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  • 1
    In: ACTA HISTOCHEMICA ET CYTOCHEMICA, Japan Society of Histochemistry & Cytochemistry, Vol. 32, No. 6 ( 1999), p. 526-534
    Type of Medium: Online Resource
    ISSN: 0044-5991 , 1347-5800
    Language: English
    Publisher: Japan Society of Histochemistry & Cytochemistry
    Publication Date: 1999
    detail.hit.zdb_id: 2106630-9
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-10-5)
    Abstract: Background and Aims: This study aimed to investigate the safety and efficacy of lenvatinib in real-world settings, including patients excluded from the REFLECT trial. Methods: This multicenter, nonrandomized, open-label prospective study was conducted at 10 medical facilities in Japan (jRCTs031190017). Eligible patients had advanced HCC and were suitable for lenvatinib therapy. The study included patients with high tumor burden (with & gt;50% intrahepatic tumor volume, main portal vein invasion, or bile duct invasion), Child–Pugh B status, and receiving lenvatinib as second-line therapy following atezolizumab plus bevacizumab. Results: From Dec 2019 to Sep 2021, 59 patients were analyzed (47 and 12 patients with Child–Pugh A and B, respectively). In patients with Child–Pugh A, the frequency of aspartate aminotransferase elevation was high (72.7%) in high-burden group. No other significant adverse events (AEs) were observed even in second-line treatment. However, patients with Child–Pugh B had high incidence of grade ≥3 AEs (100.0%) and high discontinuation rates caused by AEs (33.3%) compared to patients with Child–Pugh A (80.9% and 17.0%, respectively). Median PFS was 6.4 and 2.5 months and median OS was 19.7 and 4.1 months in Child–Pugh A and B, respectively. Lenvatinib plasma concentration was higher in Child–Pugh B patients on days 8 and 15 and correlated with dose modifications and lower relative dose intensity. Conclusion: Lenvatinib is safe and effective for advanced HCC in patients with Child–Pugh A, even with high tumor burden. However, it carries a higher risk of AEs and may not provide adequate efficacy for patients with Child–Pugh B.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 3
    In: Gene, Elsevier BV, Vol. 237, No. 1 ( 1999-09), p. 53-60
    Type of Medium: Online Resource
    ISSN: 0378-1119
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 1999
    detail.hit.zdb_id: 1491012-3
    SSG: 12
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 3_suppl ( 2021-01-20), p. 317-317
    Abstract: 317 Background: There have been considerable advances in systemic chemotherapy for hepatocellular carcinoma (HCC) in recent times. Currently, four molecular target agents (MTA) are available for HCC treatment in Japan. Sequential therapy using multiple MTAs is being considered as the gold standard of treatment. However, the effectiveness of the treatment strategy transition for HCC remains unclear. The present study aimed to clarify the current practical use of MTAs and its effectiveness in HCC treatment. Methods: In this multicenter, retrospective study, we collected and analyzed the clinical data of 877 patients who underwent MTA therapy for HCC from June 2009 to March 2019 at several institutes in Japan. The patients were classified into 3 groups as per the period of initial MTA treatment beginning (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). These 3 periods were defined to have approximately same term. Period 3 means the era of multiple MTAs because of the approval of regorafenib in Japan in 2017. We assessed the patient characteristics, MTA use, and prognosis of the 3 groups. Results: The proportion of patients with advanced-stage HCC, defined according to the Barcelona Clinic Liver Cancer staging system, in each period was 70.1%, 66.5%, and 62.0% in period 1, 2, and 3, respectively. MTA use for intermediate stages increased with the passage of time ( p = 0.052). The proportion of multiple MTAs use was remarkably increased in the 3 groups (1.1%, 10.2%, and 42.6%, respectively, p 〈 0.0001). Child-Pugh score, proportion of macrovascular invasion, extrahepatic metastasis, and α-fetoprotein (AFP) ≥400 ng/mL showed no significant difference among the 3 groups. The median overall survival was 11.9 months for the entire cohort and 10.4, 11.3, and 15.2 months, for period 1, 2, and 3, respectively. It is noteworthy that the prognosis of patients with HCC improved over time ( p = 0.016). With respect to progression-free survival, the median value was 3.0 months for the entire cohort and 2.7, 2.8, and 4.7 months for period 1, 2, and 3, respectively ( p 〈 0.0001). The treatment duration was also prolonged with time (2.7, 3.2, and 6.6 months for period 1, 2, and 3, respectively; p 〈 0.0001). Multivariate analysis using Cox proportional hazard model showed that HCV infection, Child-Pugh score, performance status, α-fetoprotein ≥400 ng/mL, presence of macrovascular invasion, and period 3 for initial MTA introduction were independent prognostic factors. Conclusions: Sequential therapy with multiple MTAs has gained popularity with time and is considered to improve patient prognosis. The development of MTA therapy for HCC is expected to continue. Therefore, further studies are needed to help determine the appropriate drugs, the sequence of MTA use, and the precise transition time.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Liver Cancer, S. Karger AG, Vol. 11, No. 1 ( 2022), p. 48-60
