Evidence that morris hepatomas are thyroid-dependent: Inhibition of hepatoma growth and prolongation of survival after induction of hypothyroidism

Mishkin, Seymour; Huang, Shucheng; Lenoff, F.; Morris, Harold P.; Pollack, Rena; Yalovsky, Morty; Murthy, Pvn

doi:10.1016/0016-5085(78)90613-3

Cited by 19 publications

(22 citation statements)

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“…In clinical oncology, correlations between hypothyroidism and outcomes occasionally have been observed 19‐25, 27. It has been suggested that the thyroid hormone itself, by stimulating other growth factors, may represent a growth‐stimulating signal in various tumor types 32.…”

Section: Discussionmentioning

confidence: 99%

“…Drug‐induced hypothyroidism may not necessarily be perceived as an unwanted, detrimental toxicity. Thyroid hormones reportedly increased the growth of glioma cells,19 whereas hypothyroidism inhibited the growth of lung, prostate, hepatocellular, and mammary tumors in animal models 20‐22. Hypothyroidism was associated with improved outcomes in patients with head and neck cancer,23 glioblastoma,24 and metastatic breast cancer 25.…”

mentioning

confidence: 97%

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Hypothyroidism in patients with renal cell carcinoma

Schmidinger

Vogl

Bojić

et al. 2010

Cancer

189

158

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BACKGROUND: Sunitinib and sorafenib are tyrosine kinase inhibitors that have important antitumor activity in metastatic renal cell carcinoma (mRCC). Hypothyroidism constitutes a commonly reported side effect of both drugs, and particularly of sunitinib. The objective of this analysis was to investigate whether the occurrence of hypothyroidism during treatment with sunitinib and sorafenib affects the outcome of patients with mRCC. METHODS: Eighty-seven consecutive patients with mRCC who were to receive treatment with sunitinib or sorafenib were included in a prospective analysis. Thyroid function was assessed in each patient every 4 weeks during the first 2 months of treatment and every 2 to 4 months thereafter. Assessment included serum levels of thyroid-stimulating hormone (TSH), tri-iodthyronine (T3), and thyroxine (T4). Subclinical hypothyroidism was defined as an increase in TSH above the upper limit of normal (>3.77 lM/mL) with normal T3 and T4 levels. RESULTS: Subclinical hypothyroidism was evident in 5 patients at baseline and occurred in 30 patients (36.1%) within the first 2 months after treatment initiation. There was a statistically significant correlation between the occurrence of subclinical hypothyroidism during treatment and the rate of objective remission (hypothyroid patients vs euthyroid patients: 28.3% vs 3.3%, respectively; P < .001) and the median duration of survival (not reached vs 13.9 months, respectively; hazard ratio, 0.35; 95% confidence interval, 0.14-0.85; P ¼ .016). In multivariate analysis, the development of subclinical hypothyroidism was identified as an independent predictor of survival (hazard ratio, 0.31; P ¼ .014). CONCLUSIONS: The current results indicated that hypothyroidism may serve as a predictive marker of treatment outcome in patients with mRCC. Thus, the interpretation of hypothyroidism during treatment with sunitinib and sorafenib as an unwanted side effect should be reconsidered.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Hypothyroidism in patients with renal cell carcinoma

Schmidinger

Vogl

Bojić

et al. 2010

Cancer

189

158

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“…In addition to the hypothesis of on-target toxicity already discussed, a direct action of thyroid hormone on cancer cell proliferation, cancer cell growth, and angiogenesis has also been proposed. In animal models, hypothyroidism inhibited the growth of diverse tumors [80,81]. Moreover, clinical studies have shown that hypothyroidism was associated with better outcomes in patients with head and neck cancer, glioblastoma, and metastatic breast cancer [82][83][84].…”

Section: Hypothyroidism As An Mbt Of Multitargeted Tkismentioning

confidence: 99%

Toxicity as a Biomarker of Efficacy of Molecular Targeted Therapies: Focus on EGFR and VEGF Inhibiting Anticancer Drugs

et al. 2011

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In addition to being present in tumor cells, many targets of signal transduction inhibitors are also found in normal tissue. Side effects attributable to the mechanism of action of molecular targeted agents thus represent "on-target" modulation in normal tissues. These mechanism-based toxicities can be pharmacodynamic effects of pathway inhibition and, in tumors depending on the inhibited pathway for proliferation, might be biomarkers of efficacy. The development of rash with tyrosine kinase inhibitors or monoclonal antibodies targeting the epidermal growth factor receptor is associated with superior outcomes in lung, head and neck, colorectal, and pancreatic cancer studies. Correlated with superior efficacy in retrospective analyses of large studies in advanced colorectal, breast, and renal cell carcinoma, arterial hypertension as an adverse event of antiangiogenic agents may also be a marker of effective target inhibition. An association between hypothyroidism and the activity of multitargeted tyrosine kinase inhibitors has been identified in renal cell carcinoma patients. Tumor growth addiction to the specific pathway that is effectively targeted may be the link between a mechanism-based toxicity and efficacy. The biological basis for this correlation can be pharmacological, with higher drug exposure being associated with greater toxicity and antitumor activity, and can also be genetic, because single nucleotide polymorphisms play an important role in drug pharmacokinetic and pharmacodynamic processes. Investigators have proposed that interpatient differences and associated toxicities can be exploited for dose selection and titration, and clinical trials are currently exploring intrapatient "dosing-to-toxicity" strategies. Ultimately, the predictive value of a side effect of molecular targeted therapies requires validation in prospective trials. The Oncologist 2011;16:1729 -1740

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“…It is thought that T 3 activation of TGF-β signaling may underlie enhanced tumor metastasis in vitro and in vivo [74]. In agreement with these findings, an early study showed that in PTU-induced hypothyroid rats, 131 I administration, or surgical thyroidectomy significantly decreased both local and metastatic growth of Morris Hepatoma [75]. …”

Section: Hepatic Cancermentioning

confidence: 74%

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

Brown

Simmen

2013

IJMS

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Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVβ3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVβ3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals.

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Evidence that morris hepatomas are thyroid-dependent: Inhibition of hepatoma growth and prolongation of survival after induction of hypothyroidism

Cited by 19 publications

References 0 publications

Hypothyroidism in patients with renal cell carcinoma

Hypothyroidism in patients with renal cell carcinoma

Toxicity as a Biomarker of Efficacy of Molecular Targeted Therapies: Focus on EGFR and VEGF Inhibiting Anticancer Drugs

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

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