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)

Elevation of established blood tumour markers correlates with the stage of breast cancer. The major role of current blood markers is therefore in the diagnosis and monitoring of metastatic disease. A combination of markers is better than a single marker with the most widely adopted combination being CEA and one MUC1 mucin, commonly detected as either CA15.3 or CA27.29. Tumour marker measurement is now used as a complementary test in the diagnosis of symptomatic metastases. In the monitoring of therapeutic response to both endocrine and cytotoxic therapies in advanced disease, biochemical assessment using blood markers not only correlates with conventional UICC criteria but has a lot of advantages which make it a potentially superior way of assessment. In this regard, CA15.3, CEA and ESR are the best validated combination. Studies are ongoing to evaluate the use of sequential blood tumour marker measurements in the follow-up of patients after treatment for their primary breast cancer, in terms of both early detection and early therapeutic intervention. Further randomized studies are also required to ascertain that marker-directed therapy is superior to the current practice for metastatic disease. In line with clinical studies, intensive laboratory work is being carried out to optimize the use of blood markers in advanced disease as well as to exploit their use in screening and diagnosis of early primary breast cancer.
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PMID:Tumour marker measurements in the diagnosis and monitoring of breast cancer. 1077 67

Mucins are large glycoproteins that form a protective layer along the lumens of the organs of the gastrointestinal and reproductive tracts. Frequently in tumors of the pancreas there are changes in the structure of mucin carbohydrates and/or levels of apomucin types. Originally mucins were of interest clinically because diagnostic tests could be based on their levels in circulation. More recently mucin directed monoclonal antibodies have been used to target tumors with cytotoxic agents. There is now a considerable literature on the development of mucin-based vaccines. Both monoclonal antibodies and vaccines could be powerful tools to specifically target tumor cells in distant metastases. Gene therapy based upon the MUC1 gene promoter is being investigated to target therapeutic genes to MUC1 expressing cells. The carbohydrates of mucins on the surface of tumor cells have been reported to inhibit cells of the immune system. These carbohydrates also act as ligands during the process of tumor cell metastasis. Another approach to therapy is to block interactions between the ligands and their receptors.
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PMID:Mucins in the diagnosis and therapy of pancreatic cancer. 1110 66

Mice transgenic for the human MUC1 carcinoma-associated antigen (MUC1.Tg) are tolerant to immunization with MUC1 antigen. Recent studies, however, have demonstrated that immunization of MUC1.Tg mice with fusions of MUC1-positive tumour and dendritic cells (FC/MUC1) reverses MUC1 unresponsiveness and results in rejection of established MUC1-positive pulmonary metastases. Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7-1, B7-2, CD28, CD40 and CD40 ligand. The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1-specific CD8+ T cells. We show that the CD8+ T cells exhibit MUC1-specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules Kb and Db. The MUC1-specific CD8+ T cells also exhibit antitumour activity against MUC1-positive metastases, but with no apparent reactivity against normal tissues. These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC-restricted MUC1-specific CD8+ T cells.
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PMID:Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells. 1110 34

Human MUC1 mucin, a membrane-bound glycoprotein, is a major component of the ductal cell surface of normal glandular cells. MUC1 is overexpressed and aberrantly glycosylated in carcinoma cells. The role MUC1 plays in cancer progression represents two sides of one coin: on the one hand, loss of polarity and overexpression of MUC1 in cancer cells interferes with cell adhesion and shields the tumor cell from immune recognition by the cellular arm of the immune system, thus favoring metastases; on the other hand, MUC1, in essence a self-antigen, is displaced and altered in malignancy and induces immune responses. Tumor-associated MUC1 has short carbohydrate sidechains and exposed epitopes on its peptide core; it gains access to the circulation and comes into contact with the immune system provoking humoral and cellular immune responses. Natural antibodies to MUC1 present in the circulation of cancer patients may be beneficial to the patient by restricting tumor growth and dissemination: early stage breast cancer patients with a humoral response to MUC1 have a better disease-specific survival. Several MUC1 peptide vaccines, differing in vectors, carrier proteins and adjuvants, have been tested in phase I clinical trials. They are capable of inducing predominantly humoral responses to the antigen, but evidence that these immune responses may be effective against the tumor in humans is still scarce.
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PMID:Human MUC1 mucin: a multifaceted glycoprotein. 1119 32

