Temporal–spatial variations in Late Cenozoic volcanic activity in the Chugoku area, southwest Japan, have been examined based on 108 newly obtained K–Ar ages. Lava samples were collected from eight Quaternary volcanic provinces (Daisen, Hiruzen, Yokota, Daikonjima, Sambe, Ooe–Takayama, Abu and Oki) and a Tertiary volcanic cluster (Kibi Province) to cover almost all geological units in the province. Including published age data, a total of 442 Cenozoic radiometric ages are now available. Across‐arc volcanic activity in an area approximately 500 km long and 150 km wide can be examined over 26 million years. The period corresponds to syn‐ and post‐back‐arc basin opening stages of the island arc. Volcanic activity began in the central part of the rear‐arc ca 26 Ma. This was followed by arc‐wide expansion at 20 Ma by eruption at two rear‐arc centers located at the eastern and western ends. Expansion to the fore‐arc occurred between 20 and 12 Ma. This Tertiary volcanic arc was maintained until 4 Ma with predominant alkali basalt centers. The foremost‐arc zone activity ceased at 4 Ma, followed by quiescence over the whole arc between 4 and 3 Ma. Volcanic activity resumed at 3 Ma, covering the entire rear‐arc area, and continued until the present to form a Quaternary volcanic arc. Adakitic dacite first occurred at 1.7 Ma in the middle of the arc, and spread out in the center part of the Quaternary volcanic arc. Alkali basalt activities ceased in the area where adakite volcanism occurred. Fore‐arc expansion of the volcanic arc could be related to the upwelling and expansion of the asthenosphere, which caused opening of the Japan Sea. Narrowing of the volcanic zone could have been caused by progressive Philippine Sea Plate subduction. Deeper penetration could have caused melting of the slab and resulted in adakites. Volcanic history in the Late Cenozoic was probably controlled by the history of evolution of the upper mantle structure, coinciding with back‐arc basin opening and subsequent reinitiation of subduction.
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a mAb conjugated to a photo-absorber dye, IR700DX, activated by NIR light. Although CD44 is a surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor types. Meanwhile, CD25targeted NIR-PIT has been reported to achieve selective and local depletion of FOXP3 þ CD25 þ CD4 þ regulatory T cells (Treg), which are primary immunosuppressive cells in the tumor microenvironment (TME), resulting in activation of local antitumor immunity. Combined NIR-PIT with CD44-and CD25-targeted agents has the potential to directly eliminate tumor cells and also amplify the immune response by removingTregs from the TME. We investigated the difference in therapeutic effects of CD44-targeted NIR-PIT alone, CD25-targeted NIR-PIT alone, and the combination of CD44-and CD25-targeted NIR-PIT in several syngeneic tumor models, including MC38-luc, LL/2, and MOC1. The combined NIR-PIT showed significant tumor growth inhibition and prolonged survival compared with CD44-targeted NIR-PIT alone in all tumor models and showed prolonged survival compared with CD25-targeted NIR-PIT alone in MC38-luc and LL/2 tumors. Combined CD44-and CD25-targeted NIR-PIT also resulted in some complete remissions. Therefore, combined NIR-PIT simultaneously targeting cancer antigens and immunosuppressive cells in the TME may be more effective than either type of NIR-PIT alone and may have potential to induce prolonged immune responses in treated tumors.
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