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Bentham Science Publishers

Publications in this journal

• Non-invasive delivery of iRNAs, proteins, peptides, cytokines and nanoparticles.

  Authors: Bingmei M Fu

  Current pharmaceutical biotechnology.

• Ultrasound-Induced Blood-Brain Barrier Opening.

  Authors: Elisa E Konofagou, Yao-Sheng Tung, James Choi, Thomas Deffieux, Babak Baseri, Fotios Vlachos

  Current pharmaceutical biotechnology.

  Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS).Over 4 million U.S. men and women suffer from Alzheimer's disease; 1 million from Parkinson's disease; 350,000 from multiple sclerosis (MS); and 20,000 from amyotrophic lateral sclerosis (ALS). Worldwide, these four diseases account for more than 20 million patients. In addition, aging greatly increases the risk of neurodegenerative disease. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of the 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. On the other hand, safe and localized opening of the BBB has been proven to present a significant challenge. Of the methods used for BBB disruption shown to be effective, Focused Ultrasound (FUS), in conjunction with microbubbles, is the only technique that can induce localized BBB opening noninvasively and regionally. FUS may thus have a huge impact in trans-BBB brain drug delivery. The primary objective in this paper is to elucidate the interactions between ultrasound, microbubbles and the local microenvironment during BBB opening with FUS, which are responsible for inducing the BBB disruption. The mechanism of the BBB opening in vivo is monitored through the MRI and passive cavitation detection (PCD), and the safety of BBB disruption is assessed using H&E histology at distinct pressures, pulse lengths and microbubble diameters. It is hereby shown that the BBB can be disrupted safely and transiently under specific acoustic (pressures under 0.45 MPa) and microbubble (diameter under 8 µm) conditions.

• Nanocarriers for the Simultaneous Co-Delivery of Therapeutic Genes and Anticancer Drugs.

  Authors: Nazia Choudhury, Huixin He

  Current pharmaceutical biotechnology.

  Due to the molecular complexity of cancer, combination therapy is becoming increasingly important for better long-term prognosis with fewer side effects. To further increase the therapeutic effects,Due to the molecular complexity of cancer, combination therapy is becoming increasingly important for better long-term prognosis with fewer side effects. To further increase the therapeutic effects, advanced drug delivery systems (DDSs), capable of simultaneously delivering multiple drugs to the site of action with specific time-programmed release profiles, are important requirements. Nanocarriers for the simultaneous co-delivery of multiple chemical drugs in combination therapy have been extensively reviewed. Here we focus on the nanotechnology enabled DDSs for the simultaneous co-delivery of therapeutic genes and chemical drugs for cancer treatment. The opportunities for this combination strategy and their challenges will be discussed.

• Release of Growth Factors, Cytokines and Therapeutic Molecules by Hyaluronan-based Hydrogels.

  Authors: Robert A Peattie

  Current pharmaceutical biotechnology.

  Hyaluronan (HA) is a highly biocompatible biopolymer that is widely used for a variety of therapeutic purposes including surgical preparations, adhesion prevention, viscosupplementation and drug andHyaluronan (HA) is a highly biocompatible biopolymer that is widely used for a variety of therapeutic purposes including surgical preparations, adhesion prevention, viscosupplementation and drug and cytokine delivery. Delivery can be accomplished effectively when HA-based carriers are synthesized in the form of hydrogels, though doing so normally requires chemical modification of the native HA structure. Solute delivery from HA-based gels can be either "simple", that is from a gel not including separate components intended to control release, or "regulated" when specific components are included for that purpose. A variety of modified forms of HA have been developed and used for delivery of desired molecules in therapeutic, clinical, veterinary and laboratory research environments, and the number of such applications is likely to grow in future years.

• Carbon Monoxide - A Toxic Gas on the Edge to Clinical Application.

  Authors: Rene Schmidt

  Current pharmaceutical biotechnology.

• Role of Carbon monoxide in vascular diseases.

