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  • Oxford University Press (OUP)  (31)
  • 1
    In: Japanese Journal of Clinical Oncology, Oxford University Press (OUP), Vol. 37, No. 1 ( 2007-01-01), p. 9-15
    Type of Medium: Online Resource
    ISSN: 1465-3621 , 0368-2811
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
    detail.hit.zdb_id: 1494610-5
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  • 2
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. 10 ( 2020-10-01), p. 1753-1760
    Abstract: Few investigations have evaluated the influences on peripheral arterial disease (PAD) risk of statin treatment in hemodialysis (HD) subjects with hyperlipidemia (HL). Methods From the National Health Insurance Research Dataset, we identified 3658 HD patients with statin therapy for HL as the statin cohort, and then selected, by 1:1 propensity score matching, 3658 HD patients with HL but without statin use as the nonstatin cohort in 2000–07. The cohorts were followed through until the end of 2011. We used Cox proportional hazards regression analysis to assess the hazard ratio (HR) of PAD development. Results The average follow-up period was 4.18 years; the incident PAD risk was 1.35-fold greater in statin users than in nonusers (16.87 versus 12.46/1000 person-years), with an adjusted HR (aHR) of 1.34 for PAD [95% confidence interval (CI) 1.12–1.62]. The PAD risk increases were significant for patients receiving fluvastatin (aHR 1.88; 95% CI 1.12–3.14) and atorvastatin (aHR 1.60; 95% CI 1.24–2.08). The risk increased with higher annual average statin dosage (P for trend & lt;0.0001); the risk was higher for those receiving moderate-intensity statin treatment. The sensitivity test revealed similar findings. Conclusions HD patients with HL on statin medication were at increased PAD risk, which increased with cumulative statin dosage. Thorough considerations are needed before prescribing statins to HD patients.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1465709-0
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  • 3
    In: The Oncologist, Oxford University Press (OUP), Vol. 17, No. 7 ( 2012-07-01), p. 970-977
    Abstract: The purpose of this study was to determine the prognostic significance of clinical factors and staging systems for survival of hepatocellular carcinoma (HCC) patients who are candidates for therapeutic clinical trials. Methods. From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into six published phase II trials assessing various therapeutic regimens. Of these, 156 chemotherapy-naive patients with Child-Pugh class A and Barcelona Clinic Liver Cancer stage C disease were included in this analysis. Twenty-seven relevant clinical characteristics were analyzed to identify prognostic factors of survival. Beyond these prognosticators, the predictive ability of eight staging systems (the tumor–node–metastasis, Okuda, Cancer of the Liver Italian Program [CLIP], Chinese University Prognostic Index, Japanese Integrated Staging, Tokyo, National Taiwan University Risk Estimation, and Advanced Liver Cancer Prognostic System [ALCPS] score) were compared using the Akaike information criteria. Results. The median overall survival time was 129 days (95% confidence interval, 111–147 days). Significant predictors of a shorter overall survival time were an Eastern Cooperative Oncology Group performance status score ≥2, the presence of symptoms, ascites, an aspartate transaminase level more than two times the upper limit of normal, and regional lymph node involvement. The ALCPS and CLIP scores were superior to the other systems for predicting survival. Conclusions. The prognosis of patients with advanced HCC who are candidates for therapeutic clinical trials is affected by several factors related to the patient, liver function, and the tumor. The ALCPS and CLIP scores appear to be superior to the other systems for predicting survival.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 2023829-0
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  • 4
    In: The Oncologist, Oxford University Press (OUP), Vol. 25, No. 8 ( 2020-08-01), p. 702-711
    Abstract: Programmed death-ligand 1 (PD-L1) expression is associated with clinical outcomes of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (ADC) treated with tyrosine kinase inhibitors (TKIs). However, whether PD-L1 expression plays a role in anaplastic lymphoma kinase (ALK)-positive lung ADC is unknown. We aimed to evaluate the impact of PD-L1 in patients with ALK-positive lung ADC receiving crizotinib. Materials and Methods PD-L1 expression was identified by immunohistochemistry (IHC). Reverse transcriptase-polymerase chain reaction was used for ALK variant detection, and immunofluorescence-based multiplex staining was applied for exploring immune cells in tumor microenvironments. Results A total of 78 patients with ALK-positive advanced ADC were enrolled in our study, of whom 52 received crizotinib. Compared with EGFR/ALK wild-type