BSA-stabilized silver nanoclusters for efficient photoresponsive colorimetric detection of chromium(VI).

Hexavalent chromium is a highly toxic substance, which will pose a serious threat to human life and health and the entire ecosystem. Therefore, it is crucial to establish a simple and rapid detection method for hexavalent chromium. In this work, we fabricated bovine serum albumin-stabilized silver nanocluster (BSA-Ag13 NC) which exhibited photoresponsive oxidase-like activity, catalyzing the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to the blue oxidized state TMB (oxTMB) in a short time. Interestingly, 8-hydroxyquinoline (8-HQ) can significantly inhibit the color reaction of TMB oxidation while Cr(VI) can interact specifically with 8-HQ to restore this chromogenic reaction. Based on the above facts, a colorimetric sensing system for detecting Cr(VI) was developed. The sensing system shows a wide linear range, and good selectivity, with a low detection limit of 2.32 nM. Moreover, this sensing system could be successfully applied to the detection of Cr(VI) in lake water, tap water, and sewage with satisfactory results.

Macrophage-mediated degradable gelatin-coated mesoporous silica nanoparticles carrying pirfenidone for the treatment of rat spinal cord injury.

The treatment of spinal cord injury is still a challenge worldwide; there is still no effective method. Our strategy is to devise a macrophage-mediated degradable gelatin coated mesoporous silica nanoparticles, which could carry pirfenidone and realize spatiotemporal control of pirfenidone release in the lesion site. For the in vivo experiment, three groups of SD rats subjected to spinal cord contusion injury were injected with GNS-PFD, PFD or PBS. Spinal cord functions were observed. In vitro, we investigated the expression of inflammatory and anti-inflammatory factors. Spinal cord function and recovery were better in the GSN-PFD and PFD than the control group. In the in vitro study, the MMPs after SCI in lesion site were lower in the experimental group. Moreover, the expression of anti-inflammatory and inflammatory factors showed better in the experimental group. The inflammatory response of the PFD to time and space can be achieved with the loading of macrophage-mediated degradable gelatin coated mesoporous silica nanoparticles.

Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models.

Development of personalized cancer vaccines based on neoantigens has become a new direction in cancer immunotherapy. Two forms of cancer vaccines have been widely studied: tumor-associated antigen (including proteins, peptides, or tumor lysates)-pulsed dendritic cell (DC) vaccines and protein- or peptide-adjuvant vaccines. However, different immune modalities may produce different therapeutic effects and immune responses when the same antigen is used. Therefore, it is necessary to choose a more effective neoantigen vaccination method. In this study, we compared the differences in immune and anti-tumor effects between neoantigen-pulsed DC vaccines and neoantigen-adjuvant vaccines using murine lung carcinoma (LL2) candidate neoantigens. The enzyme-linked immunospot (ELISPOT) assay showed that 4/6 of the neoantigen-adjuvant vaccines and 6/6 of the neoantigen-pulsed DC vaccines induced strong T-cell immune responses. Also, 2/6 of the neoantigen-adjuvant vaccines and 5/6 of the neoantigen-pulsed DC vaccines exhibited potent anti-tumor effects. The results indicated that the neoantigen-pulsed DC vaccines were superior to the neoantigen-adjuvant vaccines in both activating immune responses and inhibiting tumor growth. Our fundings provide an experimental basis for the selection of immune modalities for the use of neoantigens in individualized tumor immunotherapies.

A phase I dose-reduction study of apatinib combined with pemetrexed and carboplatin in untreated EGFR and ALK negative stage IV non-squamous NSCLC.

