Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kidney metastases from thyroid cancer are rare. We report two such patients and demonstrate that the in vivo 131I uptake by the kidney metastasis is associated with high levels of sodium iodide (Na+/I-) symporter (NIS) expression in the first case. Case 1: A 61-year-old woman with papillary thyroid carcinoma-follicular variant (PTC-FV) presented with scapular metastasis. After thyroidectomy and scapulectomy, a 131I posttherapy scan showed left upper quadrant uptake. A 3.0-cm metastatic PTC-FV deposit was removed by partial nephrectomy. Case 2: A 53-year-old woman presented with back pain. A computed tomography (CT) scan showed a 3.5-cm renal mass, a multinodular goiter, and lung metastases thought secondary to a renal cell carcinoma. A unilateral nephrectomy revealed metastatic PTC-FV. After thyroidectomy, a 131I posttherapy scan showed lung and skeletal metastases. NIS immunoreactivity in tumoral tissue was strongly positive in the primary tumor, shoulder, and kidney metastasis in case 1, as well as in the primary tumor in case 2. Spotty, low-level NIS expression was observed in the kidney metastasis in case 2. In conclusion, kidney metastases of PTC-FV may occasionally retain adequate levels of NIS expression, enabling their detection during life. Thus, intense uptake in the abdomen during 131I imaging should not be assumed to be physiological gastrointestinal tract residual radionuclide activity.
 ...
PMID:Renal metastases from thyroid papillary carcinoma: study of sodium iodide symporter expression. 1152 75

The ability of thyroid cancers to concentrate radioiodine (RAI) is dependent, in part, upon the expression and functional integrity of the sodium iodide symporter (NIS). However, some differentiated thyroid carcinomas (DTCs) and most undifferentiated thyroid carcinomas lack the ability to concentrate iodide and are thereby insensitive to 131I therapy. Variation of NIS protein expression may be an important factor in this behavior. We wished to determine whether NIS protein expression in primary DTC tumors correlated with the subsequent RAI uptake by metastatic lesions in the same patients. We obtained paraffin-embedded tissue specimens from 60 patients with metastatic thyroid cancer who had undergone total or near-total thyroidectomy at the Mayo Clinic for DTC and had known presence or absence of RAI uptake in their tumor deposits determined by total body scanning after thyroid hormone withdrawal. Tissue sections from the primary intrathyroidal tumors were subjected to immunostaining (IS) using a monoclonal antibody against human NIS. Slides were subsequently examined for specific IS by two independent reviewers. For each patient, whole body scan (WBS) uptake was recorded, and correlation between results of IS and WBS was analyzed. Of 43 patients with a positive WBS, 37 also had positive IS of their tumors. In six patients with negative IS, a positive WBS was documented, and in three of these cases TSH at the time of surgery was less than 0.3 mIU/liter. Of the 17 patients with negative WBS, 10 were also negative on IS. Positive IS accurately predicted a positive scan in our study in 84% of cases; the ability of the IS to detect all cases with a positive scan was 86%, and it increased to 90% when patients who were receiving thyroid hormone therapy at the time of surgery were excluded from the analysis. Overall, the results of our retrospective study suggest that NIS IS of the thyroidal primary tumor in patients with papillary and follicular thyroid cancers has substantial ability to predict the behavior of subsequent deposits of metastatic and recurrent cancer with respect to iodine trapping and concentration. Our findings require confirmation in prospective studies to more accurately determine the predictive ability of the test and its role in the postoperative management of patients with DTC. If confirmed, NIS IS of DTC primary lesions may prove useful in the management of patients with known or suspected metastatic thyroid cancer.
 ...
PMID:Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. 1170 45

A decreased radioiodine uptake is frequently detected in differentiated thyroid carcinomas (DTC) and is associated with high recurrence rate and reduced survival. We investigated the correlation between NIS mRNA expression levels in the primary tumor and patient outcome using a quantitative real-time RT-PCR method. NIS expression was decreased in 17 DTC (21.04+/-39.66 pg Eq) compared to four autoimmune thyroid disease (180.51+/-92.63 pg Eq) and 14 normal tissues (75.71+/-66.98 pg Eq) (p<0.0001). The 17 thyroid differentiated carcinoma patients were submitted to surgery complemented by radioiodine ablation and had at least 24 months of follow-up, under levothyroxine continued suppressive therapy. According to their outcome, we could characterize a group of papillary carcinoma patients with aggressive carcinomas, whose NIS mRNA levels were markedly lower than a group with non-aggressive carcinomas (0.62+/-0.79 versus 54.87+/-53.79; p<0.005). We suggest that the quantification of NIS mRNA relative levels in the primary tumor may predict poor outcome.
 ...
PMID:Low expression of sodium iodide symporter identifies aggressive thyroid tumors. 1455 Sep 56

