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Lung adenocarcinoma (LUAD) is the predominant subtype within the spectrum of lung malignancies. CTHRC1 has a pro-oncogenic role in various cancers. Here, we observed the upregulation of CTHRC1 in LUAD, but its role in cisplatin resistance in LUAD remains unclear. Bioinformatics analysis was employed to detect CTHRC1 and SRY-related HMG-box 4 (SOX4) expression in LUAD. Gene Set Enrichment Analysis predicted the enriched pathways related to CTHRC1. JASPAR and MotifMap databases predicted upstream transcription factors of CTHRC1. Pearson analysis was conducted to analyze the correlation between genes of interest. The interaction and binding relationship between CTHRC1 and SOX4 were validated through dual-luciferase and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction determined the expression of CTHRC1 and SOX4 genes. CCK-8 was performed to assess cell viability and calculate IC 50 value. Flow cytometry examined the cell cycle. Comet assay and western blot assessed DNA damage. CTHRC1 and SOX4 were upregulated in LUAD. CTHRC1 exhibited higher expression in cisplatin-resistant A549 cells compared to cisplatin-sensitive A549 cells. Knockdown of CTHRC1 enhanced DNA damage during cisplatin treatment and increased the sensitivity of LUAD cells to cisplatin. Additionally, SOX4 modulated DNA damage repair (DDR) by activating CTHRC1 transcriptional activity, promoting cisplatin resistance in LUAD cells. SOX4 regulated DDR by activating CTHRC1, thereby enhancing cisplatin resistance in LUAD cells. The finding provides a novel approach to address clinical cisplatin resistance in LUAD, with CTHRC1 possibly serving as a candidate for targeted therapies in addressing cisplatin resistance within LUAD., (© 2024 Wiley‐VCH GmbH.)

Constituted by various heterogeneous cells, the tumor microenvironment (TME) is capable of promoting tumor proliferation, invasion, and metastasis through extensive crosstalk. The pivotal factor influencing the survival time of patients and their response to immunotherapy lies in the intratumoral immune environment. We obtained 112 differential genes related to T cell-mediated tumor killing in LUAD by employing bioinformatics analysis on the basis of the TCGA and TISIDB databases. Then the 6-gene prognostic risk score model ( CA9 , OIP5 , TIMP1 , SEC11C , FURIN , and TLR10 ) was constructed by conducting univariate LASSO as well as multivariate Cox regression analyses. The median risk score was taken as the threshold to classify the samples into two groups. Survival analysis revealed that the low-risk group exhibited a more favorable prognosis. Subsequently, the Cox regression analysis combined with clinical information (age, gender, and pathological stage) and the risk score of LUAD patients demonstrated the potential of this model as an independent prognostic factor. The nomogram established based on clinical information and a risk score in combination with the calibration curve indicated that this model had good predictive ability. Notable enrichment of the differential genes from the high- and low-risk groups was discovered in immune-associated processes or pathways, as shown by the GO and KEGG enrichment analyses. The combined use of single-sample gene enrichment analysis (ssGSEA) and immunophenoscore (IPS) demonstrated heightened immune infiltration and IPS scores in the low-risk group, indicating that immunotherapy was likely to show good efficacy in patients from this group. To sum up, the prognostic model of LUAD constructed based on T-cell-mediated cell killing-related genes was not only capable of screening the prognosis of LUAD patients but was also used for screening those LUAD patients with high sensitivity to immunotherapy. Our study offered novel insights into the clinical treatment and prognostic prediction of LUAD patients.

