bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhance Recovery of Methane from Gas Hydrate Reservoirs with CO2 sequestration
Authors: Nisha Gulshan , Harini Ch Geeta
Published: November 2012

Gas hydrates are an energy resource composed of natural gas in a solid state, in which water molecules, are in a relatively stable composition, surround the gas molecules. One volume of gas hydrates is equivalent to about 164 volumes of methane. Gas hydrates may represent more than twice the energy content of all other hydrocarbon resources. Gas hydrates are in equilibrium under conditions of high pressures and low temperatures; they occur in arctic regions (permafrost) and on the continental shelf - in marine surface and subsurface deposits. The importance of gas hydrates is related to their potential for exploration and production as a source of natural gas; to the known problems they cause in drilling and production systems; to their climate change effects - negative (GHG) and positive (CO2 sequestration).

Presently, depressurization, thermal stimulation, inhibitor injection, or a combination of these methods have been considered as possible means of producing gas hydrate. Another method for gas hydrate production involves the injection of CO2. The idea of swapping CO2 for CH4 in gas hydrates was first advanced by Ohgaki et al. (1996) and then for ethane hydrate by Nakano et al. (1998). Their concept involves injecting CO2 gas, which is then allowed to equilibrate with methane hydrate along the three-phase equilibrium boundary. Because of the difference in chemical affinity for CO2 versus methane in the sI hydrate structure, the mole fraction of methane would be reduced to approximately 0.48 in the hydrate and rise to a value of 0.7 in the gas phase at equilibrium.

The concept for enhanced gas hydrate recovery (EGHR) discussed in this paper takes advantage of the physical and thermodynamic properties of CO2 combined with control of multiphase flow, heat, and transport processes hydrate mass in porous media carriers.
Execution of a Field Development under Changing Environments Influenced by the Arab Spring - Applied Risk Management Strategies and Mitigation Measurements
Authors: Schick Klaus Juergen , Krusche Klaus
Published: November 2012

OMV is currently developing the Habban Oil Field in the Shabwa Region of Yemen. During the Arab Spring the security situation in the Country deteriorated and OMV had to suspend its operations. This Case study describes how OMV handled the new situation dealing with increased uncertainty about the political stability in Yemen and the consequences arising from this uncertainty.
Optimized Shale Resource Development: Proper Placement of Wells and Hydraulic Fracture Stages
Authors: Kennedy Robert L. , Gupta Rajdeep , Kotov Sergey , Burton W. Aaron , Knecht William N. , Ahmed Usman
Published: November 2012

During the past six years, the technology for shale gas/oil developments in North America has seen many improvements and optimizations as the industry experiences a sharp rise in the contribution of hydrocarbons from these resources. More recently, Europe and Australia have joined the US in expanding recoverable hydrocarbons from these unconventional resources, and initial activities are on the rise in Latin America, China, Saudi Arabia and India. Despite such improvements and optimizations, a closer look at the performance reveals that not all wells are producing commercially. In addition, the hydraulic fracture stages are not all contributing within the producing wells. This scenario potentially suggests that it is important to target the field's sweet spots while dealing with shale resources (like most other hydrocarbon-bearing formations). Hence, resource development based on the current concepts of geometric placement of hydraulic fracture stages (e.g., using fixed well/fracture spacing) may not be appropriate to develop such heterogeneous unconventional resource basins. In the discussion we illustrate certain well-defined criteria that can identify the sweet spot locations within a field/basin for the optimal well placement. We further document the vital formation/zone characteristics that define the locations for hydraulic fracture stages and thus move away from the arbitrary geometric placement.

The paper will discuss the well-placement optimization process and identify the required combination of proposed special petrophysical, geochemical, and geomechanical investigations (wireline, Logging While Drilling and cores). The hydraulic fracture stage placement analysis as presented, shoulders on the need to understand the existing natural fracture system. This understanding is achieved through geophysical log measurements and comprehensive analysis of the hydraulic fracture development pattern, as well as interaction of hydraulic fractures at each stage with the natural fractures. A naturally fractured reservoir can be drained more efficiently if a complex fracture network can be created by the hydraulic fracture stimulation. This begins by drilling the well in the direction of minimum principle horizontal stress in the area.

The paper concludes by presenting examples demonstrating the practical application of some of the specific aspects of the methodology discussed and with a number of specific conclusions. In summary, the three key points to Proper Placement of Wells and Hydraulic Fracture Stages, in order to maximize the net value of an operator's asset are:

Begin With a Complete Understanding of the Reservoir Use a Multidiscipline and Integrated Approach Across Each Phase of the Life Cycle Effectively Use Modern Technology
Executing Mega Projects and Key Lessons Learned
Authors: Shaukat Azfar
Published: November 2012

Mega projects are easy to identify and are usually defined as those requiring investment of $1 billion or more. Typical projects include Olympic developments, numerous airports, hydropower and large power generation schemes, major rail developments and even relatively modest Oil & Gas projects. The Middle East, of course, is no stranger to mega projects and Masdar City, Yas Island, and the Bmj Khalifa are just some recent examples successfully completed in the UAE alone. This paper considers the challenges of managing mega projects and identifies some key lessons learned.