Because most differentiated thyroid carcinomas have an excellent prognosis, some authors have claimed that these patients are suffering from over treatment. Grouping patient- and tumor-specific factors have been proposed for prognostic stratification, but no clinicopathologic staging was demonstrated to be useful at the present time. More recently, molecular genetic tools have been used to identify and understand how the primary tumor progresses and many molecular markers have been proposed in order to distinguish the subset of patients at risk of developing metastasis. Here we analyzed some of them, with emphasis on the expression of NIS, a determinant of prognosis since the functional integrity of the iodine transport is essential to assure an uptake of radioiodine high enough to detect and destroy any tumoral thyroid tissue. More recent observations on how some relevant molecular genetics aspects of thyroid cancer impact new potential therapeutic approaches are also discussed.
 ...
PMID:[Thyroid cancer: prognostic factors and treatment]. 1561 25

Differentiating drugs may be able to re-sensitize thyroid carcinomas to radioiodine therapy. Substituted thiazolidinediones (TZDs) belong to the group of oral anti-diabetic drugs that also possess anti-proliferative and pro-apoptotic effects and, potentially, differentiating effects on several cancer cell lines. Some of the effects are mediated via the peroxisome proliferator-activated receptor gamma (PPAR-gamma). We investigated the effect of troglitazone, rosiglitazone and pioglitazone on differentiation in normal porcine thyrocytes and in the follicular carcinoma cell lines FTC 133 and FTC 238. Differentiation was investigated by measuring 125I uptake and the expression of sodium-iodide symporter and thyroglobulin proteins. The TZDs were tested in the presence of retinol and retinoic acid. Additionally, proliferation was evaluated by [3H]thymidine uptake and cell number and apoptosis by annexin V-labeling. Controls included tocopherol and unsubstituted thiazolidinedione and co-incubation of the TZDs with the PPAR-gamma antagonist GW9662. PPAR-gamma and retinol X receptor (RXR)-alpha were investigated by immunocytochemistry, Western blot and RT-PCR. Cells derived from the metastasis showed greater responses than cells derived from the primary tumor. Troglitazone showed greater effects than the other TZDs. Troglitazone significantly increased 125I uptake and apoptosis and decreased [3H]thymidine uptake and cell number. The amount of the sodium iodide-symporter in the membrane fraction was significantly increased, while that of thyroglobulin was not influenced by the treatment. Inclusion of antagonist did not abolish these effects. No synergistic effect with any retinoid was detected. All transformed cells expressed PPAR-gamma and RXR-alpha but TZDs did not change their expression. Troglitazone appears to be suited for the re-differentiation treatment of dedifferentiated thyroid carcinoma because its action is twofold. On the one hand it increases differentiation and on the other hand it inhibits proliferation.
 ...
PMID:Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture. 1594 4

