[Retracted] lncRNA­u50535 promotes the progression of lung cancer by activating CCL20/ERK signaling.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the western blotting data shown in Fig. 4B and C on p. 1952, and the Transwell invasion assay data in Fig. 2F and 4I, had already appeared in previously published articles written by different authors at different research institutes (a number of which have been retracted). Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 42: 1946­1956, 2019; DOI: 10.3892/or.2019.7302].

The Polysaccharides from Pinellia ternata and Their Derivatives: Preparation, Structure Characteristics, and Activities in Vitro.

Three polysaccharides, PTC, PTH, and PTB, were extracted from Pinellia ternata using three different extraction conditions: room temperature water, hot water, and 2 % Na2CO3 solution. PTC and PTH were composed of rhamnose, glucose, galactose, mannose, glucuronic acid, galacturonic acid, and arabinose, which combine to form complex structures. PTB was composed solely of glucose and rhamnose. Further analysis indicated that PTC and PTB exhibited triple-helix structures. PTC showed the highest scavenging capacity against DPPH, superoxide anion, and hydroxyl radicals, with half maximal inhibitory concentrations (IC50) of 1004.1, 1584.1, and 1584.1 µg/mL, respectively. Additionally, PTC, PTH, and PTB were subjected to sulfation, phosphorylation, and selenization, resulting in the production of nine derivates. The distinctive absorptive bands of these derivates were determined through infrared spectroscopy. Selenized and sulfated derivates have shown significant antitumor and immunoenhancing properties. Our findings revealed that at 400 µg/mL, the inhibition rate of selenated PTB on HeLa cells was 54.2 % and that on HepG2 cells was 43.1 %. Additionally, selenized PTC displayed significant immunoenhancing activity, with a proliferation rate of 63.7 % at 400 µg/mL in RAW264.7 cells. These results provide valuable evidence supporting the consideration of polysaccharides from Pinellia ternata as a potential candidate for the development of antineoplastic drugs.

Wee1 epigenetically modulates H2B mono-ubiquitination at K120 lysine and DNA double-strand break repair through phosphorylation of H2BY37-dependent manner in small-cell lung cancer.

BACKGROUND: DNA damage repair is a crucial mechanism highly related to therapy resistance for various therapeutic strategies. Our previous results have shown that the degree of drug resistance in small-cell lung cancer (SCLC) cell lines was proportional to both the transcription and expression levels of Wee1, indicating that Wee1, an evolutionarily highly conserved kinase, plays a vital role in the therapeutic resistance of SCLC. In the present study, we aim to determine the nonclassical mechanism of Wee1 on DNA repair regulation. METHODS: Western blot was conducted to determine the mono-ubiquitination level of H2Bub. Comet assay was used to evaluate the degree of DNA damage. Immunofluorescence was conducted to determine the DNA repair markers. Co-immunoprecipitation was utilized to assess the potential interactions with H2BY37ph. MTT assays were used to evaluate the survival rates of SCLC cells. RESULTS: Overexpression of Wee1 increases the level of H2BK120ub and alleviates ionizing radiation (IR)-induced DNA damage in SCLC cells. Moreover, H2BK120ub is a crucial molecule in Wee1-mediated double-strain break (DSB) repair in SCLC cells. Mechanisms study indicated that H2BY37ph is involved in Wee1-mediated H2BK120ub through interaction with the E3 ubiquitin ligase RNF20-RNF40 complex and upregulates its phosphorylation, mutation of H2BY37 phosphorylation sites attenuated DSB repair and enhanced the sensitivity of IR-induced SCLC cell death. CONCLUSION: H2BY37ph produces crosstalk with H2BK120ub in an E3 ubiquitin ligase-dependent manner, promoting Wee1-mediated DSB repair in SCLC cells. This study clarifies the nonclassical mechanism of Wee1 regulation of DSB repair, which provides a theoretical basis for the clinical understanding of the regulatory network of Wee1 and its use as a target for overcoming multiple types of therapeutic resistance.

Prognostic significance of 4R lymph node dissection in patients with right primary non-small cell lung cancer.

BACKGROUND: To investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection. RESULTS: Our study included 2070 patients, with 207 patients having no station 4R dissection (S4RD- group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD- group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08-1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04-1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002). CONCLUSIONS: Station 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.

Inhibitory effect of aptamer-carbon dot nanomaterial-siRNA complex on the metastasis of hepatocellular carcinoma cells by interfering with FMRP.

