Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer.

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.

Tumor Immunophenotyping-Derived Signature Identifies Prognosis and Neoadjuvant Immunotherapeutic Responsiveness in Gastric Cancer.

The effectiveness of neoadjuvant immune checkpoint inhibitor (ICI) therapy is confirmed in clinical trials; however, the patients suitable for receiving this therapy remain unspecified. Previous studies have demonstrated that the tumor microenvironment (TME) dominates immunotherapy; therefore, an effective TME classification strategy is required. In this study, five crucial immunophenotype-related molecules (WARS, UBE2L6, GZMB, BATF2, and LAG-3) in the TME are determined in five public gastric cancer (GC) datasets (n = 1426) and an in-house sequencing dataset (n = 79). Based on this, a GC immunophenotypic score (IPS) is constructed using the least absolute shrinkage and selection operator (LASSO) Cox, and randomSurvivalForest. IPSLow is characterized as immune-activated, and IPSHigh is immune-silenced. Data from seven centers (n = 1144) indicate that the IPS is a robust and independent biomarker for GC and superior to the AJCC stage. Furthermore, patients with an IPSLow and a combined positive score of ≥5 are likely to benefit from neoadjuvant anti-PD-1 therapy. In summary, the IPS can be a useful quantitative tool for immunophenotyping to improve clinical outcomes and provide a practical reference for implementing neoadjuvant ICI therapy for patients with GC.

m6A methylation mediates LHPP acetylation as a tumour aerobic glycolysis suppressor to improve the prognosis of gastric cancer.

LHPP, a histidine phosphatase, has been implicated in tumour progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. Here, we obtained GC tissues and corresponding normal tissues from 48 patients and identified LHPP as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine LHPP levels in normal and GC tissues. The prognostic value of LHPP was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of LHPP in GC growth and metastasis were evaluated in vitro and in vivo. The results showed that LHPP expression was significantly decreased in GC tissues at both the mRNA and protein levels. Multivariate Cox regression analysis revealed that LHPP was an independent prognostic factor and effective predictor in patients with GC. The low expression of LHPP was significantly related to the poor prognosis and chemotherapy sensitivity of gastric cancer patients. Moreover, elevated LHPP expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, the m6A modification of LHPP mRNA by METTL14 represses its expression; LHPP inhibits the phosphorylation of GSK3b through acetylation and mediates HIF1A to inhibit glycolysis, proliferation, invasion and metastasis of gastric cancer cells. Together, our findings suggest that LHPP is regulated by m6A methylation and regulates the metabolism of GC by changing the acetylation level. Thus, LHPP is a potential predictive biomarker and therapeutic target for GC.

An immune checkpoint score system for prognostic evaluation and adjuvant chemotherapy selection in gastric cancer.

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISSGC) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISSGC is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISSGC can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.

CDK5RAP3 inhibits angiogenesis in gastric neuroendocrine carcinoma by modulating AKT/HIF-1α/VEGFA signaling.

BACKGROUND: Angiogenesis plays critical roles in the progression and metastasis of malignant tumors. Gastric neuroendocrine carcinoma is an uncommon stomach cancer that is rich in blood vessels and exhibits highly malignant biological behavior with a poor prognosis. The role of CDK5RAP3 in GNEC has not been reported to date. METHODS: Immunohistochemistry was used to assess the expression of CDK5RAP3 in GNEC tissues and adjacent non-tumor tissues. Cell lines with stable overexpression or knockdown of CDK5RAP3 were constructed using lentiviral transfection. Wound-healing assays, invasion and metastasis assays, tube formation assays, and tumor xenograft transplantation assays were performed to evaluate the effect of CDK5RAP3 on GNEC angiogenesis in vitro and in vivo. Real-time PCR, ELISA, western blot analysis, and confocal-immunofluorescence staining were used to explore the molecular mechanism of CDK5RAP3's effect on angiogenesis. RESULTS: Compared with their respective adjacent non-tumor tissues, protein levels of CDK5RAP3 were significantly decreased in GNEC tissues. Furthermore, low expression of CDK5RAP3 was correlated with more advanced TNM stage, increased tumor microvessel density, and poor prognosis. Functionally, we found that GNEC cells with CDK5RAP3 knockdown promoted human umbilical vein endothelial cells migration and tube formation via activation of AKT/HIF-1α/VEGFA signaling, resulting in increased levels of VEGFA in GNEC cell supernatant. In addition, CDK5RAP3 overexpression in GNEC cells caused the opposing effect. Consistent with these results, nude mouse tumorigenicity assays showed that CDK5RAP3 expression downregulated angiogenesis in vivo. Lastly, patients with low CDK5RAP3 expression and high VEGFA expression exhibited the worst prognosis. CONCLUSIONS: This study demonstrated that CDK5RAP3 inhibits angiogenesis by downregulating AKT/HIF-1α/VEGFA signaling in GNEC and improves patient prognosis, suggesting that CDK5RAP3 could be a potential therapeutic target for GNEC.

UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expres7sion of PDK1 through PI3K/AKT signaling.

BACKGROUND: UFM1 has been found to be involved in the regulation of tumor development. This study aims to clarify the role and potential molecular mechanisms of UFM1 in the invasion and metastasis of gastric cancer. METHODS: Expression of UFM1 in gastric tumor and paired adjacent noncancerous tissues from 437 patients was analyzed by Western blotting, immunohistochemistry, and realtime PCR. Its correlation with the clinicopathological characteristics and prognosis of gastric cancer patients was analyzed. The effects of UFM1 on the invasion and migration of gastric cancer cells were determined by the wound and trans-well assays, and the effect of UFM1 on subcutaneous tumor formation was verified in nude mice. The potential downstream targets of UFM1 and related molecular mechanisms were clarified by the human protein kinase assay and co-immunoprecipitation technique. RESULTS: Compared with the corresponding adjacent tissues, the transcription level and protein expression level of UFM1 in gastric cancer tissues were significantly downregulated (P < 0.05). The 5-year survival rate of gastric cancer patients with low UFM1 expression was significantly lower than the patients with high UFM1 expression (42.1% vs 63.0%, P < 0.05). The invasion and migration abilities of gastric cancer cells with stable UFM1 overexpression were significantly decreased, and the gastric cancer cells with UFM1 stable knockdown showed the opposite results; similar results were also obtained in the nude mouse model. Further studies have revealed that UFM1 could increase the ubiquitination level of PDK1 and decrease the expression of PDK1 at protein level, thereby inhibiting the phosphorylation level of AKT at Ser473. Additionally, the effect of UFM1 on gastric cancer cell function is dependent on the expression of PDK1. The expression level of UFM1 can improve the poor prognosis of PDK1 in patients with gastric cancer. CONCLUSION: UFM1 suppresses the invasion and metastasis of gastric cancer by increasing the ubiquitination of PDK1 through negatively regulating PI3K/AKT signaling.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with ß-Thalassemia Major: A Meta-Analysis.

BACKGROUND: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. METHODS: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. RESULTS: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. CONCLUSION: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.

NMR-based metabolomics to select a surgical method for treating papillary thyroid carcinoma.

OBJECTIVE: This study aims to investigate differences in the metabolomic profiles of patients who received different surgeries for papillary thyroid carcinoma (PTC). METHODS: Two surgical methods, i.e., unilateral and total thyroidectomy, were employed according to different disease conditions. Sera from patients who were treated with levothyroxine sodium tablets before and after surgery was analyzed with a Bruker 500 Hz nuclear magnetic resonance (NMR) spectrometer. Data were analyzed via principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA) with SIMCA-P+ 11.0 software, and metabolites were obtained and compared. The first and second principal components were selected from PCA, PLS-DA, and orthogonal partial least squares discriminate analysis (OPLS-DA). A p-value less than 0.05 was considered statistically significant. RESULTS: There were significant differences in serum metabolomics before and after surgery. Compared with unilateral thyroidectomy, total thyroidectomy reversed some highly increased metabolite levels (e.g., taurine and betaine). More significant variations in abnormal metabolites were noted after total thyroidectomy than after unilateral thyroidectomy (e.g., alanine, choline, hippurate, and formic acid). CONCLUSIONS: The choice of surgical method for PTC patients should be based not only on the tumor condition but also on the potential consequences of metabolic variations. Total thyroidectomy reversed some increased metabolite levels but led to accumulation of some other metabolites due to the loss of thyroid function; thus, metabolic disturbances caused by thyroid hormone deficiency should be prevented in advance.