Considerable effort is being applied worldwide to understand the success factors better for mega projects so that expensive and damaging mistakes can be avoided. The following summary of lessons learned is drawn from Mott MacDonald's experience of undertaking mega projects across many sectors all over the world, particularly from Oil & Gas:

No single project owner or leader Poor project definition Technical solutions too far beyond the state-of-the-art Realism overtaken by enthusiasm for the project Political interference Not keeping stakeholders involved Weak procedures and processes to effectively manage the project Economic climate at time of construction quite different from the planning stage Client or project team inexperience Contractual disputes Not being prepared for things going wrong - they inevitably will Not retaining learnings for the next mega project

More is known now on the challenges of managing mega projects than ever before, however, the learnings from previous projects are not always disseminated to help with the next one. It is hoped this paper will go some way towards improving the understanding of why mega projects often struggle and what can be done to make sure they don't.

Mega projects are usually defined as those requiring investment of $1 billion or more and are easy to identify. Under this definition even relatively modest Oil & Gas projects easily qualify automatically as "mega-projects," as well as the more obvious major LNG and GTL schemes. Other typical examples include Olympic developments, airports, hydropower and large power generation schemes, and major rail developments. The Middle East, of course, is no stranger to mega projects and Masdar City, Yas Island, and the Bmj Khalifa are just some recent examples successfully completed in the UAE alone. Almost by definition, a specific mega project will not have been done before in that particular location, hence almost every aspect will be new, with problems being encountered for the first time there.
Increase LNG Exports by Innovative Use of Communications Technology
Authors: Khader Emad S , Voorspoels Kris
Published: November 2012

The safe loading/unloading of LNG tankers depends on high integrity communications links between the tanker and shore systems to ensure the fail-safe operation of a two way shut-down signal.

The most common existing system is fiber optic cable-based and was developed in the 1980s. While it has the advantage of simplicity and reasonable reliability, it fails to meet the changing requirements of LNG tanker operations. A more flexible system is overdue.

Our company in cooperation with international telecommunications solutions providers is developing a microwave-based system that addresses the shortcoming of the existing system. Importantly, by having the potential to shave a few hours off loading and unloading times, more shipments can be delivered from existing terminals.

The proposed system utilizes the same standards-based fiber optic multiplexing equipment currently popular with LNG plants, integrates it with carrier-grade microwave radios and automatic antennae alignment units to allow automatic connectivity while the tanker is approaching the jetty. The advantages of this approach are, Shorter loading/unloading turnaround times as system testing can start before the tanker is tied to the loading jetty.By having seamless integration with LNG plant systems and networks, smarter services and functionality can be developed in the future.By having bandwidth orders of magnitude higher than existing system and a flexible multiplexor, more services can be made available now to tanker and crew.
Petrographic Features of Kerogen in Unconventional Shales and Their Effect on Hydrocarbon Petrophysics
Authors: Chen Jin-Hong , Li Baoyan , Georgi Daniel , Chen Jacie , Yang Wendy
Published: November 2012

Despite the extensive use of new technologies for the exploration of unconventional organic rich shale resources and vast work on the prediction of the quantities of light hydrocarbons (Gas in Place, GIP), many questions remaining concerning the storage, migration and production of natural gas in unconventional gas shales. There is a need for a deeper understanding of the physics and chemistry of light hydrocarbon molecules within the micro- and nanopores in the kerogen. A number of research results have been published that emphasize the importance of nanopores in kerogen for the unconventional shale resource plays, and our previously published laboratory results have shown that it is possible for gas to condense into liquid in the nanopores of kerogen once the Kelvin equation is satisfied.

Petrographic features of several Woodford shale core samples were studied using Scanning Electron Microscopy (SEM) on splintered and Focused Ion Beam (FIB) milled surfaces. The morphologic features and the connectivity of the pores in kerogen were recorded. We performed gas condensation experiments on these samples using hexane and found that there is a close relationship between the amount of condensed gas and the porosity within the kerogen. Based on the nanopore physics the flow of gas within the organic matter will be significantly impacted by capillary condensation. Nuclear Magnetic Resonance (NMR) measurement on the samples with condensed gas components show that the relaxation is also significantly affected by the properties of the nanopores within the kerogen of the unconventional shale samples and must be properly accounted for in the formation evaluation.
H2S Risk Management
Authors: El-Sanabary Mohamed , Macwan Nancy
Published: November 2012

Manuscript

Description

This paper is developed for highlighting the required balance between establishment of minimum requirements for PREVENTING accidents related to toxic gas and Oxygen deficiency exposure and being prepared in case of emergency.

Significance of this paper

This paper could help in better understanding and prevention of future toxic or hazardous atmosphere accidents.

