase, an end product of progesterone action, in PR (+) cells. In general, we found that ER-binding herbal extracts were agonists, much like estradiol, whereas PR-binding extracts, were neutral or antagonists. The bioavailability of phytoestrogens and phytoprogestins in vivo were studied by quantitating the ER-binding and PR-binding capacity of saliva following consumption of soy milk, exogenous progesterone, medroxyprogesterone acetate, or wild mexican yam products containing diosgenin. Soy milk caused a dramatic increase in saliva ER-binding components without a concomitant rise in estradiol. Consumption of PR-binding herbs increased the progestin activity of saliva, but there were marked differences in bioactivity. In summary, we have demonstrated that many of the commonly consumed foods, herbs, and spices contain phytoestrogens and phytoprogestins that act as agonists and antagonists in vivo.


Asunto(s)
Estrógenos no Esteroides/análisis , Análisis de los Alimentos , Isoflavonas , Plantas Medicinales/química , Progestinas/análisis , Especias/análisis , Fosfatasa Alcalina/metabolismo , División Celular/efectos de los fármacos , Humanos , Fitoestrógenos , Extractos Vegetales/farmacología , Preparaciones de Plantas , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Saliva/química , Células Tumorales Cultivadas
7.
Ethn Dis ; 7(2): 137-49, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9386954

RESUMEN

We assessed distributions of breast cancer prognostic biomarkers by race/ethnicity and socioeconomic position among paraffin-embedded tumor biopsy specimens from 135 US women (48 white women, 44 black women, 43 Asian women) diagnosed with breast cancer between 1966 and 1990. No racial/ethnic or socioeconomic differences in distributions were observed for tumor stage, lymph node involvement, estrogen, progesterone, and epidermal growth factor receptors, oncogenes such as Her2/neu and p53, cytoplasmic proteins cathepsin-D and ps2, and two indices of cell growth, Ki67 and DNA ploidy, adjusting for age at diagnosis, menopausal status, place of birth and, for racial/ethnic comparisons, working class composition of census block-group at diagnosis. Black and Asian women, however, were 3.5 times (95% confidence interval [CI] = 1.2, 10.1) and 3.7 times (95% CI = 1.3, 10.6), respectively more likely than white women to have a tumor size of > or = 20 mm, and Asian women were 3.4 times (95% CI = 1.1, 10.4) more likely than black women to be positive for androgen receptor, adjusting for these same factors. No differences in distributions by socioeconomic position were observed for these latter two tumor characteristics. These data suggest that racial/ethnic and socioeconomic disparities in breast cancer survival are unlikely to be explained solely by differential distributions of molecular breast cancer prognostic biomarkers.


Asunto(s)
Pueblo Asiatico , Asiático , Población Negra , Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Población Blanca , Biomarcadores/sangre , Neoplasias de la Mama/sangre , Intervalos de Confianza , Femenino , Humanos , Oportunidad Relativa , Pronóstico , Clase Social , Factores Socioeconómicos , Análisis de Supervivencia
8.
Environ Health Perspect ; 105 Suppl 3: 637-45, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9168008

RESUMEN

We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods, herbs, and spices and in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans. Results show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked differences in their ability to induce end products of estrogen action and to regulate cell proliferation. All of the different classes of estrogens stimulated cell proliferation at concentrations that half-saturated ER, but only some classes were able to induce estrogen-regulated end products. Genistein, a common phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its effects on cell proliferation and ability to induce estrogen-regulated end products. Moreover, we found that many of the foods, herbs, and spices commonly consumed by humans contain significant amounts of phytoestrogens, and consumption of soy milk, a phytoestrogen-rich food, markedly increases the levels of phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet high in phytoestrogens would significantly reduce the binding of weak xenoestrogens to ER in target tissues in vivo.


