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)

The FHIT gene, a member of the histidine triad family has been identified as a tumor suppressor gene. Molecular genetic approaches to determine alterations in the FHIT gene in colorectal cancers have produced varying results with reported abnormalities of the FHIT gene transcripts in 13% to 50% of cases studied. FHIT has been reported to be involved in the regulation of apoptosis and cell cycle in cell culture systems. Immunohistochemical (IHC) studies of FHIT expression in human colon cancer and its correlation to apoptosis and clinical prognosis have been sparse. We studied 100 human colorectal cancers by IHC and a computerized image analysis (CIA) method to evaluate FHIT expression and the rate of apoptosis in tumors and corresponding mucosae. Follow-up data for at least five years was available for all patients. We correlated the results with tumor grade, stage and clinical prognosis. We used commercially available polyclonal anti FHIT antibody and Apoptaq kit on paraffin-embedded tumors and their corresponding mucosae and the SAMBA 4000 CIA system to evaluate the labeling index (LI), the mean optical density (MOD) of the stain and calculate a quick score (QS). The LI is the ratio of positively stained areas to the total area of the tissues examined, the MOD represents the concentration of the positive stain as measured per positive pixels and the QS a numeric product of the LI and MOD for each microscopic area examined. Image analysis of IHC staining of the tumor sections defined three main groups based on the reactivity of the anti FHIT polyclonal antibody. Group I included 23 cases where the LI was less than 55% with a mean of 36%. Eight cases in this group showed complete loss of FHIT expression. Group II included 41 cases where the LI was between 55% and 65% with a mean of 60%. Group III was composed of 36 cases where the LI was more than 65% with a mean of 69%. Our data showed that the absence or reduction of FHIT protein in the tumors, relative to morphologically normal mucosa, plays a role in the development of a few colorectal cancers (23%). Poorly differentiated carcinomas showed absent or decreased FHIT. A reduction of FHIT was positively correlated with the rate of distant metastases and worse prognosis. Over-expression of FHIT is directly proportional to the apoptotic rate in the tumors examined. CIA provides an objective and accurate assessment of the staining patterns and generates numerical data evaluating intensity better than depending on subjective light microscopy alone.
Clin Exp Metastasis 2002
PMID:FHIT protein expression and its relation to apoptosis, tumor histologic grade and prognosis in colorectal adenocarcinoma: an immunohistochemical and image analysis study. 1209 Apr 76

Despite recent advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC), most patients still present with advanced stage disease at the time of diagnosis. Recent studies suggest that IL-6 is involved in the development of lung cancer. The aim of the present study was to investigate whether the measurement of IL-6 levels in the breath condensate of NSCLC patients could be used to bring forward the moment of diagnosis and to monitor the progression of the disease. Twenty patients with histological evidence of NSCLC (14 men and 6 women, age 63+/-8 years) and 15 healthy controls (8 men and 7 women, age 45+/-6 years) were enrolled in the study. IL6 was measured in the exhaled breath condensate of patients and controls by means of a specific enzyme immunoassay kit. Higher concentrations of exhaled IL-6 were found in NSCLC patients (9.6+/-0.3 pg/mL) than in controls (3.5+/-0.2 pg/mL). A statistically significant difference was observed between patients with NSCLC at different stages: higher concentrations of IL-6 (10.9+/-0.5 pg/mL) were found in patients with metastatic disease than in those with stage III (9.7+/-0.4 pg/mL), stage II (8.9+/-0.3 pg/mL) and stage I disease (7.9+/-0.3 pg/mL). These findings suggest that the measurement of IL-6 in the breath condensate of patients with NSCLC could be proposed as a parameter to take into account in early diagnosis and disease monitoring.
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PMID:Interleukin-6 is increased in breath condensate of patients with non-small cell lung cancer. 1211 82