tumors, PD-L1 expression was lower in ALK-positive ADC. ALK fusion variants were identified in 32 patients, and those with variant 3 and 5 (short variants) had higher PD-L1 expression than those with other variants. The crizotinib objective response rate (ORR) and progression-free survival (PFS) was better in tumors with negative PD-L1 expression (ORR/PFS in PD-L1 0% vs. 1%–49% vs. 50%–100%: 60.7%/11.8 months vs. 38.5%/6.5 months vs. 36.4%/4.0 months, p = .007/.022). The multivariate Cox proportional hazards model revealed that PD-L1 0% (vs. ≥1%) was an independent factor for longer PFS (adjusted hazard ratio 0.322, 95% confidence interval 0.160–0.650, p = .002). Multiplex IHC in three cases showed a varied extent of immune cell infiltrations in tumors with different PD-L1 expression. Conclusion Positive PD-L1 expression was associated with unfavorable clinical outcomes in patients with ALK-positive lung ADC receiving crizotinib. Implications for Practice Not all lung adenocarcinoma with sensitizing driver mutations experienced durable responses to small-molecule tyrosine kinase inhibitors (TKIs). Similar to the negative impact of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor mutant tumors treated with TKIs, this study demonstrated that positive PD-L1 expression was also associated with worse response rate and shorter progression-free survival of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma treated with crizotinib. Among different ALK fusion partners, tumors with short variants (V3 and V5) had higher PD-L1 compared with long variants (V1, V2, and V6). Testing PD-L1 before initiating crizotinib for ALK-positive lung cancer could be a simple method to provide important prognostic information.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2023829-0
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  • 5
    In: The Oncologist, Oxford University Press (OUP), Vol. 24, No. 12 ( 2019-12-01), p. e1417-e1425
    Abstract: Immediate whole brain radiation (WBRT) has been the standard for patients with lung cancer with brain metastases. The study aims to evaluate the effect of immediate cranial irradiation in patients with epidermal growth factor receptor (EGFR) mutant lung cancer in the era of a new generation of EGFR inhibitors. Materials and Methods Medical records of 198 patients with EGFR mutant non-small cell lung cancer and brain metastases at initial metastatic diagnosis were reviewed. Patients were categorized into four groups: immediate WBRT, immediate cranial stereotactic radiosurgery (SRS), delayed radiation upon progression of cranial lesions (DRT), and never cranial irradiation (NRT). Overall survival (OS) and progression-free survival related to EGFR inhibitors were analyzed. Results The SRS group had the fewest brain metastases and fewest extracranial lesions, and the DRT and NRT groups had the smallest brain metastases. Median survival were 18.5, 55.7, 21.1, and 18.2 months for the WBRT, SRS, DRT, and NRT groups, respectively. Patients who had received EGFR T790M inhibitors survived longer (41.1 vs. 19.8 months). In multivariate analysis, the OS of patients in the SRS group was longer than that in the NRT group (adjusted hazard ratio [aHR]: 0.315). Patients who had fewer extracranial lesions and who had received EGFR T790M inhibitor treatments also survived longer (aHR: 0.442 and 0.357, respectively). Conclusion Immediate stereotactic radiosurgery but not whole brain radiation was associated with longer survival. Because of patient heterogeneity and the introduction of EGFR T790M inhibitors, the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted for selected patients. Implications for Practice Immediate whole brain radiation has been the standard for patients with lung cancer with brain metastases. In this study, it was observed that, for patients with epidermal growth factor receptor (EGFR) mutant advanced lung cancer who had brain metastases, there was no difference in survival between patients who never received cranial irradiation and those who received whole brain radiation immediately. Patients who received immediate stereotactic radiosurgery or who had ever received EGFR T790M inhibitors survived longer. Patients who received immediate stereotactic radiosurgery have fewer brain metastases. These findings suggest that the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted in selected patients.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2023829-0
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  • 6
    In: The Oncologist, Oxford University Press (OUP), Vol. 13, No. 12 ( 2008-12-01), p. 1276-1284