Asunto(s)
Neoplasias de la Mama/etiología , Congéneres del Estradiol/toxicidad , Estrógenos no Esteroides/toxicidad , Estrógenos/toxicidad , Isoflavonas , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , División Celular/efectos de los fármacos , DDT/metabolismo , DDT/toxicidad , Dieta , Salud Ambiental , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Congéneres del Estradiol/metabolismo , Estrógenos/metabolismo , Estrógenos no Esteroides/metabolismo , Estrógenos no Esteroides/farmacología , Femenino , Análisis de los Alimentos , Humanos , Neoplasias Hormono-Dependientes/etiología , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Hormono-Dependientes/patología , Fitoestrógenos , Preparaciones de Plantas , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Saliva/metabolismo , Células Tumorales Cultivadas
9.
Nutr Cancer ; 27(1): 31-40, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-8970179

RESUMEN

Experimental and epidemiologic studies support the view that soyfoods prevent cancer as well as diseases and symptoms associated with estrogen deficiency. Recent research suggests that the isoflavonoid genistein, a phytoestrogen found in abundance in soyfoods, may be one of the principal molecular components responsible for these health benefits. In this study we investigated the effects of a broad physiologically relevant concentration range of genistein on estrogen receptor (ER) binding, induction of the estrogen-regulated antigen pS2, and cell proliferation rate in ER(+) and ER(-) human breast cancer cells grown in vitro. Dose response to genistein was compared with that of estradiol, tamoxifen, and several other structurally similar iso- and bioflavonoids (e.g., equol, kaempferol, and quercetin). Our results revealed that genistein has potent estrogen agonist and cell growth-inhibitory actions over a physiologically achievable concentration range (10 nM-20 microM). Other flavonoids over the same concentration range were good estrogen agonists and poor cell growth inhibitors (equol) or poor estrogen agonists and potent growth inhibitors (kaempferol and quercetin). The growth-inhibitory actions of flavonoids were distinctly different from those of triphenyl antiestrogens like tamoxifen. In summary, our results reveal that genistein is unique among the flavonoids tested, in that it has potent estrogen agonist and cell growth-inhibitory actions over a physiologically relevant concentration range.


Asunto(s)
Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Estrógenos no Esteroides/análisis , Estrógenos no Esteroides/farmacología , Flavonoides/análisis , Flavonoides/farmacología , Isoflavonas/análisis , Isoflavonas/farmacología , Quempferoles , Anticarcinógenos/farmacología , Mama/citología , Mama/efectos de los fármacos , Mama/fisiología , Neoplasias de la Mama/fisiopatología , División Celular/efectos de los fármacos , División Celular/fisiología , Cromanos/farmacología , ADN de Neoplasias/análisis , Relación Dosis-Respuesta a Droga , Células Epiteliales , Epitelio/efectos de los fármacos , Epitelio/fisiología , Equol , Estradiol/farmacología , Antagonistas de Estrógenos/farmacología , Estrógenos no Esteroides/metabolismo , Femenino , Flavonoides/metabolismo , Genisteína , Humanos , Isoflavonas/metabolismo , Fitoestrógenos , Preparaciones de Plantas , Unión Proteica , Quercetina/análogos & derivados , Quercetina/farmacología , Receptores de Estrógenos/análisis , Receptores de Estrógenos/metabolismo , Tamoxifeno/análogos & derivados , Tamoxifeno/farmacología , Células Tumorales Cultivadas
10.
Chem Biol ; 2(1): 45-51, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9383402

RESUMEN

BACKGROUND: Compounds that either inhibit or induce an estrogen response in vivo are important as potential drugs and biochemical tools. Non-steroidal stilbene analogs such as tamoxifen are known to function as both estrogen agonists and antagonists depending upon the analog structure. This family of compounds is amenable to parallel-manifold synthesis because stilbene analogs are easily synthesized using a single-step olefination reaction. RESULTS: We have prepared a small 23-component hydroxystilbene library using a solid phase synthesis approach. The library was screened for estrogenic and antiestrogenic activity using a cell-based bioassay that measures estrogen receptor-mediated transcription of a reporter gene. Three of the analogs proved to have dose-dependent estrogenic activity with EC50 values between 5 microM and 15 microM. Further characterization of the hydroxystilbene-mediated estrogenic activity suggests that the agonist activity results from direct binding to the steroid site on the estrogen receptor with IC50 values of 1-10 microM. CONCLUSIONS: The results of this study show that classic olefination chemistry can be adapted to a solid-phase format for parallel synthesis of analog libraries. Although yields varied for the individual analogs, sufficient quantity of pure material was obtained directly from the resin for structural characterization and biological evaluation. This study further validates solid-phase organic synthesis as a useful approach for rapid parallel-manifold library synthesis to augment both lead compound discovery and optimization.