Using small interfering RNA (siRNA) for the specific gene-silencing has been a novel therapeutic method for the treatment of incurable diseases such as malignancies. However, it remains a challenge whether siRNA can be safely and effectively delivered into target cells. Therefore, we synthesized fluorescent carbon dots (CDs) as a gene vector at the siRNA delivery system that induced efficient gene knockdown in vitro while binding aptamer AS1411 to resolve the difficulty in cell targeting. We found that CDs with adequate biocompatibility can improve the efficiency of cellular uptake of siRNA. CLSM and FCM results showed that CDs were mainly localized in the cytoplasm and emitted bright green fluorescence. In addition, the CD/siRNA delivery system mediated by the aptamer AS1411 effectively silenced the expression of Fragile X mental retardation protein (FMRP) and successfully inhibited the migration and invasive propensity of hepatocellular carcinoma (HCC) cells. In summary, we have synthesized a valuable siRNA delivery vector enabling not only bioimaging but also effective downregulation of gene expression, which is indicative of an efficient potential for gene delivery and therapy.

Case Report: Sarcoid-Like Reactions and Tertiary Lymphoid Structures Following Dual Checkpoint Inhibition in a Patient with Early-Stage Lung Adenocarcinoma.

Immune checkpoint inhibitor-induced sarcoid-like reactions and tertiary lymphoid structures (TLSs) are increasingly recognized but rarely reported in the same patient. We report a patient with lung adenocarcinoma who displayed sarcoid-like reactions in intrathoracic lymph nodes and tertiary lymphoid structures in surgical tumor after neoadjuvant therapy with nivolumab plus ipilimumab. Pathological examination revealed 50% residual tumor cells after treatment, and the CT evaluation of the primary tumor showed a stable disease. The patient experienced a recurrence eight months after surgery. To identify immune correlates of the limited response to immunotherapy, we conducted genomic and transcriptional assays, multiplex immunoassay, and multiplex immunohistochemistry on the pre- and post-immunotherapy tumor, lymph node, and plasma samples. TP53 R181C, KRAS G12C and SMAD4 R361H were identified as driver mutations of the tumor. In addition to abundant infiltrated lymphocytes, immunotherapy induced high levels of inhibitory components in post-treatment tissue samples, especially the FOXP3+ regulatory T cells in tumor and PD-L1 expression in the lymph node. Despite abundant TLSs in the post-treatment tumor, most TLSs were immature. Moreover, increasing levels of circulating checkpoint proteins BTLA, TIM-3, LAG-3, PD-1, PD-L1, and CTLA4 were observed during immunotherapy. Collectively, our observations revealed that high levels of immunosuppressive molecules in tumor, lymph nodes and/or in peripheral blood might indicate poor outcomes after immunotherapy, even in the setting of a patient with concurrent sarcoid-like reactions and tertiary lymphoid structures.

Arginase Pathway Markers of Immune-Microenvironment in Thymic Epithelial Tumors and Small Cell Lung Cancer.

BACKGROUND: Key regulators of antitumor immunity such as arginase-1 and the adenosine pathway may have an important role in modulating the effect of immunotherapy. Here, we investigated the expression profile of these immune-related biomarkers in thymic epithelial tumors (TETs) and small cell lung cancer (SCLC), 2 solid tumors where immune checkpoint inhibitors have activity. MATERIALS AND METHODS: Immunohistochemical staining was performed using tissue microarrays of 123 TET (110 thymoma and 13 thymic carcinoma) and 125 SCLC cases. The expression profile of the following immune-related biomarkers was assessed: arginase-1, CD39, CD73, A2AR, PD-L2, and CD15. The expression profile was also correlated with clinical data. RESULTS: No sample was positive for arginase-1. In the adenosine pathway, the prevalence of positive staining for CD39, CD73, and A2AR was 4.9%, 2.5%, and 69.2%, in TETs and 0%, 1.7%, and 50.8%, in SCLC. The multivariate analysis showed that CD39 expression was significantly associated with worse disease related survival (hazard ratio [HR], 10.36; 95% confidence interval [CI]: 2.01-53.47; P= .005) and a shorter time-to progression (HR, 11.35; 95% CI, 2.11-61.23; P = .005) in TETs. Other biomarkers were not associated with disease related survival or time to progression in TETs. No biomarker was associated with survival in SCLC. CONCLUSION: Arginase-1 was not detectable in TETs and SCLC. Expression of markers in the adenosine pathway were present in both TETs and SCLC. CD39 expression in tumor cells may identify subsets of patients with TETs with an unfavorable prognosis.

