Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of high-risk patients with thyroid cancer and the preoperative differentiation between follicular adenoma and carcinoma remain clinically challenging. Our study was conducted to analyze whether the quantification of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator receptor (u-PAR) and transcription factor binding to the u-PAR promoter improve prognostic predictability and differential diagnosis of thyroid tumors. Tumor/normal tissue was collected from 69 prospectively followed patients with thyroid carcinomas (papillary, medullary, follicular and anaplastic, PTC, MTC, FTC and ATC) or follicular adenomas. U-PAR, MMP-1, MMP-7 and MMP-9 amounts were determined by ELISA, and transcription factor binding was determined by electrophoretic mobility shift assay. Binding of transcription factors to the u-PAR promoter was observed, but not associated with u-PAR expression. Carcinomas except MTC expressed significantly more u-PAR/MMPs than adenomas/normal tissues, this being associated with advanced pT- or M-stages. MMP-1 and MMP-9 were significantly higher in follicular carcinomas than in adenomas. In carcinomas, high u-PAR-gene expression correlated significantly with high MMP-9, the latter being associated with MMP-7 in normal tissues. Poor survival in differentiated tumors was associated in trend (p = 0.07); poor survival of all patients (p = 0.043) and especially of patients with carcinomas of follicular origin (including ATC), but not medullary carcinomas, were significantly associated with high u-PAR-protein (p = 0.015). Quantification of u-PAR is of prognostic relevance in thyroid carcinomas of non-c-cell origin, and u-PAR in part may be regulated nontranscriptionally in thyroid cancers. This is the first study to suggest MMP-1/-9 as significant differentiation markers between follicular adenoma and follicular carcinoma.
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PMID:Urokinase receptor, MMP-1 and MMP-9 are markers to differentiate prognosis, adenoma and carcinoma in thyroid malignancies. 1948 10

Nine patients (mean age 53) with metastasizing, progressive, medullary (MTC), thyroid carcinoma and progressive, nonradioiodine accumulating thyroid carcinoma of the follicular epithelium (follicular carcinoma, FTC and papillary carcinoma, PTC) were treated with a combination of paclitaxel and gemcitabine between 2004 and 2006. Tumors were histologically classified as follicular in 5 patients (56%), as papillary in 2 patients (22%), and medullary in 2 patients (22%). Paclitaxel (90-100 mg/m (2)) and gemcitabine (1,000 mg/m (2)) were applied for two, three, or 6 cycles every three weeks, depending on response and side effects. The effect of therapy was evaluated by radiographic imaging (CT images) and [(18)F]FDG-PET. All patients with papillary, follicular, or medullary thyroid carcinoma had continuous progression during restaging 14.8+/-8.8 weeks after initiation of chemotherapy, including one patient with stable disease after 3 cycles, but continuous progression after 6 cycles of chemotherapy. Paclitaxel and gemcitabine are not a valid chemotherapy option, in particular in patients with progressive, nonradioiodine-accumulating follicular thyroid carcinoma, who were already treated by other chemotherapeutic agents.
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PMID:Chemotherapy with paclitaxel and gemcitabine in progressive medullary and thyroid carcinoma of the follicular epithelium. 1973 58

The 5 main types of thyroid cancer (papillary, PTC, follicular, FTC, poorly differentiated, PDTC undifferentiated, UTC, medullary, MTC) not only differ regarding morphology, pathogenesis, genetics,and pathophysiology (iodine metabolism, thyroglobulin and calcitonin production), but also concerning tumor biology, metastatic behavior (lymphogenous, locally invasive and hematogenous routes) and prognosis. Knowledge of these features is the basis of the surgical concept of one or two-stage thyroidectomy, the exceptions and the concept of locoregional lymph node dissection. Lymph node surgery plays an important role in those cancers exhibiting mainly lymph node metastases (PTC, MTC) not only due to frequent recurrences but also due to its potential curative intent. Differentiated carcinomas may have an acceptable prognosis despite local invasion of the cervical aerodigestive system, thus resections are justified when technical prerequisites are given.
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PMID:[Surgery of thyroid carcinoma]. 1990 89

