Showing papers in "Expert Opinion on Biological Therapy in 2012"
TL;DR: Visual analytics of the literature provides a valuable, timely, repeatable and flexible approach in addition to traditional systematic reviews so as to track the development of new emerging trends and identify critical evidence.
Abstract: Introduction: Regenerative medicine involves research in a number of fields and disciplines such as stem cell research, tissue engineering and biological therapy in general. As research in these ar...
774 citations
TL;DR: The use of spheroids has led to many advances in basic cell sciences, including understanding cancer cell interactions, creating models for drug discovery and cancer metastasis, and they are being investigated as basic units for engineering tissue constructs.
Abstract: Introduction: Developing in vitro models for studying cell biology and cell physiology is of great importance to the fields of biotechnology, cancer research, drug discovery, toxicity testing, as well as the emerging fields of tissue engineering and regenerative medicine. Traditional two-dimensional (2D) methods of mammalian cell culture have several limitations and it is increasingly recognized that cells grown in a three-dimensional (3D) environment more closely represent normal cellular function due to the increased cell-to-cell interactions, and by mimicking the in vivo architecture of natural organs and tissues. Areas covered: In this review, we discuss the methods to form 3D multi-cellular spheroids, the advantages and limitations of these methods, and assays used to characterize the function of spheroids. The use of spheroids has led to many advances in basic cell sciences, including understanding cancer cell interactions, creating models for drug discovery and cancer metastasis, and they are being...
414 citations
TL;DR: It is indicated that although further investigation is necessary to demonstrate clinical benefit, benralizumab remains a promising treatment modality.
Abstract: Introduction: Benralizumab is a monoclonal antibody that binds the α subunit of the receptor to IL-5. As IL-5 is implicated in disease states that are mediated by eosinophils, benralizumab is an attractive option for use in the management of asthma. As a result of enhanced antibody-directed cell cytotoxicity, it has enhanced eosinophil-depleting activity as compared with neutralizing monoclonal antibody directed against IL-5. Areas covered: This review presents the available data on benralizumab, including pharmacodynamics, pharmacokinetics, preclinical data and relevant clinical studies. Expert opinion: Our review indicates that although further investigation is necessary to demonstrate clinical benefit, benralizumab remains a promising treatment modality.
192 citations
TL;DR: The metabolic properties of the natural alkaloid berberine, and its potential application to the treatment of diabetes and CVD prevention and longer trials are needed to better evaluate the safety profile of the molecule, when administered alone or in association with other anti-hyperlipidemic or anti-diabetic drugs.
Abstract: Introduction: Type 2 diabetes mellitus and hypercholesterolemia have proven to give an increased incidence of cardiovascular diseases (CVD). Recent studies have suggested that the natural alkaloid ...
138 citations
TL;DR: The biologic characteristics of CIK cells are described, focusing on those aspects that may favor their clinical translation, and the easy availability of large amounts of expandedCIK cells and their MHC-unrestricted tumor killing, potentially effective against many tumor types.
Abstract: Introduction: Cytokine-induced killer (CIK) cells are heterogeneous ex vivo-expanded T lymphocytes with mixed T-NK phenotype and endowed with a wide MHC-unrestricted antitumor activity. CIK cells can be expanded from peripheral blood mononuclear cells (PBMC) cultured with the timed addition of IFN-γ, Ab anti-CD3 and IL2. A consistent subset of mature CIK cells presents a CD3+CD56+ phenotype. The CD3+CD56+ cellular subset is the main responsible for the tumor-killing activity, mostly mediated by the interaction of NKG2D receptor with MHC-unrestricted ligands (MIC A/B; ULBPs) on tumor cells. Areas covered: In the present work, we described the biologic characteristics of CIK cells, focusing on those aspects that may favor their clinical translation. We reviewed preclinical data and analyzed reports from clinical trials. A specific paragraph is dedicated to future research perspectives in the field. Expert opinion: CIK cells represent a realistic new option in the field of cancer immunotherapy. Crucial issue...
134 citations
TL;DR: The RBC membrane-coated nanoparticles present a major breakthrough in drug delivery technology and show great promise for clinical applications and the significance and the unique features of this nature-inspired nanoparticle platform are highlighted.
Abstract: The development of nanoparticle platforms with long in vivo circulation half-life has long been one of the major goals in the field of cancer drug delivery. Long-circulating nanoparticles can more ...
