Development and validation of a prognostic nomogram model in locally advanced NSCLC based on metabolic features of PET/CT and hematological inflammatory indicators.

BACKGROUND: We combined the metabolic features of 18F-FDG-PET/CT and hematological inflammatory indicators to establish a predictive model of the outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiotherapy. RESULTS: A predictive nomogram was developed based on sex, CEA, systemic immune-inflammation index (SII), mean SUV (SUVmean), and total lesion glycolysis (TLG). The nomogram presents nice discrimination that yielded an AUC of 0.76 (95% confidence interval: 0.66-0.86) to predict 1-year PFS, with a sensitivity of 63.6%, a specificity of 83.3%, a positive predictive value of 83.7%, and a negative predictive value of 62.9% in the training set. The calibration curves and DCA suggested that the nomogram had good calibration and fit, as well as promising clinical effectiveness in the training set. In addition, survival analysis indicated that patients in the low-risk group had a significantly longer mPFS than those in the high-risk group (16.8 months versus 8.4 months, P < 0.001). Those results were supported by the results in the internal and external test sets. CONCLUSIONS: The newly constructed predictive nomogram model presented promising discrimination, calibration, and clinical applicability and can be used as an individualized prognostic tool to facilitate precision treatment in clinical practice.

Successful salvage of a severe COVID-19 patient previously with lung cancer and radiation pneumonitis by mesenchymal stem cells: a case report and literature review.

During the COVID-19 pandemic, elderly patients with underlying condition, such as tumors, had poor prognoses after progressing to severe pneumonia and often had poor response to standard treatment. Mesenchymal stem cells (MSCs) may be a promising treatment for patients with severe pneumonia, but MSCs are rarely used for patients with carcinoma. Here, we reported a 67-year-old female patient with lung adenocarcinoma who underwent osimertinib and radiotherapy and suffered from radiation pneumonitis. Unfortunately, she contracted COVID-19 and that rapidly progressed to severe pneumonia. She responded poorly to frontline treatment and was in danger. Subsequently, she received a salvage treatment with four doses of MSCs, and her symptoms surprisingly improved quickly. After a lung CT scan that presented with a significantly improved infection, she was discharged eventually. Her primary disease was stable after 6 months of follow-up, and no tumor recurrence or progression was observed. MSCs may be an effective treatment for hyperactive inflammation due to their ability related to immunomodulation and tissue repair. Our case suggests a potential value of MSCs for severe pneumonia that is unresponsive to conventional therapy after a COVID-19 infection. However, unless the situation is urgent, it needs to be considered with caution for patients with tumors. The safety in tumor patients still needs to be observed.

Genome analysis of a novel avian atadenovirus reveals a possible horizontal gene transfer.

We report the discovery and characterization of a novel adenovirus, Zoothera dauma adenovirus (ZdAdV), from a wild bird species, Zoothera dauma (Scaly thrush). This new atadenovirus was discovered by metagenomic sequencing without virus cultivation. Analyses of the full genome sequence revealed that this new virus is a distinct member of the genus Atadenovirus and represents a novel species. ZdAdV has a genome of 34,760 bp with 28 predicted genes and 39% GC content. ZdAdV is the first atadenovirus to contain ORF19, a gene previously found only in aviadenoviruses. Phylogenetic analysis of ORF19 suggests that it was acquired by ZdAdV through horizontal gene transfer from an aviadenovirus. By analyzing all orthologous genes of aviadenovirus, mastadenovirus, atadenovirus, and siadenovirus, we also found potential horizontal gene transfer for the E4 gene in Pigeon aviadenovirus B. Our study widens our knowledge concerning the genetic diversity and evolutionary history of atadenoviruses and their potential for cross-species transmission.

Clinical characteristics and establishment of a 2-year-OS predictive model of EGFR mutation-positive patients with pleural invasion of lung adenocarcinoma.

