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Direct design of complex functional materials would revolutionize technologies ranging from printable organs to novel clean energy devices. However, even incremental steps toward designing functional materials have proven challenging. If the material is constructed from highly complex components, the design space of materials properties rapidly becomes too computationally expensive to search. On the other hand, very simple components such as uniform spherical particles are not powerful enough to capture rich functional behavior. Here, we introduce a differentiable materials design model with components that are simple enough to design yet powerful enough to capture complex materials properties: rigid bodies composed of spherical particles with directional interactions (patchy particles). We showcase the method with self-assembly designs ranging from open lattices to self-limiting clusters, all of which are notoriously challenging design goals to achieve using purely isotropic particles. By directly optimizing over the location and interaction of the patches on patchy particles using gradient descent, we dramatically reduce the computation time for finding the optimal building blocks.

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Understanding the microscopic mechanisms of thermalization in closed quantum systems is among the key challenges in modern quantum many-body physics. We demonstrate a method to probe local thermalization in a large-scale many-body system by exploiting its inherent disorder and use this to uncover the thermalization mechanisms in a three-dimensional, dipolar-interacting spin system with tunable interactions. Utilizing advanced Hamiltonian engineering techniques to explore a range of spin Hamiltonians, we observe a striking change in the characteristic shape and timescale of local correlation decay as we vary the engineered exchange anisotropy. We show that these observations originate from the system's intrinsic many-body dynamics and reveal the signatures of conservation laws within localized clusters of spins, which do not readily manifest using global probes. Our method provides an exquisite lens into the tunable nature of local thermalization dynamics and enables detailed studies of scrambling, thermalization, and hydrodynamics in strongly interacting quantum systems.

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As one of the most frequently occurring tumor types, the increasing incidence of gastric cancer (GC) has been observed in the past decades. The recent studies have illustrated that epigenetic modifications mediated by DNA methyltransferases (DNMTs) are the major epigenetic hallmark in GC progression. Nowadays, DNA methylation was considered to be necessary for inducing the silence of tumor suppressor genes (TSGs). As an important group of peptides, the TFF family has been confirmed to function as a TSG in various kinds of cancers. However, whether TFFs could be modified by DNA methylation in gastric cancer remains unknown. Here, we initially screened out two transcriptional sequencing profiles about GC from Gene Expression Omnibus (GEO) database. The lower expression levels of TFF1 and TFF2 were observed in GC tumor tissues as compared to those in normal tissues. Additionally, utilizing the Kaplan-Meier analysis, the expressions of TFF1 and TFF2 were identified to be associated with the prognosis of GC patients. Subsequently, the integrative analysis was performed to estimate the DNA methylation level of each site in TFF1/TFF2 CpG islands. Importantly, our findings indicated that hyper-methylation of cg01886855 and cg26403416 were separately responsible for the downregulation of TFF1 and TFF2 in GC samples. In addition, utilizing the experiments in vitro, we demonstrated that TFF1/TFF2 could suppress the proliferation of GC cells. Based on these results, we suspected that TFF1/TFF2 could potentially act as the putative tumor suppressor in GC, and these two TFFs were of great value for predicting the overall survival (OS) status in the gastric cancer cohort. Totally, our findings revealed a potential therapeutic method for targeting the TFFs for the treatment of GC.

