Weekly induction intraperitoneal chemotherapy after primary surgical cytoreduction in patients with advanced epithelial ovarian cancer

BACKGROUND: Traditional intraperitoneal (IP) therapy administered simultaneously with intravenous (IV) chemotherapy in the primary setting has been well documented. This retrospective study was conducted to investigate the role of weekly IP therapy as an inducing intervention before front-line IV chemotherapy, particularly in patients with bulky residual disease after surgery. METHODS: A total of 426 patients with advanced ovarian cancer treated between 1990 and 1999, were reviewed. Follow-up data were available in 409 patients. Of whom, 230 patients received postoperative weekly IP therapy with a median cycles of 4, other 179 patients who did not receive any IP therapy were used as the control group. RESULTS: The median age of the patients was 51 years (range, 20–77 years). One hundred eighty-nine patients with stage III disease and 41 patients with stage IV disease were treated with postoperative IP therapy, respectively. Complications and toxicity were observed in 68 patients (29.5%), but there were no grade 4 toxicities and no patients died of complications or toxicities. In patients with residual disease > 1 cm, the median survival of those with IP delivery of chemotherapy and those without was 21.6 months and 18.8 months, respectively (hazard ratio [HR]= 0.69, P = 0.02). Whereas, in patients with residual disease ≤ 1 cm, the median survival was 46.8 months and 37.6 months, respectively (HR= 0.73, P = 0.09). Multivariate analysis suggested that the factors age ≤ 60 years, stage III, IP therapy and paclitaxel as front-line chemotherapy were associated with a better prognosis for patients with advanced ovarian cancer. CONCLUSION: Weekly postoperative IP therapy as an inducing intervention is practical for both physicians and patients with acceptable complications and associated with a lengthened survival of patients with advanced ovarian cancer. Whether this arm can be used in lieu of a traditional one needs further randomized trial to confirm the preliminary results

Four new isoflavanones from Tadehagi triquetrum

Four new isoflavanones with isoprenoid units, named triquetrumones E-H (1–4), were isolated from the whole plants of Tadehagi triquetrum. The structures were elucidated on the basis of spectroscopic analyses, including application of MS, UV, IR, 1D and 2D NMR spectroscopic techniques. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13659-011-0033-5 and is accessible for authorized users

Deletion of Aquaporin-4 in APP/PS1 Mice Exacerbates Brain Aβ Accumulation and Memory Deficits

BACKGROUND: Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer\u27s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent. RESULTS: Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignificant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples. CONCLUSIONS: These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD

Antitumor Efficacy and Mechanism in Hepatoma H22-Bearing Mice of Brucea javanica

Brucea javanica is a traditional herbal medicine in China, and its antitumor activities are of research interest. Brucea javanica oil, extracted with ether and refined with 10% ethyl alcohol from Brucea javanica seed, was used to treat hepatoma H22-bearing mice in this study. The antitumor effect and probable mechanisms of the extracted Brucea javanica oil were studied in H22-bearing mice by WBC count, GOT, GPT levels, and western blotting. The H22 tumor inhibition ratio of 0.5, 1, and 1.5 g/kg bw Brucea javanica oil were 15.64%, 23.87%, and 38.27%. Brucea javanica oil could inhibit the involution of thymus induced by H22 tumor-bearing, but it could not inhibit the augmentation of spleen and liver. Brucea javanica oil could decrease the levels of WBC count and GOT and GPT in H22-bearing mice. The protein levels of GAPDH, Akt, TGF-β1, and α-SMA in tumor tissues decreased after being treated with Brucea javanica oil. Disturbing energy metabolism and neoplastic hyperplasia controlled by Akt and immunoregulation activity were its probable antitumor mechanisms in hepatoma H22-bearing mice

Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer

AbstractThe epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell–cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl− and HCO3− conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-β1-induced EMT and enhances cell migration and invasion in MCF-7. Ectopic overexpression of CFTR in a highly metastatic MDA-231 breast cancer cell line downregulates EMT markers and suppresses cell invasion and migration in vitro, as well as metastasis in vivo. The EMT-suppressing effect of CFTR is found to be associated with its ability to inhibit NFκB targeting urokinase-type plasminogen activator (uPA), known to be involved in the regulation of EMT. More importantly, CFTR expression is found significantly downregulated in primary human breast cancer samples, and is closely associated with poor prognosis in different cohorts of breast cancer patients. Taken together, the present study has demonstrated a previously undefined role of CFTR as an EMT suppressor and its potential as a prognostic indicator in breast cancer