Modified AJCC staging of gastric neuroendocrine carcinoma based on T staging can improve the capacity of prognosis assessment.

BACKGROUND OR PURPOSE: This study was designed to determine the value of AJCC staging 7th edition and improved AJCC staging in assessing the prognosis of gastric neuroendocrine carcinoma (GNEC). METHODS: In total, GNEC 475 patients in the Surveillance, Epidemiology, and End Results (SEER) database and 129 GNEC patients in our department undergoing resection were included. The former served as the test group, and the latter served as the validation group. Those with stage IIIb disease were allocated into four subgroups, and improved AJCC staging was established. The AIC and C indices were used to evaluate the capacities of different TNM staging. RESULTS: Significant overlap between stages IIIb and IIIa in both the test and validation groups was found. In the test group, T staging and age at disease diagnosis were independent prognostic factors for patients with stage IIIb. Stage IIIb was divided into T1N1, T2N1, T3N1 and T4N1, and the improved AJCC staging-mTNM staging was created. In mTNM staging, the IIIb survival curve did not cross those of stages IIIa and IIb, which had a smaller AIC (2490 vs. 2507) value and larger C index (0.7624 vs. 0.7450, P = 0.228). Similar results were obtained for the validation group. CONCLUSION: T stage was an independent factor influencing the prognosis of stage IIIb GNEC patients, and the improved AJCC staging proposed here has good prognostic value.

NMR-based metabolomics to select a surgical method for treating papillary thyroid carcinoma

OBJECTIVE: This study aims to investigate differences in the metabolomic profiles of patients who received different surgeries for papillary thyroid carcinoma (PTC). METHODS: Two surgical methods, i.e., unilateral and total thyroidectomy, were employed according to different disease conditions. Sera from patients who were treated with levothyroxine sodium tablets before and after surgery was analyzed with a Bruker 500 Hz nuclear magnetic resonance (NMR) spectrometer. Data were analyzed via principal component analysis (PCA) and partial least squares discriminate analysis (PLS-DA) with SIMCA-P+ 11.0 software, and metabolites were obtained and compared. The first and second principal components were selected from PCA, PLS-DA, and orthogonal partial least squares discriminate analysis (OPLS-DA). A p-value less than 0.05 was considered statistically significant. RESULTS: There were significant differences in serum metabolomics before and after surgery. Compared with unilateral thyroidectomy, total thyroidectomy reversed some highly increased metabolite levels (e.g., taurine and betaine). More significant variations in abnormal metabolites were noted after total thyroidectomy than after unilateral thyroidectomy (e.g., alanine, choline, hippurate, and formic acid). CONCLUSIONS: The choice of surgical method for PTC patients should be based not only on the tumor condition but also on the potential consequences of metabolic variations. Total thyroidectomy reversed some increased metabolite levels but led to accumulation of some other metabolites due to the loss of thyroid function; thus, metabolic disturbances caused by thyroid hormone deficiency should be prevented in advance.

Prognostic significance of perigastric tumor deposits in patients with primary gastric cancer.

