ABSTRACT
PURPOSE: In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). METHODS: LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. RESULTS: Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. CONCLUSIONS: LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.
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PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.
Subject(s)
Neoplasms, Second Primary , Rectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/therapeutic use , Chemoradiotherapy/adverse effects , Fluorouracil/therapeutic use , Humans , Neoadjuvant Therapy/adverse effects , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neoplasms, Second Primary/pathology , Rectal Neoplasms/pathologyABSTRACT
The aim of the study was to investigate the survival advantage of radiotherapy (RT) in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Patients with pulmonary LCNEC were extracted from the Surveillance, Epidemiology, and End Results (SEER) dataset between January 2004 and December 2013. Propensity score matching (PSM) analysis with 1:1 was used to ensure well-balanced characteristics of all comparison groups. A total of 1480 eligible cases were identified, with a median follow-up time of 11 months (0-131 months). After PSM, 980 patients were classified in no radiotherapy (No RT) and radiotherapy (RT) groups (n = 490 each). Patients in the RT group harbored significantly higher 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates compared to those in the No RT group (both P < 0.05). Furthermore, RT was an independent favorable prognostic factor of OS as well as CSS in multivariate analysis, both before [OS: hazard ratio (HR) 0.840, 95% confidence interval (CI) 0.739-0.954, P = 0.007; CSS: HR 0.847, 95% CI 0.741-0.967, P = 0.014] and after (OS: HR 0.854, 95% CI 0.736-0.970, P = 0.016; CSS: HR 0.848, 95% CI 0.735-0.978, P = 0.023) PSM. In subgroup analysis, American Joint Committee on Cancer (AJCC) stage II and III, tumor size 5-10 cm, patients who underwent no surgery, or patients who received chemotherapy could significantly benefit from RT (all P < 0.05). To sum up, our findings suggested that RT could prolong the survival of patients with pulmonary LCNEC, especially those with stage II and III, tumor size 5-10 cm, those with no surgery, or those who received chemotherapy.
Subject(s)
Carcinoma, Neuroendocrine/radiotherapy , Lung Neoplasms/radiotherapy , Propensity Score , Aged , Aged, 80 and over , Carcinoma, Neuroendocrine/epidemiology , Female , Follow-Up Studies , Humans , Lung Neoplasms/epidemiology , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , SEER Program , Treatment OutcomeABSTRACT
Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (ILPCI) and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions. The number of blood microvessels was markedly increased on days 1 and 14, but decreased on day 60 after seizures. The surface area, diameter distribution, mean tortuosity, and number of bifurcations and network segments also showed similar trends. These pathological changes were confirmed by histological tests. Thus, SR-based ILPCI provides systematic and detailed views of cerebrovascular anatomy at the micron level without using contrast-enhancing agents. This holds considerable promise for better diagnosis and understanding of the pathogenesis and development of epilepsy.
Subject(s)
Epilepsy , Hippocampus/diagnostic imaging , Synchrotrons , Animals , Epilepsy/diagnostic imaging , Hippocampus/pathology , Imaging, Three-Dimensional , Male , Rats , Rats, Sprague-DawleyABSTRACT
[This corrects the article DOI: 10.18632/oncotarget.19856.].
