Posttranslational Modifications in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, Classification, and Treatment.

There is evidence that posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, sumoylation, glycosylation, and succinylation, may be involved in thyroid cancer. We review recent reports supporting a role of posttranslational modifications in the tumorigenesis of thyroid cancer, sensitivity to radioiodine and other types of treatment, the identification of molecular treatment targets, and the development of molecular markers that may become useful as diagnostic tools. An increased understanding of posttranslational modifications may be an important supplement to the determination of alterations in gene expression that has gained increasing prominence in recent years.

Long-term voice changes after thyroidectomy: Results from a validated survey.

Background: Long-term dysphonia may persist after thyroid surgery even in the absence of overt nerve injury. Therefore, we evaluated long-term dysphonia after thyroidectomy using a validated survey.

Methods: Patients undergoing thyroidectomy at a single institution from 1990 to 2018 were surveyed via telephone to complete the Voice Handicap Index-10 Survey.

Can Cytologic and Sonographic Features Help Prevent Overtreatment of Bethesda V Thyroid Nodules?

Background: Although nearly half of thyroid nodules with Bethesda V cytology (suspicious for malignancy) may be benign or harbor low-grade neoplasms that can be sufficiently treated with lobectomy, many patients with Bethesda V cytology continue to be treated with total thyroidectomy. The objectives of this study were to establish whether cytomorphologic and ultrasonographic features can determine appropriate surgery for thyroid nodules with Bethesda V cytology and how often patients are overtreated with total instead of partial thyroidectomy.

Methods: Utilizing a 10-y prospective database starting January 1, 2004, cytomorphologic and ultrasonographic features of thyroid nodules with Bethesda V cytology were reviewed.

Patient-Reported Financial Burden in Thyroid Cancer.

Background: The incidence of thyroid cancer is increasing at a rapid rate. Prior studies have demonstrated financial burden and decreased quality of life in patients with thyroid cancer. Here, we characterize patient-reported financial burden in patients with thyroid cancer over a 28y period.

Repeat Fine Needle Aspiration Cytology Refines the Selection of Thyroid Nodules for Afirma Gene Expression Classifier Testing.

Molecular testing (MT) refines risk stratification for thyroid nodules that are indeterminate for cancer by fine needle aspiration (FNA) cytology. Criteria for selecting nodules for MT vary and remain largely untested, raising questions about the best strategy for maximizing the usefulness of MT while minimizing the harms of overtesting. We used a unique data set to examine the effects of repeat FNA cytology-based criteria for MT on management decisions and nodule outcomes.

The Smallpox Epidemics in America in the 1700s and the Role of the Surgeons: Lessons to be Learned During the Global Outbreak of COVID-19.

Today's COVID-19 pandemic offers many similarities with previous pandemics hitting our country. In particular, the smallpox epidemics during the 1700s threatened the lives of multitudes and created panic and fear in the society, similar to the situation caused by the coronavirus. Remedies that were instituted, especially inoculations, were met with opposition and even violence when first introduced.

Papillary thyroid cancer with extrathyroidal extension of desmoid-type fibromatosis. A case report of an aggressive presentation of an uncommon pathologic entity.

Introduction: Papillary thyroid cancer with desmoid-type fibromatosis (PTC-DTF) is an uncommon tumor characterized by extensive stromal proliferation of fibroblasts and myofibroblasts with a small component of PTC. We report a case of PTC-DTF with infiltration of the mesenchymal component of tumor into perithyroidal muscle and early recurrence of desmoid after thyroidectomy, an outcome previously not reported.

Presentation Of Case: A 20-year-old man underwent left hemithyroidectomy for a thyroid nodule.

Invasive follicular variant of papillary thyroid cancer harboring the NRAS mutation Q61K and presenting with bone metastasis-A case report.

Introduction: The follicular variant of papillary thyroid cancer (FVPTC) can be noninvasive or invasive. The invasive form of FVPTC commonly harbors BRAF mutations whereas RAS mutations are more often associated with noninvasive FVPTC and a favorable clinical outcome.

Case Report: A 47-year-old man presented with a metastasis to his right iliac bone as the initial manifestation of a 1.

Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status.

Background: In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes, and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insights regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase.

The relationship between the follicular variant of papillary thyroid cancer and follicular adenomas.

Background: Reports suggest that the incidence of tumors diagnosed as follicular variant of papillary thyroid cancer (FVPTC) is increasing and that this increase may reflect changes in diagnostic criteria with tumors presently being diagnosed as FVPTC previously being defined as follicular lesions, in particular follicular adenomas. Changes during recent years in the relationship between the incidence of FVPTC and follicular adenomas have not been reported. Herein, we have compared changes in the incidence of FVPTC with changes in the incidence of follicular adenomas.

