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  • 1
    Online Resource
    Online Resource
    Long-Term Effects of Interferon-Based Therapy for Chronic Hepatitis C
    S. Karger AG ; 2007
    In:  Oncology Vol. 72, No. Suppl. 1 ( 2007), p. 16-23
    Details
    In: Oncology, S. Karger AG, Vol. 72, No. Suppl. 1 ( 2007), p. 16-23
    Abstract: Hepatitis C virus infection frequently causes chronic liver disease leading to cirrhosis and hepatocellular carcinoma (HCC) and has become the main indication for liver transplantation. Interferon (IFN)-based therapy has been used in the treatment of chronic hepatitis C (CHC) for viral clearance. Several earlier studies showed long-term beneficial effects of IFN monotherapy in reducing the progression of cirrhosis, hindering HCC development, and prolonging survival among both sustained virological responders and nonresponders. However, the benefits of preventing disease progression in CHC patients without sustained virological response (SVR) no longer existed over a longer observation period. Both IFN monotherapy and IFN-ribavirin combination therapy were shown to reduce significantly the complications of liver disease, in terms of development of cirrhosis, HCC and liver-related mortality. The significance disappeared after response to antiviral treatment was taken into account. The benefits were obtained mainly from successful antiviral treatment but were not related to the antiviral regimens, suggesting that the magnitude of this preventive effect could increase through the significant improvement of SVR rate by using a more effective regimen, such as interferon-ribavirin or peginterferon-ribavirin combination therapy. Nevertheless, about one-third of patients remain resistant to the current recommended antiviral regimens. More effective treatment is needed for the population.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000111703
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2007
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 2
    Online Resource
    Online Resource
    Efficacy, Safety, and Potential Biomarkers of Thalidomide plus Metronomic Chemotherapy for Advanced Hepatocellular Carcinoma
    S. Karger AG ; 2012
    In:  Oncology Vol. 82, No. 1 ( 2012), p. 59-66
    Details
    In: Oncology, S. Karger AG, Vol. 82, No. 1 ( 2012), p. 59-66
    Abstract: 〈 i 〉 Objectives: 〈 /i 〉 Thalidomide has been shown to have antitumor activity in some patients with advanced hepatocellular carcinoma (HCC). We initiated a phase II study to determine the safety and efficacy of adding metronomic chemotherapy to thalidomide as first-line therapy. 〈 i 〉 Methods: 〈 /i 〉 This open- labeled, single-arm, multicentered, investigator-initiated study enrolled patients with treatment-naïve advanced HCC not amenable to locoregional therapies. Treatment included oral thalidomide (100 mg twice daily) and tegafur/uracil [125 mg/m 〈 sup 〉 2 〈 /sup 〉 (based on tegafur) twice daily]. Tumor assessment was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Pretreatment plasma levels of angiogenesis factors were correlated with patient outcomes. 〈 i 〉 Results: 〈 /i 〉 Forty-three patients were included. Sixteen (37%) patients had a Cancer of the Liver Italian Program (CLIP) score of 4, and 31 (72%) patients had chronic hepatitis B virus infection. The objective response rate was 9%, and the disease stabilization rate was 33%. The median progression-free survival was 1.9 months (95% CI 1.7–2.1 months), and the median OS was 4.6 months (95% CI 2.3–6.9 months). Treatment was generally tolerable. High baseline plasma levels of interleukin (IL)-6 and IL-8 were adversely correlated with patient survivals. 〈 i 〉 Conclusions: 〈 /i 〉 The combination of thalidomide and tegafur/uracil was safe and demonstrated modest activity in patients with advanced HCC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000336126
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 3
    Online Resource
    Online Resource
    High MT2A Expression Predicts Worse Prognosis in Patients with Urothelial Carcinoma
    S. Karger AG ; 2022
    In:  Oncology Vol. 100, No. 9 ( 2022), p. 485-497
    Details
    In: Oncology, S. Karger AG, Vol. 100, No. 9 ( 2022), p. 485-497
