γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer.

Development of cancer has been linked to chronic inflammation, particularly via interleukin-23 (IL-23) and IL-17 signaling pathways. However, the cellular source of IL-17 and underlying mechanisms by which IL-17-producing cells promote human colorectal cancer (CRC) remain poorly defined. Here, we demonstrate that innate γδT (γδT17) cells are the major cellular source of IL-17 in human CRC. Microbial products elicited by tumorous epithelial barrier disruption correlated with inflammatory dendritic cell (inf-DC) accumulation and γδT17 polarization in human tumors. Activated inf-DCs induced γδT17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, γδT17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-γδT17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumor-elicited inflammation. These findings suggest that γδT17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.

Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis.

OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1ß production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.

Towards a Fuzzy Bayesian Network Based Approach for Safety Risk Analysis of Tunnel-Induced Pipeline Damage.

Tunneling excavation is bound to produce significant disturbances to surrounding environments, and the tunnel-induced damage to adjacent underground buried pipelines is of considerable importance for geotechnical practice. A fuzzy Bayesian networks (FBNs) based approach for safety risk analysis is developed in this article with detailed step-by-step procedures, consisting of risk mechanism analysis, the FBN model establishment, fuzzification, FBN-based inference, defuzzification, and decision making. In accordance with the failure mechanism analysis, a tunnel-induced pipeline damage model is proposed to reveal the cause-effect relationships between the pipeline damage and its influential variables. In terms of the fuzzification process, an expert confidence indicator is proposed to reveal the reliability of the data when determining the fuzzy probability of occurrence of basic events, with both the judgment ability level and the subjectivity reliability level taken into account. By means of the fuzzy Bayesian inference, the approach proposed in this article is capable of calculating the probability distribution of potential safety risks and identifying the most likely potential causes of accidents under both prior knowledge and given evidence circumstances. A case concerning the safety analysis of underground buried pipelines adjacent to the construction of the Wuhan Yangtze River Tunnel is presented. The results demonstrate the feasibility of the proposed FBN approach and its application potential. The proposed approach can be used as a decision tool to provide support for safety assurance and management in tunnel construction, and thus increase the likelihood of a successful project in a complex project environment.

Serum profiling by mass spectrometry combined with bioinformatics for the biomarkers discovery in diffuse large B-cell lymphoma.

The aim of this study was to identify potential serum biomarkers of diffuse large B-cell lymphoma (DLBCL) and to detect DLBCL therapy response biomarkers. DLBCL serum proteomic analysis was performed using the CM10 ProteinChip mass spectrometry (SELDI-TOF-MS) approach combined with bioinformatics. A total of 178 samples were analyzed in this study from untreated early stage DLBCL patients (38), patients with inflammatory lymphadenopathy (13), healthy donors (35), post-treatment non-relapsed DLBCL patients (53), and relapsed DLBCL patients (39). Model 1 formed by nine protein peaks (m/z: 6443, 5913, 6198, 4098, 7775, 9293, 5946, 5977, and 4628) could be used to distinguish DLBCL patients from healthy individuals with an accuracy of 95.89% (70/73). The diagnostic pattern constructed using the support vector machine including the nine proteins of model 1, showed a maximum Youden's Index. Model 2 formed by three protein peaks (m/z: 3942, 6639, and 4121) could be used to distinguish DLBCL patients from those with inflammatory lymphadenopathy with an accuracy of 94.12% (48/51). Model 3 formed by six protein peaks could distinguish patients with inflammatory lymphadenopathy from healthy individuals with an accuracy of 97.92% (47/48). Model 4 could be used to distinguish non-relapsed DLBCL patients from relapsed DLBCL patients with an accuracy of 84.78% (78/92). The four patterns were validated by leave-one-out cross-validation. These data demonstrate that the CM10 ProteinChip and SELDI-TOF-MS approach combined with bioinformatics can be used effectively to screen for the differential protein expression profiles of DLBCL patients and to predict the response to therapy.

Lycopene enhances antioxidant enzyme activities and immunity function in N-methyl-N'-nitro-N-nitrosoguanidine-enduced gastric cancer rats.