    Abstract: 〈 b 〉 〈 i 〉 Background and Aims: 〈 /i 〉 〈 /b 〉 The prognosis of patients with advanced hepatocellular carcinoma (HCC) is expected to improve as multiple molecular target agents (MTAs) are now available. However, the impact of the availability of sequential MTAs has not been fully verified yet. 〈 b 〉 〈 i 〉 Approach and Results: 〈 /i 〉 〈 /b 〉 We retrospectively collected the data on the whole clinical course of 877 patients who received any MTAs as first-line systemic therapy for advanced HCC between June 2009 and March 2019. The study population was divided into 3 groups according to the date of first-line MTA administration (period 1: 2009–2012, 〈 i 〉 n 〈 /i 〉 = 267; period 2: 2013–2016, 〈 i 〉 n 〈 /i 〉 = 352; period 3: 2017–2019, 〈 i 〉 n 〈 /i 〉 = 258). Then, we compared the number of MTAs used, overall survival (OS), and MTA treatment duration among the 3 groups. Analysis was also performed separately for advanced-stage and nonadvanced-stage HCC. The proportion of patients who received multiple MTAs was remarkably increased over time (1.1%, 10.2%, and 42.6% in periods 1, 2, and 3, respectively, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). The median OS times were prolonged to 10.4, 11.3, and 15.2 months in periods 1, 2, and 3, respectively ( 〈 i 〉 p 〈 /i 〉 = 0.016). Similarly, the MTA treatment durations were extended (2.7, 3.2, and 6.6 months in periods 1, 2, and 3, respectively; 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). We confirmed that the correlation between OS and MTA treatment duration was strengthened (period 1: 0.395, period 2: 0.505, and period 3: 0.667). All these trends were pronounced in the patients with advanced-stage HCC but limited in the patients with nonadvanced-stage HCC. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The availability of multiple MTAs had steadily improved the prognosis of patients with advanced HCC patients, particularly advanced-stage HCC patients.
    Type of Medium: Online Resource
    ISSN: 2235-1795 , 1664-5553
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 2666925-0
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  • 6
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: The Hayabusa2 spacecraft made two landings on the asteroid (162173) Ryugu in 2019, during which it collected samples of the surface material. Those samples were delivered to Earth in December 2020. The colors, shapes, and morphologies of the returned samples are consistent with those observed on Ryugu by Hayabusa2, indicating that they are representative of the asteroid. Laboratory analysis of the samples can determine the chemical composition of Ryugu and provide information on its formation and history. RATIONALE We used laboratory analysis to inform the following questions: (i) What are the elemental abundances of Ryugu? (ii) What are the isotopic compositions of Ryugu? (iii) Does Ryugu consist of primary materials produced in the disk from which the Solar System formed or of secondary materials produced in the asteroid or on a parent asteroid? (iv) When were Ryugu’s constituent materials formed? (v) What, if any, relationship does Ryugu have with meteorites? RESULTS We quantified the abundances of 66 elements in the Ryugu samples: H, Li, Be, C, O, Na, Mg, Al, Si, P, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Cd, In, Sn, Te, Cs, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Tl, Pb, Bi, Th, and U. There is a slight variation in chemical compositions between samples from the first and second touchdown sites, but the variations could be due to heterogeneity among the samples that were analyzed. The Cr-Ti isotopes and abundance of volatile elements are similar to those of carbonaceous meteorites in the CI (Ivuna-like) chondrite group. The Ryugu samples consist of the minerals magnetite, breunnerite, dolomite, and pyrrhotite as grains embedded in a matrix composed of serpentine and saponite. This mineral assemblage and the texture are also similar to those of CI meteorites. Anhydrous silicates are almost absent, which indicates extensive liquid water–rock reactions (aqueous alteration) in the material. We conclude that the samples mainly consist of secondary materials that were formed by aqueous alteration in a parent body, from which Ryugu later formed. The oxygen isotopes in the bulk Ryugu samples are also similar to those in CI chondrites. We used oxygen isotope thermometry to determine the temperature at which the dolomite and magnetite precipitated from an aqueous solution, which we found to be 37° ± 10°C. The 53 Mn- 53 Cr isotopes date the aqueous alteration at 5.2 − 0.7 + 0.8 million (statistical) or 5.2 − 2.1 + 1.6 million (systematic) years after the birth of the Solar System. Phyllosilicate minerals are the main host of water in the Ryugu samples. The amount of structural water in Ryugu is similar to that in CI chondrites, but interlayer water is largely absent in Ryugu, which suggests a loss of interlayer water to space. The abundance of structural water and results from dehydration experiments indicate that the Ryugu samples remained below ~100°C from the time of aqueous alteration until the present. We ascribe the removal of interlayer water to a combination of impact heating, solar heating, solar wind irradiation, and long-term exposure to the ultrahigh vacuum of space. The loss of interlayer water from phyllosilicates could be responsible for the comet-like activity of some carbonaceous asteroids and the ejection of solid material from the surface of asteroid Bennu. CONCLUSION The Ryugu samples are most similar to