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Dysregulation of metal ion homeostasis is associated with urothelial carcinogenesis. From a published urinary bladder urothelial carcinoma (UBUC) transcriptome, we identified metallothionein 2A (MT2A) as the most significantly upregulated gene implicated in cancer progression among metal ion binding-related genes. Therefore, we analyzed the association between MT2A expression and clinical significance in our well-characterized cohort of patients with upper tract urothelial carcinoma (UTUC) and UBUC. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We retrospectively reviewed the clinicopathological characteristics of 295 and 340 patients with UBUC and UTUC, respectively. MT2A expression was assessed using real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We further correlated MT2A expression with clinicopathological factors, disease-specific survival (DSS) and metastasis-free survival (MFS) using the Pearson’s χ 〈 sup 〉 2 〈 /sup 〉 test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 High MT2A expression was significantly associated with aggressive pathological features including high tumor stage, lymph node metastasis, high tumor grade, vascular invasion, and perineural invasion. In the Kaplan-Meier analysis, high MT2A expression was significantly correlated with poor DSS ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.0001) and MFS ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.0001); in the multivariate analysis, it was an independent predictor of CSS ( 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001) and MFS ( 〈 i 〉 p 〈 /i 〉 = 0.001). Gene coexpression analysis demonstrated that MT2A overexpression promotes UC progression through complement activation. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 High MT2A expression correlated with aggressive UC features and was an independent predictor of cancer metastasis and patient survival, suggesting its role in risk stratification and decision-making in patients with UTUC and UBUC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000525743
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 4
    Online Resource
    Online Resource
    Glucose Conferred Irinotecan Chemoresistance through Divergent Actions of Pyruvate and ATP in Cell Death and Proliferation of Colorectal Cancer
    S. Karger AG ; 2022
    In:  Oncology Vol. 100, No. 10 ( 2022), p. 555-568
    Details
    In: Oncology, S. Karger AG, Vol. 100, No. 10 ( 2022), p. 555-568
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Altered glucose metabolism is associated with chemoresistance in colorectal cancer (CRC). This study aimed to illustrate the molecular mechanisms of glucose-mediated chemoresistance against irinotecan, a topoisomerase I inhibitor, focusing on the distinct roles of metabolites such as pyruvate and ATP in modulating cell death and proliferation. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Four human CRC cell lines, tumorspheres, and mouse xenograft models were treated with various doses of irinotecan in the presence of various concentrations of glucose, pyruvate, or ATP-encapsulated liposomes. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In this study, human CRC cell lines treated with irinotecan in high glucose displayed increased cell viability and larger xenograft tumor sizes in mouse models compared to those treated in normal glucose concentrations. Irinotecan induced apoptosis and necroptosis, both mitigated by high glucose. Liposomal ATP prevented irinotecan-induced apoptosis, while it did not affect necroptosis. In contrast, pyruvate attenuated the receptor-interacting protein kinase 1/3-dependent necroptosis via free radical scavenging without modulating apoptotic levels. Regarding the cell cycle, liposomal ATP aggravated the irinotecan-induced G0/G1 shift, whereas pyruvate diminished the G0/G1 shift, showing opposite effects on proliferation. Last, tumorsphere structural damage, an index of solid tumor responsiveness to chemotherapy, was determined. Liposomal ATP increased tumorsphere size while pyruvate prevented the deformation of spheroid mass. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Glucose metabolites confer tumor chemoresistance via multiple modes of action. Glycolytic pyruvate attenuated irinotecan-induced necroptosis and potentiated drug insensitivity by shifting cells from a proliferative to a quiescent state. On the other hand, ATP decreased irinotecan-induced apoptosis and promoted active cell proliferation, contributing to tumor recurrence. Our findings challenged the traditional view of ATP as the main factor for irinotecan chemoresistance and provided novel insights of pyruvate acting as an antioxidant responsible for drug insensitivity, which may shed light on the development of new therapies against recalcitrant cancers.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000525977