To investigate the differences between lung adenocarcinoma with the pleural invasion that has EGFR (epidermal growth factor receptor) 19-del or 21L858R mutations in terms of clinical characteristics and outcomes. EGFR mutation-positive patients with pleural metastasis of lung adenocarcinoma diagnosed in the Department of Respiratory Medicine of Yuhuangding Hospital of Yantai City, Shandong Province, from January 2014 to January 2022 were selected. The clinical data of the patients were collected to retrospectively analyze whether the clinical characteristics and prognosis of patients with 19-del or 21L858R mutation subtype were different and analyze the impact of clinical characteristics on the prognosis of patients. The difference in clinical characteristics between the 2 groups was analyzed by SPSS, P < .05. There was statistical significance. Univariate and multivariate regression analysis was performed with R soft. To establish a 2-year overall survival predictive model for patients with EGFR gene 19-del and 21L858R mutations in patients with pleural invasion of lung adenomas and to provide predictive model maps. Receiver operating characteristic curve, calibration curve, and decision curve analysis were used to evaluate the value of the prediction model in this study. Of the 74 patients included, the 19-del mutation group had a higher incidence of pleural thickening (P = .023) and a lower Ki-67 level (P = .035). There was no difference in 2-year overall survival and progression-free survival between the 2 mutations. There were differences in pleural thickening and Ki-67 index between the 2 groups, but no differences in disease outcome between the 2 groups. The nomogram model established based on gender, treatment regimen, CEA, lymph node metastasis, and pleural changes is accurate and feasible.

Otus scops adenovirus: the complete genome sequence of a novel aviadenovirus discovered in a wild owl.

We present the complete genome sequence of an aviadenovirus obtained by metagenomics from cloacal swabs taken from a free-living Eurasian scops owl (Otus scops, a small raptor distributed in Europe and several parts of Asia) in China. Thirty protein coding genes were predicted in this 40,239-bp-long genome, which encodes the largest fiber protein among all reported aviadenoviruses. The viral genome sequence is highly divergent, and the encoded proteins have an average of only 55% amino acid sequence identity to those of other adenoviruses. In phylogenetic analysis, the new owl virus grouped with members of the genus Aviadenovirus and formed a common clade with another owl adenovirus reported previously in Japan. This is the second complete genome sequence of an aviadenovirus discovered in owls, and its proteins have an average of 62% amino acid sequence identity to those of the previously reported owl adenovirus. Combining this result with comparative genomic analysis of all aviadenoviruses, we propose that this owl virus and the previously described Japanese owl adenovirus can be assigned to two new species in the genus Aviadenovirus. This study provides new data on the diversity of aviadenoviruses in wild birds.

Development and validation of a nomogram for the early prediction of acute kidney injury in hospitalized COVID-19 patients.

Introduction: Acute kidney injury (AKI) is a prevalent complication of coronavirus disease 2019 (COVID-19) and is closely linked with a poorer prognosis. The aim of this study was to develop and validate an easy-to-use and accurate early prediction model for AKI in hospitalized COVID-19 patients. Methods: Data from 480 COVID-19-positive patients (336 in the training set and 144 in the validation set) were obtained from the public database of the Cancer Imaging Archive (TCIA). The least absolute shrinkage and selection operator (LASSO) regression method and multivariate logistic regression were used to screen potential predictive factors to construct the prediction nomogram. Receiver operating curves (ROC), calibration curves, as well as decision curve analysis (DCA) were adopted to assess the effectiveness of the nomogram. The prognostic value of the nomogram was also examined. Results: A predictive nomogram for AKI was developed based on arterial oxygen saturation, procalcitonin, C-reactive protein, glomerular filtration rate, and the history of coronary artery disease. In the training set, the nomogram produced an AUC of 0.831 (95% confidence interval [CI]: 0.774-0.889) with a sensitivity of 85.2% and a specificity of 69.9%. In the validation set, the nomogram produced an AUC of 0.810 (95% CI: 0.737-0.871) with a sensitivity of 77.4% and a specificity of 78.8%. The calibration curve shows that the nomogram exhibited excellent calibration and fit in both the training and validation sets. DCA suggested that the nomogram has promising clinical effectiveness. In addition, the median length of stay (m-LS) for patients in the high-risk group for AKI (risk score ≥ 0.122) was 14.0 days (95% CI: 11.3-16.7 days), which was significantly longer than 8.0 days (95% CI: 7.1-8.9 days) for patients in the low-risk group (risk score <0.122) (hazard ratio (HR): 1.98, 95% CI: 1.55-2.53, p < 0.001). Moreover, the mortality rate was also significantly higher in the high-risk group than that in the low-risk group (20.6 vs. 2.9%, odd ratio (OR):8.61, 95%CI: 3.45-21.52). Conclusions: The newly constructed nomogram model could accurately identify potential COVID-19 patients who may experience AKI during hospitalization at the very beginning of their admission and may be useful for informing clinical prognosis.