Identification and saturable nature of signaling pathways induced by metreleptin in humans: comparative evaluation of in vivo, ex vivo, and in vitro administration.

Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation.

Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of cultured myotubes.

Objective: The mechanistic role of the ubiquitin ligases atrogin-1 and MuRF1 in glucocorticoid-induced muscle wasting is not fully understood. Here, we tested the hypothesis that glucocorticoid-induced muscle atrophy is at least in part linked to atrogin-1 and MuRF1 expression and that the ubiquitin ligases are regulated by compensatory mechanisms.

Methods: The expression of atrogin-1 and MuRF1 was suppressed individually or in combination in cultured L6 myotubes by using siRNA technique.

Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat.

The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1). BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue.

PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.

FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting.

CaMKII activity is reduced in skeletal muscle during sepsis.

Exercise-induced muscle hypertrophy is associated with increased calcium/calmodulin-dependent protein kinase II (CaMKII) expression and activity. In contrast, the influence of muscle atrophy-related conditions on CaMKII is poorly understood. Here, we tested the hypothesis that sepsis-induced muscle wasting is associated with reduced CaMKII expression and activity.

Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness.

Sepsis is associated with impaired muscle function but the role of glucocorticoids in sepsis-induced muscle weakness is not known. We tested the role of glucocorticoids in sepsis-induced muscle weakness by treating septic rats with the glucocorticoid receptor antagonist RU38486. In addition, normal rats were treated with dexamethasone to further examine the role of glucocorticoids in the regulation of muscle strength.

β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.

High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes.

Acetylation and deacetylation--novel factors in muscle wasting.

We review recent evidence that acetylation and deacetylation of cellular proteins, including transcription factors and nuclear cofactors, may be involved in the regulation of muscle mass. The level of protein acetylation is balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and studies suggest that this balance is perturbed in muscle wasting. Hyperacetylation of transcription factors and nuclear cofactors regulating gene transcription in muscle wasting may influence muscle mass.

Multiple muscle wasting-related transcription factors are acetylated in dexamethasone-treated muscle cells.

Recent studies suggest that the expression and activity of the histone acetyltransferase p300 are upregulated in catabolic muscle allowing for acetylation of cellular proteins. The function of transcription factors is influenced by posttranslational modifications, including acetylation. It is not known if transcription factors involved in the regulation of muscle mass are acetylated in atrophying muscle.

Resveratrol prevents dexamethasone-induced expression of the muscle atrophy-related ubiquitin ligases atrogin-1 and MuRF1 in cultured myotubes through a SIRT1-dependent mechanism.

Resveratrol (3,5,4'-trihydroxystilbene) has been ascribed multiple beneficial biological effects but the influence of resveratrol on glucocorticoid-induced muscle atrophy is not known. We examined the effects of resveratrol on dexamethasone-induced atrogin-1 and MuRF1 expression, FOXO1 acetylation, protein degradation and atrophy in cultured L6 myotubes. In addition, the role of the deacetylase SIRT1 in the effects of resveratrol was determined by transfecting myotubes with SIRT1 siRNA.

Molecules modulating gene transcription during muscle wasting in cancer, sepsis, and other critical illness.

Muscle wasting in patients with sepsis, severe injury, and cancer is associated with increased transcription of several genes regulating different proteolytic pathways. The involvement of gene activation in muscle wasting suggests that transcription factors and nuclear cofactors play important roles in the regulation of muscle mass. Among transcription factors, NF-κB, C/EBPβ, and FOXO transcription factors are activated in atrophying muscle and stimulate the transcription of genes in the ubiquitin-proteasome proteolytic pathway, as well as genes regulating authophagy/lysosomal proteolysis.

C/EBPβ regulates dexamethasone-induced muscle cell atrophy and expression of atrogin-1 and MuRF1.

Muscle wasting in catabolic patients is in part mediated by glucocorticoids and is associated with increased expression and activity of the transcription factor C/EBPβ. It is not known, however, if C/EBPβ is causally linked to glucocorticoid-induced muscle atrophy. We used dexamethasone-treated L6 myoblasts and myotubes to test the role of C/EBPβ in glucocorticoid-induced expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF1, protein degradation, and muscle atrophy by transfecting cells with C/EBPβ siRNA.

Calpain activity is increased in skeletal muscle from gastric cancer patients with no or minimal weight loss.

The influence of cancer on skeletal muscle calpain expression and activity in humans is poorly understood. We tested the hypothesis that calpain activity is increased in skeletal muscle from gastric cancer patients with no or <5% weight loss. Muscle biopsies were obtained from rectus abdominis muscle in 15 patients who underwent surgery for gastric cancer and had <5% weight loss and also in 15 control patients.