Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

Metabolomic machine learning predictor for diagnosis and prognosis of gastric cancer.

Gastric cancer (GC) represents a significant burden of cancer-related mortality worldwide, underscoring an urgent need for the development of early detection strategies and precise postoperative interventions. However, the identification of non-invasive biomarkers for early diagnosis and patient risk stratification remains underexplored. Here, we conduct a targeted metabolomics analysis of 702 plasma samples from multi-center participants to elucidate the GC metabolic reprogramming. Our machine learning analysis reveals a 10-metabolite GC diagnostic model, which is validated in an external test set with a sensitivity of 0.905, outperforming conventional methods leveraging cancer protein markers (sensitivity < 0.40). Additionally, our machine learning-derived prognostic model demonstrates superior performance to traditional models utilizing clinical parameters and effectively stratifies patients into different risk groups to guide precision interventions. Collectively, our findings reveal the metabolic landscape of GC and identify two distinct biomarker panels that enable early detection and prognosis prediction respectively, thus facilitating precision medicine in GC.

Hsa_circ_0119412 Contributes to Development of Retinoblastoma by Targeting miR-186-5p/ELK4 Axis.

Increasing evidences indicate the crucial role of circRNAs in tumorigenesis, but little is understood about their molecular mechanism in retinoblastoma (RB). This paper was designed for exploring the circ_0119412 function in cases with RB and the potential mechanism. RT-qPCR was utilized to ascertain circ_0119412 and miR-186-5p levels in RB tissues and cells, and western blotting was used to quantify ELK4 in RB cells. In addition, CCK-8 and scratch assays were carried out for evaluation of cell proliferation and migration, respectively. Apoptosis-related proteins levels (Bax and Bcl-2) were measure by western blotting. Tumor growth in vivo was detected utilizing xenograft tumor experiment. The targeting relationship between circ_0119412, miR-186-5p, and ELK4 was validated using a dual-luciferase reporter assay and an RNA immunoprecipitation (RIP) assay. In RB tissues and cells, Circ_0119412 and ELK4 expression were upregulated, while miR-186-5p expression was downregulated. In vitro assay revealed that downregulating circ_0119412 accelerated the cell apoptosis of RB cells and slowed down their migration and proliferation, and the in vivo assay indicated that circ_0119412 downregulation reduced the weight and volume of tumor in nude mice. In addition, miR-186-5p interference promoted the malignant behavior of RB cells, while ELK4 silencing showed an opposite trend. Mechanically, circ_0119412 can promote RB malignant phenotypes via miR-186-5p/ELK4 axis. Circ_0119412 was found to be upregulated in RB, and could accelerate the progression of RB via the miR-186-5p/ELK4 axis, indicating circ_0119412 may serve a promising clinical therapeutic target of RB.

Nutritional Risk Index as a Prognostic Factor Predicts the Clinical Outcomes in Patients With Stage III Gastric Cancer.

Objective: This study is aimed to determine the potential prognostic significance of nutritional risk index (NRI) in patients with stage III gastric cancer. Methods: A total of 202 patients with stage III gastric cancer were enrolled in this study. NRI was an index based on ideal body weight, present body weight, and serum albumin levels. All patients were divided into two groups by receiver operating characteristic curve: low NRI group (NRI<99) and high NRI group (NRI≥99). The relationship between NRI and clinicopathologic characteristics was evaluated by Chi-square test. The clinical survival outcome was analyzed by Kaplan-Meier method and compared using log-rank test. The univariate and multivariate analyses were used to detect the potential prognostic factors. A nomogram for individualized assessment of disease-free survival (DFS) and overall survival (OS). The calibration curve was used to evaluate the performance of the nomogram for predicted and the actual probability of survival time. The decision curve analysis was performed to assess the clinical utility of the nomogram by quantifying the net benefits at different threshold probabilities. Results: The results indicated that NRI had prognostic significance by optimal cutoff value of 99. With regard to clinicopathologic characteristics, NRI showed significant relationship with age, weight, body mass index, total protein, albumin, albumin/globulin, prealbumin, glucose, white blood cell, neutrophils, lymphocyte, hemoglobin, red blood cell, hematocrit, total lymph nodes, and human epidermal growth factor receptor 2 (P<0.05). Through the univariate and multivariate analyses, NRI, total lymph nodes, and tumor size were identified as the independent factor to predict the DFS and OS. The nomogram was used to predict the 1-, 3-, and 5-year survival probabilities, and the calibration curve showed that the prediction line matched the reference line well for 1-, 3-, and 5-year DFS and OS. Furthermore, the decision curve analysis also showed that the nomogram model yielded the best net benefit across the range of threshold probability for 1-, 3-, 5-year DFS and OS. Conclusions: NRI is described as the potential prognostic factor for patients with stage III gastric cancer and is used to predict the survival and prognosis.