126 citations
TL;DR: A peripheral-to-central gene delivery that can affect the entire CNS without having to inject the CNS is promising for basic functional experiments, and potentially for gene therapy, although other natural serotypes and recombineered vectors may also support or improve upon wide-scale expression.
Abstract: Introduction: Straightforward studies compared adeno-associated virus (AAV) serotypes to determine the most appropriate one for robust expression in the CNS. AAV9 was efficient when directly injected into the brain, but more surprisingly, AAV9 produced global expression in the brain and spinal cord after a peripheral, systemic route of administration to neonatal mice. Areas covered: Topics include AAV9 gene delivery from intraparenchymal, intravenous, intrathecal and intrauterine routes of administration, and related preclinical studies and disease models. Systemic AAV9 gene transfer yields remarkably consistent neuronal expression, though only in early development. AAV9 is versatile to study neuropathological proteins: microtubule-associated protein tau and transactive response DNA-binding protein 43 kDa (TDP-43). Expert opinion: AAV9 will be more widely used based on current data, although other natural serotypes and recombineered vectors may also support or improve upon wide-scale expression. A periphe...
124 citations
TL;DR: Full-blown fetal aneuploidies can thus be reliably detected in maternal plasma using a multiplex MPS-by-ligation approach, and the results obtained with a sample from a pregnancy with 45,X in the cytotrophoblastic cell layer and 46,XX in the mesenchymal core cells show that ccffDNA originates from the cytoskeletal cell layer.
Abstract: Blood plasma of pregnant women contains circulating cell-free fetal DNA (ccffDNA), originating from the placenta. The use of this DNA for non-invasive detection of fetal aneuploidies using massively parallel sequencing (MPS)-by-synthesis has been proven previously. Sequence performance may, however, depend on the MPS platform and therefore we have explored the possibility for multiplex MPS-by-ligation, using the Applied Biosystems SOLiD(™) 4 system. DNA isolated from plasma samples from 52 pregnant women, carrying normal or aneuploid fetuses, was sequenced in multiplex runs of 4, 8 or 16 samples simultaneously. The sequence reads were mapped to the human reference genome and quantified according to their genomic location. In case of a fetal aneuploidy, the number of reads of the aberrant chromosome is expected to be higher or lower than in normal reference samples. To statistically determine this, Z-scores per chromosome were calculated as described previously, with thresholds for aneuploidies set at > +3.0 and < -3.0 for chromosomal over- or underrepresentation, respectively. All samples from fetal aneuploidies yielded Z-scores outside the thresholds for the aberrant chromosomes, with no false negative or positive results. Full-blown fetal aneuploidies can thus be reliably detected in maternal plasma using a multiplex MPS-by-ligation approach. Furthermore, the results obtained with a sample from a pregnancy with 45,X in the cytotrophoblastic cell layer and 46,XX in the mesenchymal core cells show that ccffDNA originates from the cytotrophoblastic cell layer. Discrepancies between the genetic constitution of this cell layer and the fetus itself are well known, and therefore, care should be taken when translating results to the fetus itself.
117 citations
TL;DR: This review summarises progress with development of this new class of drugs, Antibody–drug conjugates (ADCs), and describes separately the antibody and drug elements of ADCs and then examines the technology and consequences of linkage.
Abstract: Introduction: There is a great unmet need for effective new treatments in cancer, which continues to be a major cause of death. Antibody–drug conjugates (ADCs) are emerging, after a long gestation, as a class of biopharmaceuticals with the potential to address this need by directing highly potent cytotoxic drugs to their point of action. There is increasing interest in ADCs by major pharmaceutical companies and a growing pipeline of candidates for clinical use. This review summarises progress with development of this new class of drugs. Areas covered: The authors describe separately the antibody and drug elements of ADCs and then examine the technology and consequences of linkage. The work is presented in the light of recent developments in the design, using clinical examples where possible. Expert opinion: Since their emergence as independent drugs, antibodies and chemotherapy are being brought together in effective synergy. The conjunction is timely: many of the technical challenges in preparing antibod...
116 citations
TL;DR: The data reviewed here suggest that exosomal RNA has the potential to play an important role in the diagnosis, prognosis, and treatment of diseases in the future.
