Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IIB-BR-G is an undifferentiated, highly heterogeneous, hormone receptor negative human breast cancer cell line previously established in our laboratory from a patient's primary tumor. An in vitro growing cell line (IIB-BR-G) and a xenotransplanted tumor growing in nude mice (IIB-BR-G(NUDE)) were derived. To further characterize these systems, immunocytochemical analysis was performed for differentiation antigens (PEM 200 kDa, CEA, NCA 90 kDa), blood-group related antigens (Le(x), sTn), oncogenes and tumor suppressor gene products (Her-2/neu protein, p53), metastasis-related cathepsin D and CD63/5.01 Ag, and the chemokine monocyte chemotactic protein 1 (MCP-1). Expression of markers was heterogeneous in these different systems. Previously reported karyotypic analysis has shown extensive chromosomal alterations including double min. Searching for oncogene amplification, we detected augmented copy number of c-myc and c-fos, the last one with two rearranged fragments. No amplification was found for c-erbB-2 in the cell line or in IIB-BR-G(NUDE), although this oncogene was amplified in the patient's primary tumor DNA. The differences observed between the patient's tumor, the cell line and the IIB-BR-G(NUDE) tumors are probably due to clonal expansion of cell variants not present in the original tumor. Electron microscopy of IIB-BR-G growing cells revealed epithelial characteristics with abundant dense granules, presumably secretory, distributed all over the cytoplasm and great nuclear pleomorphism. In vitro, IIB-BR-G cells showed a significant number of invading cells by Matrigel assay. After nearly 40 sequential subcutaneous passages of the original xenograft through nude mice, 80% of recipients developed spontaneous metastases, primarily to the lung and lymph nodes. Since this experimental model allowed to analyze changes produced in cancer cells from the primary tumor during adaptation to in vitro and in vivo growth, our results provide novel insights on the behaviour of hormone independent metastatic breast cancer.
 ...
PMID:The human breast cancer cell line IIB-BR-G has amplified c-myc and c-fos oncogenes in vitro and is spontaneously metastatic in vivo. 962 Apr 46

To determine the usefulness of bone scans in detecting metastatic disease in women with early stage breast cancer, records of 193 patients who had bone scans preformed and underwent breast conservation therapy at a single institution were reviewed. Patients with invasive T1 or T2 breast carcinomas were eligible for this study; patients with a true positive bone scan were excluded from conservation therapy and, thus, were excluded from this study. The incidence of false positive bone scans in this study population was 32.6% (63/193 patients). Patients over 50 years of age had a significantly greater incidence of false positive bone scans (p<0. 05). In the 63 patients with false positive bone scans, 101 radiographs were performed to exclude metastatic disease in areas of increased uptake identified on bone scan. No significant difference in the rate of false positive bone scans was seen in relation to tumor size, pathologic or clinical nodal status or hormone receptor activity of the primary tumor. Thus, selective use of bone scans is advocated in patients with early stage (T1 or T2) breast cancer.
 ...
PMID:Evidence for selective use of bone scans in early stage breast cancer. 962 60

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer.
 ...
PMID:Mutations and amplification of oncogenes in endometrial cancer. 988 79

Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
 ...
PMID:Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer. 989 67

Following local excision, the prognosis for long-term cure of a patient with breast malignancy depends on the presence of micro-metastatic disease. The risk of occult disease present prior to removal of the primary tumor can be assessed by knowledge of the tumor size, histology and degree of differentiation, and spread to axillary nodes. It ranges from 25% in node-negative tumors to as much as 75% to 80% in the presence of multiple involved nodes. Systemic therapy can reduce the risk by approximately one-third. Present studies indicate that regardless of age or menopausal status the majority of women should be considered for chemotherapy (if hormone receptor negative) or chemotherapy and tamoxifen (receptor positive). However, it is hoped that further refinement of our knowledge of prognostic factors will allow better design of adjuvant therapy through better understanding of the mechanisms of tumor growth and spread.
 ...
PMID:Systemic adjuvant therapy of breast cancer. 1007 36

The authors analyzed the clinical and pathomorphological of T tumors for their association with the likelihood of axillary metastases. Two hundred forty three patients with early breast cancer (T1N0M0 T1N1M0) were studied. All underwent complete lymph node dissection. The parameters of the primary tumor evaluated included size, histologic subtype, hystological grade, hormone receptor status, lymphatic/vascular invasion (LVI). Clinical parameters were age, menopausal status and clinical lymph node status. Sixty two (25.5%) on 243 axillary dissection contained metastases. Univariate analysis showed that nodal involvement were associated with tumors larger than 1 cm and presence of LVI. Decision for complete axillary dissection should be individualized based on prognostic factors for lymph node involvement.
 ...
PMID:[Prognostic factors and the risk of axillary metastases in early breast cancer]. 1036 51

