Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe. The biological activity of marimastat was assessed by serial measurements of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate-specific antigen. Patients were recruited with tumor markers rising by more than 25% averaged over a 4-week screening period. A biological effect was defined as a level of tumor marker at the end of treatment no greater than at study entry; a partial biological effect was defined as a rise in the level of tumor marker over the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were collected and assessed as the studies progressed. All patients were followed up for survival.
 ...
PMID:Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. 960 66

The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.
 ...
PMID:Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers. 962 35

Epithelial glycoprotein EGP-2 and carcinoembryonic antigen (CEA) are transmembrane glycoproteins and cell surface markers. Eighty-four colorectal tumors including 23 adenomas (2 mild, 13 moderate, and 8 severe atypia) and 61 adenocarcinomas (33 well- and 28 moderately differentiated) as well as adjacent normal colonic mucosa (51 cases) were studied for the immunolocalization of EGP-2 as detected by the monoclonal antibody VU-1D9, and compared with CEA expression. In the normal colonic mucosa, basolateral VU-1D9 expression in the surface epithelial cells was constantly seen in all 51 cases, while weak apical CEA staining in the surface epithelium was seen in 25% (13/51) of the cases. In 91% (21/23) of the adenomas, regardless of the grade of atypia, VU-1D9 labeled the basolateral membrane of a few surface lining cells leaving atypically proliferating glands negative, while CEA expressed strong apical staining in the surface epithelial cells as well as atypically proliferating glands. The well-differentiated adenocarcinomas showed homogeneous basolateral staining for VU-1D9 and strong apical staining for CEA; the moderately differentiated adenocarcinomas showed membranous as well as cytoplasmic VU-1D9 staining and luminal as well as cytoplasmic CEA staining. The VU-1D9 and CEA localizations and the stage of expression in relation to tumor progression were completely different. Strong CEA expression was seen in the adenomatous stage, while the homogeneous VU-1D9 expression required tumor progression to the carcinomatous stage. VU-1D9 especially when applied in combination with CEA, will be a useful marker for colorectal lesions, and its reactivity patterns in carcinoma can predict the prognosis.
 ...
PMID:Immunohistochemical localization of epithelial glycoprotein EGP-2 and carcinoembryonic antigen in normal colonic mucosa and colorectal tumors. 985 75

Synchronous primary lung cancer (SPLC) occurs in up to 0.5% of patients with lung cancer. Among SPLC cases, coexistence of small cell carcinoma (SCLC) and non-small cell carcinoma has been reported in a very small fraction. Futhermore, there have been no reports discussing treatment and prognosis of SPLC presenting with SCLC and NSCLC. We report on two cases of SPLC presenting SCLC in limited stage and operable NSCLC. One patient developed synchronously SCLC and adenocarcinoma of the lung, while the other SCLC and squamous cell carcinoma of the lung. The clonal origin of these synchronous lung cancers was evaluated using immunohistochemical and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Both of the patients were diagnosed based on transbronchial lung biopsy (TBLB) and mediastinoscopic biopsy. They were successfully treated with chemoradiotherapy and adjuvant surgery, and are now doing well without any signs of tumor progression for about one year. In both cases, a response of mediastinal lymph node for concurrent chemoradiotherapy was quite different from that of the mass in the lung field. In case 2, p53 mutation was observed in the SCLC tissue, but not in the NSCLC tissue by PCR-SSCP. In both cases, carcinoembryonic antigen was documented in the NSCLC tissue, but not in the SCLC tissue by immunohistochemical staining. This report indicates the importance of the accurate diagnosis of SPLC by employing TBLB and/or media-stinoscopy for the optimal treatment of patients having SPLC presenting with SCLC and NSCLC. Diagnostic criteria and standard treatment of this disease should be established.
 ...
PMID:Synchronous primary lung cancer presenting with small cell carcinoma and non-small cell carcinoma: diagnosis and treatment. 986 5

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.
 ...
PMID:Immunohistopathological characterizatin of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma (HLMC) xenograft. 988 55

We have developed a novel procedure to couple enzymatically the antineoplastic agent doxorubicin (Dox) on the galactose residues of a monoclonal antibody specific for the tumor-associated carcinoembryonic antigen. The synthesis of the immunoconjugate consists of covalent attachment of the NH2 terminus of Dox to oxidized galactose residues of desialylated monoclonal antibody, followed by concurrent stabilization of Schiff bases by mild reduction with pyridine borane. The immunoconjugate preserved both antibody specificity and drug cytotoxicity. At equimolar concentrations, the immunoconjugate was 8 times more cytotoxic against two carcinoembryonic antigen-expressing carcinoma cell lines, LoVo and SW-480, than Dox alone. The intracellular drug accumulation was 8-8.5 times higher than that obtained with free Dox, and >50% of the drug delivered by the conjugate was retained for 24 h in the tumor cells. Only 4 days after treatment with a single dose of immunoconjugate carrying 2.5 ng of Dox, LoVo and SW-480 tumor transplants on the chorioallantoic membrane of embryonated hen eggs showed reduced tumor-induced angiogenesis and tumor progression by half, with no detectable damage to surrounding tissues. In contrast, the same amount of free drug induced insignificant changes in tumor progression and tumor-induced angiogenesis. Enzymatically mediated, glycosidic coupling of antineoplastic agents to antibodies specific for tumor-associated antigens may represent a novel platform for the development of more efficient anticancer agents with reduced side effects.
 ...
PMID:Antineoplastic efficacy of doxorubicin enzymatically assembled on galactose residues of a monoclonal antibody specific for the carcinoembryonic antigen. 989 95