Abstract: Introduction: Exosomes are nano-sized (40 – 100 nm), extracellular vesicles, of endosomal origin. They are released by cells and found in many body fluids, including plasma. Exosomes contain proteins, microRNAs (miRNAs), and messenger RNAs (mRNAs) that can be transferred between cells. The discovery that exosomes contain RNA, and that this encapsulated RNA could potentially be transferred over distances in vivo, reinforced the importance of exosomes in cell-to-cell communication. Areas covered: The existence of exosomes, as a naturally occurring delivery system of RNA, enables their use as both biomarkers and vectors in gene therapy. This review provides an overview of studies reporting that exosomal miRNA and mRNA in plasma can serve as a diagnostic marker in various types of cancers. In addition, the recent finding that exosomes can be used as vectors for delivery of small interfering RNA (siRNA) in mice, with therapeutic effects, is also reviewed. Expert opinion: The data reviewed here suggest that exo...
116 citations
TL;DR: There is strong evidence that this probiotic has a clinically significant benefit, whatever the cause, including in developing countries, with S. boulardii, the shortened duration of diarrhea and the reduction in hospital stay result in social and economic benefits.
Abstract: Introduction: Acute diarrhea continues to be a leading cause of morbidity, hospitalization and mortality worldwide and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. Regarding the treatment of acute diarrhea, a few probiotics including Saccharomyces boulardii seem to be promising therapeutic agents. Areas covered: We performed a systematic review and meta-analysis regarding the use of S. boulardii in the treatment of acute infectious diarrhea with relevant studies that searched with the PubMed, Embase, Scopus, Google Scholar, the Cochrane Controlled Trials Library, and the Cochrane Database of Systematic Reviews through October 2011. This review describes the effects of S. boulardii on the duration of diarrhea, the risk of diarrhea during the treatment (especially at the third day) and duration of hospitalization in patients with acute infectious diarrhea. This review also focused on the potential effects of S. boulardii for acute infectious diarrhea due to di...
TL;DR: In cancer, a selective removal or silencing of iTreg and not of nTreg should be a therapeutic goal, however, the implementation of this challenging strategy requires further studies of cellular and molecular crosstalk among immune cells in the tumor microenvironment.
Abstract: Introduction: Evidence suggests that FOXP3+CD25highCD4+ regulatory T cells (Treg) which accumulate in cancer may have beneficial or unfavorable effects on prognosis. The presence in tumor-associated inflammatory infiltrates of two subsets of Treg with distinct phenotypic and functional profiles might explain these conflicting observations. Areas covered: Human inducible (i) Treg arising by tumor-driven conversion of conventional CD4+ T cells are highly suppressive, therapy-resistant Treg which down-regulate anti-tumor immune responses, promoting tumor growth. Natural (n) Treg, normally responsible for maintaining peripheral tolerance, control cancer-associated inflammation, which favors tumor progression. This division of labor between nTreg and iTreg is not absolute, and overlap may be common. Nevertheless, iTreg play a critical and major role in cancer and cancer therapy. The tumor microenvironment determines the type, frequency and suppression levels of accumulating Treg. Expert opinion: In cancer, a s...
TL;DR: The processes of joint injury and pathology relevant to the mechanism of action of PRP, and elaborate insights into how PRP components may influence inflammation, angiogenesis, cell death and cartilage chondroprotection are described.
Abstract: Introduction: At the beginning of the new millennium, there was a breakthrough in platelet-rich plasma (PRP) therapy for tissue repair. The mechanisms governing the effects of this therapy in joint pathology remain largely unexplored. Areas covered: This review is primarily based on PubMed and Web of Knowledge searches with the terms osteoarthritis in combination with PRP, treatment, cartilage, synovium, platelets, inflammation and/or angiogenesis. This search was completed by a manual search for relevant studies. We mainly include papers from the last 5 years. The concept of dynamic reciprocity is used to shape understanding of the spatial relationship between cells and their microenvironments as well as between tissues within the joint. We describe the processes of joint injury and pathology relevant to the mechanism of action of PRP, and elaborate insights into how PRP components may influence inflammation, angiogenesis, cell death and cartilage chondroprotection. Expert opinion: PRP therapies are more...
TL;DR: The scientific foundation for ongoing and projected clinical trials in the treatment of dermal wounds, corneal injuries and in the regeneration and repair of heart and CNS tissue following ischemic insults and trauma is provided.