Ethnopharmacological Relevance: Salvia miltiorrhiza Bunge and Panax ginseng C. A. Meyer have special curative effect on cancer treatment. The optimizing component formula (OCF) extracted from those two herbs was in line with the anti-lung cancer treatment principle of activating blood and supplementing 'Qi'. However, the study on the mechanism of component formula has always been an insurmountable challenge. Nowadays, the application of network pharmacology and artificial intelligence (AI) in the field of TCM provides new ideas for the study of new targets and mechanisms of TCM, which promotes the modernization of TCM., Aim of the Study: This study aims to further explore the anti-lung cancer mechanism of OCF by using an integrated strategy of network pharmacology and AI technology., Materials and Methods: Bioinformatic analysis was used to analyze the expression levels, prognosis and survival of DTL and PDCD4 in cancer patients. The binding strength of OCF and DTL was simulated by molecular docking, and the affinity between them was detected by Bio-layer interferometry. Network pharmacology was used to predict the active components, potential targets and pathways of OCF. The association between key targets and their corresponding components and DTL was analyzed by Ingenuity Pathway Analysis (IPA). MTT assay, colony formation assay, wound-healing assay and transwell assay were used to verify the inhibitory effects of OCF on lung cancer cells in vitro. qRT-PCR and Western blot assay were used to detect the effects of OCF on mRNA and protein expression of DTL, PDCD4 and key genes in MAPK/JNK pathways., Results: Bioinformatics analysis showed that DTL was significantly up-regulated in lung cancer, which was associated with high malignancy rate, high metastasis rate and poor prognosis of primary tumor. PDCD4 was down-regulated in lung cancer, and associated with high metastasis rate and poor prognosis. The good affinity between OCF and DTL was predicted and verified by molecular docking and Bio-layer interferometry. Based on the network pharmacological databases, 40 active components and 220 corresponding targets of OCF were screened out. KEGG analysis showed that OCF component targets were mainly enriched in MAPK signaling pathway. IPA results showed the interrelationship between DTL, PDCD4, MAPK pathway genes and their corresponding OCF components. In addition, in vitro experiments demonstrated anti-lung cancer activity of OCF, as validated, via impairing cell viability and cell proliferation, as well as inhibiting migration and invasion abilities in lung cancer cells. qRT-PCR showed that OCF down-regulated the mRNA expression of DTL, MAP4K1, JNK, c-Jun and c-Myc, and up-regulated the mRNA expression of PDCD4 and P53 genes in A549 lung cancer cells. Western blot suggested that OCF suppressed the protein level of DTL and blocked the ubiquitination of PDCD4 in A549 lung cancer cells, and down-regulated the protein levels of MAP4K1, p-JNK and p-c-Jun while up-regulated the proteins expression level of P53., Conclusions: OCF might elicit an anti-lung cancer effect by blocking DTL-mediated PDCD4 ubiquitination and suppression of the MAPK/JNK pathway. Meanwhile, our work revealed that network pharmacology and AI technology strategy are cogent means of studying the active components and mechanism of TCM., Competing Interests: Declaration of competing interest All the authors have read and approved the final manuscript, and there is no known competing interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18 F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18 F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUV max , fitted K i value based on dynamic scanning, and corresponding maximum diameter ( D max ) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SUV max / D max and K i / D max (ΔSUV max / D max ; Δ K i / D max ) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between ΔSUV max / D max and Δ K i /D max from all groups was determined. There was no significant difference for ΔSUV max / D max between the IPM and sMPLC groups, while the IPM group had a significantly higher Δ K i /D max than the sMPLC group. The AUC of Δ K i / D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059, sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91, 95% CI: 0.79-0.96, p < 0.0001) between ΔSUV max / D max and Δ K i / D max in the IPM group but not in the sMPLC group (Pearson r = 0.45, p > 0.05). Dynamic 18 F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUV max in discriminating IPM from sMPLC in patients with multiple lung cancer nodules., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Weize Lv et al.)

Multimodal positron emission tomography-computed tomography (PET-CT) is used routinely in the assessment of cancer. PET-CT combines the high sensitivity for tumor detection of PET and anatomical information from CT. Tumor segmentation is a critical element of PET-CT but at present, the performance of existing automated methods for this challenging task is low. Segmentation tends to be done manually by different imaging experts, which is labor-intensive and prone to errors and inconsistency. Previous automated segmentation methods largely focused on fusing information that is extracted separately from the PET and CT modalities, with the underlying assumption that each modality contains complementary information. However, these methods do not fully exploit the high PET tumor sensitivity that can guide the segmentation. We introduce a deep learning-based framework in multimodal PET-CT segmentation with a multimodal spatial attention module (MSAM). The MSAM automatically learns to emphasize regions (spatial areas) related to tumors and suppress normal regions with physiologic high-uptake from the PET input. The resulting spatial attention maps are subsequently employed to target a convolutional neural network (CNN) backbone for segmentation of areas with higher tumor likelihood from the CT image. Our experimental results on two clinical PET-CT datasets of non-small cell lung cancer (NSCLC) and soft tissue sarcoma (STS) validate the effectiveness of our framework in these different cancer types. We show that our MSAM, with a conventional U-Net backbone, surpasses the state-of-the-art lung tumor segmentation approach by a margin of 7.6% in Dice similarity coefficient (DSC).

