The Effectiveness and Safety of Long-Term Macrolide Therapy for COPD in Stable Status: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were -0.50 (95% CI: -0.81, -0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George's Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of -4.42 (95% CI: -9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.

The ROX index (Index combining the respiratory rate with oxygenation) is a prognostic factor for acute respiratory distress syndrome.

BACKGROUND: There is no existing reliable and practical method for predicting the prognosis of acute respiratory distress syndrome (ARDS). OBJECTIVE: We aimed to clarify the association between the ROX index, which is calculated as the ratio of peripheral oxygen saturation divided by the fraction of inspired oxygen to the respiratory rate, and the prognosis of patients with ARDS under ventilator support. METHODS: In this single-center retrospective cohort study from prospectively collected database, eligible patients were categorized into three groups based on ROX tertiles. The primary outcome was the 28-day survival, and the secondary outcome was 28-day liberation from ventilator support. We performed multivariable analysis using the Cox proportional hazards model. RESULTS: Among 93 eligible patients, 24 (26%) patients died. The patients were divided into three groups according to the ROX index (< 7.4, 7.4-11, ≥ 11), with 13, 7, and 4 patients dying in the groups, respectively. A higher ROX index was associated with lower mortality; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 0.54[0.21-1.41], 0.23[0.074-0.72] (P = 0.011 for trend) and a higher rate of successful 28-day liberation from ventilator support; adjusted hazard ratios [95% CIs] for increasing tertiles of ROX index: 1[reference], 1.41[0.68-2.94], 2.80[1.42-5.52] (P = 0.001 for trend). CONCLUSIONS: The ROX index at 24 h after initiating ventilator support is a predictor of outcomes in patients with ARDS and might inform initiation of more advanced treatments.

[A Case of Stage â £ Pancreatic Head Cancer with Aortic Lymph Node Metastasis Treated with 40 Courses of mFOLFIRINOX Therapy after Surgery and Maintaining PR].

The patient was a male in his 60s who presented with obstructive jaundice and was diagnosed with pancreatic head cancer. He was referred to the Department of Surgery 2 months later due to prolonged jaundice and immediately underwent pylorus-preserving pancreatoduodenectomy with the diagnosis of resectable pancreatic cancer. Pathology showed pN1b (14/37), but 16b1 interaorticocaval was 0/1. The patient was then diagnosed with Stage ⅡB, R0. After completion of adjuvant chemotherapy with S-1, 1 year after surgery, CA19-9 was reelevated and PET/CT-positive enlarged lateroaortic lymph nodes and multiple nodules in both lungs were observed. The lymph nodes were also seen on preoperative CT, and the preoperative diagnosis was Stage Ⅳ. After insertion of an implantable central venous port, mFOLFIRINOX therapy was initiated. The patient had an anaphylactic reaction after 7 courses of L-OHP, and the treatment was continued without L-OHP. After 40 courses of mFOLFIRINOX therapy, the aortic lymph nodes reduced in size, PET results were negative, and the pulmonary nodules partially resolved. We report a case of a patient with Stage Ⅳ pancreatic head cancer who maintained PR for more than 1 year and 7 months after the initiation of mFOLFIRINOX therapy and survived for more than 2 years and 10 months since the initial diagnosis.

Clinical phenotypes from fatal cases of acute respiratory distress syndrome caused by pneumonia.

There have been no report of objective clinical characteristics or prognostic factors that predict fatal outcome of acute respiratory distress syndrome (ARDS) since the Berlin definition was published. The aim of this study is to identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia. In total, 104 cases of Japanese patients with pneumonia-induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late (≥ 7 days) death groups, and clinical variables and prognostic factors were statistically evaluated. Of the 50 patients who died within 180 days, 18 (36%) and 32 (64%) were in the early (median 2 days, IQR [1, 5]) and late (median 16 days, IQR [13, 29]) death groups, respectively. According to multivariate regression analyses, the APACHE II score (HR 1.25, 95%CI 1.12-1.39, p < 0.001) and the disseminated intravascular coagulation score (HR 1.54, 95%CI 1.15-2.04, p = 0.003) were independent prognostic factors for early death. In contrast, late death was associated with high-resolution computed tomography (HRCT) score indicating early fibroproliferation (HR 1.28, 95%CI 1.13-1.42, p < 0.001) as well as the disseminated intravascular coagulation score (HR 1.24, 95%CI 1.01-1.52, p = 0.039). The extent of fibroproliferation on HRCT, and the APACHE II scores along with coagulation abnormalities, should be considered for use in predictive enrichment and personalized medicine for patients with ARDS due to pneumonia.