Abstract: Introduction: Thymosin β4, a low molecular weight, naturally-occurring peptide plays a vital role in the repair and regeneration of injured cells and tissues. After injury, thymosin β4, is released by platelets, macrophages and many other cell types to protect cells and tissues from further damage and reduce apoptosis, inflammation and microbial growth. Thymosin β4 binds to actin and promotes cell migration, including the mobilization, migration, and differentiation of stem/progenitor cells, which form new blood vessels and regenerate the tissue. Thymosin β4 also decreases the number of myofibroblasts in wounds, resulting in decreased scar formation and fibrosis Areas covered: This article will cover the many thymosin β4 activities that directly affect the repair and regeneration cascade with emphasis on its therapeutic uses and potential. Our approach has been to evaluate the basic biology of the molecule as well as its potential for clinical applications in the skin, eye, heart and brain. Expert opinion...
TL;DR: This paper reviews TNF mechanisms of action in viral hepatitis B and C, recommendations for managing HBV and HCV-infected patients receiving treatment with anti-TNF drugs, safety and anti- TNF hepatotoxicity, and expert opinion.
Abstract: Introduction: Drugs targeting TNF-α biological activity are increasingly used for the treatment of immune-mediated diseases, like rheumatoid arthritis, inflammatory bowel diseases and psoriasis. Since TNF-α is a mediator of the immune response against viral infections, use of TNF-α inhibitors in patients with concurrent HBV or HCV infection can promote viral reactivation and potentially fatal liver failure. Areas covered: This paper reviews TNF mechanisms of action in viral hepatitis B and C, recommendations for managing HBV and HCV-infected patients receiving treatment with anti-TNF drugs, safety and anti-TNF hepatotoxicity. Expert opinion: In hepatitis B surface antigen (HBsAg) carriers undergoing anti-TNF therapy, either anti-HBV treatment or prophylaxis is mandatory to prevent hepatitis reactivation, whereas HBsAg-negative antibody to hepatitis B core antigen (anti-HBc) seropositive patients require watchful monitoring, only. Conversely, in HCV-infected patients, TNF-α inhibition by specific drugs is ...
TL;DR: The authors showed that examining the proportion of ctDNA originating from tumor, microenvironment and normal cells, through size distribution and mutation load may help to discriminate mechanisms of cTDNA release, and Detection of point mutation by quantifying theportion of mutant ct DNA fragments provides a powerful tool for assessing the proportion from different origins.
Abstract: Introduction: The pressing need to determine the KRAS/BRAF mutational status for selecting patients with colorectal cancer (CRC) for anti-EGFR therapy provides a great opportunity to use circulating DNA (ctDNA) as a theranostic tool for personalized medicine. Better understanding of ctDNA origin (necrosis, apoptosis and active release) may increase the reliability of using abnormal ctDNA as biomarker. Areas covered: The authors showed that examining the proportion of ctDNA originating from tumor, microenvironment and normal cells, through size distribution and mutation load may help to discriminate mechanisms of ctDNA release. Expert opinion: Contrary to the literature, it was observed that tumor-derived ctDNA was mostly shorter than 100 bp. Tumor-derived ctDNA from cancer patients exhibited a specific ctDNA size distribution profile and significantly higher ctDNA fragmentation than ctDNA from healthy individuals. Examination of the KRAS and BRAF mutational load in 48 mutated samples revealed very high va...
TL;DR: There is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible, and a number of vaccine candidates developed in the last decade that are highly protective in NHPs, the gold standard animal model for ebola hemorrhagic fever are reviewed.
Abstract: Introduction: Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates (NHPs), with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine...
TL;DR: There is no evidence from clinical trial data or post marketing surveillance data that switching to and from different biopharmaceuticals leads to safety concerns, and the literature on the frequency of switching is scarce.
Abstract: Introduction: The approval of several biosimilars in the past years has prompted discussion on potential safety risks associated with switching to and from these products. It has been suggested that switching may lead to safety concerns. However, data is limited on the clinical effects of switching. Areas covered: In this review we provide an overview of data related to switching between human recombinant growth hormones, erythropoietins and granulocyte colony stimulating agents. We reviewed data from clinical trials, pharmacovigilance databases and an overview of the literature on the frequency of switching between these products. The review covers both switching between innovator products within the same product class and switching to and from biosimilars. Expert opinion: Data on the frequency of switching in clinical practice is scarce, but it seems most frequent for erythropoietins. We have found no evidence from clinical trial data or post marketing surveillance data that switching to and from differ...
