Calcitonin and chromogranin A localization in medullary carcinoma of the thyroid by immunoelectron microscopy.

Silver, Marjorie A.; Hearn, Stephen; Lines, Lois D.; Troster, M

doi:10.1177/36.8.3392392

Cited by 30 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple thin sections were prepared from the Lowicryl K4M-embedded tissue, and immunolabeling was done using a protein A gold technique. 15,34 Sections were reacted with antibody to chromogranin A, and sites of antigen-antibody complexes were detected using protein A gold (20 nm). As a negative immunocytochemical control, some sections were placed in protein A gold, omitting the primary antibody.…”

Section: Methodsmentioning

confidence: 99%

Fine Needle Aspiration Cytology of Metastatic Olfactory Neuroblastoma

Collins¹,

Cramer²,

Hearn³

1997

Acta Cytologica

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Fine Needle Aspiration Cytology of Metastatic Olfactory Neuroblastoma

Collins¹,

Cramer²,

Hearn³

1997

Acta Cytologica

View full text Add to dashboard Cite

“…Stromal amyloid-like deposits are frequently found in MTC representing the distinguishing feature of this disease [300]. The major component of these deposits is calcitonin, a 32-residue polypeptide hormone with an N-terminal disulphide bridge (between residues 1 and 7) and a C-terminal proline amide residue [301,302]. Besides being involved in MTC, calcitonin is known to cause a rapid, but short-lived, decline in calcium and phosphate levels in the blood by promoting the incorporation of these ions into bone [303].…”

Section: Calcitonin and Medullary Thyroid Cancermentioning

confidence: 99%

Amyloidogenesis of Natively Unfolded Proteins

Uversky

2008

CAR

174

152

View full text Add to dashboard Cite

Aggregation and subsequent development of protein deposition diseases originate from conformational changes in corresponding amyloidogenic proteins. The accumulated data support the model where protein fibrillogenesis proceeds via the formation of a relatively unfolded amyloidogenic conformation, which shares many structural properties with the pre-molten globule state, a partially folded intermediate first found during the equilibrium and kinetic (un)folding studies of several globular proteins and later described as one of the structural forms of natively unfolded proteins. The flexibility of this structural form is essential for the conformational rearrangements driving the formation of the core cross-beta structure of the amyloid fibril. Obviously, molecular mechanisms describing amyloidogenesis of ordered and natively unfolded proteins are different. For ordered protein to fibrillate, its unique and rigid structure has to be destabilized and partially unfolded. On the other hand, fibrillogenesis of a natively unfolded protein involves the formation of partially folded conformation; i.e., partial folding rather than unfolding. In this review recent findings are surveyed to illustrate some unique features of the natively unfolded proteins amyloidogenesis.

show abstract

“…However, hCT shows an extremely high tendency to selfassociate in the form of amyloid fibrils. As a result hCT amyloid deposits can occur in vivo in patients with medullar carcinoma of the thyroid (8,9) and in vitro in preparations designed for patient administration (10). Not only does aggregation constitute a serious problem during the production, storage, and administration of hCT, but it can also lead to a significant decrease in its activity as a drug (11).…”

mentioning

confidence: 99%

Rational design of aggregation-resistant bioactive peptides: Reengineering human calcitonin

Fowler

Poon

Muff

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

105

View full text Add to dashboard Cite

A high propensity to aggregate into intractable deposits is a common problem limiting the production and use of many peptides and proteins in a wide range of biotechnological and pharmaceutical applications. Many therapeutic polypeptides are frequently abandoned at an early stage in their development because of problems with stability and aggregation. It has been shown recently that parameters describing the physicochemical properties of polypeptides can be used as predictors of protein aggregation. Here we demonstrate that these and similar tools can be applied to the rational redesign of bioactive molecules with a significantly reduced aggregation propensity without loss of physiological activity. This strategy has been exemplified by designing variants of the hormone calcitonin that show a significantly reduced aggregation propensity, yet maintain, or even increase, their potency when compared to the current therapeutic forms. The results suggest that this approach could be used successfully to enhance the solubility and efficacy of a wide range of other peptide and protein therapeutics.protein aggregation ͉ protein design ͉ biopharmaceuticals ͉ amyloid ͉ misfolding T he number of pharmacologically active peptides and proteins under development for the prevention and treatment of human disorders is increasing, and as a result, so is the pressure to overcome problems associated with aggregation and stability. Up to 96% of all drug candidates in trials are abandoned during preclinical or clinical development, often because of low solubility or aggregation problems (1). Many peptide-based drugs with great therapeutic potential are rendered ineffective simply because of an intrinsic propensity to aggregate irreversibly (2). Aggregation is one of the most significant obstacles to the development of protein-based drugs because it cannot only compromise their bioavailability and therapeutic activity but it may also increase the risk of immunogenic reactions (3, 4).A good example of a bioactive peptide with limited pharmaceutical potential due to a high tendency to aggregate is human calcitonin (hCT), a 32-residue polypeptide hormone synthesized and secreted by the C cells of the thyroid, and involved in calcium regulation and bone dynamics. In vivo, calcitonin (CT) causes a rapid, but short-lived, decline in calcium and phosphate levels in the blood by promoting the incorporation of these ions into bone (5). This activity has lead to the use of CT in the treatment of conditions such as osteoporosis and Paget's disease, as well as malignancy-caused hypercalcemia and musculoskeletal pain (5-7). However, hCT shows an extremely high tendency to selfassociate in the form of amyloid fibrils. As a result hCT amyloid deposits can occur in vivo in patients with medullar carcinoma of the thyroid (8, 9) and in vitro in preparations designed for patient administration (10). Not only does aggregation constitute a serious problem during the production, storage, and administration of hCT, but it can also lead to a significant decr...

show abstract

Calcitonin and chromogranin A localization in medullary carcinoma of the thyroid by immunoelectron microscopy.

Cited by 30 publications

References 0 publications

Fine Needle Aspiration Cytology of Metastatic Olfactory Neuroblastoma

Fine Needle Aspiration Cytology of Metastatic Olfactory Neuroblastoma

Amyloidogenesis of Natively Unfolded Proteins

Rational design of aggregation-resistant bioactive peptides: Reengineering human calcitonin

Contact Info

Product

Resources

About