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)

In a prospective study, we evaluated the diagnostic accuracy of CYFRA 8/18, TPS, CEA and CA 15-3 among 415 patients in various clinical situations of invasive breast cancer and 244 women with benign breast diseases. In comparison to TPS, the sensitivity of CYFRA 8/18 was slightly lower as well in local malignancy (25% vs. 30%) as in metastatic cancer (54% vs. 57%), but in follow up care the rate of false positive results of TPA (> or = 25%) seems to be higher than that of CYFRA 8/18 (> or = 17%). In conclusion, the clinical value of CYFRA 8/18 and TPA appears to be similar.
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PMID:Clinical value of CYFRA 8/18 and TPS in the diagnosis and follow up of invasive breast cancer. 932 76

Between 1977 and 1993, 384 breast cancer patients were followed up post-operatively every 4 or 6 months with a serum tumour marker panel (CEA-TPA-CA15-3) and the usual imaging techniques. Twenty-eight patients were treated 13.5 +/- 10 months (mean +/- s.d.) before the clinical and/or radiological occurrence of distant metastases that were suspected because of an increase in the tumour markers (patients treated 'early'). Their outcome was compared with that of 22 similar patients who were treated only after a definite radiological diagnosis was achieved (patients treated 'not early'). The median survivals from mastectomy and salvage treatment were also compared for the two groups. The groups were similar for all the major prognostic factors (menopause, staging, hormone dependency). In the group treated 'early', the lead time from the tumour marker increase to the clinical and radiological signs of metastases was significantly longer than that of the group not treated 'early' (13.5 +/- 10 vs 3.4 +/- 2.8 months respectively; P < 0.001 by unpaired t-test). For patients treated 'early', the survival curves up to 30 months after salvage treatment and up to 72 months after mastectomy showed greater survival than those for the patients treated later (42.9% vs 13.6% and 42.9% vs 22.7% respectively; P = 0.04 in both instances). These data suggest that treatment triggered by rising tumour markers before clinical and/or radiological appearance of distant metastases can be useful in prolonging both the asymptomatic interval and the duration of response of some relapsed patients. Randomized prospective trials must be encouraged to confirm these data and to better evaluate the effect on the disease-free survival (DFS) and overall survival (OS) of 'early' salvage treatment protocols.
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PMID:Prolonged survival by 'early' salvage treatment of breast cancer patients: a retrospective 6-year study. 937 74

Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (approximately 10-fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, amongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were approximately 10-fold and approximately 15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immunoreactive PAI-1 was considerably elevated (> 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only approximately 2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (approximately 10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer.
Clin Exp Metastasis 1998 Apr
PMID:Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells. 956 38

The development of tumor metastasis is a multistep process. Key aspects of this process are the interaction of tumor cells with the extracellular matrix, digestion of, and motility through the basement membrane and the induction of angiogenesis. In this study, we analysed the effects of a low dose of TPA (12-tetradecanoylphorbol-13-acetate; 0.1 microM on angiogenesis, proteolytic activity and lung colonizing potential of both weakly metastatic B16F1 cells and highly metastatic BL6 murine melanoma cells. Our results demonstrated opposite effects of TPA in the two cell lines. TPA-treated B16F1 cells showed enhanced release of basic FGF (bFGF) and vascular endothelial growth factor (VEGF) and increased angiogenic capacity and lung colony formation in vivo. In contrast, TPA-treated BL6 cells demonstrated a dramatic reduction of angiogenic and gelatinolytic activity and metastatic capacity. However, both cell lines showed an induction of VEGF as well as bFGF expression by TPA treatment suggesting that in BL6 cells antagonistic factors, inhibiting the angiogenic and metastatic capacity, are induced by this treatment.
Clin Exp Metastasis 1998 Jul
PMID:Angiogenic capacity and lung-colonizing potential in vivo is increased in weakly metastatic B16F1 cells and decreased in highly metastatic BL6 cells by phorbol esters. 1009 35

