RESUMO
Em estudo dos casos de câncer da mama masculina ocorridos no INCa-RJ, de 1983 a 1989, os autores apresentam os dados clínicos, radiológicos e histopatológicos mais encontrados, tendo sido observado o predomínio do carcinoma ductal infiltrante, 6 casos de implante secundário e 2 casos fatais. A importância deste trabalho está, principalmente, na oportunidade de reunir 11 ocorrências da lesäo, que representam apenas 0,2% dos tumores malignos no homem, e descrever suas manifestaçöes, chamando a atençäo do radiologista para esta entidade
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Mama/epidemiologia , Brasil , Neoplasias da Mama/análiseRESUMO
A simple method was developed to isolate low abundance hormone receptor poly(A)+ RNA from cells in tissue culture. Adherent cells in tissue culture plates were directly released with proteinase K and solubilized in SDS. Oligo(dT) cellulose was directly added to the lysate to obtain poly(A)+ RNA. Yields and purity of the poly(A)+ RNA were comparable to other more lengthy methods. IGF-I receptor and insulin receptor mRNA could be detected on Northern blot without any degradation.
Assuntos
Hibridização de Ácido Nucleico , Poli A/isolamento & purificação , RNA/isolamento & purificação , Receptor de Insulina/genética , Receptores de Superfície Celular/genética , Animais , Neoplasias da Mama/análise , Linhagem Celular , Sondas de DNA , Fibroblastos/análise , Humanos , Camundongos , Músculos/análise , RNA Mensageiro , Receptores de Somatomedina , Células Tumorais CultivadasRESUMO
Estramustine phosphate, an anti-prostatic cancer agent, was investigated on eleven patients to evaluate the efficacy in a treatment of advanced breast cancers. The daily dose of medication was 840 mg. According to criteria of Japan Society for Cancer Therapy, none was assessed as CR, three as PR, four as NC and PD. The response rate was 27.3%. There was no differences in response rates among estrogen receptor status. A favourable response was observed in postmenopausal patients but no response in premenopausal, as well as a good response in lesions of soft tissue and lung, a poor response in lesions of liver and bone. As to toxicity of estramustine phosphate, gastrointestinal disorders such as nausea, vomiting and diarrhea were noted frequently during the treatment, and a long term administration was not able to perform in premenopausal patients because of vaginal bleeding and discharge, and pain in breast. The estramustine phosphate therapy for advanced breast cancers was regarded as one of modalities for a treatment of postmenopausal patients as a second line therapy. This is the first report in Japan discussing the efficacy of estramustine phosphate for a treatment of breast cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estramustina/uso terapêutico , Compostos de Mostarda Nitrogenada/uso terapêutico , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/análise , Esquema de Medicação , Avaliação de Medicamentos , Estramustina/administração & dosagem , Estramustina/efeitos adversos , Feminino , Humanos , Leucorreia/induzido quimicamente , Menopausa , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Receptores de Estrogênio/análise , Vômito/induzido quimicamenteRESUMO
There are conflicting reports of seasonal changes in steroid hormone receptor levels in breast cancer tissue. Estrogen receptor and progesterone (PR) receptor levels from 1132 tumors were thus grouped according to month of initial tumor detection or month of tissue sampling/surgery. There was a significant circannual variation in the mean monthly PR receptor concentration in patients grouped according to month of tissue sampling/surgery with peak PR levels in April (late summer-early autumn) and nadir values in August and September (late winter-early spring). There was no significant cyclic variation in estrogen receptor values. A significant annual variation in tumor PR concentration was also seen when receptor levels from individual tumors were grouped according to month of initial tumor detection, with peak PR levels found in January and February. The time interval between tumor detection and biopsy/surgery was 3.3 +/- 5.3 months (mean +/- SD) which was close to the interval between the peak PR concentration expressed by month of tumor detection compared with month of tissue sampling for receptor assay. There was also a significant seasonal variation in the month of initial tumor detection, with peak detection occurring in December (summer). The close synchrony between month of maximum tumor detection and month of peak PR concentration suggests that seasonal changes in detection of breast cancer may in part relate to seasonal changes in hormone responsiveness within tumor tissue.