BACKGROUND: The presence and the prognostic significance of perigastric tumor deposits (TDs) in primary gastric cancer have not been extensively studied. The aim of this study was to evaluate the prognostic significance perigastric TDs in primary gastric cancer. METHODS: From 2005 to 2010, 1250 patients underwent R0 gastrectomy at the Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Out of 1250 patients, 132 patients with perigastric TDs were identified. Additionally, 132 patients with staged matched gastric cancer without tumor deposits were selected as a control group. RESULTS: Perigastric TDs were observed in 132 (10.5%) of the 1250 patients with gastric cancer who underwent R0 gastrectomy. There were 94 males (71.21%) and 38 females (28.79%) (2.47:1). The mean age was 57.21 years. Clinicopathologic characteristics between the two groups matched well. There was a significant difference in the overall survival of those with and without TDs by univariate (p<0.05) and multivariate (p < 0.05) survival analysis. The 1-, 3-and 5-year overall survival rates of patients with TDswere69.6%, 39.3%, and 24.2%, respectively, and were significantly poorer than those of the staged matched control group. There was no correlation between the number of TDs and patient survival in patients with gastric cancer (p>0.05); however, when comparing each pT tumor group with the perigastric TD group, the stage T4 survival rate was very similar to that observed in patients with TDs. CONCLUSIONS: Perigastric TDs are an independent predictive prognostic factor for gastric cancer and may be appropriately considered a form of serosal invasion. We suggest that TDs should be included in TNM staging system for better outcomes.

Analysis on the metabolite composition of serum samples from patients with papillary thyroid carcinoma using nuclear magnetic resonance.

OBJECTIVE: Analysis of the metabolic differences among the papillary thyroid carcinoma (group T) patients, benign thyroid tumor patients (group B) and healthy controls (group H) by nuclear magnetic resonance hydrogen spectrum. METHODS: collect twenty serum specimens each from group T, group B and group H. Collect image archive. Use Topspin software, AMIX software and SIMCA-P+ software to calibrate, integrate with PCA and PLS-DA, research the three groups' serum for endogenous metabolic differences. RESULTS: The data of group T and group H established a discrimination model, and the model is correct (P<0.05). The content of metabolites in the serum of team T increased including valine, leucine, isoleucine, lactic acid, alanine, glutamic acid, lysine, glycine, while the lipids, choline, tyrosine decreased. The data of group B and group H established a discrimination model and the model is correct (P<0.05). The content of metabolites in the serum of team B increased including Trimethyl glycine, tyrosine, phenylalanine, valine, leucine, isoleucine, lactic acid, alanine, glutamic acid, while the Lipids and lysine reduced. CONCLUSION: Compared with team H, there is an obvious metabolic difference in team T and team B. It not only involves glucose metabolism but also the metabolism of lipids, amino acids and nucleic acid.

Pilot study of intense neoadjuvant chemoradiotherapy for locally advanced rectal cancer: retrospective review of a phase II study.

AIMS AND BACKGROUND: Locally advanced rectal adenocarcinoma is typically treated with neoadjuvant chemoradiotherapy and surgery. We assessed the effect of an additional cycle of capecitabine/oxaliplatin chemotherapy before surgery in 57 patients with T3/4, N+/- or T1/2, N+ rectal cancer. MATERIALS AND STUDY DESIGN: Radiotherapy (total dose, 50.4 Gy) was combined with three cycles of chemotherapy (two cycles concomitant with radiotherapy), and each cycle consisted of oxaliplatin (130 mg/m2 on day 1) and capecitabine (825 mg/m2, twice per day from day 1 to day 14) for 21 days. In addition to assessing the safety of this treatment, the primary endpoint was pathological complete response (pCR). The secondary endpoint was the change in primary tumor and node stage from pre-treatment to post-surgery. RESULTS: Eleven patients (19%) experienced complete tumor regression and 23 patients (40%) experienced tumor regression grade 3. Tumor down-staging occurred in 31 patients (54.4%) and down-staging of nodes occurred in 25 patients (43.9%). There was a significant difference in tumor stage between pre-treatment and post-surgery (P <0.001). Patients with less advanced N stages had significantly better recurrence-free survival but similar metastasis-free survival and overall survival. Tumor regression grade was not associated with overall survival, recurrence-free survival or metastasis-free survival. The most common adverse events were pulmonary infection (n = 6, 10.5%) and intestinal obstruction (n = 6, 10.5%): CONCLUSIONS. An additional cycle of chemotherapy given after chemoradiotherapy and before surgery provided good efficacy and had a satisfactory safety profile in patients with locally advanced rectal cancer.