We investigated the correlations between serum levels of selected proinflammatory, hematopoietic and angiogenic cytokines and soluble cytokine receptors with the clinico-pathological features and prognosis in soft tissue sarcoma patients. Serum levels of 9 cytokines (TNFalpha, IL-1ra, IL-6, IL-8, IL-10, M-CSF, G-CSF, VEGF, bFGF) and 4 free cytokine receptors (sIL-2R alpha, sIL-6R, TNFRI, TNFRII) were measured by means of an enzyme-linked immunoadsorbent assay kit in 156 soft tissue sarcoma patients before the treatment and in 50 healthy controls. Serum levels of 10 cytokines and cytokine receptors were also assayed during patients' follow-up after the treatment. Significantly elevated pretreatment serum levels of 11/13 cytokines and cytokine receptors were found in sarcoma patients, as compared to healthy controls. In 40.4% of patients 6 or more cytokines and cytokine receptors (most frequently: TNF RI, IL-6, IL-8) were elevated in parallel. Serum levels of IL-6, sIL-2R, VEGF, M-CSF and TNF RI correlated significantly with tumor size and serum levels of IL-8 and IL-6 were significantly higher in patients with Grade 2/3 vs. Grade 1 tumors. We did not observe any significant differences in cytokine serum levels between patients with primary and recurrent tumors and patients with and without distant metastases. Using univariate analysis, overall survival (OS) in all patients was affected by tumor size (<5 cm vs. 5-10 cm vs. >10 cm), tumor grade (G1 vs. G2/3), presence of metastases, pretreatment serum levels of 8 cytokines (IL-6, IL-8, IL-10, sIL-2R, TNF RI, TNF RII, M-CSF, VEGF) and the number of cytokines increased (0-1 vs. 2-5 vs. < or = 6). Elevated serum levels of IL-6, IL-8, IL-10 and sIL-2R alpha, high tumor grade and larger tumor size strongly correlated with shorter disease-free survival (DFS). Multivariate analysis identified G2/3 tumor grade (p = 0.001), the presence of metastases (p = 0.004), elevated IL-6 serum level (p = 0.02), elevated IL-8 serum level (p = 0.048) and the number of cytokine serum levels above upper cut-off values (p = 0.01) as the independent prognostic factors related to OS, and G2/3 tumor grade (p = 0.005) and increased IL-6 serum level (p = 0.035) as independent prognostic factors related to DFS. In a group of patients without metastases (M0) higher tumor grade, elevated serum level of IL-6 and TNF RII, and the number of elevated cytokine serum levels correlated independently with poor survival. We found a significant decrease of several cytokine serum levels in patients after treatment (IL-1ra, IL-6, IL-8, IL-10, TNF RII, M-CSF) [p < 0.05]. Persistently elevated serum level of IL-6 after the treatment has also shown negative prognostic significance for OS (univariate analysis). Serum levels of some proinflammatory, hematopoietic and angiogenic cytokines and cytokine receptors are elevated, frequently in parallel, in a large percentage of soft tissue sarcoma patients. Significant correlations of serum cytokine levels with tumor size and grade suggest that some of these cytokines may be directly or indirectly involved in the progression of soft tissue sarcomas. Serum assays of IL-6, IL-8 and TNF RII before or after the treatment may be useful in establishing soft tissue sarcoma patients prognosis.
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PMID:Cytokine serum levels in soft tissue sarcoma patients: correlations with clinico-pathological features and prognosis. 1211 31

Amplification of the c-erbB-2 oncogene and protein overexpression are well-known in breast cancer and a basis for therapy with the monoclonal antibody trastuzumab, which binds to the receptor encoded by c-erbB-2. Regarding bladder carcinoma, several studies have examined c-erbB-2 expression, but their results are quite heterogeneous. In the present study, we evaluated the expression of this oncoprotein immunohistochemically in 203 muscle-invasive urothelial bladder carcinomas using the HercepTest. Additionally, 42 cases were studied for gene amplification by fluorescence in situ hybridization (FISH) using the PathVysion kit. Follow-up was known in 147 patients. The results were compared with pathologic characteristics and disease-related survival. Immunohistochemical c-erbB-2 overexpression was observed in 37% of the tumors (76/203). However, only 5% (2/42) showed amplification of the oncogene, indicating that predominantly other mechanisms than gene amplification may cause protein overexpression in bladder cancer. C-erbB-2 protein overexpression was significantly associated with high tumor grade (p=0.004) and infiltrative growth pattern (p=0.0001), and tendentiously associated with the presence of lymph node metastases (p=0.077). Regarding tumor stage, sex and age, no significant correlation was registered. Kaplan-Meier curves showed a significantly worse disease-related survival for patients with c-erbB-2 overexpressing tumors (p=0.0346 by log-rank test). Multivariate analysis revealed that, besides nodal status (p=0.0001) and tumor stage (p=0.028), c-erbB-2 overexpression was an independent predictor of disease-related survival (p=0.030). Thus, our results suggest that immunohistochemical c-erbB-2 detection might represent an additional tool in determining bladder cancer prognosis. Clinical trials evaluating the efficacy of trastuzumab therapy in bladder cancer patients are warranted.
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PMID:Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome. 1237 Jul 44

