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  • 1
    Online Resource
    Online Resource
    Expression of c-Met in Primary and Recurrent Hepatocellular Carcinoma
    S. Karger AG ; 2020
    In:  Oncology Vol. 98, No. 3 ( 2020), p. 186-194
    Details
    In: Oncology, S. Karger AG, Vol. 98, No. 3 ( 2020), p. 186-194
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The clinical course of hepatocellular carcinoma (HCC) is complicated, because it often recurs and shows multiple lesions, some of which progress to a more malignant form, shortening the life of the patient. The hepatocyte growth factor receptor c-Met has been shown to play an important role in the pathogenesis of HCC, but the influence of c-Met expression on the clinical course of HCC remains to be fully elucidated. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We randomly selected and included 600 tumor specimens obtained from the primary and recurrent lesions of 319 HCC cases between 1995 and 2007. The expression of c-Met was determined by immunohistochemistry using archived formalin-fixed paraffin-embedded samples. We analyzed the correlation between c-Met expression and clinical parameters, including survival. In addition, we examined c-Met expression in the malignant transition of HCC in all cases including recurrent lesions. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Survival analysis using the multivariate Cox proportional-regression model revealed that the prognosis was significantly better in the primary cases with high c-Met expression than in those with low c-Met expression (hazard ratio 0.159, 95% confidence interval 0.065–0.391; 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). During the course of recurrence, some cases with high c-Met expression returned to low c-Met expression. Among 40 cases with high c-Met expression, 29 survived more than 2 years after detecting the high c-Met expression. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 High expression of c-Met may be a prognostic factor for a good, rather than a poor, HCC prognosis. The involvement of c-Met expression in the malignant transition of recurrent HCC is obscure.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000504806
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 2
    Online Resource
    Online Resource
    Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
    Springer Science and Business Media LLC ; 2023
    In:  Nature Genetics Vol. 55, No. 5 ( 2023-05), p. 753-767
    Details
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 55, No. 5 ( 2023-05), p. 753-767
    Abstract: Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of 〉 895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    URL: Article
    DOI: 10.1038/s41588-023-01375-1
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1494946-5
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    A single arm, prospective multicenter phase II study FOLFIRINOX in patients with advanced and recurrent biliary tract cancer.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 4_suppl ( 2017-02-01), p. TPS514-TPS514
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. TPS514-TPS514
    Abstract: TPS514 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is gemcitabine and cisplatin (GC) combination chemotherapy. Despite intensive researches, no trials have proved better overall survival (OS) over GC. Recently, FOLFIRINOX provided a remarkable survival benefit over gemcitabine in patients with metastatic pancreatic cancer. Given the promising results of FOLFIRI and FOLFOX in patients with advanced BTC, FOLFIRINOX can be an attractive option in patients with advanced BTC as well. Methods: This is a single-arm, open-label, multi-center phase II study to evaluate the safety and efficacy of FOLFIRINOX in patients with advanced BTC. The major inclusion criteria are as follows; unresectable or recurrent BTC, histologically or cytologically confirmed adenocarcinoma, no prior chemotherapy or radiation therapy, age of 20-75 years, an ECOG PS of 0 or 1, at least one measurable lesion, adequate hematological, liver and renal function. The major exclusion criteria are as follows; UGT genetic polymorphisms of homozygous UGT1A1*6 or *28 or heterozygous UGT1A1*6 and *28, massive pleural effusion or ascites. FOLFIRINOX consists of oxaliplatin of 85 mg/m 2 , irinotecan of 180 mg/m 2 , leucovorin of 400 mg/m 2 administered by intravenous infusion and fluorouracil of 400 mg/m 2 by intravenous bolus and of 2,400 mg/m 2 by continuous intravenous infusion every 2 weeks. The primary outcome is progression-free survival (PFS), and the secondary outcomes are OS, tumor response and safety. PFS and OS will be calculated from the date of enrollment until the date of documentation of disease progression or death in patients without disease progression and the date of death. Tumor response will be evaluated according to the RECIST version 1.1 every 2 months. Safety will be evaluated with the CTCAE version 4.0. A total of 35 patients will be required to provide 75% power to detect an increase in median PFS from 6 months provided by standard care of GC to 10 months in patients receiving FOLFIRINOX, with a 24 months of recruitment and 18 months of follow-up. A phase III trial will be considered when this study shows the lower limit of the 80% confidence interval for PFS is longer than 6 months. Clinical trial information: UMIN000020801.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.4_suppl.TPS514
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Risk factor of thrombosis and impact on prognosis in patients with pancreatic cancer receiving chemotherapy.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. 218-218
