Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV‐related liver cirrhosis

Sorvillo, Francesca; Mazziotti, Gherardo; Carbone, Antonella; Morisco, Filomena; Cioffi, Michele; Rotondi, Mario; Stornaiuolo, Gianfranca; Amato, Giovanni; Gaeta, Giovanni Battista; Caporaso, Nicola; Carella, Carlo

doi:10.1046/j.1365-2265.2003.01697.x

Cited by 26 publications

(21 citation statements)

References 38 publications

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“…Disruption of TH signaling causes dysfunction in several organs and is closely associated with several diseases [1–7, 9]. The liver is one of the major target organs of TH, and TH levels are closely correlated with multi liver-associated diseases within a spectrum ranging from hepatic steatosis to HCC [23, 111, 115]. Thus, the complex mechanism of TH action requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study revealed that the serum levels of THs are decreased in HBV- and HCV-infected patients [17]. HCC is accompanied by a significant increase in serum rT 3 (inactive form of T 3 ) levels in patients with low-grade HCV-related liver cirrhosis [115]. Thus, it is important to determine the functions of TH signaling in HCC.…”

Section: Roles Of Thyroid Hormones and Thyroid Receptors In Liver mentioning

confidence: 99%

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Molecular Functions of Thyroid Hormones and Their Clinical Significance in Liver-Related Diseases

Cheng

Chen

Tsai

et al. 2013

BioMed Research International

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Thyroid hormones (THs) are potent mediators of several physiological processes, including embryonic development, cellular differentiation, metabolism, and cell growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate the biological functions of T3 via transcriptional regulation. TRs generally form heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3 stimulation. Research over the past few decades has revealed that disruption of cellular TH signaling triggers chronic liver diseases, including alcoholic or nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model experiments and epidemiologic studies to date imply close associations between high TH levels and prevention of liver disease. Moreover, several investigations spanning four decades have reported the therapeutic potential of T3 analogs in lowering lipids, preventing chronic liver disease, and as anticancer agents. Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of TH actions is critical for the treatment of significant public health issues. Here, we have reviewed recent studies focusing on the roles of THs and TRs in several disorders, in particular, liver diseases. We also discuss the potential therapeutic applications of THs and underlying molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Roles Of Thyroid Hormones and Thyroid Receptors In Liver mentioning

confidence: 99%

Molecular Functions of Thyroid Hormones and Their Clinical Significance in Liver-Related Diseases

Cheng

Chen

Tsai

et al. 2013

BioMed Research International

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“…Conversion of inactive to active thyroid hormone is the result of 5'-deiodination of T4 and occurs in the liver. 30 Peripheral suppression of thyroid hormone activity also occurs in 'non-thyroidal illness syndrome' (previously call the 'sick euthyroid syndrome'). Acute and chronic stress also affects the hypothalamic-pituitary-adrenal axis, which may in turn have several different effects on thyroid function.…”

Section: Hormonal Dysfunction A) Hypothyroidismmentioning

confidence: 99%

A Review of Myofascial Pain and Fibromyalgia – Factors that Promote Their Persistence

Gerwin¹

2005

Acupunct Med

146

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Chronic muscle pain (myalgia) is a common problem throughout the world. Seemingly simple, it is actually a difficult problem for the clinician interested in determining the aetiology of the pain, as well as in managing the pain. The two common muscle pain conditions are fibromyalgia and myofascial pain syndrome. Fibromyalgia is a chronic, widespread muscle tenderness syndrome, associated with central sensitisation. It is often accompanied by chronic sleep disturbance and fatigue, visceral pain syndromes like irritable bowel syndrome and interstitial cystitis. Myofascial pain syndrome is an overuse or muscle stress syndrome characterised by the presence of trigger points in muscle. The problem these syndromes pose lies not in making the diagnosis of muscle pain. Rather, it is the need to identify the underlying cause(s) of persistent or chronic muscle pain in order to develop a specific treatment plan. Chronic myalgia may not improve until the underlying precipitating or perpetuating factor(s) are themselves managed. Precipitating or perpetuating causes of chronic myalgia include structural or mechanical causes like scoliosis, localised joint hypomobility, or generalised or local joint laxity; and metabolic factors like depleted tissue iron stores, hypothyroidism or Vitamin D deficiency. Sometimes, correction of an underlying cause of myalgia is all that is needed to resolve the condition.

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“…5 Liver is one of the major target organs of T 3 , and body TH levels are closely correlated with multiple liver-associated diseases, such as hepatocellular carcinoma (HCC). 6, 7, 8, 9 …”

mentioning

confidence: 99%

Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway

et al. 2016

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and systemic chemotherapy is the major treatment strategy for late-stage HCC patients. Poor prognosis following chemotherapy is the general outcome owing to recurrent resistance. Recent studies have suggested that in addition to cytotoxic effects on tumor cells, chemotherapy can induce an alternative cascade that supports tumor growth and metastasis. In the present investigation, we showed that thyroid hormone (TH), a potent hormone-mediating cellular differentiation and metabolism, acts as an antiapoptosis factor upon challenge of thyroid hormone receptor (TR)-expressing HCC cells with cancer therapy drugs, including cisplatin, doxorubicin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TH/TR signaling promoted chemotherapy resistance through negatively regulating the pro-apoptotic protein, Bim, resulting in doxorubicin-induced metastasis of chemotherapy-resistant HCC cells. Ectopic expression of Bim in hepatoma cells challenged with chemotherapeutic drugs abolished TH/TR-triggered apoptosis resistance and metastasis. Furthermore, Bim expression was directly transactivated by Forkhead box protein O1 (FoxO1), which was negatively regulated by TH/TR. TH/TR suppressed FoxO1 activity through both transcriptional downregulation and nuclear exclusion of FoxO1 triggered by Akt-mediated phosphorylation. Ectopic expression of the constitutively active FoxO1 mutant, FoxO1-AAA, but not FoxO1-wt, diminished the suppressive effect of TH/TR on Bim. Our findings collectively suggest that expression of Bim is mediated by FoxO1 and indirectly downregulated by TH/TR, leading to chemotherapy resistance and doxorubicin-promoted metastasis of hepatoma cells.

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Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV‐related liver cirrhosis

Abstract: Our study has demonstrated that development of hepatocellular carcinoma is accompanied by a significant increase in serum rT3 levels in patients with low-grade HCV-related liver cirrhosis who had no other illness causing the 'euthyroid sick syndrome'.

Cited by 26 publications

References 38 publications

Molecular Functions of Thyroid Hormones and Their Clinical Significance in Liver-Related Diseases

Molecular Functions of Thyroid Hormones and Their Clinical Significance in Liver-Related Diseases

A Review of Myofascial Pain and Fibromyalgia – Factors that Promote Their Persistence

Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway

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