Emodin succinyl ester inhibits malignant proliferation and migration of hepatocellular carcinoma by suppressing the interaction of AR and EZH2.

Emodin is a promising anti-cancer reagent. To improve the physicochemical and anti-cancer property, we modified its structure and get a derivative called emodin succinyl ester (ESE). Here, we investigated the effect of ESE on the suppression of hepatocellular carcinoma (HCC) and the underlying mechanism. Our results showed that ESE strongly inhibited HCC cell proliferation and migration in vitro. Further study revealed that ESE treatment decreased transcription level and protein expression of androgen receptor (AR) and enhancer of zeste homolog 2 (EZH2), two key factors interacting to promote aggressive HCC development. Conversely, overexpression of AR attenuated the inhibitory effect of ESE on EZH2 expression, and vice versa. Importantly, overexpression of AR or EZH2 could counteract ESE-suppressed cell proliferation and migration. The association of ESE-targeted AR and EZH2 with the suppression of tumorigenicity was further confirmed in xenograft and diethylnitrosamine (DEN)-induced HCC mouse models. These findings validate the therapeutic effect of ESE on HCC aggression by targeting the interaction of AR and EZH2, suggesting ESE may be a potent drug in the clinical treatment of HCC.

Diagnostic Sensitivity of NLR and PLR in Early Diagnosis of Gastric Cancer.

The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are markers of systemic inflammation. However, there is little evidence of the value of inflammation in the early diagnosis of gastric cancer (GC). A total of 2,606 patients diagnosed with GC in the past three years and 3,219 healthy controls over the same period were included in this study. Peripheral blood samples were obtained to analyze the NLR, PLR, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). The optimal cutoff levels for the NLR and PLR were defined by receiver operating characteristic (ROC) curve analysis (NLR = 2.258, PLR = 147.368). The value of different biomarkers for diagnosing GC was compared by the area under the curve (AUC). The NLR and PLR showed diagnostic sensitivity in GC (AUC = 0.715, AUC = 0.707). Using the Bonferroni correction, the NLR and PLR were superior to CEA and CA19-9 in the diagnosis of GC (P < 0.0001). The systemic inflammatory markers were significantly higher in the early stage of GC than tumor markers. After grouping patients and healthy controls by gender, we found that the diagnostic significance of combined NLR and PLR for GC was greater in male patients than in female patients (P < 0.0001). The diagnostic value of the NLR and PLR in GC is higher than that of the traditional tumor markers CEA and CA19-9. Systemic markers of inflammation are more valuable in male than female patients.

RETRACTED: Baicalein inhibits proliferation and migration of bladder cancer cell line T24 by down-regulation of microRNA-106.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. A panel from Figure 2A appears similar to a panel from Figure 6C of the article published by Qiu Hong Rui, Jian Bo Ma, Yu Feng Liao, Jin Hua Dai and Zhen Yu Cai in the Brazilian Journal of Medical and Biological Research 52(4) (2019) e7728 http://dx.doi.org/10.1590/1414-431X20197728. Also, panels from Figure 4F appear similar to panels from Figure 6C of the article published by the Brazilian Journal of Medical and Biological Research 52(4) (2019) e7728 and Figure 2B of the article published by Jin Zhou, Hao Li, Na Li, Xiangpan Li, Huibo Zhang, Qibin Song and Min Peng in the International Journal of Clinical and Experimental Pathology 10(8) (2017) 8211­8221 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965428/. The journal also requested a response from the corresponding author on the post-publication comments of Dr Elisabeth Bik https://scienceintegritydigest.com/2020/02/21/the-tadpole-paper-mill/ but did not receive a response. Although this article was published earlier than the article from the Brazilian Journal of Medical and Biological Research, the Editor decided to retract this article given the concerns on the reliability of the data. Also, one of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original. As such this article represents an abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Androgen receptor drives hepatocellular carcinogenesis by activating enhancer of zeste homolog 2-mediated Wnt/ß-catenin signaling.