Well under 15% of differentiated thyroid carcinoma (DTC) is diagnosed at < or =18 years of age. The population is heterogenous and the differences between prepubertal children and pubertals and adolescents are to be considered. Although very little has been reported on children with sporadic DTC under the age of 10 years, juvenile DTC has at least some undeniable differences with adult DTC: (1) larger primary tumor at diagnosis; (2) metastatic pattern and features, namely: (a) greater prevalence of neck lymph node and distant metastases at diagnosis, (b) lungs almost the sole distant metastatic site, (c) pulmonary metastases nearly always functional; (3) closer-to-normal and more frequent sodium-iodide symporter (NIS) expression; and (4) higher recurrence rate but longer overall survival. These differences are especially distinct in prepubertal children. The goals of primary treatment of juvenile DTC are to eradicate disease and extend not only overall, but recurrence-free survival (RFS). Extending RFS is itself a desirable goal in children because it improves quality-of-life, alleviates anxiety during psychologically formative years, reduces medical resource consumption, and may increase overall survival. Primary treatment of DTC generally comprises a combination of surgery, radioiodine ((131)I) ablation, and thyroid hormone therapy applied at varying levels of intensity. Therapeutic decision-making must rely on retrospective adult and/or pediatric outcome studies and on treatment guidelines formulated mostly for adults. Differences between juvenile and adult DTC and physiology dictate distinct treatment strategies for children. We, and many others, advocate a routine intensive approach because of the more advanced disease at diagnosis, propensity for recurrence, and greater radioiodine responsiveness in children, as well as published evidence of significant survival benefits, especially regarding RFS. This intensive approach consists of total thyroidectomy and central lymphadenectomy in all cases, completed by modified lateral lymphadenectomy when necessary and followed by radioiodine administration. However, absence of prospective studies and of universal proof of overall cause-specific survival benefits of this approach have led some to propose more conservative strategies. Most European centers give radioiodine ablation to the vast majority of juvenile DTC patients. Ablation seeks to destroy any residual cancer, including microfoci, as well as healthy thyroid remnant. Large studies have documented the procedure to decrease cause-specific death rates and, in children, to significantly lessen locoregional recurrence rates (by factors of 2-11) independent of the extent of surgery. There is universal agreement on treating inoperable functional metastases with large radioiodine activities. Treatment is especially effective in small tumor foci up to 1 cm in diameter, and should be administered every 6-12 months until complete response, loss of functionality, or attainment of cumulative activities between 18.5-37 GBq (500-1000 mCi). Radioiodine therapy is generally safe. Short-term side effects include nausea and vomiting (more frequent in children than in adults), transient neck pain and edema, sialadenitis (<5% incidence), mild myelosuppression (approximately 25%), transient impairment of gonadal function both in females and males (sperm quality in boys), or nasolacrimal obstruction (approximately 3%), with most cases generally being asymptomatic-moderate, self-limiting, or easily prevented or treated. If pregnancy is ruled out before each (131)I administration, and conception avoided in the year afterward, radioiodine therapy appears not to impair fertility. However, therapeutic (131)I carries a small but definite increase in cancer risk, particularly in the salivary glands, colon, rectum, soft tissue and bone. To better guide primary treatment, different therapeutic combinations should be prospectively compared using RFS as the primary endpoint. Efforts also should be made to identify molecular signatures predicting recurrence, metastasis and mortality.
 ...
PMID:Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review. 1632 22

Anaplastic thyroid carcinoma is a rare malignant neoplasia with high biological aggressiveness and rapid and lethal clinical course. In selected patients, an aggressive multimodal therapy could decrease illness progression both in the neck e in other sites. However, it is not clear if these combined treatments improve survival. In our institution, the Department of Nuclear Medicine has a 40-year experience in monitor and treatment of a group of 48 patient with ATC confirmation that clinical presentation could overlap pre-existent nodular goitre or rapid enlarging mass of recent onset. At onset, age do not change final poor prognosis and the survival seems most favorable in patients with a primary tumor size <6 cm. A better mean survival was noticed in those patients who respond to the multimodal therapy (8 months vs 4.6 months). Radioiodine (131 I) therapy is unnecessary due to the loss of NIS expression of the ATC cells. Therefore, after quick clinical and instrumental work up, our experience and the literature data suggest that the first line therapy is represented from external radiotherapy combined also with cisplatin or doxorubicin, followed by "curative" surgical procedure of the primary lesion in the neck and subsequent chemotherapy. For those patients who show distant metastasis at onset chemotherapy is the first line therapy followed by external radiotherapy and when possible subsequent surgical procedure.
 ...
PMID:Anaplastic thyroid carcinoma. Practical aspects of multimodal therapy and data emerging from a 40-year experience at a single Italian institution. 2038 23

Glioblastoma (GBM) is the most common primary brain tumor in adults and has a dismal prognosis despite multimodality treatment. Given the resistance of glioma stem cells (GSC) to chemotherapy and radiation therapy, their eradication could prevent tumor recurrence. We sought to evaluate the antitumor activity of measles virus (MV) derivatives against GSC. We generated neurosphere cultures from patient-derived primary tumor GBM xenografts, and we characterized them for the GSC markers CD133, SOX2, Nestin, ATF5 and OLIG2. Using the MV-strains MV-GFP, MV-CEA and MV-NIS we demonstrated infection, viral replication and significant cytopathic effect in vitro against GSC lines. In tumorigenicity experiments, GBM44 GSC were infected with MV in vitro and subsequently implanted into the right caudate nucleus of nude mice: significant prolongation of survival in mice implanted with infected GSC was observed, compared with mock-infected controls (P=0.0483). In therapy experiments in GBM6 and GBM12 GSC xenograft models, there was significant prolongation of survival in MV-GFP-treated animals compared with inactivated virus-treated controls (GBM6 P=0.0021, GBM12 P=0.0416). Abundant syncytia and viral replication was demonstrated in tumors of MV-treated mice. Measles virus derivatives have significant antitumor activity against glioma-derived stem cells in vitro and in vivo.
 ...
PMID:Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. 2291 95