The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Pathological Response for Resectable Non-Small Cell Lung Cancer Treated with Neoadjuvant Chemotherapy Combined with PD-1 Checkpoint Inhibitors.

PURPOSE: The aim of our study was to investigate the value of baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) in predicting the pathological response and disease-free survival (DFS) of neoadjuvant chemotherapy alone or combined with programmed cell death-1 (PD-1) checkpoint inhibitors in patients with resectable non‒small cell lung cancer (NSCLC). MATERIALS AND METHODS: Resectable NSCLC patients who underwent neoadjuvant chemotherapy alone or combined with PD-1 checkpoint inhibitors between January 2018 and January 2020 were included. Peripheral venous blood samples of the patients were collected within 3 days prior to the first neoadjuvant treatment and within 3 days prior to surgery. RESULTS: A total of 79 patients in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group and 89 patients in neoadjuvant chemotherapy alone group were included. Thirty-five point four percent of the patients achieved pathological complete response (pCR) in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group, whereas only 9.0% reached pCR in the group of neoadjuvant chemotherapy. High NLR level were correlated with poor pathological response and DFS in neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors group. Multivariate analysis revealed that baseline NLR could independently predict pathological response and DFS in the neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group. CONCLUSION: High NLR level were correlated with poor pathological response and shorter DFS in patients with NSCLC undergoing neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors. Meanwhile, baseline NLR could independently predict response to pathological response and DFS, revealing its potential as a screening tool in NSCLC patients who received neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors.

[Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats].

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1ß(IL-1ß), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

Downregulation of LINC00665 suppresses the progression of lung adenocarcinoma via regulating miR-181c-5p/ZIC2 axis.

Long non-coding RNA (lncRNA) LINC00665 was demonstrated to be upregulated in lung adenocarcinoma (LUAD) and target miR-181c-5p. ZIC2, which is upregulated in LUAD, serves as a putative target of miR-181c-5p. In this study, we aimed to reveal whether LINC00665 regulates miR-181c-5p/ZIC2 axis to promote LUAD progression. The results showed that LINC00665, HOXA1, ZIC2, and HOXA11 levels were increased in LUAD tissues, while miR-181c-5p level was decreased when compared to the adjacent normal tissues. High expression levels of LINC00665, ZIC2, HOXA1 and HOXA11, and low expression of miR-181c-5p were closely linked to poor prognosis of LUAD patients. Knockdown of LINC00665 induced obvious inhibitions in cell viability, clone formation, invasion and tumorigenesis in LUAD cells, whereas miR-181c-5p downregulation significantly neutralized these effects. In addition, downregulation of ZIC2 obviously reversed the enhancements of cell viability, clone formation, invasion and tumorigenesis induced by miR-181c-5p knockdown. In summary, the present study reveals that silencing of LINC00665 suppresses LUAD progression through targeting miR-181c-5p/ZIC2 axis.

The Prognostic Value of Non-Predominant Micropapillary Pattern in a Large Cohort of Resected Invasive Lung Adenocarcinoma Measuring ≤3 cm.

The aim of this study was to analyze the influence of non-predominant micropapillary pattern in small sized invasive lung adenocarcinoma. A total of 986 lung adenocarcinoma patients with tumor size ≤3 cm were identified and classified according to the IALSC/ATS/ERS classification. Emphasis was placed on the impact of non-predominant micropapillary pattern on disease-free survival (DFS) and overall survival (OS). The relationship between lung adenocarcinoma subtype and lymph node involvement, EGFR mutation and KRAS mutation was also evaluated. A nomogram was developed to predict the probability of 3- and 5-year OS for these patients. The concordance index and calibration plot were used to validate this model. Among all 986 patients, the percentages of lymph node involvement were: 58.1, 50.0, 33.5, 21.4, 21.1, 10.9, 0, and 0% for micropapillary predominant, solid predominant, acinar predominant, papillary predominant, invasive mucinous adenocarcinoma (IMA), lepidic predominant, minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), respectively. The frequency of EGFR mutation in the cases of lepidic predominant, acinar predominant, MIA, micropapillary predominant, papillary predominant, solid predominant, IMA, and AIS were 51.1, 45.2, 44.4, 36.8, 29.3, 26.8, 8.3, and 0%, respectively. A non-predominant micropapillary pattern was observed in 344 (38.4%) invasive adenocarcinoma (IAC), and its presence predicted a poorer DFS (median: 56.0 months vs. 66.0 months, P <0.001) and OS (median: 61.0 months vs. 70.0 months, P <0.001). After propensity score matching, non-predominant micropapillary pattern retained its unfavorable effect on DFS (P = 0.007) and OS (P = 0.001). Multivariate analysis showed that non-predominant micropapillary pattern was identified as an independent prognostic factor for DFS (P = 0.003) and OS (P <0.001) in IAC. The nomogram showed good calibration and reliable discrimination ability (C-index = 0.775) to evaluated the 3- and 5-year OS. This retrospective analysis of patients with small sized IAC suggests the value of non-predominant micropapillary pattern to predict poor prognosis. A reliable nomogram model was constructed to provide personalized survival predictions.

