Vol 2-5 Mini Review

Expression, Functions, and Treatment Target of PD-L1 (B7-H1) in Multiple Myeloma

Hideto Tamura1*, Mariko Ishibashi2, Mika Sunakawa1, Hidemi Takahashi2, Koiti Inokuchi1

1Department of Hematology, Nippon Medical School, Tokyo, Japan

2Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan

Programmed death ligand 1 (PD-L1) expression on myeloma cells is induced by JAK2, STAT3, and MEK1/2-mediated interleukin-6 signaling, a strong inducer of PD-L1 interferon-γ produced by T and natural killer cells, and APRIL produced by osteoclasts in the tumor microenvironment. The soluble form of PD-L1, derived from extracellular domains of PD-L1 molecules expressed in the tumor environment, may also contribute to tumor immune evasion. PD-L1-expressing myeloma cells not only have the ability to escape from the attack of tumor-specific T cells but also high proliferation potential. Furthermore, PD-L1 on myeloma cells delivers a reverse signal to tumor cells through PD-1 binding, resulting in the phosphorylation of Akt accompanied by the acquisition of resistance to anti-myeloma agents. Based on the function of PD-L1 in myeloma, the blockade of the PD-1–PD-L1 pathway is a reasonable treatment in refractory patients. Phase I/II clinical trials of anti-PD-1 antibody combined with immunomodulatory drugs demonstrated excellent effects in heavily pretreated multiple myeloma patients with acceptable tolerability. The timing and combination drug of anti-PD-1/PD-L1 antibodies should be considered to improve clinical effects with low mortality in refractory myeloma patients.

DOI: 10.29245/2578-3009/2018/5.1162 View / Download Pdf View Full Text
Vol 2-5 Review Article

Identification of ω-sites of Glycosylphosphatidylinositol Anchored Proteins

Yusuke Masuishi*, Shota Endo, Hideaki Kasuga, Tomoo Hidaka, Takeyasu Kakamu, Tetsuhito Fukushima

Department of Hygiene and Preventive Medicine, Fukushima Medical University School of Medicine, 1Hikariga-oka, Fukushima City 960-1295, Japan

Unique and complex post-translational modifications are present in the outer leaflet of the plasma membrane. Glycosylphosphatidylinositol (GPI) anchoring is essential for the expression of several outer membrane proteins on the cell surface. A common GPI anchor structure is constituted by glycan moiety, lipid moiety, phosphate and ethanolamine. GPI-anchored proteins (GPI-APs) are observed among eukaryotic species. Abnormal GPI anchoring of proteins is thought to cause various diseases such as paroxysmal nocturnal hemoglobinuria. Recently, many inherited GPI deficiencies (IGDs) have been reported to cause epilepsy, mental retardation, coarse facial features, and multiple organ anomalies. Diseases caused by abnormal GPI anchoring will probably continue to increase, because it is still unknown how many causative genes of IGDs are present. Therefore, in order to study these diseases, the analytical methods of GPI-APs will become important in the future. To date, many methods have been developed for analysis of GPI- APs. In this review, we attempt to summarize the present knowledge about comprehensive analytical methods of GPI-APs and introduce briefly some GPI anchor-related diseases.

DOI: 10.29245/2578-3009/2018/5.1151 View / Download Pdf View Full Text
Vol 2-5 Mini Review

A Flow Cytometric Immunophenotyping Approach to the Detection of Regulated Cell Death Processes

A Vossenkamper1, G Warnes2*

1Centre for Immunobiology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary London University, 4 Newark Street, London E1 2AT, UK

2Flow Cytometry Core Facility, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary London University, 4 Newark Street, London E1 2AT, UK

