Treatment for Advanced Prostatic Cancer

Recently, there has been a proliferation of experimental and clinical data supporting early androgen deprivation for advanced prostatic cancer, due to the new insights provided by a more thorough understanding of prostate cancer biology. The logn term survival of patients with prostatic metastatic disease will require the development of novel treatment strategies truly effective against anti-androgen-resistant tumor cells and their use in concert with early androgen deprivation. To date, no evidence has been generated in experimental animal or human models of prostate cancer that supports the previous concept of delayed hormonal therapy. The development of luteinizing hormone-releasing hormone (LHRH) agonists and the anti-androgens has prompted a resurgence of interest in initial total androgen blockade, and the inhibition of the activity of 5-alpha reductase could provide a safe and effective way to remove prostatic intraepithelial dihydrotestosterone, resulting in a diminishing production of growth factors. The rationale for the use of Sumarin in the treatment of stage D prostatic cancer refractory to conventional hormonal manipulation is its ability to block the activity of several growth factors, including basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), etc. which have been postulated to have important roles in prostatic cell biolgy

Volumetric analysis and indocyanine green retention rate at 15 min as predictors of post‐hepatectomy liver failure

AbstractObjectivesThe actual future liver remnant (aFLR) is calculated as the ratio of remnant liver volume (RLV) to total functional liver volume (TFLV). The standardized future liver remnant (sFLR) is calculated as the ratio of RLV to standard liver volume (SLV). The aims of this study were to compare the aFLR with the sFLR and to determine criteria for safe hepatectomy using computed tomography volumetry and indocyanine green retention rate at 15 min (ICG R15).MethodsMedical records and volumetric measurements were obtained retrospectively for 81 patients who underwent right hemi‐hepatectomy for malignant hepatic tumours from January 2010 to November 2013. The sFLR was compared with the aFLR, and a ratio of sFLR to ICG R15 as a predictor of postoperative hepatic function was established.ResultsIn patients without cirrhosis, the sFLR showed a stronger correlation with the total serum bilirubin level than the aFLR (R2 = 0.499 versus R2 = 0.239). Post‐hepatectomy liver failure developed only in the group with an sFLR of <25%, regardless of ICG R15. In patients with cirrhosis, the aFLR and sFLR had no correlation with postoperative total serum bilirubin. An sFLR : ICG R15 ratio of >1.9 showed 66.7% sensitivity and 100% specificity.ConclusionsRegardless of ICG R15, an sFLR of ≥25% in patients without cirrhosis, and an sFLR of ≥25% with an sFLR : ICG R15 ratio of >1.9 in patients with cirrhosis indicate acceptable levels of safety in major hepatectomy

A High-Speed Range-Matching TCAM for Storage-Efficient Packet Classification

Abstract—A critical issue in the use of TCAMs for packet classification is how to efficiently represent rules with ranges, known as range matching. A range-matching ternary content addressable memory (RM-TCAM) including a highly functional range-matching cell (RMC) is presented in this paper. By offering various range operators, the RM-TCAM can reduce storage expansion ratio from 4.21 to 1.01 compared with conventional TCAMs, under real-world packet classification rule sets, which results in reduced power consumption and die area. A new pre-discharging match-line scheme is used to realize high-speed searching in a dynamic match-line structure. An additional charge-recycling driver further reduces the power consumption of search lines. Simulation results of a 256 64-bit range-matching TCAM, when implemented in the 0.13- m CMOS technology, achieves a 1.99-ns search time with an energy efficiency of 1.26 fJ/bit/search. While a TCAM including range encoding approach requires an additional SRAM or DRAM, the RM-TCAM can improve storage efficiency without any extra components as well as reduce the die area

Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake

Laparoscopic Total Mesorectal Excision in a Rectal Cancer Patient with Situs Inversus Totalis

Situs inversus totalis is a rare anomaly in which the abdominal and thoracic cavity structures are opposite their usual positions. A 41-yr-old woman, who had an ulcerating cancer on the rectum, was found as a case of situs inversus totalis. We present an overview of the operative technique for the first documented laparoscopic total mesorectal excision of a rectal cancer in the patient with situs inversus totalis. Careful consideration of the mirror-image anatomy permitted a safe operation using techniques not otherwise different from those used for the general population. Therefore, curative laparoscopic surgery for rectal cancer in this patient is feasible and safe

Identification of DNA methylation changes associated with human gastric cancer

<p>Abstract</p> <p>Background</p> <p>Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.</p> <p>Methods</p> <p>We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm.</p> <p>Results</p> <p>We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the <it>HOX </it>and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (<it>MDM2</it>, <it>DYRK2</it>, and <it>LYZ</it>) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.</p> <p>Conclusions</p> <p>Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.</p

Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways

BACKGROUND: Nitric oxide (NO) is generally increased during inflammatory airway diseases. This increased NO stimulates the secretion of mucin from the goblet cell and submucosal glands but the mechanism is still unknown precisely. In this study, we investigated potential signaling pathways involving protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) in the NO-induced MUC5AC mucin gene and protein expression in A549 cells. METHODS: Nitric oxide was donated to the A549 cells by NOR-1. MUC5AC mucin levels were assayed by enzyme-linked immunosorbent assay (ELISA). MUC5AC promoter activity was determined by measuring luciferase activity after the lysing the transfected cells. Activation of PKC isoforms were measured by assessing the distribution of the enzyme between cytosolic and membrane fractions using immunoblotting. Immunoblotting experiments using a monoclonal antibody specific to PKC isoforms were performed in the cytosol and membrane fractions from A549 cells. Western blot analysis for pERK and p38 were performed using the corresponding antibodies from the cell lysates after donating NO to the A549 cells by NOR-1. RESULTS: The transcriptional activity of MUC5AC promoter was maximal at the concentration of 0.1 mM NOR-1 for 1 hour incubation in transfected A549 cells. (±)-(E)-methyl-2-((E)-hydroxyimino)-5-nitro-6-methoxy-3-hexenamide (NOR-1) markedly displaced the protein kinase C (PKC)α and PKCδ from the cytosol to the membrane. Furthermore, the PKC-α,βinhibitors, GÖ6976 (10 nM) and PKCδ inhibitors, rottlerin (4 μM) inhibited the NOR-1 induced migration of PKCα and PKCδ respectively. NOR-1 also markedly increased the MUC5AC promoter activity and mRNA expression, mucin synthesis and ERK1/2 phosphorylation. The PKC inhibitors also inhibited the NOR-1 induced MUC5AC mRNA and MUC5AC protein synthesis by inhibiting the activation of PKCα and PKCδ with ERK1/2 pathways. CONCLUSION: Exogenous NO induced the MUC5AC mucin gene and protein through the PKCα and PKCδ – ERK pathways in A549 cells. Inhibition of PKC attenuated NO-mediated MUC5AC mucin synthesis. In view of this findings, PKC inhibitors might be useful in the treatment of bronchial asthma and chronic bronchitis patients where NO and mucus are increased in the bronchial airways