Objective Apatinib is an oral small molecule anti-angiogenic drug. This phase I study aimed to establish the feasible dose of apatinib in combination with pemetrexed plus carboplatin as first-line therapy for epidermal growth factor receptor (EGFR) and anaplasticlymphoma kinase (ALK) negative stage IV non-squamous non-small cell lung cancer (NSCLC). Methods Using a 3 + 3 dose-reduction design, patients received oral apatinib at four dose levels: 750 mg qd, 500 mg qd, 500 mg/day two weeks on/one week off schedule (500 mg schedule 2/1) or 250 mg qd. Pemetrexed (500 mg/m2) plus carboplatin (AUG = 5) was administered every three weeks. Maintenance therapy by apatinib or pemetrexed could be carried on until disease progression or unacceptable toxicity. The feasible dose was determined based on cycle 1 dose-limiting toxicities (DLT); other assessments included safety and antitumor activity according to response evaluation criteria in solid tumors. Result A total of twelve patients were enrolled and cycle 1 DLTs were observed in two patients at 750 mg qd dosage of apatinib (both Grade 3 hypertension), two patients at 500 mg qd (Grade 3 hypertension and Grade 3 hand-foot syndrome), and only one of six patients at 500 mg/day schedule 2/1 (Grade 3 hypertension). The most frequently drug-related adverse events (AEs) were hematological toxicity, hypertension, hand-foot syndrome, and hepatic transaminases elevation. Partial response was observed in four patients of eleven evaluable patients (objective response rate 36.4%), and six patients exhibited stable disease (disease control rate 90.9%). Conclusion In patients with advanced non-squamous NSCLC, the feasible dose of apatinib given with standard-dose pemetrexed and carboplatin was 500 mg/day schedule 2/1. The schedule was generally well tolerated and demonstrated promising clinical benefit in NSCLC.

A Novel Nomogram and Risk Classification System Predicting the Cancer-Specific Survival of Patients with Initially Diagnosed Metastatic Esophageal Cancer: A SEER-Based Study.

BACKGROUND: Metastatic esophageal cancer (mEC) is the end stage of esophageal cancer. We aimed to construct a predictive model predicting the cancer-specific survival (CSS) of mEC patients. METHODS: Data from 1917 patients with initially diagnosed mEC were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Patients were randomly divided into the training and validation cohorts (7:3). Cox regression was conducted to select the predictors of CSS. The validation of the nomogram was performed using concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: Cancer-specific death occurred in 1559/1917 (81.3%) cases. Multivariate Cox regression indicated that factors including age, sex, grade at diagnosis, number of metastatic organs at diagnosis, pathological type, local treatment, and chemotherapy were independent predictors of CSS. Based on these factors, a predictive model was built and virtualized by nomogram. The C-index of the nomogram was 0.762. The calibration curves showed good consistency of CSS between the actual observation and the nomogram prediction, and the DCA showed great clinical usefulness of the nomogram. A risk classification system was built that could perfectly classify mEC patients into three risk groups. In the total cohort, the median CSS of patients in the low-, intermediate- and high-risk groups was 11.0 months (95% confidence interval [CI] 10.1-11.9), 8.0 months (95% CI 7.3-8.7), and 2.0 months (95% CI 1.8-2.2), respectively. CONCLUSIONS: We constructed a nomogram and a corresponding risk classification system predicting the CSS of patients with initially diagnosed mEC. These tools can assist in patient counseling and guiding treatment decision making.

Monitoring the estimated glomerular filtration rate (eGFR) in patients with small-cell lung cancer during chemotherapy: equations based on serum creatinine or cystatin C?

