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  • S. Karger AG  (9)
  • Medicine  (9)
  • 1
    Online Resource
    Online Resource
    Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer
    S. Karger AG ; 2021
    In:  Oncology Vol. 99, No. 5 ( 2021), p. 336-344
    Details
    In: Oncology, S. Karger AG, Vol. 99, No. 5 ( 2021), p. 336-344
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among those SNPs, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, 〈 i 〉 p 〈 /i 〉 = 0.05), and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, 〈 i 〉 p 〈 /i 〉 = 0.03). Regarding 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher 〈 i 〉 HAX1 〈 /i 〉 promoter activity than T allele. 〈 i 〉 HAX1 〈 /i 〉 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, 〈 i 〉 ME3 〈 /i 〉 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A are associated with the clinical outcomes of patients in surgically resected NSCLC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000514131
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 2
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    Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer
    S. Karger AG ; 2020
    In:  Oncology Vol. 98, No. 12 ( 2020), p. 897-904
    Details
    In: Oncology, S. Karger AG, Vol. 98, No. 12 ( 2020), p. 897-904
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs ( 〈 i 〉 MTHFD1L 〈 /i 〉 rs6919680T & #x3e;G and rs3849794T & #x3e;C, 〈 i 〉 MTR 〈 /i 〉 rs2853523C & #x3e;A, and 〈 i 〉 MTHFR 〈 /i 〉 rs4846049G & #x3e;T) were significantly associated with survival outcomes. 〈 i 〉 MTHFD1L 〈 /i 〉 rs6919680T & #x3e;G and 〈 i 〉 MTR 〈 /i 〉 rs2853523C & #x3e;A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54–0.99, 〈 i 〉 p 〈 /i 〉 = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13–4.07, 〈 i 〉 p 〈 /i 〉 = 0.02), respectively. 〈 i 〉 MTHFD1L 〈 /i 〉 rs3849794T & #x3e;C and 〈 i 〉 MTHFR 〈 /i 〉 rs4846049G & #x3e;T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08–1.83, 〈 i 〉 p 〈 /i 〉 = 0.01; and aHR = 1.97, 95% CI = 1.10–3.53, 〈 i 〉 p 〈 /i 〉 = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, 〈 i 〉 MTHFD1L 〈 /i 〉 rs6919680T & #x3e;G and 〈 i 〉 MTR 〈 /i 〉 rs2853523C & #x3e;A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41–1.00, 〈 i 〉 p 〈 /i 〉 = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11–6.91, 〈 i 〉 p 〈 /i 〉 = 0.03), respectively, and 〈 i 〉 MTHFD1L 〈 /i 〉 rs3849794T & #x3e;C and 〈 i 〉 MTHFR 〈 /i 〉 rs4846049G & #x3e;T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17–2.56, 〈 i 〉 p 〈 /i 〉 = 0.01; and aHR = 2.78, 95% CI = 1.12–6.88, 〈 i 〉 p 〈 /i 〉 = 0.03, respectively). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000509658
    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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  • 3
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    Lipid metabolism pathway genes and lung cancer: ACADSB rs12220683G〉C is associated with better survival outcome in patients with non-small cell lung cancer
    S. Karger AG ; 2023
    In:  Oncology
    Details
    In: Oncology, S. Karger AG
    Abstract: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. Among the 176 investigated polymorphisms, ACADSB rs10902859G 〉 A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G 〉 A was located in the repressed region and had strong linkage disequilibrium (D′ = 1.00 and r2 = 0.94), with rs12220683G 〉 C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G 〉 C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30–0.94, P = 0.03; aHR = 0.37, 95% CI = 0.15–0.89, P = 0.03; and aHR = 0.47, 95% CI = 0.29–0.75, P = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (P = 3 × 10−5). These results suggest that ACADSB rs12220683G 〉 C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000533156
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1483096-6
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  • 4
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    Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
    S. Karger AG ; 2023
    In:  Oncology Vol. 101, No. 2 ( 2023), p. 96-104
    Details
    In: Oncology, S. Karger AG, Vol. 101, No. 2 ( 2023), p. 96-104
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A & #x3e;G in an enhancer which is expected to regulate the expression of 〈 i 〉 ribosomal protein S3 〈 /i 〉 ( 〈 i 〉 RPS3 〈 /i 〉 ) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, 〈 i 〉 p 〈 /i 〉 = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, 〈 i 〉 p 〈 /i 〉 = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000527492
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1483096-6
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  • 5
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    Relationship between Prostate-Specific Antigen and Body Mass Index according to Age: Lower Prostate-Specific Antigen in Middle-Aged Overweight and Obese Korean Men
    S. Karger AG ; 2010
    In:  Urologia Internationalis Vol. 85, No. 2 ( 2010), p. 143-146
    Details
    In: Urologia Internationalis, S. Karger AG, Vol. 85, No. 2 ( 2010), p. 143-146
