Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current methods of research into thyroid nodular disease (TND) based on the polymerase chain reaction (PCR) and reverse-transcription (RT) permit the detection of some markers, even in poorly cellular biological material. The findings from fine-needle aspiration biopsy (FNAB), the most commonly used procedure in TND, do not always correlate with the postoperative histopathological diagnosis, sometimes giving a false negative result. The aim of this present study was to improve the classical cytological evaluation of the material obtained with ultrasound-guided biopsy with a RT-PCR based technique in order to detect carcinoma even in a minimally invasive form. Aspirate from the 30 patients included in the study was smeared for conventional cytology (H+E and MGG staining) and the leftover material in the needle was frozen for subsequent PCR analysis. Fine-needle aspiration specimens were evaluated for the presence of galectin-3 (GAL-3), the most promising molecular marker of malignancy. As a positive control for cells of follicular origin, thyroglobulin (Tg) gene expression was performed. RT-PCR was performed on extracted RNA and with specific primers for the screened genes, based on a one-step reaction with a Biometra PCR machine. Tg expression was observed in 23 aspirates, among which 10 were positive for the expression of GAL-3 [3 cases of PTC, 1 an oxyphilic variant of FTC, 1 an oxyphilic variant of follicular adenoma (FA), 1 a foetal variant of FA, 2 of Hashimoto thyroiditis (HT) and 2 of HT with coexisting FA]. Our results are the first evidence that GAL-3 expression, previously documented in thyroid carcinoma of follicular origin, is also present in Hashimoto thyroiditis. This study reveals some limitations in nodule or multiple nodules of benign character. If the diagnosis of HT is excluded, then the usefulness of the method in the diagnosis of malignancy may still be very high.
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PMID:Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents. 1257 40

Galectin-3 is a multifunctional protein highly expressed in thyroid cancer. The galectin-3 gene (LGALS3) has several annotated candidates SNPs, however the relationship between galectin-3 SNPs and specific phenotypic variations relevant to health has not been evaluated. In this study, we investigated SNPs in the galectin-3 gene and a putative association with thyroid tumorigenesis. The presence of LGALS3 SNPs in thyroid carcinoma cell lines (NPA, TPC-1, WRO, ARO), thyroid tissues of 55 patients with multinodular goiter or papillary carcinoma diagnosis and lymphocytes of peripheral blood of 45 healthy individuals was evaluated by sequencing and SSCP. The analysis of LGALS3 coding sequence showed that the T98P site presents a great genotypic variation, since we observed both homozygous (AA or CC) and heterozygous (AC) patterns. In thyroid carcinoma cell lines, the genotype of NPA in the LGALS3 T98P site is CC, while TPC-1, WRO and ARO are AC. The genotypic frequency of T98P SNP observed in multinodular goiter (AC= 67%; AA= 23%; CC= 10%) and papillary carcinoma (AC= 68%; AA= 20%; CC= 12%) were similar to the frequency observed in the control population (AC= 60%, AA= 24%, CC= 16%). In conclusion, no association between LGALS3 T98P genotype and the phenotype of the benign or malignant thyroid tumor was observed.
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PMID:[Polymorphism on codon 98 of the galectin-3 gene is not associated to benign and malignant thyroid tumors]. 1722 Nov 14

Ten to fifteen percent of fine-needle aspiration biopsy (FNAB) of thyroid nodules are indeterminate. Galectin-3 (Gal-3) and the oncogene BRAFV600E are markers of malignancy useful to improve FNAB accuracy. The objective of this study was to determine whether the combined analysis of Gal-3 and BRAFV600E expression in thyroid aspirates could improve the diagnosis in FNAB with suspicious cytological findings. Two hundred and sixty-one surgical thyroid tissues and one hundred and forty-four thyroid aspirates were analyzed for the presence of the two markers. In surgical specimens, Gal-3 expression was present in 27.4% benign nodules, 91.9% papillary (PTC) and 75% follicular (FTC) thyroid carcinomas. BRAFV600E was not detected in 127 benign nodules, as well as in 32 FTCs, while was found in 42.9% PTC. No correlation was found between BRAF mutation and Gal-3 expression. Forty-seven consecutive FNAB suspicious for PTC were analyzed for the presence of the two markers. Of these nodules, 23 were benign at histology, 6 were positive for Gal-3, none displayed BRAFV600E, and 17 were negative for both the markers. Twenty suspicious nodules were diagnosed as PTC and four FTCs at histology. Of these 24 carcinomas, 9 resulted positive for BRAFV600E, 17 for Gal-3, and 22 for one or both the markers. The sensitivity, specificity, and accuracy for the presence of Gal-3 and/or BRAFV600E were significantly higher than those obtained for the two markers alone. Notably, the negative predictive value increased from 70.8 to 89.5%. In conclusion, the combined detection of Gal-3 and BRAFV600E improves the diagnosis in FNAB with cytological findings suspicious for PTC and finds clinical application in selected cases.
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PMID:Combined analysis of galectin-3 and BRAFV600E improves the accuracy of fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid carcinoma. 1804 60