The proto-oncogene c-kit is a transmembrane-tyrosine-kinase receptor that is structurally related to the platelet-derived growth-factor receptor (PDGFR) and is involved in cell differentiation. C-kit has been found to be expressed in certain solid tumors and may play a role in their tumorigenesis. Recently, a tyrosine-kinase inhibitor specific for the PDGFR family, bcr-abl, and c-kit (STI571) has been reported to have therapeutic effects in tumors expressing the aberrant forms or high quantities of target proteins. Expression of c-kit has not been well evaluated in endometrial adenocarcinomas. In this study, c-kit immunoreactivity was evaluated on paraffin sections of 72 endometrial adenocarcinomas (57 endometrioid, 10 serous, and 5 clear cell) with a polyclonal antibody. Immunoreactivity of c-kit was analyzed semiquantitatively and correlated with various clinicopathologic factors. Cytoplasmic c-kit immunoreactivity was detected in 42 (58%) tumors. Thirty-four (60%) endometrioid, 8 (80%) serous, and 0 of the 5 clear-cell adenocarcinomas were c-kit positive. There was a significant correlation between c-kit positivity and the depth of myometrial invasion. Patients with c-kit-positive endometrial adenocarcinomas more frequently had metastases and shorter disease-free survival. Expression of c-kit may be a potentially adverse prognostic feature in endometrial adenocarcinoma. Patients with c-kit-positive advanced endometrial adenocarcinoma might benefit from tyrosine-kinase-inhibitor therapy.
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PMID:C-kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance. 1264 69

In 21 patients with non-small-cell lung cancer subjected to radical surgery followed by 3 cycles of chemotherapy, serum cathepsin B activity and plasma E-alpha 1IP concentration in peripheral blood and tumour arterial and venous blood were studied. Cathepsin B activity was determined by a fluorometric assay. E-alpha 1IP concentration was measured with an ELISA kit. The measurements were performed before surgery, before each chemotherapy cycle and every 60 days after chemotherapy completion, for 2 years. All the patients (n = 21) were divided into 2 subgroups: without metastases n = 16 and with metastases n = 5. There was no significant difference between preoperative serum cathepsin B activity and E-alpha 1IP plasma values in peripheral blood and blood coming from tumour artery and vein. The surgery and chemotherapy caused a statistically significant decrease of serum cathepsin B activity and plasma E-alpha 1IP concentration both in the whole group and in the subgroup without metastases. A significant increase of cathepsin B activity in comparison to initial values was observed 2,5-4 months before cerebral metastasis appeared in the subgroup with metastases. The elevation of E-alpha 1IP concentration preceded the increase of cathepsin B activity in this subgroup. It was not statistically significant. A decrease of cathepsin B and E-alpha 1IP values was observed after cerebral metastasis excision.
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PMID:[Cathepsin B activity and concentration of elastase and alpha-1 proteinase inhibitor complex in non-small-cell lung cancer: 2 year follow-up study]. 1293 16

The M2 isoenzyme of pyruvate kinase (M2-PK) is specifically expressed in tumor cells (TuM2-PK) and has been detected in the peripheral blood of patients with renal cell carcinoma (RCC). TuM2-PK is not useful as a biological marker in localized RCC. We analysed TuM2-PK in 68 patients with metastatic RCC after initial surgery and prior to or during chemoimmunotherapy of metastases. In 50 patients, the levels of TuM2-PK were measured during chemoimmunotherapy with interleukin-2, interferon-alpha2a and 5-fluorouracil for up to 8 months and were correlated to response as assessed by radiological imaging techniques. TuM2-PK was quantified with a commercially available enzyme linked immunosorbent assay kit using a cut off of 15 kU/l. In 48 of 68 patients (71%), TuM2-PK was elevated above the cut-off. TuM2-PK was significantly higher in G3 tumors than in G2 tumors. In 34 of 50 patients (68%) undergoing chemoimmunotherapy, a positive correlation between TuM2-PK values and response to treatment was observed. Based on these data, we would not recommend the routine clinical use of TuM2-PK in metastatic RCC at this point.
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PMID:Tumor type M2 pyruvate kinase expression in metastatic renal cell carcinoma. 1451

