Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic mechanism for increased circulating free fatty acids in post-menopausal women with metastatic breast cancer was investigated. Hormone and metabolic response to glucose and growth hormone were compared to cancer patients and control subjects; thyroid, adrenal and pituitary function were evaluated. The results of these studies indicated that breast cancer patients had glucose intolerance and delayed and prolonged insulin secretion, increased basal growth hormone levels and insensitivity of adipose tissue to growth hormone. Cortisol and protein-bound iodine levels were normal and there was no lipolytic factor in the sera of breast cancer patients. The changes observed in breast cancer patients were not attributable to age, obesity, inanition or stress. These metabolic abnormalities may characterize host susceptibility to breast cancer or be effects of tumor.
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PMID:Metabolic parameters in women with metastatic breast cancer. 4 95

Fasting blood samples were collected from 83 patients with histologically proven breast cancer and analysed for plasma glucagon, serum immunoreactive tumour necrosis factor (TNF alpha), insulin, glucose, growth hormone, cortisol and TSH. Samples from patients with known diabetes mellitus or thyroid disease, and those on parenteral nutrition or with evidence of infection were excluded as were patients who had a history of weight loss through dieting or who were anorexic. Fasting plasma glucagon, serum cortisol and immunoreactive TNF alpha concentrations in patients with stage IV breast cancer who had developed weight loss were significantly higher than those in patients with stage IV disease who had not developed weight loss. There were no significant differences in the fasting serum concentrations of insulin, glucose, growth hormone and TSH between the two patient groups. The association between weight loss in stage IV breast cancer and increased concentrations of plasma glucagon, serum cortisol and TNF alpha suggests a possible role for these hormonal factors in the development of cancer cachexia.
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PMID:Hormonal factors associated with weight loss in patients with advanced breast cancer. 195 51

The authors assessed whether breast cancers can be detected by means of positron emission tomography (PET) with the positron-emitter-labeled glucose analogue 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG). In 12 patients with primary and/or metastatic breast cancer, PET images of F-18 distribution in vivo were obtained approximately 1 hour after intravenous injection of 10 mCi of FDG. Scan findings were correlated with other imaging data and physical examination and biopsy results. Ten of 10 primary breast cancers were imaged by means of FDG PET with a tumor:background FDG uptake ratio of 8.1 (median). Ten of 10 bone metastases were imaged with a tumor:normal bone uptake ratio of 6.05 (median). Five of five known soft-tissue metastases and four previously unsuspected nodal lesions were found with PET. No false-positive foci of FDG uptake were demonstrated. In two cases with negative mammograms due to dense breast parenchyma, FDG PET clearly delineated the primary tumors. These preliminary data demonstrate the feasibility and substantial potential of PET scanning with FDG to detect and localize both primary and metastatic breast cancers.
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PMID:Primary and metastatic breast carcinoma: initial clinical evaluation with PET with the radiolabeled glucose analogue 2-[F-18]-fluoro-2-deoxy-D-glucose. 202 89

Myelography was performed on 78 patients with breast cancer who had signs or symptoms compatible with spinal cord compression. Of 42 patients (54%) with extradural defects, 21 (50%) had a complete block. All patients with positive myelograms (M+) had a positive bone scan and 41 of 42 (97%) had positive skeletal x-rays. Except for paraplegia, paraparesis, or a sensory level abnormality, signs and symptoms were usually not precise enough to accurately predict patients with cord lesions; however, back pain, paresthesias, and bladder or bowel dysfunction were significantly more common in M+ patients. Cerebrospinal fluid (CSF) protein was elevated in almost all M+ patients but also in approximately half of the M- group. Cytology and glucose analysis of CSF were not of value in predicting cord involvement. Response to treatment was better for patients with fewer sites of metastatic disease and a shorter time from diagnosis to treatment. There was no notable difference in survival between M+ and M- patients. Myelography remains the most precise tool for diagnosing spinal cord lesions. Unfortunately, the prognosis of patients with metastatic breast cancer is poor regardless of whether spinal cord compression is present.
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PMID:Spinal cord compression in breast cancer. 399 90

