The Roles of ADAMs Family Proteinases in Skin Diseases

A disintegrin and metalloproteinases (ADAMs) are members of a new gene family of transmembrane and secreted proteins, which belong to the zinc proteinase superfamily. These molecules are involved in various biological events such as cell adhesion, cell fusion, cell migration, membrane protein shedding, and proteolysis. Growing evidence now attests to the potential involvement of ADAMs proteinases in diverse processes such as skin wound healing, inflammation, pigmentation, tumor development, cell proliferation, and metastasis. This paper focuses on the roles of ADAMs proteinases in a wide variety of skin diseases

Synthesis of 2-Acetamido-2,5-dideoxy-5-phosphoryl-D-glucopyranose Derivatives: New Phospha-sugar Analogs of N-Acetyl-D-glucosamine

Starting with N-acetyl-D-glucosamine, methyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-xylo-hexofuranosid-5-ulose (18) was prepared in 7 steps. The addition reaction of dimethyl phosphonate to 18, followed by deoxygenation of its 5-hydroxy group, provided the 5-deoxy-5-dimethoxyphosphoryl-D-glucofuranoside derivative (21a). The hydride reduction of 21a, followed by the action of hydrochloric acid and then hydrogen peroxide, afforded the first D-glucosamine analog (23) having a phosphoryl group in the hemiacetal ring. This was converted into the per-O-acetylated N-acetyl-D-glucosamine phospha-sugar (25), while the same treatment of the 5-deoxy-5-dimethoxyphosphoryl-L-idose dimethyl acetal derivative (13b) afforded the N-acetyl-L-idosamine phospha-sugar (29)

Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells

がん治療薬による乳がん細胞の老化とpH調整の解明 --新規細胞老化のメカニズム解明に貢献--. 京都大学プレスリリース. 2023-11-27.Several chemotherapeutic drugs induce senescence in cancer cells; however, the mechanisms underlying intracellular pH dysregulation in senescent cells remain unclear. Adenosine triphosphatase H+ transporting accessory protein 2 (ATP6AP2) plays a critical role in maintaining pH homeostasis in cellular compartments. Herein, we report the regulatory role of ATP6AP2 in senescent breast cancer cells treated with doxorubicin (Doxo) and abemaciclib (Abe). A decline in ATP6AP2 triggers aberrant pH levels that impair lysosomal function and cause immune profile changes in senescent breast cancer cells. Doxo and Abe elicited a stable senescent phenotype and altered the expression of senescence-related genes. Additionally, senescent cells show altered inflammatory and immune transcriptional profiles due to reprogramming of the senescence-associated secretory phenotype. These findings elucidate ATP6AP2-mediated cellular pH regulation and suggest a potential link in immune profile alteration during therapy-induced senescence in breast cancer cells, providing insights into the mechanisms involved in the senescence response to anticancer therapy

Impulse Strong Mirror Field for High-Energy Particle Handlings

The technologies for generating strong magnetic flux density of 10 T ~ 1000 T have been developed and become to be utilized for fundamental science studies, especially for solid-state physics. These technologies enable to control the high-energy particles in a compact region, and explore the new frontier of nuclei conversions and nuclear fusion studies. The methods to generate strong mirror field for high-energy particle confinement and handlings are described in this paper

Serum amyloid alpha 1-2 are not required for liver inflammation in the 4T1 murine breast cancer model

がんに起因して起こる宿主の肝臓の急性期応答と炎症 --血清アミロイドαは乳がんモデルにおける肝臓の炎症の原因ではない--. 京都大学プレスリリース. 2023-02-06.Cancers induce the production of acute phase proteins such as serum amyloid alpha (SAA) in the liver and cause inflammation in various host organs. Despite the well-known coincidence of acute phase response and inflammation, the direct roles of SAA proteins in inflammation in the cancer context remains incompletely characterized, particularly in vivo. Here, we investigate the in vivo significance of SAA proteins in liver inflammation in the 4T1 murine breast cancer model. 4T1 cancers elevate the expression of SAA1 and SAA2, the two major murine acute phase proteins in the liver. The elevation of Saa1-2 correlates with the up-regulation of immune cell-related genes including neutrophil markers. To examine this correlation in detail, we generate mice that lack Saa1-2 and investigate immune-cell phenotypes. RNA-seq experiments reveal that deletion of Saa1-2 does not strongly affect 4T1-induced activation of immune cell-related genes in the liver. Flow cytometry experiments demonstrate the dispensable roles of SAA1-2 in cancer-dependent neutrophil infiltration to the liver. Consistently, 4T1-induced gene expression changes in bone marrow do not require Saa1-2. This study clarifies the negligible contribution of SAA1-2 proteins in liver inflammation in the 4T1 breast cancer model