TL;DR: Recent studies provide evidence of the circulating nucleome organization complexity indicating that discovery of extracellular DNA generation and circulation patterns in healthy condition and cancer is essential to enable the development of proper approaches for the selection of valid diagnostic markers.
Abstract: Introduction: Extracellular nucleic acids are found in human blood and cell culture medium as cell-free or being adsorbed at cell surface. In the last years, the circulating extracellular nucleic acids in blood were shown to be associated with certain diseases. Attempts are made to develop non-invasive methods of early tumor diagnostics based on analysis of circulating DNA and RNA. Areas covered: This article reviews accumulating data regarding cell-free and cell-surface-bound extracellular nucleic acid nature and generation mechanisms. Their existence as a constituent of the naturally occurring complexes with proteins or membrane-bearing particles is discussed with regard to their homeostatic concentration and distribution in healthy donor blood which are significantly altered in cancer patients. Gene-target and whole-genome studies reveal significant differences in gene representation between extracellular DNA and genome DNA. Overrepresentation of regions with high transcription activity has led to prop...
TL;DR: In this paper, the authors provide an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering and provide a recent perspective in the treatment of heart failure.
Abstract: Introduction: A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. Areas covered: This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Expert opinion: Though many strategies have been proposed for fabrication of va...
TL;DR: CirculatingmiR-21 and miR-375 could be reliable prognostic markers for ESCC and facilitate clinical decision-making to select prospective candidates, which need meticulous follow-up for early detection of recurrences and additional treatments such as neo-adjuvant chemotherapy and postoperative chemotherapy in ESCC.
Abstract: Background: miR-21 and miR-375 are reported to be highly and poorly expressed in esophageal squamous cell carcinoma (ESCC) tissues, respectively. Recently, we demonstrated that circulating miR-21 and miR-375 were stably detectable in plasma and reflected tumor dynamics as a tumor marker for ESCC. We hypothesized that these plasma miRNA concentrations contributed to prognostic markers in patients with ESCC. Methods: Between 2008 and 2010, 50 preoperative plasma samples were collected from consecutive patients with ESCC, who underwent curative esophagectomy in our hospital. We examined the association between plasma miRNA concentrations and prognosis retrospectively. Results: i) The postoperative cause-specific survival rate of patients with high plasma miR-21 concentration tended to be poorer than low group (3-yr survival rate: 53.4 and 81.5%, p = 0.1038), while that of high plasma miR-375 group was better than low group (3-yr survival rate: 100 and 65.2%). ii) Patients with high miR-21 and low miR-375 con...
TL;DR: MSCs isolated from bone marrow have been the best characterised approach for osteogenic differentiation and their use with synthetic scaffolds such as hydroxyapatite and tricalcium phosphate has produced promising clinical results.
Abstract: Introduction: Bone grafting is used to repair large bone defects and autograft is recognised as producing the best clinical outcome, which is partly due to its cellular component. When autograft is unavailable, allograft and bone graft substitutes can be used; however, they rely on the host bed to provide cellular osteogenic activity. Areas covered: Bone graft substitutes have the potential to benefit from the addition of stem cells aimed at enhancing the rate and quality of defect repair. Mesenchymal stem cells (MSCs) can be isolated from bone marrow or periosteum and culture expanded. Other sources of primary cells include muscle, adipose tissue, human umbilical cord and the pluripotent embryonic stem cells (ESCs). Expert opinion: MSCs isolated from bone marrow have been the best characterised approach for osteogenic differentiation. Their use with synthetic scaffolds such as hydroxyapatite and tricalcium phosphate has produced promising clinical results. MSCs derived from adipose tissue, muscle or huma...
TL;DR: The aim is to provide an overview of the applications, particularly for clinical use, of this innovative formulation of L-asparaginase-loaded RBCs, one of the most promising drug delivery systems investigated in recent decades.
Abstract: The first human transfusion was performed by the pioneer Dr Jean-Baptiste Denis in France in 1667 and now, three centuries later, around 50 millions blood units are transfused every year, saving millions of lives. Today, there is a new application for red blood cells (RBCs) in cellular therapy: the effective use of erythrocytes as vehicles for chemical or biological drugs. Using this approach, the therapeutic index of RBC-entrapped molecules can be significantly improved with increased efficacy and reduced side effects. This cell-based medicinal product can be manufactured at an industrial scale and is now used in the clinic for different therapeutic applications.