Abstract: It remains unknown whether dissecting the intrapulmonary lymph nodes (stations 13 and 14) when resecting peripheral non-small cell lung cancer (NSCLC) is necessary for accurate tumor node metastasis (TNM) staging. This study investigated intrapulmonary lymph node dissection (stations 13 and 14) on the pathological staging of peripheral NSCLC and the metastatic pattern of the lymph nodes.This retrospective study included patients with primary peripheral NSCLC who underwent radical dissection between January 2013 and December 2015. The clinical data of patients and examination results of intrapulmonary stations 12, 13, and 14 lymph nodes were analyzed.Of 3019 resected lymph nodes in a total of 234 patients (12.9/patient), 263 (8.7%) had metastasis. Ninety-nine patients had lymph node metastasis (42.3%): 40 (17.1%) were N1, 11 (4.7%) were N2, 48 (20.5%) were both N1 and N2, and 135 (57.7%) had no N1 or N2 metastasis. Sixteen (6.8%) patients had metastasis of stations 13 and/or 14. Metastasis in N1 positive patients of stations 10, 11, 12, 13, and 14 were 2.7%, 10.5%, 9.8%, 10.4%, and 8.5%, respectively. Missed detection without station 13 and 14 dissection was up to 6.8% (16/234).Dissection of stations 13 and 14 could be helpful for the identification of lymph node metastasis and for the accurate TNM staging of primary NSCLC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objective: [18f]-fluorodeoxyglucose (fdg) positron emission tomography - computed tomography (pet-ct) is now the preferred imaging modality for staging many cancers. Pet images characterize tumoral glucose metabolism while ct depicts the complementary anatomical localization of the tumor. Automatic tumor segmentation is an important step in image analysis in computer aided diagnosis systems. Recently, fully convolutional networks (fcns), with their ability to leverage annotated datasets and extract image feature representations, have become the state-of-the-art in tumor segmentation. There are limited fcn based methods that support multi-modality images and current methods have primarily focused on the fusion of multi-modality image features at various stages, i.e., early-fusion where the multi-modality image features are fused prior to fcn, late-fusion with the resultant features fused and hyper-fusion where multi-modality image features are fused across multiple image feature scales. Early- and late-fusion methods, however, have inherent, limited freedom to fuse complementary multi-modality image features. The hyper-fusion methods learn different image features across different image feature scales that can result in inaccurate segmentations, in particular, in situations where the tumors have heterogeneous textures., Methods: we propose a recurrent fusion network (rfn), which consists of multiple recurrent fusion phases to progressively fuse the complementary multi-modality image features with intermediary segmentation results derived at individual recurrent fusion phases: (1) the recurrent fusion phases iteratively learn the image features and then refine the subsequent segmentation results; and, (2) the intermediary segmentation results allows our method to focus on learning the multi-modality image features around these intermediary segmentation results, which minimize the risk of inconsistent feature learning., Results: we evaluated our method on two pathologically proven non-small cell lung cancer pet-ct datasets. We compared our method to the commonly used fusion methods (early-fusion, late-fusion and hyper-fusion) and the state-of-the-art pet-ct tumor segmentation methods on various network backbones (resnet, densenet and 3d-unet). Our results show that the rfn provides more accurate segmentation compared to the existing methods and is generalizable to different datasets., Conclusions: we show that learning through multiple recurrent fusion phases allows the iterative re-use of multi-modality image features that refines tumor segmentation results. We also identify that our rfn produces consistent segmentation results across different network architectures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro . Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro . We also found that the AKT/GSK-3 β / β -catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy., Competing Interests: All the authors have read and approved the final manuscript, and there is no known competing interest., (Copyright © 2021 Yanxia Ma et al.)

Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ethnopharmacological Relevance: In traditional Chinese medicine, supplementing Qi and strengthening body resistance are an important principle of anticancer treatment. Panax ginseng C.A.Mey. (ginseng) and Astragalus membranaceus Bunge (astragalus) are the representative herbs for this therapeutic principle., Aim of the Study: This study aims to explore the effect of the water extract of ginseng and astragalus (WEGA) on regulating macrophage polarization and mediating anticancer in the tumor microenvironment., Materials and Methods: A549 cells were cultured in tumor-associated macrophage (TAM) supernatant with various concentrations of WEGA (0, 5, 10, 20 mg/mL). A549 cell proliferation was determined through methyl thiazole tetrazolium (MTT) assay and real-time cell analysis (RTCA), respectively. In vivo experiments were performed with a Lewis lung cancer (LLC) xenograft mouse model. Forty-eight mice were divided into six groups and treated with saline, WEGA, or cis-diamine dichloro platinum (DDP) with dosage of WEGA (0, 30, 60, 120 mg/kg body weight/day). The different groups were administered with drugs via oral or intraperitoneal injection once a day for 21 consecutive days. Tumor inhibition rate, spleen index, thymus index, cytokine, protein, and mRNA expression levels were detected in mice., Results: In a co-culture system, WEGA remarkably inhibited A549 cell proliferation, promoted the expression of M1 macrophage markers and inhibited M2 TAMs markers. Therefore, WEGA affected the biological behavior of cancer cells by regulating the expression of some markers relevant to macrophage polarization. In addition, the group of WEGA and DDP chemotherapy effectively inhibited the transplanted tumor growth in mice and improved weight loss and immunosuppressive with the cisplatin inducing., Conclusions: This study provides mechanistic insights into the anticancer effect of WEGA through the regulation of macrophage polarization and highlights that WEGA could be a novel option for integrative cancer therapies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Plasmacytoma variant translocation 1 (PVT1) is an lncRNA that plays vital roles in breast cancer (BC) pathogenesis. Increasing evidence suggests that miRNAs that reside in the PVT1 locus are the main driver of the oncogenic roles of PVT1 in cancer. However, the oncogenic role and underlying mechanism of miR-1204, located in the PVT1 locus, in human cancer is still unclear. In this study, we discovered that increased expression of miR-1204 is associated with poor prognosis in BC. Moreover, miR-1204 promotes proliferation, epithelial-mesenchymal transition and invasion of BC cells both in vitro and in vivo. Mechanistic investigations demonstrated that VDR is a novel target gene of miR-1204. Interference of VDR restored miR-1204-mediated BC cell proliferation, tumorigenesis, and metastasis. Collectively, our results demonstrated that the miR-1204-VDR pathway exerts oncogenic effects in BC with potential therapeutic applications in blocking BC development and progression.

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk., (© 2018 The Author(s).)

Many DDB1-CUL4 associated factors (DCAFs) have been identified and serve as substrate receptors. Although the oncogenic role of CUL4A has been well established, specific DCAFs involved in cancer development remain largely unknown. Here we infer the potential impact of 19 well-defined DCAFs in human lung adenocarcinomas (LuADCs) using integrative omics analyses, and discover that mRNA levels of DTL, DCAF4, 12 and 13 are consistently elevated whereas VBRBP is reduced in LuADCs compared to normal lung tissues. The transcriptional levels of DCAFs are significantly correlated with their gene copy number variations. SKIP2, DTL, DCAF6, 7, 8, 13 and 17 are frequently gained whereas VPRBP, PHIP, DCAF10, 12 and 15 are frequently lost. We find that only transcriptional level of DTL is robustly, significantly and negatively correlated with overall survival across independent datasets. Moreover, DTL-correlated genes are enriched in cell cycle and DNA repair pathways. We also identified that the levels of 25 proteins were significantly associated with DTL overexpression in LuADCs, which include significant decreases in protein level of the tumor supressor genes such as PDCD4, NKX2-1 and PRKAA1. Our results suggest that different CUL4-DCAF axis plays the distinct roles in LuADC development with possible relevance for therapeutic target development.

A component formula with definite compositions provides a new approach to treat various diseases. Salvia miltiorrhiza and Panax ginseng are widely used in China because of their antitumor properties. In the previous study, the optimizing component formula (OCF), prepared with salvianolic acids, ginsenosides, and ginseng polysaccharides (5, 10, and 5 mg·L-1, respectively) extracted from S. miltiorrhiza and P. ginseng on the basis of IC50 in lung cancer A549 cells and damage minimization on human bronchial epithelial cells in vitro. Currently, we also have demonstrated the inhibitory effect of OCF on A549 cell migration and invasion in vitro. According to Lewis lung cancer cells (LLC) allograft in C57BL/6 mice and A549 xenograft in nude mice experiment, we found that the anti-tumor and anti-metastasis effects of OCF treatment were related to the inhibition of epithelial-mesenchymal transition (EMT). Further studies showed that the inhibitory effect of OCF on EMT was associated with the PTEN/PI3K/AKT pathway. Therefore, all studies revealed that OCF could prevent cancer progression and tumor metastasis by inhibiting EMT involved PTEN/PI3K/AKT signaling pathway in lung cancer cells.

