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Article ; Online: Combined inhibition/silencing of diacylglycerol kinase α and ζ simultaneously and synergistically enhances interleukin-2 production in T cells and induces cell death of melanoma cells.

Takao, Saki / Akiyama, Rino / Sakane, Fumio

2021 Volume 122, Issue 5, Page(s) 494–506

Abstract: ... it promotes the nonresponsive immune state known as T-cell anergy. Moreover, a DGKα-selective inhibitor, CU-3 ... induced cell death in cancer-derived cells and simultaneously enhanced T-cell interleukin-2 production ... In addition to DGKα, DGKζ is also known to induce T-cell anergy. In the present study, we examined ...

Abstract	The α-isozyme of diacylglycerol kinase (DGK) enhances cancer cell proliferation and, conversely, it promotes the nonresponsive immune state known as T-cell anergy. Moreover, a DGKα-selective inhibitor, CU-3, induced cell death in cancer-derived cells and simultaneously enhanced T-cell interleukin-2 production. In addition to DGKα, DGKζ is also known to induce T-cell anergy. In the present study, we examined whether combined inhibition/silencing of DGKα and DGKζ synergistically enhanced T-cell activity. Combined treatment with CU-3 or DGKα-small interfering RNA (siRNA) and DGKζ-siRNA more potently enhanced T-cell receptor-crosslink-dependent interleukin-2 production in Jurkat T cells than treatment with either alone. Intriguingly, in addition to activating T cells, dual inhibition/silencing of DGKα and DGKζ synergistically reduced viability and increased caspase 3/7 activity in AKI melanoma cells. Taken together, these results indicate that combined inhibition/silencing of DGKα and DGKζ simultaneously and synergistically enhances interleukin-2 production in T cells and induces cell death in melanoma. Therefore, dual inhibition/silencing of these DGK isozymes represents an ideal therapy that potently attenuates cancer cell proliferation and simultaneously enhances immune responses that impact anticancer immunity.
MeSH term(s)	Apoptosis/physiology ; Blotting, Western ; Cell Death/physiology ; Cell Line ; Cell Survival/physiology ; Diacylglycerol Kinase/genetics ; Diacylglycerol Kinase/metabolism ; Humans ; Interleukin-2/metabolism ; Jurkat Cells/metabolism ; RNA Interference ; T-Lymphocytes/metabolism
Chemical Substances	Interleukin-2 ; Diacylglycerol Kinase (EC 2.7.1.107)
Language	English
Publishing date	2021-01-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	392402-6
ISSN	1097-4644 ; 0730-2312
ISSN (online)	1097-4644
ISSN	0730-2312
DOI	10.1002/jcb.29876
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Article ; Online: Persistent Hypoplastic Acute Promyelocytic Leukemia with a Novel Chromosomal Abnormality of 46, XY, t(15;17), t(9;11)(q13;p13).

Yamamoto, Kazuyo / Kodaka, Taiichi / Maruoka, Hayato / Sakane, Emiko / Tsunemine, Hiroko / Itoh, Kiminari / Akasaka, Hiroshi / Takahashi, Takayuki

Journal of clinical and experimental hematopathology : JCEH

2015 Volume 55, Issue 2, Page(s) 71–76

Abstract: ... 46, XY, t(15;17)(q22;q12), t(9;11)(q13;p13). Two months later, the BM remained hypoplastic with 8.5 ... a negative result regarding t(15;17), although RT-PCR was positive for PML-RARα mRNA. Six months later, APL ... of pneumonia. A persistent hypoplastic state of APL may be a rare event, and the association of t(15;17) and t ...

