The Experts below are selected from a list of 3543 Experts worldwide ranked by ideXlab platform
Jeffrey N Myers - One of the best experts on this subject based on the ideXlab platform.
-
Glycolytic inhibition alters Anaplastic Thyroid Carcinoma tumor metabolism and improves response to conventional chemotherapy and radiation.
Molecular Cancer Therapeutics, 2012Co-Authors: Vlad C Sandulache, Cristina T. Dodge, James A. Bankson, Heath D Skinner, Thomas J Ow, Yunyun Chen, Yuan Wang, Jeffrey N MyersAbstract:Anaplastic Thyroid Carcinoma (ATC) accounts for more than 50% of Thyroid cancer mortality and is generally refractory to conventional treatment. On the basis of recent studies, we hypothesized that ATC metabolism can be targeted to improve response to chemoradiotherapy. Eight established and authenticated ATC cell lines were sequenced at 140 sites contained within 26 commonly mutated genes to identify novel potential therapeutic targets. Cellular proliferation, energy, and reducing potential stores were measured under conditions of specific nutrient deprivation. Tumor metabolism was evaluated using hyperpolarized (13)C MRI in a murine orthotopic xenograft model of ATC. Sensitivity to chemotherapeutic agents and radiation (XRT) was assayed using cytotoxicity assays. We identified mutations in BRAF, NRAS, and KIT but failed to identify generalized novel targets for therapeutic intervention. ATC cell lines exhibited a mesenchymal phenotype and generalized dependence on glucose for energy, reducing potential and survival. Glycolytic inhibition using 2-deoxyglucose (2-DG) sensitized ATC cells to conventional chemotherapy and external beam radiation. In vivo, 2-DG induced a transient, but significant reduction in ATC metabolic activity. Generalized dependence of ATC cells on glucose catabolism makes them susceptible to the sensitizing effects of 2-DG for radiation therapy and chemotherapy. Under in vivo conditions, 2-DG can inhibit ATC metabolism. However, the modest magnitude and transient nature of this effect suggest the need for antimetabolic agents with more favorable pharmacodynamics to achieve therapeutic effects.
-
sorafenib inhibits the angiogenesis and growth of orthotopic Anaplastic Thyroid Carcinoma xenografts in nude mice
Molecular Cancer Therapeutics, 2007Co-Authors: Seungwon Kim, Yasemin D Yazici, Gabriel Calzada, Zhuo Ying Wang, Maher N Younes, Samar A Jasser, Adel K Elnaggar, Jeffrey N MyersAbstract:Anaplastic Thyroid Carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-β kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of Thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of Thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC. [Mol Cancer Ther 2007;6(6):1785–92]
-
sorafenib inhibits the angiogenesis and growth of orthotopic Anaplastic Thyroid Carcinoma xenografts in nude mice
Molecular Cancer Therapeutics, 2007Co-Authors: Seungwon Kim, Yasemin D Yazici, Zhuo Ying Wang, Maher N Younes, Samar A Jasser, Adel K Elnaggar, Gabriel G Calzada, Jeffrey N MyersAbstract:Anaplastic Thyroid Carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-beta kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of Thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of Thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC.
Seong Jin Lee - One of the best experts on this subject based on the ideXlab platform.
-
17 allylamino 17 demethoxygeldanamycin and herbimycin a induce cell death by modulating β catenin and pi3k akt signaling in fro Anaplastic Thyroid Carcinoma cells
Anticancer Research, 2015Co-Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:AIM The aim of the present study was to evaluate the effect of heat-shock protein 90 (HSP90) inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and herbimycin A (HMA) on survival of Anaplastic Thyroid Carcinoma (ATC) cells. MATERIALS AND METHODS Antitumor activities of 17-AAG and HMA were investigated in FRO ATC cells. RESULTS In FRO ATC cells, 17-AAG and HMA caused cell death with concomitant changes in the expression of HSP90 client proteins, increased β-catenin protein levels, and inhibited PI3K/AKT signaling. The inactivation of β-catenin by β-catenin siRNA transfection and the activation of PI3K/AKT signaling by p110α plasmid transfection abrogated cell death caused by 17-AAG and HMA. CONCLUSION 17-AAG and HMA have cytotoxic activities accompanied by regulation of HSP90 client proteins, and cytotoxicity is associated with overexpression of β-catenin and suppression of PI3K/AKT signaling in FRO ATC cells.
