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 incidence of epithelial derived thyroid cancer (papillary thyroid cancer and follicular thyroid cancer, known collectively as differentiated thyroid cancer) is rising. About 80% of patients with thyroid cancer have PTC and are best treated with thyroidectomy and functional lymph node dissection, followed by radioiodine ablation or therapy and performance of a posttreatment whole-body scan, followed by thyroid stimulating hormone (TSH) suppression. One year after radioiodine administration, the use of sensitive thyroglobulin (Tg) assays can separate the vast majority of patients with persistent disease from those who are free of disease and unlikely to have recurrent disease all without the need for repeat whole-body radioiodine imaging. Patients with detectable serum Tg during TSH suppression (Tg-on) or Tg that rises above 2 ng/mL after TSH stimulation (TSH-Tg) are highly likely to harbor residual tumor. TSH stimulation can be achieved using either thyroid hormone withdrawal or recombinant human TSH (rhTSH). Highly skilled screening neck ultrasonography can identify a few additional patients with subcentimeter residual neck lymph node metastases not detected by TSH-Tg. However, ultrasonography and chest computed tomography (CT) are most critical for tumor localization in those patients with Tg values that suggest residual disease or in those patients with persistent antithyroglobulin antibodies (TgAb) that falsely lower Tg measurement. TgAb quantitative titers typically resolve steadily over just a few years in patients free of disease after initial therapy. Another paradigm shift is the recognition that most patients who eventually achieve freedom from disease do so by surgery with fewer patients cured by repetitive radioiodine treatments, and even fewer cured with external beam radiation. Patients who appear to be free of disease require a lifetime of follow-up to optimize levothyroxine treatment, and they will undergo periodic stimulation testing because some will still manifest recurrent disease. Patients with persistent disease despite negative ultrasonography, chest CT, and whole-body radioiodine imaging may have a tumor identified by fluorodeoxyglucose positron emission tomography, optimally performed with combined TSH stimulation and image fusion with CT or magnetic resonance imaging. Patients with metastatic disease who are unresponsive to conventional treatment are encouraged to participate in increasingly available thyroid cancer-specific clinical trials using targeted experimental oral or intravenous chemotherapeutic agents to address this tumor that has historically proven resistant to conventional chemotherapeutic agents.
 ...
PMID:Papillary thyroid cancer: medical management and follow-up. 1596 85

The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions, and its dysregulation in tumors is a common finding. The molecular basis of follicular thyroid cancer metastasis is not well understood but may also be influenced by AKT activation. We previously created a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta gene (TRbetaPV mouse) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. In this study, we investigated whether our mouse model exhibits similar AKT activation as human follicular thyroid cancer. Western blot analysis on thyroids from both wild-type and TRbeta(PV/PV) mice revealed elevation of activated AKT in TRbeta(PV/PV) mice. Immunohistochemistry and confocal microscopy reveal activated AKT in both the thyroid and metastatic lesions of TRbeta(PV/PV) mice. Whereas all three AKT isoforms were overexpressed in primary tumors from TRbeta(PV/PV) mice in the cytoplasm of thyroid cancer cells, only AKT1 was also found in the nucleus, matching the localization of activated AKT in a pattern similar to human follicular thyroid cancer. In the metastases, all AKT isoforms correlated with phosphorylated AKT nuclear localization. We created primary thyroid cell lines derived from TRbeta(PV/PV) mice and found reduction of phosphorylated AKT levels or AKT downstream targets diminishes cell motility. Activated AKT is common to both human and mouse follicular thyroid cancer and is correlated with increased cell motility in vitro and metastasis in vivo. Thus, TRbeta(PV/PV) mice could be used to further dissect the detailed pathways underlying the progression and metastasis of follicular thyroid carcinoma.
 ...
PMID:AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma. 1600 27

Bone is the second most frequent site of metastasis resulting from thyroid cancer. Many studies have investigated clinical features and prognostic factors of distant metastases stemming from thyroid cancer in Western countries. The purpose of this study was to review clinical characteristics of Korean patients with bone metastasis originating from thyroid cancer. Between January 1985 and August 2004, 28 patients with thyroid cancer were diagnosed with bone metastases at the Yonsei Severance Hospital in Seoul, Korea. Their clinical characteristics were analyzed retrospectively. Incidence of bone metastasis from follicular thyroid cancer was 6.8% (9 of 132 patients), and 0.4% (13 of 3,154 patients) from papillary thyroid cancer, with an odds ratio of 17.67 (95% confidence interval; 7.41-42). Twelve patients had no symptoms of bone metastasis. Overall mean number of metastasis sites was 2.6 +/- 1.9, and 12 patients had a solitary bone metastasis. Survival rates between the synchronous and metachronous metastasis groups were not significantly different, and the number of metastasis sites did not affect survival. However, the survival of patients that underwent curative treatment was longer than those with palliation (P = 0.0317). In Korea, the overall incidence of bone metastasis resulting from thyroid cancer was less than our expectation. Many patients were asymptomatic, and had a tendency of undergoing less aggressive or palliative treatment, even though the long-term survival of distant metastasis resulting from thyroid cancer with active treatment is relatively good. Further studies of the prognostic factors and effectiveness of various treatments of these patients are needed to enhance survival.
 ...
PMID:Clinical features of bone metastases resulting from thyroid cancer: a review of 28 patients over a 20-year period. 1641 Jun 61