The "Tie Bow" graph shown hereunder is explaining barriers and controls prior to reaching the top event (accident). It is explaining as well the control and recovery measures post happening of the "top event" too. So, it is not a matter of just distributing personnel detector and emergency escape sets.
Utility and Integration of Non Seismic Data in Kurdistan
Authors: Mumaw Gary R
Published: November 2012

The increasing complexity of new exploration targets requires the use of both seismic and non-seismic methods in the exploration process. This is readily achieved by integrated workstation software that enables simultaneous interpretation and modelling of both data sets. Where 2D seismic control is sparse and highly ambiguous, Gravity and Magnetic data provide additional independent measurement of the subsurface; and a more reliable integrated interpretation of complex geologic structure, adding value and reducing risk. Further, continuous improvement in data resolution and sensitivity [from land, marine and airborne acquisition and processing systems] are making completely new applications possible, expanding Potential Fields methods from regional ‘reconnaissance’ tools into prospect scale and to some extent, reservoir scale, including both 3D full tensor gravity (3D-FTG) and magnetic gradiometry technology. Unfortunately, turmoil in the region has prevented their airborne survey deployment to date but this could readily change with improving political stability in Iraq-Kurdistan. Meanwhile, high quality public domain regional space mission ‘satellite derived’ gravity and magnetic data provides the focus for understanding and mapping the tectonic framework: basement architecture and distribution of igneous bodies. Structural information so derived can be combined with basement depth estimation to improve understanding of basin morphology, evolution and the petroleum system. It can also prove valuable in identifying continuity between well and seismic data. This paper demonstrates the utility and integration of regional scale public domain non seismic data to assist with the local scale structural model and prospectivity assessments of some high fold zone blocks of interest in NE Iraq/Kurdistan. The Bazian (Block) anticline is used to illustrate a typical local scale feature for evaluation.
Synthesis of Quinazolines as Tyrosine Kinase Inhibitors
Authors: Srivastava Sanjay K. , Kumar Vivek , Agarwal Shiv K. , Mukherjee Rama , Burman Anand C.
Published: November 2012

In the present review, the discovery and development of quinazoline as tyrosine kinase inhibitors has been described. The synthesis of most potent quinazoline inhibitors of EGFR, VEGFR and PDGRF has been discussed. Structure activity relationship for quinazoline as tyrosine kinase inhibitors has been established. It was found that C-4, C-6 and C-7 positions in quinazoline are appropriate sites for designing new tyrosine kinase inhibitors. This review should help the medicinal chemist in designing more effective tyrosine kinase inhibitors.
A Trojan Horse in Drug Development: Targeting of Thapsigargins Towards Prostate Cancer Cells
Authors: Christensen S. Brogger , Skytte Dorthe Mondrup , Denmeade Samuel R. , Dionne Craig , Moller Jesper Vuust , Nissen Poul , Isaacs John T.
Published: November 2012

Available chemotherapeutics take advantage of the fast proliferation of cancer cells. Consequently slow growth makes androgen refractory prostate cancer resistant towards available drugs. No treatment is available at the present, when the cancer has developed metastases outside the prostate (T4 stage). Cytotoxins killing cells irrespective of the phase of the cell cycle will be able to kill slowly proliferating prostate cancer cells. Lack of selectivity, however, prevents their use as systemic drugs. Prostate cancer cells secrete characteristic proteolytic enzymes, e.g. PSA and hK2, with unusual substrate specificity. Conjugation of cytotoxins with peptides, which are selective substrates for PSA or hK2, will afford prodrugs, from which the active drug only will be released in close vicinity of the cancer cells. Based on this strategy prodrugs targeted at prostate cancer cells have been constructed and evaluated as potential drugs for prostate cancer. The potency of the thapsigargins as apoptotic agents make these naturally occurring sesquiterpene lactones attractive lead compounds. Intensive studies on structure-activity relationships and chemistry of the thapsigargins have enabled construction of potent derivatives enabling conjugation with peptides. Studies on the mechanism of action of the thapsigargins have revealed that the cytoxicity is based on their ability to inhibit the intracellular sarco-/endoplasmtic calcium pump.
Quantification Techniques and Biodistribution of Semiconductor Quantum Dots
Authors: Pic Emilie , Bezdetnaya Lina , Guillemin Francois , Marchal Frederic
Published: November 2012

Quantum dots (QDs) are fluorescent inorganic nanocrystals with advantageous optical properties, which have been applied for biomedical purposes including imaging, diagnostic, drug delivery or therapy. Potential toxicity of QDs remains the major barrier to clinical translation, and as such the precise analysis of in vivo QDs distribution and pharmacokinetics is of major importance. Biodistribution studies in animal models are, however, sparse. The present review provides in a first lieu a summary of different techniques, which are currently used for relative quantification of QDs in vivo or their absolute quantification ex vivo. Fluorescence and radioactivity based techniques along with mass-spectrometry detection at the elementary level are addressed in this review. We further introduce biodistribution studies in animal models and discuss the possibilities to modify quantum dots biodistribution in function of different injection ways.
Novel Analogues of CC-1065 and the Duocarmycins for the Use in Targeted Tumour Therapies
Authors: Tietze Lutz F. , Krewer Birgit
Published: November 2012