Human epididymis protein 4 as a new diagnostic biomarker for rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: This study aimed to evaluate the role of human epididymis protein 4 (HE4) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: HE4 levels in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) samples were determined via electrochemiluminescence immunoassays in 102 RA patients (46 patients with ILD and 56 patients without ILD) and 51 healthy controls (HCs). RESULTS: Serum HE4 levels were significantly higher in RA-ILD patients (141.8±65.92 pmol/l) than those in the RA-no ILD patients (82.67±26.17 pmol/l) and healthy controls (35.72±7.6 pmol/l) (p<0.0001). Consistent with serum HE4 levels, BALF HE4 levels were significantly higher in RA-ILD patients (637.6±154.9 pmol/l) than those in the RA-no ILD patients (427.3±111.2 pmol/l) and healthy controls (206.9±30.46 pmol/l) (p<0.0001). In RA-ILD patients, HE4 levels were positively correlated with HRCT (high-resolution computed tomography) fibrosis scores, whereas a significant inverse relationship was found between HE4 levels and lung function parameters (such as, diffusion capacity of the lung for carbon monoxide (DLCO)). The logistic regression analysis showed that high levels of BALF HE4 (≥595 pmol/l) were associated with RA-ILD (odds ratio [OR] =8.09; 95% confidence interval [CI] =1.317-49.682; p=0.024). CONCLUSIONS: Serum and BALF HE4 levels were elevated in RA-ILD patients and strongly associated with the severity of ILD, thus supporting their potential clinical value as a new diagnostic aid for patients with RA-ILD.

Euphorbia angustifolia lactone B inhibits A549 proliferation and induces apoptosis.

The study is to investigate the effect of Euphorbia angustifolia lactone B (Jolkinolide B, JB) on the proliferation and apoptosis of A549 cells. The proliferation of A549 cells was detected by tetramethyl azothiolide. Activity changes of intracellular caspase-3, 8, 9 were determined by spectrophotometry. The content of cytochrome C (Cyt C) protein and the expression quantity of Bcl-2, Bax, p-ERK1/2, and p-Akt proteins were detected by Western blot and the apoptosis rates were detected by flow cytometry. JB significantly inhibited cell proliferation in a time-dose manner. With increase in JB concentrations, the expression level of Bax protein greatly increased, and the expression of caspase-3 and caspase-9 significantly increased with significant difference (P<0.01). Besides, the peak value of mitochondrial membrane potential decreased, while the number of cells distributed in the depolarized region increased, which was different from that in the control (P<0.05). Moreover, the expression levels of p-ERK1/2 and p-Akt in A549 cells gradually decreased with extending exposure duration. Moreover, 20 µ mol/L LY294002 (an PI3K inhibitor) + 120µg/mL JB and 10µmol/L PD98059 (an ERK inhibitor) +120µg/mL JB also increased apoptosis rates of A549 cells. JB could induced cell apoptosis through promoting endogenous mitochondrial signal transduction pathway and inhibiting PI3K/ERK pathway.

The value of virtual bronchoscopic navigation and radial endobronchial ultrasound-guided transbronchial lung cryobiopsies for pulmonary lymphangitic carcinomatosis.