Abstract	A diagnosis of acute promyelocytic leukemia (APL) is usually made when normal hematopoietic cells are substituted by APL cells. We encountered a unique APL patient who presented with persistent hypoplastic features of APL. An 84-year-old man presented with leukopenia (2.2 × 10(9)/L) and anemia (Hb 12.5 g/dL). Five months later, the bone marrow (BM) was hypoplastic with a normal proportion of blasts and promyelocytes (5.2%), although the latter cells were hypergranular. The karyotype of BM cells was 46, XY, t(15;17)(q22;q12), t(9;11)(q13;p13). Two months later, the BM remained hypoplastic with 8.5% hypergranular promyelocytes, some of which contained faggot of Auer rods. RT-PCR examination yielded the PML-RARα transcript, and its sequencing revealed the breakpoint of PML to be bcr2. The patient was treated with all-trans retinoic acid under a diagnosis of APL with improvement of the bicytopenia. FISH analysis of BM cells yielded a negative result regarding t(15;17), although RT-PCR was positive for PML-RARα mRNA. Six months later, APL recurred with the same karyotypic abnormalities and therapeutic resistance, and the patient died of pneumonia. A persistent hypoplastic state of APL may be a rare event, and the association of t(15;17) and t(9;11) is novel.
MeSH term(s)	Aged, 80 and over ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Chromosomes, Human/genetics ; Chromosomes, Human/metabolism ; Fatal Outcome ; Humans ; Leukemia, Promyelocytic, Acute/genetics ; Leukemia, Promyelocytic, Acute/metabolism ; Leukemia, Promyelocytic, Acute/pathology ; Leukemia, Promyelocytic, Acute/therapy ; Male ; Oncogene Proteins, Fusion/biosynthesis ; Oncogene Proteins, Fusion/genetics ; Translocation, Genetic
Chemical Substances	Oncogene Proteins, Fusion ; promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
Language	English
Publishing date	2015-10-22
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	2395568-5
ISSN	1880-9952 ; 1346-4280
ISSN (online)	1880-9952
ISSN	1346-4280
DOI	10.3960/jslrt.55.71
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Article ; Online: Palmitic acid- and/or palmitoleic acid-containing phosphatidic acids are generated by diacylglycerol kinase α in starved Jurkat T cells.

Murakami, Yuki / Murakami, Chiaki / Hoshino, Fumi / Lu, Qiang / Akiyama, Rino / Yamaki, Atsumi / Takahashi, Daisuke / Sakane, Fumio

Biochemical and biophysical research communications

2020 Volume 525, Issue 4, Page(s) 1054–1060

Abstract: ... cells whereas, in contrast, DGKα induces a nonproliferative state in T cells. We previously found ... the PA species generated by DGKα in T cells under serum-starved (nonproliferative) conditions. We found ... 18:1/18:2-, 18:1/18:1- and 18:0/18:1-PA, in Jurkat T cells. In lysates from serum-starved Jurkat ...

Abstract	Diacylglycerol kinase (DGK) α enhances the proliferation of melanoma and hepatocellular carcinoma cells whereas, in contrast, DGKα induces a nonproliferative state in T cells. We previously found that DGKα produces palmitic acid (16:0)-containing PA species, such as 16:0/16:0- and 16:0/18:0-PA, in melanoma cells under serum-starved (nonproliferative) conditions. In the present study, we identified the PA species generated by DGKα in T cells under serum-starved (nonproliferative) conditions. We found that serum starvation markedly increased the levels of many PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:1/18:2-, 16:1/18:1-, 16:0/18:1-, 16:0/18:0-, 18:1/18:2-, 18:1/18:1- and 18:0/18:1-PA, in Jurkat T cells. In lysates from serum-starved Jurkat T cells, DGKα activity, which was Ca
MeSH term(s)	Calcium/metabolism ; Cell Proliferation ; Chromatography, Liquid ; Diacylglycerol Kinase/antagonists & inhibitors ; Diacylglycerol Kinase/metabolism ; Fatty Acids, Monounsaturated/chemistry ; Fatty Acids, Monounsaturated/metabolism ; Humans ; Jurkat Cells ; Melanoma/chemistry ; Melanoma/enzymology ; Melanoma/metabolism ; Palmitic Acid/chemistry ; Palmitic Acid/metabolism ; Phosphatidic Acids/chemistry ; Phosphatidic Acids/metabolism ; Rhodanine/analogs & derivatives ; Rhodanine/pharmacology ; Sulfonamides/pharmacology ; T-Lymphocytes/chemistry ; T-Lymphocytes/drug effects ; T-Lymphocytes/enzymology ; T-Lymphocytes/metabolism ; Tandem Mass Spectrometry
Chemical Substances	5-(3-(2-furyl)prop-2-enylidene)-3-((phenylsulfonyl)amino)-2-thioxo-1,3-thiazolidin-4-one ; Fatty Acids, Monounsaturated ; Phosphatidic Acids ; Sulfonamides ; palmitoleic acid (209B6YPZ4I) ; Palmitic Acid (2V16EO95H1) ; Rhodanine (7O50LKL2G8) ; Diacylglycerol Kinase (EC 2.7.1.107) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.02.162
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Article: Palmitic acid- and/or palmitoleic acid-containing phosphatidic acids are generated by diacylglycerol kinase α in starved Jurkat T cells