Cutaneous eccrine and apocrine glands have many histologic and immunologic similarities to ducts and acini of the breast. Thus, differentiating a primary cutaneous process from a metastatic breast carcinoma can be nearly impossible. In all, 10-34% of breast carcinomas overexpress HER-2 protein, a membrane-associated protein that functions in cell differentiation, adhesion and motility. As expression of this gene in cutaneous neoplasms has not been well characterized, we sought to determine HER-2 expression in a sample of benign and malignant cutaneous eccrine and apocrine neoplasms and to determine if there is value in using this protein expression in differentiating primary cutaneous from metastatic breast lesions. Totally, 85 primary cutaneous neoplasms and 11 cutaneous metastases from HER-2-positive breast carcinomas were retrieved from archived material at our institute. All cases were evaluated for HER-2 protein expression using the Dako Hercept Test kit. Membranous HER-2 staining was noted in three of the 85 cutaneous adnexal neoplasms: one hidrocystoma and two nodular hidradenomas. Seven of the 11 cutaneous metastases from HER-2-positive breast carcinomas maintained moderate-to-strong HER-2 expression. In conclusion, while 10-34% of breast carcinomas overexpress the HER-2 protein, only 3.5% of cutaneous apocrine and eccrine neoplasms in this study stained with the HER-2 antibody. These HER-2-positive cutaneous neoplasms typically do not pose a diagnostic dilemma in the setting of differentiation from breast metastasis. Additionally, although histologically these breast and cutaneous lesions may have morphologic similarities, the relative lack of HER-2 overexpression suggests that they are different nosologically. Finally, this study suggests that HER-2 protein expression can be a useful tool in differentiating a primary cutaneous appendageal neoplasm from HER-2 expressing metastatic breast carcinoma.
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PMID:Her-2 expression in cutaneous eccrine and apocrine neoplasms. 1463 75

Serum thyroglobulin (Tg) is a suitable marker for differentiated thyroid carcinoma following total thyroid ablation. Between 1998 and 2003, serum samples from 715 papillary and 179 follicular tumor patients treated with total/nearly total thyroidectomy and radioiodine ablation therapy were collected. According to the "Guidelines for Oncotherapy in Hungary", serum Tg, antithyroglobulin antibody (TgAb), TSH and FT4 levels were measured in periods of 3 months following the first treatment and of 6 months after 2 years. In the present work the prognostic value of Tg and TgAb data of cancer patients with hormone substitution therapy were evaluated individually and retrospectively. Serum Tg and TgAb concentrations were measured with a highly sensitive immunoradiometric (IRMA) method, and with a second generation, broad epitope specificity competitive radioimmunoassay, respectively. TSH levels determined by fourth generation LIAISON kit were in a range of 0.05-0.10 mIU/L. Accuracy of measuring of Tg <1 ng/ml made it possible to select the low cut-off level (Tg <2 ng/ml) following total thyroidectomy. In the predominant part of TSH-suppressed patients (746/774, 96%) the serum Tg concentration was below the cut-off level of 2 ng/ml. The sensitivity of Tg determination in 59 TSH-suppressed thyroid cancer patients with lung and bone metastases was as high as 86 to 100%. On the contrary, the number of false negative data was high in cases with lymph node metastases of papillary cancer, and sensitivity did not exceed 62%. Specificity and sensitivity of Tg in TgAb negative patients were 91 to 100%. Based on our results it could be concluded that measuring of Tg and TgAb, using a current IRMA method and a second generation RIA kit, proved to be effective tools for the postoperative monitoring of differentiated thyroid tumours. It has to be noted that determination of TgAb is highly recommended for the adequate interpretation of serum Tg levels. Persistently high and/or increasing serum TgAb concentration with low Tg result had a diagnostic value during the follow-up and can be connected with the recurrence or persistence of the differentiated thyroid cancer.
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PMID:[Clinical significance of serum thyroglobulin and antithyroglobulin antibody in differentiated thyroid cancer after thyroid ablation]. 1510 93

Archival pathology specimens are nowadays a frequently used source in forensic identification or paternity testing, if no other material is available. A greater part of this archived material, however, consists of solid tumors known for aberrations in coding and non-coding regions of the genome. Therefore, alterations of short tandem repeats (STRs) used in forensic casework are also possible. In our study of 118 solid tumors, 46 lymph node metastases, and 16 distant metastases with the AmpFlSTR trade mark Profiler Plus PCR amplification kit comprising nine STR loci, we detected four kinds of changes between normal and tumor tissue: partial loss of one allele (pLOH), complete loss of one allele (LOH), occurrence of an additional allele and occurrence of a new allele instead of that found in normal tissue. Twenty-two percent of the tumor lesions displayed pLOH, but only in 14% one allele was completely lost. New alleles could be demonstrated in 18% of tumors, and in 8% the new allele in the tumor tissue replaced the one found in normal tissue. The changes were distributed over all nine STRs, but the STRs mostly affected were FGA, D3S1558, D18S51 and D21S11. The occurrence of new alleles in the tetra-nucleotide repeats correlated mainly with microsatellite instability in di-nucleotide and mono-nucleotide repeats. The occurrence of new alleles was most frequent in primary tumors of colon carcinomas and HNSCC metastases. In melanomas, only loss of alleles could be found. Our results demonstrate that the use of tumor tissue in forensic identification and paternity testing is questionable, especially if only tumors with known microsatellite instability are available.
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PMID:Evaluation of allelic alterations in short tandem repeats in different kinds of solid tumors--possible pitfalls in forensic casework. 1537 88


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