[An Analysis of Surgery for Colorectal Cancer Lung Metastasis].

OBJECTIVES: Resection of lung metastasis in colorectal cancer leads to a good prognosis; therefore, surgical treatment for resectable metastases is recommended by the Japanese Society for Cancer of the Colon and Rectum Guidelines for the treatment of colorectal cancer. In this study, we investigated the factors that affect the prognosis of resection of such lung cancers. RESULTS: Outcomes of 23 cases of lung resection performed from 2000 to 2019 were investigated. The 5-year overall survival rate after lung resection was 55.5%, and the 5-year relapse-free survival rate after liver resection was 27.0%. Univariate analysis identified sex(p=0.024), tumor size(p=0.0129)and complications(p=0.0129)as prognostic factors, while multivariate analysis revealed sex(p=0.0278, relative risk=5.38)to be a prognostic factor. CONCLUSION: In this study, sex was identified as a poor prognostic factor. Further evidence from cases is needed to ascertain the effects of other factors.

Handling and packaging of medical bags at acute disaster sites under high-temperature conditions.

OBJECTIVE: After the large-scale earthquake in 2011, the disaster medical assistance team (DMAT) was made responsible for medical activities during the hyperacute phase of a disaster or accident in Japan. The medicines to be administered at the disaster sites, packaged in medical bags, may be affected by the temperatures there. This study aimed at establishing a method to handle drug bags in high-temperature situations by determining the temperature changes in medical bags subject to high temperatures and examining the effect of opening the bag and using heat-insulating material (HIM) and coolants. RESULTS: Closed and semi-opened bags limited the temperature increase in the central part of the bag at both 35 and 40 °C to a greater extent than opened bags. When coolant and HIM were used in closed and semi-opened bags, the internal temperatures were significantly lower than in the opened state at 40 °C. In high-temperature disaster sites, medical bags should be maintained in a semi-opened or closed state using a HIM and coolant.

[Laparoscopic Partial Hepatectomy for the Liver Metastasis of Gastric Cancer after Nab-Paclitaxel plus Ramucirumab Combination Therapy-A Case Report].

We report a case of laparoscopic partial hepatectomy after nab-paclitaxel plus ramucirumab(nab-PTX plus RAM)combination therapy for postoperative liver recurrence of gastric cancer. The patient was a 50's man who underwent laparoscopic distal gastrectomy, D2 lymph node dissection, and Billroth-I reconstruction for gastric cancer. The pathological findings were L, Gre, Post, Type 3, por>tub2, pT3N3a, M1(CY1), fStage Ⅳ. Postoperative chemotherapy with S-1 was performed. The CT examination 6 months after the operation revealed a total of 3 tumors(maximum diameter of 5×4 cm)in liver segments S6, 7, and 8. We started nab-PTX plus RAM combination therapy for liver metastases and performed laparoscopic partial hepatectomy when 12 courses of the treatment were completed. The postoperative course was uneventful, and the patient was discharged on postoperative day 7. Pathological results suggested that the tumor was exposed on the cut surface, and 6 courses of nab-PTX plus RAM combination therapy were administered postoperatively. The patient has been recurrence-free 12 months after the operation.

[A Case of Recurrent Gastric Cancer with Clinical Complete Response after Ramucirumab plus Paclitaxel Therapy].

We report a case of a 61-year-old man who underwent open total gastrectomy and D2 lymph node dissection for gastric cancer. The pathological findings were suggestive of pT2N3M0, fStage ⅢA. S -1 was administered for 1 year post-surgery. One year and 9 months after the operation, an epigastralgia was found, and the PET-CT showed an increase of SUVmax 3.80 around the celiac artery. S -1 plus CDDP therapy was initiated. However, due to the occurrence of neutropenia, the therapy was changed to ramucirumab plus paclitaxel. After 20 courses of the same regimen, no PET-CT uptake was observed. We thus considered it cCR and discontinued further chemotherapy. The patient has been alive for 15 months without recurrence. By performing effective chemotherapy at an early stage, cCR could be observed after a secondary treatment. Therefore, longterm survival could be expected for post-operative recurrence of gastric cancer.

Measuring Attitudes Toward Nursing Safety Violations.