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Background: The aim of this study was to examine whether academic performance is associated with students' athletic ability in primary school. Methods: A 3-year follow-up study was conducted among 1,136 Chinese students. Sit-up and jump rope testers were used to measure 1-min sit-ups and 1-min jump ropes, respectively. Meanwhile, the Pittsburgh Sleep Quality Scale and the Beck Depression Inventory were used to estimate sleep quality and depression levels. The end-of-semester examinations were used to evaluate students' academic performance during the follow-up period. Results: After adjusting for confounders, the mean change in Chinese language performance for participants stratified by 1-min sit-ups at baseline was 0.35 (95% CI: -0.37 to 0.76) for level 1 (slowest), 0.52 (95% CI: -0.54 to 1.08) for level 2, and 1.72 (95% CI: 1.14 to 2.30) for level 3 (fastest) (P for trend = 0.003); the mean change in math scores was 0.28 (95% CI: -0.50 to 0.95) for level 1 (slowest), 0.95 (95% CI: 0.38 to 1.52) for level 2, and 1.41 (95% CI: 0.82 to 1.99) for level 3 (fastest) (P for trend = 0.048). The mean change in foreign language scores was -0.45 (95% CI: -0.99 to -0.93) for level 1 (slowest), -0.14 (95% CI: -0.44 to 0.41) for level 2, and 0.69 (95% CI: 0.25 to 1.13) for level 3 (fastest) (P for trend = 0.004). The mean change in Chinese language performance for participants stratified by 1-min jump ropes at the baseline was 0.30 (95% CI: -0.16 to 0.76) for level 1 (slowest), 1.09 (95% CI: 0.42 to 1.76) for level 2, and 1.74 (95% CI: 1.14 to 2.35) for level 3 (fastest) (P for trend = 0.001). The mean change in math scores was 0.41 (95% CI: -0.11 to 0.92) for level 1 (slowest), 1.44 (95% CI: 0.69 to 2.19) for level 2, and 1.43 (95% CI: 0.76 to 2.10) for level 3 (fastest) (P for trend = 0.019). The mean change in foreign language performance was -0.71 (95% CI: -1.08 to -0.33) for level 1 (slowest), 0.95 (95% CI: -0.40 to 1.50) for level 2, and 0.91 (95% CI: 0.41 to 1.41) for level 3 (fastest) (P for trend < 0.001). Conclusion: This study suggests that participation in jump rope and sit-up exercises may positively affect students' academic performance.

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BACKGROUND: Colorectal carcinoma (CRC) is one of the most leading cause of cancer death all over the world. The tumor immune microenvironment is illustrated to be necessary for the progress of CRC. And the accumulating evidence indicated that tumor mutation burden (TMB) is effective in differentiating responding population of immune checkpoint inhibitor (ICI) therapies in various cancers. In this study, we aimed to evaluated the potential relationship between TMB and the recurrence risk of CRC. METHODS: The transcriptomic and clinical data of CRC patients were collected from The Cancer Genome Atlas (TCGA) database (n= 382). Then the genomic analysis of tumor mutation burden and tumor purity were conducted by a computational method based on transcriptomic data. RESULTS: Firstly, we accessed the distribution of TMB and preferences at the gene and mutation level using somatic mutation data from TCGA data about CRC. We identified that high TMB predicted better prognosis of CRC patients. Secondly, the differentially expressed genes (DEGs) between the low TMB and high TMB group was clarified. Then the protein-protein interaction (PPI) analysis was performed, and the results confirmed ten hub genes among the DEGs. Utilizing the GEPIA web-tool, we discovered that GNG4 was up-regulated in tumor tissues, and GNG4 was related to the overall survival (OS) and tumor free survival (TFS) of CRC patients. Therefore, we considered GNG4 was essential for the tumor immune microenvironment of CRC. Furthermore, we also accessed the protein level of GNG4 in CRC and liver metastases from CRC. CONCLUSIONS: In this study, GNG4 was demonstrated to be the key element of the CRC TMB, which will be essential for the ICI therapy of CRC. Besides, GNG4 was up-regulated in CRC and liver metastases from CRC tissues. Thus, we thought that GNG4 might play an important role in colorectal cancer TMB and induce its metastasis in liver.

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Background: Standard treatments for nonparasitic hepatic cysts (NPHCs) include laparoscopic deroofing (LD), percutaneous aspiration, and alcohol sclerotherapy. However, these treatments have limitations. LD and alcohol sclerotherapy, for example, fail to prevent NPHC recurrences, although alcohol sclerotherapy is satisfactorily effective in treating small cysts (diameter <5 cm), which do not usually need treatment. The present study introduces a novel surgical procedure, laparoscopic enucleation with intact cyst (LEIC), which may prevent postoperative cyst recurrence. Materials and Methods: In this study, we enrolled 14 patients, with NPHCs larger than 9 cm in diameter, who underwent LEIC. Dissection and coagulation were performed using the harmonic shear enucleation and bipolar coagulation techniques. We attempted to completely remove the cysts intact. Results: For all patients, symptoms disappeared after complete elimination of the cyst capsule. No complications (hemorrhage or bile leakage) were found during the perioperative period. The mean follow-up period was 19.3 months (range 10-38 months), during which no recurrences or complications were noted. Conclusions: LEIC is a novel surgical approach that shows satisfactory efficacy and safety in patients with large, surficial, and symptomatic NPHCs. LEIC's main advantage is that it can efficiently prevent cyst recurrence and decrease postoperative morbidity. However, its long-term efficacy and safety require further verification, especially with huge cysts.

