Abstract Objectives The use of immune checkpoint inhibitors, particularly PD‐1 inhibitors, has revolutionized the treatment of advanced tumors and shown significant improvements in patient survival rates. However, which PD‐1 inhibitor is more effective and safer for a specific indication remains unclear. To address this problem, our study aimed to evaluate the effectiveness and safety of different PD‐1 inhibitors in combination with chemotherapy as first‐line therapy for individuals with advanced non‐small‐cell lung cancer (NSCLC) without driver genes in the real world. Materials and Methods We conducted a retrospective study of individuals diagnosed with aNSCLC who received immune checkpoint inhibitors (ICIs) with modified PD‐1 inhibitors, including Sintilimab, Toripalimab, Tislelizumab, Camrelizumab, or Pembrolizumab as first‐line treatment between March 5th, 2016 and October 20th, 2022. We assessed demographic and clinical information and analyzed clinical response, survival outcomes, and safety profiles. The primary endpoint was overall survival (OS), and the secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Results As of the date cut‐off on October 20th, 2022, the median follow‐up time was 20.62 months. A total of 204 patients were enrolled in the study, including 56 (27.5%) patients receiving modified PD‐1 inhibitors (Sintilimab, Toripalimab, Tislelizumab, or Camrelizumab) in combination with chemotherapy and 148 (72.5%) patients receiving Pembrolizumab in combination with chemotherapy. In the overall cohort, the median overall survival (OS) was 26.9 months (95%CI, 22.3–31.6), the median progression‐free survival (PFS) was 8.4 months (95%CI, 6.9–9.8), and the objective response rate (ORR) and disease control rate (DCR) were 47.6% (95%CI, 29.9–43.6) and 84.3% (95%CI, 78.4–88.9). The mOS of modified PD‐1 inhibitors group and Pembrolizumab group were 30.7 (95%CI, 17.3–44.4) months and 26.8 (95%CI, 22.2–31.4) months. The mPFS of two groups were 8.3(95%CI, 6.9–9.6) months and 8.8 (95%CI, 6.9–10.7) months, respectively. There was no statistical difference between the two groups in terms of OS or PFS. The ORR for the two groups was 48.2% (95%CI, 34.8–61.8) and 47.3% (95%CI, 39.1–5.6), respectively. However, due to the limited sample size, the difference was not statistically significant. On the other hand, the DCR tended to be higher in the Pembrolizumab group (86.5%; 95%CI, 79.7–91.4) compared to the modified PD‐1 inhibitors group (78.6%; 95%CI, 65.2–87.9), and this difference was statistically significant (p = 0.006). In terms of safety, both groups exhibited favorable clinical safety profiles. The only two types of potentially immune‐related adverse events reported were pneumonitis and reactive cutaneous capillary endothelial proliferation (RCCEP). Conclusions The modified PD‐1 inhibitors showed comparable survival outcomes and manageable safety profiles in NSCLC compared to Pembrolizumab. Moreover, these inhibitors exhibited improved accessibility and economic outcomes compared to Pembrolizumab. While there were similarities in drug‐related and immunotherapy‐related adverse reactions between the modified PD‐1 inhibitors and Pembrolizumab, there were some slight differences. Further prospective and retrospective studies would be necessary to validate these findings beyond the scope of the CTONG1901 study.

The management of patients with advanced non-small cell lung cancer (NSCLC) presents significant challenges due to cancer cells' intricate and heterogeneous nature. Programmed cell death (PCD) pathways are crucial in diverse biological processes. Nevertheless, the prognostic significance of cell death in NSCLC remains incompletely understood. Our study aims to investigate the prognostic importance of PCD genes and their ability to precisely stratify and evaluate the survival outcomes of patients with advanced NSCLC. We employed Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), univariate and multivariate Cox regression analyses for prognostic gene screening. Ultimately, we identified seven PCD-related genes to establish the PCD-related risk score for the advanced NSCLC model (PRAN), effectively stratifying overall survival (OS) in patients with advanced NSCLC. Multivariate Cox regression analysis revealed that the PRAN was the independent prognostic factor than clinical baseline factors. It was positively related to specific metabolic pathways, including hexosamine biosynthesis pathways, which play crucial roles in reprogramming cancer cell metabolism. Furthermore, drug prediction for different PRAN risk groups identified several sensitive drugs explicitly targeting the cell death pathway. Molecular docking analysis suggested the potential therapeutic efficacy of navitoclax in NSCLC, as it demonstrated strong binding with the amino acid residues of C-C motif chemokine ligand 14 (CCL14), carboxypeptidase A3 (CPA3), and C-X3-C motif chemokine receptor 1 (CX3CR1) proteins. The PRAN provides a robust personalized treatment and survival assessment tool in advanced NSCLC patients. Furthermore, identifying sensitive drugs for distinct PRAN risk groups holds promise for advancing targeted therapies in NSCLC.