BACKGROUND: This study compared the differences between the estimated glomerular filtration rate (eGFR) calculated by several equations based on serum creatinine (Scr) and cystatin C (CysC) concentrations for monitoring renal function in patients with small-cell lung cancer (SCLC) during chemotherapy. METHODS: Seventy-one patients with SCLC were retrospectively analyzed. The eGFR before and after each chemotherapy cycle was calculated by the following equations: the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, the modification of diet in renal disease (MDRD) equation, the Cockcroft-Gault (CG) equation, and five CysC-based equations. The patients were compared among the different eGFR groups. RESULTS: The mean decreases in eGFRCKD-EPI (-2.25 ± 9.89 ml/min/1.73 m2) between each treatment cycle were more significant than the decreases in eGFRCG (-0.46 ± 10.17 ml/min/1.73 m2), eGFRMDRD (-0.48 ± 9.79 ml/min/1.73 m2), and five calculated eGFRCysC (p < 0.05). Single-/multiparameter analyses showed that patients with a higher body mass index (BMI >23) and receiving more treatment cycles (>3) were at increased risk for developing renal impairment with an eGFR less than 60 ml/min/1.73 m2 during chemotherapy. CONCLUSIONS: The eGFR calculated by the CKD-EPI equation changed more significantly between each chemotherapy cycle than did the eGFR from the other equations based on Scr or CysC in patients with SCLC. Oncologists should pay more attention to the renal function of specific patient groups during treatment.

The Superior Glenohumeral Joint Capsule Alone Does Not Prevent Superior Translation of the Humeral Head: An In Vitro Biomechanical Study.

PURPOSE: To answer 2 questions: What is the main structure that prevents the superior translation of the humeral head, the supraspinatus or the superior capsule (SC)? And what mechanism does the principal structure rely on to prevent the superior translation of the humeral head, the spacer effect or the tensional hammock effect? METHODS: Eight shoulder specimens were assessed using a custom biomechanical testing system. Glenohumeral superior translation and subacromial peak pressure were compared using 6 models: the intact joint model, supraspinatus dysfunction model, supraspinatus defect model, SC tear model, SC defect model, and irreparable rotator cuff tear (IRCT) model. RESULTS: Compared with the intact joint model, the supraspinatus defect model significantly increased the superior translation (by 2.6 mm; P < .001) and subacromial peak pressure (by 0.43 MPa; P = .013) at 0° glenohumeral abduction, while the SC defect model unremarkably altered the superior translation at 0° (by 0.6 mm; P = .582) and 45° (by 0.3 mm; P = .867) of glenohumeral abduction and the subacromial peak pressure at 0° (by 0.11 MPa; P = .961), 30° (by -0.03 MPa; P = .997), and 45° (by -0.33 MPa; P = .485) of glenohumeral abduction. The supraspinatus dysfunction model significantly increased the superior translation at 0° (by 1.7 mm; P < .001), 30° (by 1.2 mm; P = .005), and 45° (by 0.8 mm; P = .026) of glenohumeral abduction, but not the subacromial peak pressure compared with the intact joint model. However, no significant differences were found between the supraspinatus defect model and the supraspinatus dysfunction model with respect to the superior translation or subacromial peak pressure (all P > .05). CONCLUSIONS: The anatomic SC has a negligible role in preventing the superior translation of the humeral head. CLINICAL RELEVANCE: SC reconstruction is not a simple anatomic reconstruction, and its promising clinical outcome may be due to tensional fixation technique and choice of graft.

[Effects of VEGF on Proliferation, Apoptosis and Insulin Secretion in Rat Pancreatic Islet Cells].

OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF) on proliferation, apoptosis, insulin secretion and related gene expression in rat pancreatic islet cell (INS-1). METHODS: INS-1 cells were treated with different concentrations of VEGF. CCK-8 kit was used to detect the proliferation of INS-1 cells and the cell apoptosis were evaluated by using Annexin V and propidium iodide (PI) double staining kit. INS-1 cells were treated with VEGF and the standard glucose stimulated insulin secretion test with ELISA was conducted. The expression of related genes in pancreatic islets was detected by real-time quantitative PCR. The effect of VEGF on isulin protein expression was evaluated with Western blot. RESULTS: No significant changes (P > 0.05) in INS-1 cells were observed after treated with different concentrations of VEGF at 24 h, 48 h and 72 h. But when VEGF concentration were 80 ng/mL and 160 ng/mL, an inhibitory effect on cell apoptosis were noticed (P < 0.01). The addition of VEGF to the high-glucose media significantly reduced the release of insulin at the concentration of 40 ng/mL. A decreasing trends of the expression level of sulfonylurea receptor gene (Sur), inwardly rectifying potassium channel gene 6. 2 (Kir6. 2) as well as the release of insulin were noticed as the increasing of VEGF concentrations. The expression of glucokinase gene (GCK) first decreased and then increased, but the expression of glucose transporter gene 2 (Glut 2) were increased first and then decreased. CONCLUSION; VEGF inhibited the secretion of insulin from INS-1 cells in the high-glucose condition. Our study provides new clues to the function of VEGF on the glucose metabolism.