Murakami, Yuki / Murakami, Chiaki / Hoshino, Fumi / Lu, Qiang / Akiyama, Rino / Yamaki, Atsumi / Takahashi, Daisuke / Sakane, Fumio

Biochemical and biophysical research communications. 2020 May 14, v. 525, no. 4

2020

Abstract	Diacylglycerol kinase (DGK) α enhances the proliferation of melanoma and hepatocellular carcinoma cells whereas, in contrast, DGKα induces a nonproliferative state in T cells. We previously found that DGKα produces palmitic acid (16:0)-containing PA species, such as 16:0/16:0- and 16:0/18:0-PA, in melanoma cells under serum-starved (nonproliferative) conditions. In the present study, we identified the PA species generated by DGKα in T cells under serum-starved (nonproliferative) conditions. We found that serum starvation markedly increased the levels of many PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:1/18:2-, 16:1/18:1-, 16:0/18:1-, 16:0/18:0-, 18:1/18:2-, 18:1/18:1- and 18:0/18:1-PA, in Jurkat T cells. In lysates from serum-starved Jurkat T cells, DGKα activity, which was Ca²⁺-dependent and sensitive to a DGKα-specific inhibitor (CU-3), was substantially increased, indicating its activation. Moreover, CU-3 (1–10 μM) significantly reduced the amounts of palmitic acid- and/or palmitoleic acid (16:1)-containing PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:0/18:1- and 16:0/18:0-PA, which were increased by serum starvation. These results indicate that DGKα generates different PA species in starved melanoma cells (palmitic acid-containing PA species) and T cells (palmitic acid- and/or palmitoleic acid (16:1)-containing PA species). Therefore, the differences in the PA molecular species may account for the opposing functions of DGKα in melanoma and T cells.
Keywords	blood serum ; diacylglycerol kinase ; hepatoma ; melanoma ; palmitic acid ; palmitoleic acid ; research ; starvation
Language	English
Dates of publication	2020-0514
Size	p. 1054-1060.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2020.02.162
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Article: [Alleviation of palmoplantar pustulosis associated with adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation].

Akasaka, Hiroshi / Imaizumi, Kisako / Sakane, Emiko / Tsunemine, Hiroko / Ito, Kiminari / Kodaka, Taiichi / Matsumoto, Mayumi / Matsuoka, Masao / Takahashi, Takayuki

Rinsho ketsueki] The Japanese journal of clinical hematology

2012 Volume 53, Issue 8, Page(s) 779–784

Abstract: ... A diagnosis of acute type adult T cell leukemia/lymphoma (ATLL) was made based on generalized lymph node ...

Abstract	A 68-year-old female with palmoplantar pustulosis was referred to our hospital in July, 2009 because of liver dysfunction, a positive test for HTLV-1, and circulating abnormal lymphocytes with irregularly shaped nuclei. A diagnosis of acute type adult T cell leukemia/lymphoma (ATLL) was made based on generalized lymph node swelling and high levels of serum LDH, in addition to the findings described above. The associated palmoplantar pustulosis responded to some extent to antibiotics, steroid ointment, and narrow band UBV light irradiation. For ATLL, she was serially treated with CHOP chemotherapy, an LSG 15 protocol, and CytaBOM protocol with consequent partial remission. These chemotherapies did not affect the palmoplantar pustulosis. For ATLL in partial remission, we performed allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from a related donor (HTLV-1-negative) with a conditioning regimen consisting of fludarabine, melphalan, and total body irradiation with 3 Gy in February, 2010. After the engraftment of donor hematopoietic cells, ATLL cells disappeared and the patient currently (as of April, 2012) remains in complete remission (CR). The residual palmoplantar pustulosis was further improved soon after allo-PBSCT and disappeared on Day 84 after transplantation. This refractory skin disease has also been in CR to date.
MeSH term(s)	Aged ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia-Lymphoma, Adult T-Cell/complications ; Leukemia-Lymphoma, Adult T-Cell/therapy ; Psoriasis/etiology ; Psoriasis/therapy ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome
Language	Japanese
Publishing date	2012-08
Publishing country	Japan
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
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Article ; Online: Polymyositis as a paraneoplastic syndrome in cytotoxic molecule-positive and Epstein-Barr virus-associated peripheral T-cell lymphoma, not otherwise specified.