e16261 Background: Tumor-infiltrating myeloid cells (TIMs) are abundant in tumor stroma and emerging evidence indicate that the presence of these cells influences clinical outcomes in many cancer types. TIMs play important roles in tumor progression and specific subsets may exhibit divergent anti-tumor or tumor-promoting functions. Currently, the molecular characteristics of TIMs in pancreatic ductal adenocarcinoma (PDAC) largely remain unknown. Like other programmed cell death procedures such as ferroptosis and pyroptosis, necroptosis has recently emerged as an important cellular event that modulates tumorigenesis and tumor progression. Combination of necroptosis and TIMs is of great interest to study the molecular mechanism of clinical outcomes for PDAC patients. Methods: This study enrolled 16 PDAC patients. The scRNA-seq data were obtained from a published dataset and each patient included primary tumor, metastatic tumor, primary tumor-adjacent and PBMC samples. All myeloid cells comprising granulocytes, monocytes, macrophages, and dendritic cells from enrolled patients were extracted for further analysis. We performed comprehensive analysis about the characteristics of myeloid lineages, differentially expressed genes, pathway enrichment analysis and novel cell subtype identification. The necroptosis-associated novel TIMs cell sub-clusters were elucidated in detail. Results: To comprehensively analyze the heterogeneous TIMs microenvironment in PDAC patients using scRNA-seq dataset, we firstly obtained consistently upregulated genes among granulocytes, monocytes, macrophages, and dendritic cell types between tumor samples and non-tumor samples. Those uniquely expressed genes represent different functions in necroptosis-associated TIMs cells. In total, we identified 10 necroptosis-associated upregulated genes in PDAC tumors and 5 upregulated genes in tumor-adjacent and peripheral blood samples, respectively. Based on the cells expressed those necroptosis-related genes, we identified three novel cell populations, including GLUL - SQSTM1 - RTM, HSP90AA1 + HSP90AB1 + mast cells, and JAK3 + TLR4 + CD16 monocytes, which were regulators of immunity either tumor-promoters or tumor-suppressors. Clinical outcomes further supported their function roles in the PDAC tumor microenvironment. Conclusions: This study comprehensively studied the heterogeneity of myeloid microenvironment in PDAC by scRNA-Seq. Several necroptosis-associated genes and myeloid cell sub-clusters were identified and they have prognostic clinical values in PDAC. These preliminary results were helpful for further understanding the molecular mechanism of PDAC treatment strategies.

BACKGROUND:Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial. METHODS:We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration. RESULTS:We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk. CONCLUSION:We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.

IntroductionTumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties in pancreatic ductal adenocarcinoma (PDAC) remain elusive.MethodIn this study, we conducted scRNA-seq data analysis of cells from 12 primary tumor (PT) tissues, 4 metastatic (Met) tumor tissues, 3 adjacent normal pancreas tissues (Para), and PBMC samples across 16 PDAC patients, and revealed a heterogeneous TIMs environment in PDAC.ResultSystematic comparisons between tumor and non-tumor samples of myeloid lineages identified 10 necroptosis-associated genes upregulated in PDAC tumors compared to 5 upregulated in paratumor or healthy peripheral blood. A novel RTM (resident tissue macrophages), GLUL-SQSTM1- RTM, was found to act as a positive regulator of immunity. Additionally, HSP90AA1+HSP90AB1+ mast cells exhibited pro-immune characteristics, and JAK3+TLR4+ CD16 monocytes were found to be anti-immune. The findings were validated through clinical outcomes and cytokines analyses. Lastly, intercellular network reconstruction supported the associations between the identified novel clusters, cancer cells, and immune cell populations.ConclusionOur analysis comprehensively characterized major myeloid cell lineages and identified three subsets of myeloid-derived cells associated with necroptosis. These findings not only provide a valuable resource for understanding the multi-dimensional characterization of the tumor microenvironment in PDAC but also offer valuable mechanistic insights that can guide the design of effective immuno-oncology treatment strategies.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer types worldwide. Despite significant advances in prevention and diagnosis, CRC is still one of the leading causes of cancer-related mortality globally. RAB27A, the member of RAB27 family of small GTPases, is the critical protein for intracellular secretion and has been reported to promote tumor progression. However, it is controversial for the role of RAB27A in CRC progression, so we explored the exact function of RAB27A in CRC development in this study. Based on the stable colon cancer cell lines of RAB27A knockdown and ectopic expression, we found that RAB27A knockdown inhibited proliferation and clone formation of SW480 colon cancer cells, whereas ectopic expression of RAB27A in RKO colon cancer cells facilitated cell proliferation and clone formation, indicating that RAB27A is critical for colon cancer cell growth. In addition, our data demonstrated that the migration and invasion of colon cancer cells were suppressed by RAB27A knockdown, but promoted by RAB27A ectopic expression. Therefore, RAB27A is identified as an onco-protein in mediating CRC development, which may be a valuable prognostic indicator and potential therapeutic target for CRC.

Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC. Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC). Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%). Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.

We presented a 67-year-old nonsmoking female lung adenocarcinoma patient with novel epidermal growth factor receptor (EGFR) A289G/F287_G288insHA cis mutations who responded positively to sintilimab combined with regorafenib and albumin paclitaxel, and sequential treatment of icotinib. Gene mutations in patients were detected by next-generation sequencing (NGS) technology, and changes in gene mutations before and after treatments were observed by ctDNA monitoring. We observed the efficacy of the patient through chest computed tomography (CT) imaging and carcinoembryonic antigen (CEA) level and found that the patient benefited from immunotherapy in combination with antiangiogenesis and chemotherapy for more than 1 year, CEA levels initially fell sharply and then rebounded during the treatment period. After changing to EGFR-TKI therapy, the CEA level of the patient does not only decreased sharply at the initial stage of treatment but also rebounded and increased at the later stage of treatment. The patient was tested for genetic mutations after 4 months of sequential EGFR-TKI therapy and was found to have lost all previous EGFR mutations, which may be the cause of resistance to targeted drug icotinib. We believe that our findings have enriched the EGFR mutation spectrum in NSCLC and highlighted the possible choice for patients harboring this mutation by immunotherapy combined with chemotherapy and antivascular therapy, and EGFR-TKI-targeted therapy.

Immune checkpoint inhibitors (ICIs) have greatly improved the treatment of advanced non-small-cell lung cancer, including lung adenocarcinoma (LUAD). Patients treated with ICIs can have long-term clinical outcomes; however, acquired resistance to ICI therapy has been frequently observed. To date, little is known about the underlying mechanisms. In this study, we report the case of a male smoker with metastatic LUAD who initially received multi-line radiotherapy and chemotherapy and achieved stable disease (SD) for almost 10 years. The patient was treated with nivolumab for about 15 months. However, the disease later progressed rapidly. A genetic profile of the patient revealed the homozygous deletion of the human leukocyte antigen (HLA)-B gene, which may have conferred the acquired resistance. Our study is the first to describe the homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to programmed cell death protein 1 (PD-1) blockade in a patient with LUAD. This evidence suggests that tumor cells can selectively lose HLA-A, B, and C to survive under strong immune pressure. This discovery enriches and develops our understanding of the mechanism of drug resistance in ICI therapy in LUAD. However, further investigations are urgently needed to be conducted to determine how this resistance can be overcome.