The value of whole body positron emission tomography using F-18 2-deoxy-2-fluoro-d-glucose in primary work-up and follow-up was prospectively evaluated in 37 patients with primary or metastatic breast cancer. From 20 primary breast masses 15 from 16 malignant and 4 from 4 benign lesions confirmed by biopsy, were detected. In 3 out of 21 patients in correlation to morphologic imaging, respectively biopsy, no metastatic disease was not identified. Generally speaking, whole body positron emission tomography appears to be a suitable diagnostic staging tool in breast cancer.
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PMID:[Whole body positron emission tomography in breast cancer]. 838 65

Interleukin-6 is associated with poor prognosis in breast cancer. Expression of GP96, a glucose regulated stress protein, is related to drug resistance in tumor cells. Interleukin-6 has previously been shown to induce GP96 expression in a murine myeloblastic cell line. BT474 or MDA-MB231 cells were incubated with recombinant Interleukin-6 (100 to 750 U/ml) for 24 hr. To establish a time course for GP96 induction, MDA-MB231 cells were incubated with 250 U/ml recombinant interleukin-6 for 0-48 hr. Following incubation, cells were washed twice in phosphate-buffered saline (PBS) and cell lysates were prepared by adding 100 microliters of PBS and freezing at -20 degrees C. GP96 was assessed by immunoblotting. Breast tumor tissue and histologically normal breast tissue were obtained within 1 hr of resection and flash frozen in liquid nitrogen. Tissue was homogenized in ice-cold PBS and cell debris was pelleted by centrifugation at 300g at 4 degrees C for 5 min. Supernatants were collected and assayed for interleukin-6 by ELISA, and GP96 by immunoblotting. Both interleukin-6 (P < 0.001) and GP96 are elevated in breast tumor tissue compared to histologically normal tissue. Interleukin-6 (> or = 250 U/ml for > or = 12 hr) induces GP96 in the metastatic breast cancer cell line, MDA-MB231, but has no effect on GP96 levels in the primary cell line, BT474. Elevated interleukin-6 in breast tumors may induce GP96 expression in tumor cells conferring a survival advantage by rendering them resistant to cytotoxic therapy and other forms of stress.
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PMID:Interleukin-6 upregulates GP96 expression in breast cancer. 920 61

The extracellular pH in malignant tumors is known to be lower than in normal tissues and may therefore facilitate extracellular activation of secreted lysosomal cathepsins. We have tested the capability of human mammary cells (continuous cell lines and primary culture) to acidify their extracellular environment, using two techniques. By measuring pH changes through alterations of phenolsulfone phthaleine absorbance, we found that the more aggressive MDA-MB-231 human breast cancer cells were more active in acidifying a non-buffered balanced salt solution than the estrogen receptor positive MCF7 and ZR75 cell lines and than normal mammary epithelial cells in primary culture. Metastatic breast cancer cells from pleural effusions were up to 200-fold more active in acidifying their extracellular milieu than non-malignant mammary cells cultured in the same conditions, strongly suggesting that this difference also occurs in vivo. The use of inhibitors in the presence or absence of glucose showed that both lactate and an ATP-driven proton pump sharing some characteristics of the vacuolar H+ pump were involved. Bafilomycin A1, a specific inhibitor of the vacuolar (V-type) ATP-H+ pump inhibited part of the acidification by MCF7 cells, but not by MDA-MB-231 cells. We also used microelectrodes to measure extracellular pH, in close contact to the MCF7 breast cancer cells. The pH at the free surface of MCF7 cells was lower by 0.33 +/- 0.14 unit than that of the surrounding medium, while insertion of the microelectrode tip beneath the attached surface of the cells showed a greater lowering of pH from 0.3 to 1.7 pH unit as long as cell attachment on the substrate prevented H+ diffusion. We conclude that breast carcinoma cells have a higher capacity for acidifying their extracellular milieu than normal mammary cells, and that both a plasma membrane H(+)-ATPase, and lactic acid production are involved in this acidification. It is therefore possible that the aspartyl and cysteinyl pro-cathepsins secreted in excess by tumor cells may be activated extracellularly in vivo close to the basement membrane.
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PMID:Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism. 921 26