CITED4 enhances the metastatic potential of lung adenocarcinoma.

BACKGROUND: CITED4 belongs to the CBP/p300-interacting transactivator with glutamic acid and aspartic acid-rich tail (CITED) family which is induced by various cytokines and participates in cytokine-induced proliferation and differentiation. CITED4 is induced by HB-EGF in lung cancer cells. However, it is unclear whether and how CITED4 contributes to the invasion and metastasis of lung adenocarcinoma (ADC). METHODS: CITED4 expression in lung adenocarcinoma and its association with disease-free survival (DFS) and overall survival were analyzed based on a cohort of 261 patients. The roles of CITED4 were validated via loss-of-function and gain-of-function experiments. The relationship between CITED4 and CLDN3 was validated by immunohistochemistry, Western blotting, and luciferase reporter assays. The function of the CITED4-CTNNB1-CLDN3 complex was fully validated and described. RESULTS: CITED4 expression was significantly upregulated in ADC tissues and cells and a predictor for DFS. Downregulation of CITED4 attenuated the proliferation and invasion, whereas CITED4 overexpression enhanced these effects. Overexpression and knockdown of CITED4 resulted in the upregulation and downregulation of CLDN3, respectively. Moreover, CITED4 downregulation suppressed CLDN3-mediated ADC cell metastasis in vivo. CITED4 was highly expressed and positively correlated with CLDN3. Mechanistically, CITED4 interacted with CTNNB1 and functioned synergistically to enhance CLDN3 transcription. Importantly, CITED4 induced ADC invasion via a CLDN3-dependent pathway. CITED4 determined the level of CLDN3, which in turn affected the sensitivity of tumors to Clostridium perfringens enterotoxin treatment. CONCLUSIONS: The CITED4-CTNNB1-CLDN3 axis plays a key role in the invasion and metastasis of ADC and provides a novel therapeutic target for lung cancer treatment.

Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up-regulation.

Platinum-based chemotherapy has been the cornerstone treatment for small cell lung cancer (SCLC) for decades, but no major progress has been made in the past 20 years with regard to overcoming chemoresistance. As the cell cycle checkpoint kinase 1 (Chk1) plays a key role in DNA damage response to chemotherapeutic drugs, we explored the mechanisms of acquired drug resistance to the Chk1 inhibitor prexasertib in SCLC. We established prexasertib resistance in two SCLC cell lines and found that DNA copy number, messengerRNA (mRNA) and protein levels of the cell cycle regulator Wee1 significantly correlate with the level of acquired resistance. Wee1 small interfering RNA (siRNA) or Wee1 inhibitor reversed prexasertib resistance, whereas Wee1 transfection induced prexasertib resistance in parental cells. Reverse phase protein microarray identified up-regulated proteins in the resistant cell lines that are involved in apoptosis, cell proliferation and cell cycle. Down-regulation of CDK1 and CDC25C kinases promoted acquired resistance in parental cells, whereas down-regulation of p38MAPK reversed the resistance. High Wee1 expression was significantly correlated with better prognosis of resected SCLC patients. Our results indicate that Wee1 overexpression plays an important role in acquired resistance to Chk1 inhibition. We also show that bypass activation of the p38MAPK signaling pathway may contribute to acquired resistance to Chk1 inhibition. The combination of Chk1 and Wee1 inhibitors may provide a new therapeutic strategy for the treatment of SCLC.

Source profile and health risk assessment of PM2.5 from coal-fired power plants in Fuxin, China.

