Sintilimab in Patients with Previously Treated Metastatic Neuroendocrine Neoplasms.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a group of diseases that show high heterogeneity but have limited treatment options. This phase I study evaluated the safety and efficacy of sintilimab, anti-PD-1 monoclonal antibody, in treating advanced NENs. METHODS: We prospectively enrolled patients pathologically diagnosed with NENs after standard treatment failure. Neuroendocrine neoplasms were classified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine cancers (NECs). Every patient received sintilimab, and response was assessed every 9 weeks. RESULTS: Twenty-four patients with a median age of 57.0 years were enrolled from November 2016 to 2017. The median Ki-67 index was 60%. Five patients had NET, 1 had NET G3, 17 had NEC, and 1 had mixed adenocarcinoma-neuroendocrine carcinoma. The most common primary tumor sites were the pancreas and gastrointestinal tract in 7 and 10 patients, respectively. In phase Ia trial, 2 patients received sintilimab 1 mg/kg every 2 weeks, one received 3 mg/kg every 2 weeks, and 21 patients enrolled in the phase Ib trial received 200 mg every 3 weeks. The objective response rate was 20.8% in all enrolled patients and 27.8% in NEC patients. The median progression-free survival was 2.2 and 2.1 months in patients with NET and NEC, respectively. The median OS was not applicable (NA) and 10.8 months (95% CI, 4.3, NA) with NET and NEC, respectively. The duration of response (DOR) was not reached, with a median follow-up time of 20.7 months. Treatment-related adverse events (TRAE) occurred in 17 (70.8%) patients. The most frequent TRAE was thyroid dysfunction (41.7%), and a grade 3 pulmonary infection occurred in 1 patient. The programmed cell death 1-ligand 1 (PD-L1)-positive (tumor proportion score ≥1%) rate was 18.8% (3 out of 16) and the expression of PD-L1 did not correlate with response. CONCLUSION: Sintilimab was well-tolerated and showed encouraging response in NECs. CLINICALTRIALS.GOV IDENTIFIER: NCT02937116.

The Upregulation of PLXDC2 Correlates with Immune Microenvironment Characteristics and Predicts Prognosis in Gastric Cancer.

Tumor microenvironment (TME) has been demonstrated to exhibit a regulatory effect on the progressions of gastric cancer (GC). However, the related functions of stromal and immune components (TME-associated genes) in TME remain largely unclear. From the TCGA dataset, we downloaded the clinical data of 375 GC cases and then estimated the percentage of tumor-infiltrating immunocytes (TICs) and the levels of immune and stromal constituents by the use of CIBERSORT and ESTIMATE tolls. Univariate assays were applied to study the differentially expressed genes. The associations between the clinical information of GC patients and the expressions of the specific genes were analyzed based on the TCGA datasets. The effect of Plexin domain containing 2 (PLXDC2) expression on TICs was conducted. We observed that PLXDC2 expression was distinctly upregulated in GC specimens compared with nontumor gastric specimens. Its upregulation was associated with advanced clinical stages and predicted a shorter overall survival of GC patients. The genes in the group of higher expressing PLXDC2 were primarily enriched in immunity-associated events. By the use of CIBERSORT, we observed that PLXDC2 expressions were related to the proportion of dendritic cells resting, T cell CD4 memory resting, eosinophils, mastocyte resting, mononuclear cells, plasma cells, T cell follicle helper, macrophage M2, and dendritic cells activated. Overall, our discoveries revealed that the expression of PLXDC2 was remarkable in GC, might be a possible biomarker for GC, and provided novel contents regarding immune infiltrates, offering novel insight for treatments of GC.

Efficacy and safety of early oral feeding in postoperative patients with upper gastrointestinal tumor: A systematic review and meta-analysis.

