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)

Patients with an elevated level of cathepsin D in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of cathepsin D detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both anterior iliac crests in 290 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: BM2, which detects tumour-associated glycoprotein TAG 12, which is typically expressed by almost all breast cancer cells, and the anti-cathepsin D antibody. 67 of 149 BM2-positive women (45%) developed metastatic disease (median follow-up time: 69 months). Of these, 15 were cathepsin D-positive (22%). Patients with cathepsin D-positive cells in bone marrow (n = 26; 9%) had a significantly shorter metastasis-free interval (38 months) compared with women who were cathepsin D-negative (64.5 months). The worst prognosis was seen in patients positive for both markers (30.5 months), followed by those who were cathepsin D-negative and BM2-positive (48 months). The detection of cathepsin D on disseminated tumour cells characterises a subgroup of patients with a poorer prognosis who should undergo more aggressive adjuvant systemic therapy.
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PMID:Prognostic relevance of cathepsin D detection in micrometastatic cells in the bone marrow of patients with primary breast cancer. 969 97

Twenty-one patients with histologically proven locally advanced breast cancer (LABC) were treated with a combined modality approach based on primary chemotherapy and radical modified mastectomy followed by adjuvant chemotherapy. Surgery was performed by using radioimmunoguided surgery (RIGS) technique with the preoperative injection of Iodine-125 labeled monoclonal antibodies (MoAbs) B72.3 anti-TAG (11 patients, Group A) and FO23C5 anti-carcinoembryonic antigen (CEA; 10 patients, Group B). The role of RIGS was defined at surgery by using an intraoperative hand-held gamma-detecting probe (GDP) to locate the primary tumor, possible clinically occult multicentric foci and ipsilateral lymph node metastases. In Group A, RIGS correctly defined the primary tumor in seven out of 11 patients (63.3%) and was able to find multicentric tumors in two out of four patients (50%). Positive lymph nodes were identified by RIGS in three out of eight patients (37.5%). In Group B, patients RIGS correctly located the primary in 4/10 cases (40%); in two RIGS-positive cases, the tumor was clinically not evident after primary chemotherapy (yT0). RIGS correctly identified multicentric foci of tumor in one out of two cases (50%). Correct lymph nodal RIGS assessment was observed in three out of nine patients (33.3%). No RIGS false-positive findings occurred in the 21 patients included in the study. RIGS appears to be a reliable technique for the intraoperative diagnosis and staging of breast cancer with a potential role especially when conservative surgery is planned after primary chemotherapy in LABC.
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PMID:Use of radioimmunoguided surgery after induction chemotherapy in locally advanced breast cancer. 982 81

The detection of malignant cells in pleural, peritoneal, and pericardial fluids of cancer patients marks the presence of metastatic disease and is associated with a grave prognosis. We evaluated five epithelial markers for the detection of cancer cells in 94 fresh pleural, peritoneal and pericardial effusions. Eighty-four of the samples were regarded as adequate for analysis after evaluation of cytological smears, including 61 samples from patients known to have gynaecological neoplasms. The other 23 samples were from patients with various non-gynaecological malignancies or tumours of unknown origin. Our control cases were 10 fallopian tubes not affected by any malignancy and 12 malignant mesotheliomas. Cell blocks from all cases were stained for CA-125, BerEP4, carcinoembryonic antigen (CEA), BG8 (Lewis Y blood antigen), and B72.3 (TAG-72). Fifty-one of 84 cases were diagnosed as malignant or suggestive of malignancy in cytological smears and/or cell block sections. However, staining for epithelial markers highlighted the presence of malignant cells in 7 additional cases. When membrane staining was evaluated, the sensitivity of the markers studied in detecting malignant cells was as follows: CA-125: 88%, BerEP4: 78%, CEA: 26%, BG8: 86%, B72.3: 79%. Membrane positivity for CEA, B72.3 and BerEP4 was not detected in reactive mesothelial cells. However, membranous staining in mesothelial cells was evident in 13% and 31% of cases with the use of BG8 and CA-125, respectively. Weak cytoplasmic staining for CEA was observed in mesothelial cells in 2 cases. When Ber-EP4, B72.3, and BG8 staining results in cancer cells were combined, the following sensitivity levels were observed: BG8+B72.3: 91%; BG8+Ber-EP4: 90%; B72.3+Ber-EP4: 93%; BG8+Ber-EP4+B72.3: 95%. The detection of malignant cells in effusions is facilitated by the use of immunocytochemistry using a wide panel of antibodies. BerEP4 and B72.3 appear to be the best markers when both sensitivity and specificity are considered, followed by BG8, while CEA and CA-125 have a limited role in the detection of metastases from gynaecological tumours owing to the low sensitivity of the former and the low specificity of the latter. Analysis of all staining results should be based on a thorough morphological examination.
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PMID:Detection of cancer cells in effusions from patients diagnosed with gynaecological malignancies. Evaluation of five epithelial markers. 1043 45