[Impact of sleeve gastrectomy with ileal interposition duodenojejunal bypass operation on lipid metabolism in non-obese type 2 diabetes mellitus patients].

OBJECTIVE: To evaluate the effect of sleeve gastrectomy with ileal interposition duodenojejunal bypass operation on lipid metabolism in non-obese type 2 diabetes mellitus patients. METHODS: Twenty-nine non-obese patients with type 2 diabetes mellitus underwent sleeve gastrectomy with ileal interposition duodenojejunal bypass operation. All the patients were subjected to the measurement of total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), homeostatic model assessment for insulin resistance (Homa-IR), glycosylated hemoglobin (HbA1c) at postoperative 12th month. RESULTS: Twelve months after ileal interposition duodenojejunal bypass operation, the blood glucose was controlled without taking hypoglycemic drugs in 28 patients (96.5%) and HbA1c decreased from (8.4±1.3)% to (6.5±1.6)% (P<0.01). Dyslipidemia were corrected in 25 cases (86.2%). TC became normal in 84.2% (15/19), and TG became normal in 82.3% (14/17). HDL became normal in 66.6% (8/12). LDL became normal in 31.2% (5/16). TC/HDL ratio decreased from 5.6±1.2 to 2.8±1.0 (P<0.01). TG/HDL ratio decreased from 3.2±1.3 to 1.5±0.8 (all P<0.01). CONCLUSION: Sleeve gastrectomy with ileal interposition duodenojejunal bypass is an effective operation for the correction of dyslipidemia in non-obese patients with type 2 diabetes mellitus.

Syntheses and cell-based phenotypic screen of novel 7-amino pyrido[2,3-d]pyrimidine-6-carbonitrile derivatives as potential antiproliferative agents.

A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC(50) value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC(50) value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.

Synthesis and biological evaluation of 2-(3-fluoro-4-nitro phenoxy)-n-phenylacetamide derivatives as novel potential affordable antitubercular agents.

A novel series of 2-(3-fluoro-4-nitrophenoxy)-N-phenylacetamide compounds were designed, synthesized and in vitro assessed for their antitubercular activities by a microdilution method. All the novel derivatives exerted potent or moderate active against M. tuberculosis H37Rv, with MIC values ranging from 4 to 64 µg/mL. The most potent derivative 3m showed an identical MIC value of 4 µg/mL for both M. tuberculosis H37Rv and rifampin-resistant M. tuberculosis 261. It demonstrated no inhibitory effects against six different tumor cell lines by a MTT assay and had a good safety profile in a vero cell line, providing a good lead for subsequent optimization in search of novel affordable antitubercular agents.

[An in vitro study of the relationship between KiSS-1 expression and hepatoma carcinoma cell proliferation, adhesion, and invasion].