BACKGROUND: Early oral feeding (EOF) is an important measure for early recovery of patients with gastrointestinal tumors after surgery, which has emerged as a safe and effective postoperative strategy for improving clinical outcomes. AIM: To determine the safety and efficacy of early oral feeding in postoperative patients with upper gastrointestinal tumor. METHODS: This meta-analysis was analyzed using Review Manager version 5.3 and Stata version 14. All clinical studies that analyzed efficacy and safety of EOF for postoperative patients with upper gastrointestinal tumor were included. RESULTS: Fifteen studies comprising 2100 adult patients met all the inclusion criteria. A significantly lower risk of pneumonia was presented in the EOF compared with TOF group [relative risk (RR) = 0.63, 95% confidence interval (CI): 0.44-0.89, P = 0.01]. Length of hospital stay was significantly shorter in the EOF group than in the TOF group [weighted mean difference (WMD) = -1.91, 95%CI: -2.42 to -1.40; P < 0.01]. Cost of hospitalization was significantly lower (WMD = -4.16, 95%CI: -5.72 to -2.61; P < 0.01), and CD4 cell count and CD4/CD8 cell ratio on postoperative day 7 were significantly higher in the EOF group than in the TOF group: CD4 count (WMD = 7.17, 95%CI: 6.48-7.85; P < 0.01), CD4/CD8 ratio (WMD = 0.29, 95%CI: 0.23-0.35; P < 0.01). There was no significant difference in risk of anastomotic leak and total postoperative complications. CONCLUSION: EOF as compared with TOF was associated with lower risk of pneumonia, shorter hospital length of stay, lower cost of hospitalization, and significantly improved postoperative immune function of patients.

Clinicopathological and prognostic significance of Fusobacterium nucleatum infection in colorectal cancer: a meta-analysis.

Background: This study aimed to clarify the relationship between F. nucleatum levels and the prognosis of CRC, which is still controversial. Methods: Relevant articles were searched on PubMed, Web of Science, PMC and Embase up to April 7, 2020. Outcomes of interest included clinical characteristics, molecular characteristic and survival analysis. HR (OR), odds ratios (OR) and 95% confidence interval (CI) were calculated to explore the prognostic value and relationship of clinical characteristics of Fusobacterium nucleatum in CRC. Results: A total of 3626 CRC patients from 13 eligible studies were included. High levels of F. nucleatum were associated with worse prognosis, as such parameters as overall survival (OS) (hazard ratio [HR] = 1.40, 95% confidence interval [CI]: 1.40 - 1.63, P < 0.0001), disease-free survival (DFS) (HR = 1.71, 95% CI: 1.29-2.26, P = 0.0002), and cancer-specific survival (OR= 1.93, 95% CI: 1.42-2.62, P <0.0001). F. nucleatum levels were related with T3-T4 stage (OR = 2.20, 95% CI: 1.66-2.91, P < 0.00001), M1 stage (OR = 2.11, 95% CI: 1.25-3.56, P = 0.005), poor tumor differentiation (OR = 1.83, 95% CI: 1.11-3.03, P =0.02), microsatellite instability-high (OR = 2.53, 95% CI: 1.53-4.20, P = 0.0003), and KRAS mutation (OR =1.27, 95% CI: 1.00-1.61, P=0.05) showed. Conclusions: High levels of F. nucleatum suggest a poor prognosis and are associated with tumor growth, distant metastasis, poor differentiation, MSI-high, and KRAS mutation in CRC patients.

Effects of lifestyle interventions on rural patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is rising rapidly in rural areas, and lifestyle interventions can effectively reduce the blood glucose levels of patients with T2DM. However, current dietary and exercise guidelines are still at experimental stages and are difficult for subjects to understand and implement. The Human Metabolism Analyzer provides real life interventions for the prevention and treatment of T2DM, and our pilot research has demonstrated its effectiveness and good compliance. AIM: To investigate the effect of and compliance with lifestyle interventions in rural patients with T2DM. METHODS: A total of ten rural villages were randomly selected in Chaoshui Township, Penglai City, Shandong Province, China, to conduct health screening among residents aged 50 years or older. Each rural village represented a group, and 12 patients with T2DM were randomly selected from each group (total: 120) to participate in this study and receive real life lifestyle interventions and medication guidance. Lifestyle interventions included changing the meal order (A), postprandial activities (B), resistance exercise (C), and reverse abdominal breathing (D). Diabetes education was conducted at least once a month with a weekly phone follow-up to monitor exercise and diet. Waist circumference, blood pressure, body mass index (BMI), motor function, body composition, fasting blood glucose, and glycated hemoglobin (HbA1c) were analyzed before and 3 mo after the intervention. Moreover, patient compliance and adjustments of hypoglycemic drugs were evaluated. RESULTS: A total of 109 subjects completed the study. The compliance rates for lifestyle interventions A, B, C, and D were 57.79%, 60.55%, 64.22%, and 75.23%, respectively. Among the subjects who received hypoglycemic drugs, the dose was reduced 2 to 3 times based on blood glucose in 54 (67.50%) subjects and was tapered and discontinued in 5 (6.25%) subjects within 3 mo, with no significant fluctuations in blood glucose after dose reduction and withdrawal. After lifestyle interventions, waist circumference, BMI, fasting blood glucose, and HbA1c significantly decreased (P < 0.001); motor function and body composition also significantly improved (P < 0.001). CONCLUSION: For patients with T2DM, compliance to real-life lifestyle interventions is good, and the interventions significantly improve metabolic indicators such as waist circumference, BMI, blood pressure, HbA1c, body composition, and motor function. Some patients are able to taper or discontinue hypoglycemic drugs.

Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling.

BACKGROUND: Omega 3 polyunsaturated fatty acid (Omega-3PUFA) is one of the essential nutrients for human body involved in intracellular metabolic regulation and cell signaling. Previous studies have shown that Omega-3PUFA is involved in the pathogenesis of digestive system tumors, including colorectal cancer (CRC), however, the effects of Omega-3PUFA on CRC has not been fully elucidated. In the current study, we evaluated whether Omega-3PUFA can alleviate N-methyl-N-nitrosourea(MNU) induced CRC in a rat model and illustrated the potential mechanism. METHODS: The effects of Omga-3PUFA on MNU-induced colorectal cancer in rats were analyzed by in vivo experiments. The viability, apoptosis, colony formation and invasion of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry, clone formation assay and transwell invasion assay. The expression of apoptosis-related proteins in CRC cells treated with Omga-3PUFA was detected by Western blotting. Finally, after adding PI3K activator, the viability, apoptosis and protein expression of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry and Western blotting. RESULTS: Our results showed that Omega-3PUFA attenuated MNU-induced CRC in rats and inhibited AKT/Bcl-2 signaling in rats. In addition, Omega-3PUFA inhibited CRC cell proliferation and induces CRC cell apoptosis. Moreover, Omega-3PUFA inhibited CRC cell colony formation and invasion, and inhibited PI3K/AKT/Bcl-2 signaling in CRC cells. Furthermore, The effects of Omega-3PUFA on cell proliferation and apoptosis were inhibited by blocking PI3K/AKT signaling. CONCLUSION: Omega-3PUFA can attenuate MNU-induced colorectal cancer in rats by blocking PI3K/AKT/Bcl-2 signaling, which suggests that Omega-3PUFA may be a potent agent for CRC treatment.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine.

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations' physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (Cmax) from 2.64 µg/mL to 20.67 and 33.09 µg/mL and also increased the area under the concentration-time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations' potential applications in drugs and healthcare products.

Determinants and nutritional assessment value of hand grip strength in patients hospitalized with cancer.

BACKGROUND AND OBJECTIVES: Hand grip strength (HGS) has emerged as a predictor of the nutritional status. However, many factors may modify the malnutrition-HGS association. This study explored the nutritional assessment value and determinants of HGS in patients hospitalized with cancer. METHODS AND STUDY DESIGN: In this multicenter, retrospective, observational study (11,314 patients), the Receiver operator characteristic curve was used to observe HGS and nutritional status sensitivity/specificity. Sex; age; height; weight; mid-upper arm circumference (MAMC); Patient-Generated Subjective Global Assessment (PG-SGA) score; Karnofsky score; physical function (PF) domain; cognitive function (CF) domain; global health and quality of life (QL) domain of EORTC QLQ-C30 (a quality of life instrument designed by the European Organization for Research and Treatment of Cancer); and albumin, prealbumin, and hemoglobin levels were included in a Stepwise analysis model to identify the factors influencing HGS. RESULTS: HGS showed a very low diagnostic value and accuracy for identifying severe malnourishment (area under the curve, 0.615-0.640; p<0.01). HGS positively correlated with sex; height; weight; MAMC; Karnofsky score; QL, PF, and CF domains; and hemoglobin and prealbumin levels (Beta= 0.02-0.42, p<=0.05), and negatively with age (Beta=-0.19, p<0.01). However, the PG-SGA score was excluded because of its very limited contribution to HGS variability. CONCLUSIONS: HGS is a mutifactorial index. The use of HGS cutoff values to identify malnutrition is markedly challenging. Thus, HGS may be of limited use as a predictor of nutritional status.

Warburg effect or reverse Warburg effect? A review of cancer metabolism.