Asunto(s)
Antagonistas de Estrógenos/química , Antagonistas de Estrógenos/farmacología , Estilbenos/química , Estilbenos/farmacología , Unión Competitiva/efectos de los fármacos , Bioensayo , Línea Celular , Relación Dosis-Respuesta a Droga , Electroporación , Estradiol/metabolismo , Antagonistas de Estrógenos/síntesis química , Humanos , Receptores de Estrógenos/antagonistas & inhibidores , Estilbenos/síntesis química
11.
Ann Oncol ; 5(4): 329-36, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8075029

RESUMEN

BACKGROUND: The prognostic significance of Cathepsin D and optimal methodologies to measure Cathepsin D in breast cancers are controversial. PATIENTS AND METHODS: Quantitative (immunoradiometric) and semiquantitative (immunohistochemical) assays for Cathepsin D expression were compared using 25 breast carcinomas. Immunohistochemical Cathepsin D results were derived using 3 different anti-Cathepsin D antibodies and significant associations between immunohistochemical and radiometric Cathepsin D data were observed for each reagent. Immunohistochemical analysis of Cathepsin D expression was performed on nearly 500 fixed-embedded archival breast cancers with long-term patient follow-up using 2 anti-Cathepsin D antibodies (CDR2-11/23, IC11). RESULTS: The immunohistochemical reagents recognized generally overlapping subsets of Cathepsin D positive tumors (correlation co-efficient 0.54; p = 0.00016). Correlations between Cathepsin D data and clinical, histologic or biologic features differed for each antibody. For the node-negative patient subset, Cathepsin D immunopositivity correlated with erbB-2 and stress-response protein 27 overexpression but not survival. Cathepsin D positivity was associated with subsequent distant metastasis and estrogen receptor positivity in node positive patients. Univariate analysis of all patients suggested that Cathepsin D immunopositivity may be predictive of a reduced metastasis-free but not overall survival. Multivariate analysis, however, failed to confirm an independent prognostic value for Cathepsin D in breast cancer patients. CONCLUSIONS: These data do not confirm an independent prognostic significance for Cathepsin D using immunohistochemical methods on breast cancers.


Asunto(s)
Neoplasias de la Mama/química , Catepsina D/análisis , Inmunohistoquímica , Ensayo Inmunorradiométrico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Inmunoensayo , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Pronóstico
12.
Cancer Res ; 51(16): 4470-5, 1991 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-1868468

RESUMEN

In T47D breast cancer cell line, progestin (R5020) induces de novo synthesis of an alkaline phosphatase enzyme. Based on inhibitor profiles and antigenic specificity, it is apparent that this enzyme belongs to the class of membrane-associated tissue-unspecific alkaline phosphatases. Enzyme induction was uniquely specific to progestins and not altered by other steroid hormones or synthetic analogues. The progestin induction of the tissue-unspecific alkaline phosphatase was time and dose dependent. The protein synthesis inhibitor cycloheximide blocks the enzyme synthesis and tunicamycin blocks the enzyme activity, showing that the induction was new synthesis of protein in its complete glycosylated form and not activation of a preexisting enzyme. To our knowledge this is the first report of progesterone-induced expression of a tissue-unspecific alkaline phosphatase gene of such magnitude (about 30- to 100-fold) in a progesterone-responsive tissue.