ABSTRACT
OBJECTIVE: Gastric cancer (GC) is the fourth most common cause of cancer-related deaths in the world. In the current study, we aim to identify the hub genes and uncover the molecular mechanisms of GC. METHODS: The expression profiles of the genes and the miRNAs were extracted from the Gene Expression Omnibus database. The identification of the differentially expressed genes (DEGs), including miRNAs, was performed by the GEO2R. Database for Annotation, Visualization and Integrated Discovery was used to perform GO and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network and miRNA-gene network were constructed using Cytoscape software. The hub genes were identified by the Molecular Complex Detection (MCODE) plugin, the CytoHubba plugin and miRNA-gene network. Then, the identified genes were verified by Kaplan-Meier plotter database and quantitative real-time PCR (qRT-PCR) in GC tissue samples. RESULTS: A total of three mRNA expression profiles (GSE13911, GSE79973 and GSE19826) were downloaded from the Gene Expression Omnibus (GEO) database, including 69, 20 and 27cases separately. A total of 120 overlapped upregulated genes and 246 downregulated genes were identified. The majority of the DEGs were enriched in extracellular matrix organization, collagen catabolic process, collagen fibril organization and cell adhesion. In addition, three KEGG pathways were significantly enriched, including ECM-receptor interaction, protein digestion and absorption, and the focal adhesion pathways. In the PPI network, five significant modules were detected, while the genes in the modules were mainly involved in the ECM-receptor interaction and focal adhesion pathways. By combining the results of MCODE, CytoHubba and miRNA-gene network, a total of six hub genes including COL1A2, COL1A1, COL4A1, COL5A2, THBS2 and ITGA5 were chosen. The Kaplan-Meier plotter database confirmed that higher expression levels of these genes were related to lower overall survival, except for COL5A2. Experimental validation showed that the rest of the five genes had the same expression trend as predicted. CONCLUSION: In conclusion, COL1A2, COL1A1, COL4A1, THBS2 and ITGA5 may be potential biomarkers and therapeutic targets for GC. Moreover, ECM-receptor interaction and focal adhesion pathways play significant roles in the progression of GC.
ABSTRACT
In this work, a novel water-stable coordination polymer with {44} network topology {[Zn(L)2(NO3)2]}n (1) (Lâ¯=â¯4,4'-Bis(triazol-1-ylmethyl)biphenyl) has been synthesized through the hydrothermal and sonochemical approaches. 1 has been characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD), Fourier Transform Infrared Spectroscopy, UV-vis absorption spectrum and scanning electron microscopy (SEM). PXRD patterns of the as-synthesized samples 1 have confirmed the purity of the bulky samples. In the sonochemical preparation approaches, different ultrasound irradiation power and ultrasound time were also used in order to investigate the impact factor for morphology and size of nano-structured 1. Photo-luminescence studies have revealed that 1 can efficiently distinguish Fe3+ from Fe2+ and other metal ions. On the other hand, 1 also can exhibit a highly sensitive, excellently selective and real-time detection of benzaldehyde and pH through photo-luminescence quenching process. As for 1, density functional theory (DFT) and time-dependent DFT (TDDFT) theory has been applied to calculate these spectroscopic data, the result agree with the experimental results for detection of benzaldehyde. Photo-luminescent recyclability results indicated 1 can be reused at least five times in the detection process. To the best of our knowledge, this is the first example of a multi-responsive regenerable luminescent sensor for highly selective, sensitive and real-time sensing of Fe3+ over Fe2+, benzaldehyde and pH values.
ABSTRACT
Zoledronic acid is used to treat patients with bone metastasis, but the optimal dosing interval remains controversial. We therefore performed a systematic review and meta-analysis to compare the efficacy and safety of a 12-week interval of zoledronic acid with the standard 4-week interval. Three randomized controlled trials comprising 2650 patients were analyzed. Using a random-effects model, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. No differences in the occurrence of skeletal-related events (SREs: RR = 0.98; 95% CI = 0.86-1.12; P = 0.80) or grade 3/4 adverse events (RR = 0.91; 95% CI = 0.69-1.20; P = 0.52) were observed between the 12-week and 4-week groups. The 12-week group tended to have lower incidences of osteonecrosis of the jaw [13 (0.98%) vs. 23 (1.73%)] and kidney dysfunction [21 (1.68%) vs. 31 (2.45%)] than the 4-week group, though the difference did not reach statistical significance (RR = 0.58, 95% CI: 0.30-1.12; P = 0.11); (RR = 0.67, 95% CI: 0.39-1.15, P = 0.15). These data show that zoledronic acid administered at 12-week intervals instead of 4-week intervals does not increase the risk of SREs, and may reduce the incidence of osteonecrosis of the jaw and kidney dysfunction. This suggests the 12-week interval with zoledronic acid may be an acceptable treatment option.
