Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1978 and 1985, 393 of 2,765 (14%) patients with operable cancer of the breast (clinical stage T0-3N0-2M0) were irradiated after excisional biopsy and staging axillary dissection. Of 77 patients with microscopic axillary metastases, 68 received systemic adjuvant therapy. Treatment failed locally in 26 cases, and there were seven patients with distant metastasis. The three major factors for increased local treatment failure were (a) age below 40 years (P = .003), (b) negative estrogen receptor assay result (P = .03), and (c) failure to deliver a radiation boost dose when tumor was present at the margin of the specimen (P = .002). The size of the tumor, the nodal status, the progesterone receptor assay result, and the presence of ductal carcinoma in situ mixed with infiltrating carcinoma did not show a significant influence on local recurrence. In 274 of 393 (70%) patients, cosmesis was evaluated. The four major factors affecting cosmesis favorably were (a) utilization of a wedge (P less than .0001); (b) treatment of two fields a day (P less than .0001); (c) failure to use a separate treatment port to the regional lymph nodes, so as to avoid field junctions (P = .0003); and (d) small size of specimen (less than 50 cm2) (P = .0171). A second or third cancer was found in 39 of the 393 (10%) patients; contralateral breast cancer was the most common form (n = 23), followed by genitourinary cancer (n = 5). The most frequent complication was arm edema (6%).
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PMID:Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma. 254 75

The presence of progesterone receptor (PR), productive fibrosis (PF), axillary nodal status and tumor size are important prognostic variables in breast cancer. In this study we have analyzed the relationship between these four parameters in 78 ductal infiltrating carcinomas of the breast. No relationship was found between PF and the presence of lymph node metastatic disease: however, in the tumors with positive nodes, a limited metastatic diffusion (1-3 lymph nodes) was significantly associated with PF (p less than 0.05). Our study failed to demonstrate any relation between estrogen receptor (ER) and both presence and extension of nodal involvement; in contrast, the tumors with limited metastatic diffusion (1-3 lymph nodes) had a significantly higher prevalence of PR positivity (p less than 0.05). Furthermore, PF was strongly associated with PR (p less than 0.001) and less well with ER (p less than 0.05). The simultaneous presence of PR and marked PF was strongly correlated with limited metastatic involvement of the axilla (p less than 0.007). Tumor size was correlated with the number of positive nodes (p less than 0.001), but not with PR or PF. The results demonstrate that PR status, PF and tumor size are related to limited metastatic diffusion of the axilla: furthermore PF and PR have been shown to be strongly related and we have demonstrated that, at least in ductal infiltrating carcinoma, the simultaneous presence of them identifies a subset of tumors with low metastatic capacity independently of tumor size.
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PMID:Relationship between progesterone receptor, axillary node status and productive fibrosis in ductal infiltrating carcinoma of the breast. 255 78

Breast cancer is a highly heterogeneous disorder with regard to biologic and clinical characteristics. Identification of patients with different biologic subtypes is important both prognostically and therapeutically. The recent introduction of estrogen and progesterone receptor measurement has considerably increased our ability to identify patients with hormone-dependent tumors who are likely to respond to endocrine therapy and enjoy a longer survival. Assessment of the tumor growth fraction by autoradiographic or flow cytometric methods and measurement of EGF receptors in tumor specimens are likely to produce additional independent information on the clinical outcome of patients with breast cancer. The endocrine therapy of breast cancer has been greatly facilitated with the introduction of newer forms of therapy such as antiestrogens and aromatase inhibitors. These forms of treatments are well established, not only in patients with metastatic disease but also in selected subgroups of women with operable breast cancer following surgery. In view of its low toxicity and ease of administration, modern endocrine therapy has obviated the need for major ablative procedures such as surgical adrenalectomy and hypophysectomy. Unfortunately, duration of response and survival have not been prolonged by these newer endocrine treatments when compared with traditional hormonal therapy. Thus, new treatment strategies need to be developed, since current therapy does not cure any patient with advanced disease and at best only a small fraction of women with early breast cancer. Hormonally induced manipulation of tumor cell kinetics may provide a tool to enhance the efficacy of cytotoxic chemotherapy, in both metastatic as well as locally advanced disease. This potential approach needs to be further evaluated in prospective randomized clinical trials. Prostate cancer is the male counterpart of hormone-dependent neoplasia. Conventional therapy of this malignancy consists of surgical or medical castration. However, despite a high initial response rate, disease progression invariably occurs with poor response to secondary forms of therapy. Potential new treatment strategies currently being tested in the attempt to improve clinical outcome include simultaneous early blockade of both adrenal and testicular androgens as well as hormonally induced tumor cell growth synchronization and recruitment prior to administration of cytotoxic chemotherapy.
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PMID:Endocrine therapy of breast and prostate cancer. 266 86