  Authors: Ignazio Barbagallo, Giuseppina Marrazzo, Alessandro Frigiola, Agata Zappala, Giovanni Li Volti

  Current pharmaceutical biotechnology.

  During the degradation of heme by the enzyme heme oxygenase (HO), Carbon monoxide (CO) is generated. Although it is considered as a non - significant and potentially toxic waste gas of hemeDuring the degradation of heme by the enzyme heme oxygenase (HO), Carbon monoxide (CO) is generated. Although it is considered as a non - significant and potentially toxic waste gas of heme catabolism, CO is a key signaling molecule used to regulate different cardiovascular functions. In this review, we focus the protective roles of CO in vascular injury/disease, which may be important to explore the overall protective roles of HO-1/CO system in the pathogenesis of human vascular disease. Key Words: Carbon monoxide, Heme oxygenase, oxidative stress, hypertension, vascular diseases.

• Heme Oxygenase-1/CO as Protective Mediators in Cigarette Smoke-Induced Lung Cell Injury and Chronic Obstructive Pulmonary Disease.

  Authors: Tamás Dolinay, Augustine Mk Choi, Stefan W Ryter

  Current pharmaceutical biotechnology.

  Chronic obstructive pulmonary disease (COPD) is a disease involving airways restriction, alveolar destruction, and loss of lung function, primarily due to cigarette smoke (CS) exposure. The inducibleChronic obstructive pulmonary disease (COPD) is a disease involving airways restriction, alveolar destruction, and loss of lung function, primarily due to cigarette smoke (CS) exposure. The inducible stress protein heme oxygenase-1 (HO-1) has been implicated in cytoprotection against the toxic action of many xenobiotics, including CS. HO-1 also protects against elastase-induced emphysema. Differential expression of HO-1 in epithelial cells and macrophages may contribute to COPD susceptibility. Genetic polymorphisms in the HO-1 gene, which may account for variations in HO-1 expression among subpopulations, may be associated with COPD pathogenesis. Carbon monoxide (CO), a primary reaction product of HO-1 has been implicated in cytoprotection in many acute lung injury models, though it's precise role in chronic CS-induced lung injury remains unclear. CO is a potential biomarker of CS exposure and of inflammatory lung conditions. To date, a single clinical trial has addressed the possible therapeutic potential of CO in COPD patients. The implications of the cytoprotective potential of HO-1/CO system in CS-induced lung injury and COPD are discussed.

• Cytoprotection by Inhaled Carbon Monoxide before Cardiopulmonary Bypass in Preclinical Models.

  Authors: Torsten Loop, Christian Schlensak, Ulrich Goebel

  Current pharmaceutical biotechnology.

  Although a potentially toxic gaseous molecule, carbon monoxide recently gains rising scientifically and clinical interest as its beneficial effects and mechanisms of action are defined substantiallyAlthough a potentially toxic gaseous molecule, carbon monoxide recently gains rising scientifically and clinical interest as its beneficial effects and mechanisms of action are defined substantially in various in vitro and in vivo experiments. Its anti-inflammatory, anti-apoptotic and anti-proliferative properties but its increasing impact concerning numerous disease models in means of protection, well describe this gas as a new and challenging therapeutic alternative. In this review, we focus on the extensively analyzed advantageous value of pre- and postconditioning with inhaled carbon monoxide in the context of lung and kidney injury, induced by the low perfusion during and after cardiopulmonary bypass. Mechanisms like the heat shock response as well as an expanded view regarding toxicity and side effects are described broadly.

• Carbon Monoxide - Toxicity of Low-Dose Application.

  Authors: Rene Schmidt, Helen Ryan, Alexander Hoetzel

  Current pharmaceutical biotechnology.

  Carbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoningCarbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoning in industrial countries. However, after two decades of intensive research, there is ample evidence that CO endogenously produced by heme oxygenase enzymes has essential physiological functions and is of vital importance for cellular hemostasis. Furthermore, exogenously applied CO in low concentrations mediates potent cytoprotective effects. An overwhelming number of different in vitro and in vivo models demonstrated the protective action of CO application, e.g., in ischemia/reperfusion, transplantation, oxidative stress, inflammation, and others. Protection by this gaseous molecule could be illustrated for most organs, most species, and for different routes of administration. Now being on the verge of entering clinical trials, the question emerges whether the administration of low-dose CO would be safe for patients when used as a potential therapeutic. Therefore, this review summarizes in particular toxicological data obtained from low-dose CO exposure and discusses its impact on a possible clinical application.

• Antibacterial Effects of Carbon Monoxide.

  Authors: Jayne Louise Wilson, Helen E Jesse, Robert K Poole, Kelly S Davidge

  Current pharmaceutical biotechnology.

  Carbon monoxide (CO) is a colourless and odourless gas that has long been considered as a potent respiratory poison. Recent advances have demonstrated its production by haem oxygenases in bothCarbon monoxide (CO) is a colourless and odourless gas that has long been considered as a potent respiratory poison. Recent advances have demonstrated its production by haem oxygenases in both mammals and microbes, and it has roles as a gasotransmitter in higher organisms. This review concentrates on the application of CO, via carbon monoxide-releasing molecules (CO-RMs), as an anti-bacterial agent. Currently, the scope of literature on the effects of CO on bacteria is small, and we have included discussions on the production of CO by bacteria via haem oxygenase enzymes, the use of CO as an energy source, and existing knowledge on CO sensors in bacteria. CO is known to target haem proteins and is an effective inhibitor of respiration, even when provided at concentrations much higher than prevailing oxygen. We review here data suggesting that CO-RMs are more effective inhibitors of respiration than is CO gas, perhaps due to the ability of CO-RMs to deliver CO selectively to intracellular targets. We also consider the recently reported transcriptomic consequences of CO-RM treatment of Escherichia coli, revealing a myriad of unexpected targets for CO and potential CO sensors. Finally, we consider the use of CO and CO-RMs as anti-bacterial agents in vivo, and the future prospects for this gaseous molecule.

• Critical Issues In Delivery of RNAi Therapeutics In Vivo.

  Authors: Stephanie Rivera, Fan Yuan

  Current pharmaceutical biotechnology.

  RNA interference (RNAi) is a fundamental mechanism of gene regulation and has been harnessed to produce a new class of drugs for treatment of various diseases. A key issue in these applications isRNA interference (RNAi) is a fundamental mechanism of gene regulation and has been harnessed to produce a new class of drugs for treatment of various diseases. A key issue in these applications is how to effectively deliver RNAi therapeutics into target cells. This review is focused on advances in RNA delivery in vivo. To achieve it, novel strategies have been developed to enhance stability of RNA in cells and tissues, overcome barriers to transport of RNA or its carriers in the body, and reduce immunogenicity and cytotoxicity of treatment. Approaches to RNA delivery are divided into three categories in this review: biological, chemical, and physical. Advantages and disadvantages of each method are discussed. At present, effective delivery of RNAi therapeutics in vivo is still a challenge although significant advances have been made in this field.

• Pharmacokinetics/Pharmacodynamics Model-Supported Early Drug Development.

  Authors: Bin Chen, Jennifer Q Dong, Wei-Jian Pan, Ana Ruiz

  Current pharmaceutical biotechnology.

  Pharmacokinetic/pharmacodynamic (PK/PD) modeling & simulation (M&S) provides quantitative assessment of dose/exposure-response relationships with extensive applications at the late stage drugPharmacokinetic/pharmacodynamic (PK/PD) modeling & simulation (M&S) provides quantitative assessment of dose/exposure-response relationships with extensive applications at the late stage drug development as well as during regulatory decision making. However, at preclinical and early phase clinical drug development, the importance of PK/PD M&S has not been as widely recognized. We reviewed selected PK/PD M&S literatures in order to convey importance of M&S in these early development phases. We focused on the application of M&S to select and optimize lead candidates, the use of preclinical PK/PD data to project the range of clinical doses, and the development of comprehensive dose/exposure-response models that can be used to forecast the probability of achieving a target response based on Phase 1 safety, PK and biomarker information. We also reviewed several other M&S approaches that are often used in early drug development such as physiologically-based pharmacokinetic (PBPK) modeling, meta-analysis, PK-pharmacogenomics modeling, and etc. Our aims were to provide expert opinions on the practical utility of PK/PD model-based approaches that have positive impact on early decision-making with the goal of improving the success rate of early to late stage drug development.