Assuntos
Neoplasias da Mama/análise , Receptores de Progesterona/análise , Estações do Ano , Feminino , Humanos , Receptores de Estrogênio/análiseRESUMO
Tumors of five groups of patients, with (1) nonpalpable primary breast cancer, (2) palpable operable primary breast cancer, (3) loco-regionally advanced primary breast cancer, (4) first and (5) late metastatic breast cancer, were studied in respect to their steroid receptor content. A statistically significant decrease of progesterone receptor positive tumors and of tumors positive for estradiol and progesterone receptors, was found with increasing advance of the disease. A reversed extrapolation of these figures supports the hypothesis that every breast cancer contains steroid receptors and is hormone-dependent from its inception.
Assuntos
Neoplasias da Mama/análise , Carcinoma/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Biologia , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Carcinoma/patologia , Carcinoma/secundário , Feminino , Humanos , Menopausa , Palpação , Fatores de TempoRESUMO
We have synthesized three peptides with amino acid sequences corresponding to amino acids 533-547, 597-611, and 765-779 of the human progesterone receptor (hPR). These peptides were conjugated to keyhole limpet hemocyanin and injected into mice and rabbits to develop antibodies to hPR. Antibodies to the undenatured form of PR were elicited only by the peptide with amino acid sequence 533-547. Fusion of SP2/0 myeloma cells with spleen cells from mice immunized with this peptide produced several active clones. Rabbit sera from immunized animals produced one antiserum that reacted with the undenatured form of PR. One monoclonal antibody (PR-AT 4.14) and one antiserum (PR-AT533) raised against peptide-(533-547) were characterized. Binding of these antibodies to the undenatured form of PR was demonstrated by analysis of the antibody-receptor complexes on sucrose density gradients and by immunoprecipitation techniques. Binding of PR to the antibodies was inhibited by excess peptide. The antibodies did not react with estrogen, glucocorticoid, or androgen receptors, but recognized PR from human breast cancer as well as calf, rabbit, mouse, and rat uteri, indicating that this epitope was conserved among these species. Based on sucrose density gradient analysis of PR prepared and labeled in the presence of proteolysis inhibitors and sodium molybdate, the antibodies bound to a site on the intact undenatured PR, but failed to bind to partially degraded steroid-binding form of the receptor, suggesting that the antibody-binding domain is at or near a site sensitive to proteolysis.
Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos/imunologia , Fragmentos de Peptídeos/imunologia , Peptídeo Hidrolases/metabolismo , Receptores de Progesterona/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Antígenos/imunologia , Sítios de Ligação de Anticorpos , Neoplasias da Mama/análise , Bovinos , Centrifugação com Gradiente de Concentração , Citosol/análise , Feminino , Hemocianinas/imunologia , Humanos , Técnicas de Imunoadsorção , Masculino , Camundongos , Dados de Sequência Molecular , Fragmentos de Peptídeos/metabolismo , Ratos , Ratos Endogâmicos , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Especificidade da EspécieRESUMO
Com o intuito de se avaliar mais precisamente a localizaçäo da cadeia ganglionar mamária interna em pacientes portadoras de câncer de mama, os autores realizaram um estudo imagenológico comparativo de 3 métodos: radiografia simples (RX), ultra-sonografia (US) e tomografia computadorizada (TC). Foi obtida variaçäo de medidas em torno de 0,45 cm quando se comparou o RX com a US e o RX com a TC. Até o momento contamos com apenas 8 pacientes que completaram o estudo. Achamos conveniente prosseguir na investigaçäo, a fim de que se possa obter uma melhor avaliaçäo da priofundidade a ser tratada, no caso da cadeia mamária interna, com um método simples e de fácil acesso ao radioterapeuta
Assuntos
Humanos , Feminino , Neoplasias da Mama/análise , Radioterapia , BrasilRESUMO
The binding of 125I-Tyr4 bombesin was investigated on plasma membranes of 8 human breast cancer cell lines and 2 long-term cultures of normal human breast epithelial cells. Scatchard plots were compatible with high-affinity, single-site class of receptors in 3 cell lines (KD of 0.75 x 10(-9) and 10(-9) M, Bmax of 0.75 x 10(-13) and 9.7 x 10(-13) M/mg protein in MDA-MB231 and in T47D cells, respectively) while no binding was observed in 5 other cell lines and normal epithelial cells. The neuropeptide and its structural analogues (natural or synthetic) inhibited the binding of 125I-Tyr4 bombesin in the following order of potency: gastrin-releasing peptide (GRP, EC50 = 1.7 x 10(-10) M) greater than BIM 26159 greater than bombesin, Tyr4 bombesin greater than BIM 26147 greater than litorin greater than neuromedin C. In contrast, 125I-Tyr4 bombesin binding was not displaced by neuromedin B, somatostatin, bradykinin and insulin. In agreement with our binding data, SDS-PAGE of the complex 125I-Tyr4 bombesin-receptor covalently linked by ethylene glycol-bis succinimidyl succinate (EGS) identified after autoradiography a single band with a molecular weight of 75,000, which disappeared in the presence of bombesin in excess. No transcription of either GRP or neuromedin B mRNA could be shown in tumor or normal cells. Exogenous gastrin-releasing peptide had no effect on growth of the cell lines when a serum-free medium was used, implicating that in breast cancer cell lines this receptor does not mediate growth but has a functional role.
Assuntos
Bombesina/análise , Neoplasias da Mama/análise , Mama/análise , Peptídeos/análise , Receptores de Neurotransmissores/análise , Northern Blotting , Bombesina/metabolismo , Bombesina/farmacologia , Mama/efeitos dos fármacos , Mama/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular , Membrana Celular/análise , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas/análise , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Reagentes de Ligações Cruzadas/farmacologia , Epitélio/análise , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Feminino , Peptídeo Liberador de Gastrina , Humanos , Peptídeos/metabolismo , Peptídeos/farmacologia , Ensaio Radioligante , Receptores da Bombesina , Receptores de Neurotransmissores/efeitos dos fármacos , Receptores de Neurotransmissores/metabolismo , Células Tumorais Cultivadas/análise , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismoRESUMO
Serum levels of tissue polypeptide antigen (TPA) are related to the proliferative activity and to the mass of the malignancy, differently from any other available tumor marker. We therefore evaluated TPA in comparison with CA15.3 and MCA (mucinous-like carcinoma-associated antigen) in patients with primary breast cancer. TPA was measured in tumor cytosol and in serum. Cytosol and serum TPA levels were not significantly correlated. Serum TPA was higher in patients with locally more advanced disease and in receptor-negative cases. The relation between TPA and disease spread was not directly dependent on tumor bulk, whereas CA15.3 and MCA were highly correlated to the number of positive lymph nodes and tumor size. No correlations were found between TPA and CA15.3 or MCA, and the positivity concordance rate between TPA and CA15.3 or MCA was very low. Patients with higher TPA serum levels showed a worse prognosis in cases with and in those without axillary metastases. From our data we conclude that TPA provides information different from that obtained with breast-specific tumor markers and could therefore be useful in association with CA15.3 and/or MCA in the management of patients with breast cancer.
Assuntos
Antígenos de Neoplasias/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Peptídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/análise , Antígenos Glicosídicos Associados a Tumores/análise , Biomarcadores Tumorais/análise , Neoplasias da Mama/análise , Citosol/análise , Estudos de Avaliação como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Peptídeos/análise , Antígeno Polipeptídico TecidualRESUMO
We reported the successful treatment of disseminated breast cancer with medroxyprogesterone acetate (MPA). The patient was a 52-year-old female with brain and bone metastasis developed 1 year after surgery. The primary tumor was ER-positive, and she had been treated previously with adjuvant therapy consisting of UFT and tamoxifen. Brain metastasis was surgically removed, but the following combination chemotherapy (epirubicin and vindesine) failed to result in further improvement. Then MPA (1,200 mg/day) was administered as the second-line therapy. After 6 months, multiple bone lesions showed remarkable calcification (PR) and disappeared completely (CR) 13 months later. But the patient was forced to discontinue MPA because of uncontrollable hyperglycemia. At this writing, CR was still being continued and the patient was enjoying favorable quality of life without any treatment. We confirmed that MPA was effective as the second-line treatment for disseminated breast cancer.