Bone metastases are often associated with osteolysis and subsequent pathological fractures. To determine if metastatic human cancer cells can directly degrade non-mineralized and mineralized bone, we used prostate PC3 adenocarcinoma cell lines, which were originally established from skeletal metastases. We show that PC3 cells and their conditioned medium degraded non-mineralized, osteoid-like radiolabelled extracellular matrices from human Saos2 and U2OS osteoblast-like cells. These cells also directly degraded mineralized bone by inducing (45)Ca release from rat fetal calvariae and forming resorption pits on bone slices, an effect increased by transforming growth factor-beta(1). A role for matrix metalloproteinases in degradation was shown by: (1) stimulation by the phorbol ester TPA of PC3-induced matrix degradation and release of matrix metalloproteinase activity; (2) abrogation of matrix degradation by 1,10-phenanthroline, a metalloproteinase inhibitor, and (3) degradation of purified type I collagen by PC3 cells and their conditioned medium. We demonstrate that human prostate cancer cells can directly degrade bone-related matrices and that matrix metalloproteinases have a role in this process.
Invasion Metastasis
PMID:Human metastatic prostate PC3 cell lines degrade bone using matrix metalloproteinases. 1072 74

The aim of this retrospective study was to assess the value of a serum tumour marker panel in selecting from among the patients with equivocal chest X-ray (CXR) or liver echography (LE) those with thoracic or liver metastases respectively. Between January 1984 and December 1999, 467 (341 non-relapsed and 126 metastatic) breast cancer patients were followed-up postoperatively. Among the 126 metastatic patients 36 showed thoracic (19 patients) or liver (17 patients) metastases, alone or in conjunction with other organs as the first evidence of distant spread. We focused on this series of 377 patients including 341 non-relapsed plus 36 with liver or thoracic metastases. The patients were followed-up after mastectomy with serial determinations of a panel of CEA-TPA-CA15.3 tumour markers, bone scintigraphy, CXR and LE. Up to December 1999, equivocal CXR occurred in 23 (6.1%) patients of whom 11 (47.8%) developed thoracic metastases; 14 (3.7%) patients showed an equivocal LE of whom 5 developed liver metastases. In the 37 patients with equivocal CXR or equivocal LE prolonged clinical and imaging follow-up over 41 +/- 36 months (mean +/- SD, range 3-163) was used to ascertain the presence or absence of thoracic or liver metastases. In the 23 patients with equivocal CXR the negative and positive predictive values of the tumour marker panel to predict thoracic metastases were 92% and 100% respectively. In the 14 patients with equivocal LE the negative and positive predictive values of the tumour marker panel for prediction of liver metastases were 90% and 100% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value for selecting those patients at high risk of developing clinically evident pulmonary or liver metastases from amongst those subjects with equivocal CXR or equivocal LE.
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PMID:The role of tumour markers in improving the accuracy of conventional chest X-ray and liver echography in the post-operative detection of thoracic and liver metastases from breast cancer. 1107 46

The skeleton is the most frequent site of metastatic disease in breast cancer and also the site of greatest morbidity. In addition, there is now recognition that accelerated bone loss associated with chemotherapy or hormonal therapy leads to an increased risk of osteoporosis in long-term breast cancer survivors. An improved range of treatment options is available and assessment of skeletal response both to the disease and to therapy is therefore of growing importance. Plain radiographs remain widely used to assess response, but are of limited sensitivity. The isotope bone scan is more sensitive, but lacks specificity. Computerised tomography, magnetic resonance imaging and positron emission tomography all have an increasing role. In treatment-induced osteoporosis, bone mineral density is now readily measured by DEXA scanning. Tumour markers such as CEA, CA 15-3, CA 549 and TPA may have a role in assessing response, but probably in combination rather than individually, using an appropriate quantitative model. Several trials have shown that bone markers, especially markers of bone resorption such as Ntx, Ctx, PYD and DPD, appear to have strong potential as rapid, convenient and inexpensive measures of response. There is also evidence that they may be used as predictive or prognostic indicators. Evidence is accumulating that the reduction of bone resorption markers into the normal range results in substantially reduced morbidity in metastatic breast cancer and that this should be a major target of therapy.
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PMID:Assessment of the effects of breast cancer on bone and the response to therapy. 1496 99