A 65-year-old woman presented with multiple metastases from thyroid follicular carcinoma to the lung, skull, and brain. The skull and brain tumors had been successfully treated by surgery, thyroxine supplementation, and radiosurgery until she died of sudden intracerebral hemorrhage which had no connection with tumor treatment. The lung tumor was treated by conventional irradiation and radioactive ablation. Well-differentiated thyroid carcinoma is a slowly progressive tumor. Follicular carcinoma is thought to have the most optimistic prognosis even with metastases to the lymph nodes and lung. Radioactive ablation using iodine-131 is widely used to treat the primary and/or metastatic lesion. However, the prognosis for patients with brain metastases is poor. Intracranial metastasis of this tumor is rare, but has a mean posttreatment survival of around 12 months. Surgical excision of the metastatic intracranial lesion may be the only effective treatment.
 ...
PMID:Thyroid follicular carcinoma metastasized to the lung, skull, and brain 12 years after initial treatment for thyroid gland--case report. 1679 52

Unusual presentations with bone, lung or soft tissue metastases in initial diagnosis of follicular thyroid carcinoma have been reported occasionally. This implies how difficult it is to diagnosis this type of cancer at the pre-operative or intra-operative stage of treatment. Fine needle aspiration cytology has been shown to be an ineffective method for diagnosing vascular or capsule invasion of follicular thyroid cancer. Multiple frozen sections, usually 5 to 12 depending on the size of the tumor, can achieve a diagnostic accuracy of 98%. Clinical application of various gene expressions in thyroid follicular tumors by needle aspiration using in situ hybridization requires further investigation. Although radioactive iodide (131I) has been used as the standard treatment for follicular thyroid carcinoma with distant metastases, the effectiveness of 131I treatment for follicular thyroid carcinoma depends on the differentiation of cancer cells. The possibility of 131I for thyroid remnant ablation replacing a secondary operation for follicular thyroid carcinoma has been debated. Recent studies applied more expressions of sodium iodide symporters to attain the effect of 131I treatment and slow the proliferation of thyroid cancer cell which, in turn, slows the progression of follicular carcinoma. Consensus for the surgical procedures for the specific prognostic risks for follicular thyroid carcinoma is needed. Dedifferentiated, anti-angiogenic, or gene therapies for follicular thyroid cancer with distant metastases or anaplastic transformation comprise the principal directions in future research for this cancer.
 ...
PMID:Follicular thyroid carcinoma: From diagnosis to treatment. 1680

The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been elucidated. Patterns for tumour behaviour and metastasic spread vary according to tumour type and whether differences in the angiogenic or lymphangiogenic phenotype influence the route for tumour metastases or determine a more aggressive behaviour has not been fully explored. The angiogenic and lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions (n=191) were studied. Using immunohistochemistry for CD34, lymphatic vessel endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic endothelium respectively), vascular endothelial growth factor (VEGF-A), VEGF-C and fibroblast growth factor-2 (FGF-2), this study analyses microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic factors in normal thyroid (NT; n=19), multinodular goitre (n=25), toxic multinodular goitre (n=8), Graves' hyperplasia (n=22), follicular adenoma (n=54), papillary carcinoma (PC; n=27), incidental papillary microcarcinoma (PMC; n=8), follicular carcinoma (FC; n=20) and medullary carcinoma (MC; n=8). MVD was decreased in proliferative lesions, benign and malignant, compared with NT (P<0.0001). In contrast, VEGF-A expression was increased in thyroid carcinomas (PC, FC and MC) when compared with PMC, benign lesions and NT (P<0.0001). LVD was higher in PC and PMC (P=0.001), and VEGF-C expression was increased in PC (P<0.0001). Despite higher LVD and increased expression of VEGF-A and VEGF-C in thyroid cancers, these markers were not related to poor prognosis in terms of tumour size, multifocality and/or presence of lymphatic or distant metastases. In conclusion, angiogenesis is reduced in thyroid proliferative lesions compared with NT tissue. However, VEGF-A expression is upregulated in thyroid cancers. Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to lymphatic metastases. This may be an important mechanism underlying the differences in metastatic behaviour between papillary and follicular thyroid cancer.
 ...
PMID:Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour. 1695 41