Regulation of autophagy of prostate cancer cells by ß-catenin signaling.

BACKGROUND/AIMS: Autophagy is a cellular degradation process for the recycling of damaged or superfluous intracellular compartments to provide an alternative energy source during periods of metabolic stress for maintaining cell homeostasis and viability. Although autophagy in different contexts have been shown to use similar signaling pathways, the exact molecular regulation of autophagy has been found to be cell-type dependent. METHODS: We used rapamycin to trigger autophagy and used nitric oxide (NO) to inhibit autophagy in prostate cancer cells. IWP-2 was used to inhibit ß-catenin signaling. Autophagy-associated proteins were examined by Western blot. RESULTS: We found that nitric oxide (NO), a potent cellular messenger, impaired rapamycin-induced autophagy in prostate cancer cells. Further analyses showed that NO induced nuclear accumulation of ß-catenin, a key factor of Wnt signaling pathway, to inhibit autophagy in prostate cancer cells. CONCLUSIONS: We demonstrate involvement of ß-catenin signaling in the regulation of autophagy of prostate cancer cells. Our results shed light on a previously unappreciated ß-catenin signaling pathway for regulating autophagy in prostate cancer.

Concurrent paclitaxel-based chemo-radiotherapy for post-surgical microscopic residual tumor at the bronchial margin (R1 resection) in non-small-cell lung cancer.

BACKGROUND: The microscopic residual tumor at the bronchial margin after radical surgery (R1 resection) affects prognosis negatively in non-small-cell lung cancer (NSCLC) patients. For patients with good performance status, a potential cure still exists. Here, we report the outcomes of concurrent paclitaxel-based chemo-radiotherapy (CRT) for NSCLC patients with microscopically positive bronchial margins or peribronchial infiltration. METHODS: A retrospective search in the clinical database was conducted in three hospitals. Patients were identified and evaluated if treated with radiotherapy combined with paclitaxel-based chemotherapy. The objects analyzed were local control time, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. RESULTS: Sixty-one patients with microscopic residual tumor at the bronchial stump following pulmonary lobectomy were identified. Forty-six patients who had received concurrent paclitaxel-based CRT were analyzed. The median follow-up was 40 months (range: 15.0-77.5 months). The 1-, 2- and 3-year survival rates were 97.8%, 60.9% and 36.9%, respectively. The local recurrences were recorded in 19.6% (9/46) patients. Median PFS and OS for the evaluated cohort were 23.0 [95% confidence interval (CI): 21.3-24.7] and 32.0 (95% CI: 23.7-40.3) months, respectively. The most common side effects were hematological toxicity (neutropenia, 93.5%; anemia, 89.1%; and thrombocytopenia, 89.1%) and no treatment-related deaths. Grade ≥2 acute radiation-induced pneumonitis and esophagitis were recorded in 43.5% (20/46) and 26.1% (12/46) patients, respectively. By univariate analysis, non-squamous cell lung cancer was associated with a significantly longer survival time (45.1 vs 26.4 months, p = 0.013). CONCLUSIONS: For NSCLC patients with post-surgical microscopic residual tumor at the bronchial stump, concurrent paclitaxel-based chemo-radiotherapy achieved promising outcomes with accepted treatment-related toxicity.

[Prognostic determinants of adrenocortical carcinoma in adults].

