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)

Osteosarcomas and rhabdomyosarcomas are vigorously invading tumors. Before they can extravasate to the parenchymal organs and form metastases, they have to adhere to the endothelial cells lining the blood vessels and then penetrate through the endothelium. We show that several human sarcoma cell lines, osteosarcomas HOS, MG-63, U2-OS, and a rhabdomyosarcoma RD, express VLA-4 molecule on their surface and bind to the VCAM-I-expressing activated endothelial cell line Ea.hy 926. The increased sarcoma-cell adhesion could be abolished by treating the sarcoma cells with monoclonal antibodies (MAbs) VLA4 (both alpha- and beta-chain, HP2/1 and 4B4 respectively) or treating endothelial cells with VCAM-I antibody (4B9). Furthermore, we show that sarcoma cells adhere to recombinant soluble VCAM-I protein. On the other hand, these sarcoma cell lines do not express marked amounts of other ligands (such as CDII/18 or sialyl-Lex) for other endothelial adhesion molecules (ICAM-I, ICAM-2, E- and P-selectin) indicating that the VLA-4-VCAM-I dependent pathway might be of major importance in sarcoma extravasation. VLA-4 is not always in an avid form and therefore the expression of VLA-4 does not directly predict adherence to VCAM-I. The avidity of VLA-4 (measured by adherence to soluble VCAM-I) of MG-63 and U2-OS cells could be increased by a 30-min PMA treatment, whereas the avidity of VLA-4 on HOS cells increased only after 48 hr of PMA induction. Our results show that sarcoma cell lines (HOS, MG-63, U2-OS and RD) adhere to stimulated endothelium via VLA-4-VCAM-I adhesion molecules and that VLA-4 avidity on sarcoma cells can be differentially modulated by PMA.
 ...
PMID:VLA-4 integrin on sarcoma cell lines recognizes endothelial VCAM-1. Differential regulation of the VLA-4 avidity on various sarcoma cell lines. 128 Nov 43

The results of this clinical trial involving 23 sites indicated that 111In-CYT-103 immunoscintigraphy identified 70% of all patients with surgically confirmed disease when interpreted by the on-site physician. The sensitivity of 111In-CYT-103 imaging was slightly lower when interpreted retrospectively by the blinded readers in the absence of any patient-specific information. 111In-CYT-103 imaging sensitivity was similar in patients with primary and recurrent disease, but lower for liver metastases than for extrahepatic disease. Thirty-three previously unknown lesions were visualized by immunoscintigraphy; tissue confirmation was available for only five lesions, and all were found to be free of tumor. Only one of the lesions evaluated was TAG-72 positive. Twenty-eight lesions were outside the surgical field or not biopsied. Although no tissue confirmation was available, seven (25%) of these lesions were identified as consistent with metastatic disease by other conventional modalities. Importantly, antibody scans detected occult tumor lesions in 11 of the 92 patients with surgically confirmed adenocarcinoma, and accurately diagnosed 7 of 10 patients with elevated serum CEA levels and negative conventional workup. Surgery confirmed the presence of tumor identified only by 111In-CYT-103 in three patients, while four patients with negative scans had no evidence of recurrent disease at surgery. Antibody scans confirmed the absence of additional disease in 18 of 22 patients with isolated hepatic or pelvic recurrences in whom curative surgery was contemplated. The results of this multicenter trial suggest that CYT-103 immunoscintigraphy can provide information that is complementary to that derived from standard diagnostic techniques. During the workup of patients with primary colorectal carcinoma, this modality assesses the entire body and allows for the identification of multiple lesions at various locations simultaneously. It can then redirect attention and further workup to those areas not originally surveyed. Of special interest in this regard is the identification of occult lesions in five patients with primary colorectal cancer. 111In-CYT-103 imaging was found superior to CT in the localization of primary colorectal cancer, but neither modality could adequately assess the extent of tumor penetration through the bowel wall (the T stage in the TNM system) or the N status. The limitations of CT in evaluating T and N are well documented, and the limitations of 111In-based immunoscintigraphy for these same lesions have recently been described. Another limitation of 111In-CYT-103 immunoscintigraphy is in the identification of liver metastases.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Multicenter clinical trials of monoclonal antibody B72.3-GYK-DTPA 111In (111In-CYT-103; OncoScint CR103) in patients with colorectal carcinoma. 157 51

