Cancer Initiation,Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.     

合作联盟资源集成计划一种新方法

合作联盟里，资源集成计划往往是联盟成员群体谈判博弈的结果。本以两人博弈为例，对联盟的资源集成计划给出一个谈判博弈模型，能够较好地模仿和反映合作联盟资源整合计划的制订过程。     

企业合作联盟成员位次竞争战略的Shapley值分析

针对Yanowitz和Bruckstein的二值字图像后处理算法存在的问题，提出了一种新的基于灰度期望值的后处理算法。实验结果表明，该算法能自动选取阈值、运算速度快、处理效果好，具有良好的噪声适应性。     

On the Convenience to Form Coalitions or Partnerships in Simple Games

A partnership in a cooperative game is a coalition that possesses an internal structure and, simultaneously, behaves as an individual member. Forming partnerships leads to a modification of the original game which differs from the quotient game that arises when one or more coalitions are actually formed. In this paper, the Shapley value is used to discuss the convenience to form either coalitions or partnerships. To this end, the difference between the additive Shapley value of the partnership in the partnership game and the Shapley alliance value of the coalition, and also between the corresponding value of the internal and external players, are analysed. Simple games are especially considered. Research partially supported by Grant BFM 2003-01314 of the Science and Technology Spanish Ministry and the European Regional Development Fund.     

技术联盟的共生演化分析

企业组建技术联盟的根本目的,就是基于自己能力缺陷,分散风险,降低研发成本,共享技术收益,是一个典型的利益共生体.Logistic生物种群共生进化模型给技术联盟共生体提供了一个分析框架.分析结果表明:对于主体不均等的技术联盟,主导企业从合作伙伴中获得的收益是非常有限的,远远低于自己对伙伴企业的贡献,并且这种联盟方式要求企业之间的分工程度要高;而对于主体均等的技术联盟而言,双方的贡献相差不大,都相对比较小.技术联盟企业通过分工形式形成各种关系,以激烈的竞争维持着共生模式的稳定性.     

A simple and simultaneous determination of acyclovir and ganciclovir in human plasma by high-performance liquid chromatography

A simple high-performance liquid chromatographic method was developed for the simultaneous determination of the therapeutic levels of acyclovir and ganciclovir in human plasma. After precipitation of plasma proteins with 6% perchloric acid, acyclovir and ganciclovir were simultaneously determined by reversed-phase chromatography with spectophotometric detection at 254 nm. The peak heights for acyclovir and ganciclovir were linearly related to their concentrations ranging from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and 99.26-103.07% for ganciclovir. The intra- and inter-day relative standard deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424% for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL determined as the signal-to-noise ratio of 3. The present method is applicable to therapeutic monitoring during antiviral medication.     

Identification and quantification of the antipsychotics risperidone,aripiprazole, pipamperone and their major metabolites in plasma using ultra‐high performance liquid chromatography–mass spectrometry

The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra‐high performance liquid chromatography–mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra‐high performance liquid chromatography–mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed‐phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli‐Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9‐OH‐risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run‐time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.     

A rapid and simple HPTLC assay for therapeutic drug monitoring of capecitabine in colorectal cancer patients

Capecitabine is a prodrug of 5‐flurouracil, employed as a broad spectrum chemotherapeutic agent. It is also used as monotherapy or a combination chemotherapy agent for the treatment of colorectal cancer. Capecitabine is administered in combination with oxaliplatin and hence it is essential to determine that co‐administration does not affect its metabolism. To determine the plasma concentration of capecitabine a simple HPTLC method was developed and validated. Blood samples from 12 patients with colorectal cancer were collected and analyzed by the HPTLC method with a reference internal standard. Out of these 12 patients, six were treated with capecitabine monotherapy and another six were treated with capecitabine + oxaliplatin combination therapy. The results of analysis indicated that there was no significant drug–drug interaction and the co‐administration of oxaliplatin did not affect the metabolism of capecitabine. This method is sensitive, robust and specific and allows analysis of multiple samples simultaneously, making it suitable for therapeutic drug monitoring of capecitabine.     

A simple,rapid and reliable liquid chromatography–mass spectrometry method for determination of methotrexate in human plasma and its application to therapeutic drug monitoring

A simple, rapid and reliable liquid chromatography–electrospray ionization tandem mass spectrometry method was established and validated for the determination of methotrexate in human plasma. After a straightforward protein precipitation by acetonitrile–water (70:30, v/v), methotrexate (MTX) and p‐aminoacetophenone (used as internal standard, IS) were separated on a Column C₁₈ column (50 × 2.1 mm, 3 µm; Column Technology, Fremont, CA, USA) using a gradient elution with mobile phase of acetonitrile and 0.03% acetic acid aqueous solution at a flow rate of 0.5 mL/min. The total chromatographic runtime was 5 min for each injection. Quantification detection was performed in a triple‐quadruple tandem mass spectrometer under positive mode monitoring the following mass transitions: m/z 455.3 → 308.3 for MTX and m/z 136.1 → 94.4 for IS. The calibration curve was linear over the range of 0.05–25.0 µmol/L with a lower limit of quantification of 0.05 µmol/L. The intra‐ and interday precisions were <5.2%, the accuracy varied from ?4.1 to 4.5%. The recovery was >94%. The LC‐MS/MS method showed an excellent agreement with the existing HPLC‐UV method using Passing–Bablok regression and Bland–Altman difference plot analysis. The validated LC‐MS/MS can be successfully applied to the routine therapeutic drug monitoring of MTX in clinical laboratories. Copyright © 2015 John Wiley & Sons, Ltd.     

Assessment of antioxidant,cytotoxicity, antibacterial,antifungal, and cutaneous wound healing activities of green synthesized manganese nanoparticles using Ziziphora clinopodioides Lam leaves under in vitro and in vivo condition

In recent decades, nanotechnology is growing rapidly owing to its widespread application in medical science. The aim of the experiment was the evaluation of cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound healing activities of green synthesized manganese nanoparticles using Ziziphora clinopodioides Lam leaves (MnNPs@ZC). The synthesized MnNPs@ZC were characterized using different techniques including UV–Vis., FT-IR spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectrometry (EDS). According to the XRD analysis, 48.10 nm was measured for the crystal size of nanoparticles. SEM images exhibited a uniform spherical morphology and size in the range of 47.58 to 70.26 nm for the biosynthesized nanoparticles. MnNPs@ZC revealed excellent non-cytotoxicity effect against human umbilical vein endothelial cells, antioxidant activity against DPPH, antibacterial properties against Gram-negative bacteria (Salmonella typhimurium, Pseudomonas aeruginosa, and Escherichia coli O157:H7) and Gram-positive bacteria (Streptococcus pneumonia, Staphylococcus aureus, and Bacillus subtilis), and antifungal potentials against Candida glabrata, Candida albicans, Candida guilliermondii, and Candida krusei. Also, use of MnNPs@ZC ointment decreased significantly (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and raised significantly (p ≤ 0.01) the wound contracture, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate compared to other groups in experimental animals. In conclusion, synthesized MnNPs@ZC indicated antibacterial, antifungal, non-cytotoxicity, antioxidant, and cutaneous wound healing effects in a dose-depended manner. After confirming in the clinical trials, these nanoparticles can be used in human for the treatment of cutaneous and infectious diseases.