Assuntos
Adenocarcinoma/secundário , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Medroxiprogesterona/análogos & derivados , Adenocarcinoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/análise , Neoplasias da Mama/patologia , Feminino , Humanos , Medroxiprogesterona/uso terapêutico , Acetato de Medroxiprogesterona , Pessoa de Meia-Idade , Receptores de Estrogênio/análise , Indução de RemissãoRESUMO
Several immunohistological methods for the demonstration of progesterone receptors were tried on routinely processed paraffin wax sections of breast carcinoma, using Abbott's PgR-ICA monoclonal antibody. The best results were obtained with the avidin-biotin-immunoperoxidase complex method with no prior trypsinisation or DNAse digestion, and with imidazole added to the final diaminobenzidine developing solution. A simple semiquantitative scoring system was used to assess the staining results which were then compared with the results obtained by a standard dextran-coated charcoal biochemical assay. Of 31 cases examined, the results of the two methods were concordant in 25 (81%) of cases. This is near the higher end of the concordance range obtained by several other authors using frozen sections. The discordance encountered in a few cases was possibly the result of sampling errors which are more likely to occur with the chemical rather than the histological method. It is concluded that the method described here is fairly reliable and would greatly simplify the process of assessment of progesterone receptors in breast, and possibly other tumours.
Assuntos
Neoplasias da Mama/análise , Receptores de Progesterona/análise , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/análise , Feminino , Humanos , Técnicas Imunoenzimáticas , Receptores de Estrogênio/análiseRESUMO
HER-2/neu protooncogene amplification and protein expression were analyzed with slot blot and Western blot techniques, respectively, in more than 300 invasive primary breast tumors of all stages. Amplification (2- greater than 30 copies) was found in 17% of these tumors and high expression was seen in 19%. There was a striking coincidence between gene amplification and high expression. Tumors associated with many involved axillary lymph nodes or with Stage IV disease were more often HER-2/neu amplified or overexpressed. Furthermore, gene alteration was strongly correlated with the absence of steroid receptors and with larger tumor size. High expression without gene amplification was seen in a minor subset of tumors of less aggressive character. Neither amplification nor overexpression was correlated with disease outcome for patients with negative axillary lymph nodes. For node-positive patients, however, HER-2/neu amplification was a significant predictor of early relapse and death (median follow-up = 45 months), and a similar trend, although not significant, existed for high gene expression. Multivariate analyses indicated that HER-2/neu alterations were not independent predictors of patient outcome.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/genética , Amplificação de Genes , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Sequência de Aminoácidos , Western Blotting , Neoplasias da Mama/análise , Neoplasias da Mama/patologia , Feminino , Expressão Gênica , Humanos , Soros Imunes , Metástase Linfática , Menopausa , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/imunologia , Prognóstico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/análise , Receptor ErbB-2 , Receptores de Estrogênio/análise , Receptores de ProgesteronaRESUMO
Application of systemic adjuvant therapy for primary breast cancer patients requires a more accurate identification of patients at high risk for recurrence. We have quantitatively assessed the cytosolic levels of estrogen-regulated pS2 protein in tumors of 205 breast cancer patients (median follow-up, 47 mo). There were no significant associations between the level of pS2 protein and tumor size, lymph node status, and differentiation grade. Using length of relapse-free survival (RFS) and overall survival (OS) as end points, 11 ng of pS2 protein/mg of cytosol protein were found as the best cutoff level to discriminate between positive (pS2+) and negative (pS2-). Patients with pS2- tumors showed significantly shorter RFS and OS (P less than 0.0001) than patients with pS2+ tumors. Also after adjustment for tumor size, lymph node status, and estrogen receptor (ER) status, pS2 negativity was associated with earlier recurrence and death. Tumors positive for pS2 (55 of 205, 27%) were almost exclusively confined to the subclass of ER+ tumors (53 of 55, 96%). The death rate for patients with pS2+ tumors was one-tenth of the death rate for patients with pS2-/ER- tumors. In the patients with ER+ tumors, the prognostic power of the pS2 status was especially present in patients whose tumors were also positive for the progesterone receptor (5-yr RFS and OS, 85% and 97% for ER+/PgR+/pS2+ tumors compared with 50% and 54% for the patients with ER+/PgR+/pS2- tumors). In patients with axillary lymph node involvement (N+), pS2 status could discriminate strongly between a good and bad prognosis group (5-yr RFS and OS, 65% and 88% for N+/pS2+ compared with 32% and 34% for N+/pS2-). A similar phenomenon was observed in patients without axillary lymph node involvement (5-yr RFS and OS, 89% and 95% for N0/pS2+ compared with 58% and 82% for N0/pS2-). We conclude that the pS2 status of human primary breast tumors is an important variable for the identification of patients at high risk for recurrence and death. Knowledge of the cytosolic pS2 status appeared of particular importance to identify patients at high risk in the ER+/PgR+ subclass of tumors, and in both the N0 and N+ subclasses of patients.