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 218-218
    Abstract: 218 Background: Thromboembolism (TE) is common in cancer patients, and pancreatic cancer is reported to be highly associated with TE. The aim of this analysis is to clarify risk factors for TE and its clinical impact in pancreatic cancer patients. Methods: Data on consecutive pancreatic cancer patients receiving systemic chemotherapy between August 1999 and July 2015 were retrospectively studied. The diagnosis of TE was made on CT scan either performed for suspicious symptoms of TE or for evaluation of chemotherapy response, and TE was classified into two groups: arterial events including coronary artery disease (CAD), cerebrovascular disease and other artery thrombosis, and venous events including deep vein thrombosis/pulmonary embolism (DVT/PE), portal vein thrombosis (PVT) and IVC thrombosis. Overall survival and time to TE (TTE) were calculated by Kaplan-Meier analysis. Risk factors for TE development were analyzed using a Cox proportional hazards model. To evaluate the impact of TE on survival, multivariate analyses were performed using a time-dependent covariate multiple Cox model. Results: A total of 475 patients (195 female, a median age of 67 years) were analyzed. TE was identified in 57 patients (12%). Venous TE were 45 (79%) including DVT/PE 24(42%), IVC thrombosis 2 (4%), PVT 19 (33%). Arterial TE were 12 (21%) including cerebrovascular infarction 9 (16%), CAD 2 (4%) respectively. The median TTE was 169 days (95% CI, 75-203). Liver metastasis was the only significant risk factor for TE in the multivariate analysis (OR 2.01, 95%CI 1.12-3.47, P = 0.012). The median survival from TE development was 57 days (95% CI, 37-65) and TE was significantly associated with poor prognosis (HR 3.31, 95%CI 2.72-5.27, P 〈 0.01) in the time-dependent covariate analysis. Conclusions: TE was not uncommon in pancreatic cancer patients receiving chemotherapy and was associated with poor prognosis. Whether the prophylaxis for TE can improve survival should be further investigated, especially in high risk patients such as patients with liver metastasis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.4_suppl.218
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Did multiagent chemotherapy improve clinical outcomes of advanced pancreatic cancer? A single center experience of 408 cases.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. 293-293
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 293-293
    Abstract: 293 Background: We previously reported the introduction of S-1 improved overall survival (OS) in advanced pancreatic cancer (PC), but in a pooled analysis of 3 RCTs, a combination of gemcitabine and S-1 (GS) improved OS in locally advanced PC (LAPC), but not in metastatic PC (MPC), compared to gemcitabine (Gem) alone. More recently, FOLFIRINOX, a multiagent chemotherapy, is shown to improve OS in MPC. We conducted clinical trials of a combination of Gem, S-1 and leucovorin (GSL) to further enhance antitumor effects. Herein, we retrospectively studied whether these multiagent regimens, GSL & FOLFIRINOX, affected the prognosis of APC, especially MPC. Methods: A total of 408 pts with APC receiving chemotherapy were grouped by treatment era into 3 groups: Group 1 (Years 2001-5: 53 pts prior to S-1 introduction), Group 2(Years 2005-11: 240 pts post S-1 introduction) and Group 3 (2012-14: 115 pts post multiagent treatment introduction), and clinical outcomes were compared. Results: Patient characteristics and protocol are shown in Table 1. Treatment protocol was single in 233, dual 142, and multiagent in 33. Response rate & disease control rate in Groups 1/2/3 were 2/8/17% & 26/67/73%. In LAPC, PFS was 6.2/8.9/7.9 & OS was 13.4/17.2/19.7 months in Groups 1/2/3. Meanwhile, in MPC, PFS was 2.0/3.5/4.8 & OS was 6.7/8.6/9.6 months in Groups 1/2/3. When treatment protocols were compared, in LAPC, PFS & OS were 7.0/11.7/8.8 & 13.6/22.6/22.6 months in singe/dual/multiagent chemotherapy. In MPC, PFS & OS were 3.1/3.5/6.0 & 8.3/8.1/13.7 months in single/dual/multiagent chemotherapy. Conclusions: While the introduction of S-1 led to longer OS in LAPC, recent introduction of multiagent chemotherapy appeared to improve OS in MPC. Whether multiagent chemotherapy would lead to longer OS than dual chemotherapy in LAPC needs further investigation. Table 1. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.4_suppl.293
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Neoadjuvant mFOLFOX6 for stage II/III rectal cancer patients with a T3/T4 tumor.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. 3554-3554
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 3554-3554
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.3554
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Enhancement of the efficacy of radiofrequency ablation by neoadjuvant oncolytic virus therapy via antitumor immunity and the booster effect of immune checkpoint inhibitors.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 4_suppl ( 2019-02-01), p. 253-253
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 253-253