To investigate anticancer effect of lycopene, we examined the effects of lycopene on the oxidative injury and immunity activities of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer rats. The animals were divided into five groups. Group I served as the normal control and was given corn oil orally for 20 weeks. Group II were induced with MNNG 200 mg/kg body weight by oral gavage at days 0 and 14, and saturated NaCl (1 mL per rats) was given once every three days for four weeks until the end of the experimental period. Group III, IV and V were posttreated with lycopene (50, 100 and 150 mg/kg body weight, dissolved in corn oil) from the sixth week of MNNG (as in group II) induction up to the end of the experimental period. In the presence of MNNG, MDA and immunity levels were significantly increased, whereas enzymatic (SOD, CAT, and GPx) antioxidant activities were decreased in the treated rats compared with normal control rats. Administration of lycopene to gastric carcinoma-induced rats largely up-regulated the redox status and immunity activities to decrease the risk of cancer compared to group II. We conclude that up-regulation of antioxidants and immunity by lycopene treatment might be responsible for the anticancer effect in gastric carcinoma.

Management of and Revitalization Strategy for Megacities Under Major Public Health Emergencies: A Case Study of Wuhan.

The outbreak of the COVID-19 pandemic in late 2019 has meant an uphill battle for city management. However, due to deficiencies in facilities and management experience, many megacities are less resilient when faced with such major public health events. Therefore, we chose Wuhan for a case study to examine five essential modules of urban management relevant to addressing the pandemic: (1) the medical and health system, (2) lifeline engineering and infrastructure, (3) community and urban management, (4) urban ecology and (5) economic development. The experience and deficiencies of each module in fighting the pandemic are analyzed, and strategies for revitalization and sustainable development in the future are proposed. The results show that in response to large-scale public health events, a comprehensive and coordinated medical system and good urban ecology can prevent the rapid spread of the epidemic. Additionally, good infrastructure and community management can maintain the operation of the city under the pandemic, and appropriate support policies are conducive to the recovery and development of the urban economy. These precedents provide insights and can serve as a reference for how to change the course of the pandemic in megacities that are still at risk, and they provide experience for responding to other pandemics.

Service Quality Improvement of Outpatient Blood Collection by Lean Management.

OBJECTIVE: To explore the application effect of lean management in improving the quality of outpatient blood collection services. METHODS: For this study, a total of 146,907 patients whose blood was sampled by outpatient services between April 2020 and September 2020 were selected. We analyzed the influence of various factors on the waiting time and satisfaction levels of the patients for blood collection and eliminated confounders based on the results of the analysis. Lean management for the outpatient blood collection service was implemented in July 2020. Thus, the 38,275 cases sampled on weekday mornings between April and June 2020 were selected as the ordinary management group, while the 39,473 cases sampled on weekday mornings between July and September 2020 belonged to the lean management group. Finally, the changes in waiting time and the satisfaction levels of the patients were evaluated. RESULTS: The age and gender of the patients and the length of service of the staff, who administered blood collection had a negligible effect on the waiting time (Z=-1.243, P=0.418; Z=-1.569, P=0.389; Z = -1.062, P= 0.563), while there was a statistical difference in the waiting time between different days and different sessions (Z = -2.581, P = 0.013 and Z = -4.672, P < 0.001). We also found that the length of service of blood collection staff, day, session, and age and gender of patients did not have a meaningful effect on patient satisfaction (P > 0.05). Overall, the median waiting time of outpatients decreased from 22 min to 13 min after the implementation of lean management (Z =10.522, P < 0.001), while the satisfaction level of outpatients increased from 95.37% to 98.33% (χ 2 = 559.580, P < 0.001). CONCLUSION: The application of lean management can significantly shorten outpatient waiting time for blood collection, improve patients satisfaction levels, and enhance the overall patient experience. Thus, lean management can significantly improve the service quality of outpatient blood collection.

[Value of imprint in bone marrow morphological examination].

