Study on the mitochondrial apoptosis pathways of small cell lung cancer H446 cells induced by Trichinella spiralis muscle larvae ESPs

Parasitology ◽  
2017 ◽  
Vol 144 (6) ◽  
pp. 793-800 ◽  
Author(s):  
JINGMEI LUO ◽  
LI YU ◽  
GUANGCHENG XIE ◽  
DAN LI ◽  
MENG SU ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Trichinella Spiralis ◽  
Negative Control ◽  
Small Cell ◽  
Control Group ◽  
Secretory Proteins ◽  
Small Cell Lung ◽  
Antineoplastic Action

SUMMARYTrichinella spiralis (T.spiralis) muscle-larva (ML) excretory–secretory proteins (ESPs) contain antitumour-active substances. ESPs have been shown to inhibit tumour growth. To explore the effects of these proteins on small cell lung cancer cells and the possible mechanisms of their antineoplastic action, H446 SCLC cells were co-cultured with different concentrations of T. spiralis ML ESPs for 12, 24 and 48 h. Our results showed that T. spiralis ML ESPs significantly inhibited H446 cell proliferation, which was dose-and time-dependent. The results of flow cytometry testing indicate a clear apoptosis trend in H446 cells co-cultured with ESPs for 24 h. Reverse transcription polymerase chain reaction and Western blotting results showed increased expression of pro-apoptosis genes Bax, Cyt-C, Apaf-1, caspase-9 and caspase-3, compared with the negative control group, and decreased the expression of anti-apoptosis genes Bcl-2 and Livin. Our results suggest that T. spiralis ML ESPs can induce apoptosis in H446 cells through a mitochondrial pathway, which may be a mechanism of antineoplastic action in T. spiralis ML ESPs.

scholarly journals Effect of Systemic Corticosteroid Therapy on the Efficacy and Safety of Nivolumab in the Treatment of Non-Small-Cell Lung Cancer

2021 ◽  
Vol 28 ◽  
pp. 107327482098579
Author(s):  
Kengo Umehara ◽  
Kaori Yama ◽  
Keisuke Goto ◽  
Azusa Wakamoto ◽  
Tae Hatsuyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
Corticosteroid Administration

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.

Efficacy and safety of recombinant human endostatin during peri-radiotherapy period in advanced non-small-cell lung cancer

2022 ◽  
Author(s):  
Jianbo Zhu ◽  
Guangpeng Chen ◽  
Kai Niu ◽  
Yongdong Feng ◽  
Lijiao Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Pneumonitis ◽  
Small Cell ◽  
Hazard Ratio ◽  
Control Group ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Recombinant Human Endostatin

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.

scholarly journals miRNA-486 and miRNA-499 in human plasma evaluate the clinical stages of lung cancer and play a role as a tumor suppressor in lung tumorigeneisis not pathogenesis

2016 ◽  
Vol 11 (1) ◽  
pp. 264 ◽  
Author(s):  
Youchao Jia ◽  
Aimin Zang ◽  
Yanguang Feng ◽  
Xiao-Fang Li ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Statistical Significance ◽  
Small Cell ◽  
Expression Level ◽  
Control Group ◽  
Small Cell Lung ◽  
Lung Cancer Patients

<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>

Effect of microRNA-4268 on Proliferation and Apoptosis of Non-Small Cell Lung Cancer Cells Through Regulating Signal Transducer and Activator of Transcription 3 Level

2021 ◽  
Vol 11 (4) ◽  
pp. 725-730
Author(s):  
Lei Han ◽  
Renzhi Yu ◽  
Xin Ni ◽  
Zenglei Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mrna Level ◽  
Annexin V ◽  
Small Cell ◽  
Control Group ◽  
Cancer Tissue ◽  
Small Cell Lung