ABSTRACT
To compare the efficacy and safety of moderate hypofractionated radiotherapy (H-RT) with those of conventional radiotherapy (C-RT) in patients with localized prostate cancer, we conducted extensive literature searches of The Web of Science, Embase, Pubmed and Cochrane Library databases. We identified nine studies with 5969 patients for a meta-analysis. We calculated pooled risk ratios (RRs) and the 95% confidence intervals (CIs) for multiple parameters and performed statistical analysis using RevMan 5.3 software. Our analysis showed that the H-RT group obtained greater improvements in the 5-year biochemical or clinical failure-free survival (RR = 1.04, 95% CI:1.01-1.08; P = 0.01) and 5-year disease-free survival(RR = 1.04, 95% CI: 1.01-1.07, P = 0.02) than the C-RT group. However, the 5-year overall survival rates were comparable in the two groups (RR = 1.02, 95% CI: 0.99-1.04; P = 0.18). Comparison of multiple secondary parameters, including grade 2-4 acute/late gastrointestinal toxicity, grade 2-4 acute/late genitourinary toxicity, biochemical failure, local failure, distant failure and prostate cancer-specific mortality between the H-RT and the C-RT groups showed no statistical differences. This meta-analysis thus indicates that in patients with localized prostate cancer, moderate H-RT exerts a great beneficial effect on the primary parameters than C-RT without enhancing adverse events.
Subject(s)
Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Radiotherapy , Humans , Male , Neoplasm Recurrence, Local , Neoplasm Staging , Odds Ratio , Prostatic Neoplasms/mortality , Radiotherapy/adverse effects , Radiotherapy/methods , Survival Analysis , Treatment Failure , Treatment OutcomeABSTRACT
To measure the safety and efficacy of oxaliplatin (OX) application in neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC), EMBASE, PubMed, Cochrane Library, and Web of Science were used for a literature search. Cochrane's risk of bias tool of randomized controlled trials (RCTs) was used for quality evaluation. The statistical analyses were performed using RevMan 5.3. In addition, 95% confidence intervals (CIs) and pooled risk ratios (RRs) were calculated. Seven RCTs were included in our meta-analysis. After adding OX to fluoropyrimidine (FU), a marginal significant improvement in disease-free survival was noted compared with FU alone (RR = 0.89, 95% CI: 0.78-1.00; P = 0.05). Neoadjuvant CRT with OX significantly decreased the distant metastasis rate (RR = 0.79, 95% CI: 0.67-0.94, P = 0.007). However, no improvement in the local recurrence rate (RR = 0.86, 95% CI: 0.68-1.08; P = 0.19) was noted. In addition, neoadjuvant CRT with OX also significantly increased the pathologic complete response (RR = 1.24, 95% CI: 1.02-1.51; P = 0.03). Grade 3-4 acute toxicity and grade 3-4 diarrhea was considerably higher for OX/FU compared with FU alone. In conclusion, the use of OX on the basis of FU/capecitabine in preoperative CRT is feasible. LARC patients are likely to benefit from CRT regimens with OX.
Subject(s)
Chemoradiotherapy, Adjuvant/methods , Neoadjuvant Therapy/methods , Organoplatinum Compounds/administration & dosage , Rectal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Fluorouracil/administration & dosage , Humans , Oxaliplatin , Rectal Neoplasms/radiotherapyABSTRACT
In this work a rigid asymmetrical tricarboxylate ligand p-terphenyl-3,4â³,5-tricarboxylic acid (H3L) has been employed, and a unique heterometallic alkaline earth-lanthanide microporous luminescent metal-organic framework (MOF) {[Ba3La0.5(µ3-L)2.5(H2O)3(DMF)]·(3DMF)}n (1·3DMF) (DMF = dimethylformamide) has been isolated under solvothermal conditions. Single-crystal X-ray structural analysis demonstrates that 2D inorganic Ba-O-La connectivity can be observed in 1, which are further bridged via rigid terphenyl backbones of L(3-), forming a unique I(2)O(1)-type microporous luminescent framework. A 1D microporous channel with dimensionality of 9.151(3) Å × 10.098(1) Å can be observed along the crystallographic a axis. PXRD patterns have been investigated indicating pure phases of 1. The luminescence explorations demonstrated that 1 exhibits highly selective and sensitive sensing for Al(3+) over other cations with high quenching efficiency Ksv value of 1.445 × 10(4) L·mol(-1) and low detection limit (1.11 µM (S/N = 3)). Meanwhile 1 also exhibits highly selective and sensitive sensing for MnO4(-) over other anions with quenching efficiency Ksv = 7.73 × 10(3) L·mol(-1) and low detection limit (0.28 µM (S/N = 3)). It is noted that, when different concentrations of MnO4(-) solutions (0.5 to 100 µM) were dropped into the suspension of 1, the bright blue luminescence of the suspension observed under UV light can gradually change into pink color, indicating visually luminescent sensing, which makes the detection process of MnO4(-) more convenient in practical. The result also reveals that 1 represents the first example of bifunctional heterometallic alkaline earth-lanthanide MOF-based luminescent probes for selectively detecting Al(3+) and MnO4(-) in the water solutions.
