CYP3A5*3 genotypes and advanced non-small cell lung cancer development

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21030-21030 ◽  
Author(s):  
A. Nogal ◽  
A. Coelho ◽  
A. Araújo ◽  
I. Azevedo ◽  
A. Faria ◽  
...  

21030 Background: Lung cancer is the most common cancer in Europe (381.500 new cases in 2004) and the third in the U.S.A (172.570 new cases in 2005). Smoking is one of the major causes of lung cancer: there are many procarcinogens present in tobacco smoke that, when activated, contribute to the development of this disease. The CYP3A subfamily represents a group of enzymes responsible for the metabolism of many currently used drugs, exogenous carcinogens and endogenous molecules such as steroids. Two of the major enzymes in this family, CYP3A4 and CYP3A5, activate polycyclic aromatic hydrocarbons such as benzo[a]pyrene and other procarcinogens present in tobacco smoke. Functional polymorphisms, such as CYP3A5*3 (associated with the lack of the CYP3A5 protein), could alter individual susceptibility to lung cancer. The aim of our study was to evaluate the influence of this polymorphism in the development of lung cancer. Methods: DNA samples were extracted from peripheral blood cells of 203 patients with non small cell lung cancer, including 42 non- smokers and 156 smokers or former smokers (no data available for the other 5 patients) and 162 blood donors. The CYP3A5*3 polymorphism was analysed through PCR-RFLP (SspI). Analysis of data was performed using the computer software SPSS for windows. The odds ratio (OR) and its 95% confidence interval (CI) were calculated as a measure of the association between CYP3A5*3 genotypes and NSCLC progression. Results: We found significant statistical differences between the control group and the patients with advanced stages (III and IV) of epidermoid and undifferentiated NSCLC (p=0.04; OR = 0.48; 95% CI = 0.232–0.977). Conclusions: Individual differences in the metabolism of carcinogens may influence the susceptibility to cancer development and behaviour. Our preliminary results suggest that the carriers CYP3A5*3 polymorphism are at lower risk of developing advanced lung cancer. This is probably due to a decreased activation of procarcinogens present in tobacco smoke in result of the lack of CYP3A5 caused by the CYP3A5*3 polymorphism. This is consistent with the hypothesis of a cumulative effect of carcinogens on the aggressive behaviour of the disease. No significant financial relationships to disclose.

2019 ◽  
Vol 7 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Akbar Soleimani Babadi ◽  
Arda Kiani ◽  
Esmaeil Mortaz ◽  
Kimia Taghavi ◽  
Adnan Khosravi ◽  
...  

BACKGROUND: Advanced lung cancer is indicated with rapid disease development. Interleukin 27 (IL-27) is regarded as a cytokine with anti-tumour activities. AIM: Since, the impact of type of lung cancer on the level of IL-27 in patient’s serum has not yet been investigated; current study evaluated the clinical stages according to American Joint Committee on Cancer (AJCC) criteria, Tumor-Node-Metastasis (TNM) stage and the lung cancer spread (localized or widespread) and it's correlation with serum IL-27. MATERIAL AND METHODS: Thirty patients with confirmed histopathological lung cancer and 30 cancer-free healthy individuals as the control group were included in the current study. Patients group were assigned to either small cell lung cancer group (SCLC) or non-small cell lung cancer (NSCLC) according to the clinical features and the results of lung biopsy specimens. Level of IL-27 was quantified with enzyme-linked immunosorbent assay (ELISA) test in serum samples. RESULTS: A significant increase in serum IL-27 level was noticed in individuals with lung cancer in comparison with the control group. The level of serum IL-27 in the NSCL squamous carcinoma (NSCLC-Sc) type was significantly greater than in the NSCLC adenocarcinoma (NSCLC-Ad) type, and in both groups, this variable was more than the control group. The serum IL-27 content level was greater in stage III versus stage IV. CONCLUSION: The current research confirmed the existence of the anti-tumour components in patients with NSCLC. IL-27 can be utilised in diagnosis and screening in early stages of lung cancer along with the management of patients. Different levels of IL-27 in different types of lung cancers in the current study can lead to design more comprehensive studies in the future.


2021 ◽  
Vol 28 ◽  
pp. 107327482098579
Author(s):  
Kengo Umehara ◽  
Kaori Yama ◽  
Keisuke Goto ◽  
Azusa Wakamoto ◽  
Tae Hatsuyama ◽  
...  

Introduction: Corticosteroids are used to treat immune-related adverse events (irAEs) associated with nivolumab. However, patients with non-small-cell lung cancer who are administered corticosteroids before the initiation of nivolumab treatment are commonly excluded from clinical trials. The appropriate timing for corticosteroid administration in relation to nivolumab treatment, effects of corticosteroids on the efficacy of nivolumab, and resulting adverse events are not clearly understood. In this study, the effects of differences in the timing of corticosteroid administration on nivolumab efficacy and the resulting adverse events were examined. Methods: A retrospective study was conducted with 109 patients who were treated with nivolumab at Sapporo Minami-Sanjo Hospital between December 2015 and March 2018. Results: Of the 109 patients treated with nivolumab, 12 patients were administered corticosteroids before the first cycle of nivolumab (pre-CS), and 33 patients were administered corticosteroids after the first cycle of nivolumab (post-CS). These 2 groups were compared with the control group comprising 64 patients who were not administered corticosteroids (non-CS). The objective response rate in the post-CS group was significantly higher than that in the non-CS group, and the disease control rate in the pre-CS group was significantly lower than that in the non-CS group. The overall survival time and progression-free survival time in the pre-CS group were significantly shorter than those observed in the non-CS group; however, these did not differ from those in the post-CS group. Conclusions: These results suggest that corticosteroids administered to patients with non-small-cell lung cancer after initiation of nivolumab treatment did not affect the disease prognosis. Thus, corticosteroids can be administered immediately for rapid treatment of irAEs.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15031-e15031
Author(s):  
Mi Young Choi ◽  
Da Hye Moon ◽  
Jong-min Jo ◽  
Hae Ung Lee ◽  
Seri Park ◽  
...  

