Correlation Between Glycemic Control and Serum Thyroglobulin Levels in a Patient With RAI-Refractory Thyroid Cancer.

Diabetes is a risk factor for thyroid cancer development. Serum thyroglobulin (Tg) levels are useful as sensitive and specific tumor markers for monitoring radioiodine (RAI)-refractory thyroid cancer; however, the impact of glycemic control on serum Tg levels is poorly understood. Here, we present a case of a female patient with lung metastases of RAI-refractory thyroid cancer in whom glycemic control may have influenced the serum Tg levels. Despite receiving thyroid-stimulating hormone suppression therapy, her serum Tg levels remained elevated. Subsequently, she developed type 2 diabetes and was administered antidiabetic medications for 6 years. Throughout the course of diabetes management, her serum Tg levels fluctuated according to the level of glycemic control, showing a strong correlation with her hemoglobin A1c levels (r = 0.92, P < .01). Similar to the serum levels of other tumor markers, such as the carcinoembryonic antigen and carbohydrate antigen 19-9, the serum levels of Tg can be influenced by glycemic control. Therefore, serum Tg levels in patients with RAI-refractory thyroid cancer and diabetes should be monitored with attention to glycemic control.

A Follow-up Report on the Diagnosis of Gastrointestinal Cancer during the COVID-19 Pandemic in Akita Prefecture, Japan in 2021.

We recently reported the decrease in the number of gastrointestinal (GI) cancer diagnoses in 2020 due to disturbance of the healthcare system by the coronavirus disease 2019 (COVID-19) pandemic, using a hospital-based cancer registration system in Akita prefecture, Japan. In this study, we extended the research by showing the latest data (2021) on the number of cancers and examinations. Information on the occurrence and stage of esophageal, gastric, and colorectal cancers was collected from the same database. The number of GI examinations (cancer screening procedures and endoscopic examinations) was also investigated. Following the immediate decrease in the numbers of both GI examinations and GI cancer diagnoses in 2020, a rebound increase in the numbers of GI cancer diagnoses-especially colorectal cancers-was observed in 2021, resulting from an increased number of GI examinations i.e., the total number of colorectal cancers in 2021 increased by 9.0% and 6.8% in comparison to 2020 and pre-pandemic era, respectively. However, the rebound increase in 2021 was largely due to an increase in early-stage cancers, and there was no apparent trend toward the increased predominance of more advanced cancers. It therefore seems that we managed to escape from the worst-case scenario of disturbance of the healthcare system due to pandemic (i.e., an increase in the number of more advanced cancers due to delayed diagnoses). We need to continue to watch the trends in Akita prefecture, which has the highest rate of mortality from the 3 major GI cancers in Japan.

A case of hepatocellular carcinoma with bleeding gingival metastasis treated by transcatheter arterial embolization.

The patient was a terminally ill 80-year-old man with multiple lung metastases from hepatocellular carcinoma, that had developed following hepatitis-C virus-associated cirrhosis. He was admitted to our hospital with gingival bleeding, and we diagnosed gingival metastasis from hepatocellular carcinoma, based on histological examination. The bleeding could not be controlled, and the patient became dyspneic. After transcatheter arterial embolization, his bleeding was successfully controlled until his death due to respiratory failure. Transcatheter arterial embolization was a safe and effective treatment in our case.

Stereoscopic viewing system for proteins using OpenRasmol: a tool for displaying a filament of proteins.

We have made a stereoscopic viewing system for a large assembly of proteins using OpenRasmol. The stable version 2.7.1 of OpenRasmol is modified for the system, which uses an eye-ware instead of trained bare-eyes. Software rendering and other benefits in OpenRasmol are reserved. A 3-D graphic board is used just for the active stereo method, not for the acceleration of rendering. Our modification is simple one. In the results, an actin filament of 16-mers, where one actin monomer has about 400 residues, in space filling model can be rendered in stereoscopic viewing mode and can be made one turn within 10 seconds as quick as non-stereoscopic mode. Other 3-D molecular graphics programs with 3-D accelerator boards cannot render such a large assembly of molecules in stereoscopic usage mode as quickly as the modified OpenRasmol. An attractive application of our system is stereoscopic viewing with a large 200 inch screen in passive stereo method. Simultaneous usage is available for more than 100 persons with inexpensive eye-wares. The large screen allows us to investigate an interior of a groove in an actin filament in detail. Our modified OpenRasmol is distributed following the license, RASLIC, as an open source code at our web site (www.irisa-lab.bio.kyutech.ac.jp/openrasmol), where video files showing rendering speeds of our modified OpenRasmol are also available.