ABSTRACT
BACKGROUND: Short-course preoperative radiation (SCRT) with delayed surgery was found to increase pathologic complete response (pCR) rates in several trials. However, there was no clear answer on whether SCRT or long-course chemo-radiotherapy (LCRT) is more effective. Therefore we conducted this meta-analysis to evaluate the safety and efficacy of SCRT versus LCRT, both with delayed surgery, for treatment of rectal cancer. MATERIALS AND METHODS: The literature was searched from PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov up to November, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the level of evidence. Review Manager 5.3 was employed for statistical analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Three RCTs, with a total of 357 rectal cancer patients, were included in this systematic review. Meta- analysis results demonstrated there were no significantly differences in sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate. Compared with SCRT, LCRT was associated with significant increase in the pCR rate [RR=0.49, 95%CI (0.31, 0.78), P=0.003]. CONCLUSIONS: In terms of sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate, SCRT with delayed surgery is as effective as LCRT with delayed surgery for management of rectal cancer. LCRT significantly increased pCR rate compared with SCRT. Due to risk of bias and imprecision, further multi-center large sample RCTs were needed to confirm this conclusion.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/therapy , Preoperative Care , Radiotherapy, Adjuvant , Rectal Neoplasms/therapy , Combined Modality Therapy , Humans , Neoadjuvant Therapy , Neoplasm Recurrence, Local/pathology , Prognosis , Randomized Controlled Trials as Topic , Rectal Neoplasms/pathology , Risk Factors , Time FactorsABSTRACT
BACKGROUND: Long-course chemoradiotherapy (LCRT) with delayed surgery or short-course radiotherapy (SCRT) with immediate surgery is probably the most frequent regimen in the treatment of rectal cancer. Debate is still going on whether SCRT or LCRT is more effective. So we performed this meta-analysis to evaluate the safety and efficacy of SCRT with immediate surgery versus LCRT with delayed surgery for the management of rectal cancer. METHODS: Literature were searched from PubMed, Embase, Web of science, Cochrane Library up to May, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. RevMan 5.3 was used for statistical analysis. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated. Subgroup analysis and sensitivity analysis were employed to explore heterogeneity. RESULTS: 16 trials were included in the qualitative systematic review. 12 trials were included in meta-analyses. 4 of them were RCTs; other 8 were non-RCTs. Meta-analysis demonstrated that there were no significant differences in overall survival (OS), disease free survival (DFS), local recurrence rate (LRR), distant metastasis rate (DMR), sphincter preservation rate, R0 resection rate and late toxicity. Compared with SCRT, LCRT obviously increased pCR rate [RR=0.15, 95%CI (0.08, 0.28), P=0.003], while LCRT obviously increased the grade 3-4 acute toxicity [RR=0.13, 95%CI (0.06, 0.28), P<0.00001]. CONCLUSIONS: SCRT with immediate surgery is as effective as LCRT with delayed surgery for treatment of rectal cancer in terms of OS, DFS, LRR, DMR, Sphincter preservation rate, R0 resection rate and late toxicity. Though LCRT increased pCR rate, LCRT also increased acute toxicity compared with SCRT. SCRT is a better choice in centers with a long waiting list or lack of medical resources.