• Experimental Methods and Transport Models for Drug Delivery across the Blood-Brain Barrier.

  Authors: Bingmei M Fu

  Current pharmaceutical biotechnology.

  The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the micro-environment of the brain. Although the special anatomical features of the BBB determine its protective role forThe blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the micro-environment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-born neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This review summarized the unique structures of the BBB, described a variety of in vivo and in vitro experimental methods for determining the transport properties of the BBB, e.g., the permeability of the BBB to water, ions, and solutes including nutrients, therapeutic agents and drug carriers, and presented newly developed mathematical models which quantitatively correlate the anatomical structures of the BBB with its barrier functions. Finally, on the basis of the experimental observations and the quantitative models, several strategies for drug delivery through the BBB were proposed.

• Challenges and Strategies in Developing Microneedle Patches For Transdermal Delivery of Protein and Peptide Therapeutics.

  Authors: Fei Wu, Sixing Yang, Weien Yuan, Tuo Jin

  Current pharmaceutical biotechnology.

  The birth of microneedles, an array of needles sufficiently long to penetrate epidermis but small enough to do not cause skin injury and pain feeling, has offered a highly promising solution forThe birth of microneedles, an array of needles sufficiently long to penetrate epidermis but small enough to do not cause skin injury and pain feeling, has offered a highly promising solution for non-invasive delivery of protein and peptide drugs, a long-cherished desire over eighty years. However, the attempts to develop clinically feasible microneedle transdermal delivery methods encountered series of difficulties, for which a decade research efforts have yet to result in a single product. Microneedles may be incorporated into devices as skin pre-treatment tools, skin microinjectors as well as transdermal patches by their functions in drug delivery. They may also be categorized to insoluble solid microneedles, hollow microneedles, soluble/degradable solid microneedles and phase-transition microneedles by their structure and forming materials. This review article is aimed to update the progress and discuss the technical challenges raised in developing protein/peptide loaded microneedle patches.

• Nanocarriers to solid tumors: considerations on tumor penetration and exposure of tumor cells to therapeutic agents.

  Authors: Manali Bhagat, Susan Halligan, Stavroula Sofou

  Current pharmaceutical biotechnology.

  Solid tumors constitute the majority of diagnosed cancers. For effective killing, therapeutic agents should ideally be delivered uniformly and at lethal doses to all cancer cells comprising theSolid tumors constitute the majority of diagnosed cancers. For effective killing, therapeutic agents should ideally be delivered uniformly and at lethal doses to all cancer cells comprising the tumors, while keeping normal organ toxicities to a minimum. This requirement sets two of the major challenges in drug delivery to solid cancers: uniformity in delivery, and delivery of at least a minimum amount of therapeutics per cancer cell. Herein we review various approaches that aim to improve the penetration and content release of delivered therapeutic agents from nanocarriers of self-assembling nature. Biophysical characteristics of solid tumors are briefly discussed to motivate and rationalize the design of reported nanoparticle structures. This review does not aim to be exhaustive of the various designs and strategies, but to mostly give a flavor of the general current directions aiming to address these challenges.

• Carbon monoxide, a Two-Face for the protection of the liver.

  Authors: Florian Bösch, Tung Yu Tsui

  Current pharmaceutical biotechnology.