OBJECTIVE: To investigate the clinical features and prognostic determinants of adrenocortical carcinoma (ACC) in adult patients. METHODS: All adult patients (aged > or =18 years old) who were admitted to West China Hospital, Sichuan University from 1st Jan., 2000 to 31st Jan., 2013 with a pathologically diagnosed ACC were included in this study. Data about the demographics, clinical characteristics, laboratory examinations and outcomes of those patients were extracted and analyzed. RESULTS: A total of 52 cases were identified, with a median follow-up of 26 months (3-159 months). The patients had a median survival time of 29 months (1-156 months), with a 1-year, 3-year; and 5-year survival rate of 71.0%, 47.0%, and 42.7%, respectively. In the univariate analysis, aged >45 years old at diagnosis (P = 0.017), advanced stage (III-IV stage, P<0.001), incomplete resection (P = 0.011), symptomatic (P = 0.017), hypoalbuminemia (P = 0.003), and elevated lactate dehydrogenase (LDH) (P = 0.017) were associated with poor prognosis of ACC. The multivariate analysis confirmed that hypoalbuminemia Chazard ratio (HR) = 5.306; 95% confidence interval (95% CI: 1.975, 14.258; P = 0.001), female (HR = 4.020; 95% CI: 1.610, 10.038; P = 0.003), advanced stage (HR = 7.405; 95% CI: 2.561, 21.410; P < 0.001), and older age (HR = 4.628; 95% CI: 1.791, 11.959; P = 0.002) were predictors of poor prognosis of ACC. CONCLUSION: Hypoalbuminemia, female, older age, and advanced stage are independent risk factors associated with poor prognosis of ACC.in adult patients.

MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway.

BACKGROUND: Trastuzumab resistance is almost inevitable in the management of human epidermal growth factor receptor (HER) 2 positive breast cancer, in which phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss is implicated. Since metadherin (MTDH) promotes malignant phenotype of breast cancer, we sought to define whether MTDH promotes trastuzumab resistance by decreasing PTEN expression through an NFκB-dependent pathway. METHODS: The correlations between MTDH and PTEN expressions were analyzed both in HER2 positive breast cancer tissues and trastuzumab resistant SK-BR-3 (SK-BR-3/R) cells. Gene manipulations of MTDH and PTEN levels by knockdown or overexpression were utilized to elucidate molecular mechanisms of MTDH and PTEN implication in trastuzumab resistance. For in vivo studies, SK-BR-3 and SK-BR-3/R cells and modified derivatives were inoculated into nude mice alone or under trastuzumab exposure. Tumor volumes, histological examinations as well as Ki67 and PTEN expressions were revealed. RESULTS: Elevated MTDH expression indicated poor clinical benefit, shortened progression free survival time, and was negatively correlated with PTEN level both in HER2 positive breast cancer patients and SK-BR-3/R cells. MTDH knockdown restored PTEN expression and trastuzumab sensitivity in SK-BR-3/R cells, while MTDH overexpression prevented SK-BR-3 cell death under trastuzumab exposure, probably through IκBα inhibition and nuclear translocation of p65 which subsequently decreased PTEN expression. Synergized effect of PTEN regulation were observed upon MTDH and p65 co-transfection. Forced PTEN expression in SK-BR-3/R cells restored trastuzumab sensitivity. Furthermore, decreased tumor volume and Ki67 level as well as increased PTEN expression were observed after MTDH knockdown in subcutaneous breast cancer xenografts from SK-BR-3/R cells, while the opposite effect were found in grafts from MTDH overexpressing SK-BR-3 cells. CONCLUSIONS: MTDH overexpression confers trastuzumab resistance in HER2 positive breast cancer. MTDH mediates trastuzumab resistance, at least in part, by PTEN inhibition through an NFκB-dependent pathway, which may be utilized as a promising therapeutic target for HER2 positive breast cancer.