In order to improve and establish the localized source profile of PM2.5 in Fuxin, the ashes under dust catcher were collected from four typical coal-fired power plants in Fuxin and twenty-eight components were measured. The source profile of PM2.5 in the soot of the four coal-fired power plants was established. SO42- was the most abundant component in the PM2.5 of the soot of the four coal-fired power plants, followed by Ca2+ and organic carbon (OC). The content of element components in PM2.5 smoke ranges from 5.06 to 10.97%, the content of ionic components ranges from 36.53 to 48.59%, and the total carbon content ranges from 9.43 to 11.36%. The divergence coefficient of PM2.5 source profile in Fuxin coal burning smoke is mostly similar to that of Fushun, whereas the divergence coefficient of Colorado reaches 0.65, indicating that Fuxin coal burning power plant smoke has no similarity to Colorado. The order of the geological accumulation index of Ni, Cu, V, Mn, and Cr was Cr (4.58) > Mn (4.42) > V (4.38) > Cu (4.09) > Ni (4.06), showing a heavy pollution level. The health risk assessment model recommended by the USEPA was used to assess the health risk of heavy metals in soot of coal-fired power plants, and the non-carcinogenic risk values of As for children and adults were 45.7 and 4.90, respectively. The carcinogenic risk values of Cr for adults and children were the highest, with values of 3.66 × 10-5 and 2.06 × 10-5, respectively, followed by As.

Genomic characteristics in Chinese non-small cell lung cancer patients and its value in prediction of postoperative prognosis.

BACKGROUND: The genomic profile of non-small cell lung cancer (NSCLC) in Asians is distinct from that of Caucasians, but comprehensive genetic profiling reports have been limited for Asian patients. We aimed to elucidate genomic characteristics of Chinese NSCLC patients and develop potential model including genomic characteristics to predict postoperative prognosis. METHODS: Resected tumor samples from 511 patients with stage I-IV lung cancer were subjected to targeted sequencing using a panel of 295 cancer-related genes. Based on the molecular profiles and clinical features, we established nomogram models with predictors consisting of integrated clinical and genomic characteristics to provide post-operative risk stratification. RESULTS: Compared to the TCGA population (mainly Caucasians), there was a significantly higher frequency of EGFR (53.7% vs. 14.4%) and NOTCH3 (8.4% vs. 1.3%) mutations and less mutated KRAS (11.0% vs. 32.6%), KEAP1 (4.4% vs. 17.4%) and LRP1B (16.3% vs. 29.6%) in Chinese lung adenocarcinomas (LUAD). Distinct patterns of mutually exclusive and co-occurring mutations were identified between LUAD and lung squamous cell carcinoma (LUSC), indicating the unique histology-specific tumorigenesis mechanism of each subtype. We observed alterations in pathways correlated with clinical characteristics. Additionally, we constructed nomogram model with predictors consisting of clinical and genomic characteristics, which were more accurate than models with clinical characteristics or TNM staging only both in stage I-IIIA patients and T1-2N0M0 sub-cohort. CONCLUSIONS: This study revealed Chinese NSCLC patients have unique genomic profile. Furthermore, the nomogram model combining clinical features with genomic characteristics could improve risk stratification in early-stage NSCLC.

Selective and sensitive detection of chronic myeloid leukemia using fluorogenic DNAzyme probes.

One of the major challenges facing the early diagnosis of chronic myelogenous leukemia (CML) patients today is enhancing the simplicity, rapidness, sensitivity and specificity of detection assay for easy clinical implementation. RNA-cleaving fluorogenic DNAzymes (RFDs) are single-stranded DNA molecules with catalytic activity and can produce fluorescent signals when combined with specific targets. As K562 cells were the first established human immortalized myelogenous leukemia line, we try to screen several RFDs using the crude extracellular mixture of K562 cells through the SELEX process. We obtained an RFD probe A1-3 that is able to distinguish K562 cells from other tumor cell lines. 10 nM of A1-3 can induce an increase of detectable fluorescence signal. Moreover, the RFD assay system can work well for target detection in complex serum matrix. The optimized RFD assay system with low cost also has a desirable ability to exactly distinguish K562 cells after truncation of 20 bases in the 5'end of A1-3. This study is the first report to investigate the RFD system for detection of K562 cells using cell culture supernatants as the complex target. This RFD assay system could potentially be applied for the diagnosis of CML.

Oligomannuronate prevents mitochondrial dysfunction induced by IAPP in RINm5F islet cells by inhibition of JNK activation and cell apoptosis.