STAT3 is closely related to non-small cell lung cancer (NSCLC). miR-4268 is predicted to regulate STAT3 level by MiRDB analysis. Therefore, our study investigated whether miR-4268 affects NSCLC cells by regulating STAT3. The control group (NC group), miR-4268 Mimics group, and miR-4268 Mimics +pFBD-STAT3 group were set up followed by analysis of miR-4268 and STAT3 mRNA level by QRT-PCR, relationship between miR-4268 and STAT3 by dual fluorescein reporter assay, STAT3 and Tubulin protein level by Western blot, cell proliferation by MTT assay and apoptosis by Annexin V-FITC/PI staining. Compared with normal tissue, miR-4268 expression in cancer tissue was significantly reduced (P <0.01), while STAT3 level was elevated (P <0.01). STAT3 was a target gene of miR-4268. Compared with NC group, STAT3 level was significantly reduced in miR-4268 Mimics group (P <0.01) and increased in miR-4268 Mimics+pFBD-STAT3 group compared with miR-4268 Mimics group (P <0.05). Compared to NC group, miR-4268 Mimics group had reduced cell proliferation and increased cell apoptosis and opposite changes were observed in miR-4268 Mimics+pFBD-STAT3 group which had increased cell proliferation and decreased apoptosis (P < 0.05). miR-4268 regulates STAT3 mRNA level and inhibits NSCLC cell proliferation and promotes apoptosis. However, over-expression of STAT3 can inhibit the effect of miR-4268.

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 ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tobacco Smoke ◽  
Small Cell ◽  
Cancer Development ◽  
Advanced Lung Cancer ◽  
Control Group ◽  
Small Cell Lung ◽  
Functional Polymorphisms

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.

scholarly journals MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case–control study

2016 ◽  
Vol 23 (2) ◽  
pp. 86 ◽  
Author(s):  
R. Razzak ◽  
E.L.R. Bédard ◽  
J.O. Kim ◽  
S. Gazala ◽  
L. Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Sputum Sample ◽  
Locally Advanced ◽  
Small Cell ◽  
Control Group ◽  
Unsupervised Hierarchical Cluster ◽  
Small Cell Lung

Background Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample.Methods A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis.Results Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively.Conclusions A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool.

scholarly journals Antitumor Effect of Membrane-type PBLs on Non-Small Cell Lung Cancer Cell of ICR Mice

2020 ◽  
Author(s):  
Junli Cao ◽  
Peng Su ◽  
Yuefeng Zhang ◽  
Xin Wang ◽  
Xiwei Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Synergistic Effect ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Time Dependent ◽  
Control Group ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
Icr Mice

Abstract This study aims at probing the inhibitory effect of transmembrane PBLs on non-small cell lung cancer (NSCLC) H446 cells and the potential application of PBLs on immune system of the experimental mice loaded with H446 cells. The changes of the gene expression of microRNA-25 and 223 in ICR mice with NSCLC were also investigated. Sixty ICR mice were randomly divided into experimental and control groups. The animal model was established via inoculation of NSCLC H446 cells at the hind thigh of mice. The plasmid PBLs was dissolved in saline solution and injected into the muscle of left thigh of the mice in experimental groups with different doses (0.1 mg, 0.2 mg and 0.3 mg per ICR mouse) using in situ injection method. After injection of PBLs solution, each three mice were killed at 12 h, 24 h, 36 h, and 48 h, respectively. The expression of microRNA-25 and 223 were detected by semi-quantitative reverse transcription-polymerase chain reaction. Tumor Necrosis Factor-γ (TNF-γ), Interleukelin-2 (IL-2) and Heat Shock Protein 70 (HSP70) in Bronchoalveolar Lavage Fluid (BALF) were detected by enzyme-linked immunosorbent assay. The expression of TNF-γ and IL-2 protein in lung tissue were detected by western blotting. The expression of microRNA-25 was up-regulated in the tissues and BALF with a dose- and time-dependent manner while microRNA-223 was down-regulated. The difference were statistically significant comparing the control group (P<0.05). The TNF-γ and IL-2 levels in BALF of ICR mice in experimental group were increased comparing the control group with a dose-dependent manner (P<0.05). Synergistic effect between PBLs and HSP70 was also studied. It was found that the growth of tumor was significantly suppressed after the transfection of PBLs. In the presence of PBLs, the proliferation of splenocytes and cytolysis in early phase of tumor development was significantly enhanced. Thus, such anti-tumor effect was further improved by the synergistic effect of PBLs with HSP70. The expression of microRNA-25 and 223 are associated with NSCLC in a dose- and time-dependent manner, they might be considered as potential biomarkers for early diagnosis of NSCLC.

