Smad3 is involved in TGF-β-mediated the up-regulation of IL-21-producing cells.

<p>Naïve CD4⁺ T cells from CBMCs were stimulated for 2 d with immobilized anti-CD3 and anti-CD28 mAbs (neutral condition), rested overnight and re-stimulated for 15 min with or without IL-21, TGF-β or IL-21 plus TGF-β. A. The cells were lysed and subjected to western blotting. A single membrane and phosphotyrosine specific antibodies had been used. The total Smad3 were as the positive controls. Data were representative of three separate experiments with similar results. B. The ratio of pSmad3 to tSmad3 was quantified by desitometry, and statistical data shown were mean±SD from three independent experiments as described in A. P<0.05 was considered significant.</p

The kinetics of IL-21 and IFN-γ production by CD4⁺ T cells.

<p>A. Naïve CD4⁺ T cells from CBMCs were stimulated with immobilized anti-CD3 and anti-CD28 mAbs (neutral condition) in the presence or absence of IL-21 or IL-21 plus TGF-β. The cells were re-stimulated with PMA plus ionomycin after the primary culture and harvested at different times. The expression of IL-21 and IFN-γ was determined by flow cytometry. Data were representative of four separate experiments with similar results. B. Naïve CD4⁺ T cells from CBMCs were stimulated for 3 days with immobilized anti-CD3 and anti-CD28 mAbs (neutral condition) in the presence or absence of IL-21 or IL-21 plus TGF-β at the indicated concentrations. The cells were re-stimulated with PMA plus ionomycin. IL-21 and IFN-γ-producing cells were determined by flow cytometry. C. Statistical data shown were mean±SD from three separate experiments as described in B. P<0.05 and P<0.01 were considered significant.</p

IL-21 significantly inhibits the expression of Foxp3⁺ T cells by TGF-β-induced naïve CD4⁺ T cells.

<p>A. Naïve CD4⁺ T cells from CBMCs were stimulated for 3 d with immobilized anti-CD3 and anti-CD28 mAbs (neutral condition) in the presence or absence of IL-21, TGF-β or IL-21 plus TGF-β. The cells were re-stimulated with PMA plus ionomycin. The expression of Foxp3 was determined by flow cytometry. Data were representative of three independent experiments with similar results. B. Statistical results shown were mean±SD from three independent experiments as described in A. P<0.05 was considered significant.</p

Neutralizing of IFN-γ enhances the production of IL-21 from CD4⁺ T cells.

<p>A. Naïve CD4⁺ T cells from CBMCs were stimulated for 3 d with immobilized anti-CD3 and anti-CD28 mAbs (neutral condition) in the presence or absence of IL-21, IL-21 plus TGF-β and the mAb against IFN-γ. The cells were re-stimulated with PMA and ionomycin. IL-21 and IFN-γ-producing cells were determined by flow cytometry. Data were representative of four independent experiments with similar results. B. Statistical results shown were mean±SD from four independent experiments as described in A. P<0.05 was considered significant.</p

Association between RET/PTC rearrangement and pathological parameters in thyroid cancer patients.

<p>Association between RET/PTC rearrangement and pathological parameters in thyroid cancer patients.</p

RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease

<div><p>RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39–22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto's thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer.</p></div

Association between RET/PTC rearrangements and changes in thyroid function in thyroid cancer patients.

<p>Association between RET/PTC rearrangements and changes in thyroid function in thyroid cancer patients.</p

Association between haplotypes of RET tagSNPs and susceptibility to thyroid cancer.

<p>Association between haplotypes of RET tagSNPs and susceptibility to thyroid cancer.</p

Association between haplotypes of RET tagSNPs and the occurrence of distant metastasis in thyroid cancer.

<p>Association between haplotypes of RET tagSNPs and the occurrence of distant metastasis in thyroid cancer.</p

Association between RET tagSNP and clinicopathological features of thyroid cancer.

<p>Association between RET tagSNP and clinicopathological features of thyroid cancer.</p