Immunohistochemical localization of CA 125 using murine monoclonal antibody OC 125 was performed on fresh frozen tissue from 44 endometrial adenocarcinomas and 26 benign endometria. Immunohistochemical evaluation incorporated both intensity and distribution of staining (CA 125 HSCORE). Thirty-seven cancers (84%) and 23 benign endometria (88%) expressed immunohistochemically detectable CA 125. Staining was confined to epithelial cells and was present both on the cell membrane and in the cytoplasm. Among the 44 endometrial cancers, CA 125 HSCORE did not correlate with histological grade, depth of myometrial invasion or estrogen/progesterone receptor levels. Following surgical staging, 13 patients (30%) were found to have extrauterine metastatic disease. The median CA 125 HSCORE of patients with metastatic disease (2.25) was significantly higher than that of patients with disease confined to the uterus (0.6) (P less than 0.001). In addition, high CA 125 HSCORE also correlated with the presence of lymph node metastasis (P less than 0.001). The results of this study suggest that high CA 125 expression by endometrial adenocarcinomas is associated with increased metastatic potential.
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PMID:Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential. 270 50

Age, clinical stage, histologic grade, depth of myometrial penetration, adnexal status, peritoneal cytology, and progesterone and estrogen receptor status were available for 139 patients with clinical stage IA, IB, or II endometrial adenocarcinoma who had therapy at Indiana University Hospital or St. Vincent Hospital in Indianapolis. These features were analyzed for their association with survival and disease-free survival. Patients treated at Indiana University Hospital were similar to those from St. Vincent Hospital when comparisons were made by chi 2 test for age, clinical stage, grade, adnexal metastases, peritoneal cytologic results, progesterone receptor status, or estrogen receptor status. However, patients treated at Indiana University Hospital had lesions that were deeper (p = 0.03) than those treated at St. Vincent Hospital. Survival differences were observed for patients with progesterone receptor-rich versus progesterone receptor-poor tumors (p = 0.004), grades 1 and 2 versus grade 3 lesions (p = 0.013), and malignant versus benign peritoneal cytologic results (p = 0.01). Differences in disease-free survival were observed for those patients with adnexal metastases versus those with no adnexal disease (p = 0.002), those with estrogen receptor-rich versus estrogen receptor-poor tumors, outer third myometrial invasion (p = 0.002), and patients with clinical stage I versus clinical stage II disease (p = 0.03). A stepwise Cox proportional hazards model was constructed to determine correlates of disease-free survival. In the final model, grade (p = 0.0002), peritoneal cytologic results (p = 0.0002), progesterone receptor status (p = 0.004), and age as a continuous variable (p = 0.008) were most closely associated with disease-free survival.
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PMID:Features associated with survival and disease-free survival in early endometrial cancer. 273 64

To assess the value of measuring the estrogen- and progesterone-receptor content of metastatic nodal disease, 38 women with node-positive breast cancer were prospectively evaluated. Receptor content of the primary tumor and a pathologically confirmed positive node were measured simultaneously using a dual-isotope, dextran-coated, charcoal-binding assay. A receptor content of greater than or equal to 10 fmol/mg of cytosol protein was considered positive for both the estrogen-receptor and progesterone-receptor assays. Overall concordance between the primary tumors and the nodal metastases was 82% (31/38 patients) for the estrogen-receptor measurements and 84% (31/37 patients) for the progesterone-receptor measurements. Paired receptor levels were significantly correlated: r = .745 for the estrogen-receptor measurements and r = .805 for the progesterone-receptor measurements. Despite this correlation, 6 (25%) of 24 patients with an estrogen receptor-positive primary tumor had an estrogen receptor-negative nodal metastasis. Four (20%) of 20 patients with a progesterone receptor-positive primary tumor had a progesterone receptor-negative nodal metastasis. Six (24%) of 25 patients with tumors labeled as hormonally sensitive on the basis of the receptor content of the primary tumor had receptor-negative nodal disease. In reflecting the hormonal status of the more aggressive elements of the primary tumor, receptor levels of metastatic nodes may provide more useful information than the levels of the primary tumor as a guideline for further therapy.
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PMID:Value of measuring hormone receptor levels of regional metastatic carcinoma of the breast. 280 74

The activity of gamma-glutamyltranspeptidase (gamma GT) (EC 2.3.2.2) was examined by histoenzymatic labelling on frozen sections derived from normal breast tissue, benign lesions and carcinomas. In biopsies from normal tissue and benign lesions, labelling was very intense in lumina and in the apical pole of the cells lining the lumina whilst in the cytoplasm it was slightly positive. In 34 out of 70 carcinomas, gamma GT activity was either undetectable or slightly positive while in the remaining 36 there was intense activity. Statistical examination of the results revealed no obvious correlation of gamma GT activity with histological grade of the tumour, progesterone receptor content or classification of patients by pre- or postmenopausal status. A good correlation between gamma GT activity and the following unfavourable prognostic signs: lymph node metastases and absence of oestradiol receptors. Patients with gamma GT-negative tumours may have a more favourable prognosis than those with gamma GT-positive tumours.
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PMID:gamma-Glutamyltranspeptidase activity in human breast lesions: an unfavourable prognostic sign. 287 9