A seminar dedicated to this field of research, debating on this inventive formulation for drugs, was held in Lyon (France) on 28 January 2011. Drs KC Gunter and Y Godfrin co-chaired the meeting and international experts working on the encapsulation of drugs within erythrocytes met to exchange knowledge on the topic ‘The Red Blood Cells as Vehicles for Drugs’. The meeting was composed of oral presentations providing the latest knowledge and experience on the preclinical and clinical applications of this technology. This Meeting Highlights article presents the most relevant messages given by the speakers and is a joint effort by international experts who share an interest in studying erythrocyte as a drug delivery vehicle. The aim is to provide an overview of the applications, particularly for clinical use, of this innovative formulation. Indeed, due to the intrinsic properties of erythrocytes, their use as a drug carrier is one of the most promising drug delivery systems investigated in recent decades. Of the different methods developed to encapsulate therapeutic agents into RBCs [1,2,] the most widely used method is the lysis of the RBCs under tightly controlled hypotonic conditions in the presence of the drug to be encapsulated, followed by resealing and annealing under normotonic conditions (Figure 1). This results in uniform encapsulation of the material into the cells and a final product with good stability, reproducibility and viability. This process, which has now been developed to an industrial scale, is the technique chosen by the majority of the experts presenting their work in this seminar (by R Franco).
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Figure 1
The process of reversible hypotonic lysis of RBCs to entrap molecules
RBCs are submitted to a hypotonic stress creating pores in the erythrocyte membrane. Drug can pass through the pores and be permanently entrapped after a resealing step using a hypertonic solution.
RBC: Red blood cell.
TL;DR: The known biological properties of ASCs suggest a potential role in enhancing fat graft retention and facilitating minimally invasive reconstructive treatments, and future directions for rendering soft tissue reconstructive therapies more effective are discussed.
Abstract: Introduction: Since their isolation and characterization nearly a decade ago, adipose-derived stem cells (ASCs) have become one of the most popular adult stem cell populations for research in soft tissue engineering and regenerative medicine applications. Compared with other stem cell sources, ASCs offer several advantages including an abundant autologous source, minor invasive harvesting (liposuction), significant proliferative capacity in culture and multi-lineage potential. Numerous preclinical studies have been pursued, with early clinical data appearing in the literature. Areas covered: Autologous fat grafting has gained tremendous momentum in clinical practice over the past several years due to its potential applications in trauma and reconstructive surgery. This review focuses on the published clinical and pre-clinical (i.e., animal) data to date using ASCs for soft tissue reconstruction, with particular attention to experimental models and methodologies. Future directions for rendering soft tissue...
TL;DR: Although no evident rise in anti-VEGF-induced thromboembolic side effects was reported, more data are required to evaluate hemodynamic and pharmacokinetics of these compounds, since only few studies have focused on these aspects.
Abstract: Introduction: The consistent association between choroid neovascularization (CNV) and increased VEGF-A expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of neovascular age-related macular degeneration (AMD). The authors report the systemic side effects secondary to intravitreal administration of these compounds, that is, the main cardiovascular effects, as well as the less frequent cerebrovascular accidents, myocardial infarction, transient ischemic attacks, deep vein thrombosis, pulmonary embolism and thromboflebitis. Areas covered: The authors reviewed major Clinical Trials and publications concerning systemic adverse events of anti-VEGF drugs in order to identify the main thromboembolic events related to the use of these agents and their occurrence. Anti-VEGF efficacy, safety and tolerability are also discussed. Expert opinion: Three compounds (pegaptanib, ranibizumab and aflibercept) have been approved for the treatment of AMD; a fourth ag...
TL;DR: It is believed that therapeutic genetic cancer vaccines have the strong potential to become an established therapeutic modality for cancer in next coming years, in a manner similar to what have now become monoclonal antibodies.
Abstract: Introduction: The recent approval of the first therapeutic cancer vaccine by the US Regulatory Agency represents a breakthrough event in the history of cancer treatment. The past scepticism towards this type of therapeutic intervention is now replaced by great expectations. The field is now moving towards the development of alternative vaccination technologies, which are capable of generating stronger, more durable and efficient immune responses against specific tumour-associated antigens (TAAs) in combination with cheaper and more standardised manufacturing. Areas covered: In this context, genetic vaccines are emerging among the most promising methodologies. Several evidences point to combinations of different genetic immunisation modalities (heterologous prime/boost) as a powerful approach to induce superior immune responses and achieve greater clinical efficacy. In this review, we provide an overview of the current status of development of genetic cancer vaccines with particular emphasis on adenoviral ...
