Объем остаточной тиреоидной ткани и эффективность постоперационной радиойодтерапии больных с дифференцированными формами рака щитовидной железы

Резюме. У 210 больных с дифференцированными формами рака щитовидной железы изучено влияние массы участков остаточной ткани щитовидной железы (ОТЩЖ) на эффективность радиойодтерапии (РЙТ). Через 4–6 нед после хирургического лечения выполняли диагностическую сцинтиграфию с 70–80 МБк 131I, по данным которой на основании эллипсоидной модели рассчитывали объем ОТЩЖ. РЙТ проводили активностями 1,9–4,7 ГБк, контрольную сцинтиграфию выполняли через 4–6 мес. Эффективность первого курса РЙТ при объеме ОТЩЖ 1 см3 и менее составляла 88,9%, при объеме более 4 см3 — 69,3% (р < 0,05). Установлена достоверная корреляция между объемом ОТЩЖ и эффективностью первого курса РЙТ. При наличии нескольких участков ОТЩЖ эффективность РЙТ определяется не столько их количеством и суммарным объемом, сколько объемом каждого участка. Ключевые слова: дифференцированный рак щитовидной железы, тиреоидэктомия, радиойодтерапия, остаточная ткань щитовидной железы.Summary. The influence of the mass of the residual thyroid tissue (RTT) on the efficacy of radioiodine therapy (RT) was investigated in 210 patients with differentiated forms of thyroid cancer (DFTC). 4 to 6 weeks after surgery, diagnostic 131J scintigraphy (70–80 MBq) was applied. On the basis of data obtained, the RTT size was measured based on an ellipsoidal model. Activities applied in RT ranged between 1,9–4,7 GBq; control scintigraphy was performed in 4 to 6 months. The efficacy of the first RT course was 88,9% in patients with RTT of 1 cm3 or smaller and 69,3% in patients with RTT of 4 cm3 or larger (р<0,05). A significant correlation was found between the size of RTT and the efficacy of the first RT course. In cases where there were several RTT areas, the RT efficacy depended on the overall size of each area rather than on the number of such areas. Key Words: differentiated thyroid cancer, thyreoidectomy, radioiodine therapy, residual thyroid tissue

Growth Hormone Receptor Regulation in Cancer and Chronic Diseases

The GHR signaling pathway plays important roles in growth, metabolism, cell cycle control, immunity, homeostatic processes, and chemoresistance via both the JAK/STAT and the SRC pathways. Dysregulation of GHR signaling is associated with various diseases and chronic conditions such as acromegaly, cancer, aging, metabolic disease, fibroses, inflammation and autoimmunity. Numerous studies entailing the GHR signaling pathway have been conducted for various cancers. Diverse factors mediate the up- or down-regulation of GHR signaling through post-translational modifications. Of the numerous modifications, ubiquitination and deubiquitination are prominent events. Ubiquitination by E3 ligase attaches ubiquitins to target proteins and induces proteasomal degradation or starts the sequence of events that leads to endocytosis and lysosomal degradation. In this review, we discuss the role of first line effectors that act directly on the GHR at the cell surface including ADAM17, JAK2, SRC family member Lyn, Ubc13/CHIP, proteasome, βTrCP, CK2, STAT5b, and SOCS2. Activity of all, except JAK2, Lyn and STAT5b, counteract GHR signaling. Loss of their function increases the GH-induced signaling in favor of aging and certain chronic diseases, exempli

Heterologous in vitro Synthesis of Lens α-Crystallin Polypeptide

Contains fulltext : 143169.pdf (publisher's version ) (Open Access

Biosynthesis of a-crystallin polypeptides: initiation and N-terminal acetylation

Contains fulltext : mmubn000001_241443539.pdf (publisher's version ) (Open Access)Promotor : H. Bloemendal89 p

Synthesis of Lens Protein in vitro : N-Terminal Acetylation of α-Crystallin

Contains fulltext : 142257.pdf (publisher's version ) (Open Access

Role of galactosyl-transferases in rat gastric epithelial glycoprotein synthesis

Two galactosyl-transferases have been found in the Golgi-enriched sub-cellular fractions derived from rat gastric mucosa. One incorporates galactose into ovomucoid at optimal pH 6.8. The reaction can be completely inhibited by acetylglucosamine. The apparent Km for UDPgalactose is 0.024 mM. The other galactosyl-transferase incorporates galactose into desialated ovine submaxillary mucin at optimal pH 7.5 and the transfer cannot be inhibited by acetylglucosamine. The apparent Km for UDPgalactose is 0.191 mM. Both enzymes require Mn2+ and Triton X-100 for optimal galactose incorporation. The enzymes could be separated by polyacrylamide gel electrophoresis. Incorporation into endogenous glycoprotein was studied in conditions optimal for the two galactosyl-transferases: (1) at pH 6.8, using Mes as buffer system, and (2) at pH 7.5, using Tris-HCl in the presence of an inhibitory excess of acetylglucosamine. In both cases, most radioactive galactose is incorporated into macromolecules, which could be identified as epithelial glycoprotein. Endogenous incorporation in the presence of excess acetylglucosamine results in the formation of a substantial amount of a disaccharide (probably galactose-β-(1–3)acetylgalactosamine), whereas upon incorporation at pH 6.8 almost no disaccharide is formed. Quantitative immunoprecipitaton experiments with specific antibodies to the endogenous product, labelled by [3H]galactose in the presence of varying amounts of desialated ovine submaxillary mucin and/or acetylglucosamine, indicated that other galactosyl-transferases are involved in the biosynthesis of epithelial glycoprotein