A subset of patients with papillary thyroid cancer (PTC) present with aggressive disease that is refractory to conventional treatment. Novel therapies are needed to treat this group of patients. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with anti-apoptotic activity. Over 30 studies in the last 3 years have reported that Gal-3 is highly expressed in PTC relative to normal thyrocytes. In this study, we show that Gal-3 silencing with RNA interference stimulates apoptosis, while Gal-3 overexpression protects against both TRAIL- and doxorubicin-induced apoptosis in PTC cells. The anti-apoptotic activity and chemoresistance related to Gal-3 function can be partially reversed through the inhibition of the PI3K-Akt pathway, suggesting that Gal-3 acts, at least in part, on the PI3K-Akt axis. These observations support further evaluation of Gal-3 as a potential therapeutic target in patients with aggressive PTC.
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PMID:Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells. 1912 5

Galectin-3 (Gal-3) is an anti-apoptotic molecule of the beta-galactoside-binding lectin family. Gal-3 is down-regulated by wt-p53 and this repression is required for p53-induced apoptosis. Since poorly differentiated thyroid carcinomas (PDTCs) and anaplastic thyroid carcinomas (ATCs) frequently harbour p53 mutations, we asked whether Gal-3 expression and activity could be influenced by such mutations in these tumours. We found a positive correlation between Gal-3 expression and p53 mutation in human thyroids and in thyroid carcinoma cell lines (TCCLs) harbouring different p53 mutations. Gal-3 was over-expressed in most ATCs and TCCLs, especially those with the most frequently detected p53 mutation (p53(R273H)). Over-expression of p53(R273H) in two p53-null cells (SAOS-2 and SW-1736) as well as in two wt-p53-carrying TCCLs (TPC-1 and K1), stimulated Gal-3 expression, while interference with p53(R273H) endogenous expression in ARO cells down-regulated Gal-3 expression. Conversely, over-expression of wt-p53 in ARO cells restored the inhibitory effect on Gal-3 expression. ARO cells are highly resistant to apoptosis and express both p53 and Gal-3, which are increased upon cisplatin treatment. Interference with Gal-3 expression in these cells stimulated their chemosensitivity. In conclusion, gain-of-function p53 mutant acquires the de novo ability to stimulate Gal-3 expression and to increase chemoresistance in ATCs.
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PMID:Gal-3 is stimulated by gain-of-function p53 mutations and modulates chemoresistance in anaplastic thyroid carcinomas. 1919 18

Although most patients with papillary thyroid cancer (PTC) have favorable outcomes, some have advanced PTC that is refractory to external beam radiation and systemic chemotherapy. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with antiapoptotic activity that is consistently overexpressed in PTC. The purpose of this study is to determine if Gal-3 inhibition promotes apoptosis, chemosensitivity, and radiosensitivity in PTC. PTC cell lines (8505-C and TPC-1) and human ex vivo PTC were treated with a highly specific small molecule inhibitor of Gal-3 (Td131_1). Apoptotic activity was determined by flow cytometric analysis as well as caspase-3 and PARP cleavage. The minimum inhibitory concentrations of Td131_1 and doxorubicin were determined, and their combined effects were measured to test for synergistic activity. The effects of Td131_1 on radiosensitivity were determined by a clonogenic assay. Td131_1 promoted apoptosis, improved radiosensitivity, and synergistically enhanced chemosensitivity to doxorubicin in PTC cell lines. In PTC ex vivo, Td131_1 treatment alone induced the cleavage of caspase-3 and PARP. Td131_1 and doxorubicin together activated apoptosis in PTC ex vivo to a greater degree than their combined individual effects. Td131_1 activated apoptosis and had synergistic activity with doxorubicin in PTC. We conclude that Gal-3 targeted therapy is a promising therapeutic strategy for advanced PTC that is refractory to surgery and radioactive iodine therapy.
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PMID:Galectin-3 targeted therapy with a small molecule inhibitor activates apoptosis and enhances both chemosensitivity and radiosensitivity in papillary thyroid cancer. 1982 87

Although fine-needle aspiration biopsy (FNA) remains the mainstay of the preoperative workup of thyroid nodules, it does not provide a diagnosis in up to 20% of nodules. This group of indeterminate lesions, including lesions with cellular atypia, suspicious cytology, and demonstrating a follicular pattern, provides one of the greatest challenges to researchers in thyroid cancer today. Over the last 2 decades, considerable work has been done to find molecular markers to resolve this diagnostic dilemma. This article explores some of the markers including galectin-3, HBME-1, BRAF, RET/PTC, PAX8-PPARgamma, hTERT, telomerase, miRNA, and microarray and multigene assays. Although no one marker has proven to be a panacea, several combinations of markers have shown great promise as an adjunct to FNA.
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PMID:Molecular markers in thyroid cancer diagnostics. 1983 89