Malignant peripheral nerve sheath tumor arising from the greater omentum: Case report

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue tumors that arise from a peripheral nerve or exhibit nerve sheath differentiation. Most of these tumors arise on the trunk, extremities, or head and neck regions; they are very rarely located in the abdominal cavity. The patient was a 71-year-old man who was referred to our hospital for a mass and pain in the right lower abdomen. Abdominal computed tomography revealed a large (9 × 9 cm), well-circumscribed, lobulated, heterogeneously enhanced mass in the pelvis. Exploratory laparotomy revealed a large mass in the greater omentum, and the tumor was completely excised. Histopathological analysis revealed that the tumor was composed of spindle cells with high mitotic activity. On staining the tumor, positive results were obtained for S-100 but negative results were obtained for c-kit, cluster of differentiation (CD)34, α-smooth muscle actin, and desmin. These findings strongly supported a diagnosis of MPNST primarily arising from the greater omentum. To the best of our knowledge, this is the first reported case of an MPNST arising from the greater omentum. In this report, we have described the case of a patient with an MPNST arising from the greater omentum and have discussed the clinical characteristics and management of MPNSTs

Alterations of circulating endothelial cell and endothelial progenitor cell counts around the ovulation.

Context:Circulating endothelial cells (CECs) and progenitor cells (CEPs) have been intensively studied as a promising tool for treating ischemic diseases and monitoring cancer treatments, but how the menstrual cycle affects the variation in their counts remains unclear. Objective:The aims of the study were to determine the influence of the menstrual cycle on the number of CECs and CEPs and to investigate the association of their counts with circulating hormones and angiogenesis-associated factors. Design:CEP and CEC counts by flow cytometry and the CellSearch system and circulating factor levels were measured eight times during the menstrual cycle in 18 volunteers. The menstrual cycle was divided into six phases based on hormone concentrations. Results:CEP counts peaked in the periovulatory and middle luteal phases with a drop in the early luteal phase. CEC counts showed no significant variation. There were significant correlations between the CEP counts and the serum concentrations of estradiol (E2), LH, and granulocyte colony-stimulating factor (G-CSF) (P < 0.0001, P < 0.0001, and P = 0.01, respectively). The difference in CEP counts between two adjacent phases was significantly correlated with that in E2, LH, G-CSF, and serum vascular endothelial growth factor (P < 0.0001, P < 0.0001, P = 0.02, and P = 0.006, respectively). Conclusion:CEP counts peaked in the periovulatory and middle luteal phases, with a drop in the early luteal phase, and were correlated with serum E2, LH, and G-CSF concentrations. Consideration of the variation in CEP counts would be important for the clinical application of CEPs

Murine breast cancers disorganize the liver transcriptome in a zonated manner

がんが宿主の臓器に及ぼす悪影響を捉えた --がんをもつ個体における「肝機能の空間的制御」の破綻--. 京都大学プレスリリース. 2023-02-01.The spatially organized gene expression program within the liver specifies hepatocyte functions according to their relative distances to the bloodstream (i.e., zonation), contributing to liver homeostasis. Despite the knowledge that solid cancers remotely disrupt liver homeostasis, it remains unexplored whether solid cancers affect liver zonation. Here, using spatial transcriptomics, we thoroughly investigate the abundance and zonation of hepatic genes in cancer-bearing mice. We find that breast cancers affect liver zonation in various distinct manners depending on biological pathways. Aspartate metabolism and triglyceride catabolic processes retain relatively intact zonation patterns, but the zonation of xenobiotic catabolic process genes exhibits a strong disruption. The acute phase response is induced in zonated manners. Furthermore, we demonstrate that breast cancers activate innate immune cells in particular neutrophils in distinct zonated manners, rather than in a uniform fashion within the liver. Collectively, breast cancers disorganize hepatic transcriptomes in zonated manners, thereby disrupting zonated functions of the liver