This study measured implicit and explicit attitudes toward major nursing safety violations using the Implicit Association Test (IAT) and self-reported questionnaires, respectively. Experiment 1 sampled nursing students (n = 71), and Experiment 2 sampled patient safety nurses (n = 38). Although reaction time to IAT stimuli of major nursing safety violations was quicker than of general nursing behaviors, error trials did not reveal a significant difference between IAT stimuli of major nursing safety violations and of general nursing behaviors in Experiment 1. Explicit attitude was related with intention to violate safety protocols in Experiment 1. In Experiment 2, both reaction time and error trials showed significant differences between IAT stimuli of major nursing safety violations and of general nursing behaviors. This was interpreted in that patient safety nurses had formed a firm implicit attitude, unlike the nursing students; however, the findings suggested that attitudes were not related to violations in nursing.

Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC.

BACKGROUND: Glycoprotein expression profile is dramatically altered in human cancers; however, specific glycogenes have not been fully identified. MATERIALS AND METHODS: A comprehensive real-time polymerase chain reaction (PCR) system for glycogenes (CRPS-G) identified several outstanding glycogenes. GCNT2 was of particular interest after GCNT2 expression and epigenetics were rigorously investigated in primary colorectal cancer (CRC). RESULTS: The highlights of this work can be summarized as follows: (i) Expression of GCNT2 was remarkably suppressed. (ii) Silenced expression of GCNT2 was reactivated by combined demethylating agents. (iii) Promoter DNA methylation of GCNT2 was silenced in CRC cell lines and tissues. Hypomethylation of GCNT2 variant 2 is tightly associated with lymph node metastasis in primary CRC. (iv) GCNT2 methylation level in the normal tissues also showed a close association with that in the tumor tissues and reflected lymph node metastasis. CONCLUSION: We identified aberrant expression of GCNT2, which can be explained by promoter DNA hypermethylation. Hypomethylation of the GCNT2 variant 2 reflected lymph node metastasis of CRC in the tumor and normal tissues.

Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer.

Metastatic lymph node density (ND) has been reproducibly proven to be a prognostic factor in gastric cancer. The molecular mechanisms that underlie this aggressiveness are underexplored. Here, we aimed to identify molecules associated with this unique phenotype. Tumor specimens from patients with stage III gastric cancer with high or low ND (n = 4 for both) were compared at the mRNA level using Affymetrix microarray (harboring 54,675 genes). The expression data were prioritized, and genes that correlated with ND were selected. Ultimately, the EGFR was validated as such a candidate molecule in patients with primary advanced gastric cancer who underwent standard treatment (n = 167). Expression data of the microarray were prioritized based on gene expression ratio and frequency of gene expression. The first priority genes to be selected were genes that are known to be amplified in cancer, which included NKX2.1, CHST9, CTNND2, SLC25A27, FGFR2, EGFR, and PTGER1. Of these genes, the EGFR gene was of particular interest. EGFR expression in primary gastric cancer was examined using immunohistochemistry (IHC). The Student's t-test elucidated a significant difference in EGFR expression between IHC 2+/3+ and IHC 1+ according to ND (P = 0.0035). The Chi-square test also indicated a significant difference between high and low levels of EGFR immunohistochemical staining (IHC2+/3+ and IHC1+, respectively) and ND status (P = 0.0023). According to the least squares method, as ND increased, the risk that EGFR staining levels changed from IHC 1+ to IHC 2+ also increased. In this study, we determined that high EGFR expression may underlie the aggressive mechanism of advanced gastric cancer with high ND.

Prognostic significance of Ki-67 in chemotherapy-naive breast cancer patients with 10-year follow-up.

BACKGROUND/AIM: In order to define accurate survival outcome in breast cancer, 10-year follow-up is required and such long-term survival information are few and difficult to gather. PATIENTS AND METHODS: We recruited 253 breast cancer patients who undertook operation with no prior chemotherapy. Ten-year survival outcomes were evaluated by clinicopathological factors. RESULTS: Significant univariate prognostic factors were: T factor, N factor, preoperative values of tumor markers, and biological factors. T-factor, CEA, hormone receptor, and Ki-67 were the final independent prognostic factors of recurrence-free survival through multivariate analysis. The Luminal A group except for the Ki-67-positive cases showed the best survival outcomes, while the HER2-positive or triple-negative (TN) groups showed worse prognosis than the Luminal A group, and Ki-67 was shown to be an excellent prognostic factor in each stage (p<0.01). CONCLUSION: Ki-67 has a great potential as a prognostic biomarker while prognostic information of this sort could be beneficial for development of novel therapeutic strategies.