Objective To study the effect of Water Extract of Ginseng (WEG) on the prolifera- tion/metastasis of lung cancer A549 cells and the expression of F-actin in co-culture system of tumor as- sociated macrophages (TAMs) and A549 cells. Methods Human acute leukemia mononuclear strain THP-1 was induced to become TAMs using Phorbol-12-myristate-13-acetate (PMA) combined IL-4 and IL- 13. The supernant of TAMs and A549 cells were co-cultured. A co-culture model was set up by simulating microenvironment of lung cancer. Then cells were divided into the blank control group (A549) , the co- culture group (A549 +TAMs) , high, middle, and low dose WEG groups (TAMs +A549 + high, middle, and low dose WEG). The effects of WEG on the proliferation/metastasis of lung cancer A549 cells and the expression of F-actin under various conditions were detected using MTT method, Real time cell analysis (RTCA) , and high content screening (HCS). Results Compared with the blank control group, the pro- liferation of A549 cells was obviously increased, cell migration was obviously elevated, and the area of cell skeleton was markedly enlarged in the TAMs + A549 group, with statistical difference (P <0. 05). Compared with the TAMs +A549 group, the proliferation and migration of A549 cells were inhibited, the area of cell skeleton and the number of microfilaments were reduced dose-dependently (P <0. 05). Conclusion WEG could effectively inhibit the proliferation and migration of A549 cells, which might be a- chieved by adjusting immunoactivities of TAMs, and further it affected biological behaviors of tumor cells.

This paper was aimed to investigate the microRNA associated with multidrug resistance gene MDR1 of salvianolic acid A reversal in lung cance. Human lung cancer A549 cells were divided into normal control group and drug group, and the MDR1 expression levels were determined by real-time quantitative PCR. MicroRNA expression profiling of normal control group and drug group were detected by using the latest microRNA microarray. Quantitative RT-PCR was used to validate the differentially expressed miRNA. Forecast of miRNA associated with MDR1 multi-resistant genes of up-regulated miRNA. Experimental results showed that the dosage of MDR1 expression level significantly lowered compared with control group. The miRNA expression spectrum analyses of human lung cancer A549 cells to drug group and the control group were detected by microRNA microarray, 426 differentially expressed miRNA were screened out. Then target prediction were performed for difference up-expression of miRNA and found that there were four obvious increase of miRNA associated with MDR1 multi-resistant genes. Real-time quantitative PCR for 4 microRNA verification, the results were consistent with the chip. So the author considered that salvianolic acid A down lung cancer multidrug resistance gene MDR1 is likely to be affected by the miRNA expression and regulation of target genes, to further clarify the traditional Chinese medicine to reverse multi-drug resistant mechanism provides the experimental basis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study aims to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 using the orthogonal design method, and to investigate its effects of the component formula on cell proliferation, apoptosis and cytoskeleton in lung cancer A549 cells. The orthogonal design method was introduced to optimize the most effective component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on lung cancer A549 cells. CCK-8 assay and Real-time cell analysis were adapted to analyze the effect of component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma on A549 cells viability at different time and dose. Cell apoptosis was measured by Annexin V- FITC/PI double staining and flow cytometry. Cell skeleton protein F-actin was detected by high content screening (HCS). The optimizing component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma for total salvianolic acid, total saponins of panax ginseng and ginseng polysaccharide doses were 5, 10, 5 mg L(-1). CCK-8 assay and real-time cell analysis demonstrated that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma treatment could significantly decrease the A549 cell viability in both dose- and time-dependent manner compared with control group (P < 0.01). Moreover, the increase of cell apoptosis was detected by Annexin V-FITC/PI double staining and flow cytometry when cells treated with the component formula, which indicating that the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma could induce A549 cell apoptosis in a time-dependent manner compared with control group (P < 0.01). Furthermore, compared with control group, a significant decrease in A549 cell skeleton area was found in the component formula-exposed cells in the dose-dependent manner (P < 0.01). In summary, the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma inhibits A549 cell proliferation by inducing cell apoptosis and decreasing cell microfilament formation. All of these results will be helpful to reveal antitumor mechanism of the component formula of Salviae Miltiorrhizae Radix et Rhizoma and Ginseng Radix et Rhizoma, which provides a basis for the exploration of antitumor mechanism of the component formula on lung cancer.

Positron emission tomography (PET) is unique for quantitatively assessing treatment response before marked morphological changes are detectable by Computed Tomography (CT). PET response criterion (PERCIST) is a widely accepted approach of assessing metabolic response of malignant lesions by using Standardized uptake value (SUV) normalized by lean body mass (LBM) with a volume of interest (VOI) reference defined in the right lobe of liver. However, the operator-dependent delineation of VOI reference is a time consuming and subjective task. Although the VOI reference can be estimated from the co-aligned CT, the low-dose CT data in PET-CT poses challenge in liver segmentation. In this study, we propose a fully automatic framework to calculate the PERCIST-based thresholding for whole-body PET-CT studies. The framework consists of multi-atlas registration and voxel classification for CT data to segment liver structure and delineate the VOI reference, which is then mapped to the PET data to derive the value of SUVLBM thresholding for PET to select regions of high metabolism. We evaluated our framework with 28 clinical studies diagnosed with lung cancer or lymphoma, and demonstrated both reliability and efficiency in depicting lesions using PERCIST thresholding.