In recent years, a series of new and highly cytotoxic analogues of CC-1065 and the duocarmycins have been developed that can be transformed into much less toxic prodrugs for the use in antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) and prodrug monotherapy (PMT) of cancer. In all these approaches, a relatively non-toxic prodrug is applied and subsequently converted selectively in the tumour tissue into a highly cytotoxic drug, thus reducing undesired side effects accompanying conventional chemotherapy. Here, the design and biological evaluation of prodrugs based on analogues of CC-1065 and the duocarmycins for the use in tumour selective cancer therapies is reviewed. The advantage of this approach is the excellent therapeutic index of some of the new prodrugs of over 5000 and the high cytotoxicity of the corresponding drugs with IC50 values of as low as 16 pM (IC50: concentration required for 50 % growth inhibition of target cells). In addition, a novel method for the correlation of the alkylation efficiency and the cytotoxicity based on mass spectrometry is described.
Current Development of Pd(II) Complexes as Potential Antitumor Agents
Authors: Gao Enjun , Liu Cong , Zhu Mingchang , Lin Huakuan , Wu Qiong , Liu Lei
Published: November 2012

Research has proven that the most effective and widely used metal-containing chemotherapy anticancer drugs are cisplatin ([cis-PtCl2(NH3)2]) and many platinum complexes, however, these compounds have significant disadvantages including poor water solubility and serious side effects. Thus researches in order to overcome these shortcomings have never interrupted. Many non-platinum complexes have been synthesized and tested, in which some palladium complexes show significant antitumor activity in normal tumor cells and lower resistance of tumor cells to clinical treatments as well as lower side effects. Mononuclear palladium complexes with aromatic N-containing ligands, amino acid ligands, S-donor ligands, and P-containing ligands have respective qualities and properties due to the different structures and properties of the ligands; some dinuclear palladium complexes possess interesting steric structures and good antitumor activity; a try to modify natural medicines with Pd2+ leads the research to a new route. In this review, medicinal chemistry, the development status and interactions of palladium complexes with DNA are discussed in order to provide guidance and determine structure and antitumor activity relationships for continuing studies of these systems.
The Effects of Cantharidin and Cantharidin Derivates on Tumour Cells
Authors: Liu Dongwu , Chen Zhiwei
Published: November 2012

Natural product extracts are a rich source of small molecules that display antitumor activity. Cantharidin, in the form of the dried body of the Chinese blister beetles: Mylabris phalerata or M. cichorii, displays antitumor activity and induces apoptosis in many types of tumor cells. Cantharidin has been used as an anticancer agent by the Chinese for the treatment of hepatoma and oesophageal carcinoma for a long time. Although cantharidin is a natural toxin that possesses potent anti-tumor properties, its clinical application is limited due to severe side-effects and highly toxic nature. Therefore, some modified cantharidin analogues are synthesized chemically in order to achieve a comparable antitumour property to the mother compound but simultaneously produce a less toxic effect on non-cancer cells. In recent years, based on the structure of cantharidin, there has been intense interest in developing potent and selective inhibitors of PP1 and PP2A on tumour cells. Though numerous analogues of cantharidin have been synthesized and researched with tumour cell lines, there is little success on clinical application because of the potential toxicity of cantharidin derivates. The focus of this review is to describe how cantharidin and cantharidin derivates participate in antitumour processes in tumour cells, and discuss the molecular mechanisms of cantharidin and cantharidin derivates on tumour cells.
Cytotoxic and Anticancer Activities of Isatin and Its Derivatives: A Comprehensive Review from 2000-2008
Authors: Vine K. L. , Matesic L. , Locke J. M. , Ranson M. , Skropeta D.
Published: November 2012

Isatin (1H-indole-2,3-dione) and its derivatives demonstrate a diverse array of biological and pharmacological activities including anticonvulsant, antibacterial, antifungal, antiviral and anticancer properties. This broad spectrum of biochemical targets has been facilitated by the synthetic versatility of isatin, which has allowed the generation of a large number of structurally diverse derivatives including analogues derived from substitution of the aryl ring, and/or derivatisation of the isatin nitrogen and C2/C3 carbonyl moieties. The recent FDA approval of the oxindole sunitinib malate, as a kinase inhibitor for the treatment of advanced renal carcinoma and gastrointestinal stromal tumours, underscores the increasing interest in isatins as a new class of antineoplastic agents. In addition to potent kinase inhibition, the mechanism of action of other isatin derivatives includes the inhibition and/or modulation of proteases, translation initiation, neo-vascularisation and tubulin polymerisation. It was therefore the objective of this review to systematically evaluate the cytotoxic and anticancer properties of various substituted isatins and collate these findings to be used as a guide for future structure-activity relationship and mode of action studies. This is the first review to comprehensively discuss the in vitro and in vivo anticancer activities of isatin and its substituted derivatives.
Recent Advances in the Development of P-gp Inhibitors
Authors: Baumert Christiane , Hilgeroth Andreas
Published: November 2012