Subject(s)
Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Anal Canal , Chemoradiotherapy, Adjuvant/adverse effects , Clinical Trials as Topic , Disease-Free Survival , Humans , Neoadjuvant Therapy/adverse effects , Neoplasm Metastasis , Neoplasm, Residual , Organ Sparing Treatments , Radiotherapy, Adjuvant/adverse effects , Survival Rate , Time FactorsABSTRACT
INTRODUCTION: Although most prostate cancers initially respond to castration with luteinizing hormone- releasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. METHODS: Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. RESULTS: Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. CONCLUTIOS: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-naive, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.
Subject(s)
Androstenols/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Prednisone/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Androstenes , Androstenols/adverse effects , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Progression , Disease-Free Survival , Humans , Kallikreins/blood , Male , Placebos/therapeutic use , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti-inflammatory, anti-oxidative and anti-fibrinolytic properties, which is used extensively for the treatment of cardiovascular diseases in clinic. AIM OF THIS STUDY: The present study aimed to investigate the preventive and therapeutic effects of DHI on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. MATERIALS AND METHODS: Lung injury was induced by intranasal instillation with 10 µg LPS. Mice were randomly divided into four groups: Control group; LPS group; LPS+5 ml/kg DHI group and LPS+10 ml/kg DHI group. The effects of DHI on LPS-induced neutrophils influx, inflammatory cytokines release, protein leakage, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) level were examined. In addition, the NF-κB activation in lung tissues was detected by Western blot. RESULTS: In LPS challenged mice, DHI significantly reduced the infiltration of activated neutrophils and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). DHI also inhibited protein extravasation in BALF, attenuated edema and the pathological changes in the lung. In addition, DHI markedly prevented LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that DHI effectively inhibited the NF-κB activation in lung tissues. CONCLUSION: DHI has been demonstrated to protect mice from LPS induced acute lung injury by its anti-inflammatory and anti-oxidant activities.
Subject(s)
Acute Lung Injury/prevention & control , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Ethnopharmacology , Lung/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/immunology , Acute Lung Injury/pathology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Antioxidants/administration & dosage , Antioxidants/pharmacology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , China , Cytokines/immunology , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Injections, Intraperitoneal , Lipopolysaccharides/pharmacology , Lung/immunology , Lung/pathology , Male , Mice , Mice, Inbred BALB C , Neutrophil Infiltration/drug effects , Organ Size , Pulmonary Edema/immunology , Pulmonary Edema/pathology , Pulmonary Edema/prevention & controlABSTRACT
The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in potato dextrose liquid medium, and one rare thiophene compound (1), together with anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4), botryosphaerone D (5), 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6), 3ß,5α-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (7), 3ß,5α,14α-trihydroxy-(22E,24R)-ergosta-7, 22-dien-6-one (8), NGA0187 (9) and beauvericin (10), were isolated. Their structures were elucidated by analysis of spectroscopic data. This is the first report of a natural origin for compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine microorganism for the first time. In the bioactive assays in vitro, compounds 2, 3, 9 and 10 displayed remarkable inhibiting actions against α-acetylcholinesterase (AChE) with IC50 values 2.01, 6.71, 1.89, and 3.09 µM, respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10 exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and KB cell lines with IC50 values 4.98 and 2.02 (MCF-7), 1.95 and 0.82 (A549), 0.68 and 1.14 (Hela), and 1.50 and 1.10 µM (KB), respectively; compound 8 had weak inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6 and 9 exhibited no inhibitory activities against them.