TL;DR: This review summarizes the structures and functions of integrin α5β1 and its ligand fibronectin, provides an overview of the early development of volociximab, a targeted monoclonal antibody that specifically binds and inhibits activation ofIntegrin α 5β1, and discusses the relevant data from pre-clinical and clinical studies.
Abstract: Introduction: Volociximab is a first-in-class chimeric monoclonal antibody that targets α5β1 integrin. Preclinical studies have shown the ability of volociximab to inhibit tumor neoangiogenesis by blocking the interaction between α5β1 and fibronectin. Volociximab's safety profile, pharmacokinetics and pharmacodynamics have been established. Ongoing clinical trials are evaluating its efficacy in the treatment of different types of solid tumors as a single agent or in combination with chemotherapy. In this review we focus on the biological effect of volociximab and results of completed clinical trials. Areas covered: This review summarizes the structures and functions of integrin α5β1 and its ligand fibronectin, provides an overview of the early development of volociximab, a targeted monoclonal antibody that specifically binds and inhibits activation of integrin α5β1, and discusses the relevant data from pre-clinical and clinical studies. Expert opinion: Volociximab has been well tolerated as monotherapy or...
TL;DR: This review summarizes the current knowledge regarding lipids and DR and will conclude by evaluating current lipid-lowering therapies in DR and also give an overview of other novel treatments targeting lipid pathways.
Abstract: Introduction: Diabetic retinopathy (DR) is a significant cause of visual impairment worldwide. The association between hyperlipidemia or dyslipidemia and DR has been investigated extensively, but a conclusive link remains elusive. This review summarizes the current knowledge regarding lipids and DR. Areas covered: The clinical literature on the associations between the ‘traditional’ lipid markers and DR will be critically evaluated, along with some of the postulated biological mechanisms underlying the associations. The emergence of several novel ‘non-traditional’ lipid fractions as possible biomarkers for DR will also be discussed. The review will conclude by evaluating current lipid-lowering therapies in DR and also give an overview of other novel treatments targeting lipid pathways. Expert opinion: Future studies need to address three important issues. First, the role of novel lipid biomarkers needs to be clarified in light of the persistent failure of epidemiological studies to demonstrate a clear ass...
TL;DR: Investigations into oral probiotic therapies are proving promising, but investigations into clinical efficacy, delivery/dose optimization, mechanism(s) of action and other related parameters are yet to be fully explored.
Abstract: Introduction: Oral health is affected by its resident microorganisms. Three prominent oral disorders are dental caries, gingivitis and periodontitis, with the oral microbiota playing a key role in the initiation/progression of all three. Understanding the microbiota and the diseases they may cause is critical to the development of new therapeutics. This review is focused on probiotics for the prevention and/or treatment of oral diseases. Areas covered: This review describes the oral ecosystem and its correlation with oral health/disease. The pathogenesis and current prevention/treatment strategies of periodontal diseases (PD) and dental caries (DC) are depicted. An introduction of probiotics is followed by an analysis of their role in PD and DC, and their potential role(s) in oral health. Finally, a discussion ensues on the future research directions and limitations of probiotics for oral health. Expert opinion: An effective oral probiotic formulation should contribute to the prevention/treatment of micro...
TL;DR: Recent studies of nimotuzumab indicate the reason for the lack of toxicity, which is the most attractive argument for its clinical use besides modest efficacy, and upcoming genomic results of the different tumour entities may suggest certain combination partners of the antibody.
Abstract: Introduction: In spite of new alkylating medication and recently accumulated knowledge about genomics, the prognosis of malignant gliomas remains poor. The introduction of single substances interfering with tumour proliferation dynamics has been disappointing and the lessons learned indicate that a complicated network of proliferation needs time consuming, in-depth analysis in order to more specifically treat now distinguishable subgroups of a disease, which too long was thought of as a uniform entity. Areas covered: The clinical trials using the EGFR antibody nimotuzumab in the treatment of malignant gliomas are reviewed. Pending conformation in future studies the antibody might be part of the treatment of MGMT-negative, EGFR-amplified, not completely resected gliomas of adulthood and juvenile DIPG (pontine gliomas). Upcoming genomic results of the different tumour entities may suggest certain combination partners of the antibody. Recent studies of nimotuzumab indicate the reason for the lack of toxicity...