Synthesis and biological evaluation of 4-(1,2,3-triazol-1-yl)coumarin derivatives as potential antitumor agents.

In this research, a series of 4-(1,2,3-triazol-1-yl)coumarin conjugates were synthesized and their anticancer activities were evaluated in vitro against three human cancer cell lines, including human breast carcinoma MCF-7 cell, colon carcinoma SW480 cell and lung carcinoma A549 cell. To increase the biological potency, structural optimization campaign was conducted focusing on the C-4 position of 1,2,3-triazole and the C-6, C-7 positions of coumarin. In addition, to further evaluate the role of 1,2,3-triazole and coumarin for antiproliferative activity, 9 compounds possessing 4-(piperazin-1-yl)coumarin framework and 3 derivatives baring quinoline core were also synthesized. By MTT assay in vitro, most of the compounds display attractive antitumor activities, especially 23. Further flow cytometry assays demonstrate that compound 23 exerts the antiproliferative role through arresting G2/M cell-cycle and inducing apoptosis.

Effects of temperature and initial pH on the growth of four dominant cyanobacteria species in biological soil crusts.

Biological soil crusts are of great significance for environment health and sustainable development in arid and semi-arid areas. Cyanobacteria, Microcoleus vaginatus, Scytonema sp., Nostoc sp., and Anabaena sp. are the dominant species in microbial community of biological soil crusts worldwide. Considering their broad application prospect, it is meaningful to cultivate them extensively. We examined the effects of temperature (10, 20, 25, 30, 35 ℃) and initial pH (4, 6, 8, 10, 12) on biomass and solution pH towards the four species of cyanobacteria with liquid culture in laboratory. The results showed that the biomass of the four cyanobacterial species grew slowly under 20 ℃, and that all species could grow in 25-35 ℃, with the highest growth rate at 25 and 30 ℃. The optimum culture temperature of different cyanobacterial species was slightly different. The optimum culture temperature was 25-30 ℃ for Scytonema sp. and Nostoc sp., and 30 ℃ for M. vaginatus and Anabaena sp. The four cyanobacterial species had a strong ability to adjust solution pH and proliferate in five different initial pH conditions. The highest maximum biomass and specific growth rate were recorded in the culture environment with initial pH of 4, while the lowest maximum biomass and specific growth rate were observed in initial pH of 12. Our results would provide scientific basis for the propagation of dominant cyanobacteria in biological soil crusts.

Surface photogalvanic effect in Ag2Te.

The bulk photovoltaic effect (BPVE) in non-centrosymmetric materials has attracted significant attention in recent years due to its potential to surpass the Shockley-Queisser limit. Although these materials are strictly constrained by symmetry, progress has been made in artificially reducing symmetry to stimulate BPVE in wider systems. However, the complexity of these techniques has hindered their practical implementation. In this study, we demonstrate a large intrinsic photocurrent response in centrosymmetric topological insulator Ag2Te, attributed to the surface photogalvanic effect (SPGE), which is induced by symmetry reduction of the surface. Through diverse spatially-resolved measurements on specially designed devices, we directly observe that SPGE in Ag2Te arises from the difference between two opposite photocurrent flows generated from the top and bottom surfaces. Acting as an efficient SPGE material, Ag2Te demonstrates robust performance across a wide spectral range from visible to mid-infrared, making it promising for applications in solar cells and mid-infrared detectors. More importantly, SPGE generated on low-symmetric surfaces can potentially be found in various systems, thereby inspiring a broader range of choices for photovoltaic materials.

Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells.