Cancer is a major threat to human health. A considerable amount of research has focused on elucidating the nature of cancer from its pathogenesis to treatment and prevention. Tumor cell metabolism has been considered a hallmark of cancer. Cancer cells differ from normal cells through unlimited cell division, and show a greater need for energy for their rapid growth and duplication. Research on glycometabolism, as the key point of energy metabolism, has played a unique role. In the 1920s, Warburg found that cancer cells prefer to produce adenosine triphosphate (ATP) by glycolysis, which is a less efficient pathway compared to oxidative phosphorylation. This striking discovery, called 'the Warburg effect', has influenced and guided the study of the mechanism and treatment of tumors for generations, but its causal relationship with cancer progression is still unclear. Some studies have now shown contradicting evidence and a new hypothesis, the reverse Warburg effect, has been put forward, in which cancer cells produce most of their ATP via glycolysis, even under aerobic conditions. In this review we discuss the new points concerning the energy metabolism of a tumor, as well as the current facts and perspectives.

Heterogeneity research in muscle-invasive bladder cancer based on differential protein expression analysis.

The aim of this study was to study the expression profiles of muscle-invasive bladder cancer (MIBC) cells of different risk groups and to explore the crucial role of biological pathway change in heterogeneity of MIBC cells. Thirty individual samples (cancer and non-cancerous specimens) were obtained from patients with MIBC. Laser capture microdissection was employed to harvest the homogeneous MIBC cells and normal urothelial cells. iTRAQ and 2D-LC-MS/MS were used to quantify and identify the differently expressed proteins. Then, the significantly changed proteins were further analyzed using Arraytrack ™ software. The interested proteins were compared with the published literatures to discuss the exact functions. A total of 3,073 non-redundant proteins were identified in this research; therefore, 855/2,210/633 (fold change >1.5 relative to normal group) presented in high-/median-/low-risk groups, respectively. 617/1,620/463 proteins with SWISS-ACC number output from Arraytrack ™ software and presented in high-/median-/low-risk groups, respectively. Pathway analysis revealed that the mainly changed pathways (top-10, p < 0.05) in Genetic information processing category were similar in high- and median-risk groups, including Kyoto Encyclopedia of Genes and Genomes (KEGG) spliceosome, protein export, ribosome pathways. The mainly altered pathways in Metabolism category included glycolysis/gluconeogenesis, pentose phosphate, pyruvate metabolism pathway for high-risk group, and glutathione metabolism, citrate cycle, oxidative phosphorylation pathways for median-risk group. The major changed pathways for low-risk group included focal adhesion pathway and ECM-receptor interaction pathway. The changed biological pathways are closely related to the regulation of heterogeneity for MIBC. The KEGG pathways of Genetic information processing category and Metabolism (anaerobic or aerobic) category play a crucial role in determining the malignant phenotype of MIBC cells. The quantification analysis of proteins combining with the KEGG pathway analysis contributes to screening candidate biomarkers and guides the biological molecular therapy of MIBC.

Far from resolved: stromal cell-based iTRAQ research of muscle-invasive bladder cancer regarding heterogeneity.

The aim of the present study was to globally characterize the cancer stroma expression profile of muscle-invasive bladder cancer in different metastatic risk groups and to discuss the decisive role of biological pathway change in cancer heterogeneity. Laser capture microdissection was employed to harvest purified muscle-invasive bladder cancer stromal cells derived from 30 clinical samples deriving from 3 different metastatic risk groups. Isobaric tags for relative and absolute quantitation (iTRAQ) and two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) were used to identify the differentially expressed proteins. Subsequently, the differentially expressed proteins were further analyzed by bioinformatics tools. After completing the above tasks, the proteins of interest were further compared with the published litterature. We identified 1,049 differentially expressed proteins by paired comparison (high risk vs. median, low risk and normal groups; median risk vs. low risk and normal groups, low risk vs. normal group; a total of 6 comparisons). A total of 510,549,548 proteins as significantly altered (ratio fold-change≥1.5 or ≤0.667 between the metastatic potential risk group and the normal group) were presented in the low/median/high metastatic risk group, respectively. Pathway analysis revealed that the differentially expressed proteins were mainly located in the Kyoto Encyclopedia of Genes and Genomes pathways, including focal adhesion pathway, systemic lupus erythematosus pathway and ECM-receptor interaction pathway. In addition, several proteins such as EXOC4, MYH10 and MMP-9 may serve as candidate biomarkers of muscle-invasive bladder cancer. Our study confirmed that stromal cells, an important part of the cancer tissue, are pivotal for regulating the heterogeneity of cancer. Common changes in biological pathways determined the malignant phenotype of muscle-invasive bladder cancer, and biomarker discovery should take into account both neoplastic cells and their corresponding stromata.

