American Journal of Translational Research 

About: American Journal of Translational Research is an academic journal published by e-Century Publishing Corporation. The journal publishes majorly in the area(s): Medicine & Cell growth. It has an ISSN identifier of 1943-8141. Over the lifetime, 5274 publications have been published receiving 65793 citations. The journal is also known as: AJTR & Am J Transl Res.

Lost in translation: animal models and clinical trials in cancer treatment.

Abstract: Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal models can serve as an important source of in vivo information, but alternative translational approaches have emerged that may eventually replace the link between in vitro studies and clinical applications. This review summarizes the current state of animal model translation to clinical practice, and offers some explanations for the general lack of success in this process. In addition, some alternative strategies to the classic in vivo approach are discussed.

The antimicrobial peptides and their potential clinical applications

Abstract: Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules. The membrane permeability is mostly recognized as the well-accepted mechanism to describe the action of cationic AMPs. These cationic AMPs can bind and interact with the negatively charged bacterial cell membranes, leading to the change of the electrochemical potential on bacterial cell membranes, inducing cell membrane damage and the permeation of larger molecules such as proteins, destroying cell morphology and membranes and eventually resulting in cell death. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even overcome bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable with a short half-life, more or less toxic side effects, and particularly may have severe hemolytic activity. To open the clinical applications, it is necessary and important to develop the synthetic and long-lasting AMP analogs that overcome the disadvantages of their natural peptides and the potential problems for the drug candidates.

Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs

Abstract: Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells Recently, their use has been clinically validated in cancer patients resulting in the approval of two HDAC inhibitors, vorinostat and depsipetide, by the FDA Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing However, the molecular mechanisms underlying the response to HDAC inhibitors in cancer patients are not fully understood In this review, we summarize our understanding of the molecular and biological events that underpin the anticancer effects of HDAC inhibitors and the outcomes of recent clinical trials involving these drugs

Physiological regulation of Akt activity and stability.

Abstract: The serine/threonine protein kinase B (PKB, also known as Akt) constitutes an important node in diverse signaling cascades downstream of growth factor receptor tyrosine kinases Akt plays an essential role in cell survival, growth, migration, proliferation, polarity, and metabolism (lipid and glucose); cell cycle progression; muscle and cardiomyocyte contractility; angiogenesis; and self-renewal of stem cells Altered Akt activity has been associated with cancer and other disease conditions, such as diabetes mellitus, neurodegenerative diseases, and muscle hypotrophy In the past decade, the upstream signals that lead to Akt activation, the downstream substrates that exert the effects of Akt, and the secondary binding proteins that regulate Akt activation have been well documented Recent reports from our group and others have revealed how the stability of Akt protein is regulated through phosphorylation on its Thr-Pro motifs This literature review details findings of those reports and others relevant to the regulation of Akt activation by its upstream kinases, with a focus on mammalian target of rapamycin complexes (mTORCs) and inactivation by PHLDA3 and the protein phosphatases PP2A and pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) Reports on ubiquitin-dependent Akt degradation, caspase-dependent cleavage, and the roles of molecular chaperone heat shock protein 90 (Hsp90) in the regulation of Akt stability are summarized The highlight will be on the role of "turn motif" phosphorylation and an isomerase, Pin1, in the regulation of Akt stability We also discuss issues related to the intricate mTORC2-AktmTORC1 loop and the contradictory regulation of Akt phosphorylation and stabilization of Akt by mTORC2 Finally, we offer perspective on potential future directions for investigation, particularly on translating the knowledge we learned on the regulation of Akt stability into therapeutic intervention on human cancer with Akt alteration

Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer

Abstract: Macrophages are the dominant leukocyte population found in the tumor microenvironment. Accumulating evidence suggests that these tumor-associated macrophages (TAMs) actively promote all aspects of tumor initiation, growth, and development. However, TAMs are not a single uniform population; instead, they are composed of multiple distinct pro- and anti-tumoral subpopulations with overlapping features depending on a variety of external factors. Defining and differentiating these subsets remains a challenging work-in-progress. These difficulties are apparent in prognostic studies in lung cancer that initially demonstrated conflicting evidence regarding the significance of TAMs but which have more recently clarified and confirmed the clinical importance of these subsets through improved phenotypic capabilities. Thus, these cells represent potential targets for cancer therapeutic initiatives through translational approaches. In this review, we summarize the current understanding of how the tumor microenvironment takes advantage of macrophage plasticity to mold an immunosuppressive population, the phenotypic heterogeneity of TAMs, and their link to prognosis in human lung cancer.