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)

Thyroid nodules are frequently found in association with Graves' disease. Papillary carcinoma can arise from these nodules. We report a 65-year-old gentleman who presented with classical features of Graves disease. Technetium 99 scintigraphy revealed diffuse goiter with a cold nodule over the isthmus. Papillary thyroid cancer was suggested by the enlarging thyroid gland, and by the presence of cold nodule, and was proven by fine needle aspiration biopsy of this nodule. The diagnosis was confirmed by histopathology of thyroid specimen after total thyroidectomy, which also showed local invasion; metastatic work up revealed pulmonary and liver metastasis. Despite treatment by total thyroidectomy, twice radioactive iodine I131 ablation and levothyroxine replacement in a thyroid stimulating hormone suppressive dose, he still harbors metastases with elevated thyroglobulin level. This case should raise the index of suspicion of the treating physician to consider similar association, and to prompt early diagnosis and surgical treatment to prevent dreadful consequences that might adversely affect the outcome.
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PMID:Graves disease and papillary thyroid cancer. An association that can be missed. 1612 29

This report concerns a 79-year-old woman with coexisting anaplastic thyroid carcinoma (ATC) and Graves' disease (GD). The patient was referred to our clinic because of palpitation and a palpable mass on the left side of her neck. Thyroid function tests showed hyperthyroidism with elevated thyroid-stimulating antibodies. Ultrasonography of the thyroid demonstrated an adenomatous nodule-like marcated nodule (27.6 x 26.5 x 36.4 mm) with cystic degeneration inside the left lobe. (123)I thyroid scintigraphic imaging showed a cold area corresponding to the nodule with continuous uptake in the remaining thyroid tissue despite suppressed TSH levels. These findings led to a diagnosis of GD. On the other hand, the thyroid nodule could not be definitely diagnosed even after fine needle aspiration biopsy (FNAB) which produced findings suggestive of both papillary thyroid carcinoma and ATC. Open biopsy of the nodule showed an ATC. Regional lymph node metastases as well as multiple lung metastases, which could not be found at the initial visit, had been already developed by that time. Our case is pathophysiologically interesting because it suggests that GD or thyroid-stimulating antibodies (TSAb) may stimulate malignant transformation of differentiated carcinoma. It is also clinically important because it indicates that all thyroid nodules, particularly palpable cold nodules, associated with GD require careful management to detect malignancy because they are at higher risk of harboring malignancy.
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PMID:Anaplastic thyroid carcinoma associated with Graves' disease. 1628 32

Secondary neoplasm of the thyroid mimicking a primary thyroid lesion is a rare finding, especially in an individual without a past history of malignancy. A case of squamous cell carcinoma metastatic to the thyroid (presenting as a solitary thyroid nodule), who had an unsuspected primary in the esophagus is described. Usually, multiple areas of the gland are involved in the secondary involvement of the thyroid. The clinical presentation of an apparently asymptomatic mass with neck lymphadenopathy, normal thyroid functions, and a cold nodule on 99mTcO4- thyroid scan can often lead to a misdiagnosis as primary thyroid neoplasm. The present case underscores the fact that due importance to the subtle signs and symptoms and a high degree of suspicion, whenever the histology is unusual for a thyroid primary, is needed and the workup should include ruling out other primary malignancies.
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PMID:Squamous cell carcinoma of esophagus masquerading as solitary thyroid nodule. 1639 40

Metastasis is a multistep and multifunctional biological cascade that is the final and most life-threatening stage of cancer progression. Understanding the biological underpinnings of this complex process is of extreme clinical relevance and requires unbiased and comprehensive biological scrutiny. In recent years, we have utilized a xenograft model of breast cancer metastasis to discover genes that mediate organ-specific patterns of metastatic colonization. Examination of transcriptomic data from cohorts of primary breast cancers revealed a subset of site-specific metastasis genes that are selected for early in tumor progression. High expression of these genes predicts the propensity for lung metastasis independently of several classic markers of poor prognosis. These genes fulfill dual functions-enhanced primary tumorigenicity and augmented organ-specific metastatic activity. Other metastasis genes fulfill functions specialized for the microenvironment of the metastatic site and are consequently not selected for in primary tumors. These findings improve our understanding of metastatic progression, facilitate the interpretation of primary tumor gene expression data, and open several important possibilities for future clinical application.
Cold Spring Harb Symp Quant Biol 2005
PMID:Identifying site-specific metastasis genes and functions. 1686 48

Lung tumors are usually classified into small-cell lung cancer (SCLC) or non-SCLC (NSCLC) depending on their pathological and histological characteristics. SCLC is defined not only by its characteristic neuroendocrine differentiation, aggressiveness, and metastatic potential, but also by a specific set of genetic aberrations, including the loss of the tumor suppressor genes p53 and Rb1 and the amplification of any member of the Myc family of oncogenes. We have previously described a mouse model of SCLC by somatic conditional disruption of Trp53 and Rb1 genes that closely resembles the human condition. Based on the possibility to study early tumor lesions and to culture and subclone progressed tumors and metastases, we discuss here a strategy to define genotype-phenotype relationships that can explain the underlying biology of lung neuroendocrine tumors. We have found that tumors may be constituted by genetically variant cell populations, which might represent different progression stages. Interestingly, we observed L-myc amplification and Ascl-1 expression in those populations showing neuroendocrine differentiation. Non-neuroendocrine cell populations from the same tumors did not show L-myc amplification nor Ascl-1 expression. We propose that this genetic divergence can play a relevant role in the definition of some phenotypic characteristics like metastasis potential or chemoresistance.
Cold Spring Harb Symp Quant Biol 2005
PMID:Genotype-phenotype relationships in a mouse model for human small-cell lung cancer. 1686 58

