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Macrophage inhibitory cytokine-1 induced by a high-fat diet promotes prostate cancer progression by stimulating tumor-promoting cytokine production from tumor stromal cells

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Cancer Communications 2021年第5期41卷 389-403页

作者： Mingguo Huang Shintaro Narita Atsushi Koizumi Taketoshi Nara Kazuyuki Numakura shigeru satoh Hiroshi Nanjo Tomonori Habuchi Department of Urology Akita University Graduate School of Medicine1-1-1 HondoAkita 010-8543Japan Department of Clinical Pathology Akita University Graduate School of Medicine1-1-1 HondoAkita 010-8543Japan

Background:Recent studies have indicated that a high-fat diet(HFD)and/or HFD-induced obesity may influence prostate cancer(PCa)progression,but the role of HFD in PCa microenvironment is *** study aimed to delineate the molecular mechanisms of PCa progression underHFDmilieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine-1(MIC-1)***:We investigated the effects of HFD on PCa stromal microenvironment and MIC-1 signaling activation using PC-3M-luc-C6 PCa model mice fed with HFD or control ***,we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal *** patterns and roles of MIC-1 signaling on human PCa stroma activation and progression were also ***:HFD stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequently increased the secretion of interleukin(IL)-8 and IL-6 from prostate stromal fibroblasts in PC-3M-luc-C6 PCa *** addition,periprostatic adipocytes directly stimulatedMIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid *** increased serum MIC-1 was significantly correlated with human PCa stroma activation,high serum IL-8,IL-6,and lipase activity,advanced PCa progression,and high body mass index of the ***-derived neurotrophic factor receptor α-like(GFRAL),a specific receptor of MIC-1,was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts,and the expression levelwas decreased by androgen deprivation therapy and ***:HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity-induced PCa progression.

关键词： macrophage inhibitory cytokine-1 tumor microenvironment high-fat diet prostate cancer metabolism

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Outcome of Combination Chemotherapy with Docetaxel, Estramustine Phosphate, and Carboplatin after Docetaxel and Prednisolone Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer

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Journal of Cancer Therapy 2016年第7期7卷 471-479页

作者： Ryuichi Ito Shintaro Narita Hiroshi Tsuruta Kazuyuki Numakura Atsushi Maeno Mitsuru Saito Takamitsu Inoue Norihiko Tsuchiya shigeru satoh Tomonori Habuchi Department of Urology Akita University School of Medicine Akita Japan

We retrospectively reviewed the outcome of docetaxel, EMP, and carboplatin (DEC) as second-line chemotherapy in castration-resistant prostate cancer (CRPC) patients previously treated with docetaxel-prednisolone (DP). Nineteen patients pretreated with DP received a DEC regimen which consisted of a 28-day cycle of docetaxel [60 mg/m2 intravenously (IV) on day 1)], carboplatin (IV to an area under the curve of 5 on day 1), and EMP (560 mg orally daily). The DEC therapy was continued intermittently after two consecutive courses. End points were DEC effect on prostate-specific antigen (PSA), radiographic response, progression-free survival (PFS), and overall survival (OS). All patients received DP before DEC administration with a median of 6 cycles (range, 1 - 12). Mean follow-up duration was 19.0 months after starting DEC therapy;median total number of the therapy cycles was 2 (range, 1 - 11). Thirteen patients (68.4%) showed a PSA decrease;6 (31.6%) showed a decrease in the PSA level of ≥50%, including 4 with no PSA response to DP. Grade 3/4 neutropenia and febrile neutropenia were observed in 13 (68.4%) and 2 (10.5%) patients, respectively. The median PFS following DEC was 3.7 months. The median OS was 18.0 months. In univariate analyses, patients with ≤12 months from CRPC to DEC had shorter PFS and OS, whereas PSA response to DP was not associated with PFS or OS in CRPC patients treated with DEC after DP. In conclusion, DEC retains some clinical benefits for CRPC patients pretreated with DP, even in patients without any response to DP. Therefore, they may be an effective and feasible treatment option for CRPC patients after first-line docetaxel therapy, particularly for those deemed unfit for novel endocrine and chemotherapeutic drugs.

关键词： Chemotherapy Carboplatin Docetaxel Estramustine Phosphate Prostate Cancer

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高脂饮食诱导的巨噬细胞抑制因子-1通过激活肿瘤间质细胞产生促肿瘤细胞因子促进前列腺癌的进展

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癌症 2022年第2期41卷 65-79页

背景与目的最近研究表明高脂饮食(high-fat diet,HFD)和/或HFD诱导的肥胖可影响前列腺癌(prostate cancer,PCa)的进展,但HFD在PCa微环境中的作用尚不清楚。本研究旨在阐明HFD环境下PCa进展的分子机制,描述以巨噬细胞抑制因子-1(macroph... 详细信息