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 5
    Online Resource
    Online Resource
    Evaluation of Prognosis for Carcinoma of Unknown Origin in Elderly Patients
    S. Karger AG ; 2012
    In:  Oncology Vol. 83, No. 1 ( 2012), p. 24-30
    Details
    In: Oncology, S. Karger AG, Vol. 83, No. 1 ( 2012), p. 24-30
    Abstract: 〈 b 〉 〈 i 〉 Purpose: 〈 /i 〉 〈 /b 〉 Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site (CUP) for treatment considerations. 〈 b 〉 〈 i 〉 Patients and Methods 〈 /i 〉 〈 /b 〉 : Patients 〉 70 years old with histologically proven carcinoma were retrospectively reviewed. The prognostic factors were analyzed with univariate and multivariate Cox regression. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We included 63 patients aged 70–79 years and 51 patients ≥80 years old. The results of multivariate Cox regression in the 70–79 years age group revealed white blood cell count ≤10 〈 sup 〉 4 〈 /sup 〉 /ml [p = 0.033; hazard ratio (HR) 2.51, range 1.079–5.840] and albumin ≥3.5 g/dl (p = 0.007; HR 3.38, range 1.398–8.177) as independent factors. In the group of patients ≥80 years old, Eastern Cooperative Oncology Group performance status 〈 1 (p = 0.020), white blood cell count ≤10 〈 sup 〉 4 〈 /sup 〉 /ml (p = 0.001), albumin ≥3.5 g/dl (p = 0.006), lactate dehydrogenase (LDH) ≤250 U/l (p = 0.002) and non-chest metastasis (p = 0.043) were significantly better with univariate analysis. Multivariate Cox regression revealed albumin ≥3.5 g/dl (p = 0.007; HR 3.28, range 1.389–7.745) and LDH ≤250 U/l (p = 0.045; HR 3.18, range 1.026–9.848) as independent factors. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 For elderly patients with CUP, the serum albumin level seems to be a consistently independent prognostic factor. In patients 〉 80 years old, serum LDH plays an important role in prognosis. This study is helpful in predicting the outcome and management for this group of patients.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000337983
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2012
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 6
    Online Resource
    Online Resource
    The Germline 〈b〉〈i〉BIM〈/i〉〈/b〉 Deletion Polymorphism Is Not Associated with the Treatment Efficacy of Sorafenib in Patients with Advanced Hepatocellular Carcinoma
    S. Karger AG ; 2013
    In:  Oncology Vol. 85, No. 5 ( 2013), p. 312-316
    Details
    In: Oncology, S. Karger AG, Vol. 85, No. 5 ( 2013), p. 312-316
    Abstract: 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 A germline 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism has been proposed to predict a poor treatment efficacy of certain kinase inhibitors. The current study aimed to explore whether the 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism predicts the treatment efficacy of sorafenib for advanced hepatocellular carcinoma (HCC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 All patients who were enrolled in clinical trials to receive sorafenib-containing regimens as first-line therapy for advanced HCC and consented to providing peripheral blood samples were included. Polymerase chain reaction followed by gel electrophoresis was used to detect the germline 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A total of 89 patients were enrolled; 69 (77%) patients had chronic hepatitis B infection, and 18 (20%) had chronic hepatitis C infection. The heterozygous 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism was identified in 9 (10%) patients. Patients with and without the 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism had similar response rates (11 vs. 6%) and disease control rates (56 vs. 61%). The time to progression, progression-free survival, and overall survival were similar between patients with and without the 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism. After adjusting for basic clinicopathologic variables and treatment regimens, the 〈 i 〉 BIM 〈 /i 〉 polymorphism still could not predict treatment outcomes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 The 〈 i 〉 BIM 〈 /i 〉 deletion polymorphism was not associated with the treatment efficacy of sorafenib for advanced HCC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000356019
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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