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分子バイオマーカーと診断のジャーナル

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音量 10, 問題 1 (2019)

研究論文

Immune Modulatory Effects of Hypercholesterolemia: Can Atorvastatin Convert the Detrimental Effect of Hypercholesterolemia on the Immune System?

Zeinab Emruzi, Pegah Babaheidarian and Ghasem Ahangari

Background and purpose: Many observations showed that hypercholesterolemia can disrupts immune response. Statin drugs that were used for the treatment of hypercholesterolemia patients can interfere in regulation of the immune response and cytokine secretion. The primary aim of the current study was to investigate the immune response among hypercholesterolemia patients, who were treatment-naïve and healthy subjects. The secondary goal of the study was to determine whether atorvastatin can reverse the detrimental effect of hypercholesterolemia on the immune system.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients afflicted with hypercholesterolemia who were treatment-naïve along with 50 sex- and age-matched hypercholesterolemia patients receiving atorvastatin and 50 sex- and age-matched healthy subjects. Quantitative PCR and ELISA methods were used for gene and protein expression analysis of T helper 1 (Th1) and Th2 related cytokines. Additionally, the expression of the cluster of differentiation (CD) markers on T, B, and NK cells were measured by flow cytometry method.
Results: The results showed that hypercholesterolemia and atorvastatin downregulated the expression of Th1- related cytokines and elevated the levels of Th2-related cytokines. The expression of cell surface markers, CD25 and CD69, was significantly decreased in the treatment-naïve, and atorvastatin groups.
Conclusion: It seems that atorvastatin is not able to repair the deleterious effects of hypercholesterolemia on the immune system, and elevated levels of cholesterol along with the administration of atorvastatin tilt the Th1/Th2 balance in favor of Th2 and reduce T cell activation.

総説

HNSCC and Immunotherapy: The Beginning of a Long Story

Thibault Gauduchon, Thibaut Reverdy, Andy Karabajakian, Laetitia Collet, Max Gau, Eve-Marie Neidhardt and Jérôme Fayette

The immunotherapy revolution has not spared Head and neck squamous cell carcinoma (HNSCC). Checkpoint inhibitors (anti-PD-1 / PD-L1) were the first to be validated in second line treatment and soon come to the first line in local or metastatic recurrence. Many studies are currently underway to expand the indications of these new therapies, whether as monotherapy or in combination. In addition, immunotherapy is not limited to checkpoint inhibitors and many other immunotherapy molecules are currently under study. The selection of patients who benefit from immunotherapy and the evaluation of the response to these treatments are problems not completely solved. The aim here is to present the state of art on immunotherapy in HNSCC.

研究論文

The Role of 16s Ribosomal RNA in Diagnosing Spontaneous Bacterial Peritonitis

Sally Abed, Mohamed Egezy, Tarek sheta and Maysaa El-Sayed Zaki

Background: Cancer, the accurate clinical diagnosis of spontaneous bacterial peritonitis (SBP) is challenging due to frequent absence of the symptoms and signs which are non-specific. The laboratory diagnosis of SBP depends mainly on the ascetic fluid neutrophil count. Therefore, it is recommended to inoculate the ascitic fluid into blood culture but cultures are time consuming and have a limited value to urgently direct the initiation of specific effective antibiotic treatment.
Aim of study: To evaluate the role of 16s ribosomal RNA in early diagnosis of SBP.
Patients and methods: The present study was cross-sectional study that was carried out in Mansoura University hospital from January 2016 till March 2017. The study included 120 patients complaining of chronic hepatitis C. Each patient was subjected to full clinical history including symptoms of spontaneous bacterial peritonitis such as fever, constipation and abdominal pain. The severity of liver affection was classified according to Child score. Complete liver function tests were performed. The peritoneal fluid was divided to three samples, one sample for total leucocytic count by hemocytometer, the other sample was centrifuged and the sediment was cultured on blood agar, MacConkey agar and Sabouraud’s dextrose agar at 37C for 24-48 hours DNA Extraction the sediment pellet of the peritoneal fluid was subjected to DNA extraction by QIAampDNAM; ini kit (QIAGEN, Germany) according to the manufacturer’s instruction.
Results: The culture positive cases were 21 patients 20 of them were positive for 16sRNA and only 1 patient was negative for 16sRNA. While 16s RNA was positive in 26 patients in which 6 were negative culture. The WBCS count was >250/mm3 in 31 patients of which 26 patients were positive for 16s RNA and 21 were culture positive. The 16sRNA had higher sensitivity (81.25%), while the culture the sensitivity was (67.7%).
Conclusion: In the current study, we assessed the 16s ribosomal RNA detection by PCR and it was more rapid and sensitive than bacterial cultures to confirm bacterial infection of the ascetic fluid even after cultures with bedside inoculation of the ascetic fluid samples.

研究論文

Genome-Wide Analysis of Epstein-Barr Virus Isolated from Extra Nodal NK/T-Cell Lymphoma, Nasal Type

Wenjing Ku, Ningjing Lin and Zheming Lu

Extra-nodal natural killer (NK) cell/T cell lymphoma (NKTCL), a rare type of non-Hodgkin’s lymphoma, has strongly been associated with Epstein-Barr virus (EBV) infection. However, there is no EBV genomes isolated from NKTCL, and the roles of the variations of EBV strains played in the pathogenesis of NKTCL is still unclear. In this study, whole EBV genomes from eight primary NKTCL biopsy specimens were obtained using next generation sequencing, designated NKTCL-EBV1 to 8. Compared to the six mostly referenced EBV strains, NKTCL-EBVs were closely resemble to GD1 strain, but still harbors 2072 variations, including 1938 substitutions, 58 insertions and 76 deletions. Moreover, the results from phylogenetic analysis of whole NKTCL genomes and specific genes demonstrated that all the NKTCL-EBVs were related to Asian EBV strains. Furthermore, changes in CD4+ and CD8+ T-cell epitopes of EBNA1 and LMP1 may affect the efficacy for a CTL-based therapy. In conclusion, this is the first large study to our knowledge to obtain EBV genomes isolated from NKTCL and show the diversity of EBV genomes in a whole genome level by phylogenetic analysis.

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