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Introduction: There is evidence for the anticancer effects of L-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear., Methods: Various upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains. Furthermore, effects of arginine were evaluated using a mitochondrial stress test, cell cycle assay, comprehensive metabolic analysis, and tracer study using [¹³C₆] L-arginine., Results: In OE33 (but not in OE19), the maximal respiratory capacity of mitochondria was lower in the treated group than in the control group. In OE33, S phase cells (determined using BrdU) were significantly reduced. In a comprehensive metabolic analysis of OE33, citrulline/ornithine levels were significantly lower in arginine-treated than in untreated cells. Using OE33, carbamoyl aspartic acid (CAA) levels were significantly lower in arginine-treated than in untreated cells. A tracer study suggested that arginine promotes the urea cycle., Conclusion: Arginine affected urea cycle metabolism, thereby decreasing CAA, which is required for pyrimidine nucleotide synthesis. These findings provide insight into the mechanism underlying the anticancer effects of arginine., (The Author(s). Published by S. Karger AG, Basel.)

In classical cell culture techniques, cancer cells typically proliferate in a single layer by adhering to the undersurface of laboratory vessels. Consequently, concerns have been raised regarding the fidelity of the morphological and functional characteristics of these cultured cancer cells compared to those of their in vivo counterparts. Our previous studies have investigated various epithelial malignant tumors utilizing the Tissueoid cell culture system, a three-dimensional (3D) cultivation method employing Cellbed-a nonwoven sheet composed of high-purity silica fibers as a scaffold. In this investigation, we have achieved successful 3D culturing of glioblastoma cells (A172 and T98G), which are non-epithelial in nature. As such our focus is to juxtapose their morphological features against that of those cultivated via conventional two-dimensional (2D) methods. Our findings will be elucidated using immunostaining, immunofluorescence staining, and scanning electron microscopy, substantiated with accompanying imaging. Notably, cells cultured in the 3D environment exhibited distinct morphological attributes compared to those of their 2D counterparts, notably featuring pronounced cellular protrusions. We envisage the continued utilization of the 3D culture platform to facilitate diverse avenues of research, encompassing the exploration of novel therapeutic modalities for glioblastoma cells and beyond., Competing Interests: VThis research was done in collaboration with Japan Vilene Company, Ltd. The company provided Cellbed and information on Cellbed materials., (2024 The Japan Society of Histochemistry and Cytochemistry.)

A 46-year-old woman was referred for hypertension and a right adrenal tumor. Primary aldosteronism (PA) was suspected because of the high plasma aldosterone concentration-to-plasma renin activity ratio. However, a subsequent evaluation revealed coexistent PA and pheochromocytoma. We performed laparoscopic right adrenalectomy. Histology of the resected adrenal gland confirmed pheochromocytoma and multiple aldosterone-producing adrenocortical micronodules. Following adrenalectomy, the urinary catecholamine levels normalized, and hyperaldosteronism improved but persisted. Hypertension also improved but persisted and was normalized with spironolactone. The clinical course indicated that the PA lesions were likely bilateral. This was a histologically proven case of coexistent pheochromocytoma and PA due to multiple aldosterone-producing micronodules.

A 72-year-old man was followed as an outpatient at our hospital for 6 years after surgery for small cell carcinoma of left adrenal gland origin. Follow-up abdominal computed tomography showed a 6-cm mass in the left lower mesentery. The patient underwent open laparotomy. The histological diagnosis was sclerosing mesenteritis. The previous specimens of the left adrenal mass were then re-examined with a microscope, and panniculitis was found around the small cell carcinoma. Both lesions were histologically similar to IgG4-related disease (RD), but they did not completely meet the diagnostic criteria of IgG4-RD clinically or histologically.