The antiapoptotic factor Livin has been considered critical for tumor progression and poor prognosis for variant types of tumors. However, there are only limited reports regarding its expression and biological functions in colon cancer. Here, we examined Livin expression in four colon cancer cell lines (HCT116, RKO, KM12C, and SW620) in the presence or absence of cisplatin that was used as a model reagent. We found the different response to cisplatin was related to endogenous Livin expression level. From among a panel of apoptosis-related factors (p53, Bcl-2, Bcl-XL, BAX, and survivin), the expression of Livin was upregulated after cisplatin treatment in a dose-dependent manner. Both immunocytochemistry and nuclear cytoplasmic fractionation indicated Livin remained in the cytoplasm after treatment with cisplatin. In an attempt to explore the mechanism, we found the elevated expression of Livin was not due to the decreased degradation by proteosome but was enhanced at the mRNA level. Besides, cisplatin treatment activated the mammalian target of rapamycin (mTOR) pathway as shown by increased phosphorylation of Akt1, mTOR, S6K, and 4E-BP1, together with the elevated Livin. The PI3K inhibitor LY294002 inhibited both the phosphorylation of mTOR and upregulation of Livin. The stable overexpression of Livin inhibited the activation of caspase-3 and led to resistance to cisplatin, while the knockdown of Livin by siRNA rendered colon cancer cells more sensitive to cisplatin. Our study, along with others, highlighted the potential of Livin for cancer therapy in colon cancer.

Analysis of furo[3,2-c]tetrahydroquinoline and pyrano[3,2-c]tetrahydroquinoline derivatives as antitumor agents and their metabolites by liquid chromatography/electrospray ionization tandem mass spectrometry.

RATIONALE: Tetrahydroquinoline derivatives possess a broad range of biological activities. Since few studies have been reported concerning metabolites of furo[3,2-c]tetrahydroquinoline- and pyrano[3,2-c]tetrahydroquinoline-derived antitumor agents, the proposed fragmentation mechanisms and their metabolites were investigated in this study. METHODS: The fragmentation pathways of eight furo[3,2-c]tetrahydroquinoline derivatives and six pyrano[3,2-c]tetrahydroquinoline derivatives were analyzed using electrospray ionization tandem mass spectrometry. Hydrogen/deuterium (H/D) exchange reactions were employed to identify the proposed structures of the product ions. In addition, compounds were incubated with human liver microsomes (HLM) at 37 °C for 8 h and the related metabolites were analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). RESULTS: Two protonation modes were summarized and protonation occurring on the oxygen atom of furan or pyran ring could trigger the cleavage of the C-O bond, followed by the elimination of a molecule of water and the substituent at the C2 site, respectively. On the other hand, a proton added to the nitrogen atom may lead to the loss of dihydrofuran or dihydropyran from the protonated molecules. Apart from the general proposed fragmentation pathways above, the variations on the C2 site could result in some specific fragmentation patterns. Further incubating compound B1 with HLM in vitro produced two major metabolites, and the structures were proposed by tandem mass experiments together with the fragmentation mechanisms of these compounds. CONCLUSIONS: These observations play an important role in monitoring and characterization of the presence and metabolites of furo[3,2-c]tetrahydroquinoline and pyrano[3,2-c]tetrahydroquinoline derivatives in complex mixtures, and can provide some applications in further pharmaceutical and therapeutic research.

[Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: a prospective study].