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BACKGROUND: Tripterine (TRI), an active monomer in Tripterygium wilfordii, has significant pharmacological activities, such as anti-inflammatory, immunosuppressive and anti-tumor activities. TRI may be used to treat allergic diseases because of its characteristics of immunosuppression. OBJECTIVE: This study aims to explore the anti-allergic effect of TRI. METHODS: It was tested in vivo and in vitro in this study. RESULTS: The results showed that TRI could significantly inhibit histamine release from rat peritoneal mast cells; the inhibitory effect of TRI on histamine release was stronger than that of other known histamine inhibitors such as disodium cromoglyceride. TRI also significantly inhibited systemic anaphylactic shock induced by compound 48/80 and skin allergy induced by IgE, and inhibited the expression of inflammatory factors secreted by Human Mast Cells (HMC-1) induced by Phorbol 12-Myristate 13- Acetate (PMA) and calcium carrier A23187. In the animal model of allergic rhinitis induced by Ovalbumin (OA), the scores of friction, histamine, IgE, inflammatory factors and inflammatory cells decreased after TRI was administered orally or nasally. CONCLUSION: TRI, as an active immunoregulatory factor, has great potential in the treatment of mast cell-mediated allergic diseases.

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BACKGROUND: Although pyruvate kinase M2 (PKM2) has been shown to be among the crucial enzymes that regulate aerobic glycolysis in multiple tumour cells, its role in the treatment and prognosis of intrahepatic cholangiocarcinoma (ICC) remains unclear. This study primarily aimed to determine whether the expression status of PKM2 is potentially associated with the clinical outcomes of ICC. METHODS: PKM2 expression was evaluated in ICC cell lines and tissues via real-time quantitative reverse-transcription polymerase chain reaction, immunofluorescence assays, and Western blot, and its prognostic value was determined according to its impact on the overall survival of patients. RESULTS: We found that PKM2 is highly expressed in ICC, and this was correlated with patient survival. Moreover, we found that PKM2 knockdown could considerably inhibit ICC cell proliferation, invasion, and migration in vitro. CONCLUSIONS: PKM2 was overexpressed in ICC, and it may regulate proliferation, invasion, and migration and lead to poor prognosis. Thus, PKM2 might be a potential independent prognostic factor for ICC.

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BACKGROUND: The aim of this study was to compare epidermal growth factor receptor (EGFR) mutations between primary tumors and corresponding bone metastases (BMs) in lung adenocarcinoma. MATERIALS AND METHODS: In total, 115 paired primary lung adenocarcinoma and corresponding BM tumors were analyzed for EGFR mutations by Amplification Refractory Mutation System. RESULTS: EGFR mutations were detected in 61 primary lung adenocarcinomas (53.04%) and in 67 corresponding metastases (58.26%), respectively. The EGFR mutation rate was significantly higher in female and in never-smoker patients. The consistency of EGFR mutations between the 115 matched BMs and primary tumor tissue samples reached to 80.87%, and the disparity was 19.13%. Mutations in exons 19 (19-del) and 21 (point mutation L858R) were the predominant mutation type. CONCLUSIONS: The concordance rate demonstrated the feasibility of EGFR mutations in corresponding metastases using Amplification Refractory Mutation System when the primary tumor tissue is unavailable in the lung adenocarcinoma patients, and the inconsistency indicates that corresponding metastasis being screened simultaneously with the primary tumor samples may present some supplementary information for the patients.