Uptake of pullulan in cultured rat liver parenchymal cells.

Uptake of pullulan, including a binding process followed by internalization, was examined in cultured rat liver parenchymal cells. A tyramine derivative of pullulan was labeled with [125I]iodine and used as a ligand. Pullulan bound to the cell surface was released by EDTA treatment, indicating that pullulan binding requires Ca2+ and a contribution from the asialoglycoprotein receptor. Binding of pullulan reached a steady state and internalization represented a biphasic mode, which included first- and zero-order processes in the initial stage and after 20 min incubation, respectively. The uptake of pullulan could be estimated by a similar model for intracellular disposition of asialofetuin. Kinetic parameters of pullulan constituting both binding and internalization were below those found for asialofetuin. These results suggest that pullulan is taken up by liver parenchymal cells via the asialoglycoprotein receptor; however, uptake availability is lower than that of asialofetuin.

Intracellular disposition of polysaccharides in rat liver parenchymal and nonparenchymal cells.

Binding and internalization of arabinogalactan, pullulan, dextran, and mannan were examined in rat liver parenchymal and nonparenchymal cells using 125I or fluorescein isothiocyanate (FITC) labeled polysaccharides. Binding and uptake of arabinogalactan and pullulan into parenchymal cells was inhibited by asialofetuin, indicating that the asialoglycoprotein receptor is involved in the intracellular disposition of arabinogalactan and pullulan. Uptake of 125I-labeled dextran to parenchymal cells was unchanged upon addition of excess unlabeled dextran, suggesting that dextran uptake occurs via fluid phase endocytosis. Of the polysaccharides tested, mannan showed the strongest specific association with liver nonparenchymal cells. FITC-labeled polysaccharides showed arabinogalactan and pullulan are internalized to liver parenchymal cells, whereas mannan is internalized to nonparenchymal cells. This study demonstrates that intracellular disposition of polysaccharides in the liver occurs via receptor-mediated endocytosis (RME), indicating that RME plays a role in the biodisposition of these polysaccharides as drug carriers.

Cellular disposition of arabinogalactan in primary cultured rat hepatocytes.

To characterize a targeting property of arabinogalactan (AG) as a carrier to the liver, we examined cellular disposition, such as binding and internalization in primary cultured rat hepatocytes, comparing them to those of asialofetuin (AF). A tyramine derivative of AG was synthesized to allow labeling with 125I. Binding of AG to the cells was concentration-dependent and saturable. The number of binding sites (n) of AG on the cell surface was 4.0 x 10(5) +/- 0.1 x 10(5) sites per cell which was about similar to that of AF. The value of Ka of AG was 2.2 x 10(8) +/- 0.1 x 10(8) M-1 being seven-fold higher than that of AF. The binding of AG was competitively inhibited by AF and was decreased by calcium depletion. These results indicate that AG can bind strongly to hepatocytes probably through the recognition by the asialoglycoprotein receptor (ASGP-R). Both 125I-labeled AG and fluorescein-labeled AG were internalized into the cells. The rate of internalization of AG was faster than that of AF, indicating that AG is effectively endocytosed. Microscopic observations showed that FITC labeled AG accumulated in granules within the primary cultured rat hepatocytes. Subcellular fractionation indicated that the internalized AG was mainly associated with the lysosomal fraction. However, the internalized AG seemed to remain intact in the hepatocytes. In conclusion, we found that AG is effectively internalized in primary cultured rat hepatocytes. Although AG seems a good candidate for targeting to the liver due to its high affinity binding and rapid internalization, it remains to be established whether the apparent lack of biodegradation will result in cytotoxic effects at chronic administration in vivo.