In this study we demonstrate anticancer activity of novel fully water soluble cationic porphyrins. The two cationic porphyrins 5,10,15-tris(N-methylpyridinium-4-yl)-20-[1-phenyl-4-(3-N-phenylsulfonylindolyl)]-21H,23H-porphyrin chloride (TMPy(3)PhenIndolprot(1)P-Cl(3)) and 5-{5-[2-(9,9-Dimethyl)fluorenyl]-N-methylpyridinium-3-yl}-10,15,20-tris(N-methyl-pyridinium-4-yl)-21H,23H-porphyrin chloride (TMPy(3)PyFluorenyl(1)P-Cl(4)) were prepared and their antiproliferative effects were studied in two human tumor cell lines and a normal human fibroblast cell line. Effects of the novel porphyrin compounds were evaluated in the small intestinal neuroendocrine tumor cell line KRJ-I, the medullary thyroid carcinoma cell line MTC-SK and the normal human fibroblast cell line HF-SAR by cell counting, cell proliferation assays and cell cytotoxicity analyses. TMPy(3)PhenIndolprot(1)P-Cl(3) and TMPy(3)PyFluorenyl(1)P-Cl(4) showed antiproliferative effects in the tumor cell lines MTC-SK and KRJ-I; cell viability was decreased and cytotoxic effects were quantified, while no significant alterations of the human fibroblasts were noted. With the advantage of full water solubility and antiproliferative effects in tumor cell lines, the novel porphyrin compounds TMPy(3)PhenIndolprot(1)P-Cl(3) and TMPy(3)PyFluorenyl(1)P-Cl(4) could be a new therapeutic option in anticancer treatment.
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PMID:Asymmetrically substituted cationic indole- and fluorene porphyrins inhibit tumor proliferation in small intestinal neuroendocrine tumors and medullary thyroid carcinomas. 1993 15

Completion operations after thyroid surgery due to incidental postoperative diagnosis of thyroid cancer are indicated in differentiated thyroid cancer with tumor size > 1 cm, extrathyroidal invasion, multifocality, angioinvasion or metastases. By thorough preoperative clinical work-up of nodular goiter (ultrasonography, fine needle aspiration cytology the frequency of completion thyroidectomies are aimed to be less than 10% of all thyroid cancer operations. To facilitate postoperative radioiodine ablation prophylactic completion operations can be postponed to 3 months postoperatively to minimize surgical morbidity, if not performed during the early postoperative period. Prophylactic central node dissection as part of the completion operation is reserved for papillary (PTC) and medullary carcinomas (MTC) but not for follicular cancer. Lateral node dissection is recommended in nodal-positive MTC and in PTC with more than 5 lymph node metastases in the central compartment.
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PMID:[Thyroid carcinoma found incidentally after thyroidectomy: postoperative strategy]. 1994 Dec 36

Beta-catenin is involved in cell adhesion through catenin-cadherin complexes and as a transcriptional regulator in the Wnt signaling pathway. Its deregulation is important in the genesis of a number of human malignancies, particularly colorectal cancer. A range of studies has been undertaken in breast cancer, with contradictory associations reported among beta-catenin expression, clinicopathologic variables, and disease outcome. We undertook an immunohistochemical study measuring the levels and subcellular localization of beta-catenin in 292 invasive ductal breast cancers with known treatment and outcome. No association with breast cancer-specific death was observed for cytoplasmic or membrane expression alone; however, a continuous score representing both locations (membrane minus cytoplasmic expression: MTC score) was associated with a worse outcome in univariate analysis (P = 0.004), and approached significance in a multivariate analysis model that included lymph node, progesterone receptor (PR), and HER2 status (P = 0.054). Therefore, the MTC score was used for further statistical analyses due to the importance of both the subcellular location and the levels of expression of beta-catenin. An association was identified between high cytoplasmic expression (low MTC score), and high tumor grade (P = 0.004), positive Ki67 (P = 0.005), negative estrogen receptor (ER) (P = 0.005), positive HER2 (P = 0.04) status, and an active phosphoinositide 3-kinase pathway (P = 0.005), measured as PIK3CA mutations (P = 0.05) or PTEN loss (P = 0.05). Low cytoplasmic expression (high MTC score) was associated with the luminal A subtype (P = 0.004). In conclusion, a low beta-catenin MTC score is associated with an adverse outcome in breast cancer, which may be of mechanistic significance in the disease process.
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PMID:Cytoplasmic localization of beta-catenin is a marker of poor outcome in breast cancer patients. 2005 51