KAI-1 is a tumor suppressor gene whose down-regulation has been shown to be associated with the development of metastases of cancer cells. Here, we demonstrated that KAI-1 expression was induced by activating protein kinase C even in metastatic prostate cancer cell lines in which its expression was significantly down-regulated. KAI-1 expression was enhanced in a dose-dependent manner by PMA, and its induction is at least in part due to transcriptional activation. Pretreatment with calphostin C abrogated its induction by PMA. Our findings may provide useful information for developing a novel drug capable of inducing KAI-1 expression and thereby inhibiting metastasis.
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PMID:Induction of KAI-1 expression in metastatic cancer cells by phorbol esters. 1077 34

Analyses were performed on 40 patients with TAG-72 expressing metastatic cancer who were entered into three phase II clinical trials. The dose selected was the maximum tolerated dose in phase I studies. Patients all had unresectable metastatic colon or prostate cancer and had recovered from prior therapies. Patients in trials #1 and #2 received 75 mCi/m2 131I-CC49 antibody whereas those in trial #3 received a total of 75 mCi/m2 with equal amounts of 131I-CC49 and 131I-COL-1. The three trials have resulted in a reproducible degree of reversible marrow suppression; 72.5% of patients experienced moderate or severe toxicity. Comparisons were made between demographic, clinical and pharmacokinetical variables and the grade of WBC toxicity, platelet toxicity and the sum of the two as total toxicity. Whole body radiation dose had a statistically significant relationship with platelet toxicity (r = 0.38, p = 0.015) and total toxicity (r = 0.34, p = 0.035). The bone marrow radiation dose is significantly related to all toxicity indicators with correlation coefficients with WBC and platelet toxicities of 0.47 (p = 0.002) and 0.34 (p = 0.033), respectively. Plasma half-life had the strongest correlation with WBC toxicity and combined toxicities. Multivariate models were developed to help describe the simultaneous effect of these variables on toxicity. The results show that the MTD dose was safely given to patients who varied in age, disease burden and degree of marrow compromise. This supports the contention that a fixed dose of radiolabeled antibody per body mass or m2 can be given to a diverse group of non-lymphoma patients with a predictable toxicity range.
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PMID:Correlation of toxicity with treatment parameters for 131I-CC49 radioimmunotherapy in three phase II clinical trials. 1085 51

A phase II study to evaluate the safety and efficacy of the 125I-radiolabeled anti-TAG-72 monoclonal antibody, CC49, as a component of a system for the intraoperative detection of occult ovarian cancer deposits was carried out at the University of Nebraska Medical Center. Patients entered into the study were to have surgery for evaluation of their disease status. The primary objective of this study was to determine the ability of a gamma-detecting probe (GDP), the Neoprobe 1000, to intraopertively localize sites of disease not identified by traditional surgical or radiographic evaluation. It was postulated that improved detection of cancer foci might allow for therapeutic excision or might result in an alteration of subsequent treatment. Ten patients were enrolled in the study between May 1993 and March 1994. Nine of the patients were undergoing second-look surgery after completing primary chemotherapy. The remaining patient was having surgery to assess possible cancer recurrence. All patients received an intravenous injection of 2 mCi/1 mg 125I-radiolabeled CC49 without complication. After a mean of 24.5 days, the patients' background radiation counts were deemed low enough for accurate intraoperative cancer localization, and surgery was performed. Any visibly or palpably abnormal areas were biopsied after being evaluated with the GDP. Any areas suspicious for malignancy by GDP evaluation were also biopsied. Two patients without evident disease by radiographic or surgical examination had histologically confirmed metastases localized by the GDP. Four patients had obvious disease at surgery which was variably confirmed by the GDP; two of these patients had baseline elevations in circulating TAG-72 antigen levels that may have affected binding of antibody to the tumor. This system of radioimmunoguided surgery was well tolerated and practical in its application, and it permitted disease detection that resulted in potentially beneficial changes in patient management.
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PMID:The intraoperative detection of ovarian adenocarcinoma using radiolabeled CC49 monoclonal antibody and a hand-held gamma-detecting probe. 1085 78

