The Experts below are selected from a list of 471 Experts worldwide ranked by ideXlab platform
James A Bibb - One of the best experts on this subject based on the ideXlab platform.
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abstract 4741 targeting tumor growth in a medullary thyroid carcinoma mouse model using a combinatorial treatment with a tyrosine kinase inhibitor and histone deacetylase inhibitor
Cancer Research, 2016Co-Authors: Karine Pozo, Stefan Zahler, Chunfeng Tan, Keisuke Ishimatsu, Masaya Takahashi, James A BibbAbstract:Neuroendocrine tumors are rare forms of cancers arising from hormone-producing Cells that are scattered throughout the body. Medullary thyroid carcinoma (MTC) originates from the thyroid gland Parafollicular Cells. Treatment options for progressive, metastatic MTC patients are limited to the recently FDA-approved tyrosine kinase inhibitors (TKIs), Vandetanib and Cabozantinib, which target multiple receptor tyrosine kinases, including VEGFR2. However, the efficacy of TKIs is limited and development of TKI resistance is common. Here we examined, the effect of a combinatorial drug therapy using the TKI, Nintedanib, and the histone deacetylase (HDAC) inhibitor, Romidepsin, on MTC growth in the NSE/p25-gfp bi-transgenic mouse line, an inducible MTC mouse model (see Pozo et al. 2013). The TKI- and HDAC inhibitors were administered intraperitoneally for 3 weeks and tumor growth progression was monitored using a T2 weighted magnetic resonance imaging on a 7 Tesla system. Tumor tissues were analyzed for oncogenic signaling pathways by immunoblotting and immunohistochemistry. We find that co-administration of Nintedanib and Romidepsin stops tumor growth and increases the number of necrotic foci within the tumor tissue. Interestingly, Nintedanib treatment alone reduced tumor vascularization as shown by decreased density of the vascular marker, CD31, but did not stop Parafollicular Cell proliferation. Taken together, these results suggest that a combinatorial drug therapy with a TKI- and an HDAC inhibitor may be a more efficient strategy to target MTC progression and overcome recurrence. Citation Format: Karine Pozo, Stefan Zahler, Chunfeng Tan, Keisuke Ishimatsu, Masaya Takahashi, James Bibb. Targeting tumor growth in a medullary thyroid carcinoma mouse model using a combinatorial treatment with a tyrosine kinase inhibitor and histone deacetylase inhibitor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4741.
Danish Pardhan - One of the best experts on this subject based on the ideXlab platform.
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Crinophagy in thyroid follicular and Parafollicular Cells of male obese Zucker rat
Ultrastructural Pathology, 2015Co-Authors: Jacques Gilloteaux, Danish PardhanAbstract:AbstractComparison between lean (Fa/?) and obese (fa/fa) young adult male Zucker rat thyroids reveals that obese rats display larger clusters of Parafollicular Cells than the lean ones with a lesser blood supply. Fa/? thyroid typically shows single or “twin” C Cells in follicles; fa/fa Parafollicular Cells appear with three functional aspects. Crinophagy is found in the fa/fa C Cells amassing numerous aberrant calcitonin-containing vesicles among which lysosomes build these autophagic bodies by capturing vesicle contents, other organelles and, fusing with each other, increase their size. Other C Cells contain many secretory vesicles but show few or no crinophagic structures. Another Parafollicular Cell type is revealed with scant organelles and highly contrasted secretory vesicles, different from calcitonin. Hypercalcemia of fa/fa rats corresponds to increased C Cells population with accrued calcitonin production but a low calcitonin plasma level – verified by others – is likely caused by crinophagy of th...
Pardhan Danish - One of the best experts on this subject based on the ideXlab platform.
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Crinophagy in thyroid follicular and Parafollicular Cells of male obese Zucker rat
'Informa UK Limited', 2015Co-Authors: Gilloteaux Jacques, Pardhan DanishAbstract:Comparison between lean (Fa/?) and obese (fa/fa) young adult male Zucker rat thyroids reveals that obese rats display larger clusters of Parafollicular Cells than the lean ones with a lesser blood supply. Fa/? thyroid typically shows single or “twin” C Cells in follicles; fa/fa Parafollicular Cells appear with three functional aspects. Crinophagy is found in the fa/fa C Cells amassing numerous aberrant calcitonin-containing vesicles among which lysosomes build these autophagic bodies by capturing vesicle contents, other organelles and, fusing with each other, increase their size. Other C Cells contain many secretory vesicles but show few or no crinophagic structures. Another Parafollicular Cell type is revealed with scant organelles and highly contrasted secretory vesicles, different from calcitonin. Hypercalcemia of fa/fa rats corresponds to increased C Cells population with accrued calcitonin production but a low calcitonin plasma level – verified by others – is likely caused by crinophagy of the altered vesicles. In addition, the T thyrocytes of fa/fa rats exhibit crinophagy bodies; this can confirm their hypothyroidism. Possibly, the known leptin mutation along with other unknown paracrine secretions alter both T and C thyrocytes’ functions of the fa/fa rats, allowing high intraCellular calcium and lower pH favoring autophagocytosis. Other longitudinal, interdisciplinary studies should further clarify the complex paracrine interactions existing between these endocrine structures because this animal model could be useful to understand human defects, such as the metabolic syndrome that involves obesity, cardiovascular, renal, hepatic, non-insulin dependent diabetes mellitus (NIDDM), hypothyroidism defects, as well as the etiology of thyroid medullary tumors
Karine Pozo - One of the best experts on this subject based on the ideXlab platform.