Asunto(s)
Fosfatasa Alcalina/metabolismo , Promegestona/farmacología , Fosfatasa Ácida/metabolismo , Fosfatasa Alcalina/biosíntesis , Neoplasias de la Mama/enzimología , Línea Celular , Cicloheximida/farmacología , Inducción Enzimática , Femenino , Humanos , Cinética , Especificidad de Órganos , Esteroides/farmacología , Tunicamicina/farmacología
13.
Int J Biol Markers ; 6(3): 151-8, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1791309

RESUMEN

A radioreceptor assay (RRA) for the determination of total estrogen activity, was set up and used to assess the possible presence of exogenous molecules with estrogen activity in serum; a comparison was made with the specific radioimmunoassay (RIA) for the endogenous estrogen 17-B estradiol (17-B-E2). The assay was first performed on sera from healthy people taking estrogens in the form of oral contraceptives or lotions for local application whose total estrogenic activity in the blood was assumed to be abnormal. The assay was then performed on serum from 98 patients with early breast cancer and 20 patients with metastasis, not undergoing hormone therapy. A higher estrogen activity was found in 2.5% of sera compared to the activity found using the RIA method which is specific for endogenous estrogen 17-B-E2, the RRA/17-B-E2 ratio being higher than 3. Increased estrogen activity was found in 10% serum samples from digoxin treated cardiopathic patients, with an RRA/17-B-E2 ratio ranging from 4.4 to 20. The RRA assay could prove useful for showing up exogenous estrogen activity from various sources (drugs, food) in sera of people in whom estrogen stimulation could be potentially dangerous (i.e. in patients with hormone-sensitive tumors). This exogenous activity could support a certain degree of neoplastic stimulation and, therefore, unfavourably condition the patients' therapeutic response.


Asunto(s)
Neoplasias de la Mama/sangre , Estrógenos/sangre , Ensayo de Unión Radioligante/métodos , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/tratamiento farmacológico , Digoxina/sangre , Digoxina/uso terapéutico , Estradiol/sangre , Estudios de Evaluación como Asunto , Femenino , Cardiopatías/sangre , Cardiopatías/tratamiento farmacológico , Humanos , Radioinmunoensayo/métodos , Tamoxifeno/sangre , Tamoxifeno/uso terapéutico
14.
Hybridoma ; 9(3): 221-35, 1990 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2365381

RESUMEN

The preparation of monoclonal antibodies (MAbs) against the human milk fat globule membrane with preferential binding to breast carcinoma cells is described. Using BALB/c mouse myeloma cells; inter-specific, intra-strain, and inter-strain hybridomas were isolated that identified three different components of the human milk fat globule of approximately 46,000, and 70,000 daltons and a mucin-like glycoprotein complex (NPGP) ranging from 400,000 to over a million daltons, respectively. Three MAbs (BrE1, BrE2, BrE3) identified the latter component which consists of at least three different size molecules for which the aforementioned MAb's have different binding specificities. MAbs, BrE2 and BrE3, bound to normal breast epithelial cells but to a lesser extent than to tumors and only at the apical surface facing the lumen, while they bound breast carcinomas strongly, and often in the cytoplasm as well as on the surface. Higher concentrations of BrE3 were required to stain normal breast compared to breast tumors. BrE1 also stained breast carcinomas both on the surface and cytoplasmically but did not stain normal breast tissue. The MAb, Mc13, as well as the previously reported MAb McR2, both against the 70,000 dalton component, did not significantly stain either normal or cancerous breast tissue in histological sections but did bind significantly to cultured breast epithelial cells and to the milk fat globule membrane. The MAbs, Mc8 and Mc3, reported previously to be against the 46,000 dalton component, stained histologically only malignant breast tissue but only weakly; however, they bound strongly to intact breast carcinoma cells and breast cell membrane preparations with a radioimmunobinding assay. These MAbs should be useful in characterizing the surface of breast epithelial cells, studying surface alterations in malignancy, and possibly in breast cancer diagnosis and therapy.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Neoplasias de la Mama/inmunología , Glicoproteínas de Membrana/inmunología , Animales , Mama/inmunología , Citoplasma/inmunología , Humanos , Hibridomas/inmunología , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Peso Molecular , Mucina-1 , Mucinas/inmunología
15.
Cancer Res ; 48(22): 6462-74, 1988 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-3180062