BACKGROUND: Androgen receptor (AR) plays a crucial role as a transcription factor in promoting the development of hepatocellular carcinoma (HCC) which is prone to aberrant chromatin modifications. However, the regulatory effects of AR on epigenetic mediators in HCC remain ill-defined. Enhancer of zeste homolog 2 (EZH2), an oncogene responsible for the tri-methylation of histone H3 at lysine 27 (H3K27me3), was identified to be overexpressed in approximate 70-90% of HCC cases, which prompted us to investigate whether or how AR regulates EZH2 expression. METHODS: Colony formation, soft agar assay, xenograft and orthotopic mouse models were used to determine cell proliferation and tumorigenicity of gene-manipulated HCC cells. Gene regulation was assessed by chromatin immunoprecipitation, luciferase reporter assay, quantitative RT-PCR and immunoblotting. Clinical relevance of candidate proteins in patient specimens was examined in terms of pathological parameters and postsurgical survival rates. FINDINGS: In this study, we found that AR upregulated EZH2 expression by binding to EZH2 promoter and stimulating its transcriptional activity. EZH2 overexpression increased H3K27me3 levels and thereby silenced the expression of Wnt signal inhibitors, resulting in activation of Wnt/ß-catenin signaling and subsequently induction of cell proliferation and tumorigenesis. In a cohort of human HCC patients, concordant overexpression of AR, EZH2, H3K27me3 and active ß-catenin was observed in tumor tissues compared with paired non-tumor tissues, which correlated with tumor progression and poor prognosis. These findings demonstrate a novel working model in which EZH2 mediates AR-induced Wnt/ß-catenin signaling activation through epigenetic modification, and support the application of EZH2-targeted reagents for treating HCC patients.

Marine Natural Products for Drug Discovery: First Discovery of Kealiinines A-C and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents.

Leucetta alkaloid kealiinines A-C and kealiinine B derivatives were designed, synthesized, and characterized on the basis of NMR and HR-MS. The anti-TMV and antiphytopathogenic fungus activities of these alkaloids were evaluated for the first time. Kealiinine B exhibited a higher anti-TMV activity than kealiinines A and C. Kealiinine B derivatives 2m (inhibitory rates: 68, 66, and 71% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively) and 2y (inhibitory rates: 69, 64, and 63% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively) showed significantly higher antiviral activity than ningnanmycin (inhibitory rates: 56, 56, and 58% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively), thus emerging as new lead compounds for novel antiviral agent development. Structure-activity relationship research provided the basis for structural simplification of these alkaloids. Further fungicidal activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds 2i and 2p displayed good fungicidal activities in vitro against Sclerotinia sclerotiorum and Rhizoctonia cerealis with inhibition rates of 71%/50 mg/kg and 70%/50 mg/kg, respectively.

Various Bioactivity and Relationship of Structure-Activity of Matrine Analogues.

For the first time, the botanic source natural product matrine was reported to have more potent inhibitory activity against tobacco mosaic virus (TMV) than the commercial virucide ribavirin. On the basis of the structural diversity modification strategy, a series of matrine derivatives was synthesized and systematically evaluated for their antiviral activity against TMV, fungicidal activity, and insecticidal activity. As a result, compounds 3 (inhibitory rate 67.3%, 69.5%, 63.7%, 63.0% at 500 µg/mL for in vitro activity, inactivation, curative, and protection activities in vivo, respectively), 16 (66.7%, 60.7%, 63.8%, 68.9% at 500 µg/mL), and 32 (74.6%, 76.9%, 72.3%, 75.7% at 500 µg/mL) were found to have much higher anti-TMV activity than ribavirin (40.8%, 37.5%, 38.2%, 37.7% at 500 µg/mL), even exhibiting as well as NK-007 (70.3%, 66.1%, 68.4%, 67.5% at 500 µg/mL), which was an efficient compound created by our group previously. At the same time, it was found that matrine and its derivatives had a broad spectrum fungicidal activity (14 fungi), especially the inhibition of compound 32 against Phytophthora capsici Leonian reached 96.4% at a concentration of 50 µg/mL. What's more, all compounds exhibited very good insecticidal activity to five kinds of insects (including Mythimna Separate, Helicoverpa Armigera, Ostrinia Nubilalis, Plutella xylostella, and Culex Pipiens Pallens); especially, the inhibition rate of C. Pipiens Pallens of compound 22 could still reach 70% at 1 µg/mL.