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abstract 4741 targeting tumor growth in a medullary thyroid carcinoma mouse model using a combinatorial treatment with a tyrosine kinase inhibitor and histone deacetylase inhibitor
Cancer Research, 2016Co-Authors: Karine Pozo, Stefan Zahler, Chunfeng Tan, Keisuke Ishimatsu, Masaya Takahashi, James A BibbAbstract:Neuroendocrine tumors are rare forms of cancers arising from hormone-producing Cells that are scattered throughout the body. Medullary thyroid carcinoma (MTC) originates from the thyroid gland Parafollicular Cells. Treatment options for progressive, metastatic MTC patients are limited to the recently FDA-approved tyrosine kinase inhibitors (TKIs), Vandetanib and Cabozantinib, which target multiple receptor tyrosine kinases, including VEGFR2. However, the efficacy of TKIs is limited and development of TKI resistance is common. Here we examined, the effect of a combinatorial drug therapy using the TKI, Nintedanib, and the histone deacetylase (HDAC) inhibitor, Romidepsin, on MTC growth in the NSE/p25-gfp bi-transgenic mouse line, an inducible MTC mouse model (see Pozo et al. 2013). The TKI- and HDAC inhibitors were administered intraperitoneally for 3 weeks and tumor growth progression was monitored using a T2 weighted magnetic resonance imaging on a 7 Tesla system. Tumor tissues were analyzed for oncogenic signaling pathways by immunoblotting and immunohistochemistry. We find that co-administration of Nintedanib and Romidepsin stops tumor growth and increases the number of necrotic foci within the tumor tissue. Interestingly, Nintedanib treatment alone reduced tumor vascularization as shown by decreased density of the vascular marker, CD31, but did not stop Parafollicular Cell proliferation. Taken together, these results suggest that a combinatorial drug therapy with a TKI- and an HDAC inhibitor may be a more efficient strategy to target MTC progression and overcome recurrence. Citation Format: Karine Pozo, Stefan Zahler, Chunfeng Tan, Keisuke Ishimatsu, Masaya Takahashi, James Bibb. Targeting tumor growth in a medullary thyroid carcinoma mouse model using a combinatorial treatment with a tyrosine kinase inhibitor and histone deacetylase inhibitor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4741.
Catharina Larsson - One of the best experts on this subject based on the ideXlab platform.
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the age and shorter telomere dependent tert promoter mutation in follicular thyroid Cell derived carcinomas
Oncogene, 2014Co-Authors: Tiantian Liu, Na Wang, Anastasios Sofiadis, Andrii Dinets, Jan Zedenius, J Cao, Catharina LarssonAbstract:Telomerase activation through induction of its catalytic component telomerase reverse transcriptase (TERT) expression is essential for malignant transformation. TERT promoter mutations namely C228T and C250T that stimulate TERT transcription and telomerase activation have recently been identified in many human malignancies. We thus determined these mutations and their biological and clinical implications in thyroid carcinomas in the present study. The TERT promoter was sequenced in 10 thyroid cancer Cell lines and 144 tumors from 20 patients with anaplastic thyroid carcinoma (ATC), 51 with papillary thyroid carcinoma (PTC), 36 with follicular thyroid carcinoma (FTC), and 37 with medullary thyroid carcinoma (MTC). We identified C228T or C250T mutation in 6/8 of ATC Cell lines, as well as in tumor tissue from 10/20, 13/51, 8/36 and 0/37 patients with ATC, PTC, FTC and MTC, respectively. In PTC patients, these mutations were exclusively present in the group with age >45 years (P 45 years (P=0.021). ATC patients carrying the mutation survived shorter than those without mutations, although not statistically significant (P=0.129). The TERT promoter mutation was associated with overall survival (P=0.038) and DRS (P=0.058) of FTC patients. Taken together, age- and shorter telomere-dependent TERT promoter mutations occur frequently in follicular Cell-derived thyroid carcinoma (ATC, PTC and FTC) but not in Parafollicular Cell-originated MTC, and may serve as a marker for aggressive disease and poor outcome.