OBJECTIVE: To investigate the impact of expression of kisspeptin-1 (KiSS-1) metastasis-suppressor gene on the proliferative, adhesive and invasive abilities of human hepatocellular carcinoma (HCC) using an in vitro cell system. METHODS: The highly metastatic human hepatoma cell line MHCC97-H was transiently transfected with the pcDNA3.1/HisC vector expressing the KiSS-1 gene (experimental group) or the vector without the KisS-1 gene (blank control group). Untransfected cells served as the negative control group. Proliferative abilities of the three groups were assessed by flow cytometry and MTT assay. Adhesive abilities were assessed by MTT assays using matrigel and fibronectin. Invasive abilities and cell motility were assessed by chemoinvasion chamber assay using reconstituted matrigel and migration chamber assay using polycarbonate filters, respectively. RESULTS: The experimental group showed significantly lower adhesion capacity to matrigel (0.257+/-0.029) than either the blank control group (0.374+/-0.016; t=-7.90345, P less than 0.01) or the negative control group (0.394+/-0.031; t=-7.22752, P less than 0.01). Similarly, the experimental group showed significantly lower adhesion capacity to fibronectin (0.292+/-0.004) than either the blank control group (0.394+/-0.010; t=-20.93138, P less than 0.01) or the negative control group (0.412+/-0.023; t=-11.31371, P less than 0.01). The experimental group also showed significantly lower numbers of cells with invasive capacity (42.40+/-1.14) than either the blank control group (66+/-1.58; t=-27.0711, P less than 0.01) or the negative control group (67.80 +/- 1.92; t=-25.4, P less than 0.01). Similarly, the experimental group showed significantly lower numbers of cells with chemotactic movement (65.80+/-1.92) than either the blank control group (93.80+/-2.28; t=-30.11750, P less than 0.01) or the negative control group (96.40+/-2.07; t=-24.19142, P less than 0.01). The experimental group showed slightly, but not significantly, lower cell proliferation (0.644+/-0.027) than either the blank control group (0.669+/-0.022; t=-1.60371, P?>?0.05) or the negative control group (0.678+/-0.027; t=-1.97828, P?>?0.05). In addition, there were no obvious differences between the three groups in the amounts of cells arrested in either the G1 phase or the S phase. CONCLUSION: KiSS-1 overexpression suppresses the adhesion, invasion and motility, but not the proliferation, of hepatoma carcinoma cells in vitro. These findings imply that KiSS-1 might represent a promising new candidate for gene therapy against human hepatocellular carcinoma.

(E)-1-(5-Hy-droxy-2,2-dimethyl-2H-chromen-6-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one.

The title compound, C(23)H(24)O(6), crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. The dihedral angles between the benzopyran ring and the α,ß-unsaturated ketone unit and between the α,ß-unsaturated ketone group and the benzene ring are 9.4 (10) and 12.96 (13)°, respectively, in mol-ecule A and 1.40 (17) and 4.44 (17)°, respectively, in mol-ecule B. The two meth-oxy groups at the meta positions of the benzene ring are close to being coplanar with the ring [C-O-C-C = 6.2 (3) and -1.4 (3)° in mol-ecule A and -4.2 (4) and 3.7 (3)° in mol-ecule B], whereas the third meth-oxy group, at the para position, is (+)-anti-clinal with respect to the benzene ring [C-O-C-C = 81.7 (3)°] in mol-ecule A and is (-)-synclinal with respect to the benzene ring [C-O-C-C = -103.2 (3)°] in mol-ecule B. In both independent mol-ecules, the hy-droxy group is involved in an intra-molecular O-H⋯O hydrogen bond.

Adjuvant imatinib treatment after R0 resection for patients with high-risk gastrointestinal stromal tumors: a median follow-up of 44 months.

BACKGROUND: The optimal duration of Imatinib adjuvant treatment for patients with high-risk gastrointestinal stromal tumors (GISTs) is uncertain. PATIENTS AND METHODS: A total of 90 patients with high-risk GISTs after curative resection were recruited into this non-randomized case-control study, including 35 having Imatinib adjuvant therapy and 55 having follow-up alone. The recurrence-free survival (RFS) was compared. RESULTS: After a median follow-up of 44.0 months, a significantly reduced recurrence rate was observed in the treatment group than the control group (17.1% vs. 78.2%, P = 0.000). One-year, 2-year, and 3-year RFS rates were 100% vs. 70.9%, 88.0% vs. 37.8%, and 88.0% vs. 27.5%, respectively; with a significant advantage for Imatinib adjuvant therapy versus the surgery only (P = 0.000, HR 0.122, 95% CI 0.041-0.363). Continuation Imatinib treatment further improved RFS by comparison with the interruption treatment (both 2-year and 3-year RFS were 95.8% vs. 63.6%, P = 0.011, HR 0.103, 95% CI 0.012-0.883). There were no serious adverse events in the adjuvant therapy group. CONCLUSIONS: Imatinib Adjuvant therapy could significantly prolong the RFS of patients with high-risk GISTs. Extended Imatinib adjuvant treatment strategy may further reduce the risk of relapse with a low drug resistance rate and toxicity profile.