BACKGROUND: Pulmonary lymphangitic carcinomatosis (PLC) is characterized by malignant infiltration into lung lymphatic channels from a primary site and is often observed in advanced malignant tumors. This study aimed to evaluate the diagnostic yield of transbronchial lung cryobiopsy in PLC guided by radial endobronchial ultrasound and virtual bronchoscopic navigation (VBN). METHODS: This prospective study enrolled 40 patients with clinical and radiologic features indicating PLC. The radial endobronchial ultrasound probe was initially advanced to the region of interest of the desired lobe near the pleura with guidance by VBN. Transbronchial lung biopsy and transbronchial lung cryobiopsy were both performed in the same ROI of all patients with the obtained samples being sent to the pathology laboratory for diagnostic analysis. Procedural complications were recorded. RESULTS: The average number of transbronchial lung biopsy and transbronchial lung cryobiopsy specimens were 4 (3 to 6) and 2 (1 to 3), respectively (t=10.43, P<0.01), with the corresponding mean diameters per biopsy being 3.7 and 8.7 mm (t=12.37, P<0.01). The diagnostic yields of transbronchial lung biopsy and transbronchial lung cryobiopsy were 70% (28/40) and 92.5% (37/40), respectively. The final positive predictive values of transbronchial lung cryobiopsy and transbronchial lung biopsy for PLC were 94.4% (34/36) and 77.8% (28/36), respectively (χ2=23.94, P<0.01). Further, 52.2% (12/23) and 81.5% (22/27) of the patients in the transbronchial lung biopsy and transbronchial lung cryobiopsy groups, respectively, were diagnosed with non-small lung cancer after further molecular analysis (χ2=19.56, P<0.01). Only 2 (5%) cases presented postoperative pneumothorax. Moreover, 0 (0%), 3 (7.5%), and 17 (42.5%) patients presented severe, moderate, and mild bleeding, respectively. There were no other adverse events or deaths. CONCLUSIONS: Transbronchial lung cryobiopsy with the guidance of radial endobronchial ultrasound and VBN without fluoroscopy has a good diagnostic yield for PLC; moreover, it allows one to obtain adequate and intact tissue samples for further molecular analysis.

Downregulation of microRNA­30a in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis patients.

MicroRNAs (miRs) are short, highly conserved small noncoding RNA molecules with fundamental roles in regulating gene expression. To identify miR biomarkers associated with idiopathic pulmonary fibrosis (IPF), the expression pattern of miRs in exosomes from bronchoalveolar lavage fluid (BALF) of elderly patients with IPF were evaluated. High­throughput quantitative detection of miR expression using a microarray indicated that miR­125b, miR­128, miR­21, miR­100, miR­140­3p and miR­374b were upregulated in patients with IPF, while let­7d, miR­103, miR­26 and miR­30a­5p were downregulated. The expression level of miR­30a­5p was further examined, and its potential target genes were predicted using target gene prediction analysis software. A direct regulatory association was confirmed between miR­30a­5p and TGF­ß activated kinase 1/MAP3K7 binding protein 3 (TAB3) via a dual­luciferase reporter assay. Overexpression of miR­30a­5p decreased TAB3, α­smooth muscle actin and fibronectin expression in A549 cells with or without transforming growth factor­ß1 treatment. The decreased expression of miR­30a in the BALF of patients with IPF, along with the consequential increase in TAB3 expression, may be a crucial factor in IPF progression.

Time course changes of oxidative stress and inflammation in hyperoxia-induced acute lung injury in rats.

OBJECTIVES: Therapies with high levels of oxygen are commonly used in the management of critical care. However, prolonged exposure to hyperoxia can cause acute lung injury. Although oxidative stress and inflammation are purported to play an important role in the pathogenesis of acute lung injury, the exact mechanisms are still less known in the hyperoxic acute lung injury (HALI). MATERIALS AND METHODS: In this study, we investigated the time course changes of oxidative stress and inflammation in lung tissues of rats exposed to >95% oxygen for 12-60 hr. RESULTS: We found that at 12 hr after hyperoxia challenge, the activities of superoxide dismutase and glutathione peroxidase were significantly reduced with remarkably increased lipid peroxidation. At 12 hr, NF-κB p65 expression was also upregulated, but Iκ-Bα expression showed a remarkable decline. Significant production of inflammatory mediators, e.g, interleukin-1ß, occurred 24 hr after hyperoxia exposure. In addition, the expression of intracellular adhesion molecule 1 expression and the activity of myeloperoxidase were significantly increased at 24 hr with a peak at 48 hr. CONCLUSION: Our data support that hyperoxia-induced oxidative damage and NF-κB pathway activation implicate in the early phase of HALI pathogenesis.

Cbl participates in shikonin-induced apoptosis by negatively regulating phosphoinositide 3-kinase/protein kinase B signaling.