During the last decades multidrug resistance (MDR) emerged as main problem in the anti-cancer therapy with cytostatically active agents. Classical as well as recently developed cytostatics develop the phenomenon of loosing activity in former drug-sensitive cells. Although MDR is a multifactorial process, the main obstacle is the expression of multidrug-efflux pumps that lowers the intracellular drug levels. P-glycoprotein (P-gp) is the longest identified efflux pump. As the attempt to overcome MDR by the use of inhibitors of the efflux pump activities turned out as most promising effect, the development of P-gp inhibitors has been a challenge for medicinal chemists. The article reviews the advances in P-gp inhibitor development by focussing on structure-activity relationships in the different compound classes to document improvements. The success has been the reduction of cytotoxic properties. The undesired activities could be much lowered in the case of compound classes that were derived from pharmacologically active drugs. Undesired drug interactions and limited in vivo activities are still a problem.
Discovery of 4-Aryl-4H-Chromenes as Potent Apoptosis Inducers Using a Cell- and Caspase-Based Anti-Cancer Screening Apoptosis Program (ASAP): SAR Studies and the Identification of Novel Vascular Disrupting Agents
Authors: Cai Sui Xiong , Drewe John , Kemnitzer William
Published: November 2012

Many cancer cells are known to have defects in the apoptosis machinery. Therefore identification of compounds that can activate or promote apoptosis in cancer cells is an attractive approach for targeted therapies. By applying a novel cell- and caspase-based Anti-cancer Screening Apoptosis Program (ASAP) HTS assay, 4-aryl-4H-chromenes were identified as potent apoptosis inducers. 4- Aryl-4H-chromenes were found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G2/M stage followed by apoptosis as determined by the flow cytometry analysis assay in multiple human cell lines (e.g. Jurkat, T47D). These compounds were found to be highly active in the growth inhibition MTT assay, including for paclitaxel resistant, p-glycoprotein overexpressed, MESSA/ DX5 tumor cells. Functionally, they were found to be potent inhibitors of tubulin polymerization and to effectively inhibit the binding of colchicine to tubulin. In addition, several 4-aryl-4H-chromenes were also found to be effective vascular disrupting agents (VDA). One of the lead compounds, EPC2407, is currently in clinical trials as a novel tumor vascular disrupting agent.
Urea Derivatives as Anticancer Agents
Authors: Li Huan-Qiu , Lv Peng-Cheng , Yan Tao , Zhu Hai-Liang
Published: November 2012

Within the past ten years, a huge volume of research on the synthesis, structure-activity relationships (SAR), and anticancer activities of the urea derivatives was reported. Many aromatic urea derivatives such as N-phenyl-N-(2-chloroethyl)ureas (CEUs) and benzoylureas (BUs) show good anticancer activity, and these compounds have mainly been proved to be tubulin ligands that inhibit the polymerization of tubulin. Heterocyclic urea derivatives play an important role in anticancer agents because of their good inhibitory activity against receptor tyrosine kinases (RTKs), raf kinases, protein tyrosine kinases (PTKs), and NADH oxidase, which play critical roles in many aspects of tumorigenesis. Thiourea derivatives are also of wide interest because of their diverse anticancer activity against various leukemias and solid tumors. In this review, the anticancer activity of the urea derivatives mentioned above is summarized in detail. It is hoped that increasing knowledge of the SAR and cellular processes underlying the antitumor-activity of urea derivatives will be beneficial to the rational design of new generation of urea anticancer drugs.
Silibinin – A Promising New Treatment for Cancer
Authors: Wing Ying Cheung Catherine , Gibbons Norma , Wayne Johnson David , Lawrence Nicol David
Published: November 2012

Silymarin and its major constituent, Silibinin, are extracts from the medicinal plant Silybum marianum (milk thistle) and have traditionally been used for the treatment of liver diseases. Recently, these orally active, flavonoid agents have also been shown to exert significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. The aim of the present review is to examine the pharmacokinetics, mechanisms, effectiveness and adverse effects of silibinins anti-cancer actions reported to date in pre-clinical and clinical trials. The review will also discuss the results of current research efforts seeking to determine the extent to which the effectiveness of silibinin as an adjunct cancer treatment is influenced by such factors as histologic subtype, hormonal status, stromal interactions and drug metabolising gene polymorphisms. The results of these studies may help to more precisely target and dose silibinin therapy to optimise clinical outcomes for oncology patients.
Telomere Maintenance as Therapeutic Target in Embryonal Tumours
Authors: Shalaby T. , Hiyama E. , Grotzer M.A.
Published: November 2012

Embryonal tumours most commonly occur in the first few years of life and account for approximately 30% of childhood malignancies. Knowledge of these tumours genetics has already impacted on their clinical management and further knowledge of their cellular immortalization will hopefully result in novel therapies. The ends of human chromosomes are capped and protected by telomeres; cellular replication, however, causes their loss. A critical length of telomere repeats is required to ensure proper telomere function and avoid the activation of DNA damage pathways that result in senescence and cell death. To proliferate beyond the senescence checkpoint, cells must restore their telomere length. Hence stabilization of telomere is an important step in cell immortalization and carcinogenesis. Telomere maintenance is evident in virtually all types of malignant cells, including embryonal tumours, where either a telomerase-dependent or alternative lengthening of telomeres (ALT) mechanism is employed in order to ensure their limitless replicative potential. For this reason effective strategies targeting telomere maintenance in cancer cells require a combination of telomerase and ALT inhibitors. In this review, we are giving an overview about telomere maintenance in childhood tumours and discussing its potential as a new therapeutic target.
The Vitamin D/CYP24A1 Story in Cancer
Authors: N. King Amanda , G. Beer David , J. Christensen Paul , U. Simpson Robert , Ramnath Nithya
Published: November 2012

