Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults

Patel, Aneeta; Pluim, Thomas; Helms, Amy E.; Bauer, Andrew J.; Tuttle, R. Michael; Francis, Gary L.

doi:10.1007/s00280-003-0732-7

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…S-1 is converted into fluorouracil after P r e p r i n t 12 internalization into cells, and S-1 shares similar anticancer properties as intravenous 5-Fu [34].The clinical study of 84 patients with advanced gastric cancer showed that the progression free survival (PFS) of patients was overtly longer in the Apatinib + S-1(a fluorouracil drug) group than that in S-1 group [35]. Capecitabine is a novel drug that can be well absorbed after oral administration, and converted into 5-FU by thymidine phosphorylase in tumor tissues [36]. Capecitabine has been confirmed to replace 5-FU for the gastrointestinal chemoradiation therapy [37].…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor effects of 5-FU and Apatinib on papillary thyroid cancer in vitro and in vivo

Meng

Yang

et al. 2022

Arch Med Sci

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IntroductionPapillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy with increased incidence rapidly occurring in most countries. The study aimed to investigate the antitumor effects of the combination of 5-FU and Apatinib on PTC.Material and methodsTPC-1 and SW579 cells were treated with 5-FU, Apatinib, or a combination of 5-FU and Apatinib. Cell viability was assessed by the CCK-8 assay. Edu staining and colony formation were used to evaluate the cell proliferation ability. Flow cytometry was used to analyze the cell apoptosis. Wound healing and the Transwell assay were conducted to analyze cell migration and invasion. The angiogenesis of TPC-1 and SW579 cells was assessed by conducting the tube formation assay. Xenograft tumor models were established by injecting TPC-1 cells into nude mice. Expressions of CD31, VEGFA, and VEGFR2 were determined using immunofluorescence and Western blotting.ResultsCompared with 5-FU or Apatinib treatment alone, the combination of 5-FU and Apatinib produced stronger suppressive effects on cell proliferation, migration, invasion, and angiogenesis. An in vivo experiment showed that the combination of 5-FU and Apatinib strongly suppressed tumor growth. The combination of 5-FU and Apatinib remarkably suppressed expressions of CD31, VEGFA, and VEGFR2, associated with angiogenesis.ConclusionsOur data demonstrated that 5-FU combined with Apatinib therapy obtained synergistic antitumor effects in PTC, compared with either 5-FU or Apatinib alone by down-regulating VEGFA/VEGFR2 signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Synergistic antitumor effects of 5-FU and Apatinib on papillary thyroid cancer in vitro and in vivo

Meng

Yang

et al. 2022

Arch Med Sci

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“…Because of its mechanism of action, it is suspected that high levels of thymidine phosphorylase and low thymidylate synthetase and dihydropyrimidine dehydrogenase would predict response to capecitabine. In one study looking at immunohistochemistry of thyroid tumors, 43% of PTC and 25% of FTC had favorable characteristics (Patel et al 2004).…”

Section: Chemotherapeutic Agentsmentioning

confidence: 99%

New therapeutic advances in the management of progressive thyroid cancer

Woyach¹,

Shah²

2009

Endocrine-Related Cancer

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The spectrum of thyroid cancers ranges from one of the most indolent to one of the most aggressive solid tumors identified. Conventional therapies for thyroid cancers are based on the histologic type of thyroid cancers such as papillary or follicular thyroid cancer (differentiated thyroid cancer (DTC)), medullary thyroid cancer (MTC), or anaplastic thyroid cancer (ATC). While surgery is one of the key treatments for all such types of thyroid cancers, additional therapies vary. Effective targeted therapy for DTC is a decades-old practice with systemic therapies of thyroid stimulating hormone suppression and radioactive iodine therapy. However, for the iodinerefractory DTC, MTC, and ATC there is no effective systemic standard of care treatment. Recent advances in understanding pathogenesis of DTC and development of molecular targeted therapy have dramatically transformed the field of clinical research in thyroid cancer. Over the last five years, incredible progress has been made and phases I-III clinical trials have been conducted in various types of thyroid cancers with some remarkable results that has made an impact on lives of patients with thyroid cancer. Such history-making events have boosted enthusiasm and interest among researchers, clinicians, patients, and sponsors and we anticipate ongoing efforts to develop more effective and safe therapies for thyroid cancer.

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“…Patient MTC samples have not been analyzed in detail for the enzyme expression pattern so far. FTTiv-derived cells had favorable profile according to the data by Patel et al (40), but they are not responsive to 5FU treatment in general. The link between expression as predictive markers and the therapeutic response is more complex (22).…”

mentioning

confidence: 93%

“…Favorable enzyme profiles (high TP and low DPD) should generate high intratumor levels of 5FU that are effective against many tumors, especially those with low TS. A total of 32% of papillary thyroid cancers exhibited this profile, and therefore the authors suggested them to be sensitive to 5FUbased treatment (40). Patient MTC samples have not been analyzed in detail for the enzyme expression pattern so far.…”

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confidence: 99%

In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+ Tumor–Initiating Cell Subset

Kučerová

Feketeova²,

Kozovská³

et al. 2014

Thyroid

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Enzyme expression profiles suggest the novel tumor-activated fluoropyrimidine carbamate capecitabine (Xeloda) might be effective against papillary thyroid cancers of children and young adults

Cited by 6 publications

References 21 publications

Synergistic antitumor effects of 5-FU and Apatinib on papillary thyroid cancer in vitro and in vivo

Synergistic antitumor effects of 5-FU and Apatinib on papillary thyroid cancer in vitro and in vivo

New therapeutic advances in the management of progressive thyroid cancer

In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+ Tumor–Initiating Cell Subset

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