Shikonin, a naturally occurring naphthoquinone, exhibits anti-tumorigenic activity. However, its precise mechanisms of action have remained elusive. In the present study, the involvement in the action of shikonin of the ubiquitin ligases Cbl-b and c-Cbl, which are negative regulators of phosphoinositide 3-kinase (PI3K) activation, was investigated. Shikonin was observed to reduce cell viability and induce apoptosis and G2/M phase arrest in lung cancer cells. In addition, shikonin increased the protein levels of B-cell lymphoma 2 (Bcl-2)-associated X and p53 and reduced those of Bcl-2. Additionally, shikonin inhibited PI3k/Akt activity and upregulated Cbl protein expression. In addition, a specific inhibitor of PI3K, LY294002, was observed to have a synergistic effect on the proliferation inhibition and apoptotic induction of A549 cells with shikonin. In conclusion, the results of the present study suggested that Cbl proteins promote shikonin-induced apoptosis by negatively regulating PI3K/Akt signaling in lung cancer cells.

The protection of glycyrrhetinic acid (GA) towards acetaminophen (APAP)-induced toxicity partially through fatty acids metabolic pathway.

BACKGROUND: Acetaminophen (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, and herbs are the important sources for isolation of compounds preventing APAP-induced toxicity. AIMS: To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. METHODS: APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg). Glycyrrhetinic acid was dissolved in corn oil, and intraperitoneal injection (i.p.) of glycyrrhetinic acid (500 mg/kg body weight) was performed for 20 days before the injection of APAP. UPLC-ESI-QTOF MS was employed to analyze the metabolomic profile of serum samples. RESULTS: The pre-treatment of glycyrrhetinic acid significantly protected APAP-induced toxicity, indicated by the histology of liver, the activity of ALT and AST. Metabolomics showed that the level of palmtioylcarnitine and oleoylcarnitine significantly increased in serum of APAP-treated mice, and the pre-treatment with GA can prevent this elevation of these two fatty acid-carnitines. CONCLUSION: Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.

PPM1D overexpression predicts poor prognosis in non-small cell lung cancer.

It has been reported that protein phosphatase, Mg(2+)/Mn(2+) dependent, 1D (PPM1D) plays an important role in cancer tumorigenesis. However, the clinical and functional significance of PPM1D expression has not been characterized previously in non-small cell lung cancer (NSCLC). The purpose of this study was to assess PPM1D expression and to explore its contribution to NSCLC. We examined PPM1D messenger RNA (mRNA) expression in 53 NSCLC tissues and matched adjacent noncancerous tissues by quantitative reverse transcription PCR (qRT-PCR). Furthermore, the PPM1D protein expression was analyzed by immunohistochemistry in 157 NSCLC samples. The relationship between PPM1D expression and clinicopathological features was analyzed by appropriate statistics. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between PPM1D expression and prognosis of NSCLC patients. The relative mRNA expression of PPM1D was significantly elevated in NSCLC tissues as compared with adjacent noncancerous tissues (P < 0.001). The high expression of PPM1D in NSCLC tissues was significantly correlated with tumor grade (P = 0.006), tumor size (P = 0.017), clinical stage (P = 0.001), and lymph node metastases (P = 0.002). Kaplan-Meier survival analysis revealed that high PPM1D expression correlated with poor prognosis of NSCLC patients (P < 0.001). Multivariate analysis showed that PPM1D expression was an independent prognostic marker for overall survival of NSCLC patients. In conclusion, PPM1D plays an important role in the progression of NSCLC. PPM1D may potentially be used as an independent biomarker for the prognostic evaluation of NSCLC.

Bone formation in adipose-derived stem cells isolated from elderly patients with osteoporosis: a preliminary study.

We have explored the osteogenic potency of adipose-derived stem cells from osteoporotic patients (opASCs). opASCs were osteogenically induced in vitro with collagen I hydrogel or in culture plate. Detection of alkaline phosphatase (ALPase) and cell mineralisation, and quantitative RT-PCR of collagen I, osteocalcin and bone sialoprotein were undertaken. Proliferation and morphology studies were also performed. After 14 days, opASCs-collagen I hydrogel composite was implanted into nude mice for 4 weeks prior to radiographic and histological analysis. Staining of ALPase and cell mineralisation was strongly positive in opASCs. Fibroblast-like opASCs induced with collagen I hydrogel were evenly distributed and proliferated at a higher rate than in culture plates, showing similar growth curves for both genders. Expression of ALPase activity, cell mineralisation and osteogenic specific genes were higher in opASCs with collagen I hydrogel (male samples had better osteogenicity than female samples) than in culture plates. After implantation for 4 weeks, radiopaque area signifying new bone tissue was observed in opASCs-collagen I hydrogel composite, with no donor gender differences. Thus opASCs with collagen I hydrogel have adequate osteogenic potency and offer new possibilities for osteoporosis-related bone tissue engineering in male and female patients.

