Antineoplastic activity of taxol against human anaplastic thyroid carcinoma cell lines in vitro and in vivo.

Ain, Kenneth B.; Tofiq, Sharmen; Taylor, Kimberly D.

doi:10.1210/jcem.81.10.8855817

Cited by 38 publications

(19 citation statements)

References 10 publications

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“…Despite this small number, the cell lines we used are among the most well established in the literature (30,32,33). We are currently working with a larger panel of cell lines to verify our findings.…”

Section: Discussionmentioning

confidence: 90%

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer

Younes¹,

Kim²,

Yigitbasi³

et al. 2005

Molecular Cancer Therapeutics

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We investigated integrin-linked kinase (ILK), a focal adhesion serine-threonine protein kinase, as a new molecular target for treating anaplastic thyroid cancer. ILK mediates cell growth and survival signals and is overexpressed in a number of cancers. Therefore, we hypothesized that inhibition of ILK leads to growth arrest and apoptosis of thyroid cancer cells. According to Western blotting, the level of ILK protein was highly expressed in one papillary (NPA187) and four of five (Hth74, DRO, ARO, KAT4, and K4) anaplastic thyroid cancer cell lines. Immunohistochemical analysis of a human tissue microarray revealed that ILK was highly expressed in anaplastic thyroid cancer but not in normal human thyroid tissue. Treating thyroid cancer cell lines with a new ILK inhibitor, QLT0267, inhibited epidermal growth factor -induced phosphorylation of AKT, inhibited cell growth, and induced apoptosis in the NPA187, DRO, and K4 cell lines. QLT0267 also inhibited the kinase activity of immunoprecipitated ILK in four of five cell lines. Tumor volumes in mice treated with QLT0267 were significantly reduced compared with those in untreated mice. In immunohistochemical studies, QLT0267 suppressed phosphorylated p-AKT and angiogenesis (i.e., reduced mean vascular density) and induced apoptosis in both tumor cells and tumor-associated endothelial cells of the thyroid DRO xenografts. In summary, we found that ILK expression and activity were elevated in human anaplastic thyroid cancer and ILK inhibition led to growth arrest and apoptosis in vitro and in vivo. Our results provide preliminary evidence that ILK is a potential therapeutic target for treating anaplastic thyroid cancer.

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Section: Discussionmentioning

confidence: 90%

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer

Younes¹,

Kim²,

Yigitbasi³

et al. 2005

Molecular Cancer Therapeutics

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“…We used six cancer cell lines in this study: (a) the anaplastic thyroid carcinoma cell lines ARO (25), FB1 (26), KAT4 (27), and FRO (28); (b) the 8505C cell line (29), established from an anaplastic thyroid carcinoma containing areas of papillary thyroid carcinoma; (c) the NPA cell line (28) established from a poorly differentiated thyroid carcinoma. The ARO (11), KAT4 (12), and FB1 (12) cells harbor a heterozygous BRAF V600E mutation, whereas 8505C (12), NPA, and FRO (13) express only the mutated BRAF allele.…”

Section: Methodsmentioning

confidence: 99%

BRAF Is a Therapeutic Target in Aggressive Thyroid Carcinoma

Salvatore

Falco

Salerno

et al. 2006

Clinical Cancer Research

161

123

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Purpose: Oncogenic conversion of BRAF occurs in f44% of papillary thyroid carcinomas and 24% of anaplastic thyroid carcinomas. In papillary thyroid carcinomas, this mutation is associated with an unfavorable clinicopathologic outcome. Our aim was to exploit BRAF as a potential therapeutic target for thyroid carcinoma. Experimental Design: We used RNA interference to evaluate the effect of BRAF knockdown in the human anaplastic thyroid carcinoma cell lines FRO and ARO carrying the BRAF V600E ( V600E BRAF) mutation. We also exploited the effect of BAY 43-9006 [N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoyl pyridin-4-yl)oxyphenyl)urea], a multikinase inhibitor able to inhibit RAF family kinases in a panel of six V600E BRAF-positive thyroid carcinoma cell lines and in nude mice bearing ARO cell xenografts. Statistical tests were two sided. Results: Knockdown of BRAF by small inhibitory duplex RNA, but not control small inhibitory duplex RNA, inhibited the mitogen-activated protein kinase signaling cascade and the growth of ARO and FRO cells (P < 0.0001).These effects were mimicked by thyroid carcinoma cell treatment with BAY 43-9006 (IC 50 = 0.5-1 Amol/L; P < 0.0001), whereas the compound had negligible effects in normal thyrocytes. ARO cell tumor xenografts were significantly (P < 0.0001) smaller in nude mice treated with BAY 43-9006 than in control mice. This inhibition was associated with suppression of phospho^mitogen-activated protein kinase levels. Conclusions: BRAF provides signals crucial for proliferation of thyroid carcinoma cells spontaneously harboring the V600E

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“…In this case, we used paclitaxel as a single agent, administered weekly at a dose of 80-120 mg/mq, for 6 consecutive weeks out of 8 weeks. This took into account the established low efficacy of platinum and doxorubicin when not associated with radiotherapy and reports of the effectiveness of paclitaxel against human ATC, both in experimental models and in ATC patients (16)(17)(18).…”

Section: Methodsmentioning

confidence: 99%

Anaplastic thyroid carcinoma: clinical outcome of 30 consecutive patients referred to a single institution in the past 5 years

et al. 2007

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Objective: Treatment options for anaplastic thyroid carcinoma (ATC), which is one of the most lethal human malignant tumors, include surgery, chemotherapy and radiotherapy usually combined in a multimodal approach, to improve survival and avoid death from local invasion. However, there is no standard protocol for ATC treatment and the optimal sequence within multimodal therapy is debated. We retrospectively report the clinical outcome of 30 ATC patients referred consecutively to the Oncological Endocrinology Unit of San Giovanni Battista Hospital (Turin, Italy) between 2000 and 2005. Design: Patients were treated by one of the following approaches: i) surgery followed by adjuvantcombined chemoradiotherapy; ii) neo-adjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy; or iii) chemotherapy alone. The surgical procedures were classified as 'maximal debulking' or 'palliative resection'. Maximal debulking entailed total or near-total thyroidectomy and complete resection of all gross tumor or minimal residual disease adherent to vital structures, independently of the presence or absence of distant metastases. In palliative resections, macroscopic residual disease was left in the neck. Survival of patients stratified by treatment was assessed. Results: Analysis of multivariate hazard ratios showed that maximal debulking followed by adjuvant chemoradiotherapy was the only treatment that modified survival of ATC patients (hazard ratioZ 0.23, 95% CI: 0.07-0.79), even if factors determining poor prognosis or increased surgical risk were present. Conclusions: Despite the overall grim outcome of ATC, these results justify an attempt at maximal debulking surgery, followed by adjuvant chemoradiotherapy, possibly in all ATC patients. 156 425-430 European Journal of Endocrinology

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Antineoplastic activity of taxol against human anaplastic thyroid carcinoma cell lines in vitro and in vivo.

Cited by 38 publications

References 10 publications

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer

BRAF Is a Therapeutic Target in Aggressive Thyroid Carcinoma

Anaplastic thyroid carcinoma: clinical outcome of 30 consecutive patients referred to a single institution in the past 5 years

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