The value of whole body positron emission tomography using 18F-fluoro-deoxy-glucose (18FDG) in primary work-up and follow-up was evaluated retrospectively in 104 patients with primary or metastatic breast cancer. Compared to other imaging methods, FDG-PET sensitivity was superior to sonography, CT or MRT. Another advantage is the possibility of whole body imaging and the earlier detection of lymph node metastasis due to the recognition of functional metabolic changes compared to structural changes found with conventional imaging methods.
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PMID:[PET scan in general practice for diagnosis of breast carcinoma]. 927 8

RC-160 (octastatin/vapreotide) is a potent octapeptide analogue of somatostatin with growth inhibitory activity in experimental tumours in vitro and in vivo, including breast cancer. We evaluated the efficacy and tolerability of high-dose RC-160, 3 mg day(-1) on week 1 increased to 4.5 mg day(-1) for weeks 2-4 and subsequently 6 mg day(-1) until the end of treatment, administered by continuous subcutaneous infusion in the management of 14 women with previously treated metastatic breast cancer. The age range was 37-80 years (median 58.5 years) and performance status 0-2. The treatment was well tolerated with no dose reductions being required. No grade 3 or 4 toxicities were seen. Abscess formation developed at the infusion site in eight patients and erythema and discomfort was seen in a further three patients. A significant reduction in IGF-I levels occurred by day 7 and was maintained throughout the treatment. The lowest dose of RC-160 produced the maximal IGF-I response. Although there was no reduction in prolactin levels in patients whose baseline levels were normal, elevated prolactin levels found in three patients fell to within the normal range 7 days after commencing RC-160 treatment. A small but significant rise in fasting blood glucose levels was also recorded, the highest level on treatment being 7.6 mmol l(-1). No objective tumour responses were observed, all patients showing disease progression within 3 months of commencing treatment. These findings demonstrate that high-dose RC-160, administered as a continuous subcutaneous infusion, can reduce serum levels of the breast growth factors IGF-I and prolactin but is ineffective in the management of metastatic breast cancer. Encouraging preclinical anti-tumour activity and the favourable toxicity profile in patients suggest the merit of future studies combining RC-160 with anti-oestrogen, cytotoxic and anti-angiogenic agents.
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PMID:Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin, in the treatment of metastatic breast cancer. 1018 84

Gene therapy strategies employing the HSVtk/ganciclovir (GCV) suicide gene offer promising approaches towards the treatment of metastatic breast cancer. These include bystander effects on non-transduced tumor cells, lower systemic toxicity, and the possibility of inducing immunity against the tumor. Previously we have demonstrated the ability of the grp78 stress-inducible promoter to stimulate expression of reporter genes within the tumor microenvironment. However, experimental evidence demonstrating the ability of this promoter to activate therapeutic agents within the breast cancer environment causing tumor eradication is needed prior to clinical trials. In this report, we test the efficacy of the grp78 promoter in a retroviral system to drive the expression of the HSVtk suicide gene in a murine mammary adenocarcinoma cell line (TSA) in syngeneic, immune-competent hosts. Our results show that under glucose-starvation conditions in vitro, the expression of HSVtk and GCV induced cell death are enhanced in tumor cells in which the HSVtk gene is driven by the internal grp78 promoter compared to cells in which the Moloney murine leukemia virus LTR drives HSVtk. In in vivo studies, in tumors in which the HSVtk gene is driven by the grp78 promoter, GCV treatment causes complete tumor eradication, whereas tumors persist when the HSVtk gene is driven by the retroviral LTR. Our study suggests that the grp78 promoter may be useful to enhance the effectivity of therapeutic agents within a breast tumor. In addition, it is shown that immune memory is induced in syngeneic, immune-competent hosts. This new retroviral vector might therefore be useful for breast cancer gene therapy.
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PMID:Eradication of murine mammary adenocarcinoma through HSVtk expression directed by the glucose-starvation inducible grp78 promoter. 1075 83


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