The aim of this study was to determine the prevalence of trapping-only nodules of the thyroid gland. The study was prospectively performed in patients bearing hot or warm thyroid nodules at pertechnetate scan in the presence of circulating thyrotropin (TSH) within the normal range. The study was restricted to these patients because nodules that suppress TSH are certainly autonomous. In 140 patients showing hot or warm nodules at 30-minute pertechnetate scintigraphy, and normal TSH levels, radioiodine scintigraphy was performed at 24 hours. The trapping-only pattern, i.e., the presence of a cold nodule in late radioiodine scintigraphy was observed in seven patients (5%). Five had benign thyroid nodules, one follicular carcinoma, and one extrathyroid metastases of papillary-follicular carcinoma. Despite controversy on this issue, trapping-only nodules of thyroid should be searched because they have risk of malignancy and must be differentiated from autonomous adenomas at the compensated stage. The search may be limited to patients with normal serum TSH.
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PMID:The trapping-only nodules of the thyroid gland: prevalence study. 1691 Aug 77

The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a 'cold' or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize beta-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10-20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of 'differentiation' agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in 'scan-negative' thyroid cancer and some breast cancer.
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PMID:Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. 1695 31

Pain associated with cancer, particularly when tumors metastasize to bone, is often severe and debilitating. Better understanding of the neurobiological mechanisms underlying cancer pain will likely lead to the development of more effective treatments. The aim of this study was to characterize changes in response properties of nociceptive dorsal horn neurons following implantation of fibrosarcoma cells into and around the calcaneus bone, an established model of cancer pain. Extracellular electrophysiological recordings were made from wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in mice with tumor-evoked hyperalgesia and control mice. WDR and HT neurons were examined for ongoing activity and responses to mechanical, heat, and cold stimuli applied to the plantar surface of the hind paw. Behavioral experiments showed that mice exhibited hyperalgesia to mechanical and heat stimuli applied to their tumor-bearing hind paw. WDR, but not HT, nociceptive dorsal horn neurons in tumor-bearing mice exhibited sensitization to mechanical, heat, and cold stimuli and may contribute to tumor-evoked hyperalgesia. Specifically, the proportion of WDR neurons that exhibited ongoing activity and their evoked discharge rates were greater in tumor-bearing than in control mice. In addition, WDR neurons exhibited lower response thresholds for mechanical and heat stimuli, and increased responses to suprathreshold mechanical, heat, and cold stimuli. Our findings show that sensitization of WDR neurons contributes to cancer pain and supports the notion that the mechanisms underlying cancer pain differ from those that contribute to inflammatory and neuropathic pain.
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PMID:Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. 1793 3

Breast cancer is the most commonly diagnosed malignancy in women worldwide. Metastatic development is associated with poor prognosis and current therapies provide only limited success. Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a wild-type common-cold producing enterovirus, is an effective oncolytic agent against human melanoma xenografts in vivo. CVA21 specifically targets and lytically infects susceptible cells expressing the CVA21 cellular receptors, intercellular adhesion molecule-1 (ICAM-1) and/or decay-accelerating factor (DAF). Herein, the efficacy of CVA21 as a therapeutic agent against human breast cancer was investigated both in vitro and in vivo. Flow cytometric analysis revealed that the human breast cancer cell lines examined expressed significantly elevated levels of surface ICAM-1 and DAF compared to normal breast cell lines, and that all cancerous lines were more susceptible to lytic infection by CVA21 than the normal cells. Through the use of subcutaneous (T47D cells) and orthotopic (MDA-MB-231-luc cells) xenograft SCID mouse models it was demonstrated that a single intravenous injection of CVA21 produced significant regression of pre-established tumors in vivo, as well as targeting and elimination of metastases in the orthotopic model. Taken together, these findings highlight the exciting potential of CVA21 as a therapeutic agent against both primary and metastatic human breast cancer.
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PMID:Systemic targeting of metastatic human breast tumor xenografts by Coxsackievirus A21. 1825 29

Cardiac metastatic squamous cell laryngeal carcinoma is rare. We report the case of a 49-year-old man with recurrent squamous laryngeal carcinoma presenting with right leg acute ischaemia and large mobile right and left cardiac masses. The patient has history of laryngeal squamous cell cancer surgically treated with total laryngectomy, thyroidectomy, and tracheostomy 2 years ago. He was admitted to our intensive care unit with acute right leg pain, left sided chest pain, hypotension 92/55, and tachycardia 112 bpm. On physical exam, he had a faint pulse of his right Posterior Tibial artery with a cold foot, but no discoloration. Heart sounds were normal with no murmur. Initial workup showed a Troponin of 0.27. An electrocardiogram showed sinus tachycardia, with inverted T waves in the Infero-lateral leads. Emergent surgical thrombectomy was done on his right leg with restoration of arterial blood flow to the affected limb. An echocardiogram showed a preserved left ventricular function with multiple areas of echogenic masses in all four cardiac chambers located at the annulus of the tricuspid valve, the right ventricular free wall and along the inter-ventricular septum. No intracardiac shunt was detected by contrast study. Computed tomography scan of the heart confirmed the presence of multiple exophytic intracardiac masses within the left atrium, the right ventricle, interventricular septum, and lateral free wall of the left ventricle. Immunohistochemical staining with cytokeratin of the emboli was consistent with malignant squamous cell carcinoma consistent with metastases of his known laryngeal squamous cell cancer.
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PMID:Unusual sites of metastatic involvement: intracardiac metastasis from laryngeal carcinoma. 1849 Mar 28


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