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice.

Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide. Although we have made steady progress in chemotherapy and targeted therapy, evidence suggests that the majority of patients undergoing drug therapy experience severe, debilitating, and even lethal adverse drug events which considerably outweigh the benefits. The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments. Prognostic and predictive biomarkers have been the subjects of many published papers, but few have been widely incorporated into clinical practice. Here, we want to review recent biomarker data related to colorectal cancer, which may have been ready for clinical use.

Differential protein expression during colonic adaptation in ultra-short bowel rats.

AIM: To investigate the proteins involved in colonic adaptation and molecular mechanisms of colonic adaptation in rats with ultra-short bowel syndrome (USBS). METHODS: Sprague Dawley rats were randomly assigned to three groups: USBS group (10 rats) undergoing an approximately 90%-95% small bowel resection; sham-operation group (10 rats) undergoing small bowel transaction and anastomosis; and control group (ten normal rats). Colon morphology and differential protein expression was analyzed after rats were given post-surgical enteral nutrition for 21 d. Protein expression in the colonic mucosa was analyzed by two-dimensional electrophoresis (2-DE) in all groups. Differential protein spots were detected by ImageMaster 2D Platinum software and were further analyzed with matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight-mass spectrometric (MALDI-TOF/TOF-MS) analysis. RESULTS: The colonic mucosal thickness significantly increased in the USBS group compared with the control group (302.1 ± 16.9 µm vs 273.7 ± 16.0 µm, P < 0.05). There was no statistically significant difference between the sham-operation group and control group (P > 0.05). The height of colon plica markedly improved in USBS group compared with the control group (998.4 ± 81.2 µm vs 883.4 ± 39.0 µm, P < 0.05). There was no statistically significant difference between the sham-operation and control groups (P > 0.05). A total of 141 differential protein spots were found in the USBS group. Forty-nine of these spots were down-regulated while 92 protein spots were up-regulated by over 2-folds. There were 133 differential protein spots in USBS group. Thirty of these spots were down-regulated and 103 were up-regulated. There were 47 common differential protein spots among the three groups, including 17 down-regulated protein spots and 30 up-regulated spots. Among 47 differential spots, eight up-regulated proteins were identified by MALDI-TOF/TOF-MS. These proteins were previously reported to be involved in sugar and fat metabolism, protein synthesis and oxidation reduction, which are associated with colonic adaption. CONCLUSION: Eight proteins found in this study play important roles in colonic compensation and are associated with sugar and fat metabolism, protein synthesis, and molecular chaperoning.

Primary gastric signet ring cell carcinoma presenting as cardiac tamponade.

Primary gastric signet ring cell carcinoma presenting as cardiac tamponade is difficult to diagnosis early. Patients are generally asymptomatic until the disease is advanced. General practitioners usually focus on the initial symptoms related to pericarditis and pericardial effusion. We report a case of signet-ring cell carcinoma of the stomach presenting as cardiac tamponade with pericarditis and pericardial effusion but without any gastrointestinal symptoms. A 49-year old woman was admitted because of progressive dyspnea and cough. Chest X-ray revealed an increased cardiothoracic ratio and a small amount of bilateral pleural effusion. Two dimensional ultrasonographic echocardiography pericardial effusions with atrial and right ventricular early diastolic collapse were found, establishing the diagnosis of cardiac tamponade. Pericardiocentesis was performed and 420 mL of bloody fluid was taken. The patient died of respiratory failure and cardiac arrest on October 28, 2009. Post-mortem examination revealed diffuse gastric mucosa erosion and edema with stomach mucosa incrassation in the greater curvature. The primary lesion was histopathologically diagnosed as signet-ring cell carcinoma of the stomach.

[Apoptosis resistance induced by leptin and its mechanism in breast cancer cells].