To evaluate the prognostic relevance of Ki-67 and topoisomerase IIalpha expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki-S11 (Ki-67) and Ki-S4 (topoisomerase IIalpha). pS2, c-erbB2, and p53 were additionally considered as prognostic variables. The median follow-up time was 149 months. Eight-hundred-and-sixty-three tumors reacted with Ki-S11 and Ki-S4; the labeling indices of the two antigens were closely associated (r = 0.93). Both correlated positively with the tumor size, c-erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki-S11 and Ki-S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis-free survival (p < 0.00001). Estrogen receptor status, p53, and c-erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki-S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki-S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki-S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIalpha expression as assessed by monoclonal antibody Ki-S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.
 ...
PMID:Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases. 1047 80

The lectin from Helix pomatia, the Roman snail (HPA), recognises terminal alpha N-acetylgalactosamine residues. A large number of lectin histochemical studies have demonstrated that expression of HPA-binding glycoproteins by cancer cells to be a marker of metastatic competence and poor prognosis in a range of common human adenocarcinomas, including those of breast, stomach, ovary, oesophagus, colorectum, thyroid and prostate. Around 80% of metastases arising from primary breast cancer are predictably HPA positive, but, intriguingly, around 20% do not express HPA binding glycoproteins reflecting the complexity of metastatic mechanisms and the further disruptions in cellular glycosylation that attend tumour progression. HPA binding is not an independent prognostic factor, but is strongly associated with the presence of metastases in local lymph nodes. It does appear to be independent of other clinical features of prognostic importance such as tumour size, histological grade, S-phase fraction, ploidy, and there is little convincing evidence of any association with oncogene expression or hormone receptor positivity. The precise nature of the metastasis-associated HPA binding partner(s) is a question of some interest, but thus far remains unclear. HPA will recognise, for example, the Tn epitope and blood group A antigen, but its prognostic significance appears to be through recognition of a much broader and heterogeneous array of N-galactosaminylated glycoproteins. Their synthesis appears to be mediated through alteration in expression or activity of one or more of the enzymes of glycosylation. The most likely putative roles of HPA-binding ligands in the metastatic cascade may be enhancement of invasive capacity, or interaction with an as yet unidentified lectin-like receptor facilitating adhesion processes. The prognostic information provided by HPA lectin histochemistry may be used clinically to inform the physician and aid treatment decisions; far more interesting is the challenge of further understanding the precise nature of the HPA-binding ligands, and defining their role in the complex mechanisms of metastasis.
 ...
PMID:The involvement of Helix pomatia lectin (HPA) binding N-acetylgalactosamine glycans in cancer progression. 1066 5

Although metastasis is a frequent event in breast cancer patients, insight into the clinical course, prognosis and therapy with respect to the site of the first metastases has been poor and contradictory in former investigations. Follow-up data from 648 patients with metastatic breast cancer were statistically analyzed. Patients with bone metastases at first relapse had better overall survival (median 71 vs. 48 months; p < 0.001) and survival after first metastases (median 24 vs 12 months; p < 0.001) than patients with visceral metastases at first relapse. Bone was the site of first metastasis in 46%, and 71% of patients with metastatic breast cancer developed bone metastases. The localization of the second metastatic site was of prognostic relevance in patients with first visceral metastases, but not in patients with first bone metastases. The presence of osseous metastases correlated significantly with estrogen and progesterone receptor positivity, tumor grading I/II and S-phase fraction <5%. The better prognosis of patients with bone metastases is not determined exclusively by hormone receptor status. The disease is significantly more stable in patients with first bone metastases than in those with first visceral metastases.
 ...
PMID:Metastatic breast cancer: clinical course, prognosis and therapy related to the first site of metastasis. 1083 97

We report 7 rare cases of recurrent breast cancers who presented with central nervous system (CNS) metastases as the initial relapse site without any other organ metastases. The average age of the patients at surgery was 42.6 years old of age (median 45:range 32-60), and 6 of the 7 cases (86%) were premenopausal. The mean disease-free period was 25.7 months (median 22, range 2-60 months). The primary tumors were all invasive ductal carcinomas. The estrogen receptor and progesterone receptor status of the 3 tumors available for study were all negative. The metastatic CNS lesions included the cerebrum (4 cases), cerebellum, cervical spinal cord, and meninges. In 6 out of these 7 cases (86%), the CNS metastasis was the initial recurrent lesion. Multidisciplinary treatments including surgery, radiotherapy and systemic or intrathecal chemotherapy were given. Although the mean survival time from clinical manifestations of the metastases of the 4 deceased patients was 20 months (median 20.5; range 6-33), one patient treated with surgery and radiotherapy is been still alive18 years later. These cases were also notable for the fact that the only metastatic site was in the CNS only during the entire clinical course, except for 2 cases, one with ocular adnexa metastasis, and the other with cervical lymph node metastasis. Premenopausal patients with negative hormone receptor status are more likely to develop this type of recurrence, regardless of the histological type. It is necessary to pay attention to neurological symptoms and signs during follow-up of breast cancer patients.
 ...
PMID:Seven cases of breast cancer recurrence limited to the central nervous system without other visceral metastases. 1102 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>