Assuntos
Neoplasias da Mama/mortalidade , Proteínas de Neoplasias/análise , Recidiva Local de Neoplasia , Proteínas , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/análise , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Fator Trefoil-1 , Proteínas Supressoras de TumorRESUMO
The purpose of this study was to investigate the biological behavior of male breast cancer. We evaluated 11 cases of male breast cancer with respect to tumor growth, extent of disease, hormone receptor status, and histological grade of the malignancy, in comparison with 241 cases of female breast cancer. The duration of symptoms was 8.6 +/- 9.1 months in males and 8.5 +/- 18.6 months in females. The incidences of stages I, II, and III were 46%, 27%, and 27%, respectively, in male breast cancer, and 38%, 49%, and 13% in female breast cancer. Metastasis to the lymph node was negative in 60% of the male patients and 54% of the female patients. All cases of male breast cancer were histologically grade I according to Bloom's classification; the histological grades were as follows for the female breast cancer cases: grade I in 99 patients, grade II in 87, and grade III in 55. The rates of hormone receptor positively were 89% for ER and 86% for PgR in male breast cancer, and 64% for ER and 44% for PgR in female breast cancer. Therefore, there was no significant difference in the growth of male breast cancer and female breast cancer, but in male breast cancer the rate of hormone receptor positivity was high, endocrine therapy was effective, and the histological grade was low. Accordingly, the result following appropriate treatment of male breast cancer should be at least comparable to the results with female breast cancer.
Assuntos
Neoplasias da Mama/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/análise , Neoplasias da Mama/terapia , Terapia Combinada , Humanos , Metástase Linfática , Masculino , Mastectomia/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , RecidivaRESUMO
Thrombospondin (TSP), an adhesive glycoprotein found in platelets and extracellular matrix, has been shown previously to interact with plasminogen and tissue plasminogen activator, resulting in efficient plasmin generation. We now demonstrate specific complex formation of TSP with both the single-chain and two-chain forms of urokinase (scuPA and uPA). Binding of uPA and scuPA to immobilized TSP was detected and quantified using colorimetric immunoassays and a functional amidolytic assay. Binding was time and concentration dependent with apparent affinity constants of 40-50 nM. Binding was not affected by serine protease inhibitors, EDTA, or epsilon-aminocaproic acid. scUPA and uPA bound to TSP retained functional activity. Using a sensitive amidolytic assay we found that TSP. scuPA complexes were efficiently converted to TSP. uPA by catalytic plasmin concentrations. Additionally, TSP.uPA complexes were found to have plasminogen-activating activity equivalent to fluid-phase uPA and to be protected from inhibition by plasminogen activator inhibitor type 1, the major plasma and matrix plasminogen activator inhibitor. Using immunohistochemical techniques, we also demonstrated co-distribution of TSP and uPA in normal and malignant breast tissue. Complex formation of TSP with uPA may serve to localize, concentrate, and protect these enzymes on cell surfaces and within the extracellular matrix, thereby providing a reservoir of plasminogen activator activity.
Assuntos
Plaquetas/análise , Glicoproteínas de Membrana/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Sequência de Aminoácidos , Mama/análise , Neoplasias da Mama/análise , Colorimetria , Ensaio de Imunoadsorção Enzimática , Matriz Extracelular/análise , Fibrinolisina/metabolismo , Humanos , Imuno-Histoquímica , Cinética , Glicoproteínas de Membrana/farmacologia , Dados de Sequência Molecular , Plasminogênio/metabolismo , Ativadores de Plasminogênio/farmacologia , Trombospondinas , Distribuição Tecidual , Ativador de Plasminogênio Tipo Uroquinase/farmacologiaRESUMO
A number of investigators have suggested treatment of precursor lesions for invasive breast cancer such as ductal carcinoma in situ with antiestrogen. However, very little information is available on the incidence of estrogen receptor in such lesions and the probability of treatment success. Fourteen formalin-fixed tissue specimens of intraductal carcinoma in situ from 14 female patients aged 40 to 66 years were evaluated for the presence of estrogen receptor by immunoperoxidase technique using estrogen receptor antibody. Eight of the 14 lesions (57%) were positive for estrogen receptor. The incidence of estrogen receptor in intraductal carcinoma in situ is very similar to that of invasive carcinoma of breast, leading to the speculation that ER-positive invasive carcinoma originates from ER-positive precursor lesions. Since only 70 per cent of positive receptor lesions are expected to respond to antiestrogens, it appears that only 40 per cent of patients with ductal carcinoma in situ of breast will benefit from endocrine therapy.
