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)

The reverse transcriptase-polymerase chain reaction (RT-PCR) of tumor-specific or -associated genes is a sensitive assay for detecting a minimal number of tumor cells in peripheral blood (PB) or bone marrow (BM). In this study, we determined whether mRNA of bombesin receptors is detectable in PB or peripheral blood progenitor cell (PBPC) samples from patients with small cell lung cancer. Among three bombesin-like peptide receptors, we used the neuromedin B receptor (NMB-R) gene as a target, because of the most frequent expression on SCLC cell lines. The lower limit of detection was one tumor cell in one million normal PB cells and there was no detection in normal PB or BM cells unlike a cytokeratin 19 gene. The NMB-R gene was detected in 14 (31.8%) of 44 PB samples from patients with SCLC at diagnosis and 2 (15.4%) of 13 samples of PBPC collected during a recovery phase after chemotherapy followed by administration of G-CSF (filgrastim). At diagnosis, patients whose PB was positive for the NMB-R gene had a significantly shorter survival than those who were negative. Our observation suggests that this assay may be useful in diagnosing metastatic disease and monitoring minimal residual disease in patients with SCLC.
 ...
PMID:Detection of occult tumor cells in peripheral blood from patients with small cell lung cancer by reverse transcriptase-polymerase chain reaction. 1081 Apr 12

We optimized the assay for detection of cytokeratin 19 (CK19) mRNA by the reverse transcriptase-polymerase chain reaction (RT-PCR) in blood as an index of circulating tumor cells in breast cancer patients. The limit of detection of < 1 MCF7 tumor cells per 10(6) peripheral blood leukocytes (PBL) was achieved in mixing experiments. We did not detect CK19 mRNA in control bloods (0/30) or in the blood of patients with benign breast disease (0/15). In blood samples from 109 patients with invasive breast cancer, CK19 mRNA was detected in 7/23 patients with node-negative disease, in 21/58 with node-positive disease, and in 20/28 with distant metastases. There was a significant association (P < 0.01) of CK19 positivity with distant metastatic versus both node-negative and node-positive disease, but not with any other histopathological parameter examined. In a small number of patients with distant metastases, increased intensity of the CK19 RT-PCR signal was associated with a reduced survival.
 ...
PMID:RT-PCR amplification of CK19 mRNA in the blood of breast cancer patients: correlation with established prognostic parameters. 1084 77

The presence of axillary lymph node metastasis in patients with breast cancer is a major prognostic factor and also determines the use of adjuvant chemotherapy. Micrometastasis has been arbitrary defined as deposits of < 2 mm dimension. Earlier studies of micrometastases failed to demonstrate prognostic relevance. However, when larger numbers of patients were followed up for longer periods, micrometastasis was shown to be a significantly poor prognostic parameter with patients having a survival rate similar to those with macrometastasis or nodal disease. There are no compelling reasons to retain the term "micrometastasis" in the light of these findings and our understanding of tumor biology. Routine histological examination of axillary lymph nodes is a notoriously inaccurate method for the detection of metastases. When serial or multilevel sectioning and/or immunohistochemical staining for cytokeratin were employed, detection rates increased by as much as 33%. Reverse transcriptase-polymerase chain reaction and Southern blotting for CK19 may be a more accurate method of examination. However, there are inherent technical problems associated with this method, and the recent finding of a pseudogene with great homology to CK19 in normal peripheral blood nucleated cells further emphasises the need for caution in this approach. It is not cost-effective to employ serial sectioning and immunohistochemistry when examining the axillary contents. However, the introduction of sentinel-node biopsy may allow detailed examination of the single node most likely to harbour a metastatic tumor.
 ...
PMID:The prognostic dilemma of nodal micrometastases in breast carcinoma. 1089 73