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OBJECTIVE: To analyze the consistency of gene mutation sites between bone marrow DNA (BM-tDNA) and perepheral plasma circulating tumor DNA (PP-ctDNA) in patients with myelodysplastic syndrome (MDS). METHODS: The simultaneous sampled BM and PP from 19 patients (SBPP) was detected by NGS-127 gene panel, and the consistency of VAF between BM-tDNA and PP-ctDNA was analyzed. The peripheral blood cell tumor DNA (PC-tDNA) of 5 out of 19 patients was detected randomly, the consistency of VAF among PC-tDNA，BM-tDNA and PP-ctDNA was analyzed. The non simultaneous sampled BM and PP from 13 patients (NBPP) was detected, and the difference value of VAF between BM-tDNA and PP-ctDNA in SBPP and NBPP was analyzed. RESULTS: The average concentration of PP-ctDNA in SBPP was 0.59 ng/µl and 0.604 ng/µl in NBPP. The median concentration of PP-ctDNA in SBPP and NBPP was 0.330 ng/µl and 0.338 ng/µl, respectively. The study showed a good consistency of VAF between BM-tDNA and PP-ctDNA in the SBPP (R2=0.9693, P<0.05), and the consistency of VAF between BM-tDNA and PP-ctDNA in single base replacement (SNP) sites (R2=0.9712) was better than that in insertion deletion (Indel) sites (R2=0.6813). The results showed a good consistency of VAF between BM-tDNA and PP-ctDNA both in 12 patients before treatment (R2=0.9325, P<0.05) and 5 patients (R2=0.9875, P<0.05) after treatment. The results also showed that the VAF of PC-tDNA had a good consistency with the VAF of BM-tDNA (R2=0.8783) and PP-ctDNA (R2=0.8783) (P<0.05). The difference value of VAF between BM-tDNA and PP-ctDNA in SBPP was significantly lower than that in NBPP (P<0.05). CONCLUSION: PP can replace BM as a biological sample for genes mutation detection in patients with MDS due to its stable concentration, high degree of consistency with bone marrow in clinical significant mutation sites and easy collection.

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OBJECTIVE@#To analyze the consistency of gene mutation sites between bone marrow DNA (BM-tDNA) and perepheral plasma circulating tumor DNA (PP-ctDNA) in patients with myelodysplastic syndrome (MDS).@*METHODS@#The simultaneous sampled BM and PP from 19 patients (SBPP) was detected by NGS-127 gene panel, and the consistency of VAF between BM-tDNA and PP-ctDNA was analyzed. The peripheral blood cell tumor DNA (PC-tDNA) of 5 out of 19 patients was detected randomly, the consistency of VAF among PC-tDNA，BM-tDNA and PP-ctDNA was analyzed. The non simultaneous sampled BM and PP from 13 patients (NBPP) was detected, and the difference value of VAF between BM-tDNA and PP-ctDNA in SBPP and NBPP was analyzed.@*RESULTS@#The average concentration of PP-ctDNA in SBPP was 0.59 ng/µl and 0.604 ng/µl in NBPP. The median concentration of PP-ctDNA in SBPP and NBPP was 0.330 ng/µl and 0.338 ng/µl, respectively. The study showed a good consistency of VAF between BM-tDNA and PP-ctDNA in the SBPP (R=0.9693, P<0.05), and the consistency of VAF between BM-tDNA and PP-ctDNA in single base replacement (SNP) sites (R=0.9712) was better than that in insertion deletion (Indel) sites (R=0.6813). The results showed a good consistency of VAF between BM-tDNA and PP-ctDNA both in 12 patients before treatment (R=0.9325, P<0.05) and 5 patients (R=0.9875, P<0.05) after treatment. The results also showed that the VAF of PC-tDNA had a good consistency with the VAF of BM-tDNA (R=0.8783) and PP-ctDNA (R=0.8783) (P<0.05). The difference value of VAF between BM-tDNA and PP-ctDNA in SBPP was significantly lower than that in NBPP (P<0.05).@*CONCLUSION@#PP can replace BM as a biological sample for genes mutation detection in patients with MDS due to its stable concentration, high degree of consistency with bone marrow in clinical significant mutation sites and easy collection.