Subject(s)
Aquatic Organisms/chemistry , Aquatic Organisms/metabolism , Aspergillus/chemistry , Aspergillus/metabolism , Biological Products/chemistry , Biological Products/pharmacology , Cell Line, Tumor , China , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Humans , KB Cells , MCF-7 Cells , Oceans and SeasABSTRACT
OBJECTIVE: This study was performed to detect the phosphorylation state of Cx43 in human left ventricular myocardium among sudden deaths caused by acute myocardial ischemia (AMI) especially sudden coronary death (SCD) and control groups. And then evaluate the significance of these findings in diagnosing the early pathological changes of acute myocardial ischemia. METHODS: Immunohistochemistry (IHC) SP techniques were adopted to detect the phosphorylation state of Cx43 in the left ventricular myocardium samples of 45 deceased, which classified as group I--SCD, group II & III (other two groups of AMI) and Group IV & V (two control groups, sudden death caused by lethal acute cranio-cerebral injury or pathologic intracranial hemorrhage). In addition, we selected anti-Pan-Cadherin (construction protein of adherent junctions on the intercalated disc) and PHA-E+L/Bio, to detect the integration of myocardial mechanical coupling and membranes (applying affinityhistochemistry, AHC) respectively. RESULTS: (1) Phosphorylated Cx43 positive staining was almost invisible in Group I, II and III or scattered in sarcoplasm in few samples; but it was assembling at the IDs clearly in group IV and V. (2) Strongly positive staining of Pan-Cadherin could be observed at the IDs and (3) integrated myocardial membranes were found in all samples. CONCLUSION: These findings suggested that compared with the control groups, the integration of myocardial mechanical coupling and membranes did not alter in AMI. But Cx43, the key protein of electrical coupling on myocardial gap junctions, occurred dephosphorylation remarkably in AMI. Thus applying IHC techniques to detect the Cx43 dephosphorylation in human left ventricular myocardium maybe useful to recognize the onset of arrhythmia in AMI, especially in SCD whose myocardium without apparent morphological changes.
Subject(s)
Connexin 43/metabolism , Heart Ventricles/metabolism , Myocardial Ischemia/metabolism , Myocardium/metabolism , Acute Disease , Adolescent , Adult , Aged , Arrhythmias, Cardiac/pathology , Death, Sudden, Cardiac/pathology , Female , Gap Junctions/metabolism , Heart Ventricles/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Myocardial Ischemia/pathology , Myocardium/pathology , Myocardium/ultrastructureABSTRACT
OBJECTIVE: To summarize the experience of treatment on wound infection by non-tuberculous Mycobacterium (NTM) after operations. METHODS: A hundred and sixty-eight patients with NTM incision infection were retrospectively reviewed in terms of diagnosis, treatment and follow-up in a period of 4.5 years. On the basis of the results of in vitro drug sensitivity test, the main antibiotics used were clarithromycin and amikacin. The course of therapy was 4 - 8 months. An extirpative excision was performed in 104 cases following one month treatment by antibiotics and then followed by antibiotic therapy for 3 - 5 months after excision. RESULTS: Primary closure was achieved in 98 of the 104 cases. Fifty patients were cured by the use of antibiotics with dressing change. Eight patients were cured by dressing change without antibiotics. Five children with wound infection by NTM after circumcision were cured by antibiotics with local laser therapy. One patient with infection after hernia operation was cured by amikacin blocking of the area surrounding the lesion. There was no relapse after follow-up for four and half years. CONCLUSION: The study demonstrates that sensitive antibiotics combined with surgery extirpative excision is effective for wound infection by NTM.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium chelonae , Surgical Wound Infection/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Amikacin/administration & dosage , Child , Child, Preschool , Clarithromycin/administration & dosage , Combined Modality Therapy , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Infant , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/surgery , Surgical Wound Infection/surgeryABSTRACT
Gap junctions construct hydrophilic trans-membrane channels which adjust the intercellular communication of chemistry and electricity. In the heart, individual cardiac myocytes are linked by gap junctions. These junctions form low resistance pathways along which the electrical impulse flows rapidly and repeatedly between all the myocardium, ensuring their synchronous contraction. In recent years, some researchers have found that connexins, the protein molecules of gap junction channels, are reduced in number or redistributed from intercalated disks (ID) to lateral cell borders in a variety of cardiac disease, especially in ischemic heart disease. The gap junction remodeling is considered to be arrhythmogenic. These findings will lead us to a new realm in the diagnostic of sudden death caused by coronary heart disease.