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 To analyze the relationship between serum prostate-specific antigen (PSA) and body mass index (BMI) according to age in a population of ostensibly healthy Korean men. 〈 i 〉 Patients and Methods: 〈 /i 〉 Between 2002 and 2006, data from 13,025 men who visited health promotion centers were evaluated. All men underwent anthropometric measurements and serum PSA determination. The relationship between serum PSA and BMI according to age was analyzed. 〈 i 〉 Results: 〈 /i 〉 The median age was 50.0 years and the median serum PSA level was 0.69 ng/ml. There was no relationship between serum PSA and BMI in the group whose BMI was 〈 23 kg/m 〈 sup 〉 2 〈 /sup 〉 . The serum PSA showed a significant inverse relationship in those with BMI of ≧23 kg/m 〈 sup 〉 2 〈 /sup 〉 . However, this finding was only true among 40- to 59-year-old middle aged men and no such relationship between serum PSA and BMI was seen in the older groups (60–79 years of age). 〈 i 〉 Conclusion: 〈 /i 〉 Our study revealed serum PSA had a significant inverse relationship with BMI in overweight and obese men aged between 40 and 59 years; however, there was no relationship between serum PSA and BMI in men whose age was older than 60 years.
    Type of Medium: Online Resource
    ISSN: 0042-1138 , 1423-0399
    URL: Article
    DOI: 10.1159/000317037
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2010
    detail.hit.zdb_id: 1464417-4
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  • 6
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    Prognostic Impact of Microsatellite Instability in Asian Gastric Cancer Patients Enrolled in the ARTIST Trial
    S. Karger AG ; 2019
    In:  Oncology Vol. 97, No. 1 ( 2019), p. 38-43
    Details
    In: Oncology, S. Karger AG, Vol. 97, No. 1 ( 2019), p. 38-43
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Caucasian patients with microsatellite instability (MSI)-high gastric cancer (GC) may have better prognosis but worse outcomes. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 Here we explored the prognostic role of MSI in Asian patients. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 This post hoc analysis comprehended radically resected GC patients randomized to XP (capecitabine/cisplatin) or XPRT. MSI status was assessed by combining immunohistochemistry with multiplex polymerase chain reaction. The MSI prognostic effect on disease-free survival (DFS) and overall survival (OS) was evaluated. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 393 tissue samples were analyzed and 35 (9%) were MSI-high. This subgroup was characterized by: older age, Borrmann classification 1–2, antral localization, T3–4 stage, and intestinal type. At univariable analysis, the microsatellite-stable subgroup showed a trend toward a worse prognosis as compared to the MSI-high group: 3-year DFS was 76.3 versus 85.4% ( 〈 i 〉 p 〈 /i 〉 = 0.122); 3-year OS was 81.7 versus 91.4% ( 〈 i 〉 p 〈 /i 〉 = 0.046). Multivariable analyses confirmed it in both DFS (hazard ratio, HR = 2.32 [95% CI 0.91, 5.88]; 〈 i 〉 p 〈 /i 〉 = 0.077) and OS (HR = 3.17 [95% CI 0.97, 10.43]; 〈 i 〉 p 〈 /i 〉 = 0.057). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 MSI-high status was associated with specific clinical-pathological features and a trend toward better outcomes of Asian GC patients.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000499628
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2019
    detail.hit.zdb_id: 1483096-6
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  • 7
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    Medication Adherence of Statin Users after Acute Ischemic Stroke
    S. Karger AG ; 2018
    In:  European Neurology Vol. 80, No. 1-2 ( 2018), p. 106-114
    Details
    In: European Neurology, S. Karger AG, Vol. 80, No. 1-2 ( 2018), p. 106-114
    Abstract: Although statins are established therapy for the secondary prevention of ischemic stroke, factors associated with adherence to statin treatment following ischemic stroke are not well known. To address this, we assessed the 6-month statin adherence using 8-item Morisky Medication Adherence Scale-8 in patients with acute ischemic stroke. Of 991 patients, 65.6% were adherent to statin at 6-month after discharge. Multiple logistic regression analysis showed that patients’ awareness of hyperlipidemia (OR 1.62; 95% CI 1.07–2.43), large artery stroke subtype (versus non-large artery stroke, OR 1.79; 95% CI 1.19–2.68), and alcohol drinking habits (OR 1.64; 95% CI 1.06–2.53) were positively associated, while high statin dose (versus low dose, OR 0.6; 95% CI 0.40–0.90) and higher daily number of medication pills (OR 0.93; 95% CI 0.88–0.97) were found to have a negative association with self-reported good adherence to statin medication after acute ischemic stroke. However, stroke severity and diagnosis of hyperlipidemia were not associated with adherence. These results suggest that educational and motivational interventions may enhance statin adherence because modifiable factors were associated with statin adherence.