Two New Clerodane-type Diterpenoids from Gomphostemma microdon

Two new clerodane-type diterpenoids, along with seven known compounds have been isolated from the aerial parts of Gomphostemma microdon. All structures were established on the basis of spectroscopic analyses, including application of MS, UV, IR, 1D and 2D NMR techniques

What Differs on the Enzymatic Acetylation Mechanisms for Arylamines and Arylhydrazines Substrates? A Theoretical Study

The acetylation mechanisms of several selected typical substrates from experiments, including arylamines and arylhydrazines, are investigated with the density functional theory in this paper. The results indicate that all the transition states are characterized by a four-membered ring structure, and hydralazine (HDZ) is the most potent substrate. The bioactivity for all the compounds is increased in a sequence of PABA ≈ 4-AS < 4-MA < 5-AS ≈ INH < HDZ. The conjunction effect and the delocalization of the lone pairs of N atom play a key role in the reaction. All the results are consistent with the experimental data

Clock Synchronization in Wireless Sensor Networks: A New Model and Analysis Approach Based on Networked Control Perspective

Motivated by the importance of the clock synchronization in wireless sensor networks (WSNs), this paper proposes a new research approach and model approach, which quantitatively analyzes clock synchronization from the perspective of modern control theory. Two kinds of control strategies are used as examples to analyze the effect of the control strategy on clock synchronization from different perspectives, namely, the single-step optimal control and the LQG global optimal control. The proposed method establishes a state space model for clock relationship, thus making dimension extension and parameter identification easier, and is robust to changes under the condition of node failures and new nodes. And through the design of different control strategies and performance index functions, the method can satisfy various requirements of the synchronization precision, convergence speed, energy consumption and the computational complexity, and so on. Finally, the simulations show that the synchronization accuracy of the proposed method is higher than that of the existing protocol, and the former convergence speed of the synchronization error is faster

Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression

Background and objectiveDepression is a complex neuropsychiatric disease with extensive morbidity. Its pathogenesis remains unclear, and it is associated with extremely low rates of cure and complete remission. It is vital to study the pathogenesis of depression to develop effective treatments. This study aimed to explore the therapeutic effects and mechanisms of fecal microbiota transplantation (FMT) for the treatment of depression in rats.MethodsThirty Sprague-Dawley (SD) rats were randomly divided into three groups: control, chronic unpredictable mild stress (CUMS) to model depression, and CUMS+FMT. For the CUMS and CUMS+FMT groups, after CUMS intervention (four weeks), the rats were given normal saline or FMT (once/week for three weeks), respectively. Behavior, colonic motility, 16S rDNA amplicon sequencing, and untargeted metabolomics on fecal samples were compared between the three rat groups. The following markers were analyzed: 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), and brain-derived neurotrophic factor (BDNF) levels in the hippocampus; glucagon-like peptide 1 (GLP-1), lipopolysaccharide (LPS), and interleukin (IL)-6 levels in the serum; and GLP-1, GLP-1 receptor (GLP-1R), and serotonin 4 receptor (5-HT4R) levels in colonic tissues.ResultsFMT improved symptoms of depression and colonic motility in rats exposed to CUMS. The expression levels of 5-HT, GABA, BDNF, and other biochemical indices, significantly differed among the three groups. Meanwhile, the intestinal microbiota in the CUMS+FMT group was more similar to that of the control group with a total of 13 different fecal metabolites.ConclusionFMT exerted antidepressant effects on CUMS-induced depression in rats, and the mechanism involved various neurotransmitters, inflammatory factors, neurotrophic factors, and glucagon-like peptides

Clock Synchronization in Wireless Sensor Networks: Analysis and Design of Error Precision Based on Lossy Networked Control Perspective

Motivated by the importance of the clock synchronization in wireless sensor networks (WSNs), due to the packet loss, the synchronization error variance is a random variable and may exceed the designed boundary of the synchronization variance. Based on the clock synchronization state space model, this paper establishes the model of synchronization error variance analysis and design issues. In the analysis issue, assuming sensor nodes exchange clock information in the network with packet loss, we find a minimum clock information packet arrival rate in order to guarantee the synchronization precision at synchronization node. In the design issue, assuming sensor node freely schedules whether to send the clock information, we look for an optimal clock information exchange rate between synchronization node and reference node which offers the optimal tradeoff between energy consumption and synchronization precision at synchronization node. Finally, simulations further verify the validity of clock synchronization analysis and design from the perspective of synchronization error variance