RESUMEN

Monoclonal antibodies (MAbs), recently produced against human progesterone receptors (PR), were used for immunocytochemical localization of PR. The specificity of the immunocytochemical assay for PR was demonstrated by incubation with control MAbs, preabsorption of MAbs with highly purified human PR, and by the cell and tissue distribution of the immunostaining reaction. With human breast cancer cell lines, immunoreactivity was confined to cells that contain PR by steroid-binding assay. Moreover, immunostaining was induced by estradiol in estrogen-responsive cells, MCF-7 and ZR-75-1. In a preliminary study with 33 breast carcinomas, a good correspondence was obtained between immunocytochemical staining and PR content assessed by conventional steroid-binding assay. Immunoperoxidase localization was also obtained with other human target tissues. In normal breast and benign breast disease, immunoreactivity was observed with nuclei of ductal epithelial cells and hyperplastic epithelium. In uterus, immunostaining of endometrium was localized to nuclei of stromal and glandular epithelial cells and in myometrium to nuclei of smooth muscle cells. The effect of the progestin agonist, R5020, and antagonist, RU 486, on PR localization was investigated with the PR-rich T47D human breast cancer cell line. In the absence of hormone, immunostaining was exclusively nuclear. This was true under a number of cell culture conditions designed to eliminate endogenous progestins from the culture medium. Exclusive nuclear localization of PR was not due to a failure of the MAbs to recognize unoccupied PR, since each MAb bound equally well in vitro with different receptor forms. These included liganded and unliganded cytosol PR, molybdate stabilized PR, and nuclear-transformed receptors. Nor was failure to detect cytoplasmic staining due to a selective destruction or loss of unoccupied PR from the cytoplasmic compartment as a result of cell fixation. This was assessed by dot blot immunoassay of PR antigen distribution in subcellular fractions of fixed and unfixed cells. Continuous exposure of cells to R5020 resulted in a transient (30-60 min) increase in nuclear staining intensity (without change in cytoplasmic reactivity), followed by a progressive decline in immunoreactivity. By 24 h of R5020 treatment, the vast majority of cells displayed no immunostaining reaction. These immunocytochemical data are consistent with progestins down regulating their own receptors due to a loss in cellular PR content and not to inactivation of receptors.(ABSTRACT TRUNCATED AT 400 WORDS)


Asunto(s)
Anticuerpos Monoclonales , Neoplasias de la Mama/análisis , Receptores de Progesterona/análisis , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Carcinoma/análisis , Núcleo Celular/análisis , Citosol/análisis , Estrenos/farmacología , Femenino , Humanos , Inmunohistoquímica , Mifepristona , Peso Molecular , Promegestona/farmacología , Receptores de Estrógenos/análisis , Receptores de Glucocorticoides/análisis , Receptores de Progesterona/inmunología
16.
Schweiz Med Wochenschr ; 116(29): 971-3, 1986 Jul 19.
Artículo en Alemán | MEDLINE | ID: mdl-3020682

RESUMEN

The estrogen and progesterone receptor content of liver cytosol was measured in female patients with focal nodular hyperplasia associated with oral contraceptive use and compared with the receptor content of non-tumorous liver and of primary hepatocellular carcinomas. Receptors were found in very low concentrations or were not measurable at all. In one case of focal nodular hyperplasia the estrogen receptor content of the tumor was higher than that in the adjacent normal liver. Malignant liver tumors and the male liver were characterized by a low or non-measurable receptor content. The study of nuclear receptors combined with the use of monoclonal antibodies may be more helpful in elucidating the complex relationship between oral contraceptive use, benign liver tumors and hepatic steroid receptors.


Asunto(s)
Carcinoma Hepatocelular/análisis , Neoplasias Hepáticas/análisis , Hígado/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Carcinoma Hepatocelular/inducido químicamente , Anticonceptivos Orales/efectos adversos , Femenino , Humanos , Hiperplasia , Hígado/patología , Hepatopatías/patología , Neoplasias Hepáticas/inducido químicamente , Masculino , Persona de Mediana Edad
17.
Cancer Res ; 46(3): 1306-17, 1986 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3510721