OBJECTIVE: To explore the role of bone marrow (BM) imprint in the diagnosis of hematological diseases. METHODS: Between January 2002 and June 2008, a total of 3024 cases with BM smears, imprints and sections conducted simultaneously were recruited. There were 1667 males and 1357 females with a median age of 55 years old (range: 7 to 92). The cellularity on imprint and smear was evaluated with the standard cellularity on BM section. With the integrative diagnosis (including all examinations and clinical outcomes) as the standard, the diagnostic accuracy of hematological diseases were compared between BM imprint, smear and section groups. Another 79 cases of lymphoma and 114 cases of plasma cell myeloma (PCM) were selected for a correlation analysis of tumor cell infiltration patterns. RESULTS: BM imprint contained hematopoietic and non-hematopoietic regions and cells retained integrated structure. The cellularity evaluation by imprint was superior to smear overall. In BM imprint group, the diagnostic accuracy for hypersplenism (n = 130), metastatic carcinoma (n = 67), refractory anemia with excess blasts, myeloproliferative neoplasm (n = 174), and PCM (n = 94) were better than smear group (96.9% vs 80.7%, 91.0% vs 76.1%, 92.6% vs 81.5%, 92.5% vs 76.4%, and 97.8% vs 92.6% respectively, all P < 0.05); And the diagnostic accuracy for megaloblastic anemia (n = 69), acute myeloid leukemia (n = 104), refractory cytopenia with unilineage dysplasia (n = 15), refractory cytopenia with multilineage dysplasia (n = 22), and lymphoplasmacytic lymphoma (n = 12) were higher than biopsy section group (100% vs 84.0%, 91.3% vs 74.0%, 86.7% vs 60.0%, 90. 9% vs 72.7%, and 66.6% vs 50.0% respectively, all P < 0.05); And the diagnostic accuracy for myelodysplastic/myeloproliferative neoplasm (n = 26) was higher than smear group (76.3%, P < 0.05) and biopsy section group (78.2%, P < 0.05). Excellent correlations existed between BM imprint and section of the patients with lymphoma or with PCM (r = 0.90, r = 0.78, both P < 0.05). CONCLUSIONS: BM imprint contains the characteristics of both smear and section. BM imprint is superior to smear for an evaluation of cellularity. And it is also better than section for an analysis of cytological changes.

Evaluation of plasma urokinase-type plasminogen activator and urokinase-type plasminogen-activator receptor in patients with acute and chronic hepatitis B.

INTRODUCTION: Urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR) are known to be important factors in the pathogenesis of tumors and certain non-viral inflammatory diseases. However, their role in infectious virus diseases such as hepatitis B has been less well studied. This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the inflammatory damage to liver cells caused by the hepatitis B virus. We therefore analyzed their role and clinicopathological significance in patients with acute or chronic hepatitis B. MATERIALS AND METHODS: Eighty patients with acute or chronic hepatitis B, together with 30 healthy controls, were enrolled. uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The levels of uPA and uPAR in patients with acute or chronic hepatitis B significantly exceeded those in healthy controls (p<0.05). Patients with severe chronic hepatitis B had significantly higher levels of uPA and uPAR than those with moderate and mild chronic disease (p<0.05) and those with acute hepatitis B (p<0.05). Moreover, the plasma uPA and uPAR markedly increased in the acute stage (p<0.05) and dramatically decreased in the remission stage (p<0.05), but in all stages levels exceeded those in healthy subjects (p<0.05). In addition, the concentration of plasma uPAR was positively correlated with prothrombin (PT) (r=0.605, p<0.01) and total bilirubin (TBIL) (r=0.649, p<0.01). CONCLUSIONS: It is suggested that the plasma levels of uPA and uPAR are closely related to the degree and period of inflammation in patients with acute or chronic hepatitis B, and that uPA and uPAR might be important indicators for disease progression.

Aspirin inhibits colon cancer cell line migration through regulating epithelial-mesenchymal transition via Wnt signaling.

The mechanism responsible for the initiation of tumor metastasis and epithelial-mesenchymal transition (EMT) is not well understood. During EMT, epithelial cells lose their polarity and adhesion to surrounding cells and migrate, resulting in transition into mesenchymal cells. Canonical Wnt signaling has been implicated in controlling gene transcription and body axis pattern formation during development. However, canonical Wnt signaling has also been indicated to serve a role in carcinogenesis by regulating EMT. In the present study, it was demonstrated that the expression of several positive regulators of EMT and Wnt signaling was repressed by aspirin treatment in SW480 tumor cells, and that this reduction was due to alterations in the localization of zinc finger E-box binding homeobox 1 and Snail family transcriptional repressor 2. It was also demonstrated that aspirin may be an effective inhibitor of EMT, reducing the viability and migration ability of SW480 tumor cells, including cells induced by TGF-ß1.

Novel distribution pattern of fibrinolytic components in rabbit tissues extract: a preliminary study.