Follicular thyroid cancer (FTC) is known to metastasize to distant sites via hematogenous spread; however, the underlying pathways that contribute to metastasis remain unknown. Recent creation of a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta (TRbeta(PV/PV) mouse) that spontaneously develops thyroid cancer with metastasis similar to humans has provided new opportunities to study contributors to FTC metastasis. This study evaluates the role of gelsolin, an actin-regulatory protein, in modulating the metastatic potential of FTC. Gelsolin was previously found by cDNA microarray analysis to be down-regulated in TRbeta(PV/PV) mice as compared with wild-type mice. This study found an age-dependent reduction of gelsolin protein abundance in TRbeta(PV/PV) mice as tumorigenesis progressed. Knockdown of gelsolin by small interfering RNA resulted in increased tumor cell motility and increased gelsolin expression by histone deacetylase inhibitor (trichostatin A) led to decreased cell motility. Additional biochemical analyses demonstrated that gelsolin physically interacted with TRbeta1 or PV in vivo and in vitro. The interaction regions were mapped to the C terminus of gelsolin and the DNA binding domain of TR. The physical interaction of gelsolin with PV reduced its binding to actin, leading to disarrayed cytoskeletal architectures. These results suggest that PV-induced alteration of the actin/gelsolin cytoskeleton contributes to increased cell motility. Thus, the present study uncovered a novel PV-mediated oncogenic pathway that could contribute to the local tumor progression and metastatic potential of thyroid carcinogenesis.
 ...
PMID:Gelsolin: a novel thyroid hormone receptor-beta interacting protein that modulates tumor progression in a mouse model of follicular thyroid cancer. 1717 Jan 1

In well-differentiated thyroid carcinoma, only a subset of patients develop distant metastases, predominantly to the lungs and the skeletal system. Only a few cases of metastatic spread to the kidneys are described in the literature. We report the case of a 64-year-old woman with a long history of follicular thyroid cancer who developed renal metastases. The lesions were detected with I-131 scintigraphy, SPECT/CT and thin-collimated contrast-enhanced CT. Subsequent surgery and histopathologic analysis of the renal lesions confirmed the diagnosis.
 ...
PMID:Renal metastases from follicular thyroid cancer on SPECT/CT. 1771 39

Connexin26 (Cx26), a component of GAP junctions and until recently believed to be a tumor suppressor gene, has been shown to play an important role in lymphatic invasion as well as lymph node and distant metastases in squamous lung cancer and breast cancer. In the study presented here, we investigated Cx26 expression in human papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) and its relationship with various clinicopathological parameters. Of 69 PTCs, 33 were positive for Cx26 (47.8%), as were five of 11 FTCs (45.5%), all follicular thyroid adenomas (n=22) and normal thyroid tissues (n=20) were negative for Cx26. A statistically significant association was observed between Cx26 expression and large tumor size (p=0.028 for PTC) and lymph node metastases (p=0.053 (marginally significant) for PTC and p=0.035 for FTC). Presence of intra-glandular dissemination of tumor cells was significantly (p=0.048) more frequent in Cx26-positive (30.3%) than Cx26-negative PTCs (11.1%). Lymphatic vessel invasion was more frequent in Cx26-positive PTCs (6.1%) than in Cx26-negative PTCs (0%) though the difference was not statistically significant. These results suggest that Cx26 may be implicated in the pathogenesis of PTC and FTC and is associated with the biologically aggressive phenotypes of these tumors.
 ...
PMID:Connexin26 expression is associated with aggressive phenotype in human papillary and follicular thyroid cancers. 1819 Oct 19

The presence of distant metastases from differentiated thyroid carcinoma decreases the 10-year survival of patients by 50%. Bone metastases represent a frequent complication especially of follicular thyroid cancer and severely reduce the quality of life causing pain, fractures, and spinal cord compression. Diagnosis is established by correlating clinical suspicion with imaging. Imaging is essential to detect, localize, and assess the extension of the lesions and should be used in conjunction with clinical evidence. Bone metastases are typically associated with elevated markers of bone turnover, but these markers have not been evaluated in differentiated thyroid cancer. Skeletal and whole-body magnetic resonance imaging and fusion 2-deoxy-2-[18F]fluoro-D-glucose whole-body positron emission tomography/computed tomography (PET/CT) are the best anatomic and functional imaging techniques available in specialized centers. For well-differentiated lesions, iodine-PET scan combined (124)I-PET/CT is the newest imaging development and (131)I is the first line of treatment. Bisphosphonates reduce the complications rate and pain, alone or in combination with radioiodine, radionuclides, or external beam radiotherapy and should be employed. Surgery and novel minimally invasive consolidation techniques demand an appropriate patient selection for best results on a multimodal approach. Basic research on interactions between tumor cells and bone microenvironment are identifying potential novel targets for future more effective therapeutic interventions for less differentiated tumors.
 ...
PMID:Bone metastases from differentiated thyroid carcinoma. 1831 Feb 74


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