There is increasing evidence linking the incidence of certain cancers to low serum Vitamin D levels. The active metabolite of Vitamin D, calcitriol (1, 25-Dihydroxyvitamin D3, 1,25(OH)2D3) apart from a crucial role in maintaining mineral homeostasis and skeletal functions, has antiproliferative, apoptosis and differentiation inducing as well as immunomodulatory effects in cancer. In studying the role of 1,25(OH)2D3 in cancer, it is imperative to examine the potential pathways that control local tissue levels of 1,25(OH)2D3. The enzyme CYP24A1 or 24-hydroxylase converts 1,25(OH)2D3 to inactive calcitroic acid. Extra-renal production of this enzyme is observed and has been increasingly recognized as present in cancer cells. This enzyme is rate limiting for the amount of local 1,25(OH)2D3 in cancer tissues and elevated expression is associated with an adverse prognosis. The gene that encodes CYP24A1 has been reported as an oncogene and may contribute to tumor aggressiveness by abrogating local anti-cancer effects of 1,25(OH)2D3. It is imperative to study the regulation of CYP24A1 in cancer and especially the local metabolism of 1,25(OH)2D3 in cancer cells. CYP24A1 may be a predictive marker of 1,25(OH)2D3 efficacy in patients with cancer as an adjunctive therapy. The following review summarizes the available literature on CYP24A1 as it relates to 1,25(OH)2D3 in cancer and outlines potential ways to inhibit CYP24A1 in an effort to improve the efficacy of exogenous 1,25(OH)2D3.
Recent Advances and Future Directions in the Management of Metastatic Renal Cell Carcinoma
Authors: Ansari J. , Glaholm J. , McMenemin R. , James N.D. , Hussain S.A.
Published: November 2012

A better understanding of the molecular biology of renal cell carcinoma (RCC) and the emergence of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for patients with metastatic RCC (mRCC). Multikinase inhibitors (sunitinib and sorafenib) and the inhibitors of mammalian target of rapamycin (temsirolimus and everolimus) have recently shown superiority over IFN-α or placebo; and bevacizumab + IFN-α have demonstrated improved activity when compared to IFN-α alone in patients with mRCC. Newer antivascular endothelial growth factor (VEGF) agents such as axitinib, pazopanib and cediranib are currently under investigation to expand and elucidate future treatment options. Several studies have investigated the synergistic potential of TKIs with a view to blocking multiple signalling pathways simultaneously, but this approach has resulted in a significant increase in toxicity. Sequential TKI administration has demonstrated encouraging results but the optimal sequence of TKIs is yet to be determined. Studies combining TKIs with immunotherapy have resulted in varying degrees of success; with bevacizumab + IFN-α being the only studies with positive outcomes. The purpose of this review is to summarize the current evidence supporting the role of TKIs and to discuss potential future directions in the management of mRCC. The role of TKIs as monotherapy, in combination with immunotherapy or other TKIs (combined or sequential approach) will be discussed.
Recent Researches in Metal Supramolecular Complexes as Anticancer Agents
Authors: Zhou Cheng-He , Zhang Yi-Yi , Yan Cong-Yan , Wan Kun , Gan Lin-Ling , Shi Yuan
Published: November 2012

The research and development of metal supramolecular complexes as anticancer supramolecular drugs, which are aggregates mainly formed by one or more inorganic metal compounds with one or more either inorganic or organic molecules in general via coordination bonds, has been a quite rapidly developing, increasingly active and newly rising highlight interdisciplinary field. Numerous efforts have been directed toward metal supramolecular complexes as potential anticancer agents and the unprecedented progress has been made. This has opened up a wholly new and infinite space to create novel metal-based bioactive supermolecules. More importantly, metal-based complex supermolecules as potential anticancer agents with wide potential applications have become highlight topics in recent years, and are becoming increasingly useful and important in preventing and treating cancer diseases. In view of the rapid progress in metal complex anticancer supermolecules with rich variation of structural types, this work systematically reviewed the recent research and development of the whole range of metal-based supramolecular complexes as anticancer agents mainly in 2009. The perspectives of the foreseeable future and potential application of metal supramolecular complexes in cancer therapy were also presented. It is hoped that this review will serve as a stimulant for new thoughts in the quest for rational designs of more active and less toxic metal supramolecular complex anticancer drugs.
Therapeutic Exploitation of Apoptosis and Autophagy for Glioblastoma
Authors: Kogel Donat , Fulda Simone , Mittelbronn Michel
Published: November 2012