Integrated analysis identifies microRNA-195 as a suppressor of Hippo-YAP pathway in colorectal cancer.

BACKGROUND: With persistent inconsistencies in colorectal cancer (CRC) miRNAs expression data, it is crucial to shift toward inclusion of a "pre-laboratory" integrated analysis to expedite effective precision medicine and translational research. Aberrant expression of hsa-miRNA-195 (miR-195) which is distinguished as a clinically noteworthy miRNA has previously been observed in multiple cancers, yet its role in CRC remains unclear. METHODS: In this study, we performed an integrated analysis of seven CRC miRNAs expression datasets. The expression of miR-195 was validated in The Cancer Genome Atlas (TCGA) datasets, and an independent validation sample cohort. Colon cancer cells were transfected with miR-195 mimic and inhibitor, after which cell proliferation, colony formation, migration, invasion, and dual luciferase reporter were assayed. Xenograft mouse models were used to determine the role of miR-195 in CRC tumorigenicity in vivo. RESULTS: Four downregulated miRNAs (hsa-let-7a, hsa-miR-125b, hsa-miR-145, and hsa-miR-195) were demonstrated to be potentially useful diagnostic markers in the clinical setting. CRC patients with a decreased level of miR-195-5p in tumor tissues had significantly shortened survival as revealed by the TCGA colon adenocarcinoma (COAD) dataset and our CRC cohort. Overexpression of miR-195-5p in DLD1 and HCT116 cells repressed cell growth, colony formation, invasion, and migration. Inhibition of miR-195-5p function contributed to aberrant cell proliferation, migration, invasion, and epithelial mesenchymal transition (EMT). We identified miR-195-5p binding sites within the 3'-untranslated region (3'-UTR) of the human yes-associated protein (YAP) mRNA. YAP1 expression was downregulated after miR-195-5p treatment by qRT-PCR analysis and western blot. CONCLUSIONS: Four downregulated miRNAs were shown to be prime candidates for a panel of biomarkers with sufficient diagnostic accuracy for CRC in a clinical setting. Our integrated microRNA profiling approach identified miR-195-5p independently associated with prognosis in CRC. Our results demonstrated that miR-195-5p was a potent suppressor of YAP1, and miR-195-5p-mediated downregulation of YAP1 significantly reduced tumor development in a mouse CRC xenograft model. In the clinic, miR-195-5p can serve as a prognostic marker to predict the outcome of the CRC patients.

Feasibility of a novel one-stop ISET device to capture CTCs and its clinical application.

INTRODUCTION: Circulating tumor cells (CTCs) play a crucial role in cancer metastasis. In this study, we introduced a novel isolation method by size of epithelial tumor cells (ISET) device with automatic isolation and staining procedure, named one-stop ISET (osISET) and validated its feasibility to capture CTCs from cancer patients. Moreover, we aim to investigate the correlation between clinicopathologic features and CTCs in colorectal cancer (CRC) in order to explore its clinical application. RESULTS: The capture efficiency ranged from 80.3% to 88% with tumor cells spiked into medium while 67% to 78.3% with tumor cells spiked into healthy donors' blood. In detection blood samples of 72 CRC patients, CTCs and clusters of circulating tumor cells (CTC-clusters) were detected with a positive rate of 52.8% (38/72) and 18.1% (13/72) respectively. Moreover, CTC positive rate was associated with factors of lymphatic or venous invasion, tumor depth, lymph node metastasis and TNM stage in CRC patients (p < 0.01). Lymphocyte count and neutrophil to lymphocyte ratio (NLR) were significantly different between CTC positive and negative groups (p < 0.01). MATERIALS AND METHODS: The capture efficiency of the device was tested by spiking cancer cells (MCF-7, A549, SW480, Hela) into medium or blood samples of healthy donors. Blood samples of 72 CRC patients were detected by osISET device. The clinicopathologic characteristics of 72 CRC patients were collected and the association with CTC positive rate or CTC count were analyzed. CONCLUSIONS: Our osISET device was feasible to capture and identify CTCs and CTC-clusters from cancer patients. In addition, our device holds a potential for application in cancer management.

The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis.