    Abstract: 253 Background: A third generation oncolytic herpes simplex virus type 1, G47Δ, destroys tumor cells selectively and induces antitumor immune responses. Radiofrequency ablation (RFA) is a standard local therapy for hepatocellular carcinoma (HCC). Here, we examined the efficacy of G47Δ used in combination with RFA and evaluated the antitumor immune responses. Methods: In A/J mice harboring bilateral poorly immunogenic Neuro2a subcutaneous tumors, tumors on one side were treated with intratumoral injections with G47Δ (2×10 6 pfu) on days 0, 2 and 4 followed by RFA treatment on day 6, which results in complete regression of the treated tumors. We further treated with an immune checkpoint inhibitor (ICI) in combination. Tumor infiltrating lymphocytes in contralateral tumors were analyzed with flow cytometric analysis. To examine the contribution of CD8 + T cells, CD8 + T cells were depleted by treatment with anti-CD8 monoclonal antibody. To mimic a remote recurrence, unilateral subcutaneous tumors were treated with G47Δ and RFA, and Neuro2a cells were implanted on the same day of RFA. In a separate experiment without rechallenge, antitumor immunity was evaluated using ELISpot assay on day 20. Results: The G47Δ+RFA treatment caused smaller volumes of contralateral tumors and increased infiltration of CD8 + /CD45 + T cells within the tumor, compared with RFA or G47Δ monotherapy. Without CD8 + T cells, the antitumor effect on the contralateral tumors was completely abolished. When mice were rechallenged, those cured by G47Δ+RFA rejected the Neuro2a more frequently than those cured by RFA alone. ELISpot assay revealed that the number of Neuro2a reactive splenocytes was significantly greater in the G47Δ+RFA group than the RFA group. The G47Δ+RFA+anti-PD-L1 treatment caused smaller volumes of contralateral tumors compared with G47Δ+RFA treatment, whereas anti-PD-L1 alone showed no effect. Conclusions: Intratumoral administration of G47Δ prior to RFA would enhance systemic antitumor immunity that is further enhanced by ICI.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.4_suppl.253
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    A multicenter randomized controlled trial to evaluate the efficacy of surgery vs. radiofrequency ablation for small hepatocellular carcinoma (SURF trial).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 4002-4002
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4002-4002
    Abstract: 4002 Background: Surgery (SUR) and radiofrequency ablation (RFA) are both known to be effective therapy for treating patients with small oligonodular hepatocellular carcinoma (HCC), however there is only insufficient evidence about which therapy is more preferred approach. This randomized controlled trial was designed to prospectively compare the efficacy of SUR and RFA as the first approach to primary HCC. Methods: In this open-label trial undertaken at 49 hospital in Japan, we recruited patients having primary HCC with tumor foci numbering less than 3, each measuring 3 cm or less, Child-Pugh score of 7 or less, ages between 20 and 79 year. Before randomization, technical and liver functional feasibility for both treatment arms were confirmed by joint chart review by surgeons and hepatologists. Patients were then randomly assigned in a 1:1 ratio to undergo SUR or RFA, stratified by age, infection of hepatitis-C virus, number of tumors, tumor size and institution. The primary endpoint was recurrence free survival (RFS) and overall survival (OS). Results: Between April 2009 and August 2015, total 308 patients were enrolled to this trial. Because of ineligibility 15 patients were excluded, therefore 145 patients underwent SUR and 148 patients underwent RFA finally. There was no perioperative mortality. Under the median follow-up of 5 years, the 3-year RFS of patients underwent SUR and RFA was 49.8%, 47.7%, respectively (hazard ration [HR] 0.96, 95% CI 0.72-1.28; p = 0.793). OS will be analyzed and published after two years. Conclusions: SUR and RFA were both safe therapeutic approaches and provided equally RFS for early stage HCC smaller than 3 cm. Clinical trial information: UMIN000001795.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.4002
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    Intravenous and intraperitoneal paclitaxel with S-1 for refractory pancreatic cancer with malignant ascites: An interim analysis.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 4_suppl ( 2013-02-01), p. 267-267
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 267-267
    Abstract: 267 Background: Here we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites. Methods: Paclitaxel was administered intravenous at 50 mg/m 2 and intraperitoneal at 20 mg/m 2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m 2 /day for 14 consecutive days, followed by 7 days rest. Results: Between April 2011 to February 2012, 10 patients were enrolled. A partial response was achieved in two (20%) and a disease control rate of 50%. The median time to progression and overall survival were 3.2 and 5.9 months, respectively. Malignant ascites was completely resolved in two (20%). Major grade 3/4 adverse events weremyelosuppression including neutropenia (50%) and catheter-related infection (10%). Conclusions: This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites. Clinical trial information: UMIN000005306.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.4_suppl.267
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 10
    Online Resource
    Online Resource
    Efficacy and Safety of Early vs Elective Colonoscopy for Acute Lower Gastrointestinal Bleeding
    Elsevier BV ; 2020
    In:  Gastroenterology Vol. 158, No. 1 ( 2020-01), p. 168-175.e6
    Details
    In: Gastroenterology, Elsevier BV, Vol. 158, No. 1 ( 2020-01), p. 168-175.e6
    Type of Medium: Online Resource
    ISSN: 0016-5085
    URL: Article
    DOI: 10.1053/j.gastro.2019.09.010
    RVK:
    XA 44500
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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