OBJECTIVE: The purpose of this work was to investigate the distribution pattern of fibrinolytic factors and their inhibitors in rabbit tissues. METHODS: The components of the fibrinolytic system in extracts from a variety of rabbit tissues, including tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), plasminogen (Plg), plasmin (Pl) and alpha(2) plasmin inhibitor (alpha(2)PI), were determined by colorimetric assay. RESULTS: The tissue extracts in renal, small intestine, lung, brain and spleen demonstrated strong fibrinolytic function, in which high activity of tPA, Plg and Pl was manifested; whereas in skeletal muscle, tongue and stomach, higher activity of PAI-1 and alpha(2)PI showed obviously. Also excellent linear correlations were found between levels of tPA and PAI-1, Pl and alpha(2)PI, Plg and Pl. In related tissues, renal cortex and renal marrow showed distinctly higher activity of tPA and lower activity of PAI-1, with the levels of Plg and Pl in renal cortex being higher than those in renal marrow, where the alpha(2)PI level was higher than that in renal cortex. Similarly, the levels of tPA, Plg and Pl in small intestine were higher than those in large intestine, but with respect to PAI-1 and alpha(2)PI, the matter was reverse. In addition, the fibrinolytic activity in muscle tissue was lower, however, the levels of tPA, Plg, and Pl in cardiac muscle were obviously higher than those in skeletal muscles, and the levels of PAI-1 and alpha(2)PI were significantly lower than those in skeletal muscle. CONCLUSION: Our data demonstrate that a remarkable difference of the fibrinolytic patterns exists in rabbit tissues, which has probable profound significance in understanding the relationship between the function of haemostasis or thrombosis and the physiologic function in tissues.

[Preoperative molecular staging of colorectal cancers by CM10 ProteinChip and SELDI-TOF-MS analysis].

OBJECTIVE: To detect the serum proteomic patterns by using SELDI-TOF-MS and CM10 ProteinChip techniques in colorectal cancer (CRC) patients, and to evaluate the significance of the proteomic patterns in colorectal cancer staging. METHODS: A total of 76 serum samples were obtained from CRC patients at different clinical stages, including Dukes A (n = 10), Dukes B (n = 19), Dukes C (n = 16) and Dukes D (n = 31). Different stage models were developed and validated by bioinformatics methods of support vector machines, discriminant analysis and time-sequence analysis. RESULTS: The model I formed by six proteins of peaks at m/z 2759.6, 2964.7, 2048.0, 4795.9, 4139.8 and 37 761.6 could do the best as potential biomarkers to distinguish local CRC patients (Dukes A and Dukes B) from regional CRC patients (Dukes C ) with an accuracy of 86.7%. The model II formed by 3 proteins of peaks at m/z 6885.3, 2058.3 and 8567.8 could do the best to distinguish locoregional CRC patients (Dukes A, B and C) from systematic CRC patients (Dukes D) with an accuracy of 75.0%. The mode III could distinguish Dukes A from Dukes B with an accuracy of 86.2% (25/29). The model IV could distinguish Dukes A from Dukes C with an accuracy of 84.6% (22/26). The model V could distinguish Dukes B from Dukes C with an accuracy of 85.7% (30/35). The model VI could distinguish Dukes B from Dukes D with an accuracy of 80.0% (40/50). The model VII could distinguish Dukes C from Dukes D with an accuracy of 78.7% (37/47). Different stage groups could be distinguished by the two-dimensional scattered spots figure obviously. CONCLUSION: Our findings indicate that this method can well be used in preoperative staging of colorectal cancers and the screened tumor markers may serve for guidance of integrating treatment of colorectal cancers.

Preoperatively molecular staging with CM10 ProteinChip and SELDI-TOF-MS for colorectal cancer patients.

OBJECTIVES: To detect the serum proteomic patterns by using SELDI-TOF-MS (surface enhanced laser desorption/ ionization-time of flight-mass spectrometry) technology and CM10 ProteinChip in colorectal cancer (CRC) patients, and to evaluate the significance of the proteomic patterns in the tumour staging of colorectal cancer. METHODS: SELDI-TOF-MS and CM10 ProteinChip were used to detect the serum proteomic patterns of 76 patients with colorectal cancer, among them, 10 Stage I, 19 Stage II, 16 Stage III and 31 Stage IV samples. Different stage models were developed and validated by support vector machines, discriminant analysis and time-sequence analysis. RESULTS: The Model I formed by 6 protein peaks (m/z: 2759.58, 2964.66, 2048.01, 4795.90, 4139.77 and 37761.60) could be used to distinguish local CRC patients (Stage I and Stage II) from regional CRC patients (Stage III) with an accuracy of 86.67% (39/45). The Model II formed by 3 protein peaks (m/z: 6885.30, 2058.32 and 8567.75) could be used to distinguish locoregional CRC patients (Stage I, Stage II and Stage III) from systematic CRC patients (Stage IV) with an accuracy of 75.00% (57/76). The Model III could distinguish Stage I from Stage II with an accuracy of 86.21% (25/29). The Model IV could distinguish Stage I from Stage III with accuracy of 84.62% (22/26). The Model V could distinguish Stage II from Stage III with accuracy of 85.71% (30/35). The Model VI could distinguish Stage II from Stage IV with accuracy of 80.00% (40/50). The Model VII could distinguish Stage III from Stage IV with accuracy of 78.72% (37/47). Different stage groups could be distinguished by the two-dimensional scattered spots figure obviously. CONCLUSION: This method showed great success in preoperatively determining the colorectal cancer stage of patients.