The use of the Western Blot technique has been the gold standard to determine protein expression and to semi-quantitate this expression in cell lysates. The recent publication of a flow cytometric immunophenotyping method employing fluorescently labelled antibodies to the intracellular labelling of antigens involved in Regulated Cell Death (RCD) processes has allowed the detection of three of these processes simultaneously which gave clarity to the interpretation of the relationship between apoptosis, RIP1 dependent apoptosis and necroptosis. Flow cytometry can now immunophenotype necroptosis by virtue of the up-regulation of RIP3 with simultaneous estimations of the degree of classic apoptosis (Caspase-3+ve/RIP3-ve) and of RIP1-dependent apoptosis (Caspase-3+ve/RIP3+ve) in live and dead cell populations. This approach for detecting multiple forms of cell death has been confirmed by the use of apoptosis and necroptosis blocking agents, zVAD and necrostatin-1 after treatment with etoposide or shikonin which induced apoptosis and necroptosis. The addition of anti-PARP and H2AX antibodies for the detection of parthanatos and DNA damage showed that double negative Caspase-3-ve/RIP3-ve cells detected in a previous study have undergone parthanatos or still display a negative phenotype for any cell death process.

DOI: 10.29245/2578-3009/2018/5.1159 View / Download Pdf View Full Text
Vol 2-5 Review Article

Pathological Approach to A Special Benign Tumor with Regard to its Differential Diagnose Spectrum: Intranodal Palisaded Myofibroblastoma

Yasemin Yuyucu Karabulut*

Mersin University Medical School, Department of Pathology, Mersin, Turkey

Intranodal palisaded myofibroblastoma, also known as “intranodal hemorrhagic spindle cell tumor with amianthoid fibers,” is a benign mesenchymal tumor of the lymph node originating from smooth muscle cells and myofibroblasts often with the presence of amianthoid fibers. Ninety-three cases of intranodal palisaded myofibroblastoma have been reported in the literatüre since its first description and most of them have the same clinical history “painless firm nodüle”. It is mostly seen in inguinal region there are few cases have been described in other locations. It’s large and important differential diagnostic spectrum makes this tumor special.

DOI: 10.29245/2578-3009/2018/5.1158 View / Download Pdf View Full Text
Vol 2-5 Commentary

Commentary on Paper "Drug-Induced HSP90 Inhibition Alleviates Pain in Monoarthritic Rats and Alters the Expression of New Putative Pain Players at the DRG"

Fani L. Moreira Neto1,2,3*

1Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal

2IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal

3Departamento de Biomedicina – Unidade de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal

Heat shock protein 90 (HSP90) belongs to a highly conserved family of molecular chaperones and is responsible for regulating the protein folding quality control of specific client proteins. In a recent study published in Molecular Neurobiology, HSP90mRNA levels were found significantly decreased after knock-down in vitro of activating transcription factor 3 (ATF3), indicating that this stress-inducible gene that mediates pro-apoptosis or cytoprotection might act as positive regulator of HSP90 expression. In the rodent model of Monoarthritis, characterized by being accompanied by chronic joint inflammatory pain, the mRNA and protein levels for HSP90 were significantly increased in dorsal root ganglia (DRG). Additionally, a reversal in the HSP90 mRNA upregulation and in the 70kDa protein isoform levels following intrathecal delivery of a HSP90 inhibitor, along with an attenuation of movement-induced mechanical allodynia, and reduced neuronal sensitization and satellite glial cells (SGC) activation in ipsilateral DRG of the arthritic animals were also observed. This suggests a putative role of HSP90 in chronic inflammatory pain pathophysiology at sensory ganglia level that is still unexplored. To date only a few studies demonstrated a link between pain and HSP90 modulation, but there are several evidences that HSP90 is involved in inflammation, tumorigenesis and neurodegeneration. Here, we discuss the status of the studies demonstrating a role for HSP90 in inflammation and comment on their possible involvement in neuronal/glial driven pain mechanisms.