Introduction Glioma is the primary malignant brain tumor with poor prognosis. Berberine (BBR) was the potential drug for anti-tumor in glioma cells. Based on its limitation of poor aqueous solubility and instability, little information of BBR nanoparticles is reported in glioma. Methods Different solutions including 5% glucose, 1*PBS, ddH2O, 0.9% NaCl, cell culture medium were selected, and only 5% glucose and ddH2O exhibited BBR-related nanoparticles. After heating for a longer time or adding a higher concentration of glucose solution, BBR nanoparticles were detected by TEM analysis. The uptake of BBR-Glu or BBR-Water nanoparticles were detected by immunofluorescence analysis for BBR autofluorescence. Cell viability was measured by MTT assay and Western blotting analysis. Apoptosis was performed with flow cytometric analysis and was detected by cleaved caspase-3 immuno-fluorescent staining. Cell cycle was used by flow cytometric analysis. Cytoskeleton was observed by confocal analysis using the neuron specific Class III ß-tubulin and ß-tubulin antibodies. Mitochondrial-related proteins were detected by Western blotting analyses and mito-tracker staining in live cells. Mitochondrion structures were observed by TEM analysis. ROS generation and ATP production were detected by related commercial kits. The tracking of BBR-Glu or BBR-Water nanoparticles into blood–brain barrier was observed in primary tumor-bearing models. The fluorescence of BBR was detected by confocal analyses in brains and gliomas. Results BBR-Glu nanoparticles became more homogenized and smaller with dose- and time-dependent manners. BBR-Glu nanoparticles were easily absorbed in glioma cells. The IC50 of BBR-Glu in U87 and U251 was far lower than that of BBR-Water. BBR-Glu performed better cytotoxicity, with higher G2/M phase arrest, decreased cell viability by targeting mitochondrion. In primary U87 glioma-bearing mice, BBR-Glu exhibited better imaging in brains and gliomas, indicating that more BBR moved across the blood–brain tumor barrier. Discussion BBR-Glu nanoparticles have better solubility and stability, providing a promising strategy in glioma precision treatment.

Gastric cancer (GC) is often diagnosed in the advanced stages and is associated with a poor prognosis. Obtaining an in depth understanding of the molecular mechanisms of GC has lagged behind compared with other cancers. This study aimed to identify candidate biomarkers for GC. An integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between GC and normal tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to identify the functions of the DEGs. Furthermore, a protein-protein interaction (PPI) network of the DEGs was constructed. The expression levels of the DEGs were validated in human GC tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A set of 689 DEGs were identified in GC tissues, as compared with normal tissues, including 202 upregulated DEGs and 487 downregulated DEGs. The KEGG pathway analysis suggested that various pathways may play important roles in the pathology of GC, including pathways related to protein digestion and absorption, extracellular matrix-receptor interaction, and the metabolism of xenobiotics by cytochrome P450. The PPI network analysis indicated that the significant hub proteins consisted of SPP1, TOP2A and ARPC1B. RT-qPCR validation indicated that the expression levels of the top 10 most significantly dysexpressed genes were consistent with the illustration of the integrated analysis. The present study yielded a reference list of reliable DEGs, which represents a robust pool of candidates for further evaluation of GC pathogenesis and treatment.

PURPOSE:Extramammary Paget's disease (EMPD) is a rare neoplasm with only a limited number of cases reported in the literature. Little was known about the availability of systemic chemotherapy for metastatic EMPD.METHODS:We report one case of heavily pretreated EMPD with multiple organ metastases and successfully treated by pemetrexed.RESULT:The tumor was progression after multi-line therapy including erlotinib, radiotherapy, combined chemotherapy and radioactive particles implantation. Pemetrexed monotherapy was applied and progression free survival of more than 5 months with partial remission (PR) response was achieved. Only 1 time of grade 3 neutropenia was observed during the pemetrexed chemotherapy.CONCLUSION:Due to the significant response and tolerability in the present case, pemetrexed monotherapy was recommended as a potent candidate for patients with advanced EMPD.