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BACKGROUND: Previous research connects p120-catenin (p120ctn) with epidermal growth factor receptor (EGFR) signaling pathways, which presents a potential role for p120ctn in EGFR tyrosine kinase inhibitor (EGFR-TKIs) resistance. However, a direct correlation between the expression pattern of p120ctn in solid tumors and the therapeutic effect of EGFR-TKIs has not yet been demonstrated. METHODS AND RESULTS: In this study, the expression pattern of p120ctn was examined in patients with the EGFR gene mutation in lung adenocarcinoma, and p120ctn was found to have different patterns of expression even in the same mutation type. The therapeutic effect of EGFR-TKIs was investigated in these patients, and patients with an abnormal expression of p120ctn were found to be more likely to have drug resistance. A gefitinib-resistant lung cancer cell line was established and alterations in the p120ctn expression pattern were also observed in vitro. CONCLUSIONS: Therefore, this study demonstrates that the expression pattern of p120ctn is associated with acquired resistance to EGFR-TKIs in lung cancer, providing information toward addressing the problem of drug resistance in patients with non-small cell lung cancer.

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BACKGROUND: Although the use of pleural effusion samples for epidermal growth factor receptor (EGFR) testing in lung cancer is increasing, the accuracy rate and effectiveness of identifying EGFR mutations using these samples, rather than primary tumor tissue samples, is not established. MATERIALS AND METHODS: One hundred ninety-two advanced, non-small cell lung cancer patients were enrolled into this study. All patients had primary tumor tissue and corresponding pleural effusion samples, and we employed the Amplification Refractory Mutation System to detect EGFR gene mutations in these samples. RESULT: The number of EGFR mutations detected in primary tumor tissue and pleural effusion samples was 119 (61.98%) and 113 (58.85%), respectively. The EGFR-mutation rate was significantly higher in female than in male patients, and in adenocarcinoma than in nonadenocarcinoma patients (P=0.000). Single mutations in exons 19 and 21 were the predominant observed mutation type, and the overall concordance rate of EGFR-mutation status between the 192 matched pleural effusion and primary tumor tissue samples was 86.98%. CONCLUSIONS: We observed a high concordance rate between EGFR mutations identified using primary tumor tissue and corresponding pleural effusion samples by Amplification Refractory Mutation System. Thus, it is likely that pleural effusion sampling from advanced non-small cell lung cancer patients, especially those with adenocarcinoma, may be effective in EGFR-mutation screening.

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Exploring methods for increasing epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) sensitivity has become a major focus in non-small cell lung cancer (NSCLC). Major downstream effectors of the Rho family small guanosine triphosphatases, P21-activated kinases (PAKs) activate the main signaling pathways downstream of EGFR and thus promote tumor cell proliferation. In this study, we explored the expression pattern of phosphorylated PAKs in NSCLC and their potential value as drug targets for treating cancer. The expression and prognostic significance of phosphorylated group I and II PAKs were evaluated in 182 patients with NSCLC. Immunohistochemical analysis revealed low group I PAK expression in normal lung tissues and increased expressed in the cytoplasm, particularly in lung squamous cell carcinoma. Abnormal group I PAK expression was associated with lymph node metastases and high tumor-node-metastases (TNM) stage in NSCLC patients and correlated with poor prognosis. We used group I PAK inhibitor (IPA3) to specifically decrease group I PAK activity in human lung cancer cell lines. Decreased group I PAK activity inhibited cell proliferation and combined IPA3 and EGFR-TKI (gefitinib) treatment inhibited cell proliferation in an obvious manner. Together, our results revealed the PAK expression pattern in NSCLC, and a role for group I PAK in cell proliferation, which provides evidence that decreased PAK activity may have a potential application as a molecular targeted therapy in advanced NSCLC.