BACKGROUND: MDM4 is the important negative regulator of the tumor suppressor protein p53, which is overexpressed in various human cancers. This study evaluates the MDM4 expression in patients with gastric adenocarcinoma (GTAC) at the mRNA and protein levels and examines relationships among MDM4 expression, clinicopathological features, and prognosis. RESULTS: The qRT-PCR and the Western blot analysis showed that the MDM4 expression level was high in GTACN+ but not in GTACN-. The high expression level of MDM4 was significantly associated with age (P = 0.047), lymph node metastasis (LNM) (P < 0.001), pathological stage (P < 0.001), differentiation status (P = 0.001), and preoperative serum CA19-9 level (P < 0.001). Moreover, the survival analysis showed that Borrmann type, depth of invasion, LNM, and preoperative serum CA19-9 level were independent prognostic factors. The univariate analysis revealed that MDM4 expression influenced GTAC prognosis. Furthermore, the influence of overall prognosis relies on whether or not the high MDM4 expression level could lead to LNM. MATERIALS AND METHODS: We investigated MDM4 expression in primary GTAC and paired normal gastric tissues (30 pairs) through qRT-PCR and Western blot analyses. We also performed immunohistochemistry analysis on 336 paraffin-embedded GTAC specimens and 33 matched normal specimens. CONCLUSIONS: MDM4 expression may result in LMN of GTAC. High MDM4 expression levels are associated with LMN of GTAC and influence the prognosis of patients with GTAC.

Capture and Identification of Heterogeneous Circulating Tumor Cells Using Transparent Nanomaterials and Quantum Dots-Based Multiplexed Imaging.

BACKGROUND: Capture and identification of circulating tumor cells (CTCs) in the blood system can help guide therapy and predict the prognosis of cancer patients. However, simultaneous capture and identification of CTCs with both epithelial and mesenchymal phenotypes remains a formidable technical challenge for cancer research. This study aimed at developing a system to efficiently capture and identify these CTCs with heterogeneous phenotypes using transparent nanomaterials and quantum dots (QDs)-based multiplexed imaging. METHODS: Hydroxyapatite-chitosan (HA-CTS) nanofilm-coated substrates were modified based on our previous work to increase the capture efficiency of cancer cell lines by extending baking and incubating time. QDs-based imaging was applied to detect cytokeratin, epithelial cell adhesion molecule (EpCAM), and vimentin of cancer cells to demonstrate the feasibility of multiplexed imaging. And QDs-based multiplexed imaging of CD45, cytokeratin and vimentin was applied to detect CTCs from different cancer patients that were captured using HA-CTS nanofilm substrates. RESULTS: Comparisons of the capture efficiencies of cancer cells at different baking time of film formation and incubating time of cell capture revealed the optimal baking and incubating time. Optimal time was chosen to develop a modified CTCs capture system that could capture EpCAM-positive cancer cells at an efficiency > 80%, and EpCAM-negative cancer cells at an efficiency > 50%. QDs-based imaging exhibited comparable detection ability but higher photostability compared to organic dyes imaging in staining cells. In addition, QDs-based multiplexed imaging also showed the molecular profiles of cancer cell lines with different phenotypes well. The integrated CTCs capture and identification system successfully captured and imaged CTCs with different sub-phenotypes in blood samples from cancer patients. CONCLUSION: This study demonstrated a reliable capture and detection system for heterogeneous CTCs that combined enrichment equipment based on HA-CTS nanofilm substrates with QDs-based multiplexed imaging.

Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients.

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.

Clinicopathological features of gastric adenocarcinoma patients with metachronous distant metastasis.

Metachronous distant metastasis influences the postoperative survival of gastric adenocarcinoma patients with radical gastrectomy. We retrospectively reviewed 108 gastric adenocarcinoma patients with metachronous distant metastasis admitted to our hospital between January 2006 and December 2011. First, these patients were divided into two groups according to the time of metastasis: the early metastasis group (EMG) and late metastasis group (LMG). Second, according to the survival time after metastasis, these patients were divided into the longer survival group (LSG) and shorter survival group (SSG). Chi-square and Fisher exact tests were used to analyze associations between categorical variables. Survival data were estimated using the Kaplan-Meier method. Multivariate analyses of the prognostic factors related to overall survival were conducted using the Cox stepwise proportional hazards test. Results shows that the EMG was significantly associated with depth of invasion (p = 0.005), Union for International Cancer Control (UICC) stage (p = 0.003), degree of differentiation (p = 0.002), and vascular invasion (p = 0.001). The SSG was significantly associated with depth of invasion (p = 0.026) and normal carcinoembryonic antigen (CEA) level of after metastasis (p = 0.003). Survival analysis showed that depth of invasion (p < 0.001), degree of differentiation (p = 0.001), and vascular invasion (p = 0.011) were independent prognostic factors for gastric adenocarcinoma patients with metachronous distant metastasis. Gastric adenocarcinoma patients with metachronous distant metastasis exhibit characteristics that can be used to effectively estimate the possibility of early distant metastasis and the prognosis of these patients.