In 95% of patients with primary breast cancer, the extent of metastases cannot be proven by conventional methods. Nevertheless, more than 50% of these patients have a relapse within five years. To improve the predictive value for recurrency, we examined bone marrow aspirates of 128 patients with primary breast cancer. Bone marrow aspirates from 2-6 sites of the skeleton (iliac crest and sternum) were taken as well as biopsies for histological examination. The immunohistochemical studies were carried out on interphase smears and stained with cytoceratin antibodies (PKK 1) and antibodies against tumor-specific antigen TAG 12 (12 H 12). All patients were screened for distant metastases (X-ray, ultrasound, bone scan). Tumor cells and micrometastases in bone marrow were detected in 41 patients (32%). Their presence was correlated to other prognostic factors (tumor size, lymph node status, oestrogen/progesterone receptors). The median duration of follow-up was 39.5 months. 14 patients (45%) in the tumor cell positive group relapsed, compared to only 4 out of 36 patients in the tumor cell negative group. In 29% we found bone metastases. The relapse free interval was shorter for patients with micrometastases (8 vs. 15.8 months). The presence of tumor cells in bone marrow aspirates detected at the time of primary surgery, is a useful prognostic factor and a good predictor of metastases and may help in selecting patients for systemic adjuvant treatment.
 ...
PMID:[The prognostic significance of tumor cell detection in bone marrow of patients with breast cancer]. 170 40

We analyzed the immunohistochemical expression of three epitopes of the tumor-associated glycoprotein 72 (TAG-72) in whole cross-sections of primary colorectal carcinomas and in regional lymph node metastases using monoclonal antibodies (MAbs) B72.3, CC-49, and CC-83, which recognize distinct carbohydrate antigenic determinants. B72.3, CC-49, and CC-83 reacted with 13 of 27 (48%), 25 of 27 (92%), and 21 of 27 (77%) carcinomas, respectively. The immunoreactivity with lymph node metastases followed a similar pattern; MAb CC-49 was again the most reactive of the three antibodies, since it labeled 13 of 15 metastatic lesions. Positive reactions of the MAbs with the primary tumors were not always predictive of the immunorecognition of their metastases. Distinct areas within whole cross-sections of TAG-72-positive primary carcinomas demonstrated marked differences in the expression of the three epitopes. CC-49 tended to react with the highest number of areas and with the highest percentages of carcinoma cells within each area. In no instances did B72.3 demonstrate reactivity superior to that of either CC-49 or CC-83. Tumors negative for the CC-49 epitope in any area also did not express the other two TAG-72 epitopes. However, the comparison of the immunostaining obtained with each MAb in TAG-72-positive primary lesions revealed areas where CC-83 was clearly more reactive than CC-49. Moreover, one lymph node metastasis, negative for CC-49, was recognized by CC-83. Thus, the combined use of MAbs CC-49 and CC-83 resulted in additive immunostaining of primary and metastatic colorectal carcinoma cells. The study provides evidence of intratumoral heterogeneity in the glycosylation pattern of the TAG-72 antigen in colorectal cancer and emphasizes the advantages of cocktails of anti-tumor-associated antigen MAbs in the immunodetection of colorectal tumor cells.
 ...
PMID:Regional heterogeneity and complementation in the expression of the tumor-associated glycoprotein 72 epitopes in colorectal cancer. 171 50

Monoclonal antibodies against a tumor-associated antigen (TAG-72) with mucin-like properties have been generated. MAb B72.3 was used to identify and help characterize this antigen. B72.3 has been successfully used for the localization of tumor metastases in situ after i.v. administration. MAb B72.3 has also been used in conjunction with CC49, another anti-TAG-72 MAb, to measure TAG-72 levels in sera and effusions. TAG-72 can be found in the fluids of patients with adenocarcinomas from many different sites. This CA 72-4 double determinant radioimmunoassay in conjunction with assays for carcinoembryonic antigen can identify patients with malignancies with greater sensitivity than either assay alone.
 ...
PMID:In vivo and in vitro clinical applications of monoclonal antibodies against TAG-72. 186 28

Differentiation between primary colonic adenocarcinoma arising in flat mucosa and carcinoma metastatic to the colon is often difficult. Examination of the mucosa adjacent to the tumor, the so-called transitional mucosa (TM), may be helpful. The morphologic, ultrastructural, and histochemical characteristics of the TM have been reported previously in detail. In this study the morphologic and immunohistochemical characteristics of the TM have been compared in 18 cases of primary colonic adenocarcinoma and 13 cases of metastasis to the colon. Five immunophenotypic markers were used: carcinoembryonic antigen (CEA), Lewis (x) and (y) blood group antigens, ras oncogene p21, and tumor-associated glycoprotein (TAG-72). Neoplastic transformation of colonic epithelium is associated with altered expression of these antigens. The morphologic and immunohistochemical profile of the TM was similar in both primary colonic adenocarcinomas and metastases to the colon. In some cases the TM adjacent to colonic metastases stained with one or more antibodies while the metastatic tumor was negative. Therefore, in cases where differentiation between primary colonic adenocarcinoma arising in flat mucosa and metastasis is difficult, the use of these reagents, particularly CEA, TAG-72, or ras oncogene p21, may be helpful. The similar immunohistochemical staining pattern of the TM in both primary and metastatic colon lesions supports a reactive, non-neoplastic origin of the TM. Furthermore, expression of these antigens is not limited to neoplastic epithelial cells.
 ...
PMID:Role of the transitional mucosa of the colon in differentiating primary adenocarcinoma from carcinomas metastatic to the colon. An immunohistochemical study. 198 61