Amplification of cytokeratin 19 (CK19) transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a highly sensitive assay for the detection of bone marrow micrometastases (BMM) of breast cancer, but recent studies have demonstrated the occurrence of false-positive results due to low-level, illegitimately transcribed CK19 in normal bone marrow tissue. One approach to solve this problem is to develop a quantitative CK19 RT-PCR assay and to introduce a cut-off value which can distinguish between illegitimate expression and cancer-specific expression levels. In the present paper, we describe a quantitative CK19 RT-PCR assay using a real-time automated PCR system. The number of CK19 transcripts was normalized to that of GAPDH transcripts as an internal control for quality and quantity of cDNA. The cut-off value for the ratio of CK19 to GAPDH transcripts was set at 10(-4) since the ratio never exceeded this value in the control bone marrow samples (n = 12). In total, 117 bone marrow aspirates from stage I - III patients with invasive breast cancers were subjected to CK19 RT-PCR assay and immunocytological examination. Forty (34.2%) were found to be BMM-positive by CK19 RT-PCR assay whereas only three (2.6%) were found to be BMM-positive by immunocytology. Multivariate analysis has shown that occult BMM detected by CK19 RT-PCR is a significant risk factor for relapse, being independent of axillary lymph node metastases.
 ...
PMID:Prognostic significance of occult bone marrow micrometastases of breast cancer detected by quantitative polymerase chain reaction for cytokeratin 19 mRNA. 1101 Nov 20

Spontaneous hepatic neoplasms were identified in two adolescent (<5 years of age) male cynomolgus monkeys (Macaca fascicularis). Monkey No. 1 had a solitary hepatocellular carcinoma (HCC). Monkey No. 2 had multiple discrete tumors consisting of several poorly circumscribed HCCs and a mixed hepatocholangiocellular carcinoma (MHC). Metastases were not evident in either monkey. Histochemical and immunohistochemical stains were used to assess phenotypic alterations in the tumors. Many or most neoplastic hepatocytes (NHs) of both monkeys stained positive for low-molecular-weight cytokeratin (LMWCK), cytokeratin (CK) 8, and CK 18. In monkey No. 1, small aggregates of NHs were positive for carcinoembryonic antigen (CEA), glutathione S-transferase-pi (GST), and alpha-fetoprotein (AFP), but NHs were uniformly negative for CK 7. NHs in monkey No. 2 were negative for CEA and AFP but were multifocally positive for GST and CK 7. Broad-spectrum cytokeratin (BSCK), high-molecular-weight cytokeratin (HMWCK), and CK 19 did not react with NHs of either animal. Neoplastic cells forming ductlike structures in the MHC of monkey No. 2 stained with LMWCK, CK 7, CK8, CK 18, BSCK, and GST but not with HMWCK or CK 19. Tumors in both monkeys had enhanced pericellular fibronectin staining. Nonneoplastic parenchyma of both monkeys contained multiple discrete foci of cellular alteration and scattered aggregates of hepatocytes with strong cytoplasmic staining for fibronectin. Staining patterns of these tumors demonstrate immunophenotypic heterogeneity of the neoplastic cells within individual tumors and variability among tumors. This information may serve as a useful reference for others encountering similar lesions in primates.
 ...
PMID:Spontaneously occurring hepatocellular neoplasia in adolescent cynomolgus monkeys (Macaca fascicularis). 1110 57

We prospectively analyzed the circulating tumor burden in colorectal cancer patients using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and cytokeratin 19 (CK19 ). We distinguished the mRNA levels in peripheral blood between 33 patients and 26 healthy controls with reference to SK-BR-3 cell line. We found CEA-mRNA in 88% of patients and 92% of controls, and CK19 mRNA in 64% of patients and 19% of controls. Our CK19 mRNA assay was sufficiently sensitive to detect one SK-BR-3 cell among 10(6) normal blood cells. The upper limit of CK19 mRNA among controls was exceeded by 14 patients, and 12 patients (86%) developed systemic metastases/recurrence. Significantly elevated CK19 mRNA levels appeared to originate from circulating malignant cells (P<0.0001). Of relevance, the CK19 mRNA level increased with advancing Dukes' stage and correlated directly with the serum CEA level (P=0.016). CK19 mRNA quantification may prove valuable for cancer staging and disease monitoring.
 ...
PMID:Quantitative relationship of the circulating tumor burden assessed by reverse transcription-polymerase chain reaction for cytokeratin 19 mRNA in peripheral blood of colorectal cancer patients with Dukes' stage, serum carcinoembryonic antigen level and tumor progression. 1112 64