The Rab27 subfamily of secretory small GTPase plays a vital role in vesicle trafficking and regulates tumor growth and metastasis in several cancer types. Thus, this research was designed to explore the clinical and prognostic significance of Rab27A and Rab27B in colorectal cancer (CRC) patients. Reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry (IHC) analysis were used to examine Rab27A and Rab27B expression in human CRC cell lines and primary tumors. The correlation of gene expression with clinicopathological features and prognosis was also evaluated. Our results indicated that Rab27A expression was down-regulated in primary tumors compared with matched adjacent tissues (100%, 8/8), as detected by western blot. IHC analysis revealed that the positive expression rate of Rab27A in primary CRC tissues was lower than in adjacent normal tissues (P = 0.005). Negative expression of Rab27A and Rab27B significantly correlated with poor tumor differentiation (both P < 0.001) and positive vascular invasion (P = 0.005, P = 0.021, respectively). Moreover, absence of Rab27A was associated with advanced tumor node metastasis (TNM) stage (P = 0.006), distant metastasis (P = 0.002), and local recurrence (P = 0.038). Survival analysis also showed a significant correlation between unfavorable survival and negative expression of Rab27A (P = 0.002). In addition, positive expression of both Rab27A and Rab27B was a protective factor in CRC. In conclusion, decreased expression of Rab27A and Rab27B, especially Rab27A, closely correlated with tumor progression and are valuable prognostic indicators in CRC patients.

OBJECTIVES:To identify the problems and principles of treatment decisions in treatment-naïve limited-stage small cell esophagus carcinoma (LD-SCEC).METHODS:Clinical data from 39 patients with LD-SCEC treated in the Chinese People's Liberation Army General Hospital, Beijing, China between 2000 and 2013 were retrospectively collected with regard to pathologic characteristics, overall survival (OS), and relevant prognostic factors.RESULTS:The median OS was 21.1 months (95% confidence interval [CI]: 12.4-29.7 months). The one-year OS was 76%, 3-year was 25%, and the 5-year OS was 8%. Depth of invasion, lymph metastasis status, and chemotherapy were independent prognostic factors. Of the 39 cases, only 38.4% (15 cases) were diagnosed as SCEC by the biopsy specimen. Eight of the 15 patients (group A) received chemotherapy and/or radiotherapy, while the remaining 7 patients (group B) and the other 24 patients (group C) received surgery as initial treatment. The one-year survival of group A was 87%, of group B was 69%, and of group C was 74% (p=0.037). The accuracy of the biopsy diagnosis influenced the treatment decisions and prognosis.CONCLUSION:Small cell esophagus carcinoma is a systemic disease, with depth of invasion, lymph metastasis status, and chemotherapy as independent prognostic factors. Systemic therapy based on chemotherapy is recommended. The top priority is to improve the accuracy of diagnosis before deciding on the initial treatment option.

Objective:To assess the efifcacy and safety of temozolomide (TMZ) combined with whole brain radiotherapy in the treatment of lung cancer patients with brain metastases.Methods:A total of 24 lung cancer patients with brain metastases were enrolled in this retrospective study. The whole brain radiotherapy with the total dose of 40 Gy (2 Gy per time, 5 times per week) was given to all the patients, and another 10–20 Gy of intensity-modulated boosting therapy for local lesion was given if necessary. All patients took temozolomide (75 mg·m-2) concurrently during the whole course of radiotherapy. Temozolomide should be stopped, if the patient can not tolerate adverse reactions. After radiotherapy, the patients received systematical chemotherapy or continued TMZ therapy (150–200 mg·m-2·d-1, 5/28 d) for additional 0–6 cycles according to the condition of the patients. The efifcacy and adverse reactions were evaluated statistically.Results:All the patients ifnished the radiotherapy combined with concurrent TMZ. Afterwards, 10 patients received systematical chemotherapy, 7 patients received the best supportive treatment, 3 patients received additional 4 cycles of TMZ adjuvant therapy, and 3 patients continued 6 cycles of TMZ chemotherapy. After radiotherapy and chemotherapy, 2 patients had complete response, 7 patients had partial response, 12 patients had stable disease, while the other 3 patients had progressed disease by evaluation of intracranial lesion. Therefore, the total effective rate achieved 37.5%, the disease control rate obtained 87.5%, the median PFS was 5 months, the median intracranial lesions PFS was 6 months. Acute side-effects were developed in 18 patients. GradeⅢorⅣhematologic toxicities were developed in 3 patients (12.5%), but gradeⅢ–Ⅳnon-hematologic side-effects were developed in 4 patients (16.7%).Conclusion:Temozolomide was well tolerant, and showed signiifcant improvements in response rate when combined with whole brain radiotherapy in lung cancer with brain metastases. While, the beneift of long-term survival needs to be veriifed by further clinical studies.