Two-dimensional isoelectric focusing and gel electrophoresis followed by mass spectrometry were used to detect, measure, and identify changes in protein expression correlated with differences in the metastatic potential of cultured rat mammary adenocarcinoma cells. MTC is a non-metastatic cell clone derived from a primary tumor. MTLn2 and MTLn3 are low and high metastatic potential cell clones derived from lung metastases of the primary tumor. A total of 1,500 proteins was detected. The patterns of protein expression of MTLn2 and MTLn3 cells were similar. Only five spots had a threefold or greater statistically significant difference in staining intensity between MTLn2 and MTLn3 cells, whereas 70 spots differed between MTC and MTLn3 cells. Twenty spots were selected for further study, ten that had a positive correlation of staining intensity with metastatic potential and ten that had a negative (inverse) correlation. Of the 17 unique proteins that were identified, five have often been cited as tumor biomarkers. These included the positive biomarkers nucleophosmin (NPM) and 14-3-3 protein sigma and the negative biomarkers raf kinase inhibitor protein (RKIP), peroxiredoxin-2, and galectin-1. The only identified protein that was markedly higher in MTLn3 cells than in the less-metastatic MTLn2 cells was 14-3-3 protein sigma. The results indicate that increased metastatic potential is associated with positive and negative changes in expression of particular proteins. Proteins that are positively correlated with metastatic potential may prove more useful as clinical biomarkers, but those with negative correlations may still provide useful information about underlying mechanisms of metastatic spread.
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PMID:Biomarkers of metastatic potential in cultured adenocarcinoma clones. 2110 27

The introduction of PET(-CT) has brought about a major paradigm shift in the management of thyroid carcinoma, especially from the diagnostic standpoint. From the viewpoint of patient management, the areas where it has made significant impact include the following: (1) the detection of disease focus in patients with differentiated thyroid carcinoma with elevated Tg levels and negative radioiodine scan. When localized disease is identified with F-18 FDG-PET-CT, surgery or focused radiotherapy could be utilized to eradicate the tumor; (2) the localization of disease in patients of MTC with elevated serum calcitonin levels; (3) the detection of unsuspected focal F-18 FDG uptake in the thyroid in patients undergoing whole body F-18 FDG PET for a different indication. This would prompt a workup to rule out thyroid carcinoma. The use of I-124 is evolving at this time and has been of great promise with regard to (a) its better efficacy of lesion detection and (b) the ability to provide lesion-specific dosimetry. In addition, F-18 FDG PET appears to be of potential value in patients with thyroid lymphoma in making the initial diagnosis, monitoring therapeutic response, and assessing for residual disease and/or recurrence.
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PMID:PET and PET/CT in the management of thyroid cancer. 2133 36

1 (MTC-220), a conjugate of paclitaxel and a muramyl dipeptide analogue, has been synthesized as a novel agent of dual antitumor growth and metastasis activities. In vitro and in vivo tests show that 1 retains its ability to inhibit tumor growth. It is superior to paclitaxel in its ability to prevent tumor metastasis in Lewis lung carcinoma and 4T1-tumor-bearing mice. The present studies indicate that 1 suppresses myeloid derived suppressor cell accumulation in the spleen and bone marrow of tumor-bearing mice and also represses inflammatory cytokines in tumor tissue. These results demonstrated that 1 could be a potential therapeutic and preventive agent for cancer growth and metastasis.
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PMID:Conjugate (MTC-220) of muramyl dipeptide analogue and paclitaxel prevents both tumor growth and metastasis in mice. 2140 30

Increased expression of EGFR in metastases of human mammary carcinoma as compared to cells of the primary cancer suggests a contribution of EGFR to mammary carcinoma metastasis. To test for a positive correlation, we investigated 13762NF rat mammary adenocarcinoma cloned tumor cell lines of high (MTLn3) or low (MTC) metastatic potential. While MTC cells expressed barely detectable amounts of EGFR, MTLn3 cells expressed readily detectable levels of receptor. This was demonstrated in Northern blot analysis, in immunoprecipitation studies using metabolically labeled whole cell lysates and in Western blot analysis of membrane fractions. Cross-linking of radiolabeled ligand to intact cells identified on both cell types specific binding to a 170 kd protein, however, at much lower levels on low-metastatic MTC cells and not in sufficient amounts to estimate receptor numbers by Scatchard analysis. In contrast, Scatchard plot analysis of I-125-EGF binding to MTLn3 cells revealed the expression of about 10,000 high and 46,000 low affinity sites. Both cell lines expressed the ligand in comparable amounts as was demonstrated by using a specific rat TGFalpha cDNA probe in Northern blot and an antibody recognising membrane bound TGF in FACS analysis. Adhesion of MTC cells to immobilized collagen or fibronectin was rapid reaching 50% after 30 min while control MTLn3 cells demonstrated lower adhesion to collagen. Addition of 10 ng/ml EGF increased the rate and the maximal adhesion of MTLn3 cells to collagen G, while the adhesion kinetics of MTC cells to collagen G or fibronectin were unaffected.
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PMID:Expression of epidermal growth-factor receptor correlates with metastatic potential of 13762nf rat mammary adenocarcinoma cells. 2156 31


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