Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib

Azuma, Shintaro; Uojima, Haruki; Chuma, Makoto; Shao, Xue; Hidaka, Hiroyoshi; Nakazawa, Takahide; Kondo, Masaaki; Numata, Kazushi; Iwabuchi, Shogo; Kako, Makoto; Maeda, Shin; Koizumi, Wasaburo; Atsuda, Koichiro

doi:10.1038/s41598-020-73930-3

Cited by 6 publications

(5 citation statements)

References 44 publications

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“…We also expected a correlation between the change in NO levels and HBP. Previous studies have shown that patients who experienced hypertension after administration of lenvatinib had signi cantly better outcomes than did those who did not develop these AEs [15]. A subsequent reduction in NO production lead to HBP.…”

Section: Discussionmentioning

confidence: 99%

“…Of those, 68 patients were excluded due to the following exclusion criteria: (i) lenvatinib discontinued within 14 days, (ii) malignancies other than HCC, (iii) no genomic DNA extracted from blood, and ( ) end-stage liver failure. Therefore, the previous study analyzed 100 patients [15]. Of those patients, 30 did not receive blood serum to identify the biomarkers of the response of HCC to lenvatinib.…”

Section: Patientsmentioning

confidence: 99%

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Change Rate in Serum Nitric Oxide May Affect Lenvatinib Therapy in Hepatocellular Carcinoma

Kawamura

Uojima

Chuma

et al. 2022

Preprint

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Background: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated whether or not NO influence a therapeutic response and adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC).Methods: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO3–) to nitrite (NO2–) with nitrate reductase, followed by quantitation of NO2– based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of maximal therapeutic response and SAE on the change rate of NO from baseline after administration of lenvatinib.Results: After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (P = 0.193). However, the change rate of NO was significantly higher in patients with AEs than in those without AEs (P = 0.013). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (P = 0.040 and P = 0.005, respectively)ConclusionDecreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Change Rate in Serum Nitric Oxide May Affect Lenvatinib Therapy in Hepatocellular Carcinoma

Kawamura

Uojima

Chuma

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We also expected a correlation between the change in NO levels and HBP. Previous studies have shown that patients who experienced hypertension after lenvatinib administration had significantly better outcomes than those who did not develop AEs [ 15 ]. A subsequent reduction in NO production lead to HBP.…”

Section: Discussionmentioning

confidence: 99%

“…This study was performed using previously collected data under another study that was conducted across three medical institutions in Japan from 2017 to 2020 [ 15 ]. The preliminary study enrolled 168 patients aged > 20 years who received lenvatinib for advanced or unresectable HCC (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Of those, 68 patients were excluded due to the following exclusion criteria: (i) lenvatinib discontinued within 14 days, (ii) malignancies other than HCC, (iii) no genomic DNA extracted from blood, and (iv) end-stage liver failure. Therefore, the previous study analyzed 100 patients [ 15 ]. Of those patients, 30 did not receive blood serum to identify the biomarkers of the response of HCC to lenvatinib.…”

Section: Methodsmentioning

confidence: 99%

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The change rate in serum nitric oxide may affect lenvatinib therapy in hepatocellular carcinoma

et al. 2022

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Background Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated the correlation between the change rate of NO levels and clinical responses including adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC). Methods This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO3−) to nitrite (NO2−) with nitrate reductase, followed by quantitation of NO2− based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of the change rate of NO from baseline after administration of lenvatinib on maximal therapeutic response and SAE. Results After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (p = 0.632). However, the change rate of NO was significantly lower in patients with AEs than in those without AEs (p = 0.030). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (p = 0.029 and p = 0.005, respectively). Conclusion Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC.

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Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development

Alkanlı

Çevik

2022

Ind J Clin Biochem

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Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib

Cited by 6 publications

References 44 publications

Change Rate in Serum Nitric Oxide May Affect Lenvatinib Therapy in Hepatocellular Carcinoma

Change Rate in Serum Nitric Oxide May Affect Lenvatinib Therapy in Hepatocellular Carcinoma

The change rate in serum nitric oxide may affect lenvatinib therapy in hepatocellular carcinoma

Determination of the Roles of Endothelial Nitric Oxide Synthase 4VNTR (4a/b), G894T, T786C Gene Variations in the Bladder Cancer Development

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