Isolation and partial characterization of rat gastric mucous glycoprotein

Mucus glycoproteins from the rat stomach were characterized after their isolation from homogenates of the superficial gastric mucosa by equilibrium centrifugation in CsCl density gradients. Water-soluble as well as water-insoluble glycoproteins were studied. The latter were solubilized by 2-mercaptoethanol reduction of the homogenate. From both homogenate fractions the same two glycoproteins 1 and 2 were purified, glycoprotein 1 being present in considerably higher amount than glycoprotein 2. Their respective buoyant densities in a CsCl gradient were 1.47–1.50 g/ml and 1.56–1.58 g/ml. The two glycoproteins expressed slight differences in gel electrophoresis and gel filtration. The results from column chromatographic comparisons between reduced and unreduced glycoproteins indicated strongly that both glycoproteins 1 and 2 were built from subunits kept together by S---S bonds. The s20,w values of the reduced glycoproteins 1 and 2 were 15.7 S and 11.6 S. Glycoprotein 1 contained 5% protein, 70% carbohydrate and 1–2% sulphate, whereas these percentages for glycoprotein 2 were 10% protein, 65% carbohydrate and 10% sulphate. The molar proportions of the main sugar components galactose, fucose, glucosamine and galactosamine were 4 : 2 : 4 : 1 (glycoprotein 1) and 3 : 2 : 3 : 1 (glycoprotein 2). Blood-group activity A was expressed by glycoprotein 1, whereas glycoprotein 2 showed mainly blood-group activity Leb, some B activity and also some A activity, but to a lesser extent than glycoprotein 1

Differential effects of brefeldin A on transport of secretory and lysosomal proteins

Brefeldin A (BFA) rapidly blocks anterograde exocytotic transport through the Golgi complex. Sustained retrograde traffic induced by brefeldin A causes redistribution of constituents of the Golgi, but not the trans-Golgi network (TGN), to the endoplasmic reticulum (ER). In the present study on HepG2 cells, we have observed a differential effect of BFA on transport from the TGN of two soluble proteins: α1-antitrypsin as a representative of secretory proteins and cathepsin D as a prototype of lysosomal enzymes. The Golgi complex of HepG2 cells is sensitive to BFA, as within minutes after its addition nearly all activity of three resident Golgi enzymes was recovered in the ER as monitored by cell fractionation on sucrose density gradients. In accordance with this, 'high mannose'-glycosylated α1-antitrypsin was retained in or transported back to the ER. 'Complex'-glycosylated α1- antitrypsin was neither secreted into the medium nor transported back to the ER. Most of it was retained in vesicles with the buoyant density of Golgi. These vesicles contained the fluid phase endocytotic marker horseradish peroxidase when this was added to the culture medium prior to the BFA, suggesting that the vesicles derived from the TGN. After BFA addition, the compartment became inaccessible to endocytosed horseradish peroxidase. In contrast to blocking transport of complex α1-antitrypsin, BFA did not affect processing of newly synthesized complex-glycosylated procathepsin D (53 kDa) to the mature 31-kDa form. Neither did it interfere with processing of endocytosed procathepsin D. That the mature cathepsin D had indeed reached the lysosomes was verified by Percoll density gradient fractionation. In conclusion, in HepG2 cells, BFA induces two blocks in the secretory pathway: one at the level of the ER-Golgi juncture and the other in the TGN. In contrast, transport from the Golgi complex to the lysosomes and from the plasma membrane to the lysosomes continued

Intracellular receptor sorting during endocytosis: Comparative immunoelectron microscopy of multiple receptors in rat liver

Using double-label quantitative immunoelectron microscopy on ultrathin cryosections of rat liver, we have compared the endocytotic pathways of the receptors for asialoglycoprotein (ASGP-R), mannose-6-phosphate ligands (MP-R), and polymeric IgA (IgA-R). All three were found within the Golgi complex, along the entire plasma membrane, in coated pits and vesicles, and within a compartment of uncoupling of receptors and ligand (CURL). The receptors occurred randomly at the cell surface, in coated pits and vesicles. Within CURL tubules ASGP-R and MP-R were colocalized, but IgA-R and ASGP-R displayed dramatic microheterogeneity. Thus, in addition to its role in uncoupling and sorting recycling receptor from ligand, CURL serves as a compartment to segregate recycling receptor (e.g. ASGP-R) from receptor involved in transcytosis (e.g. IgA-R)