Intrapancreatic and subcutaneous (SC) inoculation of cultured pancreatic cancer cells, derived from an induced primary pancreatic cancer in a Syrian hamster, resulted in tumor take in all recipient hamsters. The intrapancreatic allografts grew rapidly, were invasive, and metastasized into the lymph nodes and liver in 2 of 9 cases. In comparison, SC tumors grew relatively slower and formed a large encapsulated mass without invasion and metastases. Histologically, tumors of both sites showed fairly well-differentiated adenocarcinomas of ductal/ductular type resembling the induced primary cancer. Similar to the primary induced pancreatic cancers, tumor cells of both allografts expressed blood-group-related antigens, including A, B, H, Le(b), Le(y), Le(x), and tumor-associated antigen TAG-72. The tumor cells did not express Le(a), CA 19-9, 17-1A, or DU-PAN-2. The expression of these antigens was retained in the metastases and presented the same patterns of reactivity as the allografts. Thus intrapancreatic transplantation provides a rapid model for production of pancreatic cancer with morphologic similarities to human pancreatic cancer.
 ...
PMID:Development of intrapancreatic transplantable model of pancreatic duct adenocarcinoma in Syrian golden hamsters. 200 Sep 35

Sixteen patients with primary breast cancer were studied with a pancarcinoma monoclonal antibody B72.3, an IgG1 molecule directed against tumor-associated glycoprotein (TAG-72) present in several tumors. Five millicuries of 111In was used to label 0.2 mg (six patients), or 2 mg (six patients), or 20 mg using the site-directed bifunctional DTPA method (at carbohydrate moiety). Digital, planar, and SPECT images were obtained at 2, 48, 72 and 96 hr when possible. HAMA levels were obtained before the Mab infusion and at 1, 3, and 6 wk postinfusion. Fourteen of 14 known primary breast lesions were detected by imaging (100% sensitivity). Two fibrocystic lesions were negative. Seven of 14 patients had lymph node metastases by histologic methods, but all were missed by radioimmunoscintigraphy. Tumor uptake of Mab ranged 0.00054%-0.0038% of the ID/g. The tumor-to-normal breast tissue ratio was 4.3 +/- 0.91 (mean +/- s.e.m.). Lymph nodes localization of 111In-B72.3 by tissue analysis was similar for tumor-bearing and normal nodes (0.0039 +/- 0.0023 versus 0.0025 +/- 0.0019). Pharmacokinetics revealed mean plasma half-life of 33.3-41.2 hr for the different doses. There was no statistical difference between any of the pharmacokinetic parameters of different doses. HAMA was positive only in 17% of the patients. The study suggests that this antibody has 100% sensitivity for primary breast cancers, but very poor detection rate of metastatic lesions in axillary lymph nodes; thus making it of questionable value in the initial staging process of this disease.
 ...
PMID:Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study. 206 85

A monoclonal antibody 7A9 was raised against the tumour-associated glycoprotein TAG-12 purified from T47-D breast carcinoma cells. In immunoblots from cytosol of T47-D cells and from sera of breast cancer patients, antibody 7A9 detects the high molecular weight mucin-like TAG-12 antigen. A series of paraffin sections of normal, benign and malignant mammary tissues have been studied with monoclonal antibody 7A9 and the immunoalkaline phosphatase method. In resting gland, proliferating gland and fibroadenoma ducts, reactivity of 7A9 was mainly restricted to luminal membranes of epithelial cells and secretions. 77/79 primary breast carcinomas including ductal, lobular and various other carcinoma types showed cytoplasmic and/or membrane-associated staining with 7A9 in most tumour cells. Metastases (31/31) from different sites were also positive. Strong immunoreactivity with single tumour cells was noted in cytological preparations from freshly resected breast cancer tissue. Thus, monoclonal antibody 7A9 seems to be very useful for the targeting of breast carcinoma cells.
 ...
PMID:Analysis of the tumour-associated antigen TAG-12 by monoclonal antibody 7A9 in normal, benign and malignant mammary tissues. 215 77

Immunohistochemical techniques were used to evaluate the expression of six antigens (CA 125, TAG 72, CA 19-9, OVTL3, DF3, and transferrin receptor) in frozen sections from the primary tumor and metastases of 20 patients with epithelial ovarian cancer. Heterogeneous expression of most antigens was observed within a given tumor nodule, but in each patient the proportion of cells expressing an antigen was similar in the primary tumor and metastases. To explore the stability of the antigenic phenotype of individual cells, we studied CA 125 expression in an ovarian cancer cell line. Cells were separated into CA 125-positive and -negative groups using fluorescence-activated cell sorting. After the two groups of cells were recultured separately, only 38% of cells originally sorted as CA 125 positive still expressed CA 125, whereas 27% of cells sorted as CA 125 negative expressed CA 125. That cells may gain or lose CA 125 expression in culture suggests that expression of CA 125 by ovarian cancer cells is not a stable trait.
 ...
PMID:Heterogeneity of antigen expression in advanced epithelial ovarian cancer. 232 61


1 2 3 4 5 6 7 Next >>