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  • 1
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    Online Resource
    A randomized, double‐blind, placebo‐controlled, phase 3 study of tivantinib in Japanese patients with MET‐high hepatocellular carcinoma
    Wiley ; 2020
    In:  Cancer Science Vol. 111, No. 10 ( 2020-10), p. 3759-3769
    Details
    In: Cancer Science, Wiley, Vol. 111, No. 10 ( 2020-10), p. 3759-3769
    Abstract: A previous randomized phase 2 study of hepatocellular carcinoma revealed that the c‐Met inhibitor tivantinib as second‐line treatment significantly prolonged progression‐free survival in a subpopulation whose tumor samples highly expressed c‐Met (MET‐high). Accordingly, this phase 3 study was conducted to evaluate the efficacy of tivantinib as a second‐line treatment for Japanese patients with MET‐high hepatocellular carcinoma. This randomized, double‐blind, placebo‐controlled study was conducted at 60 centers in Japan. Hepatocellular carcinoma patients with one prior sorafenib treatment and those with MET‐high tumor samples were eligible for inclusion. Registered patients were randomly assigned to either the tivantinib or placebo group at a 2:1 ratio and were treated with twice‐a‐day oral tivantinib (120 mg bid) or placebo until the discontinuation criteria were met. The primary endpoint was progression‐free survival while the secondary endpoints included overall survival and safety. Between January 2014 and June 2016, 386 patients provided consent, and 195 patients were randomized to the tivantinib (n = 134) or placebo (n = 61) group. Median progression‐free survival was 2.8 (95% confidence interval: 2.7‐2.9) and 2.3 (1.5‐2.8) mo in the tivantinib and placebo groups, respectively (hazard ratio = 0.74, 95% confidence interval: 0.52‐1.04, P  = .082). Median overall survival was 10.3 (95% confidence interval: 8.1‐11.6) and 8.5 (6.2‐11.4) mo in the tivantinib and placebo group, respectively (hazard ratio = 0.82, 95% confidence interval: 0.58‐1.15). The most common tivantinib‐related grade ≥3 adverse events were neutropenia (31.6%), leukocytopenia (24.8%), and anemia (12.0%). This study did not confirm the significant efficacy of tivantinib as a second‐line treatment for Japanese patients with MET‐high hepatocellular carcinoma. (NCT02029157).
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    URL: Article
    DOI: 10.1111/cas.v111.10
    DOI: 10.1111/cas.14582
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2115647-5
    detail.hit.zdb_id: 2111204-6
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  • 2
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    Online Resource
    Dopamine modulates the optomotor response to unreliable visual stimuli in Drosophila melanogaster
    Wiley ; 2020
    In:  European Journal of Neuroscience Vol. 51, No. 3 ( 2020-02), p. 822-839
    Details
    In: European Journal of Neuroscience, Wiley, Vol. 51, No. 3 ( 2020-02), p. 822-839
    Abstract: State‐dependent modulation of sensory systems has been studied in many organisms and is possibly mediated through neuromodulators such as monoamine neurotransmitters. Among these, dopamine is involved in many aspects of animal behaviour, including movement control, attention, motivation and cognition. However, the precise neural mechanism underlying dopaminergic modulation of behaviour induced by sensory stimuli remains poorly understood. Here, we used Drosophila melanogaster to show that dopamine can modulate the optomotor response to moving visual stimuli including noise. The optomotor response is the head‐turning response to moving objects, which is observed in most sight‐reliant animals including mammals and insects. First, the effects of the dopamine system on the optomotor response were investigated in mutant flies deficient in dopamine receptors D1R1 or D1R2, which are involved in the modulation of sleep‐arousal in flies. We examined the optomotor response in D1R1 knockout (D1R1 KO) and D1R2 knockout (D1R2 KO) flies and found that it was not affected in D1R1 KO flies; however, it was significantly reduced in D1R2 KO flies compared with the wild type. Using cell‐type‐specific expression of an RNA interference construct of D1R2, we identified the fan‐shaped body, a part of the central complex, responsible for dopamine‐mediated modulation of the optomotor response. In particular, pontine cells in the fan‐shaped body seemed important in the modulation of the optomotor response, and their neural activity was required for the optomotor response. These results suggest a novel role of the central complex in the modulation of a behaviour based on the processing of sensory stimulations.