  Carbon monoxide is generally believed to be a 'toxic' gas molecule due to its binding capability with hemoglobin. Overexposure to carbon monoxide leads to a hypoxic state that may cause the death ofCarbon monoxide is generally believed to be a 'toxic' gas molecule due to its binding capability with hemoglobin. Overexposure to carbon monoxide leads to a hypoxic state that may cause the death of a mammalian. In contrast, directly exposure of carbon monoxide may protect cells or organs from various disease insults. The paradox effects of carbon monoxide might vary on the ways of exposure and the amounts being exposed. Here we highlighted the characteristics of this gas molecule and summarized its protective effects and therapeutic potentials in liver diseases and liver transplantation.

• Role of Carbon Monoxide in Kidney Function: Is a little Carbon Monoxide Good for the Kidney?

  Authors: Eva Csongradi, Luis A Juncos, Heather A Drummond, Trinity Vera, David E Stec

  Current pharmaceutical biotechnology.

  Carbon monoxide (CO) is an endogenously produced gas resulting from the degradation of heme by heme oxygense or from fatty acid oxidation. Heme oxygenase (HO) enzymes are constitutively expressed inCarbon monoxide (CO) is an endogenously produced gas resulting from the degradation of heme by heme oxygense or from fatty acid oxidation. Heme oxygenase (HO) enzymes are constitutively expressed in the kidney (HO-2) and HO-1 is induced in the kidney in response to several physiological and pathological stimuli. While the beneficial actions of HO in the kidney have been recognized for some time, the important role of CO in mediating these effects has not been fully examined. Recent studies using CO inhalation therapy and carbon monoxide releasing molecules (CORMs) are demonstrating that increases in CO alone can be beneficial to the kidney in several forms of acute renal injury by limiting oxidative injury, decreasing cell apoptosis, and promoting cell survival pathways. Renal CO is also emerging as a major regulator of renal vascular and tubular function acting to protect the renal vasculature against excessive vasoconstriction and to promote natriuresis by limiting sodium reabsorption in tubule cells. Within this review, recent studies on the physiological actions of CO in the kidney will be explored as well as the potential therapeutic avenues that are being developed targeting CO in the kidney which may be beneficial in diseases such as acute renal failure and hypertension.

• Carbon Monoxide In Acute Lung Injury.

  Authors: Simone Faller, Alexander Hoetzel

  Current pharmaceutical biotechnology.

  Despite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new andDespite modern clinical practice in critical care medicine, acute lung injury still causes unacceptably high rates of morbidity and mortality. Therefore, the challenge today is to identify new and effective strategies in order to improve the outcome of these patients. Carbon monoxide, endogenously produced by the heme oxygenase enzyme system, has emerged as promising gaseous therapeutic that exerts protective effects against inflammation, oxidative and mechanical stress, and apoptosis, thus potentially limiting acute lung injury. In this review we discuss the effects of inhaled carbon monoxide on acute lung injury that results from ischemia-reperfusion, transplantation, sepsis, hyperoxia, or mechanical ventilation, the latter referred to as ventilator-induced lung injury. Multiple investigations using in vivo and in vitro models have demonstrated anti-inflammatory, anti-apoptotic, and anti-proliferative properties of carbon monoxide in the lung when applied at low dose prior to or during stressful stimuli. The molecular mechanisms that are modulated by carbon monoxide exposure are still not fully understood. Carbon monoxide mediated lung protection involves several signaling pathways including mitogen activated protein kinases, nuclear factor-κB, activator protein-1, Akt, peroxisome proliferating-activated receptor-γ, early growth response-1, caveolin-1, hypoxia-inducible factor-1α, caspases, Bcl-2-family members, heat shock proteins, or molecules of the fibrinolytic axis. At present, clinical trials on the efficacy and safety of CO investigate whether the promising laboratory findings might be translatable to humans.

• Application of Carbon Monoxide for Transplantation.

  Authors: Atsunori Nakao, Yoshiya Toyoda

  Current pharmaceutical biotechnology.

  Carbon monoxide (CO) is an invisible, chemically inert, colorless and odorless gas and is toxic at high concentrations due to its interference with oxygen delivery. However, CO is endogenously andCarbon monoxide (CO) is an invisible, chemically inert, colorless and odorless gas and is toxic at high concentrations due to its interference with oxygen delivery. However, CO is endogenously and physiologically generated in mammalian cells via the catabolism of heme in a rate-limiting step of heme oxygenase systems, and CO potently protects against cellular injury. CO relaxes blood vessels and exerts anti-thrombotic effects by inhibiting platelet aggregation and derepressing fibrinolysis. In addition, CO reduces ischemia/reperfusion injury and inflammatory responses. CO inhibits apoptosis of endothelial and epithelial cells and reduces proliferation of smooth muscle cells, fibroblasts and T lymphocytes. Thus, there is accumulating evidence to support the notion that CO treatment of transplant donors, organs, or recipients can prevent graft dysfunction due to rejection or ischemia/reperfusion injury. This invited review discusses recent advances and current knowledge pertaining to CO research in the field of transplantation. In addition, we will discuss the clinical applicability of CO as a promising therapeutic strategy for the treatment of transplant patients.

• Carbon Monoxide and the Pancreas.

  Authors: Christian I Schwer

  Current pharmaceutical biotechnology.

  Carbon monoxide (CO), often referred to as the silent killer, is a colorless, odorless and tasteless gas. It combines with hemoglobin to produce carboxyhemoglobin, which is ineffective for deliveringCarbon monoxide (CO), often referred to as the silent killer, is a colorless, odorless and tasteless gas. It combines with hemoglobin to produce carboxyhemoglobin, which is ineffective for delivering oxygen to animal and human tissues. On the other hand, CO is endogenously produced in the body as a byproduct of heme degradation catalyzed by the heme oxygenase (HO) enzymes. In the past decade, evidence has accumulated to suggest important physiological roles for CO in mammalian tissues. In the pancreas, modulation of endogenous CO production or administration of exogenous CO may represent a therapeutic option for the treatment of endocrine and exocrine pancreatic disorders. In cell culture, CO exerts anti-diabetic effects and brief exposure of purified mouse islets to CO ameliorates functional performance after transplantation. Recent advances include the observation that CO carriers possess potent anti-proliferative effects in an in vitro model of pancreatic fibrosis. In vivo, CO confers tissue protection in animal models of pancreatic disease, including those with hyperglycemia and inflammatory injury of the gland. However, there are still a number of unanswered questions surrounding its physiological and pathophysiological relevance and the preferred route of CO administration in the pancreas still remains to be settled. This brief review focuses on the roles, effects and mechanisms of action of CO in the pancreas.

• The bioenergetics of cancer, the Warburg hypothesis and the mitochondrial function.

  Authors: Jiri Neuzil, Rafael Moreno-Sánchez

  Current pharmaceutical biotechnology.

• p53 Regulation of Energy Metabolism and Mitochondria Regulation of p53 in Cancer Cells: An Insight into the Role of Manganese Superoxide Dismutase.

  Authors: Yulan Sun, Aaron K Holley, Daret K St Clair

  Current pharmaceutical biotechnology.

  Accumulated evidence suggests that p53 plays an important role in the regulation of metabolism and intracellular redox homeostasis through transcription-dependent and -independent mechanisms.Accumulated evidence suggests that p53 plays an important role in the regulation of metabolism and intracellular redox homeostasis through transcription-dependent and -independent mechanisms. Mitochondria, the power plant of cells, provide cells with ATP for their functions by regulating energy metabolism. In addition, as the byproducts of metabolism, reactive oxygen species (ROS) generated in the mitochondria can serve as signaling molecules to regulate p53 function. The regulation of p53 by mitochondria, especially redox-mediated regulation, may be involved in controlling the cellular switch between survival and death. The interplay between p53 and manganese superoxide dismutase (MnSOD), an important mitochondrial antioxidant enzyme, is an example of how nuclear and mitochondrial p53 coordinate their response to different levels of stress and contribute to the fate of cells.

