Interleukin-34 cancels anti-tumor immunity by PARP inhibitor

Takayoshi Nakamura,Nabeel Kajihara,Naoki Hama,Takuto Kobayashi,Ryo Otsuka,Nanumi Han,Haruka Wada,Yoshinori Hasegawa,Nao Suzuki,Ken-ichiro Seino 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3

Objective: Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). Methods: In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. Results: We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. Conclusion: These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.

Effects of a vertical and horizontal console position on operator muscular stress during ultrasonic diagnosis

Hiroyuki Suzuki,Takayoshi Saito,Tetsuo Katsuura,Yoshihiro Shimomura 대한인간공학회 2014 대한인간공학회 학술대회논문집 Vol.2014 No.5

A diagnostic ultrasound system is an apparatus to aid in examination and diagnosis by displaying cross sectional images of body tissues, their movements, and blood flow produced based on the intensities and phases of reflected echoes. Most the operators operate the probe by the right hand and the operation panel by the left hand during ultra -sonic diagnosis in Japan.Ultrasound examinations tend to put sonographers in unnatural postures, which may lead to musculoskeletal disorders. In this study, we focused on the height and the horizontal positioning of the operation panel of the diagnostic ultra -sound system to quantitatively assess the influence of panel height (work plane height) and work plane position on musculoskeletal stress during scanning in a sitting position. Eight subjects (6 males and 2 females) were asked to perform a simulated scanning task that involved touching 9 points on the operation panel at 4 different panel heights. Five subjects (2 males and 3 females) were asked to perform a simulated scanning task that involved touching five points on the control panel, with the work plane set at different positions in space. Electromyograms of each part of the body and wrist joint angles indicated that the optimum height of the operation panel during scanning in a sitting position was elbow height, the least stressful position of the left hand was about 350 mm from the center of the trunk in the longitudinal (front–back) direction and 100 mm left of the center of the trunk in the lateral (right–left) direction. The height of the operation panel during scanning in a sitting position affects the stress on the forearm and shoulder. We indicated that the optimum height of the operation panel was elbow height. The longitudinal position of the control panel during scanning in a sitting position affected the stress in the left forearm and left lumbar regions. The lateral position of the control panel during scanning in a sitting position affected the stress in the left shoulder rgion.We indicated that the least stressful position of the left hand was these on the horizontal positioning of the operation panel.

Variance Component Estimates with Dominance Models for Milk Production in Holsteins of Japan Using Method R

Kawahara, Takayoshi,Gotoh, Yusaku,Yamaguchi, Satoshi,Suzuki, Mitsuyoshi Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.6

Fractions of herd-year-season, sire by herd interaction, additive genetic and dominance genetic variances were estimated for milk production traits in Holsteins of Japan using Method R. Inbreeding depressions for milk production traits were also estimated. Estimated fractions of herd-year-season variances ranged from 0.056 to 0.074 for yield traits and from 0.033 to 0.035 for content traits. Estimated fractions of additive genetic variances to phenotypic variances (heritabilities across a herd in the narrow sense) were 0.306, 0.287, 0.273, 0.255, 0.723, 0.697 and 0.663 for milk, fat, SNF and protein yields, and fat, SNF and protein contents, respectively. Estimated fractions of dominance genetic variances ranged from 0.019 to 0.022 for yield traits and from 0.014 to 0.018 for content traits. Fractions of variances for sire by herd interaction were estimated to range from 0.020 to 0.025 for yield traits and 0.011 to 0.012 for content traits. Estimates of inbreeding depression for milk, fat, SNF and protein yields were -36.16 kg, -1.42 kg, -3.24 kg and -1.15 kg per 1% inbreeding for milk, fat, SNF and protein yields, respectively. Estimates of depression per 1% inbreeding for content traits were positive at $0.39{\times}10^{-3}%$, $0.31{\times}10^{-3}%$ and $0.82{\times}10^{-3}%$ for fat, SNF and protein contents, respectively.