Induction of caspase-dependent apoptosis (type I cell death) is a major mechanism by which most chemotherapeutic drugs and radiation kill tumor cells. However, conventional cancer therapies fail to mediate their effects in a target-specific fashion. The extremely unfavorable prognosis for patients suffering from glioblastomas (GBMs) is strongly correlated to the intrinsic apoptosis resistance of GBM cells which especially occurs in diffusely migrating tumor cells. The ultimate goal for molecular, apoptosis-based therapies is to target specific components of the two major apoptotic pathways, i.e. the extrinsic and the intrinsic pathway to trigger tumor-selective apoptosis, while at the same time limiting toxicity in normal tissues. Induction of autophagic cell death (type II cell death) by proautophagic drugs is an alternative and emerging concept to trigger glioma cell death and to exploit caspase-independent programmed cell death pathways for the development of novel glioma therapies. This review provides an up to date and comprehensive report on the relevant pre-clinical and clinical drugs interfering with the major apoptosis and autophagy pathways, their therapeutic potential in glioma and adresses potential future perspectives in this exciting field of research.
Exploiting Cyclooxygenase-(in)Dependent Properties of COX-2 Inhibitors for Malignant Glioma Therapy
Authors: H. Schonthal Axel
Published: November 2012

Cyclooxygenase 2 (COX-2) is frequently found up-regulated during pathological conditions and in cancer, where it is thought to support carcinogenesis and tumor angiogenesis. The development of newer-generation non-steroidal anti-inflammatory drugs (NSAIDs) able to more selectively inhibit cyclooxygenase 2 (COX-2) raised expectations that these agents might be beneficial for cancer prevention and therapy. However, while chemopreventive effects of some selective COX-2 inhibitors have been established, it has remained unpersuasive whether these new NSAIDs, such as celecoxib, rofecoxib or etoricoxib, are able to exert cancer therapeutic effects, i.e., whether they would be beneficial for the treatment of advanced cancers that are already grown and established. This issue was further complicated by findings that celecoxib was able to exert pronounced pro-apoptotic effects in vitro and in vivo in the absence of any apparent involvement of COX-2. In fact, newly synthesized close structural analogs of the celecoxib molecule revealed that it was possible to separate COX-2 inhibitory function from the ability to trigger apoptosis; for example, the analog 2,5-dimethyl-celecoxib (DMC) has lost COX-2 inhibitory function, yet exerts increased cytotoxic potency. This review will summarize pertinent results from the exploratory therapeutic use of NSAIDs, in particular celecoxib, in preclinical and clinical studies of malignant glioma. Several COX-2 independent targets will be presented, and it will be discussed how DMC has helped to delineate their relevance for the surmised COX-2 independent tumoricidal effects of celecoxib.
Mouse Induced Glioma-Initiating Cell Models and Therapeutic Targets
Authors: Kondo Toru
Published: November 2012

Both stem cells and cancer cells are thought to be capable of unlimited self-renewal. Moreover, a small number of cancer cells express stem cell markers, including CD133 and ATP-binding cassette transporters through which the cells can pump out anti-cancer drugs or specific fluorescence dyes such as Hoechst33342, suggesting that either cancer cells resemble stem cells or that cancers contain stem cell-like cancer cells, called cancer-initiating cells (CICs) or cancer stem cells. Using the common characteristics of tissue-specific stem cells, malignant tumors and cancer cell lines were shown to contain CICs, which self-renew and are tumorigenic. CICs are also resistant to both irradiation and chemotherapy. These findings suggest that CICs are critical targets for successful therapy. However, CICs have not been well characterized, due to a lack of specific markers. We recently established mouse glioma-initiating cell (GIC) lines by overexpressing oncogenic HRasL61 in p53-deficient neural cells. These cells form transplantable glioblastoma multiforme (GBM) with features of human GBM when as few as 10 cells are transplanted in vivo, suggesting that these GIC-like cells are enriched in CICs. Characterization of these GICs showed that they expressed little or no Sox11. The overexpression of exogenous Sox11 in GICs blocked their tumorigenesis by inducing their neuronal differentiation, which was accompanied by decreased levels of a novel oncogene, plagl1. These findings suggest that Sox11 and Plagl1 work as a tumor suppressor and oncogene, respectively, in GBM and are potential therapeutic targets.
Obesity Modulation - The Role in Carcinogenesis
Authors: Legakis Ioannis , Syrigos Kostantinos
Published: November 2012

Obesity has been recognized as an important risk factor for many serious medical conditions. The association of obesity with an increased risk of many cancers is of enormous economic importance to the health industry.The metabolic syndrome and visceral obesity have an increasing prevelance and incidence in the general population.The actual prevelance of the metabolic syndrome is 24% in US population and between 24.6% and 30.9% in Europe. Recent evidence from epidemiologic and basic research studies, as well as clinical and intervention studies, supports the emerging hypothesis that metabolic syndrome may be an important etiologic factor for the onset of cancer. In addition, increased body weight has recently been shown to be associated with an increased risk of cancers at multiple specific sites. The close interaction between cancer cells and adipocytes is an intriguing issue in tumor biology. In nowdays, several metabolic markers are implicated in the development and progression of several malignancies. This review describes the emerging data concerning the role of metabolic markes in tumor cell growth and relates them to their future clinical prospects.
Combination Therapy with Arsenic Trioxide for Hematological Malignancies
Authors: Takahashi Shinichiro
Published: November 2012