-
herbimycin a inhibits cell growth with reversal of epithelial mesenchymal transition in Anaplastic Thyroid Carcinoma cells
Biochemical and Biophysical Research Communications, 2014Co-Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:We aimed to elucidate the effect of herbimycin A (HMA), a heat shock protein 90 inhibitor, on cell growth and epithelial-mesenchymal transition (EMT) in Anaplastic Thyroid Carcinoma (ATC) cells. HMA inhibited cell growth and migration concomitantly with increase of E-cadherin as well as decrease of N-cadherin and vimentin. Moreover, HMA upregulated p21 and p27, while it downregulated p53 and Akt. In HMA-treated condition, knockdown of E-cadherin and overexpression of p53 increased N-cadherin and vimentin, and mitigated the inhibitory effects of HMA on cell growth and migration. Furthermore, knockdown of p21 and p27 ameliorated inhibition of cell growth and reversal of EMT. In addition, the activation of Akt attenuated growth inhibition, cell death and EMT reversal. Therefore, we propose that HMA suppresses cell growth, and reverses EMT in conjunction with the activation of E-cadherin, p21 and p27 and the inactivation of p53 and PI3K/Akt signaling in ATC cells.
-
the hsp70 inhibitor ver155008 induces paraptosis requiring de novo protein synthesis in Anaplastic Thyroid Carcinoma cells
Biochemical and Biophysical Research Communications, 2014Co-Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:In this study, we evaluated the effect of the hsp70 inhibitor VER155008 on survival of Anaplastic Thyroid Carcinoma (ATC) cells. In ATC cells, VER155008 increased the percentages of dead cells and vacuolated cells. VER155008 did not lead to the cleavage of caspase-3 protein regardless of pretreatment with z-VAD-fmk. VER155008 increased LC3-II protein levels but the protein levels were not changed by autophagy inhibitors. VER155008 caused the dilatation of endoplasmic reticulum (ER), and the increased mRNA levels of Bip and CHOP, suggesting paraptosis. VER155008-induced paraptosis was attenuated by pretreatment with cycloheximide. In conclusion, VER155008 induces paraptosis characterized by cytoplasmic vacuolation, independence of caspase, dilatation of ER and induction of ER stress markers in ATC cells. Moreover, VER155008-induced paraptosis requires de novo protein synthesis in ATC cells.
-
tunicamycin induces paraptosis potentiated by inhibition of brafv600e in fro Anaplastic Thyroid Carcinoma cells
Anticancer Research, 2014Co-Authors: Si Hyoung Kim, Haeyoung Shin, Yongsun Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:BACKGROUND/AIM The aim of the present study was to elucidate whether tunicamycin (TM) induces paraptosis as a cell death subroutine in Anaplastic Thyroid Carcinoma (ATC) cells. MATERIALS AND METHODS 8505C, CAL62 and FRO cells were used. After treatment of TM, cell survival and morphology were investigated. The effect of the BRAF(V600E) inhibitor PLX4032 in combination with TM was evaluated. RESULTS In FRO cells, TM induced paraptosis characteristic of cytoplasmic vacuolation and endoplasmic reticulum (ER) swelling, which was not associated with caspase activation and ER stress. TM-induced paraptosis was ameliorated by pre-treatment with the translation inhibitor cycloheximide, while it was accelerated by pre-treatment with the proteasome inhibitor MG132. PLX4032 augmented TM-induced paraptosis. CONCLUSION TM induces paraptosis relevant to de novo protein synthesis and proteasomal activity, and inhibition of BRAF(V600E) potentiates TM-induced paraptosis in FRO cells harboring BRAF(V600E).
Si Hyoung Kim - One of the best experts on this subject based on the ideXlab platform.
-
17 allylamino 17 demethoxygeldanamycin and herbimycin a induce cell death by modulating β catenin and pi3k akt signaling in fro Anaplastic Thyroid Carcinoma cells
Anticancer Research, 2015Co-Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:AIM The aim of the present study was to evaluate the effect of heat-shock protein 90 (HSP90) inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and herbimycin A (HMA) on survival of Anaplastic Thyroid Carcinoma (ATC) cells. MATERIALS AND METHODS Antitumor activities of 17-AAG and HMA were investigated in FRO ATC cells. RESULTS In FRO ATC cells, 17-AAG and HMA caused cell death with concomitant changes in the expression of HSP90 client proteins, increased β-catenin protein levels, and inhibited PI3K/AKT signaling. The inactivation of β-catenin by β-catenin siRNA transfection and the activation of PI3K/AKT signaling by p110α plasmid transfection abrogated cell death caused by 17-AAG and HMA. CONCLUSION 17-AAG and HMA have cytotoxic activities accompanied by regulation of HSP90 client proteins, and cytotoxicity is associated with overexpression of β-catenin and suppression of PI3K/AKT signaling in FRO ATC cells.
