This week’s selection of recently published papers from MDPI journals.
TRPV1: A Potential Drug Target for Treating Various Diseases
Rafael Brito 1,2, Sandeep Sheth 1, Debashree Mukherjea 3, Leonard P. Rybak 1,3 and Vickram Ramkumar 1
1Department of Pharmacology and Neuroscience, Southern Illinois University School of Medicine, Springfield, IL 62702, USA, 2Department of Neurobiology and Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niteroi 24020141, RJ, Brazil, 3Department of Surgery (Otoloryngalogy), Southern Illinois University School of Medicine, Springfield, IL 62702, USA
Abstract: Transient receptor potential vanilloid 1 (TRPV1) is an ion channel present on sensory neurons which is activated by heat, protons, capsaicin and a variety of endogenous lipids termed endovanilloids. As such, TRPV1 serves as a multimodal sensor of noxious stimuli which could trigger counteractive measures to avoid pain and injury. Activation of TRPV1 has been linked to chronic inflammatory pain conditions and peripheral neuropathy, as observed in diabetes. Expression of TRPV1 is also observed in non-neuronal sites such as the epithelium of bladder and lungs and in hair cells of the cochlea. At these sites, activation of TRPV1 has been implicated in the pathophysiology of diseases such as cystitis, asthma and hearing loss. Therefore, drugs which could modulate TRPV1 channel activity could be useful for the treatment of conditions ranging from chronic pain to hearing loss. This review describes the roles of TRPV1 in the normal physiology and pathophysiology of selected organs of the body and highlights how drugs targeting this channel could be important clinically.
For Open Access Article, see: Brito, R.; Sheth, S.; Mukherjea, D.; Rybak, L.P.; Ramkumar, V. TRPV1: A Potential Drug Target for Treating Various Diseases. Cells 2014, 3, 517-545.
Advanced Cell Culture Techniques for Cancer Drug Discovery
Carrie J. Lovitt, Todd B. Shelper and Vicky M. Avery
Discovery Biology, Griffith University, N27, Don Young Road, Nathan, Queensland, 4111, Australia
Abstract: Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.
For Open Access Article, see: Lovitt, C.J.; Shelper, T.B.; Avery, V.M. Advanced Cell Culture Techniques for Cancer Drug Discovery. Biology 2014, 3, 345-367.
Analysis of Benzo[a]pyrene in Vegetable Oils Using Molecularly Imprinted Solid Phase Extraction (MISPE) Coupled with Enzyme-Linked Immunosorbent Assay (ELISA)
Michael Pschenitza 1, Rudolf Hackenberg 2, Reinhard Niessner 1 and Dietmar Knopp 1
1Institute of Hydrochemistry and Chemical Balneology, Chair for Analytical Chemistry, Technische Universität München, Marchioninistrasse 17, 81377 Munich, Germany,2Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Standort Marienfelde, Diedersdorfer Weg 1, 12277 Berlin, Germany
Abstract: This paper describes the development of a molecularly imprinted polymer-based solid phase extraction (MISPE) method coupled with enzyme-linked immunosorbent assay (ELISA) for determination of the PAH benzo[a]pyrene (B[a]P) in vegetable oils. Different molecularly imprinted polymers (MIPs) were prepared using non-covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and dichloromethane as porogen. Imprinting was done with a template mixture of phenanthrene and pyrene yielding a broad-specific polymer for PAHs with a maximum binding capacity (Q) of ~32 μg B[a]P per 50 mg of polymer. The vegetable oil/n-hexane mixture (1:1, (v/v)) was pre-extracted with acetonitrile, the solvent evaporated, the residue reconstituted in n-hexane and subjected to MISPE. The successive washing with n-hexane and isopropanol revealed most suitable to remove lipid matrix constituents. After elution of bound PAHs from MISPE column with dichloromethane, the solvent was evaporated, the residue reconstituted with dimethyl sulfoxide and diluted 100-fold with methanol/water (10:90, (v/v)) for analysis of B[a]P equivalents with an ELISA. The B[a]P recovery rates in spiked vegetable oil samples of different fatty acid composition were determined between 63% and 114%. The presence of multiple PAHs in the oil sample, because of MIP selectivity and cross-reactivity of the ELISA, could yield overestimated B[a]P values.
For Open Access Article, see: Pschenitza, M.; Hackenberg, R.; Niessner, R.; Knopp, D. Analysis of Benzo[a]pyrene in Vegetable Oils Using Molecularly Imprinted Solid Phase Extraction (MISPE) Coupled with Enzyme-Linked Immunosorbent Assay (ELISA). Sensors 2014, 14, 9720-9737.
Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma
Yuling Zhang1,8,†, Hongzheng Ren2,†, Lu Wang3,8,†, Zhifeng Ning3,8, Yixuan Zhuang9, Jinfeng Gan3,8,Shaobin Chen4, David Zhou5, Hua Zhu6, Dongfeng Tan 7 and Hao Zhang3,8,9
1 Department of Information, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China2 Department of Pathology, the Central Hospital of Kaifeng, Kaifeng 475000, China3 Department of Biotherapy and Gastrointestinal Medical Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China4 Department of Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China5 Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA6 Department of Surgery, Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, OH 43210, USA7 Department of Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA8 Cancer Research Center, Shantou University Medical College, Shantou 515031, China9 Tumor Tissue Bank, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515031, China
Abstract: Primary small cell esophageal carcinoma is a rare and aggressive type of gastrointestinal cancer with poor prognosis. In the present study, the impact of tumour infiltrating inflammatory cells on clinico-pathological characteristics and the patients’ prognosis were analysed. A total of 36 small cell esophageal carcinomas, 19 adjacent normal tissues and 16 esophageal squamous cell carcinoma samples were collected. Qualified pathologists examined eosinophils, neutrophils, lymphocytes and macrophages on histochemical slides. The infiltration of eosinophils and macrophages in small cell esophageal carcinoma was significantly increased as compared with tumor adjacent normal tissues, and was significantly less in esophageal squamous cell carcinoma. Macrophage count was significantly associated with (p = 0.015) lymph node—stage in small cell esophageal carcinoma. When we grouped patients into two groups by counts of infiltrated inflammatory cells, Kaplan-Meier analysis revealed that high macrophage infiltration group (p = 0.004) and high eosinophil infiltration group (p = 0.027) had significantly enhanced survival. In addition, multivariate analysis unveiled that eosinophil count (p = 0.002) and chemotherapy (Yes vs. No, p = 0.001) were independent prognostic indicators. Taken together, infiltration of macrophages and eosinophils into the solid tumor appear to be important in the progression of small cell esophageal carcinoma and patients’ prognosis.
For Open Access Article, see: Zhang, Y.; Ren, H.; Wang, L.; Ning, Z.; Zhuang, Y.; Gan, J.; Chen, S.; Zhou, D.; Zhu, H.; Tan, D.; Zhang, H. Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma. Int. J. Mol. Sci. 2014, 15, 9718-9734.