    Type of Medium: Online Resource
    ISSN: 0014-3022 , 1421-9913
    URL: Article
    DOI: 10.1159/000493530
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482237-4
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  • 8
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    Efficacy and Safety of S-1 Monotherapy in Patients with Advanced Biliary Tract Adenocarcinoma
    S. Karger AG ; 2009
    In:  Oncology Vol. 76, No. 2 ( 2009), p. 126-132
    Details
    In: Oncology, S. Karger AG, Vol. 76, No. 2 ( 2009), p. 126-132
    Abstract: 〈 i 〉 Aim: 〈 /i 〉 We investigated the efficacy and safety of S-1 monotherapy for the treatment of advanced biliary tract adenocarcinoma (BTA) in a clinical practice setting. 〈 i 〉 Methods: 〈 /i 〉 We reviewed clinical data from 217 patients with advanced BTA who were treated with S-1 monotherapy between August 2004 and September 2007. 〈 i 〉 Results: 〈 /i 〉 162 eligible patients were identified. The primary tumors were intrahepatic (n = 57), in the gall bladder (n = 50), in extrahepatic bile ducts (n = 41) and in the ampulla of Vater (n = 14). Sixteen of 120 assessable patients achieved partial responses, with a response rate of 13.3% (95% CI 7.2–19.4%). Another 51 patients had stable disease, with an overall tumor control rate of 55.8% (95% CI 46.9–64.7%). The median time to progression was 2.7 months and the median overall survival time was 6.9 months. Response rates and survival differed significantly according to the primary site of the tumor (p = 0.002 and p 〈 0.001, respectively), with extrahepatic bile duct adenocarcinoma having the best prognosis. The treatment regimen produced only mild toxicity in most cases (grade 1 or 2), even for patients with hyperbilirubinemia. 〈 i 〉 Conclusion: 〈 /i 〉 S-1 has a favorable toxicity profile and can be safely administered to BTA patients with hyperbilirubinemia. The efficacy of S-1 against advanced BTA depends on the tumor site and is most effective in patients with extrahepatic BTA.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000195538
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 9
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    Polymorphisms in Glycolysis-Related Genes Are Associated with Clinical Outcomes of Paclitaxel-Cisplatin Chemotherapy in Non-Small Cell Lung Cancer
    S. Karger AG ; 2020
    In:  Oncology Vol. 98, No. 7 ( 2020), p. 468-477
    Details
    In: Oncology, S. Karger AG, Vol. 98, No. 7 ( 2020), p. 468-477
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate whether polymorphisms in glycolysis-related genes are associated with clinical outcomes of patients with advanced-stage non-small cell lung cancer (NSCLC) undergoing chemotherapy. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 377 patients with NSCLC were enrolled. Sixty-five single-nucleotide polymorphisms in 26 genes involved in the glycolytic pathway were evaluated. The associations of the variants with the chemotherapy response and overall survival (OS) were analyzed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the 65 variants investigated, 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G and 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G significantly correlated with clinical outcomes after chemotherapy in multivariate analyses. 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G was significantly associated with both a worse response to chemotherapy (adjusted odds ratio [aOR] = 0.64, 95% CI = 0.45–0.90, 〈 i 〉 p 〈 /i 〉 = 0.01) and a worse OS (adjusted hazard ratio [aHR] = 1.35, 95% CI = 1.14–1.61, 〈 i 〉 p 〈 /i 〉 = 0.001). 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G was significantly associated with both a better chemotherapy response (aOR = 1.58, 95% CI = 1.07–2.23, 〈 i 〉 p 〈 /i 〉 = 0.02) and a better OS (aHR = 0.80, 95% CI = 0.66–0.98, 〈 i 〉 p 〈 /i 〉 = 0.03). When stratified by tumor histology, 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G was significantly associated with OS only in squamous cell carcinoma, whereas 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G exhibited a significant association with the chemotherapy response and OS only in adenocarcinoma. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 This result suggests that the 〈 i 〉 PFKL 〈 /i 〉 rs2073436C & #x3e;G and 〈 i 〉 GPI 〈 /i 〉 rs7248411C & #x3e;G are useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000504175
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
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