With the availability of new chemotherapeutic agents such as S-1 and paclitaxel (TXL) for advanced gastric cancer, the development of a strategy for a third-line chemotherapy is urgently needed. We treated a patient with recurrent gastric cancer using TXL, irinotecan hydrochloride (CPT-11) and cisplatin (CDDP) as a third-line chemotherapy. The patient was a 46-year-old man who had undergone total gastrectomy for advanced gastric cancer with lymph node metastases. For postoperative recurrence, he was first treated with S-1 as an outpatient; however, tumor markers increased, and para-aortic lymph node metastasis was revealed by thoracic and abdominal CT scan. A second-line therapy with weekly TXL and CDDP was then added, but resulted in PD. Therefore, combination chemotherapy with TXL, CPT-11 and CDDP was started biweekly as a third-line chemotherapy. TXL (80mg/m2) was infused over 1 hour after short premedication, followed by CPT-11 (25mg/m2) and CDDP (15mg/m2) over 30 min. After 6 courses of this therapy, the serum AFP and TPA returned to normal, and the size of the metastatic para-aortic lymph nodes reduced. The effect of this therapy was judged as PR and the toxicity of this regimen was tolerable. The patient has undergone 10 courses of this therapy and is maintaining a clinical PR. The patient was able to resume his full social activities. TXL, CPT-11 and CDDP combination chemotherapy may be useful and safe for patients with recurrent gastric cancer, even after first-or second-line therapy with S-1 or taxanes.
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PMID:Third-line chemotherapy with paclitaxel, irinotecan hydrochloride and cisplatin for recurrent gastric cancer: a case report. 1578 61

Here, the structure, function, biological and pathological significance and clinical utility of the principal biomolecular markers of breast cancer is reviewed. Each marker was scored for clinical utility using a recently developed tumor marker utility grading system (TMUGS). Among the tissue markers, ERs and PRs are important prognostic/predictive factors and the only tissue markers routinely determined. ER cross-talks with other growth factors while co-regulatory factors enhance (co-activators) or decrease (co-repressors) its transcriptional activity. C-erbB-2 and Ki67/MIB-1 select for adjuvant chemotherapy a subgroup of lymph-node negative patients at a high risk of relapse. Monoclonal antibodies (trastuzumab, gefitinib, erlotinib and bevacizumab) targeting tissue markers and involved in tumor growth and metastasization (EGFR, C-erbB-2, VEGF) have been developed; they showed therapeutical single agent activity as well as potent synergy with chemotherapy agents in metastatic cancer. Among circulating markers, some are potentially useful in the early detection and monitoring of metastatic disease; nevertheless, none is routinely recommended. To suspect distant metastases, CEA-TPA-CA15.3 panel attained accuracy of about 90%. ECD HER2-neu, p53 and nucleophosmin antibodies seem suitable candidates for different associations. Preliminary observations suggest that an early detection with tumor markers and successive treatment of relapses significantly prolongs disease-free and overall survival in selected patients. In conclusion, biomolecular markers are improving understanding of biology and management of breast cancer.
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PMID:Biomolecular markers of breast cancer. 1636 59

Reactive oxygen species (ROS) are recently proposed to be involved in tumor metastasis which is a complicated processes including epithelial-mesenchymal transition (EMT), migration, invasion of the tumor cells and angiogenesis around the tumor lesion. ROS generation may be induced intracellularly, in either NADPH oxidase- or mitochondria-dependent manner, by growth factors and cytokines (such as TGFbeta and HGF) and tumor promoters (such as TPA) capable of triggering cell adhesion, EMT and migration. As a signaling messenger, ROS are able to oxidize the critical target molecules such as PKC and protein tyrosine phosphates (PTPs), which are relevant to tumor cell invasion. PKC contain multiple cysteine residues that can be oxidized and activated by ROS. Inactivation of multiple PTPs by ROS may relieve the tyrosine phosphorylation-dependent signaling. Two of the down-stream molecules regulated by ROS are MAPK and PAK. MAPKs cascades were established to be a major signal pathway for driving tumor cell metastasis, which are mediated by PKC, TGF-beta/Smad and integrin-mediated signaling. PAK is an effector of Rac-mediated cytoskeletal remodeling that is responsible for cell migration and angiogenesis. There are several transcriptional factors such as AP1, Ets, Smad and Snail regulating a lot of genes relevant to metastasis. AP-1 and Smad can be activated by PKC activator and TGF-beta1, respectively, in a ROS dependent manner. On the other hand, Est-1 can be upregulated by H2O2 via an antioxidant response element in the promoter. The ROS-regulated genes relevant to EMT and metastasis include E-cahedrin, integrin and MMP. Comprehensive understanding of the ROS-triggered signaling transduction, transcriptional activation and regulation of gene expressions will help strengthen the critical role of ROS in tumor progression and devising strategy for chemo-therapeutic interventions.
Cancer Metastasis Rev 2006 Dec
PMID:The signaling mechanism of ROS in tumor progression. 1716 Jul 8


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