RESUMEN

A monoclonal antibody (323/A3) with a high degree of selectivity for binding to breast cancer cells was produced by immunization of mice with MCF-7 human breast cancer cells. The antigen recognized by 323/A3 on MCF-7 appears to be surface localized, and by enzyme-linked immunosorbent assay, the antibody was found to bind strongly with four of six breast cancer cell lines examined while no binding was detectable with nonbreast cancer cell lines. In vivo distribution of the 323/A3 antigen was screened by immunoperoxidase staining of formalin-fixed paraffin sections of normal human tissues and tumors. Among breast tissues, positive staining was detected with 75% (6 of 8) of metastatic lymph nodes, 59% (76 of 128) of primary breast tumors, 20% (13 of 63) of benign breast lesions, and 0% (0 of 10) of normal breast. No immunostaining was detected with a large variety and number of other normal human tissues with the exception of staining observed with epithelium of normal colon. Antigen distribution appears not to be disease specific, since positive staining was also observed with adenocarcinomas other than breast. The antigen recognized by the 323/A3 antibody was identified by Western blot analysis as a Mr 43,000 protein. The glycoprotein nature of the antigen was demonstrated by its binding to concanavalin A, specific elution with sugar, and immunoprecipitation of a Mr 43,000 radiolabeled protein from extracts of MCF-7 cells after pulse labeling with [3H]glucosamine. The 323/A3 antigen appears to be the same Mr 43,000 protein in cell lines as in breast tumors in vivo. Based on a comparison with the molecular weights of other known tumor-associated antigens and with their immunocytochemical tissue distribution, the Mr 43,000 glycoprotein described here represents a tumor-associated antigen previously undescribed in breast cancer or in other tumors. Since the Mr 43,000 glycoprotein is present on the surface of most breast cancer cells and is either absent or expressed at very low levels in most normal tissues including normal breast, the monoclonal antibody described here may have potential applications in diagnosis and management of breast cancer.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Antineoplásicos/inmunología , Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/inmunología , Especificidad de Anticuerpos , Mama/inmunología , Enfermedades de la Mama/inmunología , Línea Celular , Membrana Celular/inmunología , Femenino , Técnica del Anticuerpo Fluorescente , Glicoproteínas/inmunología , Humanos , Técnicas para Inmunoenzimas , Peso Molecular , Distribución Tisular
19.
Surg Neurol ; 24(3): 245-9, 1985 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-4023903

RESUMEN

Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the antiestrogenic agent tamoxifen (Nolvadex) during an 8-12-month period. Computer tomographic, scintigraphic, and clinical evidence of an unspecific tumor response was only encountered in one patient after 4 months of therapy with tamoxifen. The 2-year results did not indicate a favorable response to antiestrogenic treatment. The significance of sex-steroid receptors and their possible prognostic value in endocrine therapy of meningiomas is discussed.


Asunto(s)
Neoplasias Meníngeas/tratamiento farmacológico , Meningioma/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/metabolismo , Meningioma/diagnóstico por imagen , Meningioma/metabolismo , Persona de Mediana Edad , Proyectos Piloto , Radiografía , Receptores de Estrógenos/metabolismo
20.
J Steroid Biochem ; 20(5): 1083-8, 1984 May.
Artículo en Inglés | MEDLINE | ID: mdl-6539408

RESUMEN

Specific uptake of tritiated 17 beta-oestradiol and R5020, a synthetic progestin, in breast cancer cell lines ( MCF7 and T47D) growing in monolayer culture in multiwell plates has been shown. Binding characteristics, calculated by Scatchard analysis, indicate the presence of steroid receptors of similar affinities and capacities to those already obtained with broken cell preparations. Lysis of the cells by treatment with a hypotonic buffer reveals the subcellular localization of the receptors so the method can be used to study receptor dynamics such as nuclear translocation and processing. Cell growth can be measured by DNA determination directly in the multiwell plates. Thus, the method provides a convenient way of studying the effects of steroid hormones (or any antihormone or chemotherapeutic agent) on growth and receptor content of breast cancer cells in monolayer culture.


Asunto(s)
Neoplasias de la Mama/metabolismo , Estradiol/metabolismo , Progesterona/metabolismo , División Celular , Línea Celular , ADN/análisis , Humanos , Métodos , Promegestona/metabolismo , Fracciones Subcelulares/metabolismo , Factores de Tiempo
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