Prospective safety performance evaluation on construction sites.

This paper presents a systematic Structural Equation Modeling (SEM) based approach for Prospective Safety Performance Evaluation (PSPE) on construction sites, with causal relationships and interactions between enablers and the goals of PSPE taken into account. According to a sample of 450 valid questionnaire surveys from 30 Chinese construction enterprises, a SEM model with 26 items included for PSPE in the context of Chinese construction industry is established and then verified through the goodness-of-fit test. Three typical types of construction enterprises, namely the state-owned enterprise, private enterprise and Sino-foreign joint venture, are selected as samples to measure the level of safety performance given the enterprise scale, ownership and business strategy are different. Results provide a full understanding of safety performance practice in the construction industry, and indicate that the level of overall safety performance situation on working sites is rated at least a level of III (Fair) or above. This phenomenon can be explained that the construction industry has gradually matured with the norms, and construction enterprises should improve the level of safety performance as not to be eliminated from the government-led construction industry. The differences existing in the safety performance practice regarding different construction enterprise categories are compared and analyzed according to evaluation results. This research provides insights into cause-effect relationships among safety performance factors and goals, which, in turn, can facilitate the improvement of high safety performance in the construction industry.

Thymosin alpha1 enhanced cytotoxicity of iNKT cells against colon cancer via upregulating CD1d expression.

Increasing evidence showed invariant NKT cells (iNKT cell) are an attractive candidate for cancer immunotherapy, but its role in colorectal cancer treatment was still unclear. Here we reported iNKT cells exerted moderate cytotoxic effect against colorectal cancer cells (CRC cells) with the stimulation of α-Galcer, and the mutual recognition between CRC and iNKT cells could be greatly enhanced by Thymosinα1 (TA), which resulted in stronger killing efficiency both in vitro and in vivo. TA is widely used as an immune adjuvant for cancer therapy, but how it works on cancer cells still remains unclear. We found TA could upregulate CD80, B7H2 and CD1d expression on CRC cells. However, neutralization assay revealed iNKT cells' activation depended on CD1d expression rather than CD80 or B7H2. Moreover, colon cancer stem cells expressed higher CD1d level, which accounted for their greater sensitization to iNKT cells. Mechanistically, inhibition of Erk/MAPK pathway greatly attenuated the upregulation of CD1d by TA. Taken together, depending on Erk/MAPK pathway, TA promoted the activation and cytotoxicity of iNKT cells via upregulating CD1d expression on CRC cells, which indicated a novel immunotherapeutic strategy of iNKT cells against CRC.

Ex vivo expanded human circulating Vδ1 γδT cells exhibit favorable therapeutic potential for colon cancer.

Gamma delta T (γδT) cells are innate-like lymphocytes with strong, MHC-unrestricted cytotoxicity against cancer cells and show a promising prospect in adoptive cellular immunotherapy for various malignancies. However, the clinical outcome of commonly used Vγ9Vδ2 γδT (Vδ2 T) cells in adoptive immunotherapy for most solid tumors is limited. Here, we demonstrate that freshly isolated Vδ1 γδT (Vδ1 T) cells from human peripheral blood (PB) exhibit more potent cytotoxicity against adherent and sphere-forming human colon cancer cells than Vδ2 T cells in vitro. We also develop an optimized protocol to preferentially expand Vδ1 T cells isolated from PB of both healthy donors and colon cancer patients by in vitro short-term culture with phytohemagglutinin (PHA) and interleukin-7 (IL-7). Expanded Vδ1 T cells highly expressed cytotoxicity-related molecules, chemokine receptors and cytokines with enhanced cytolytic effect against adherent and sphere-forming colon cancer cells in a cell-to-cell contact dependent manner. In addition, PHA and IL-7 expanded Vδ1 T cells showed proliferation and survival advantage partly through an IL-2 signaling pathway. Furthermore, ex vivo expanded Vδ1 T cells also restrained the tumor growth and prolonged the tumor-burdened survival of human colon carcinoma xenografted mice. Our findings suggest that human PB Vδ1 T cells expanded by PHA and IL-7 are a promising candidate for anticancer adoptive immunotherapy for human solid tumors such as colon cancer.