DOI: 10.29245/2578-3009/2018/5.1160 View / Download Pdf View Full Text
Vol 2-5 Research Article

Demonstration of Mosquito Midgut Antigen for the Effective Control of Mosquito Population

Sabahat Abdullah, Sajjad Ur Rahman, Ahsan Naveed*, Qamar Majeed

Institute of Microbiology, University of Agriculture Faisalabad, 3840, Pakistan

Mosquito-borne diseases can be reduced drastically with the aid of vaccines which provoke mosquitocidal or mosquito-killing effect. The midgut of mosquito performs a fundamental role in the development and the transmission of ailment. Anti-midgut antibodies show the extensive variety of activity, blockading the development of pathogen in various species of mosquitoes. In addition to reducing the egg-laying ability of mosquitoes and survivorship also block the transmission activity of pathogen. Mitsuhashi and Maramorosch media was used to culture the mosquito midgut cells. The cells were formalin inactivated and injected into the rabbits in plain and adjuvanted form to raise hyperimmune serum. The serum was processed for IHA and serum showing high titre were selected for blood feeding assay. The blood from the rabbits was fed to the mosquitos to observe the mosquitocidal effect of the antigen. In blood feeding assay killing of mosquitoes was also observed after regular interval of time. The overall results proved that mosquito midgut contains antigenic peptides that may be able to induce the antibody response. These antigenic peptides somehow irritate digestive mucosa of the mosquitoes on blood feeding and have the potential to kill or reduce the mosquito population.

DOI: 10.29245/2578-3009/2018/5.1148 View / Download Pdf View Full Text
Vol 2-5 Review Article

Emerging Evidence Supports the Hypothesis that Neutrophil Extracellular Traps are a Major Factor in Genesis and Progression of Chronic Obstructive Pulmonary Disease

Astrid Obermayer1*, Walter Stoiber1, Fikreta Grabcanovic-Musija2, Michael Studnicka2

1Department of Biosciences, Biomedical Ultrastructure Research, University of Salzburg, Salzburg, Austria

2University Clinic of Pneumology, Paracelsus Medical University, Salzburg, Austria

Since their discovery about fifteen years ago, neutrophil extracellular traps (NETs) have been recognized as an intrinsic part of vertebrate innate immunity and inflammatory response. Consisting of entangled strands of extracellular DNA decorated with histones, elastase, myeloperoxidase and other proteins, NETs entrap and kill pathogens, but are increasingly also found to contribute to acute and chronic inflammatory disease due to their toxicity to host cell and autoimmunity induction. Chronic obstructive pulmonary disease (COPD) turned out to be among the major disorders involving overshooting formation of NETs and associated adverse effect. In the present review, we summarize the progress in knowledge on the role of NETs in COPD pathology made since our first reports on this subject. We highlight recent substantial advances and discuss possible cause-and-effect relationships, connections with common comorbidities and interactions with drugs, also to illustrate the importance of NETs as a future diagnostic tool and target for new medication strategies.

DOI: 10.29245/2578-3009/2018/5.1161 View / Download Pdf View Full Text
Vol 2-5 Mini Review

A Review of a Diagnostic Tool: Galactomannan

Gulhadiye Avcu1, Deniz Yilmaz Karapinar2*

1Ege University Faculty of Medicine, Children’s Hospital, Department of Pediatric Infectious Disease, 35040 Bornova Izmir, Turkey

2Ege University Faculty of Medicine, Children’s Hospital, Pediatric Hematology, 35040 Bornova Izmir, Turkey

Invasive fungal infections, including invasive aspergillosis are associated with a high morbidity and mortality especially in immunocompromised patients. Diagnosis is often difficult due to several factors such as delay in clinical suspicion and the lack of spesific clinical findings. Galactomannan is a polysaccharide cell wall component of Aspergillus and galactomannan antigen detection has become widely used for diagnosis of invasive aspergillosis. Here, we tried to discuss the diagnostic value of the galactomannan test in the context of literature review.

DOI: 10.29245/2578-3009/2018/5.1137 View / Download Pdf View Full Text