Crenotalea thermophila gen. nov., sp. nov., a member of the family Chitinophagaceae isolated from a hot spring.

A thermophilic aerobic bacterium designated strain STH-1-Y1(T) was isolated from sulfur-turf in a Japanese hot spring (Okuhodaka hot spring, Gifu Pref.). Colonies of strain STH-1-Y1(T) were yellow and low convex morphology with a slightly irregular fringe. Cells were slender long rods, 0.4-0.6 µm wide and 1.2-3.0 µm long. The isolate was an obligate aerophilic organism, and could not grow by fermentation or nitrate respiration. The isolate had a thermophilic trait, and could grow at 35-60 °C and pH 5.5-7.5; maximum growth occurred at 55 °C and pH 7.0 with a doubling time of 1.9 h. The Biolog and API tests suggested that strain STH-1-Y1(T) was able to use various sugars such as glucose, lactose, mannose, maltose, trehalose, cellobiose and sucrose, but could not use sugar alcohols other than glycerol, i.e. adonitol, arabitol, erythritol, inositol, mannitol, sorbitol and xylitol. Lactate and glutamate could be used, but other fatty acids, i.e. acetate, citrate, propionate and succinate could not. Gelatin, casein, starch and glycogen were hydrolysed, but neither chitin nor agar was degraded. Cells lacked flexirubin and showed oxidase and catalase activities. The major respiratory quinone was menaquinone-7 (MK-7), and major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C17 : 0 and anteiso-C15 : 0. No unsaturated fatty acids were detected. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain STH-1-Y1(T) was closely related to the family Chitinophagaceae within the phylum Bacteroidetes. However, the isolate was evenly distant from all members in this family with sequence similarities of 87-89 %. These significantly low sequence similarities strongly suggested that strain STH-1-Y1(T) represents a novel species in a new genus of the family Chitinophagaceae within the phylum Bacteroidetes. Based on phenotypic and phylogenetic characteristics, the name Crenotalea thermophila gen. nov., sp. nov. is proposed. The type strain of the type species is STH-1-Y1(T) ( = JCM 11541(T) = DSM 14807(T)).

Perineural invasion and preoperative serum CA19-9 as predictors of survival in biliary tract cancer.

BACKGROUND: Billiary tract cancer requires invasive surgical procedures for cure, and the risk factors related to patient prognosis remain controversial. PATIENTS AND METHODS: Out of the 111 patients who underwent resection of extrahepatic biliary tract tumors from 1986 to 2010, the records for 88 with both ampullary and extrahepatic bile duct cancer, which included all information for evaluation of the clinicopathological factors, were employed in a multivariate analysis. RESULTS: On univariate analysis, significant prognostic factors of poor survival unrelated to TNM factors were preoperative biliary drainage, high preoperative CA19-9 value, high preoperative CEA value, lymphatic invasion, perineural invasion, macroscopic growth pattern, histology, operative procedures (surgery), tumor persistence, high postoperative CA19-9 value, and postoperative chemotherapy. On multivariate analysis, perineural invasion (p=0.025) was the only prognostic factor independent of stage, for survival of patients with biliary tract cancer including ampullary cancer. When ampullary cancer was excluded, both perineural invasion and preoperative CA19-9 were the remaining prognostic factors independent of stage. The combination of both factors can very accurately identify long-term and short-term survivors of biliary tract cancer. CONCLUSION: The present study, to our knowledge, for the first time shows that both perineural invasion and preoperative CA19-9 are important prognostic factors in biliary tract cancer, and this would be beneficial for clinical clarification of the optimal strategies for this type of cancer.

Methanothermobacter tenebrarum sp. nov., a hydrogenotrophic, thermophilic methanogen isolated from gas-associated formation water of a natural gas field.