[Determination of trace arsenic in sulfur by graphite furnace atomic absorption spectrometry with La(NO3)3-Ni(NO3)2 matrix modifier].

In this paper, the decomposition method of sulfur and the determination of trace arsenic in sulfur by GFAAS with La(NO3)3-Ni(NO3)2 matrix modifier were studied in detail. The decomposition of sulfur with mixed acid HNO3-HClO4 by controlled temperature electrothermal method or pressure crucible method was efficient and safe. The sensitivity of the determination of arsenic with La(NO3)3-Ni(NO3)2 matrix modifier was higher than with Ni(NO3)2 or Mg(NO3)2 matrix modifiers. The detection limit was 0.034 microgram.mL-1 (k = 3). The analytical results of the sulfur samples were coincident with the results of determination by HG-ICP-AES. The adding recoveries were 97.5%-110% and the relative standard deviation was less than or equal to 2.1% (n = 4).

Cancer stem cell theory: therapeutic implications for nanomedicine.

Evidence continues to accumulate showing that tumors contain a minority population of cells responsible for tumor initiation, growth, and recurrence. These are termed "cancer stem cells" (CSCs). Functional assays have identified the self-renewal and tumor-initiation capabilities of CSCs. Moreover, recent studies have revealed that these CSCs is responsible for chemotherapy resistance within a tumor. Several mechanisms of chemoresistance have been proposed, including increased Wnt/ß-catenin and Notch signaling, as well as high expression levels of adenosine triphosphate-binding cassette transporters, an active DNA repair capacity, and slow rate of self-renewal. Nanoscale drug-delivery systems, which transport therapeutically active molecules, prolong circulation, and improve biodistribution in the body, may allow more effective and specific therapies to address the challenges posed by CSCs. In particular, some nanovehicles are being exploited for selective drug delivery to CSCs and show promising results. In this review, we highlight the mechanisms of drug resistance and the novel strategies using nanoscale drugs to eliminate CSCs.

Novel SN38 conjugate-forming nanoparticles as anticancer prodrug: in vitro and in vivo studies.

The clinical utility of CPT-11 is restricted by factors such as the low conversion rate to SN38, high interpatient variability and dose-limiting toxicity. SN38 is significantly more potent than CPT-11, but parental administration of SN38 is impossible due to its poor solubility and low stability. This study aimed to develop a novel SN38 prodrug (OEG-SN38) that may overcome the various drawbacks of CPT-11 and SN38 and be useful for clinics. We attached a very low molecular weight oligo (ethylene glycol) (OEG) chain selected as the hydrophilic part to hydrophobic SN38 via ester bond at the C20 position to form the amphiphilic OEG-SN38. In aqueous solution OEG-SN38 formed micelles with diameter of 28.74±2.51 nm, and showed greatly improved drug loading, solubility and stability, with drug loading as high as 36% (wt.%). Moreover, these micelles were stable in PBS with only 4.71% SN38 released from the prodrug even after 35 h incubation, but released SN38 promptly by esterase hydrolysis. Most importantly, OEG-SN38 exhibited potent antitumor activity against a panel of human tumor cell lines, as well as favorable antitumor activity and high safety in human xenograft models. These encouraging data merit further preclinical and clinical investigation on this novel SN38 delivery system.

miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent cancers globally and is one of the leading causes of cancer-related deaths due to therapy resistance and metastasis. Understanding the mechanism underlying colorectal carcinogenesis is essential for the diagnosis and treatment of CRC. microRNAs (miRNAs) can act as either oncogenes or tumor suppressors in many cancers. A tumor suppressor role for miR-27b has recently been reported in neuroblastoma, while no information about miR-27b in CRC is available. In this study, we demonstrated that miR-27b expression is decreased in most CRC tissues and determined that overexpression of miR-27b represses CRC cell proliferation, colony formation and tumor growth in vitro and in vivo. We identified vascular endothelial growth factor C (VEGFC) as a novel target gene of miR-27b and determined that miR-27b functioned as an inhibitor of tumor progression and angiogenesis through targeting VEGFC in CRC. We further determined that DNA hypermethylation of miR-27b CpG islands decreases miR-27b expression. In summary, an anti-tumor role for miR-27b and its novel target VEGFC in vivo could lead to tumor necrosis and provide a rationale for developing miR-27b as a therapeutic agent.