Mature adult mice of the C57BL/6-TgN(Amy1TAg)501Knw transgenic mouse lineage, 501, containing a liver alpha-amylase promoted-SV40 Tag hybrid gene, routinely develop SV40 Tag-induced metastatic osteosarcomas. This form of alpha-amylase was known to be expressed in the liver, salivary glands, pancreas, and fat. Cells in the normal rib adjacent to the periosteum also express alpha-amylase suggesting that transgene expression is correctly targeted to generate osteosarcomas. 501 mice express SV40 Tag in the salivary glands but do not develop abnormalities in these organs by the time of their death from SV40-induced osteosarcomas. Mice of the C57BL/6 strain make a strong and effective anti-tumor immune response to SV40 Tag immunization. However, immunization of 501 mice with SV40 Tag early in life does not alter or prevent SV40 Tag-induced osteosarcomagenesis. 501 mice mount a significantly less effective cytotoxic T-lymphocyte response following SV40 Tag immunization while 501 osteosarcoma-derived cells are fully susceptible to SV40 Tag-specific T-cell lysis. This suggests that partial tolerance, not loss of antigen presentation by tumor cells, characterizes this mouse model of endogenous bone tumor development. To determine whether the immune recognition of endogenous SV40 Tag could influence tumorigenesis, the metastatic potential and time of death from tumor was investigated in CD4-null mutant 501 mice and beta-2 microglobulin-null mutant 501 mice. The size and number of metastases in these strains and longevity of these strains varied. We suggest that components of both the innate and adaptive immune response control tumor appearance and progression.
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PMID:Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas. 1095 95

L-selectin mediates homing of lymphocytes to lymph nodes (LN). Transgenic mice that express rat insulin promoter regulated simian virus 40 Tag (RIP-Tag) develop large, local cancers that metastasize to liver but not LN. To test whether this lack of LN metastases reflects their absence from the circulation, transgenic mice were produced that express Tag (T), L-selectin (L), and Escherichia coli LacZ (Z), in pancreatic beta cells. LTZ mice developed insulinomas that specifically had LN metastases; metastasis was blocked by an anti L-selectin mAb. LacZ(+) tumor cells from these LN homed to secondary LN upon transfer. These results suggest that the highly vascularized islet carcinomas are shedding tumor cells into the bloodstream, which is a necessary but insufficient condition for metastasis to occur; L-selectin can facilitate homing of such tumor cells to LN, resulting in metastasis.
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PMID:L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis. 1127 19

We analysed the differential expression pattern of the three distinct TAG-72 carbohydrate epitopes detected by monoclonal antibodies (MAbs) B72.3, CC83 and CC49 in a consecutive series of 114 patients with primary breast cancer and in 39 synchronous lymph node metastases. B72.3, CC83 and CC49 were expressed in respectively 81 (71%), 68 (60%) and 96 (84%) of the 114 cases. Interestingly, MAb B72.3 was significantly expressed in a subgroup of patients characterised by larger tumour size (p=0.013), lymph node metastasis (p=0.0002), high histopathological grade (p=0.006), high cell kinetics (p=0.04) and advanced clinical stage (p=0.0019). In 20 (51%) of the 39 pairs of matched primary breast cancers and synchronous lymph node metastases, TAG-72 was expressed in the tumour but not in the corresponding metastatic lymph node; tumours with TAG-72-negative lymph nodes appeared to be clinicopathologically more aggressive. CC49, the most immunoreactive and widely used MAb, was not detected in 34% of the metastases of expressing primary tumours. All three MAbs were found in a significantly lower per cent of synchronous metastases with respect to primary tumours (p<0.001).
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PMID:Differential TAG-72 epitope expression in breast cancer and lymph node metastases: a marker of a more aggressive phenotype. 1174 71

We have analysed the importance of fibroblast growth factor 2 (FGF2) in tumor development. In a transgenic mouse model (Tyrp1-Tag) tumors form in the retinal pigment epithelium (RPE), invade surrounding tissues, and metastasize to lymph node and spleen. To address whether RPE tumor formation is dependent on FGF2, we generated FGF2-deficient mice. Such mice appeared healthy and exhibited no impairment of growth or development. Tyrp1-Tag transgenic mice, which are lacking FGF2 (FGF2-/-) developed RPE tumors that metastasize to spleen and lymph nodes. Tumor growth and survival rate are identical to Tyrp1-Tag transgenic littermates expressing FGF2. Cell lines were isolated from RPE tumors of wild-type and FGF2-deficient mice. They grow in culture, are pigmented and form vascularized tumors, when injected subcutaneously into nude mice of either FGF2-/- or FGF2+/+ genetic background. Kinetics of tumor growth was identical and independent of presence of FGF2. Together, these results demonstrate that FGF2 is not essential for tumor formation of the RPE thus suggesting that tumor growth in general may not be dependent on FGF2.
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PMID:Absence of fibroblast growth factor 2 does not prevent tumor formation originating from the RPE. 1189 16


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