Tubuloclustin analogues with ether moiety: synthesis and evaluation of tubulin clustering and antimitotic activity in cancer cells

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Discovery of lung squamous carcinoma biomarkers by profiling the plasma peptide with LC/MS/MS

Biomarkers can be used for the screening and clinical diagnosis of cancer, and peptidomics approach has been proven successful in the research of biomarkers. To develop better peptidomic technologies for fast, accurate, and reliable detection of peptides biomarkers for lung cancer, we have improved the procedures of blood collection to minimize the degradation of the blood proteins and optimize the extraction of peptidome peptides from plasma samples based on acetonitrile precipitation associated with size exclusion chromatography (SEC). Studies show that squamous cell carcinomas are found to express CAGE1, SPAT9 and TEX28 genes at significantly higher rates, and the results suggest that as tumors progress, the level of CAGE1, SPAT9 and TEX28 genes are likely to increase and lead to immunization. This suggests a potentially important therapeutic method for cancer testis-based cancer vaccines.     

Serum Metabolic Fingerprinting to Detect Human Nasopharyngeal Carcinoma Based on Gas Chromatography-Mass Spectrometry and Partial Least Squares-Linear Discriminant Analysis

In this paper, metabolic fingerprints were obtained from 102 nasopharyngeal carcinoma (NPC) patients and 107 healthy adults by gas chromatography-mass spectrometry (GC/MS). Partial least squares-discriminant analysis (PLS-DA) has revealed a pattern recognition discriminating the patients from controls, which sensitivity is 89.72% (96/107) and specificity is 85.29% (87/102). Furthermore, double-blind experiment was carried out and satisfactory results were obtained (total correct rate 87.30%). In addition, metabolites that most strongly influence this separation were obtained. The results indicated that a metabonomic approach is feasible and efficient and deserves further evaluation as a potential novel strategy for the detection of nasopharyngeal carcinoma.     

Nasopharyngeal carcinoma detection by tissue smears using surface-enhanced Raman spectroscopy

Nasopharyngeal carcinoma is one of the most common malignant neoplasms in head and neck. In this work, surface-enhanced Raman spectroscopy technique was used to study the molecular differences between cancerous and noncancerous smear samples which were obtained after clinical biopsy by smearing the tissue on the slides. Principal component analysis combined with linear discriminant analysis provided a sensitivity of 79.4% and a specificity of 81.8% for differentiation between cancerous and noncancerous nasopharyngeal tissue smears. This work provides a good basis for the methodology of nasopharyngeal tissue smear based on surface-enhanced Raman spectroscopy technique and is worth further studying.     

A strategy with label-free quantification of the targeted peptides for quantitative peptidome analysis of human serum

Peptidomics draws more and more attention in discovering useful biomarkers for early diagnosis of disease. However, there is lack of efficient quantification strategy in peptidome analysis. In this study, a strategy with label-free quantification of the targeted endogenous peptides based on peak intensity using μUPLC-Q-TOF-MS/MS was developed for quantitative peptidome analysis of human serum. Different amounts of standard BSA tryptic digesting peptides were added into the same serum extracts for evaluation...     

Phytochemical profiling,molecular docking,and in vitro anti-hepatocellular carcinoid bioactivity of Suaeda vermiculata extracts

The ATP-binding cassette is the major class of transporters responsible for the efflux of chemotherapeutic agents from cancer cells, resulting in treatment failures of cancer’s patients. Suaeda vermiculata Forssk. ex. J. F. Gmel. is traditionally known for its liver protective activity. The LC-MS based chemical profilings of the sequentially partitioned sub-extracts obtained from the alcoholic extract of S. vermiculata using n-hexane, chloroform, ethyl acetate, and n-butanol as fractionating solvents, identified a total of thirty six compounds. These sub-extracts were evaluated for their anti-hepatocarcinoma activity against the sensitive HepG2 and doxorubicin (DOX)-resistant, HepG-2/ADR cell lines. A mixture of doxorubicin and sub-extracts at 20 μg/ml doses were also tested for their anti-hepatocarcinoma activity. The exhibited IC₅₀ values for the chloroform, ethyl acetate, n-hexane, and n-butanol sub-extracts, and the doxorubicin against HepG2, and HepG-2/ADR cell lines were found at 64.5, 66.8, 81.25, 125, 1.3 μg/ml, and 110.1, 91.82, 138.2, 265.7, 4.77 μg/ml levels, respectively. However, the treatment of resistant cells with 20 μg/ml of different sub-extracts in combination with the doxorubicin showed significant improvements in the doxorubicin activity against the resistant cells, and the IC₅₀ values for DOX + chloroform, DOX + ethyl acetate, DOX + n-hexane, and DOX + n-butanol against resistant cells, were at 1.77, 2.05, 2.66, and 2.71 μg/ml levels, respectively. The IC₅₀ values exhibited 2.69x, 2.33x, 1.79x and 1.76x-folds reversal of the sensitivity in the resistant cancer cell lines. The molecular docking studies of the compounds identified in the LC-MS chemical profilings, against three ATP-binding cassette proteins i.e., ABCB1, ABCC1, and ABCG2, showed that flavonoids as the major class of compounds responsible for reversal of the resistant cells sensitivities. The predicted binding affinity for the flavonoids against the above mentioned three ATP-binding cassette proteins’ are in the ranges of ～?8 to ?11 kcal/mol. Our results clearly indicate that the presence of flavonoids, as the major class of compounds in the S. vermiculata is responsible for the chemosensitization of the resistant HCC-cell lines. Moreover, the structures, 21 (5‐O‐methyl visamminol), 22 (N-trans-feruloyl tyramine), 27 (atractylenolide-III), and 32 (ginsenoside-Rh2) were also identified among the potential ATP-binding cassette’s modulators during the current study. These observations put the S. vermiculata in perspective with the traditionally claimed liver protective efficacy of the plant.     

Voltammetric Determination of 2′‐Deoxyadenosine and Adenine in Urine of Patients with Hepatocellular Carcinoma Using Fullerene‐C60‐modified Glassy Carbon Electrode

A fullerene‐C₆₀‐modified glassy carbon electrode has been examined for the simultaneous determination of 2′‐deoxyadenosine (2′‐dAdo) and adenine in human blood and urine using Osteryoung square‐wave voltammetry (OSWV) at pH 7.2. Compared to bare glassy carbon electrode (GCE), the modified electrode displays a shift of the oxidation potential in the negative direction with significant increase in the peak current for both the analytes. At modified electrode well‐defined anodic peaks at potential of 1248 mV and 994 mV are observed for 2′‐dAdo and adenine respectively. Linear calibration curves were obtained within the concentration range 10 nM to 100 μM for both the compounds in 0.1 M phosphate buffer solution (PBS) with the limit of detection 0.8×10^?8 M and 0.95×10^?8 M for 2′‐dAdo and adenine respectively. The analytical utility of the present method is demonstrated by quantitative detection of 2′‐dAdo and adenine in human urine of normal subjects as well as in patients with hepatocellular carcinoma. Interfering effect of some coexisting metabolites has also been reported.     

��-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells

Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of α-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage.