This study was conducted to clarify the taxonomic status of Bacteroides type A strains with high vitamin B₁₂-producing ability that is widely distributed in the intestinal tracts of freshwater fish. ...Seventeen strains of Bacteroides type A isolated from five fish species were all rod-shaped and gram-negative. The strains were positive for esculin hydrolysis, nitrate reduction, resistance to bile, acid phosphatase, and negative for the production of catalase and urease and the susceptibility to vancomycin. The G+C content of DNA from the 17 strains was 29·1-31·9 mol%, and 16S rDNA sequence analysis revealed a close phylogenetic relationship between Bacteroides type A strains and Cetobacterium somerae sharing 99·7-100% sequence similarity. In addition, strains were capable of producing vitamin B₁₂ at a rate of 1·82-13·98 ng ml⁻¹ in 48 h. Phenotypic and phylogenetic characteristics indicated that all isolates previously classified as Bacteroides type A strains belong to C. someare. This study provided the important finding of novel niche of vancomycin-resistant bacteria such as C. somerae in the intestinal tract of freshwater fish.
While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin‐induced ...antiproliferative effects and its underlying mechanism were examined using six CRC cell lines. Statins except pravastatin showed antiproliferative effects (simvastatin ≥ fluvastatin > atorvastatin) even though both of simvastatin and pravastatin could activate mevalonate pathways, suggesting the statin‐mediated antiproliferative effects depended on non‐mevalonate pathway. Indeed, statin induced p27KIP1 expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27KIP1 by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. In the clinical setting, Statin intake (except pravastatin) displayed the downregulated EZH2 expression and inversely upregulated p27KIP1 expression in the resected CRC by immunohistochemical staining and resulted in the significantly better prognoses both in overall survival (p = 0.02) and disease free survival (p < 0.01) compared to patients without statin intake. Statins may inhibit tumor progression via an EZH2‐mediated epigenetic alteration, which results in survival benefits after resected CRC. Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC.
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Although statin use is associated with reduced colorectal cancer risk, the mechanism by which the drugs exert antitumor effects and their benefits for survival remain unclear. Here, experimental and clinical statin‐associated anticancer effects were found to differ for different kinds of statins. For example, while both simvastatin and pravastatin activated the mevalonate pathway in colon cancer cells, of the two drugs, only simvastatin displayed non‐mevalonate‐pathway antiproliferative effects via induction of p27KIP1 and epigenetic silencing by enhancer of zeste homolog 2 (EZH2). Statin‐induced downregulation of EZH2 and upregulation of p27KIP1 was associated with improved overall and disease‐free survival.
The objective of the present study was to understand the immune response induced by different forms of the probiont
Lactobacillus rhamnosus JCM 1136 in rainbow trout
Oncorhynchus mykiss and to ...clarify the carry over effect after withdrawal of the probiotic diet. A prebiotic-based diet was formulated, which served as the control diet, and to it the selected lactic acid bacteria (LAB) was incorporated in one of the three forms: (1) heat-killed, (2) live-sprayed or (3) freeze-dried. A rearing trial was conducted in triplicate with juvenile rainbow trout (average 126 g), which were fed on the control and three other diets containing the respective forms of the probionts, two times daily until the satiation level for a period of 30 days, following which the test diets were withdrawn and control diet was fed up to 45 days. Sampling was done at 10, 20, 30 and 45 days for gut microflora composition and the non-specific humoral and cellular immune responses of the fish. The viable forms (live spray or freeze-dried) were found to induce better phagocytic activity and complement activity compared to that of the non-viable heat-killed form. The plasma immunoglobulin level showed an increasing trend in the fish groups that received the viable probiont, but the trend did not exist towards the end of the study. Upon withdrawal of the probiotic diets, the LAB disappeared from the intestine and the elevated immune parameters returned to the prefed level. This study elucidates that probiont viability could probably influence the immune responses they induce.