Activation of PI3K/Akt and ERK signaling pathways antagonized sinomenine-induced lung cancer cell apoptosis.

Sinomenine (SIN) is a bioactive component derived from a Chinese medicinal plant. Our previous studies demonstrated that SIN has cytotoxic effects on human lung cancer cells. However, the antitumor molecular mechanisms of SIN have yet to be elucidated in detail. In the present study, we further explored the effects of SIN on NCI-H460 human lung cancer cell viability and apoptosis and investigated the regulation and function of PI3K/Akt and ERK signaling pathways during SIN-induced apoptosis in various lung cancer cell lines. NCI-H460 cells were incubated with 200 µg/ml SIN for the indicated times (0, 24, 48 or 72 h). Cell viability was assessed by MTT assay. Akt, p-Akt, ERK1/2 and p-ERK1/2 protein levels were detected by western blotting, respectively. Two different selective inhibitors (LY294002 for the PI3K pathway; PD98059 for the MEK/ERK pathway) were used to characterize the relative roles of PI3K/Akt and ERK in SIN-induced apoptosis. Apoptosis was determined by flow cytometry. SIN inhibited the proliferation of NCI-H460 cells in a time-dependent manner, which was accompanied with significant activation of pAkt and pERK. LY294002 and PD98059 both significantly increased SIN-induced apoptosis in NCI-H460, NCI-H226 and NCI-H522 cells. Our findings suggest that the activation of the PI3K/Akt and ERK signaling pathways antagonize SIN-induced lung cancer cell apoptosis and molecules that inhibit these pathways should potentiate the effects of SIN. This study represents a significant step forward in our understanding of the signal transduction pathways associated with the apoptosis elicited by SIN.

Osthole induces G2/M arrest and apoptosis in lung cancer A549 cells by modulating PI3K/Akt pathway.

BACKGROUND: To explore the effects of Osthole on the proliferation, cell cycle and apoptosis of human lung cancer A549 cells. METHODS: Human lung cancer A549 cells were treated with Osthole at different concentrations. Cell proliferation was measured using the MTT assay. Cell cycle was evaluated using DNA flow cytometry analysis. Induction of apoptosis was determined by flow cytometry and fluorescent microscopy. The expressions of Cyclin B1, p-Cdc2, Bcl-2, Bax, t-Akt and p-Akt were evaluated by Western blotting. RESULTS: Osthole inhibited the growth of human lung cancer A549 cells by inducing G2/M arrest and apoptosis. Western blotting demonstrated that Osthole down-regulated the expressions of Cyclin B1, p-Cdc2 and Bcl-2 and up-regulated the expressions of Bax in A549 cells. Inhibition of PI3K/Akt signaling pathway was also observed after treating A549 cells with Osthole. CONCLUSIONS: Our findings suggest that Osthole may have a therapeutic application in the treatment of human lung cancer.

Effects of sinomenine on proliferation and apoptosis in human lung cancer cell line NCI-H460 in vitro.

Sinomenine (SIN) is an herbal ingredient isolated from Sinomenium acutum Rehd. et Wils. We evaluated the effects of SIN on the growth and apoptosis of human lung cancer NCI-H460 cells. SIN inhibited the proliferation of the cells in a dose- and time-dependent manner. Apoptosis was confirmed by flow cytometry, the TUNEL assay and transmission electron microscopy. SIN-induced apoptosis was accompanied by the collapse of mitochondrial membrane potential, the release of cytochrome C and the activation of caspase-9 and -3. SIN also increased Bax and decreased Bcl-2 protein levels in the NCI-H460 cells. Data analysis suggested that SIN exerted a significant apoptotic effect on NCI-H460 cells through the mitochondrial pathway. SIN is therefore a promising chemopreventive candidate for lung carcinoma.