As previously reported, ovarian epithelial carcinomas may respond to endocrine therapy. We examined the direct effect of progesterone, medroxyprogesteroneacetate, gestoneron, 17-beta-estradiol, tamoxifen, 4-OH-tamoxifen, or N-desmethyltamoxifen on the proliferative capacity of ovarian carcinoma cells by means of the colony assay described by Hamburger and Salmon. The growth rate of 25 tested tumors (ascitic fluid, primary tumor, metastases) was 68%. The plating efficiency was 0.078%. Beside the drug testing estrogen and progesterone receptor levels were determined. The inhibition of colony survival was slightest with 17-beta-estradiol, more pronounced with medroxyprogesteroneacetate, gestoneron, N-desmethyltamoxifen, and progesterone, and greatest with 4-OH-tamoxifen and tamoxifen. Significant and dose-dependent inhibition of greater than 70% was observed with tamoxifen and 4-OH-tamoxifen in 80% of the tested tumors. There was no significant correlation between the in vitro responsiveness and the level of hormonal act not only via an estrogen receptor but also via an antiestrogen-binding site.
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PMID:In vitro responsiveness of ovarian epithelial carcinomas to endocrine therapy. 293 76

Methylthioadenosine (MTA) phosphorylase activity was measured in 47 biopsies from primary breast cancers (n = 34) and metastatic tumors (n = 13). Most specimens were also evaluated by DNA flow cytometry and determination of estrogen and progesterone receptor contents. Median MTA phosphorylase activity was 317 pmol/mg protein/min (range 50-1312 pmol/mg protein/min), but great variations were observed. Samples from four individuals had very low MTA phosphorylase activity (less than or equal to 70 pmol/mg protein/min). No correlation with aneuploidy, receptor status, or the presence of metastases in the lymph nodes could be demonstrated. However, MTA phosphorylase activity showed a significant (p = 0.009) negative correlation with the fraction of cells in the S-phase of the cell cycle.
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PMID:Methylthioadenosine phosphorylase in human breast cancer. 310 30

alpha Transforming growth factors (alpha-TGFs) are polypeptides that stimulate anchorage-independent growth of various nontransformed cells in vitro and are believed to be involved in autocrine stimulation of tumor cells. alpha-TGF activity is secreted by a variety of human cancers leading to the possibility that it may serve as a tumor marker. alpha-TGF activity was measured in 130 effusions from patients with various types of cancer with a radioimmunoassay using sheep antibodies against the C-terminal 17 amino acids of linear rat alpha-TGF. Forty-two % of the effusions contained immunoreactive alpha transforming growth factor (Ir-alpha-TGF) activity, including 13 of 34 (38%) breast cancer, 12 of 24 (50%) lung cancer, and 13 of 31 (42%) ovarian cancer specimens. Concentrations ranged from 1.56 to 50 ng/ml. Only 3 of 17 control effusions from noncancer patients had low levels of activity, all less than 2 ng/ml. The presence of Ir-alpha-TGF activity correlated with patients' performance status (PS) and tumor burden. It was present in 18 of 67 (27%) effusions of patients with PS less than or equal to 2 and in 23 of 33 (70%) with PS 3 or 4 (P less than 0.0001). Only 2 of 43 (4%) patients with one site of metastatic disease had detectable Ir-alpha-TGF (mean, 0.23 ng/ml); 18 of 37 (48%) with two sites (mean, 5.22 ng/ml, P less than 0.0001); and 33 of 34 (97%) with greater than two sites (mean, 5.93 ng/ml, P = 0.002). It was present in a larger percentage of effusions from breast cancer patients with estrogen- and progesterone receptor-negative tumors. Univariate analysis revealed that detectable Ir-alpha-TGF activity, PS 3 or 4, and the number of sites of disease correlated with a shorter survival. Only Ir-alpha-TGF and PS 3 or 4 retained significance in a multivariate analysis. In conclusion, Ir-alpha-TGF is frequently detectable in effusions from cancer patients, it correlates with other known adverse prognostic factors, and its presence predicts for a poor survival. Further studies of alpha-TGF activity in more readily accessible body fluids such as serum or urine are warranted.
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PMID:Immunoreactive alpha transforming growth factor activity in effusions from cancer patients as a marker of tumor burden and patient prognosis. 316 7


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