Assuntos
Neoplasias da Mama/análise , Carcinoma in Situ/análise , Carcinoma Intraductal não Infiltrante/análise , Receptores de Estrogênio/análise , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-IdadeRESUMO
Size of tumor has not been established as a predictor of tumor recurrence in the breast following conservative surgery and radiation therapy. We analyzed 783 patients with infiltrating carcinoma treated with simple excision and radiation therapy. Median follow-up was 91 months. Median age at diagnosis was 50 years. There was a 13% recurrence among patients with T1 lesions compared with a 12% recurrence among patients with T2 tumors. Size did not predict for local recurrence when the tumor was analyzed by 1-cm increments and whether the tumor was estrogen receptor protein positive or estrogen receptor protein negative. Patients with an extensive intraductal component had a significantly higher local recurrence rate for every tumor size compared with patients with extensive intraductal component-negative tumors. We concluded that size did not predict local recurrence.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Mama/análise , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/análise , Carcinoma Intraductal não Infiltrante/terapia , Feminino , Seguimentos , Humanos , Incidência , Mastectomia/métodos , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Radioterapia , Receptores de Estrogênio/análiseRESUMO
Four courses of ifosfamide with mesna given by intravenous infusions were combined with bolus doxorubicin in a phase II trial to treat patients with breast cancer. Ifosfamide can deplete intracellular glutathione levels and because doxorubicin resistance may be associated with elevated levels of intracellular glutathione these drugs were combined in an attempt to overcome clinical cytotoxic drug resistance. There were 31 women with poor prognosis advanced breast cancer in the study. Forty-five percent were younger than 40 years old, 68% had visceral dominant disease, 59% had more than two disease sites, and each of the five women tested had increased expression of primary tumor epidermal growth factor receptor. The objective response rate was 71% with manageable toxicity (95% confidence interval, 54% to 85%). The response rate in 22 patients not given prior chemotherapy was 72% and in 9 patients with cancers resistant to previous mitoxantrone monotherapy it was 67%. The high antitumor activity of this combination suggests further exploration of its use in breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/análise , Neoplasias da Mama/mortalidade , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Receptores ErbB/análise , Feminino , Humanos , Ifosfamida/administração & dosagem , Mesna/administração & dosagem , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
The membrane glycoprotein, PAS-O, is a major differentiation antigen on mammary epithelial cells and is located exclusively in the apical domain of the plasma membrane. We have used 734B cultured human mammary carcinoma cells as a model system to study the role of tight junctions, cell-substratum contacts, and submembraneous cytoskeletal elements in restricting PAS-O to the apical membrane. Immunofluorescence and immunoelectronmicroscopy experiments demonstrated that while tight junctions demarcate PAS-O distribution in confluent cultures, apical polarity could be established at low culture densities when cells could not form tight junctions with neighboring cells. In such cultures the boundary between apical and basal domains was observed at the point of cell contact with the substratum. Immunocytochemical analysis of these cell-substratum contacts revealed the absence of a characteristic basement membrane containing laminin, collagen (IV), and heparan sulfate proteoglycan. However, serum-derived vitronectin was associated with the basal cell surface and the cells were shown to express the vitronectin receptor on their basolateral membranes. Additionally, treatment of cultures with antibodies against the vitronectin receptor caused cell detachment. We suggest, then, that interactions between vitronectin and its receptor, are responsible for establishment of membrane domains in the absence of tight junctions. The role of cytoskeletal elements in restricting PAS-O distribution was examined by treating cultures with cytochalasin D, colchicine, or acrylamide. Cytochalasin D led to a redistribution of PAS-O while colchicine and acrylamide did not. We hypothesize that PAS-O is restricted to the apical membrane by interactions with a microfilament network and that the cytoskeletal organization is dependent upon cell-cell and cell-substratum interactions.