Thyroid nodules are quite common and present approximately in 10% of the population. Fine-needle aspiration biopsy has become the mainstay of thyroid nodule evaluation and the overall accuracy is excellent; however, some aspirates demonstrating indeterminate cytology results do not permit definitive diagnosis of malignancy, and in addition, there are no clear guidelines for the management of these lesions because the incidence of malignancy in indeterminate aspirates varies in the different studies published. In order to find molecular markers in an attempt to predict malignancy based on cytology, at least 70 molecular or cellular and genetic markers have been studied in thyroid nodules. This review focuses on some potential markers such as thyroid peroxidase, thyroglobulin, telomerase, galectin-3, RET/PTC and protein p53; some of them, such as thyroid peroxidases, thyroglobulin and galectin-3, can be studied in a routine pathology laboratory and are promising, but do not yet fulfil criteria required for their use in clinical practice. The American guidelines and the European consensus for the management of thyroid nodules and differentiated thyroid cancer do not recommend their systematic use because the evidence that they have provided is insufficient. On the other hand, information obtained through cytological smears permits the study of complex metabolic or genetic pathways, providing researchers with a high throughput tool to elucidate changes in the global expression patterns seen in tumour cells. This ability to take tumour biology into account would allow the selection of different drugs, considering the predominant altered pathways observed in these samples. Finally, all these data may provide the molecular groundwork for permitting future preoperative discrimination of follicular adenomas from hyperplastic nodules, and may ultimately guide therapeutic strategies.
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PMID:Diagnostic usefulness of tumor markers in the thyroid cytological samples extracted by fine-needle aspiration biopsy. 2008 14

Introduction. Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid. An accurate cytological diagnosis is based on distinctive cytological features in combination with immunocytochemistry. Methods. A number of 83 fine needle aspirations, positive for papillary thyroid cancer (44 from thyroid nodules and 39 from cervical lymph nodes), were studied using Thin Layer Cytology. A panel of the immunomarkers Cytokeratin-19, Galectin-3, HBME1, CD-44, CD-56, and E-Cadherin was performed. Results. Positive expression of CK-19 was observed in 77 cases (92.7%), of Galectin-3 in 74 cases (89.1%), of HBME1 in 65 (78.3%), and of CD-44 in 72 cases (86.7%). Loss of expression of CD-56 was observed in 80 cases (96.4%) and of E-cadherin in 78 (93.9%). Conclusions. Our data suggest that Thin Layer Cytology increases the diagnostic accuracy in papillary carcinoma and seems to be a promising technique for further investigation of thyroid lesions permitting the possibility to use archive material. Positive immunoexpression of CK-19, Galectin-3, HBME-1, and CD-44 improves the diagnostic accuracy of papillary thyroid cancer. Furthermore, loss of E-cadherin and of CD-56 expression is a feature of malignancy.
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PMID:The Immunocytochemistry Is a Valuable Tool in the Diagnosis of Papillary Thyroid Cancer in FNA's Using Liquid-Based Cytology. 2105 76

There is a continuous debate regarding the classification of thyroid follicular lesions and the term "well-differentiated tumor of uncertain malignant potential (WDT-UMP)" was recently introduced to cover this problematic spectrum of tumors. The objective of this study was to reappraise WDT-UMP using morphological, immunochemical, and molecular analysis and to shed more light on encapsulated thyroid follicular-patterned tumors. A total of 30 cases of WDT-UMP with equivocal papillary thyroid carcinoma-type nuclear changes (PTC-N) or focal unequivocal PTC-N were examined. As a control, follicular adenoma (n = 29), follicular carcinoma (n = 8), hyalinizing trabecular adenoma (n = 5), and PTC (n = 48) were included. HBME-1, cytokeratin 19, and galectin-3 were positive in 12 (40.0%), 10 (33.3%) and 11 (36.7%) cases of WDT-UMP, respectively. According to the positivity of those markers, significant differences were obtained between WDT-UMP and PTC encapsulated common type (P = 0.028, 0.010, and 0.004, respectively), infiltrative follicular variant (P = 0.020, 0.026, and 0.008, respectively), and infiltrative common type (P = 0.004, 0.001, and 0.005, respectively), but not between WDT-UMP and follicular adenoma or follicular carcinoma. BRAF(V600E) mutation was absent but RET/PTC1 rearrangement was found in only two (6.7%) cases of WDT-UMP. None of the 20 patients with WDT-UMP developed recurrence, with an average follow-up of 80 months. These findings indicate that WDT-UMP has a favorable outcome and is distinct from PTC in morphological, immunohistochemical, and molecular characteristics. We propose that WDT-UMP should be classified as "well-differentiated tumor with uncertain behavior".
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PMID:Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called well-differentiated tumor of uncertain malignant potential: a morphological, immunohistochemical, and molecular appraisal. 2107 Apr 78


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