Kaempferol inhibits gastric cancer tumor growth: An in vitro and in vivo study.

Kaempferol, which is one of the general flavonoids, has recently been reported to suppress proliferation, induce cell cycle arrest and promote apoptosis in various human cancer cell lines. In the present study, the effect and mechanism of kaempferol on gastric cancer (GC) was examined. The results showed that kaempferol significantly inhibited the proliferation of MKN28 and SGC7901 cell lines. However, no significant inhibition in the GSE-1 normal gastric epithelial cell line in our experimental dose was detected. Additionally, significant apoptosis and G2/M phase cell cycle arrest were identified following the treatment of kaempferol. More importantly, we observed that kaempferol inhibited the growth of the tumor xenografts although no marked effects on liver, spleen or body weight were induced. The expression levels of G2/M cell cycle­regulating factors, cyclin B1, Cdk1 and Cdc25C, were significantly reduced. In addition, kaempferol treatment markedly decreased the level of Bcl-2 concomitant with an increase in Bax expression, resulting in the upregulation of cleaved caspase-3 and -9, which promoted PARP cleavage. Kaempferol-treated cells also led to a decrease in p-Akt, p-ERK and COX-2 expression levels. The present study therefore provided evidence that kaempferol may be a therapeutic agent for GC.

Quantification of rare cancer cells in patients with gastrointestinal cancer by nanostructured substrate.

Detecting the cancer cells in the peripheral blood, i.e. circulating tumor cell (CTC), have been considered as the "liquid biopsy" and become a particular area of focus. A deep insight into CTC provides a potential alternative method for early diagnosis of solid tumor. Previous studies showed that CTC counts could be regarded as an indicator in tumor diagnosis, predicting clinical outcomes and monitoring treatment responses. In this report, we utilize our facile and efficient CTC detection device made of hydroxyapatite/chitosan (HA/CTS) for rare cancer cells isolation and enumeration in clinical use. A biocompatible and surface roughness controllable nanofilm was deposited onto a glass slide to achieve enhanced topographic interactions with nanoscale cellular surface components, anti-EpCAM (epithelial cell adhesion molecule, EpCAM) were then coated onto the surface of nanosubstrate for specific capture of CTCs. This device performed a considerable and stable capture yields. We evaluated the relationship performance between serial CTC changes and the changes of tumor volume/serum tumor marker in gastrointestinal cancer patients undergoing anti-cancer treatments. The present study results showed that changes in the number of CTC were associated with tumor burden and progression. Enumeration of CTCs in cancer patients may predict clinical response. Longitudinal monitoring of individual patients during the therapeutic process showed a close correlation between CTC quantity and clinical response to anti-cancer therapy. Effectively capture of this device is capable of CTCs isolation and quantification for monitoring of cancer and predicting treatment response.

Transparent, biocompatible nanostructured surfaces for cancer cell capture and culture.

Circulating tumor cells (CTCs) in the blood which have detached from both the primary tumor and any metastases may be considered as a "liquid biopsy" and are expected to replace tumor biopsies in the monitoring of treatment response and determining patient prognosis. Here, we introduce a facile and efficient CTC detection material made of hydroxyapatite/chitosan (HA/CTS), which is beneficial because of its transparency and excellent biological compatibility. Atomic force microscopy images show that the roughness of the HA/CTS nanofilm (HA/CTSNF) substrates can be controlled by changing the HA:CTS ratio. Enhanced local topographic interactions between nano-components on cancer cell membranes, and the antibody coated nanostructured substrate lead to improved CTC capture and separation. This remarkable nanostructured substrate has the potential for CTC culture in situ and merits further analysis. CTCs captured from artificial blood samples were observed in culture on HA/CTSNF substrates over a period of 14 days by using conventional staining methods (hematoxylin eosin and Wright's stain). We conclude that these substrates are multifunctional materials capable of isolating and culturing CTCs for subsequent studies.