OBJECTIVE: To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy. METHODS: One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study, and they were randomized into 2 groups, i.e., treatment group, which received the therapy of CIK cells transfusion, and control group, which was given regular follow-up. Meanwhile, patients with positive hormone receptor in the two groups were given endocrine therapy, and the patients with positive axillary lymph nodes were given radiotherapy to the chest wall and regional lymph nodes. The difference of quality of life between the two groups was analyzed according to the EORTC QLQ-BR53 quality of life questionnaire, and the adverse reactions were monitored. RESULTS: As regarding the functional evaluation, the physical function scores of patients of the treatment group were (83.43 ± 14.87) and (88.55 ± 11.62) at 3 and 6 months after the CIK cell therapy, respectively, significantly higher than the baseline value [(74.83 ± 13.82), P < 0.05)]. Global health status/QOL scores were (83.30 ± 19.09) and (89.68 ± 10.81), significantly higher than the baseline value [(77.72 ± 21.05), P < 0.05]. As regarding symptoms, the scores of fatigue, nausea, vomiting and loss of appetite of patients in the treatment group were higher than the baseline value, with significant differences (P < 0.05). The nausea and vomiting scores in the control group at 3 and 6 months of followed-up were (26.67 ± 22.56) and (21.47 ± 21.06), significantly lower than the baseline values [(33.31 ± 27.07), P < 0.05]. The scores of worrying about the future in the patients of treatment group were (47.56 ± 30.84) and (42.33 ± 26.95) after 3 and 6 months, significantly better than the baseline value [(57.41 ± 30.63), P < 0.05]. The systematic therapy side effects scores were (31.95 ± 27.52) and (23.72 ± 22.87), significantly better than the baseline value [(40.56 ± 26.28), P < 0.05]. The scores of arm edema were (45.26 ± 25.42) and (36.61 ± 20.51), significantly milder than the baseline value [(55.11 ± 22.82), P < 0.05]. In the control group, the scores of arm edema were (44.85 ± 28.94) and (38.64 ± 23.68), significantly lower than the baseline values [(53.26 ± 23.84) points, P < 0.05]. Alopecia scores were (29.93 ± 24.72) and (24.18 ± 22.66), significantly lower than the baseline values [(35.92 ± 22.08), P < 0.05]. In the treatment group, the patients' physical function, social function and global health status/QOL, fatigue, insomnia, and worrying about the future rates were significantly higher than that of the control group (P < 0.05 for all). Three patients after CIK reinfusion had transient fever, and 6 cases felt pain in the lower limb, but the symptoms were relieved after symptomatic treatment. CONCLUSIONS: Therapy of autologous CIK cells transfusion can significantly improve the quality of life of breast cancer patients, and the adverse reactions during the treatment can be alleviated by symptomatic treatment.

[Comparison of platinum-containing doublet chemotherapy and liposome paclitaxel monotherapy for the treatment of elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: Given controversy remains on monotherapy and combinatory chemotherapy in elderly patients (> or = 70 years) with advanced non-small cell lung cancer (NSCLC), we conducted this study to compare the safety and efficacy of liposome paclitaxel and platinum-containing doublets. METHODS: From January 2007 to March 2009, totally 65 patients (age > or = 70 years) with pathologically confirmed NSCLC were enrolled. 33 patients received liposome paclitaxel monotherapy (monotherapy group) and 32 patients received platinum-containing doublets chemotherapy (combinatory group). RESULTS: No CR was observed in all patients. Both groups had similar objective response rate (ORR) (6.1% vs. 15.6%, P = 0.399). However, a statistically significant higher disease control rate (DCR) (65. 6%) was observed in he combinatory group when compared with that of monotherapy group (39.4%, P = 0.034). The combinatory group had longer time-to-progression (TTP) (94 days, 95% CI: 60-127 days) than the monotherapy group (51 days, 95% CI: 22-79 days, P = 0.046). The median overall survival days in the combinatory group was 524 days (95% CI: 146-901 days) where as in the monotherapy group only 146 days (95% CI 32-259 days) (P = 0.001). The most common adverse reactions were myelosuppression, gastrointestinal reactions and elevated transaminase in the monotherapy group, while those were myelosuppression, gastrointestinal reactions and infection in the combinatory group. Generally there was no significant difference in the adverse reaction, except grade 3-4 thrombocytopenia (P = 0.004). It should be addressed that 1 patient (3.0%) in the monotherapy group had an onset of severe infection, while the number rose to 5 (15.6%) in the combinatory group (P = 0.079). CONCLUSION: Platinum-containing doublet chemotherapy achieved a higher response rate, longer time-to-progression and overall survival compared with liposome paclitaxel monotherapy in the treatment of elderly patients with advanced NSCLC. However thrombocytopenia and severe infection should be monitored for the combinatory chemotherapy.