Mucin1 (MUCI) is a class of high molecular weight glycoproteins found in the cell membranes of human epithelial cells. Epithelial glycoprotein 40 (EGP40) is a homophilic cell-cell adhesion molecule and expressed on the surface of most simple epithelial cells and the majority of carcinomas. We analyzed the expression of MUC1 and EGP40 in human bone marrow (BM) and peripheral blood (PB) by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC). Eight BM and 95 PB samples from healthy donors, 39 BM and 17 PB samples from patients with haematological malignancies and 45 BM samples from patients with breast cancer were analyzed. MUC1 mRNA and EGP40 mRNA and protein were detected in BM samples and PB samples from healthy donors and from patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and chronic myelogenous leukaemia (CML). The positive cells showed erythroblast-like and plasmacell-like morphology by immunocytochemistry. The MUC1 and EGP40 nested PCR were positive in 83.3% (10/12) and in 100% (33/33) respectively of BM from patiens with breast cancer who had no evidence of distant metastases. It is concluded that MUC1 and EGP40 is expressed in haematopoietic tissues and haematological malignancies. Therefore, MUC1 and EGP40 expression as a marker for detection of breast cancer cells and micrometastatic epithelial cells in BM and PB is not specific using RT-PCR technique and immunocytochemistry.
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PMID:Evaluation of MUC1 and EGP40 in bone marrow and peripheral blood as a marker for occult breast cancer. 1120 3

A correlation between MUC1 expression in renal cell carcinomas (RCCs) and the clinical stages was previously demonstrated. To assess whether MUC1 expression is causally related to malignant tumor behavior, MUC1 cDNA was stably transfected into a renal carcinoma cell line SN12C that expresses trace levels of MUC1. MUC1 with sialylated carbohydrate chains was detected on the surface of transfected cells in two independent experiments. There was no correlation between MUC1 expression and in vitro growth and motility. In vivo growth of the transfectants at the site of orthotopic transplantation in nude mice was slower than mock transfected cells. Therefore, MUC1 alone did not seem to confer a malignant phenotype to RCCs.
Clin Exp Metastasis 2000
PMID:Absence of correlation of MUC1 expression to malignant behavior of renal cell carcinoma in experimental systems. 1120 42

MUC1 is a large (>400 kDa), heavily glycosylated transmembrane protein that is aberrantly expressed on greater than 90% of human breast carcinomas and subsequent metastases. The precise function of MUC1 overexpression in tumorigenesis is unknown, although various domains of MUC1 have been implicated in cell adhesion, cell signaling, and immunoregulation. Stimulation of the MDA-MB-468 breast cancer line as well as mouse mammary glands with epidermal growth factor results in the co-immunoprecipitation of MUC1 with a tyrosine-phosphorylated protein of approximately 180 kDa. We have generated transgenic lines overexpressing full-length (MMF), cytoplasmic tail deleted (DeltaCT), or tandem repeat deleted (DeltaTR)-human MUC1 under the control of the mouse mammary tumor virus promoter to further examine the role of MUC1 in signaling and tumorigenesis. Immunoprecipitation experiments revealed that full-length transgenic MUC1 physically associates with all four erbB receptors, and co-localizes with erbB1 in the lactating gland. Furthermore, we detected a sharp increase in ERK1/2 activation in MUC1 transgenic mammary glands compared with Muc1 null and wild-type animals. These results point to a novel function of increased MUC1 expression, potentiation of erbB signaling through the activation of mitogenic MAP kinase pathways.
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PMID:Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland. 1127 68