BACKGROUND: Oligomannuronates (OM) are natural products from alginate that is frequently used as food supplement. The aim of this study was to investigate the in vitro protective effects of OM on RINm5F cells against human Islet amyloid polypeptide (IAPP) induced mitochondrial dysfunction, as well as the underlying mechanisms. METHODS: In the present study, we obtained several kinds of OM with different molecular masses, and then we used RINm5F cells as a model to elucidate the involvement of JNK signal pathway in hIAPP-induced mitochondrial dysfunction in pancreatic beta cells, and the protective effects of OM are associated with its ability to attenuate the mitochondrial dysfunction. RESULTS: Our results demonstrated that human IAPP induced mitochondrial dysfunction, as evidence by loss of ΔΨm and ATP content, and decrease in oxygen consumption and complex activities, was accompanied by JNK activation, changes in the expressions of Bcl-2 and Bax proteins, release of cytochrome c (Cyto-c) and apoptosis inducing factor (AIF) from mitochondria into cytosol. Interestingly, the human IAPP induced damage in RINm5F cells were effectively restored by co-treatment of OM. Moreover, JNK activation was required for the OM mediated changes in RINm5F cells. CONCLUSIONS: OM prevented mitochondrial dysfunction induced by human IAPP in RINm5F islet cells through JNK dependent signaling pathways.

Mutant GTF2I induces cell transformation and metabolic alterations in thymic epithelial cells.

The pathogenesis of thymic epithelial tumors (TETs) is poorly understood. Recently we reported the frequent occurrence of a missense mutation in the GTF2I gene in TETs and hypothesized that GTF2I mutation might contribute to thymic tumorigenesis. Expression of mutant TFII-I altered the transcriptome of normal thymic epithelial cells and upregulated several oncogenic genes. Gtf2i L424H knockin cells exhibited cell transformation, aneuploidy, and increase tumor growth and survival under glucose deprivation or DNA damage. Gtf2i mutation also increased the expression of several glycolytic enzymes, cyclooxygenase-2, and caused modifications of lipid metabolism. Elevated cyclooxygenase-2 expression by Gtf2i mutation was required for survival under metabolic stress and cellular transformation of thymic epithelial cells. Our findings identify GTF2I mutation as a new oncogenic driver that is responsible for transformation of thymic epithelial cells.

[Robot-assisted Lobectomy under Port-only Mode with Artificial Pneumothorax].

BACKGROUND: Da Vinci robotic system is currently widely used in thoracic surgery. The ports employment and procedures vary in different medical center in China. Usually, a small incision was used for assistant. METHODS: Based on clinical practice, we summarized domestic and foreign experience, combined with the characteristics of the Chinese body anatomy, employ portal technique and artificial pneumothorax, summarized a set of simplified and easier surgical method. RESULTS: Port-only artificial pneumothorax robot-assisted lobectomy has further improvement in anatomical safety, hemostatic effect and aesthetic appearance of the wound. CONCLUSIONS: This study optimizes the procedure of port-only artificial pneumothorax robot-assisted lobectomy in order to serve lung cancer patients better.

A Humanized Cancer-Bone Metastasis Mouse Model Based on Silica Nanoparticles-Incorporated Human Demineralized Bone Matrix.

Breast cancer tends to spread to other organs and bone metastasis has the highest frequency in breast cancer metastasis, while its mechanisms are not clear and the current treatments are not very effective. To better study the mechanisms and facilitate drug screening for breast cancer bone metastasis, an in vivo mouse model needs to be constructed. However, the construction of the humanized mouse model for cancer bone metastasis which will mimick real interactions between cancer tissue and bone tissue in the human microenvironment remains a challenge. In this study, we constructed a human engineering bone tissue composed with the human osteoblast-like cells (SaOS-2 cells) and the silica nanoparticlesincorporated human demineralized bone matrix (Si/DBM). The engineered bone was then transplanted into a nude mouse to build a humanized bone microenvironment. The human breast cancer cells were then injected into the fat pads of the nude mouse to form an orthotopic tumor. The results showed that the engineered bone tissue-constructed humanized bone microenvironment had significant advantages when inducing human cancer cells to metastasize into the engineered bone tissue. Further, the SaOS-2/Si/DBM had a stronger ability to entice cancer-bone metastasis through promoting osteogenesis compared to the SaOS-2/DBM. Accordingly, this study highlights a novel, facile and effective mouse model for human cancer-bone metastasis, which will provide a platform to explore the mechanisms and anti-tumor drug screening for cancer-bone metastasis.