e15031 Background: Stage IV lung cancer is the most advanced lung cancer state accompanied by metastasized to the area around the lungs or distant major organs. The most common type of lung cancer is non-small cell lung cancer, which is more aggressive and may spread quickly due to organ-specific complex networks such as lymph and major blood vessels. Thus, only precise diagnostic strategy approaches will determine the effectiveness of the actual and successful clinical treatment. Until a recent date, Immunohistochemistry (IHC) for programmed death-ligand 1(PD-L1) test is the only available biomarker test that purpose diagnostics (CDx) and guide the treatment with immune checkpoint inhibitors in NSCLC. Methods: Given that CDx strategy, tissue biopsy has inevitable limitations, including patient risk, repetitive examination, sample preparation, sensitivity, and accuracy. For this reason, our research team contrived the best strategy for biomarker, PD-L1-specific CTCs in stage IV NSCLC group (N = 30) compared to pulmonary inflammatory patient groups (N = 30) CytoGen Smart biopsy platform. Herein, we removed false-positive cells for the first strategy of distinguishing between lymphoid/myeloid cells and the enriched-CTCs. And the second strategic approach is to calculate the pure CTCs (without false-positive cells) and then CTPS) as measured by the PD-L1 expression among pure-CTCs. That application is the percentage of viable CTCs showing partial or complete stained cells at the deducted cut-off value in each fluorescence, respectively. Results: Consequently, we demonstrated over 80% of the concordance rate between VENTANA PD-L1(SP263) and DAKO PD-L1(SP263) assay tested by the PD-L1 expression on stage IV NSCLC in tissue and pure-CTCs based CTPS from the blood. In contrast, pure-CTCs based CTPS in the pulmonary inflammatory group were all negative (recorded as zero). Conclusions: Conclusively, this study implicates that pure-CTCs based CTPS could be deployed for innovative diagnosis strategies as alternatives for tissue biopsy. Our clinical study's data suggested that the possibility for prompt decision for diagnosis and gain powerful insights to guide the personalized treatment in NSCLCs. Clinical trial information: 2020-0553.


2022 ◽  
Author(s):  
Jianbo Zhu ◽  
Guangpeng Chen ◽  
Kai Niu ◽  
Yongdong Feng ◽  
Lijiao Xie ◽  
...  

Background: This study aimed to retrospectively investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) combined with radiotherapy in advanced non-small-cell lung cancer (NSCLC). Methods: Patients with unresectable stage III and IV NSCLC who treated with radiotherapy were enrolled. Patients who received Rh-endostatin infusion throughout the whole peri-radiotherapy period formed the Endostar group, and those who received no Rh-endostatin infusion were the control group. Results: The median progression-free survival was 8.0 and 4.4 months (hazard ratio: 0.53; 95% CI: 0.32–0.90; p = 0.019) and median overall survival was 40.0 and 13.1 months (hazard ratio: 0.53; 95% CI: 0.28–0.98; p = 0.045) for the Endostar and control groups, respectively. The Endostar group exhibited a numerically lower rate of radiation pneumonitis relapse, radiation pneumonitis death and pulmonary fibrosis. Conclusion: Rh-endostatin infusion throughout the peri-radiotherapy period enhanced radiosensitivity and showed better survival outcomes and a tendency toward fewer radiation-related pulmonary events in patients with NSCLC.


Oncogene ◽  
2018 ◽  
Vol 38 (14) ◽  
pp. 2580-2594 ◽  
Author(s):  
Yo-Taro Shirai ◽  
Anna Mizutani ◽  
Saori Nishijima ◽  
Masafumi Horie ◽  
Chisato Kikuguchi ◽  
...  

2016 ◽  
Vol 11 (1) ◽  
pp. 264 ◽  
Author(s):  
Youchao Jia ◽  
Aimin Zang ◽  
Yanguang Feng ◽  
Xiao-Fang Li ◽  
Ke Zhang ◽  
...  

<p class="Abstract">It was aimed to explore the expression level of miRNA-486 and miRNA-499 in the plasma of lung cancer patients and analysis their differences in expre-ssion. The expression level of both miRNA-486 and miRNA-499 in the plasma of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were lower than that of the control group (p&lt;0.05) and the decrease was more obvious in NSCLC. Compare with the miRNA-499,expression quantity in NSCLC patients plasma. There was statistical significance difference (p&lt;0.05) between III~Ⅳstage and I~II stage. The expression quantity of miRNA in plasma of patients with extensive-stage SCLC was lower than that of patients with limited-stage SCLC (p&lt;0.05). The sensitivity and specificity of plasms miRNA-486 respectively were 88.5% and 83.3%. The expression of miRNA-499 and miRNA-486 in lung cancer patients were up-regulated, and might be closely related to the occurrence and prognosis of lung cancer, and might be used as potential screening and prognosis index for lung cancer.</p><p> </p>


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