A thermophilic and hydrogenotrophic methanogen, strain RMAS(T), was isolated from gas-associated formation water of a gas-producing well in a natural gas field in Japan. Strain RMAS(T) grew solely on H(2)/CO(2) but required Casamino acids, tryptone, yeast extract or vitamins for growth. Growth of strain RMAS(T) was stimulated by acetate. Cells were non-motile, straight rods (0.5×3.5-10.5 µm) and occurred singly or in pairs. Bundles of fimbriae occurred at both poles of cells and the cell wall was thick (approximately 21 nm, as revealed by ultrathin section electron microscopy). Strain RMAS(T) grew at 45-80 °C (optimum, 70 °C), at pH 5.8-8.7 (optimum, pH 6.9-7.7) and with 0.001-20 g NaCl l(-1) (optimum, 2.5 g NaCl l(-1)). Phylogenetic analysis revealed that Methanothermobacter thermautotrophicus ΔH(T) was most closely related to the isolate (95.7 % 16S rRNA gene sequence similarity). On the basis of morphological, phenotypic and phylogenetic characteristics, it is clear that strain RMAS(T) represents a novel species of the genus Methanothermobacter, for which we propose the name Methanothermobacter tenebrarum sp. nov. The type strain is RMAS(T) ( = DSM 23052(T) = JCM 16532(T) = NBRC 106236(T)).

Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis.

BACKGROUND: We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). METHODS: Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. RESULTS: PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor forming and invasive ability. CONCLUSION: Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.

Deciphering the genome of polyphosphate accumulating actinobacterium Microlunatus phosphovorus.

Polyphosphate accumulating organisms (PAOs) belong mostly to Proteobacteria and Actinobacteria and are quite divergent. Under aerobic conditions, they accumulate intracellular polyphosphate (polyP), while they typically synthesize polyhydroxyalkanoates (PHAs) under anaerobic conditions. Many ecological, physiological, and genomic analyses have been performed with proteobacterial PAOs, but few with actinobacterial PAOs. In this study, the whole genome sequence of an actinobacterial PAO, Microlunatus phosphovorus NM-1(T) (NBRC 101784(T)), was determined. The number of genes for polyP metabolism was greater in M. phosphovorus than in other actinobacteria; it possesses genes for four polyP kinases (ppks), two polyP-dependent glucokinases (ppgks), and three phosphate transporters (pits). In contrast, it harbours only a single ppx gene for exopolyphosphatase, although two copies of ppx are generally present in other actinobacteria. Furthermore, M. phosphovorus lacks the phaABC genes for PHA synthesis and the actP gene encoding an acetate/H(+) symporter, both of which play crucial roles in anaerobic PHA accumulation in proteobacterial PAOs. Thus, while the general features of M. phosphovorus regarding aerobic polyP accumulation are similar to those of proteobacterial PAOs, its anaerobic polyP use and PHA synthesis appear to be different.

Quantitative detection of previously characterized syntrophic bacteria in anaerobic wastewater treatment systems by sequence-specific rRNA cleavage method.

Quantitative monitoring method of two important trophic groups of bacteria in methanogenic communities was established and applied to six different anaerobic processes. The method we employed was based upon our previous sequence-specific rRNA cleavage method that allows quantification of rRNA of target groups so that the populations reflecting in situ activity could be determined. We constructed a set of scissor probes targeting the Chloroflexi group known as 'semi-syntrophic' heterotrophic bacteria and fatty acid-oxidizing syntrophs to determine their relative abundance in the processes. By using the method, we found that several reactors harbored a large amount of organisms belonging to the phylum Chloroflexi accounting for up to 20% of the total prokaryotic populations. Propionate-oxidizing syntrophs, Syntrophobacter, Smithella and Pelotomaculum were also found to be significant comprising up to 3.9% of the total populations, but their distribution is highly dependent on the process examined. This is the first clear, non-PCR based quantitative evidence that those organisms play active roles under in situ methanogenic conditions.

A six-well plate method: less laborious and effective method for cultivation of obligate anaerobic microorganisms.

We developed a simple, less laborious method to cultivate and isolate obligate anaerobic microorganisms using a six-well plate together with the AnaeroPack System, designated as the six-well plate method. The cultivation efficiency of this method, based on colony-forming units, colony formation time, and colony size, was evaluated with four authentic obligate anaerobes (two methanogenic archaea and two sulfate-reducing bacteria). The method was found to be comparable to or even better than the roll tube method, a technique that is commonly used at present for the cultivation of obligate anaerobes. Further experiments using 21 representative obligate anaerobes demonstrated that all examined anaerobes (11 methanogens, 5 sulfate- or thiosulfate-reducing bacteria, and 5 syntrophs) could form visible colonies on the six-well plate and that these colonies could be successfully subcultured in fresh liquid media. Using this method, an unidentified sulfate-reducing bacterium was successfully isolated from an environmental sample.

Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer.

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer. METHODS: PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status. RESULTS: PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression. CONCLUSIONS: We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.