The Incidence of Breast Tumor during Experimental Hyperthyroidism

Glushakov, Ruslan I.; Proshin, S. N.; Tapilskaya, Natalya I.

doi:10.1007/s10517-013-2322-y

Cited by 10 publications

(5 citation statements)

References 5 publications

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“…Thyroid hormone activity is related to breast cancer. Hypothyroidism is associated with low incidence of breast cancer, and conversely, hyperthyroidism with high incidence and aggressiveness of breast cancer [99]. Statistical studies suggest that high T 3 levels in women are associated with increased overall risk and occurrence of breast cancer.…”

Section: Functional Significance Of Thyroid Hormone and Receptors mentioning

confidence: 99%

“…In human breast cell lines MCF-7 and T47D, both T 4 and T 3 promote cell proliferation in a dose-dependent manner [104,105,106]. Hyperthyroidism and hypothyroidism are correlated with the incidence of tumor induction and reduction and aggressiveness of breast cancer in female mice [99]. Interestingly, other reports support anticancer activity of THs, for instance, via downregulation of SMP30 expression and induction of apoptosis in MCF-7 cells through T 3 [76].…”

Section: Functional Significance Of Thyroid Hormone and Receptors mentioning

confidence: 99%

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Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis

Liu

Yeh

Lin

2019

IJMS

108

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Several physiological processes, including cellular growth, embryonic development, differentiation, metabolism and proliferation, are modulated by genomic and nongenomic actions of thyroid hormones (TH). Several intracellular and extracellular candidate proteins are regulated by THs. 3,3,5-Triiodo-L-thyronine (T3) can interact with nuclear thyroid hormone receptors (TR) to modulate transcriptional activities via thyroid hormone response elements (TRE) in the regulatory regions of target genes or bind receptor molecules showing no structural homology to TRs, such as the cell surface receptor site on integrin αvβ3. Additionally, L-thyroxine (T4) binding to integrin αvβ3 is reported to induce gene expression through initiating non-genomic actions, further influencing angiogenesis and cell proliferation. Notably, thyroid hormones not only regulate the physiological processes of normal cells but also stimulate cancer cell proliferation via dysregulation of molecular and signaling pathways. Clinical hypothyroidism is associated with delayed cancer growth. Conversely, hyperthyroidism is correlated with cancer prevalence in various tumor types, including breast, thyroid, lung, brain, liver and colorectal cancer. In specific types of cancer, both nuclear thyroid hormone receptor isoforms and those on the extracellular domain of integrin αvβ3 are high risk factors and considered potential therapeutic targets. In addition, thyroid hormone analogs showing substantial thyromimetic activity, including triiodothyroacetic acid (Triac), an acetic acid metabolite of T3, and tetraiodothyroacetic acid (Tetrac), a derivative of T4, have been shown to reduce risk of cancer progression, enhance therapeutic effects and suppress cancer recurrence. Here, we have reviewed recent studies focusing on the roles of THs and TRs in five cancer types and further discussed the potential therapeutic applications and underlying molecular mechanisms of THs.

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Section: Functional Significance Of Thyroid Hormone and Receptors mentioning

confidence: 99%

Section: Functional Significance Of Thyroid Hormone and Receptors mentioning

confidence: 99%

Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis

Liu

Yeh

Lin

2019

IJMS

108

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“…Increased risk for breast cancer, especially in women with multiple hospitalizations, was also shown in a large Swedish cohort of GD patients 35 . Specific receptivity of breast cells to thyroid hormones and/or thyroid Abs stimuli may play a role in oncogenesis, as suggested from the high incidence and aggressiveness of breast cancer observed in hyperthyroidism 38 …”

Section: Discussionmentioning

confidence: 82%

“…35 Specific receptivity of breast cells to thyroid hormones and/or thyroid Abs stimuli may play a role in oncogenesis, as suggested from the high incidence and aggressiveness of breast cancer observed in hyperthyroidism. 38 It is not excluded that the association between GD and breast cancer can be partially related to shared predisposing factors, as for instance smoking is a well-described risk factor for both entities. 39,40 Epidemiological studies have not highlighted a significant correlation between GD or GO and increased risk of urinary tract cancer.…”

Section: Discussionmentioning

confidence: 99%

Long‐term outcomes in corticosteroid‐refractory Graves' orbitopathy treated with tocilizumab