Arsenic trioxide (ATO) has shown great promise in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APL). However, the risk/benefit ratios of ATO in hematologic malignancies other than APL are still unclear. In this review, the author attempts to provide current experimental and clinical challenges to gain more knowledge of the effects of ATO by examining combination therapies with other agents, especially for non-APL hematologic malignancies, such as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and multiple myeloma (MM). The drugs combined with ATO can be roughly classified into (1) signaling inhibitors (imatinib, PD184352, LY294002, 17-Allylamino- 17-demethoxygeldanamycin: 17-AAG), (2) oxidative stress pathway modulators (ascorbic acid, 2-methoxyestradiol: 2-ME, dlbuthionine-[ S,R]-sulfoximine: BSO), (3) a chemotherapeutic drug (melphalan) and (4) others (bortezomib, ATRA). Some of these combination therapies have shown promising results in MM not only at the experimental level but also at the clinical level. However, studies are still ongoing for other non-APL hematologic malignancies. Since ATO is well tolerated and its toxicities are manageable and reversible, cell type-specific and efficient combination therapies with ATO are advantageous for non-APL hematological malignancies and should be developed in the near future.
Development of a Terminal Control System with Variable Minimum Airflow Rate
Authors: Cho Young-Hum
Published: November 2012

A constant minimum airflow rate is used in conventional Single Duct Variable Air Volume Terminal Box control sequences. This control sequence can cause occupant discomfort or use excessive energy under partial load conditions. If the minimum airflow rate is higher than required; terminal boxes will have significantly more simultaneous heating and cooling; and AHUs will consume more fan power. Buildings will have indoor air quality problems if the minimum airflow rate is less than required. Many engineers and researchers have investigated advanced variable air volume terminal box control algorithms without a system retrofit for thermal comfort; indoor air quality and energy savings. In this study a developed control system with variable minimum airflow rate for Single Duct Variable Air Volume Terminal Boxes was applied and validated using an actual building and evaluated for comfort; indoor air quality and energy consumption. The energy consumption and thermal performance of terminal boxes using the conventional and proposed control algorithms were compared.
A Statistical Assessment of the Impact of Agricultural Land Use Intensity on Regional Surface Water Quality at Multiple Scales
Authors: Zhang Weiwei , Li Hong , Sun Danfeng , Zhou Liandi
Published: November 2012

Understanding the effects of intensive agricultural land use activities on water resources is essential for natural resource management and environmental improvement. In this paper, multi-scale nested watersheds were delineated and the relationships between two representative water quality indexes and agricultural land use intensity were assessed and quantified for the year 2000 using multi-scale regression analysis. The results show that the log-transformed nitrate-nitrogen (NO3-N) index exhibited a relationship with chemical fertilizer input intensity and several natural factors, including soil loss, rainfall and sunlight at the first order watershed scale, while permanganate index (CODMn) had a positive relationship with another two input intensities of pesticides and agricultural plastic mulch and organic manure at the fifth order watershed scale. The first order watershed and the fifth order watershed were considered as the watershed adaptive response units for NO3-N and CODMn, respectively. The adjustment of agricultural input and its intensity may be carried out inside the individual watershed adaptive response unit. The multiple linear regression model demonstrated the cause-and-effect relationship between agricultural land use intensity and stream water quality at multiple scales, which is an important factor for the maintenance of stream water quality.
Characteristics and Trends of Hospitalized Pediatric Abuse Head Trauma in Wuhan, China: 2002–2011
Authors: Xia Xin , Xiang Joe , Shao Jianbo , Smith Gary , Yu Chuanhua , Zhu Huiping , Xiang Huiyun
Published: November 2012

This study investigated characteristics and trends of hospitalized abuse-related traumatic brain injuries (TBI) treated at a large pediatric medical center in Wuhan, China during the past 10 years. De-identified hospital discharge data for patients 0–4 years old hospitalized at the Wuhan Medical Care Center for Women and Children were analyzed, and ICD-10 codes were used to identify cases of TBI. Medical notes provided by doctors in the medical record were used to identify TBI cases in which suspected child abuse was the cause. From 2002 to 2011, 3,061 pediatric TBI patients were hospitalized and 4.6% (140) of these cases were suspected child abuse-related. The majority of suspected child abuse cases involved children younger than 1 year of age (68.6%) and usually affected males (63.6%). Children with non-Abusive Head Trauma (AHT) were more likely to have full recovery outcome (68.4%, 95% CI: 66.6%–70.0%) than children with suspected AHT (44.3%, 95% CI: 36.1%–52.5%). The proportion of all childhood TBI attributable to abuse did not appear to have increased in the 10-year period at this medical center. This is the first comprehensive study highlighting the important role of suspected child abuse in causing TBIs among Chinese children. Child abuse as a major cause of TBIs among infants in China should be studied further, and there should be greater awareness of this important social and medical problem in China.