CI chondrite meteorites but are more chemically pristine. The chemical composition of the Ryugu samples is a closer match to the Sun’s photosphere than to the composition of any other natural samples studied in laboratories. CI chondrites appear to have been modified on Earth or during atmospheric entry. Such modification of CI chondrites could have included the alteration of the structures of organics and phyllosilicates, the adsorption of terrestrial water, and the formation of sulfates and ferrihydrites. Those issues do not affect the Ryugu samples. Those modifications might have changed the albedo, porosity, and density of the CI chondrites, causing the observed differences between CI meteorites, Hayabusa2 measurements of Ryugu’s surface, and the Ryugu samples returned to Earth. Representative petrography of a Ryugu sample, designated C0002-C1001. Colors indicate elemental abundances determined from x-ray spectroscopy. Lines of iron, sulfur, and calcium are shown as red, green, and blue (RGB) color channels in that order. Combinations of these elements are assigned to specific minerals, as indicated in the legend. All visible minerals were formed by aqueous alteration on Ryugu’s parent body.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 512-512
    Abstract: 512 Background: Lenvatinib has been widely used as a leading oral multikinase inhibitor for advanced hepatocellular carcinoma (HCC) patients in real-world practice worldwide. However, in the global phase 3 study comparing the effectiveness of lenvatinib and sorafenib, only a limited population of patients were enrolled, excluding those who had a high-burden intrahepatic lesion or Child-Pugh class (C-P) B, who were likely to receive systemic therapy in the clinical practice. Currently, combination immunotherapy has replaced multikinase inhibitors as the standard first-line treatment. Therefore, this prospective study explored the safety and efficacy of lenvatinib in the patient population, which would be used in real-world practice. Methods: This was an open-label, multicenter, prospective study that enrolled patients who had advanced HCC with C-P A or B, treated with lenvatinib as first-line or second-line after atezolizumab plus bevacizumab (Atz + Bv) at 10 sites in Japan. The study included patients who had high tumor burden, defined as identifying either tumor volume of more than 50% of the liver, portal vein tumor thrombosis reaching the main trunk or the contralateral branch, or bile duct invasion at baseline (jRCTs031190017). Results: Between December 1, 2019, and September 30, 2021, 59 patients were recruited for this study. At the time of enrollment, 47 and 12 patients were classified as C-P A and B, respectively. This study included 11 patients with high tumor burden and 12 treated with second-line after Atz + Bv. All patients with high tumor burden and second-line treatment were classified as C-P A. Median overall survival of C-P A and B patients was 20.3 and 4.2 months, respectively. Similarly, progression-free survival according to modified RECIST (mRECIST) of C-P A and B patients was 4.8 and 2.8 months, respectively. Objective response rate (ORR) according to mRECIST in C-P A patients was 61.9%, whereas in C-P B patients was 25.0%. ORRs of high-burden group and second-line group were 80.0% and 40.0%, respectively. Major severe adverse events (AE) (≥grade 3) in C-P A patients were hypertension (41.3%) and proteinuria (23.9%). In contrast, those in C-P B patients were hyponatremia (41.7%), elevated aspartate aminotransferase (41.7%), hypertension (33.3%), decreased appetite (16.7%), diarrhea (16.7%), and proteinuria (16.7%). Discontinuation rate due to AE of C-P A and B patients was 17.4% and 33.3%, respectively. In high-burden and second-line groups, 10% and 20% discontinued lenvatinib due to AE, respectively. Conclusions: Lenvatinib is expected to be safe and effective in patients with advanced HCC who have a high tumor burden and second-line treatment after Atz + Bv, whereas liver function was maintained with C-P A. However, in C-P B, this study found lower efficacy and higher discontinuation rates due to AE compared with C-P A. Clinical trial information: s031190017 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Transplant International, Frontiers Media SA, Vol. 23, No. 5 ( 2010-05), p. e1-e4
    Type of Medium: Online Resource
    ISSN: 0934-0874
    Language: English
    Publisher: Frontiers Media SA
    Publication Date: 2010
    detail.hit.zdb_id: 1463183-0
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2009
    In:  Fisheries Science Vol. 75, No. 6 ( 2009-11), p. 1489-1498
    In: Fisheries Science, Springer Science and Business Media LLC, Vol. 75, No. 6 ( 2009-11), p. 1489-1498
    Type of Medium: Online Resource
    ISSN: 0919-9268 , 1444-2906
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 2020302-0
    detail.hit.zdb_id: 1192654-5
    SSG: 21,3
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Japan Society of Mechanical Engineers ; 2005
    In:  The Proceedings of Ibaraki District Conference Vol. 2005, No. 0 ( 2005), p. 83-84
    In: The Proceedings of Ibaraki District Conference, Japan Society of Mechanical Engineers, Vol. 2005, No. 0 ( 2005), p. 83-84
    Type of Medium: Online Resource
    ISSN: 2424-2683
    Uniform Title: 404 アルミニウム合金の延性に及ぼす水素の影響(関東支部 茨城講演会)
    Language: English , Japanese
    Publisher: Japan Society of Mechanical Engineers
    Publication Date: 2005
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