p53 protein overexpression was found to induce the production of antibodies in patient serum and, recently, the easy detection of serum antibodies has been made possible. The aim of this study is to determine the significance of serum p53 antibodies in patients with primary colorectal adenocarcinoma in comparison with their clinicopathological features, and the tumor marker sensitivities of carcinoembryonic antigen (CEA), carcinoma antigen 19-9 (CA19-9) and alpha-fetoprotein (AFP). Thirty-nine of 86 patients (45.3%) were positive for serum p53 antibodies. However, there was no relation with the cancer progression or clinicopathological findings. The sensitivities of CEA, CA19-9 and AFP were 36.0%, 38.4%, and 8.1% respectively, but there was no relation between serum p53 antibodies and these three markers. When the sensitivity of serum p53 antibodies and CEA was evaluated according to clinical stage, the presence of serum p53 antibodies was more significantly associated with stage 0, I and II colorectal cancer than was CEA. Thirty-three patients who showed preoperative positivity for serum p53 antibodies were followed by serial evaluation of circulating antibodies after resection. Negative conversions after resection were significantly higher in the "Cur A" group than in the "Cur B" or "Cur C" groups. Serum p53 antibodies appear to be a useful tumor marker independent of the other markers, especially in the early stage, and are expected to be useful in the development of a method of early diagnosis for mass screening, and as a postoperative monitoring marker for colorectal cancer.
 ...
PMID:[Detection of serum p53 antibodies in colorectal cancer patients and the clinical significance of postoperative monitoring]. 1063 3

In antibody-directed enzyme prodrug therapy, an enzyme conjugated to an antitumor antibody is given i.v. and localizes in the tumor. A prodrug is then given, which is converted to a cytotoxic drug selectively in the tumor. Ten patients with colorectal carcinoma expressing carcinoembryonic antigen received antibody-directed enzyme prodrug therapy with A5B7 F(ab')2 antibody to carcinoembryonic antigen conjugated to carboxypeptidase G2 (CPG2). A galactosylated antibody directed against the active site of CPG2 (SB43-gal) was given to clear and inactivate circulating enzyme. A benzoic acid mustard-glutamate prodrug was given when plasma enzyme levels had fallen to a predetermined safe level, and this was converted by CPG2 in the tumor into a cytotoxic form. Enzyme levels derived from quantitative gamma camera imaging and from direct measurements in plasma and tumor biopsies showed that the median tumor:plasma ratio of enzyme exceeded 10000:1 at the time of prodrug administration. Enzyme concentrations in the tumor (median, 0.47 units g(-1)) were sufficient to generate cytotoxic levels of active drug. The concentration of prodrug needed for optimal conversion (Km) of 3 microM was achieved. Prodrug conversion to drug was shown by finding detectable levels of drug in plasma. There was evidence of tumor response; one patient had a partial response, and six patients had stable disease for a median of 4 months after previous tumor progression (one of these six had a tumor marker response). Manageable neutropenia and thrombocytopenia occurred. Conditions for effective antitumor therapy were met, and there was evidence of tumor response in colorectal cancer.
 ...
PMID:Antibody-directed enzyme prodrug therapy: efficacy and mechanism of action in colorectal carcinoma. 1074 95

The soluble form of carcinoembryonic antigen (sCEA), an oncofetal glycoprotein, is frequently produced by human epithelial-tumor cells, particularly of colorectal origin, and evaluated as a prognostic index of tumor progression and patient survival. sCEA molecules are often present at high concentrations in the peripheral blood of colorectal cancer patients, but the function and significance of this are not well understood. Reported data have demonstrated that sCEA can interfere in NK-cell/tumor-cell interaction by drastically reducing the lysis of tumor cells in a dose-dependent manner and can also suppress T and B cell functions. The aim of our study was to evaluate this situation in colorectal cancer by determining peripheral blood immunological parameters in a group of patients and healthy subjects. We evaluated the interleukin (IL)-2, interferon (IFN) gamma, IL-4, sIL-2R and IL-10 levels in the serum and the release of IFN gamma, IL-4 and IL-10 from peripheral blood mononuclear cells (PBMC); the PBMC expression of CD3, CD16 and CD19 phenotypic antigens; the PBMC proliferative responses to IL-2, IL-2 + anti-CD3 monoclonal antibody (mCD3) and mCD3. The statistical evaluation of our overall results strongly indicates that the high level of the sCEA molecules in the patient's serum might act as a suppressive factor for NK and TH1 immunocompetent cells. This may be the cause of sCEA involvement in tumor progression, and indicates the possibility of an improvement in cancer treatment through its manipulation.
 ...
PMID:The sCEA molecule suppressive role in NK and TH1 cell functions in colorectal cancer. 1085 73

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)a (CA19-9), sialyl Lex (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior.
 ...
PMID:The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer. 1100 66


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