This study elucidates the immune modulation including the expression of cytokine genes following dietary administration of three selected probiotic bacteria—
Lactobacillus rhamnosus,
Enterococcus ...faecium and
Bacillus subtilis to fish, rainbow trout
Oncorhynchus mykiss. They were fed for 45 days on either a basal control diet or one of the three probiotic diets containing the specific bacteria in freeze-dried form at a density of 10
9
CFU
g
feed
−1.
The non-specific immune parameters examined—superoxide anion production by the head kidney leukocytes and the alternate complement activity of serum was improved by probiotic feeding. Besides this, the relative gene expressions of interleukin-1
β1, tumor necrosis factor 1 and 2 and transforming growth factor-
β were up regulated in the spleen and the head kidney. The comparatively better performance of
E. faecium could possibly be linked to their suitable ambient temperature conditions. Thus, probiotic bacteria delivered in feed exerts its influence on the immune system of fish, both at cellular and molecular levels.
This study was undertaken to examine the effect of supplementing a suggested probiotic bacteria
Lactobacillus rhamnosus JCM 1136 in feed on immune response and gut flora composition of rainbow trout
...Oncorhynchus mykiss. The probiotic bacteria were incorporated into a commercial feed to constitute two experimental diets containing either 10
9 or 10
11 colony forming unit of live bacteria/g of feed while a third diet without the bacterial supplement served as the control diet. The diets were offered to rainbow trout (75
g average weight) in triplicate tanks for 30 days. Fish were sampled at 10, 20 and 30 days after commencement of the feeding trial to determine the proportion of the given probiont in the gut microflora composition and the nonspecific humoral and cellular immune responses on the 30th day.
The relative proportion of the probiont increased with the feeding duration in the intestine, but not in the stomach. The proportion of
L.
rhamnosus in the stomach corresponded to the intake levels while no such relation existed in the intestine. The serum lysozyme and complement activities were significantly greater in fish fed the higher level of probiont compared with the control fish. The phagocytic activity of head kidney leucocytes also showed similar tendencies. These observations indicate the potential immuno-regulatory role of probiotic organisms in rainbow trout.
While previous studies have reported on the prognostic value of total plasma cell-free deoxyribonucleic acid (cfDNA) in lung cancers, few have prospectively evaluated its predictive value for ...systemic therapy response.
We conducted a prospective study to evaluate the association between changes in total cfDNA and radiologic response to systemic therapy in patients with stage IIIB/IV non-small-cell lung cancers (NSCLCs). Paired blood collections for cfDNA and computed tomography (CT) assessments by RECIST v1.0 were performed at baseline and 6–12 weeks after therapy initiation. Total cfDNA levels were measured in plasma using quantitative real-time polymerase chain reaction. Associations between changes in cfDNA and radiologic response, progression-free survival (PFS), and overall survival (OS) were measured using Kruskal–Wallis and Kaplan–Meier estimates.
A total of 103 patients completed paired cfDNA and CT response assessments. Systemic therapy administered included cytotoxic chemotherapy in 57% (59/103), molecularly targeted therapy in 17% (17/103), and combination therapy in 26% (27/103). Median change in cfDNA from baseline to response assessment did not significantly differ by radiologic response categories of progression of disease, stable disease and partial response (P = 0.10). However, using radiologic response as continuous variable, there was a weak positive correlation between change in radiologic response and change in cfDNA (Spearman's correlation coefficient 0.21, P = 0.03). Baseline cfDNA levels were not associated with PFS hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.93–1.20, P = 0.41 or OS (HR = 1.04, 95% CI 0.93–1.17, P = 0.51), neither were changes in cfDNA.
In this large prospective study, changes in total cfDNA over time did not significantly predict radiologic response from systemic therapy in patients with advanced NSCLC. Pretreatment levels of total cfDNA were not prognostic of survival. Total cfDNA level is not a highly specific predictive biomarker and future investigations in cfDNA should focus on tumor-specific genomic alterations using expanded capabilities of next-generation sequencing.