    Abstract: Epidermal growth factor receptor (EGFR) mutations are usually detected in lung adenocarcinoma and are associated with a response to EGFR tyrosine kinase inhibitors (TKIs). However, not all EGFR mutations have similarly high clinical response rates. This study aimed to investigate the clinical characteristics and response to gefitinib in lung adenocarcinoma patients with complex EGFR mutations. Materials and Methods. Three hundred thirty-nine specimens of lung adenocarcinoma from patients treated with gefitinib were collected for EGFR sequencing. Nineteen patients with complex EGFR mutations were enrolled for the study after excluding three patients with the EGFR T790M mutation, which confers resistance to gefitinib. Results. Among the 19 patients, 12 had complex mutations with the classical mutation pattern (L858R or deletion in exon 19). When compared with those without the classical mutation pattern, patients with this mutation pattern had a higher response rate (83% versus 29%), longer progression-free survival duration (median, 12.7 months versus 4.9 months), and longer overall survival time (median, 24.7 months versus 12.3 months) after gefitinib treatment. Comparing patients harboring complex EGFR mutations with a classical mutation pattern with those harboring single classical mutations, there were no statistical differences in the response rate (83% versus 73%), progression-free survival time (median, 12.7 months versus 8.1 months,) or overall survival time (median, 24.7 months versus 16.4 months). Conclusion. Patients with complex EGFR mutations with the classical mutation pattern had the same response rate, progression-free survival duration, and overall survival time as those with single classical mutations. EGFR TKIs may be the choice of treatment for this type of lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 2023829-0
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2013
    In:  Carcinogenesis Vol. 34, No. 7 ( 2013-7), p. 1669-1679
    In: Carcinogenesis, Oxford University Press (OUP), Vol. 34, No. 7 ( 2013-7), p. 1669-1679
    Type of Medium: Online Resource
    ISSN: 1460-2180 , 0143-3334
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
    detail.hit.zdb_id: 1474206-8
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  • 8
    In: Carcinogenesis, Oxford University Press (OUP), Vol. 30, No. 2 ( 2009-2), p. 258-268
    Type of Medium: Online Resource
    ISSN: 1460-2180 , 0143-3334
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
    detail.hit.zdb_id: 1474206-8
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  • 9
    In: The Oncologist, Oxford University Press (OUP), Vol. 20, No. 9 ( 2015-09-01), p. 1051-1057
    Abstract: Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC. Patients and Methods. We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I–IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality. Results. A total of 2,946 patients had primary stage I–IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55). Conclusion. In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments. Implications for Practice: Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2023829-0
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  • 10
    In: Stem Cells, Oxford University Press (OUP), Vol. 33, No. 7 ( 2015-07-01), p. 2243-2255
    Abstract: Endothelial progenitor cells (EPCs) promote angiogenesis and are therefore key contributors to a wide variety of angiogenesis-related autoimmune diseases such as rheumatoid arthritis (RA). However, the signaling mechanisms through which these progenitor cells influence RA pathogenesis remain unknown. The aim of this study was to examine whether resistin plays a role in the pathogenesis of and angiogenesis associated with RA by circulating EPCs. We found that levels of resistin in synovial fluid and tissue from patients with RA and from mice with collagen-induced arthritis were overexpressed and promoted the homing of EPCs into the synovium, thereby inducing angiogenesis. EPCs isolated from healthy donors were used to investigate the signal transduction pathway underlying EPC migration and tube formation after treatment with resistin. We found that resistin directly induced a significant increase in expression of vascular endothelial growth factor (VEGF) in EPCs. We also found that the expression of microRNA-206 (miR-206) was negatively correlated with the expression of resistin during EPC-mediated angiogenesis. Notably, the increased expression of VEGF was associated with decreased binding of miR-206 to the VEGF-A 3′ untranslated region through protein kinase C delta-dependent AMP-activated protein kinase signaling pathway. Moreover, blockade of resistin reduced EPC homing into synovial fluid and angiogenesis in vivo. Taken together, our study is the first to demonstrate that resistin promotes EPCs homing into the synovium during RA angiogenesis via a signal transduction pathway that involves VEGF expression in primary EPCs. These findings provide support for resistin as a therapeutic target for the patients with RA. Stem Cells 2015;33:2243–2255
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
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    detail.hit.zdb_id: 1143556-2
    detail.hit.zdb_id: 605570-9
    SSG: 12
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