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BACKGROUND: The different outcomes of deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) are currently being debated. We aimed to retrospectively compare the outcomes following LDLT and DDLT and to analyse the factors influencing this. METHODS: We compared the overall survival (OS) and disease-free survival (DFS) rates of HCC patients after LDLT (n=389) and DDLT (n=6471) from 81 centres over a 10-year period. OS and DFS rates were calculated with the Kaplan-Meier method. And univariate and multivariate Cox proportional hazards regressions were performed on the entire cohort to identify predictors. RESULTS: Of 6860 patients, the 1-, 3-, and 5-year OS rates were 86.79%, 70.16%, and 66.31% after LDLT, respectively, and 74.2%, 54.21%, and 46.97% after DDLT, respectively (P<0.001). The 1-, 3-, and 5-year DFS rates were 78.46%, 63.68%, and 61.63% after LDLT, respectively, and 65.65%, 48.61%, and 41.87% after DDLT, respectively (P<0.001). The multivariate Cox regression model determined that the DFS and OS of HCC patients post-liver transplantation (LT) were strongly associated with tumour morphology and biology, but not graft type. CONCLUSIONS: With regards to OS and DFS, there were no disadvantages to LDLT as compared with DDLT; tumour morphology and biology may affect the prognosis of LT.

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BACKGROUND: Salvage liver transplantation (SLT) has been proposed for recurrent hepatocellular carcinoma (HCC) after hepatectomy; however, it is unclear how the time interval to tumor recurrence from previous hepatectomy affects prognosis. METHODS: We analyzed retrospectively the outcomes of 62 patients who underwent SLT in the Liver Transplantation Center of the First Affiliated Hospital of Zhejiang University between 2001 and 2012. SLT recipients were divided into 2 groups based on whether the time interval to recurrence was >1 year (L group) or <1 year (S group). RESULTS: Baseline characteristics were similar between the 2 groups. The 1-, 3-, and 5-year overall survival rates were 81%, 45%, and 45% in the L group, which were better than in the S group, with 47%, 21%, and 21%, respectively (P = .005). The corresponding tumor-free survival rates were similar (P = .60) between 2 groups, with 71%, 51%, and 41% in the L group versus 55%, 55%, and 55% in the S group. Macrovascular invasion (hazard ratio [HR], 3.30), greatest tumor diameter (HR, 3.92), and time interval to tumor recurrence from previous hepatectomy (HR, 0.29) were independent predictors for overall survival. Furthermore, the diameter of the largest tumor was the only independent predictor of tumor-free survival (HR, 25.64). CONCLUSION: The time interval to HCC recurrence from a previous hepatectomy is an important factor associated with survival after SLT. This finding should be helpful in guiding patient selection criteria for SLT in patients with previous hepatectomy.

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BACKGROUND: We have reported that p120-catenin could regulate ß-catenin transcription in lung cancer cells, but the specific mechanism is unclear. METHODS AND RESULTS: In this study, bisulfite sequencing PCR showed that the ß-catenin promoter region in SPC-A-1 and LTEP-a-2 lung cancer cell lines has Kaiso binding sites sequences and CpG islands which may combine with Kaiso. The demethylating reagent 5-Aza-2'-deoxycytidine significantly upregulated ß-catenin mRNA expression in lung cancer cell lines, whereas expression was significantly reduced following transfection with Kaiso. However, the upregulation of ß-catenin mRNA expression after treatment with 5-Aza-2'-deoxycytidine was not reduced by subsequent transfection with Kaiso cDNA. Chromatin immunoprecipitation showed that, in lung cancer cell lines, methylated CpG-dinucleotides sequences combined with Kaiso and the Kaiso binding sites sequence did not. The capacity of Kaiso to combine with p120-catenin isoforms was confirmed by immunoprecipitation. CONCLUSIONS: Based on these results, we concluded that Kaiso participates in the regulation by p120ctn of ß-catenin mRNA expression in the lung cancer cell lines.