Abstract Background To clarify the patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy. Methods From January 1999 to March 2012, 577 patients underwent ...laparoscopic or laparoscopy-assisted gastrectomy for curative resection of gastric cancer. Recurrence patterns were classified as locoregional, hematogenous, peritoneal, distant lymph node and mixed. Recurrence patterns and time to recurrence were retrospectively examined and risk factors for recurrence were analyzed. Results Recurrence occurred in 28 (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%), hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to recurrence was 384 days (range 83–1497 days). Recurrence was detected within a year in 13 cases (46.4%), within two years in 21 (75%), and within three years in 25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of operation, tumor depth, and lymph node classification as risk factors for recurrence. Multivariate analysis indicated tumor depth and lymph node classification as risk factors of recurrence. Conclusions Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are similar to those after open gastrectomy, with no peculiarities specific to laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed according to the present inclusion criteria, follow-up can be similarly performed as for open gastrectomy.
Aims: To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking‐related ...interstitial lung disease.
Methods and results: Patients who had undergone lobectomy for lung cancer were reviewed. Subjects included 230 non‐smokers and 587 smokers, of whom 572 had a known smoking index (SI). They were classified into mild, moderate and heavy smokers. Centrilobular emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis (AEF), the presence of foci resembling usual interstitial pneumonia pattern (UIP/P) and the rate of postoperative respiratory failure were assessed. The incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers (P < 0.01) with lower lobe predominance. There were significant correlations (P < 0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but was not seen in patients with AEF alone (P < 0.01).
Conclusions: AEF is an important smoking‐related change in the lung that appears to correlate with the smoking history, and its distinction from UIP/P may be important.
The aim of the present study was to clarify the taxonomic status of intestinal bacteria isolated from Japanese flounder (Paralichthys olivaceus) and describe their ability to digest chitin.
...Phylogenetic analysis based on 16S ribosomal DNA (rDNA) sequences showed that 82 representative isolates were closely related to three major species of marine vibrios, Vibrio scophthalmi-Vibrio ichthyoenteri group (41 isolates), Vibrio fischeri (39 isolates) and Vibrio harveyi (two isolates), with similarities of 97.2-99.8%, 96.4-100% and 98.6-99.5% respectively. These findings indicate that V. scophthalmi-V. ichthyoenteri group is indigenous to the intestinal tract of Japanese flounder. Moreover, the ability of 82 isolates to digest chitin was examined using the agar plate method and PCR amplification of the chiA gene. The two V. harveyi isolates and 36 of 41 V. scophthalmi-V. ichthyoenteri isolates digested chitin and were chiA PCR positive, whereas all 39 V. fischeri isolates digested chitin but were chiA PCR negative.
Intestinal bacteria from Japanese flounder were mainly composed of Vibrio scophthalmi-V. ichthyoenteri group and V. fischeri. Taken together, the results showed that 81 of 82 isolates could digest chitin. However, only 38 of these isolates possessed a chiA homologue which could be identified by PCR.
The present study shows that Japanese flounder harbours bacteria of the V. scophthalmi-V. ichthyoenteri group, and these results are similar to what has been found for turbot (Scophthalmus maximus).
A chitin-degrading bacterial strain, KN1699, isolated from Yatsu dry beach (Narashino, Chiba Prefecture, Japan), was identified as Vibrio parahaemolyticus. Treatment of powdered chitin with crude ...enzyme solution prepared from the supernatant of KN1699 cultures yielded a disaccharide, β-d-N-acetylglucosaminyl-(1,4)-d-glucosamine (GlcNAc-GlcN), as the primary chitin degradation product. The extracellular enzymes involved in the production of this heterodisaccharide, chitinase (Pa-Chi; molecular mass, 92 kDa) and chitin oligosaccharide deacetylase (Pa-COD; molecular mass, 46 kDa), were isolated from the crude enzyme solution, and their hydrolysis specificities were elucidated. These studies confirmed that (1) Pa-Chi hydrolyzes chitin to produce (GlcNAc)₂ and (2) Pa-COD hydrolyzes the acetamide group of reducing end GlcNAc residue of (GlcNAc)₂. These findings indicate that GlcNAc-GlcN is produced from chitin by the cooperative hydrolytic reactions of both Pa-Chi and Pa-COD.
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