The present study explored the use of methylated NDRG4 gene as a candidate biomarker for diagnosis of colorectal cancer (CRC). Methylated NDRG4 gene expression from colorectal carcinoma tissue, paracarcinoma tissues, stools, blood and urine were detected successfully in DNA samples from 84 patients, by nested methylation-specific polymerase chain reaction and denaturing high-performance liquid chromatography. The sensitivity and specificity of methylated NDRG4 gene expression for us as a biomarker in colorectal cancer was analyzed and compared with 16 age-matched healthy controls. The positive detection rate of methylated NDRG4 was 81% in carcinoma tissue, 8.3% in paracarcinoma tissues, 54.8% in blood, 72.6% in urine and 76.2% in stools. Considering the convenience of the acquisition of urine samples, an additional group of 76 patients with CRC were recruited for verification of detecting methylated NDRG4 in the urine. The positive detection rate of methylated NDRG4 was 72.4% (55/76) in this cohort. The detection of methylated NDRG4 in stools and urine could be used as a novel diagnostic technique for highly sensitive and specific detection of CRC. Due to the ease of collecting urine samples, this novel method could be a potential biomarker for early diagnosis of CRC.

Swanson's literature-based discovery focus on resurrecting previously published but neglected knowledge. In this study, we propose a two-step model of the discovery process and generate a hypothesis between anandamide and gastric cancer. Further, the potential relationship was confirmed by follow-up experimentation. The anandamide treatment resulted in cell cycle redistribution of gastric cancer cells. Most importantly, the variation of cell cycle was mediated by some genes from the B-terms of the closed discovery, indicating the potential role of the B-terms. Swanson's literature-based discovery not only collates data for possible interactions, but also provides the potential to observe the larger background behind these direct links and is an invaluable discovery tool for investigators.

目的 比较贝伐单抗联合培美曲塞加顺铂(Avastin+ PP)化疗方案与单用培美曲塞加顺铂(PP)化疗方案治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效及不良反应.方法 收集2009年9月-2013年6月在我院应用贝伐单抗联合培美曲塞加顺铂治疗的晚期非小细胞肺癌患者32例为联合治疗组,取同时期、同TNM分期、同病理类型,采用培美曲塞加顺铂化疗方案的患者35例为对照组,所有患者均符合化疗要求.对照组:培美曲塞500 mg/m2,静脉滴注,d1;顺铂75 mg/m2静脉滴注,d1或d1 ～ d3;每21d为1个周期.联合治疗组:培美曲塞和顺铂用法及用量同对照组,贝伐单抗7.5 mg/kg静脉滴注,d1,每21d为1个周期.结果 联合治疗组和对照组疾病控制率分别为90.6％和60.0％(P＜0.05);客观有效率分别为56.9％和25.7％(P＜0.05);中位无进展生存期分别为7.3个月和4.2个月(P＜0.05);中位总生存期分别为20.7个月和9.0个月(P＜0.05),不良反应有骨髓抑制、恶心呕吐、肝肾功能损伤等,但两组差异无统计学意义.结论 贝伐单抗联合培美曲塞加顺铂化疗方案治疗晚期非小细胞肺癌在远期疗效和近期疗效方面均优于单用培美曲塞加顺铂化疗方案,且没有增加严重不良反应.

Previous studies examining the association between p73 G4A and gastric cancer risk have produced inconsistent results. The objective of this study was to clarify whether p73 G4A plays a major role in the development of gastric cancer. Studies that had examined the association between p73 G4A and gastric cancer risk were identified through PubMed, Science Direct, and CNKI. We selected eligible studies based on inclusion criteria. Odds ratios were estimated using distinct genetic models, and the heterogeneity between studies was explored using Cochran's Q statistic along with the I(2) statistic. Overall, we found no evidence of a significant association between p73 G4A and risk of gastric cancer. A same trend was also indicated in subgroup analysis by ethnicity. The heterogeneity tests revealed that there was no significant heterogeneity across studies. Our meta-analysis indicates that p73 G4A might not have a major effect on risk of gastric cancer. A much larger study is required to validate our findings.