scholarly journals Multimodal Prehabilitation in Patients with Non-Small Cell Lung Cancer Undergoing Anatomical Resection: Protocol of a Non-Randomised Feasibility Study

2020 ◽  
Author(s):  
Charlotte Johanna Laura Molenaar ◽  
Erik Martin Von Meyenfeldt ◽  
Carlijn Tini Ireen de Betue ◽  
Goof Schep ◽  
Magdolen Youssef El Soud ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Feasibility Study ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Health Care Facilities ◽  
Teaching Hospitals ◽  
Ethical Review ◽  
Control Group ◽  
Small Cell Lung

Abstract BackgroundThe preoperative period can be used to enhance a patient’s functional capacity with multimodal prehabilitation and, consequently improve and fasten postoperative recovery. Especially non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is a challenge, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to pulmonary surgery and conduct a study to assess feasibility and efficacy of the programme. Publication of this protocol may help other health care facilities to implement such a programme. MethodsThe multimodal prehabilitation programme consists of an exercise programme, nutritional support, mental support, smoking cessation programme, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme and 20 will be assessed in the control group, according to patient preference. Assessments take place at four time points: baseline, week before surgery, six weeks postoperatively and three months postoperatively. Feasibility and efficacy of the prehabilitation programme will be assessed as primary outcomes. DiscussionSince the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible and effective. The non-randomised fashion of the study might result in a selection bias. However, the control group is necessary, to put the prehabilitation group in perspective and to assess feasibility further. By publishing this protocol of our feasibility study, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical lung cancer patients.Trial registrationThis feasibility study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080. Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

scholarly journals Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for Advanced Nonsquamous Non–Small-Cell Lung Cancer: ECOG-ACRIN 5508

2019 ◽  
Vol 37 (26) ◽  
pp. 2360-2367 ◽  
Author(s):  
Suresh S. Ramalingam ◽  
Suzanne E. Dahlberg ◽  
Chandra P. Belani ◽  
Joel N. Saltzman ◽  
Nathan A. Pennell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Control Group ◽  
Combination Regimen ◽  
Small Cell Lung ◽  
Nonsquamous Nsclc

PURPOSE Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non–small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy. PATIENTS AND METHODS Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group. RESULTS Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P < .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen. CONCLUSION Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.

Improved Chemotherapy Outcomes of Patients With Small-cell Lung Cancer Treated With Combined Alkalization Therapy and Intravenous Vitamin C

2021 ◽  
Vol 1 (3) ◽  
pp. 157-163
Author(s):  
REO HAMAGUCHI ◽  
RYOKO NARUI ◽  
HIROMASA MORIKAWA ◽  
HIROMI WADA
Keyword(s):  
Lung Cancer ◽  
Vitamin C ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Intervention Group ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
Urine Ph ◽  
Intravenous Vitamin

Background/Aim: This study aimed to investigate the effects of the combination of alkalization therapy (an alkaline diet and bicarbonate therapy) and intravenous vitamin C treatment on chemotherapy outcomes in patients with small-cell lung cancer (SCLC) (study registration: UMIN000043056). Patients and Methods: Twelve patients with SCLC in the intervention group (receiving both alkalization therapy and vitamin C treatment together with chemotherapy) were retrospectively compared to 15 patients with SCLC in the control group (receiving chemotherapy only). Results: The mean urine pH of the intervention group was significantly higher than that of the control group (7.32±0.45 vs. 6.44±0.74, respectively; p<0.005). The median overall survival for the intervention group was 44.2 months (95% confidence interval=22.0−not reached), as compared with 17.7 months for the control group (95% confidence intervaI=13.5−not reached; p<0.05). Conclusion: The combination of alkalization therapy and intravenous vitamin C treatment may be associated with favorable outcomes in patients with SCLC receiving chemotherapy.

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