Moi

Hamédani

Ribi

2021

Clinical Endocrinology

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Background Up to 20% of patients with moderate to severe Graves' orbitopathy (GO) do not respond to high‐dose glucocorticoids (GC). A few studies, including a randomized trial, have demonstrated the efficacy of interleukin‐6 (IL‐6) blockade with tocilizumab (TCZ) in GC‐refractory GO. However, data on predictors of response to TCZ and long‐term outcomes are lacking. Methods Observational single‐center study on ten consecutive patients treated with TCZ for GC‐refractory GO, between 2016 and 2020. Median (interquartile range) follow‐up was 24 (12–36) months. Results Inflammation and exophthalmos improved dramatically in all patients within months after starting TCZ. Mean Clinical Activity Score decreased from 4.80 ± 1.13 to 0.70 ± 0.82 points at 6 months (mean change: −4.10 ± 1.52; p < .0001). Proptosis improved from 23.2 ± 2.1 to 20.6 ± 2.0 mm at 6 months (mean change: −2.9 ± 1.4 mm; p < .0001). Diplopia resolved in 7 patients. Thyroid receptor antibodies decreased markedly during TCZ treatment. Baseline serum IL‐6 levels did not predict clinical response. TCZ was well‐tolerated. During follow‐up, 3 patients were diagnosed with cancer (breast cancer in 2 and urothelial cancer in 1). Conclusions TCZ was rapidly effective and well‐tolerated in our patients with GC‐refractory GO. Four patients experienced mild/moderate adverse events as neutropenia, hyperlipidemia, and infections; nearly a third developed cancer during the follow‐up. The increased incidence observed could be explained by the high prevalence of smokers, that are at higher risk for Graves' orbitopathy and solid malignancies as breast cancer. Thus, regular cancer screening could be proposed to this vulnerable population receiving high doses of immunosuppressants.

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“…A potential link between thyroid conditions and breast cancer has been discussed for decades [10][11][12] . It has been shown that hyperthyroidism is related to an increased incidence and aggressiveness of breast cancer whereas hypothyroidism (HypoT) is associated with a lower incidence of the disease 13,14 . In our laboratory, we have reported that animal growth, breast morphology and body fat mass were modi ed by HypoT 15 .…”

Section: Introductionmentioning

confidence: 99%

Hypothyroidism and Mammary Cancer: Role of Peritumoral Adipose Tissue

Zyla

Santiano

Bruna

et al. 2023

Preprint

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To study the effects of HypoT on rat mammary tumor-associated adipose tissue and its ability to modify the biological behavior of breast cancer epithelial cells, we evaluated changes in the viability, proliferation, apoptosis, adhesion, and migration of tumorigenic (MCF-7, MDA-MB-231) and non-tumorigenic (MCF-10A) mammary cells incubated with the conditioned media from mammary adipose tissue (MAT-CMs) of HypoT and euthyroid (EUT) rats with and without mammary tumors. Female Sprague-Dawley rats were treated with 7, 12-Dimethylbenz[a]anthracen (15mg/rat) at 55 days of age to induce mammary tumors and were divided at random in HypoT (0.01% 6-N-propyl-2-thiouracil in drinking water, n = 30) and EUT (tap water, n = 30). Fragments of MAT were incubated for 24 h with M199 medium, and MAT-CMs were collected. MCF-7, MDA-MB-231, and MCF-10A were incubated with non-tumor and tumor MAT-CMs, and viability, proliferation, apoptosis, adhesion, and migration were quantified. Non-tumor MAT-CMs of HypoT rats favored apoptosis of MCF-10A; decreased the viability and adhesion of MCF-7; promoted proliferation, and decreased the adhesion of MDA-MB-231. Tumor MAT-CMs of HypoT rats stimulated proliferation in tumorigenic cells and inhibited apoptosis of MCF-10A. Non-tumor MAT-CMs of HypoT rats may protect against tumorigenesis while tumor MAT-CMs of HypoT may favor a more tumorigenic behavior of mammary tumor cells.

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The Incidence of Breast Tumor during Experimental Hyperthyroidism

Cited by 10 publications

References 5 publications

Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis

Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis

Long‐term outcomes in corticosteroid‐refractory Graves' orbitopathy treated with tocilizumab

Hypothyroidism and Mammary Cancer: Role of Peritumoral Adipose Tissue

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