    Type of Medium: Online Resource
    ISSN: 0953-816X , 1460-9568
    URL: Issue
    URL: Article
    DOI: 10.1111/ejn.v51.3
    DOI: 10.1111/ejn.14648
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2005178-5
    SSG: 12
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  • 3
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    Online Resource
    Lipopolysaccharide preconditioning reduces liver metastasis of Colon26 cells by enhancing antitumor activity of natural killer cells and natural killer T cells in murine liver
    Wiley ; 2021
    In:  Journal of Gastroenterology and Hepatology Vol. 36, No. 7 ( 2021-07), p. 1889-1898
    Details
    In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 36, No. 7 ( 2021-07), p. 1889-1898
    Abstract: Lipopolysaccharide (LPS) preconditioning drastically augments bactericidal activity but reduces the host inflammatory response. Therefore, it may be beneficial to prevent postoperative infectious complications and mitigate host damage by surgical stress. Considering its clinical application, how LPS preconditioning influences the antitumor effect in the liver is an important issue. We then investigated the effect of LPS preconditioning on antitumor activity against Colon26 tumor cells in mice. Methods Lipopolysaccharide preconditioning was induced in mice by the intraperitoneal injection of 5 μg/kg LPS for three consecutive days. Intraportal inoculation of Colon26 cells, which express luminescent protein called Nano‐lantern, was performed to evaluate the effect of LPS preconditioning on tumor liver metastasis. The antitumor activities of cytotoxic liver lymphocytes, especially natural killer (NK) cells and natural killer T (NKT) cells, against Colon26 cells were also examined in LPS preconditioned mice. Results Lipopolysaccharide preconditioning remarkably prevented liver metastasis of Colon26 cells, as observed by IVIS imaging system, and prolonged survival after tumor inoculation. LPS preconditioning increased the proportions and number of liver NK cells and NKT cells and augmented their intracellular perforin and granzyme B expression, while reducing their intracellular expression of IFN‐γ. An in vitro antitumor cytotoxicity assay revealed that LPS preconditioning significantly augmented antitumor cytotoxicities of the liver NK cells and NKT cells, especially NKT cells, against Colon26 cells. Conclusions Lipopolysaccharide preconditioning potently augmented antitumor cytotoxicity of liver NK cells and NKT cells, thereby improving mouse survival after intraportal inoculation of Colon26 tumor cells. It may be useful for perioperative care in oncological patients.
    Type of Medium: Online Resource
    ISSN: 0815-9319 , 1440-1746
    URL: Issue
    URL: Article
    DOI: 10.1111/jgh.v36.7
    DOI: 10.1111/jgh.15375
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2006782-3
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  • 4
    Online Resource
    Online Resource
    Association of crossing capillaries in the finger nailfold with diabetic retinopathy in type 2 diabetes mellitus
    Wiley ; 2021
    In:  Journal of Diabetes Investigation Vol. 12, No. 6 ( 2021-06), p. 1007-1014
    Details
    In: Journal of Diabetes Investigation, Wiley, Vol. 12, No. 6 ( 2021-06), p. 1007-1014
    Abstract: Crossing capillaries in the finger nailfold might potentially be a novel diabetic retinopathy (DR) biomarker that could be assessed non‐invasively in the clinical setting. However, the association between crossing capillaries and DR is controversial. This study aimed to investigate the association between the percentage of crossing capillaries in the finger nailfold and DR in patients with type 2 diabetes mellitus. Materials and Methods This cross‐sectional study enrolled 108 type 2 diabetes mellitus patients (aged 40–75 years) who visited the outpatient diabetic clinic at Osaka University Hospital, Osaka, Japan, between May and October 2019. Capillary morphology was assessed using nailfold capillaroscopy based on the simple capillaroscopic definitions of the European League Against Rheumatism Study Group. Details of DR and other laboratory data were obtained from medical records. The association between the tertile of the percentage of the crossing capillary and DR was analyzed using multivariable logistic regression. Results After adjusting for age, sex, diabetes duration, glycated hemoglobin, systolic blood pressure, body mass index, and use of renin–angiotensin system inhibitor and antihyperlipidemic medication, the percentage of crossing capillaries was significantly associated with DR (multivariable‐adjusted odds ratios for increasing tertiles of the percentage of crossing capillary: 1 [reference], 2.05 [95% confidence interval 0.53–7.94] , and 4.33 [95% confidence interval 1.16–16.21]; P ‐trend = 0.028). Conclusions A higher percentage of crossing capillaries in the nailfold was associated with a higher risk of DR, independent of traditional risk and inhibiting factors, in patients with type 2 diabetes mellitus.
    Type of Medium: Online Resource
    ISSN: 2040-1116 , 2040-1124
    URL: Issue
    URL: Article
    DOI: 10.1111/jdi.v12.6
    DOI: 10.1111/jdi.13444
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2542077-X
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