Analysis of oral microbiota in Japanese oral cancer patients using 16S rRNA sequencing

ObjectivesIt is important to determine the cause of increasing oral cancer occurrence and mortality rates in Japan, because the mortality rate has recently decreased in other developed countries. The impact of microbiota in carcinogenesis, especially in the digestive tract has been reported. This study aimed to clarify the relationship between oral cancer and oral microbiota in Japanese patients.MethodsDNA was extracted from salivary samples of 60 oral cancer patients and 80 non-cancer individuals as controls. We performed metagenomic analysis using 16S rRNA amplicon sequencing. Statistical analysis in this study was performed using R (version 3.5.0).ResultsOral cancer patients showed higher α-diversity compared to the control group, and the β-diversity between the two groups differed significantly. Further, there was a significant difference in the abundance ratio of bacterial genera between the two groups. Peptostreptococcus, Fusobacterium, Alloprevotella, and Capnocytophaga were more abundant in the cancer group compared to the control, whereas Rothia and Haemophilus were less abundant (p < 0.01). A negative correlation in the microbiota composition was confirmed between the operational taxonomic units (OTU) of genus Rothia and T-stage progression using the TNM classification method. We performed logistic regression analysis to investigate the impact factor for the oral cancer group, and the result showed that Chao 1 index and sex are statistically significant variables.ConclusionsIn this study, we observed an increased bacterial diversity in oral cancer patients and found distribution changes for some bacteria.     

Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi

Protozoan parasites of the genus Trypanosoma can infect virtually all mammalian species. Within this genus, Trypanosoma dionisii from bats and Trypanosoma cruzi that causes Chagas' disease, belonging to the subgenus Schizotrypanum, can invade mammalian cells. The mechanisms of cell invasion by T. dionisii are poorly understood. To address that question, metacyclic trypomastigotes (MT) and human epithelial HeLa cells were used. Similarly to genetically divergent T. cruzi strains G (TcI) and CL (TcVI), associated, respectively with marsupial and human infections, T. dionisii infectivity increased under nutritional stress, a condition that induces host cell lysosome exocytosis required for parasite internalization. For efficient internalization, T. dionisii depended on MT protein tyrosine kinase (PTK) and Ca(2+) mobilization from acidocalcisomes, whereas T. cruzi strains also relied on phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC) and Ca(2+) released from thapsigargin-sensitive compartments. T. dionisii-induced signaling in host cells implicated PKC and Ca(2+) mobilized from thapsigargin-sensitive stores, like T. cruzi, but without PI3K involvement. Unlike T. cruzi, T. dionisii metacyclic forms did not use l-proline as source of energy required for internalization. Molecules related to T. cruzi surface glycoproteins involved in MT-host cell interaction were undetectable in T. dionisii. The difference in the surface profile of the two species was also inferred from the susceptibility of T. dionisii metacyclic forms to complement-mediated lysis, as opposed to complete resistance of T. cruzi. In summary, the two Trypanosoma species display distinct surface profiles but invade host cells through a common mechanism involving lysosome mobilization to the site of parasite entry.     

Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response

Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B and host response to peginterferon α (PEG-IFNα) and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNα-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFNλ). Both IL28B SNPs were 100% identical; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (≈ 3.3-fold, P < 0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P = 0.028). Expressions of viral sensors and modulators were significantly higher in nonvirological responders (NVR) than that in others despite stratification by IL28B genotype (≈ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was confirmed by western blotting, and the extent of IPS-1 protein cleavage was associated with the variable treatment response. CONCLUSION: Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFNα/RBV. Both IL28B minor allele and higher RIG-I and ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.     

Effect of Arthrocentesis on TMJ Disturbance of Mouth Closure with Loud Clicking: A Preliminary Study

The objective of this study was to evaluate the short-term effect of arthrocentesis on temporomandibular joint disturbance of mouth closure with loud clicking compared to the effect of one-time pumping into the joint space previous to arthrography. Twenty-one consecutive patients (22 joints) with loud clicking during mouth closure were enrolled. All were unable to smoothly close the mouth without effort. Eleven patients (12 joints) were examined using magnetic resonance imaging (MRI) to determine disk position. They then underwent arthrocentesis. Ten patients (10 joints) underwent arthrography alone as controls. Six months later, changes in clicking and temporomandibular joint movement were analyzed and the disk position was re-examined. There was improvement of mouth closing and clicking occurred in nine joints from the arthrocentesis group and two joints from the control group, with a significant difference between the two groups. Arthrocentesis may be indicated for patients with temporomandibular joint dysfunction and loud clicking when mouth closing.     

Causes of thrombocytopenia in chronic hepatitis C viral infection

We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.     

Case with metastatic cutaneous malignant melanoma that developed Vogt–Koyanagi–Harada-like uveitis following pembrolizumab treatment

Documenta Ophthalmologica - The study reports a case with metastatic cutaneous malignant melanoma that developed Vogt–Koyanagi–Harada-like uveitis during pembrolizumab treatment. The...     

The Prognostic Nutritional Index Predicts Long-term Outcomes of Gastric Cancer Patients Independent of Tumor Stage

Purpose

The aim of this study was to investigate the impact of the prognostic nutritional index (PNI) on the long-term outcomes in gastric cancer patients.

Methods

This study reviewed the medical records of 548 patients with gastric cancer who underwent gastrectomy. The PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm³). The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PNI. The multivariate analysis was performed to identify the prognostic factors.

Results

The mean PNI was significantly lower in patients with T3–T4 tumors (P < 0.001) and lymph node metastasis (P < 0.001) than in those without such factors. Patients who had a postoperative complication had a lower mean PNI than those without (P = 0.023). When the ROC curve analysis was performed, the optimal cutoff value of the PNI for predicting the 5-year survival was 48. In the multivariate analysis, a low PNI was an independent predictor for poor overall survival (P < 0.001). In the subgroup analysis, the overall and relapse-free survival rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III disease.

Conclusions

The PNI is a simple and useful marker for predicting the long-term outcomes of gastric cancer patients independent of the tumor stage. Based on our results, we suggest that the PNI should be included in the routine assessment of gastric cancer patients.