背景与目的最近研究表明高脂饮食(high-fat diet,HFD)和/或HFD诱导的肥胖可影响前列腺癌(prostate cancer,PCa)的进展,但HFD在PCa微环境中的作用尚不清楚。本研究旨在阐明HFD环境下PCa进展的分子机制,描述以巨噬细胞抑制因子-1(macrophage inhibitory cytokine-1,MIC-1)活性为主的肿瘤间质微环境的特征。方法我们利用HFD或正常饮食的PC-3M-luc-C6 PCa小鼠模型,研究了HFD对PCa间质微环境和MIC-1信号活性的影响。我们分离了原发PCa患者来源的前列腺周围脂肪细胞,并研究了其对前列腺间质成纤维细胞活性及其分泌细胞因子的影响。进一步研究了MIC-1信号的表达模式及其对人PCa间质活性和肿瘤进展的影响。结果在PC-3M-luc-C6 PCa小鼠模型中,HFD通过上调前列腺间质成纤维的MIC-1信号通路活性,增加了白介素(interleukin,IL)-8和IL-6的分泌,促进了PCa细胞的生长和侵袭。另外,前列腺周围脂肪细胞通过增加脂肪分解和游离脂肪酸的释放,直接促进了PC-3细胞产生MIC-1和前列腺间质成纤维细胞分泌IL-8。前列腺癌患者血清MIC-1水平增高与人PCa间质活性、高血清IL-8、IL-6水平、脂肪酶高活性、PCa患者疾病进展及高体重指数具有显著相关性。胶质细胞源性神经营养因子受体α(glial-derived neurotrophic factor receptor α-like,GFL)是MIC-1的特异性受体,在PCa细胞和癌周间质成纤维细胞中都出现高表达,雄激素去势治疗和化疗都降低了其表达水平。结论 HFD通过增加游离脂肪酸水平,在代谢水平上调了MIC-1信号活性,从而激活了PCa间质微环境,这可能是HFD和/或脂肪诱导的PCa进展的关键机制。

关键词：巨噬细胞抑制因子-1 肿瘤微环境高脂饮食前列腺癌代谢

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Alkali Treatment of Commercial Silicoaluminophosphate Molecular Sieves (SAPO<sub>-</sub>34) Enhances the Water Adsorption and Desorption Properties

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Journal of Encapsulation and Adsorption Sciences 2019年第4期9卷 149-158页

作者： Masahiro Katoh Kota Horiuchi Ayaka satoh Kota Aoyagi shigeru Sugiyama Department of Applied Chemistry Graduate School of Technology Industrial and Social Sciences Tokushima University Tokushima Japan Department of Chemical Science and Technology Tokushima University Tokushima Japan

Commercial silicoaluminophosphate molecular sieves (SAPO-34) received alkali treatment with either NaOH (0.2, 0.01, 0.005, or 0.001 M) or NH4OH (0.005 M). Treatment with NaOH (0.005 M) increased the water adsorption initial rate of SAPO-34 by 1.4-fold. The alkali treatment introduced Na+ adsorption sites into the SAPO-34. The desorption ratio (adsorption at 30°C and desorption at 100°C) was 88.2% higher than the original rate (84.3%). On the other hand, after alkali treatment of SAPO-34 using NH4OH (0.005 M), calcination resulted in the highest desorption ratio at 91.3%. When combined with calcination, alkali treatment with NH4OH introduced H+adsorption sites into SAPO-34, H+ adsorption sites feature low levels of interaction with water, which enhanced the desorption ratio, but decreased the initial adsorption rate. These results indicate that treating commercial SAPO-34 with 0.005 M NaOH enhances both the adsorption and desorption behaviors.

关键词： Alkali Treatment Silicoaluminophosphate Molecular Sieves Water Adsorption Desorption

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Change in Filler Network and Nonlinear Viscoelasticity of Rubbers

Change in Filler Network and Nonlinear Viscoelasticity of Ru...

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The 4th Pacific Rim Conference on Rheology

作者： Youji satoh shigeru Kagami Sheiichi Kawahara Yoshinobu Isono Department of Chemistry Nagaoka University of Technology 1603-1 Kamitomioka Nagaoka Niigata 940-2188 Japan The Yokohama Rubber Co. Ltd Hiratsuka Kanagawa 254-8601 Japan Department of Chemistry Nagaoka University of Technology 1603-1 Kamitomioka Nagaoka Niigata 940-2188 Japan Department of Chemistry Nagaoka University of Technology 1603-1 Kamitomioka Nagaoka Niigata 940-2188 Japan

＜正＞ Uncured, filled rubbers show remarkable nonlinear viscoelasticity as well as cured, filled rubbers. The nonlinearity may come from change in entanglement and filler network structures. Many people use dynamic modulus to characterize rubber materials. However, dynamic modulus cannot be defined at large strain amplitude. Hence we must study a viscoelastic function to be defined at large strain. In addition, we need another information to separate the effects of the change in entanglement and filler network structures on nonlinear viscoelasticity. In this work, we have measured relaxation modulus G（γ,t） and electrical resistivity p（γ,t） simultaneously for carbon black （CB）-filled, uncured SBRs in a wide range of strain. Electrical resistivity at equilibrium, p（0,t）, showed step-off like change at the threshold of CB loading based on particle size. The threshold of N330 CB exists between 20 and 35phr, indicating threshold for filler network formation should exist in the range of values in CB loading. Both G（γ,t） and p（γ,t） for the samples having CB loading to be higher than the threshold showed nonlinearity at the strain larger than shear strain γ=0.1, indicating rupture in filler network at large strain. The threshold shifted to lower CB content for fine CB（N220）, and no threshold was observed for coarse CB（N660） in the range measured from 20 to 50phr, indicating that the threshold depends on primary particle size. Moreover it has been found that filler network structures rupture easily when the CB content close to the threshold. Furthermore, recovery rate in filler network has been found to be very slow in comparison with that in entanglement structure.

关键词： uncured styrene-butadiene rubber filler-network nonlinear viscoelasticity electrical resistivity.

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