Mortality among patients with breast cancer (BC) is mainly caused by metastasis. We determined the circulating tumor burden in BC patients by semiquantitative reverse transcription-polymerase chain reaction using carcinoembryonic antigen (CEA) and cytokeratin 19 (CK19) mRNAs as molecular markers. We distinguished the mRNA levels in circulation between BC patients and healthy controls with reference to a BC-derived cell line, SK-BR-3. We prospectively analyzed peripheral blood samples from 33 BC patients and 26 healthy controls. We found CEA mRNA in 97% of patients and 92% of normal controls, and CK19 mRNA in 72% of patients and 19% of controls. CEA and CK19 mRNAs in normal peripheral blood were most likely derived from illegitimate transcription. In 10 patients, of whom 9 (90%) developed systemic metastases, the upper limit of CK19 mRNA of normal controls was exceeded. As compared with normal controls, significantly elevated CK19 mRNA levels in the patients appeared to originate from circulating malignant BC cells (P<0.0001). It was clinically significant that the mean CK19 mRNA level increased with advancing disease stage. Of prognostic value, we report for the first time that BC patients with CK19 mRNA elevation had notably shorter (approximately 3-year reduction) overall survival than patients with normal CK19 mRNA levels (P=0.045). Quantification of CK19 mRNA may prove useful for cancer staging, disease monitoring and prognostic assessment among BC patients.
 ...
PMID:Quantitative correlation of cytokeratin 19 mRNA level in peripheral blood with disease stage and metastasis in breast cancer patients: potential prognostic implications. 1117 98

The identification of specific tumor mRNA markers by reverse transcription-polymerase chain reaction might be a valuable diagnostic adjunct for the detection of breast cancer metastases in axillary sentinel lymph nodes (SLNs). In this study we have compared the diagnostic accuracy of an extensive histopathologic examination of 146 SLNs from 123 breast carcinoma patients with that of the evaluation of 5 mRNA markers. When analyzed individually, none of the different markers attained a sensitivity higher than 77.8%, and the general concordance with the histopathologic findings ranged from 78.8 to 83.6%. In a multiple-marker assay, taking into account the expression of at least 1 of the 5 tumor markers, the sensitivity of the test rose to 95.6%, with a specificity of 66.3% and a general concordance with the histopathologic status of 75.3%. Finally, when at least 2 of 3 markers (maspin, cytokeratin 19 and mammaglobin 1) were expressed, the concordance with either SLN or axillary lymph node status was highest (88.4% and 84.6%, respectively). The high prevalence of positive reverse transcription-polymerase chain reaction assays in histologically uninvolved SLNs, however, may hamper extensive application of these techniques in the clinical setting.
 ...
PMID:Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes. 1149 30

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.
 ...
PMID:mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients. 1159 97

Recent studies point out that cytokeratins (CKs) are involved in dynamic cell remodeling during cancer progression and particularly, CK expression patterns have been associated with invasion and metastasis. In oesophageal squamous cell cancer (ESCC), lymph node (LNN) metastasis is an important step in disease progression, invariably associated with an ominous prognosis. To assess whether specific CK expression patterns could represent reliable markers of tumor progression, a series of 111 ESCCs (59 lymph node-positive, 52-negative) derived from the high- incidence area of Linxian (Northern China), were subjected to immunohistochemical (IHC) analysis with an extensive panel of CK antibodies. Statistically significant differences were observed for CK18 (p=0.01), CK19 (p=0.04) and PKK1 (p=0.02) expression between the LNN-negative and LNN-positive ESCCs. Furthermore, significant correlation between specific CK distribution pattern and progressive disease (i.e., LNN metastasis) was evidenced. The results suggest that CK8, CK18 and CK19 expression and distribution pattern could be of predictive value as a marker of disease progression as defined by the appearance of lymph node metastases in oesophageal squamous cell cancer.
 ...
PMID:Cytokeratin expression patterns as an indicator of tumour progression in oesophageal squamous cell carcinoma. 1191 18


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