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BACKGROUND: Salvage liver transplantation (SLT) has recently been proposed for recurrent hepatocellular carcinoma after liver resection; however, criteria for candidate assessment in SLT have not been thoroughly evaluated. METHODS AND FINDINGS: We retrospectively analyzed outcomes and factors affecting survival of 53 recipients who received SLT in the Liver Transplantation Center, The First Affiliated Hospital of Zhejiang University between 2004 and 2012. Thirty recipients fulfilled the Hangzhou criteria, of which 16 also fulfilled the Milan criteria, while the remaining 23 exceeded both criteria. The 1-year, 3-year and 5-year overall survival rates and tumor-free survival rates were both superior in patients fulfilling Milan or Hangzhou criteria compared with those exceeding the criteria. For recipients outside Milan criteria but within Hangzhou criteria, the 1-year, 3-year overall survival rates were 70.1%, 70.1%, similar to recipients within Milan criteria, with the 1-year, 3-year and 5-year overall survival of 93.8%%, 62.1% and 62.1% (P = 0.586). The tumor-free survival rates were also similar between these two subgroups, with 51.9% and 51.9% vs. 85.6%, 85.6% and 64.2% during the same time interval, respectively (P = 0.054). Cox regression analysis identified Hangzhou criteria (within vs. outside, hazard ratio (HR) 0.376) and diameter of the largest tumor (HR 3.523) to be independent predictors for overall survival. The only predictor for tumor-free survival was diameter of the largest tumor (HR 22.289). CONCLUSIONS: Hangzhou criteria safely expanded the candidate pool and are feasible in assessment of candidates for SLT. This is helpful in donor liver allocation in transplant practice.

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BACKGROUND: Pygopus 2 (Pygo2) is a Pygo family member and an important component of the Wnt signaling transcriptional complex. Despite this data, no clinical studies investigating Pygo2 expression in lung cancer have yet been reported. METHODS: In the present study, the expression patterns of Pygo2 were evaluated by immunochemistry in 168 patients with non-small cell lung cancer (NSCLC). We used small interfering RNA (siRNA) to specifically silence Pygo2, and investigated its effect on cell growth by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis in human lung cancer cell lines. RESULTS: Immunohistochemical analysis showed low expression of Pygo2 in normal lung tissues and increased nuclear expression in lung cancer tissues, either with or without perinuclear expression. Abnormal Pygo2 expression was associated with poor differentiation and a high Tumor (T), Node (N) and Metastases (M) stage in NSCLC patients, and correlated with poor prognosis. Using MTT assay we observed that Pygo2 downregulation inhibited cell proliferation; in addition, flow cytometry analysis showed that Pygo2 knockdown induced apoptosis and increased numbers of G1-phase cells and a reduction in S-phase cells. CONCLUSIONS: We therefore conclude that abnormal Pygo2 protein expression may be a marker for advanced NSCLC. Furthermore, Pygo2 knockdown suppresses cell growth.

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Previous studies suggested Ataxia-telangiectasia group D complementing gene (ATDC) as an oncogene in many types of cancer. However, its expression and biological functions in non-small cell lung cancer (NSCLC) remain unclear. Herein, we investigated its expression pattern in 109 cases of human NSCLC samples by immunohistochemistry and found that ATDC was overexpressed in 62 of 109 NSCLC samples (56.88%). ATDC overexpression correlated with histological type (p<0.0001), tumor status (p = 0.0227) and histological differentiation (p = 0.0002). Next, we overexpressed ATDC in normal human bronchial epithelial cell line HBE and depleted its expression in NSCLC cell lines A549 and H1299. MTT and colony formation assay showed that ATDC overexpression promoted cell proliferation while its depletion inhibited cell growth. Furthermore, cell cycle analysis showed that ATDC overexpression decreased the percentage of cells in G1 phase and increased the percentage of cells in S phase, while ATDC siRNA treatment increased the G1 phase percentage and decreased the S phase percentage. Further study revealed that ATDC overexpression could up-regulate cyclin D1 and c-Myc expression in HBE cells while its depletion down-regulated cyclin D1 and c-Myc expression in A549 and H1299 cells. In addition, ATDC overexpression was also associated with an increased proliferation index, cyclin D1 and c-Myc expression in human NSCLC samples. Further experiments demonstrated that ATDC up-regulated cyclin D1 and c-Myc expression independent of wnt/ß-catenin or p53 signaling pathway. Interestingly, ATDC overexpression increased NF-κB reporter luciferase activity and p-IκB protein level. Correspondingly, NF-κB inhibitor blocked the effect of ATDC on up-regulation of cyclin D1 and c-Myc. In conclusion, we demonstrated that ATDC could promote lung cancer proliferation through NF-κB induced up-regulation of cyclin D1 and c-Myc.

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