Current radiological techniques for staging bladder cancer are inaccurate, especially in the identification of pelvic lymph node metastases. Immunoscintigraphy has the potential to offer improved staging for bladder cancer. The aim of this study was to label the anti-MUC1 monoclonal antibody C595 with 99mtechnetium (Tc), the most widely used diagnostic radionuclide, and assess the potential of the resultant conjugate for intravenous immunoscintigraphy of bladder cancer. A direct, reduction-mediated technique was used to label the antibody. The resultant conjugate was shown to be highly immunoreactive, stable and bound specifically to MUC1. The ability of the conjugate to bind to bladder tumours was demonstrated in an ex vivo model where the mean tumour:normal urothelial uptake was 5.7:1 and by intravesical administration in patients with bladder cancer where the mean tumour:normal urothelial uptake was 20.4:1. The ability of the conjugate to localise MUC1-expressing tumours was demonstrated in a nude mouse xenograft model. A conjugate of 99mTc-C595 has been produced and characterised, and it may be suitable for intravenous immunoscintigraphy, a potential novel staging tool for bladder cancer.
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PMID:Production and characterisation of a C595 antibody-99mTc conjugate for immunoscintigraphy of bladder cancer. 1131 Feb 9

The fate of breast cancer patients is dependent upon elimination or control of metastases. We studied the effect of antibody-targeted liposomes containing entrapped doxorubicin (DXR) on development of tumours in two models of breast cancer, pseudometastatic and metastatic, in mice. The former used the mouse mammary carcinoma cell line GZHI, which expresses the human MUC-1 gene (L. Ding, E.N. Lalani, M. Reddish, R. Koganty, T. Wong, J. Samuel, M.B. Yacyshyn, A. Meikle, P.Y.S. Fung, J. Taylor-Papadimitriou, B.M. Longenecker, Cancer Immunol. Immunother. 36 (1993) 9--17). GZHI cells seed into the lungs of Balb/c mice following intravenous injection. The latter used the 4T1-MUC1 cell line, a MUC-1 transfectant of the mouse mammary carcinoma cell line 4T1, which metastasizes from a primary mammary fatpad (mfp) implant to the lungs (C.J. Aslakson, F.R. Miller, Cancer Res. 52 (1992) 1399--1405). B27.29, a monoclonal antibody against the MUC-1 antigen, was used to target sterically stabilized immunoliposomes (SIL[B27.29]) to tumour cells. In vitro, SIL[B27.29] showed high specific binding to both GZHI and 4T1-MUC1 cells. The IC(50) of DXR-loaded SIL[B27.29] was similar to that of free drug for GZHI cells. In the pseudometastatic model, mice treated with a single injection of 6 mg DXR/kg in DXR-SIL[B27.29] at 24 h after cell implantation had longer survival times than those injected with non-targeted liposomal drug. In the metastatic model, severe combined immune deficiency mice given weekly injectionsx3 of 2.5 mg DXR/kg encapsulated in either targeted or non-targeted liposomes were almost equally effective in slowing growth of the primary tumour and reducing development of lung tumours. Surgical removal of the primary tumour from mfp, followed by various chemotherapy regimens, was attempted, but removal of the primary tumour was generally incomplete; tumour regrowth occurred and metastases developed in the lungs in all treatment groups. DXR-SL reduced the occurrence of regrowth of the primary tumour, whereas neither targeted liposomal drug or free drug prevented regrowth. We conclude that monoclonal antibody-targeted liposomal DXR is effective in treating early lesions in both the pseudometastatic and metastatic models, but limitations to the access of the targeted liposomes to tumour cells in the primary tumour compromised their therapeutic efficacy in treating the more advanced lesions.
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PMID:Anti-MUC-1 immunoliposomal doxorubicin in the treatment of murine models of metastatic breast cancer. 1134 46

The serum tumor markers CA 125, MUC1 and CEA were measured in 221 breast cancer patients over a period of 2 years. Patients examined on at least three occasions were included in the study. Thirty-three patients had increasing or continuously high concentrations of CA 125. Thirty (91%) of these had involvement of the pleura, either as pleural metastasis or metastasis in surrounding tissue i.e. bone structures in the thorax cavity or lung parenchyma. MUC1 and CEA were elevated in 27 (82%) and 24 (73%) of the 33 patients, respectively. Increased concentrations of these two markers did not relate to the site of metastasis. However, the three tumor markers complemented each other in detecting early metastases. Increased CA 125 was associated with metastasis in or near the pleura, and in stage IV breast cancer it was related to poor prognosis.
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PMID:Elevated CA125 in breast cancer--A sign of advanced disease. 1139 47


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