• Regulation of the metabolism of polyunsaturated fatty acids and butyrate in colon cancer cells.

  Authors: Jiřina Hofmanová, Alena Vaculová, Alois Kozubík

  Current pharmaceutical biotechnology.

  Experimental and epidemiological evidence supports the idea that dietary fat and fiber influence colon carcinogenesis. Particularly, their components, n-3 polyunsaturated fatty acids (PUFAs) andExperimental and epidemiological evidence supports the idea that dietary fat and fiber influence colon carcinogenesis. Particularly, their components, n-3 polyunsaturated fatty acids (PUFAs) and butyrate, have been proven to exhibit beneficial effects on colon epithelial cell metabolism, signaling, and kinetics, thus preventing colon inflammation and cancer. Moreover, these effects may be strengthened by PUFA and butyrate combination. It appears that administration of these compounds might be a relatively nontoxic form of supportive therapy improving cancer treatment outcomes and slowing down or preventing recurrence of certain types of cancer. However, their efficient application has to be based on solid scientific evidence of their mechanisms of action from the molecular and cellular to the organismal level. In this review, we emphasize the role of lipids and their metabolism during tumor development, describe some important mechanisms considering cellular and molecular levels of PUFA and butyrate action in colon epithelial cells, and particularly focus on the interaction of their metabolism and the signaling pathways with respect to the differences in response of normal and cancer colon cells.

• Targeting the Mitochondrial Electron Transport Chain Complexes for the Induction of Apoptosis and Cancer Treatment.

  Authors: Jakub Rohlena, Lan-Feng Dong, Jiri Neuzil

  Current pharmaceutical biotechnology.

  Treatment of cancer is by no means universally successful and often manifests harmful side effects. The best way to improve the success rate and reduce the side effects would be to develop compoundsTreatment of cancer is by no means universally successful and often manifests harmful side effects. The best way to improve the success rate and reduce the side effects would be to develop compounds that are able to kill cancer cells while leaving normal cells unaffected. In this respect, mitocans (an acronym from 'mitochondria' and 'cancer'), a summary term we proposed for compounds that induce cell death by targeting mitochondria, show an encouraging trend. Here we provide an overview of mitocans specific for the mitochondrial electron transport chain. These mitocans are particularly interesting, because a frequent consequence of electron transport chain inhibition is the induction of superoxide formation resulting in the preferential killing of cancer cells, as these tend to be more sensitive than normal cells to sudden increases in oxidative stress. Furthermore, macromolecular complexes of the electron transport chain only rarely mutate in cancer, and represent useful targets for anti-cancer drug development when widely-applicable agents are sought.

• Potentiation of anti-cancer Treatment by Modulators of Energy Metabolism.

  Authors: Maria C Shoshan

  Current pharmaceutical biotechnology.

  Oncogene-driven proliferative signaling in tumor cells requires comprehensive upregulation of cellular energy metabolism and macromolecule syntheses. These alterations are now known to include notOncogene-driven proliferative signaling in tumor cells requires comprehensive upregulation of cellular energy metabolism and macromolecule syntheses. These alterations are now known to include not only upregulated glycolysis, but also increased fatty acid metabolism, glutaminolysis, deregulated mitochondrial function and more. Many prospective targets for tumor-specific pharmacological modulation of metabolism have therefore been identified. While the prospective drugs do not necessarily show very high antitumor activity by themselves, they may by depriving tumor cells of energy and building blocks for repair and proliferation come to be of major clinical use as potentiators of standard chemotherapeutic drugs and/or radiation. To this end, not only inhibitors of specific enzyme functions are being investigated, but also drugs affecting the complex signaling networks that regulate organismal and cellular energy status. This review provides examples of how modulators of energy metabolism (MEMs) targetting different aspects of tumor cell metabolism have been found to potentiate cancer treatment in vitro and in vivo.

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