Effects of a Vertical and Horizontal Console Position on Operator Muscular Stress During Ultrasonic Diagnosis

( Hiroyuki Suzuki ),( Takayoshi Saito ),( Tetsuo Katsuura ),( Yoshihiro Shimomura ) 한국감성과학회 2014 춘계학술대회 Vol.2014 No.-

A diagnostic ultrasound system is an apparatus to aid in examination and diagnosis by displaying cross-sectional images of body tissues, their movements, and blood flow produced based on the intensities and phases of reflected echoes. Most the operators operate the probe by the right hand and the operation panel by the left hand during ultrasonic diagnosis in Japan. Ultrasound examinations tend to put sonographers in unnatural postures, which may lead to musculoskeletal disorders. In this study, we focused on the height and the horizontal positioning of the operation panel of the diagnostic ultrasound system to quantitatively assess the influence of panel height (work plane height) and work plane position on musculoskeletal stress during scanning in a sitting position. Eight subjects (6 males and 2 females) were asked to perform a simulated scanning task that involved touching 9 points on the operation panel at 4 different panel heights. Five subjects (2 males and 3 females) were asked to perform a simulated scanning task that involved touching fie points on the control panel, with the work plane set at different positions in space. Electromyograms of each part of the body and wrist joint angles indicated that the optimum height of the operation panel during scanning in a sitting position was elbow height, the least stressful position of the left hand was about 350 mm from the center of the trunk in the longitudinal (front-back) direction and 100 mm left of the center of the trunk in the lateral (right-left) direction.

Inhibition of plasminogen activator inhibitor-1 attenuates against intestinal fibrosis in mice

( Jin Imai ),( Takashi Yahata ),( Hitoshi Ichikawa ),( Abd Aziz Ibrahim ),( Masaki Yazawa ),( Hideaki Sumiyoshi ),( Yutaka Inagaki ),( Masashi Matsushima ),( Takayoshi Suzuki ),( Tetsuya Mine ),( Kiyo 대한장연구학회 2020 Intestinal Research Vol.18 No.2

Background/Aims: Intestinal fibrosis is a major complication of Crohn’s disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. Methods: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. Results: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. Conclusions: PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment. (Intest Res 2020;18:219-228)

Crystal Structure and Spectroscopic Properties of Cyclic Dipeptide: A Racemic Mixture of cyclo(ᴅ-Prolyl-ʟ-Tyrosyl) and cyclo(ʟ-Prolyl-ᴅ-Tyrosyl)

Hong, Yong Pyo,Lee, Sung-Hong,Choi, Jong-Ha,Kashima, Ayana,Nakamura, Go,Suzuki, Takayoshi Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.8

Two diastereoisomers of cyclo(Pro-Tyr) have been synthesized simultaneously. The crystal structures and conformations of both cyclo($\small{L}$-Pro-$\small{L}$-Tyr) and a racemic mixture of cyclo($\small{D}$-Pro-$\small{L}$-Tyr) and cyclo($\small{L}$-Pro-$\small{D}$-Tyr), abbreviated as rac-cyclo($\small{D}$-Pro-$\small{L}$-Tyr/$\small{L}$-Pro-$\small{D}$-Tyr), have been determined by a single-crystal X-ray diffraction study at low temperature. The crystals of rac-cyclo($\small{D}$-Pro-$\small{L}$-Tyr/$\small{L}$-Pro-$\small{D}$-Tyr) belong to orthorhombic space group $Pna2_1$ with a = 10.755 (1), b = 12.699 (1), c = 9.600 (1) ${\AA}$ and Z = 4. The tyrosine side chain is folded towards the diketopiperazine (DKP) ring. The DKP ring adopts a twist boat conformation with pseudo symmetry $C_{2v}$. The pyrrolidine ring has an envelope conformation with the N5, C4, C7 and C8 atoms in a plane. The crystal of rac-cyclo($\small{D}$-Pro-$\small{L}$-Tyr/$\small{L}$-Pro-$\small{D}$-Tyr) is stabilized by hydrogen bonds between amide N2-H2 and carbonyl oxygen O2 in the neighbor. The hydroxyl group of tyrosine residue is also hydrogen bonded to the oxygen of the carbonyl group of the DKP ring in the next molecule. The spectroscopic properties of both isomers are also described.