-
herbimycin a inhibits cell growth with reversal of epithelial mesenchymal transition in Anaplastic Thyroid Carcinoma cells
Biochemical and Biophysical Research Communications, 2014Co-Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:We aimed to elucidate the effect of herbimycin A (HMA), a heat shock protein 90 inhibitor, on cell growth and epithelial-mesenchymal transition (EMT) in Anaplastic Thyroid Carcinoma (ATC) cells. HMA inhibited cell growth and migration concomitantly with increase of E-cadherin as well as decrease of N-cadherin and vimentin. Moreover, HMA upregulated p21 and p27, while it downregulated p53 and Akt. In HMA-treated condition, knockdown of E-cadherin and overexpression of p53 increased N-cadherin and vimentin, and mitigated the inhibitory effects of HMA on cell growth and migration. Furthermore, knockdown of p21 and p27 ameliorated inhibition of cell growth and reversal of EMT. In addition, the activation of Akt attenuated growth inhibition, cell death and EMT reversal. Therefore, we propose that HMA suppresses cell growth, and reverses EMT in conjunction with the activation of E-cadherin, p21 and p27 and the inactivation of p53 and PI3K/Akt signaling in ATC cells.
-
the hsp70 inhibitor ver155008 induces paraptosis requiring de novo protein synthesis in Anaplastic Thyroid Carcinoma cells
Biochemical and Biophysical Research Communications, 2014Co-Authors: Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:In this study, we evaluated the effect of the hsp70 inhibitor VER155008 on survival of Anaplastic Thyroid Carcinoma (ATC) cells. In ATC cells, VER155008 increased the percentages of dead cells and vacuolated cells. VER155008 did not lead to the cleavage of caspase-3 protein regardless of pretreatment with z-VAD-fmk. VER155008 increased LC3-II protein levels but the protein levels were not changed by autophagy inhibitors. VER155008 caused the dilatation of endoplasmic reticulum (ER), and the increased mRNA levels of Bip and CHOP, suggesting paraptosis. VER155008-induced paraptosis was attenuated by pretreatment with cycloheximide. In conclusion, VER155008 induces paraptosis characterized by cytoplasmic vacuolation, independence of caspase, dilatation of ER and induction of ER stress markers in ATC cells. Moreover, VER155008-induced paraptosis requires de novo protein synthesis in ATC cells.
-
tunicamycin induces paraptosis potentiated by inhibition of brafv600e in fro Anaplastic Thyroid Carcinoma cells
Anticancer Research, 2014Co-Authors: Si Hyoung Kim, Haeyoung Shin, Yongsun Kim, Jun Goo Kang, Chul Sik Kim, Sunghee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin LeeAbstract:BACKGROUND/AIM The aim of the present study was to elucidate whether tunicamycin (TM) induces paraptosis as a cell death subroutine in Anaplastic Thyroid Carcinoma (ATC) cells. MATERIALS AND METHODS 8505C, CAL62 and FRO cells were used. After treatment of TM, cell survival and morphology were investigated. The effect of the BRAF(V600E) inhibitor PLX4032 in combination with TM was evaluated. RESULTS In FRO cells, TM induced paraptosis characteristic of cytoplasmic vacuolation and endoplasmic reticulum (ER) swelling, which was not associated with caspase activation and ER stress. TM-induced paraptosis was ameliorated by pre-treatment with the translation inhibitor cycloheximide, while it was accelerated by pre-treatment with the proteasome inhibitor MG132. PLX4032 augmented TM-induced paraptosis. CONCLUSION TM induces paraptosis relevant to de novo protein synthesis and proteasomal activity, and inhibition of BRAF(V600E) potentiates TM-induced paraptosis in FRO cells harboring BRAF(V600E).
Iwao Sugitani - One of the best experts on this subject based on the ideXlab platform.
-
sorafenib in japanese patients with locally advanced or metastatic medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma
Thyroid, 2017Co-Authors: Yasuhiro Ito, Iwao Sugitani, Naoyoshi Onoda, Kenichi Ito, Shunji Takahashi, Iku Yamaguchi, Koki Kabu, Katsuya TsukadaAbstract:Background: Therapeutic options for treating advanced or metastatic medullary Thyroid Carcinoma (MTC) and Anaplastic Thyroid Carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated Thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Methods: Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. P...
-
histopathological analysis of Anaplastic Thyroid Carcinoma cases with long term survival a report from the Anaplastic Thyroid Carcinoma research consortium of japan
Endocrine Journal, 2016Co-Authors: Mitsuyoshi Hirokawa, Iwao Sugitani, Kennichi Kakudo, Atsuhiko Sakamoto, Takuya Higashiyama, Kiminori Sugino, Kazuhisa Toda, Satoshi Ogasawara, Seiichi Yoshimoto, Yasuhisa HasegawaAbstract:The aim of this study was to clarify the histopathological features of Anaplastic Thyroid Carcinoma in patients who achieved long-term survival. We reviewed 88 Anaplastic Thyroid Carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 Anaplastic Thyroid Carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be Anaplastic Thyroid Carcinoma after central review. Of these, 12 were revised to papillary Carcinoma with squamous cell Carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell Carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with Anaplastic Thyroid Carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell Carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in Anaplastic Thyroid Carcinoma.