Tsunemine, Hiroko / Maruoka, Hayato / Akasaka, Hiroshi / Udaka, Kengo / Yamamoto, Kazuyo / Ishikawa Sakane, Emiko / Hiramoto, Nobuhiro / Ito, Kiminari / Kodaka, Taiichi / Itoh, Tomoo / Takahashi, Takayuki

Internal medicine (Tokyo, Japan)

2013 Volume 52, Issue 8, Page(s) 901–905

Abstract: ... peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which was clinically preceded by polymyositis ...

Abstract	We encountered a rare case of cytotoxic molecule-positive and Epstein-Barr virus (EBV)-associated peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which was clinically preceded by polymyositis. A 50-year-old woman with a 4-year history of steroid-refractory polymyositis developed ulcerative skin swelling on her left arm. A diagnosis of cytotoxic molecule (TIA-1)-positive and EBV-associated PTCL-NOS was made on the basis of immunohistochemical and molecular examinations of the biopsied brachial muscle. Combination chemotherapies were ineffective, with a fatal outcome. Reassessment of the biopsy specimens of the muscle taken at the age of 46 years showed that the PTCL was already present, indicating that the polymyositis was likely a paraneoplastic manifestation.
MeSH term(s)	Cytotoxicity Tests, Immunologic/methods ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/diagnosis ; Epstein-Barr Virus Infections/immunology ; Female ; Humans ; Lymphoma, T-Cell, Peripheral/complications ; Lymphoma, T-Cell, Peripheral/diagnosis ; Lymphoma, T-Cell, Peripheral/virology ; Middle Aged ; Paraneoplastic Syndromes/complications ; Paraneoplastic Syndromes/diagnosis ; Paraneoplastic Syndromes/virology ; Polymyositis/complications ; Polymyositis/diagnosis ; Polymyositis/virology
Language	English
Publishing date	2013-04-15
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.52.8519
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Article ; Online: Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to beta-3 adrenergic receptor gene polymorphism Trp64Arg(C/T): Results from the Japan Diabetes Prevention Program.

Sakane, Naoki / Sato, Juichi / Tsushita, Kazuyo / Tsujii, Satoru / Kotani, Kazuhiko / Tominaga, Makoto / Kawazu, Shoji / Sato, Yuzo / Usui, Takeshi / Kamae, Isao / Yoshida, Toshihide / Kiyohara, Yutaka / Sato, Shigeaki / Tsuzaki, Kokoro / Takahashi, Kaoru / Kuzuya, Hideshi

Journal of diabetes investigation

2015 Volume 7, Issue 3, Page(s) 338–342

Abstract: The beta-3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention ... ...

Abstract	The beta-3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance. Data were analyzed from 112 patients with impaired glucose tolerance in the Japan Diabetes Prevention Program, a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group or usual care group. Changes in weight and metabolic parameters were measured after the 6-month intervention. The ADRB3 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. Non-carriers showed a greater weight reduction compared with the carriers in both the lifestyle intervention group and usual care group, and a greater increase of high-density lipoprotein cholesterol levels than the carriers only in the lifestyle intervention group. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance patients.
MeSH term(s)	Adult ; Body Weight ; Diabetes Mellitus/prevention & control ; Diet, Reducing ; Energy Metabolism ; Exercise Therapy ; Female ; Glucose Intolerance/genetics ; Glucose Intolerance/metabolism ; Glucose Intolerance/prevention & control ; Humans ; Japan ; Leisure Activities ; Life Style ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-3/genetics ; Treatment Outcome
Chemical Substances	Receptors, Adrenergic, beta-3
Language	English
Publishing date	2015-10-29
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2625840-7
ISSN	2040-1124 ; 2040-1116
ISSN (online)	2040-1124
ISSN	2040-1116
DOI	10.1111/jdi.12426
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Book ; Online: Diacylglycerol Kinase Signalling

Sakane, Fumio / Graziani, Andrea / Merida, Isabel

2017

Abstract: ... by the presence of particular regulatory motifs.- ...