OBJECTIVE: To explore the apoptosis resistance induced by Leptin and its mechanism in breast cancer cells in vitro. METHODS: The leptin-mediated reduction of docetaxel-induced apoptosis in human breast cancer T47D cells was evaluated by TransAM ELISA, MTT and caspase-9 assay. The leptin-promoted survivin expression was analyzed by Western-blot and RT-PCR. The reversing effect of STAT3 knockdown on leptin-induced survivin upregulation was measured by Western-blot and RT-PCR. RESULTS: Leptin promoted T47D cells proliferation and the inhibitory rate was -63.6%. It reduced docetaxel-induced apoptosis in T47D cells by 31.9%. Leptin at different concentrations promoted survivin protein and mRNA expression in T47D cells. The expression of survivin mRNA was 4.6 fold compared with the T47D cells not treated with leptin(10 nmol/L). The expression of survivin mRNA in T47D cells was 0.55 +/- 0.15 fold after transfected with small interfering RNA (siRNA) of STAT3. The expression of survivin mRNA in STAT3 siRNA group and mock transfected group were 0.56 +/- 0.18 fold and 1.61 +/- 0.22 fold after treated by leptin, respectively. The survivin protein level of T47D mock transfected cells was increased after treated by leptin, but the protein level of T47D transfected with STAT3 siRNA cells were not changed significantly. CONCLUSION: Leptin/STAT3 signaling is a novel pathway for up-regulation of survivin expression in breast cancer cells.

Dammarane-type saponins from Panax quinquefolium and their inhibition activity on human breast cancer MCF-7 cells.

A new compound, named quinquefoloside-L(c) (1), together with nine known compounds, was isolated from leaves of Panax quinquefolium, and its structure was elucidated as 3beta,12beta, 20S-trihydroxy-25-methoxydammar-23-ene 3-O-beta-D-glucopyranosyl (1-->2)beta-D-glucopyranosyl-20-O-beta-D-xylopyanosyl (1-->6) beta-D-glucopyranoside (1), on the basis of MS, 1D-and 2D-NMR experiments as well as by chemical degradation. The cytotoxicity of these compounds against human breast cancer MCF-7 cell line was also tested by MTT method.

[Intestinal mucosal barrier dysfunction after abdominal operation and its clinical significance].

OBJECTIVE: To investigate the plasma glutamine (Gln) level and relationships between the intestinal mucosal permeability and bacterial translocation and between bacterial translocation and systemic inflammatory response syndrome (SIRS) after abdominal operation. METHODS: The peripheral blood was collected from 42 patients before and 2 and 7 days after elective abdominal operation. The plasma Gln concentration and lactulose/mannitol (L/M) ratio were measured and the whole blood bacterial DNA concentration was determined by polymerase chain reaction (PCR). The relationship between intestinal mucosal barrier dysfunction and the occurrence of postoperative SIRS was analyzed. RESULTS: The plasma Gln level was significantly lowered (P<0.01) and L/M ratio increased (P<0.01) in these patients 2 and 7 days after the operation in comparison with the preoperative level. No bacterial DNA was detected before surgery, but PCR yielded positive results in 4 patients (9.5%, 4/42) at 2 days and in another patient at 7 days (2.4%, 1/42) after the operation. The 4 patients with positive PCR results 2 days after the operation showed significantly lower plasma Gln concentration (P<0.01) and higher L/M ratio (P<0.01) than those with negative results. SIRS occurred in 24 patients after surgery, whose plasma Gln level was significantly lower (P<0.01) and L/M ratio significantly higher (P<0.01) than that in the SIRS-free patients 2 days after the operation. Five of the 26 SIRS patients showed positive PCR results, while none of the 16 non-SIRS patients were positive, but this difference was not statistically significant (P>0.05). CONCLUSION: Decreased plasma Gln and increased intestinal mucosal permeability are closely related to postoperative bacterial translocation and the intestinal mucosal barrier dysfunction, which may contribute to the occurrence of postoperative infection.

Differences in shotgun protein expression profile between superficial bladder transitional cell carcinoma and normal urothelium.

This study was undertaken to identify differences in protein expression profiles between superficial bladder transitional cell carcinoma (BTCC) and normal urothelial cells. We used laser capture microdissection (LCM) to harvest purified cells, and used two-dimensional liquid chromatography (2D-LC) followed by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to separate and identify the peptide mixture. A total of 440/438 proteins commonly appeared in 4 paired specimens. Multi-step bioinformatic procedures were used for the analysis of identified proteins; 175/179 of the 293/287 proteins that were specific expressed in tumor/normal cells own gene ontology (GO) biological process annotation. Compared with the entire list of the international protein index (IPI), there are 52/46 GO terms exhibited as enriched and 6/10 exhibited as depleted, respectively. Significantly altered pathways between tumor and normal cells mainly include oxidative phosphorylation, focal adhesion, etc. Finally, descriptive statistics show that the shotgun proteomics strategy has practice directive significance for biomarker discovery by two-dimensional electrophoresis (2-DE) technology.