-
prognostic factors and treatment outcomes for Anaplastic Thyroid Carcinoma atc research consortium of japan cohort study of 677 patients
World Journal of Surgery, 2012Co-Authors: Iwao Sugitani, Kiminori Sugino, Akira Miyauchi, Takahiro Okamoto, Akira Yoshida, Shinichi SuzukiAbstract:Background Anaplastic Thyroid Carcinoma (ATC) accounts for only 1 to 2% of all Thyroid Carcinomas, but it is one of the most lethal neoplasms in humans. To date, most findings about ATC have been derived from single-institution studies with limited numbers of cohorts. To obtain further insights into this “orphan disease,” we have established a multicenter registry, the ATC Research Consortium of Japan (ATCCJ). We analyzed prognostic factors and treatment outcomes using the large cohort database of the ATCCJ.
-
prospective application of our novel prognostic index in the treatment of Anaplastic Thyroid Carcinoma
Surgery, 2011Co-Authors: Yorihisa Orita, Iwao Sugitani, Takeshi Amemiya, Yoshihide FujimotoAbstract:Background We have previously performed retrospective analysis of patients with Anaplastic Thyroid Carcinoma (ATC) treated between April 1976 and March 1999, revealing acute symptoms, large tumor (>5 cm), distant metastasis, and leukocytosis ≥10,000/mm 3 as the most important prognostic factors. We devised a novel prognostic index (PI) as the total number of these 4 factors present, giving a PI of 0–4. Methods We have adopted this PI since April 1999. In principle, multimodal treatment has been encouraged for a PI of ≤1, whereas aggressive treatment has been avoided to maintain quality of life for a PI of ≥3. The validity of this therapeutic strategy was prospectively investigated in 74 patients with ATC. Results Six-month survival rates for PI ≤ 1 and PI ≥ 3 were 72% and 12%, respectively. Among patients with a PI of ≤1,11 (42%) underwent multimodal treatment and showed significantly better survival than previous cases. Survival rates did not differ between stages. For patients with a PI of ≥3, survival rates were equally dismal, regardless of stage. Numbers of patients who underwent tracheostomy or died from local disease were significantly decreased compared with previous cases. Conclusion Our PI is valid for anticipating prognosis and aiding timely decisions on treatment policy for ATC patients.
Seungwon Kim - One of the best experts on this subject based on the ideXlab platform.
-
sorafenib inhibits the angiogenesis and growth of orthotopic Anaplastic Thyroid Carcinoma xenografts in nude mice
Molecular Cancer Therapeutics, 2007Co-Authors: Seungwon Kim, Yasemin D Yazici, Gabriel Calzada, Zhuo Ying Wang, Maher N Younes, Samar A Jasser, Adel K Elnaggar, Jeffrey N MyersAbstract:Anaplastic Thyroid Carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-β kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of Thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of Thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC. [Mol Cancer Ther 2007;6(6):1785–92]
-
sorafenib inhibits the angiogenesis and growth of orthotopic Anaplastic Thyroid Carcinoma xenografts in nude mice
Molecular Cancer Therapeutics, 2007Co-Authors: Seungwon Kim, Yasemin D Yazici, Zhuo Ying Wang, Maher N Younes, Samar A Jasser, Adel K Elnaggar, Gabriel G Calzada, Jeffrey N MyersAbstract:Anaplastic Thyroid Carcinoma (ATC) remains one of the most lethal human cancers. We hypothesized that sorafenib, a multikinase inhibitor of the BRaf, vascular endothelial growth factor receptor-2, and platelet-derived growth factor receptor-beta kinase, would decrease tumor growth and angiogenesis in an orthotopic model of ATC. The in vitro antiproliferative and proapoptotic effects of sorafenib on ATC cell lines were examined. To study the in vivo effects of sorafenib on orthotopic ATC tumors in nude mice, sorafenib was given p.o. at 40 or 80 mg/kg daily. Intratumoral effects were studied using immunohistochemical analysis. The effect of sorafenib on survival of the mice was also studied. Sorafenib inhibited the in vitro proliferation of ATC cell lines. Sorafenib also significantly inhibited tumor angiogenesis via the induction of endothelial apoptosis in an orthotopic model of Thyroid cancer. As result, the growth of orthotopic ATC xenografts was reduced and the survival of the test animals was improved. Sorafenib exerts significant antitumor activity in an orthotopic xenograft model of ATC via a potent antiangiogenic effect. The antiangiogenic effects of sorafenib suggest that its use in clinical setting may not depend on the BRAF mutational status of Thyroid tumors. Given the lack of curative options for patients with ATC, sorafenib warrants further study as a therapeutic agent against ATC.