Abstract	Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DG), catalyzing its conversion into phosphatidic acid (PA). This reaction attenuates membrane DG levels, limiting the localization/activation of signaling proteins that bind this lipid. Initially recognized as modulators of classical and novel PKC family members, the function of the DGK has further expanded with the identification of novel DG effectors including Ras Guanyl nucleotide-releasing proteins (RasGRP) and chimaerin Rac GTPases. The product of the DGK reaction, PA, is also a signaling lipid that mediates activation of multiple proteins including the mammalian target of rapamycin (mTOR). The DGK pathway thus modulates two lipids with important signaling properties that are also key intermediates in lipid metabolism and membrane trafficking. The DGK family in eukaryotes comprises 10 different members grouped into five different subfamilies characterized by the presence of particular regulatory motifs.- These regions allow the different DGK isoforms to establish specific complexes and/or to be recruited to specific subcellular compartments. The subtle regulation of DG and PA catalyzed byspecific DGKs is sensed by a restricted set of molecules, providing the means for spatio-temporal regulation of signals in highly specialized cell systems.In the recent years, multiple studies have unveiled the functions of specific isoforms, their mechanisms of regulation and their participation in different pathways leading to and from DG and PA. Animal models have greatly helped to understand the specialized contribution of DGK mediated signals, particularly in the immune and central nervous systems. Mice deficient for individual DGK isoforms show defects in T and B cell functions, dendritic spine maintenance, osteoclast and mechanical-induced skeletal muscle formation. Studies in flies and worms link DGK mediated DAG metabolism with mTOR- mediated regulation of lifespan and stress responses.- In plants DGK mediated PA formation contributes to plant responses to environmental signals.Aberrant DGK function has been recently associated with pathological states, an expected consequence of the essential role of these enzymes in the regulation of multiple tissue and systemic functions. DGK mutations/deletions have been related to human diseases including diabetes, atypical hemolytic-uremic syndrome, Parkinson disease and bipolar disorders. On the contrary DGK upregulation emerges as a non-oncogenic addition of certain tumors and represents one of the main mechanism by which cancer evades the immune attack. As a result, the DGK field emerges an exciting new area of research with important therapeutic potential
Keywords	Science (General) ; Biology (General)
Size	1 electronic resource (96 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020097466
ISBN	9782889453351 ; 2889453359
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article: Diacylglycerol kinase-dependent formation of phosphatidic acid molecular species during interleukin-2 activation in CTLL-2 T-lymphocytes.

Mizuno, Satoru / Sakai, Hiromichi / Saito, Masafumi / Kado, Sayaka / Sakane, Fumio

FEBS open bio

2012 Volume 2, Page(s) 267–272

Abstract: ... developed LC/MS method, we showed that stimulation of CTLL-2 murine T-lymphocytes by interleukin-2 (IL-2 ...

Abstract	Although effective liquid chromatography (LC)/mass spectrometry (MS) methods enabling the separation of phospholipid molecular species have been developed, there are still problems with an intracellular signaling molecule, phosphatidic acid (PA). In this study, we optimized LC/MS conditions to improve the quantitative detection of PA molecular species from a cellular lipid mixture. Using the newly developed LC/MS method, we showed that stimulation of CTLL-2 murine T-lymphocytes by interleukin-2 (IL-2) induced a significant increase of 36:1-, 36:2-, 40:5- and 40:6-diacyl-PA. A diacylglycerol kinase (DGK) inhibitor, R59949, attenuated the increase of 36:1-, 40:5-, 40:6-diacyl-PA, suggesting that DGK IL-2-dependently and selectively generated these diacyl-PA species.
Language	English
Publishing date	2012-09-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1016/j.fob.2012.08.006
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Article ; Online: Development of an in silico evaluation system that quantitatively predicts skin sensitization using OECD Guideline No. 497 ITSv2 defined approach for skin sensitization classification.

Asai, Takaho / Umeshita, Kazuhiko / Sakurai, Michiko / Sakane, Shinji

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2024 Volume 185, Page(s) 114444

Abstract: The Integrated Testing Strategy version 2 (ITSv2) Defined Approach, which is a reliable skin sensitization hazard and multi-step risk assessment method, does not support quantitative risk assessment such as local lymph node assay EC3 values. In this ... ...

Abstract	The Integrated Testing Strategy version 2 (ITSv2) Defined Approach, which is a reliable skin sensitization hazard and multi-step risk assessment method, does not support quantitative risk assessment such as local lymph node assay EC3 values. In this study, we developed a high-performance in silico evaluation system that quantitatively predicts the EC3 values of chemical substances by combining the ITSv2 Defined Approach for hazard identification (ITSv2 HI) with machine learning models. This system uses in chemico/in vitro test data, molecular descriptors, and distance information based on read-across concepts as explanatory variables. The system achieves an R
MeSH term(s)	Humans ; Animals ; Dermatitis, Allergic Contact ; Organisation for Economic Co-Operation and Development ; Skin/metabolism ; Local Lymph Node Assay ; Risk Assessment/methods ; Animal Testing Alternatives/methods
Language	English
Publishing date	2024-01-20
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2024.114444
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