The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

Brown, Adam R.; Simmen, Rosalia C. M.; Simmen, Frank A.

doi:10.3390/ijms140816240

Cited by 49 publications

(39 citation statements)

References 122 publications

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“…However the final consequence of this influence depends on the sampled population and the tumor type. Excellent reviews have been published in the last years on this respect [61][62][63][64][65]. Some examples of these studies are shown in Table 1 for hyperthyroid conditions and Table 2 for hypothyroidism.…”

Section: Thyroid Status and Tumor Progressionmentioning

confidence: 99%

“…Respect to digestive system cancers, TH signaling has been associated to the prevention of disease [63], and accordingly it was demonstrated that long-term thyroid hormone replacement treatment in hypothyroid patients was related to a significantly reduced relative risk of colorectal cancer [74,75]. Also, increased risk of hepatocellular carcinoma in hypothyroid subjects was also demonstrated by 2 case-control studies [76,77] However contradictory results were found in the relation between hypothyroidism and the development of other cancer types.…”

Section: Thyroid Status and Tumor Progressionmentioning

confidence: 99%

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Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas

Cremaschi

Cayrol

Sterle

et al. 2016

Pharmacological Research

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Thyroid hormones (THs) are important regulators of metabolism, differentiation and cell proliferation. They can modify the physiology of human and murine T cell lymphomas (TCL). These effects involve genomic mechanisms, mediated by specific nuclear receptors (TR), as well as nongenomic mechanisms, that lead to the activation of different signaling pathways through the activation of a membrane receptor, the integrin αvβ3. Therefore, THs are able to induce the survival and growth of TCL. Specifically, the signaling induced by THs through the integrin αvβ3 activates proliferative and angiogenic programs, mediated by the regulation of the vascular endothelial growth factor (VEGF). The genomic or pharmacologic inhibition of integrin αvβ3 reduces the production of VEGF and induces cell death both in vitro and in xenograft models of human TCL. Here we review the mechanisms involved in the modulation of the physiology of TCL induced by THs, the analysis of the interaction between genomic and nongenomic actions of THs and their contribution to T cell lymphomagenesis. These actions of THs suggest a novel mechanism for the endocrine modulation of the physiopathology of TCL and they provide a potential molecular target for its treatment.

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Section: Thyroid Status and Tumor Progressionmentioning

confidence: 99%

Section: Thyroid Status and Tumor Progressionmentioning

confidence: 99%

Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas

Cremaschi

Cayrol

Sterle

et al. 2016

Pharmacological Research

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“…Components of thyroid hormone signaling are implicated in the development and progression, as well as in the prevention of various cancers including hepatocellular carcinoma (HCC) [ 1 – 3 ]. HCC usually develops in patients with liver cirrhosis [ 4 , 5 ] and represents the second most common cause of cancer-related mortality in men globally [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The impact of thyroid hormones on patients with hepatocellular carcinoma

et al. 2017

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Background & aimsHypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients.MethodsOf 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated.ResultsThyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9–15.7 months) vs. 7.3 months (5.4–9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5–13.6 months) vs. 3.3 months (2.2–4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3–3.3); p = 0.002) in multivariate analysis.ConclusionsTSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

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“…For example, in the epithelial domain our analysis shows the enrichment of Thyroid hormone signaling pathway that has been associated with a tumor suppressive role in CRC development. 55,56 In contrast, the bacterial invasion pathway, enriched in epithelial-stromal boundary region, has been implicated in the oncogenic role of the colonic microbiome in CRC development. 57,58 Our analysis also reveals enrichment of certain other pathways, such as the hypoxiainducible factor 1 (HIF-1), human epidermal growth factor receptor 2 (HER2) and T-cell receptor signaling pathways in the epithelial domain.…”

Section: Spatial Domain Network Reveal Domain-specific Network Biolomentioning

confidence: 99%

Spatial domain analysis predicts risk of colorectal cancer recurrence and infers associated tumor microenvironment networks

Uttam

Stern

Furman

et al. 2019

Preprint

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An unmet clinical need in solid tumor cancers is the ability to harness the intrinsic spatial information in primary tumors that can be exploited to optimize prognostics, diagnostics and therapeutic strategies for precision medicine. We have developed a transformational spatial analytics (SpAn) computational and systems biology platform that predicts clinical outcomes and captures emergent spatial biology that can potentially inform therapeutic strategies. Here we apply SpAn to primary tumor tissue samples from a cohort of 432 chemo-naïve colorectal cancer (CRC) patients iteratively labeled with a highly multiplexed (hyperplexed) panel of fifty-five fluorescently tagged antibodies. SpAn predicted the 5-year risk of CRC recurrence with a mean area under the ROC curve of 88.5% (SE of 0.1%), significantly better than current state-of-the-art methods. SpAn also inferred the emergent network biology of the tumor spatial domains revealing a synergistic role of known features from CRC consensus molecular subtypes that will enhance precision medicine. MainColorectal Cancer (CRC) is the second most common type of cancer and the third leading cause of cancer-related deaths worldwide. 1 This multi-factorial disease like other carcinomas, develops and progresses through the selection of epithelial clones with the potential to confer malignant phenotypes in the context of a reciprocally coevolving tumor microenvironment (TME) comprising immune and stromal cells. 2-4 CRC patients are staged using the well-established tumor-nodemetastases (TNM) classification. 5,6 However, there is significant variability in patient outcomes within each stage. For example, CRC will recur in up to 30% of Stage II patients despite complete tumor resection, no residual tumor burden and no signs of metastasis. 7 In contrast, more advanced CRC has been known to show stability or indeed even to spontaneously regress. 7,8 The intrinsic plasticity of the TME underlying this variability in outcome is controlled by complex network biology emerging from the spatial organization of diverse cell types within the TME and their heterogeneous states of activation. 3,[9][10][11] The important role of the TME in CRC progression and recurrence has recently been highlighted by the identification of four consensus molecular subtypes (CMS) 12,13 , functional studies defining the critical role of stromal cells in determining overall survival, 14 and the development of Immunoscore® 14 which quantifies tumorinfiltrating T-lymphocytes in different regions of the tumor and associates their infiltration with CRC recurrence. 15,16 However the TME can be further harnessed to significantly improve CRC prognosis through the identification of biomarkers mechanistically linked to disease progression and the development of novel therapeutic strategies.Deeper understanding of the TME may arise from imaging methods capable of labeling > 7 cellular and tissue components in the same sample (hyperplexed 17 (HxIF) fluorescence and other imaging modalities). [17][18][19][20][21] To...

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The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

Cited by 49 publications

References 122 publications

Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas

Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas

The impact of thyroid hormones on patients with hepatocellular carcinoma

Spatial domain analysis predicts risk of colorectal cancer recurrence and infers associated tumor microenvironment networks

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