Helicobacter pylori is recognised as a main risk factor for gastric cancer. However, approximately half of the patients with gastritis are negative for H. pylori infection, and the abundance of H. ...pylori decreases in patients with cancer. In the current study, we profiled gastric epithelium-associated bacterial species in patients with gastritis, intestinal metaplasia, and gastric cancer to identify additional potential pathogenic bacteria. The overall composition of the microbiota was similar between the patients with gastritis and those with intestinal metaplasia. H. pylori was present in half of the non-cancer group, and the dominant bacterial species in the H. pylori-negative patients were Burkholderia, Enterobacter, and Leclercia. The abundance of those bacteria was similar between the cancer and non-cancer groups, whereas the frequency and abundance of H. pylori were significantly lower in the cancer group. Instead, Clostridium, Fusobacterium, and Lactobacillus species were frequently abundant in patients with gastric cancer, demonstrating a gastric cancer-specific bacterial signature. A receiver operating characteristic curve analysis showed that Clostridium colicanis and Fusobacterium nucleatum exhibited a diagnostic ability for gastric cancer. Our findings indicate that the gastric microenvironment is frequently colonised by Clostridium and Fusobacterium in patients with gastric cancer.
A straightforward roll‐to‐roll process for fabricating flexible and stretchable superaligned carbon nanotube films as transparent conducting films is demonstrated. Practical touch panels assembled by ...using these carbon nanotube conducting films are superior in flexibility and wearability—and comparable in linearity—to touch panels based on indium tin oxide (ITO) films. After suitable laser trimming and deposition of Ni and Au metal, the carbon nanotube film possesses excellent performance with two typical values of sheet resistances and transmittances (208 Ω □−1, 90% and 24 Ω □−1, 83.4%), which are comparable to ITO films and better than the present carbon nanotube conducting films in literature. The results provide a route to produce transparent conducting films more easily, effectively, and cheaply, an important step for realizing industrial‐scale applications of carbon nanotubes for transparent conducting films.
A roll‐to‐roll process for fabricating flexible and stretchable transparent conducting films (TCFs) using superaligned carbon nanotubes is demonstrated. Practical touch panels are assembled based on these TCFs, which are superior in flexibility and wearability and comparable in linearity to touch panels based on indium tin oxide TCFs. Combined with obtained improvements in the transparency and sheet resistance of such films, this approach has immediate industrial potential.
Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with “resolved” HBV infection (hepatitis B surface antigen HBsAg negative and hepatitis B core antibody anti‐HBc positive) can occur, ...but the true incidence and severity remain unclear. From June 2009 to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)‐based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab‐CHOP chemotherapy. Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10‐fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3‐fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV‐related hepatitis flares was 10.4 and 6.4 per 100 person‐year, respectively. Severe HBV‐related hepatitis (ALT >10‐fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P = 0.003). Conclusion: In lymphoma patients with resolved HBV infections, chemotherapy‐induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV‐related hepatitis flare. (Hepatology 2014;59:2092–2100)
Display omitted
•The risk of HBV reactivation for patients with lymphoma and resolved HBV infection varied.•High anti-HBc and low anti-HBs at baseline predicted high risk of HBV ...reactivation.•Quantification of baseline anti-HBc/anti-HBs may optimize preventive strategies.
Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation.
We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab–cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation.
HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (≥6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio HR 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92–76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15–5.05; p = 0.02).
Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients.
In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources.
Clinical trial number: NCT 00931229.
Patients with cirrhosis and acute myocardial infarction (AMI) present dilemma whether dual antiplatelet therapy (DAPT) should be used.
Electronic medical records between 2001-2013 were retrieved from ...Taiwan National Health Insurance Research Database. Patients were excluded for missing information, age <20 years old, history of AMI, liver transplant, autoimmune disease, coagulopathy, taking DAPT 3 months before index date, follow-up <3 months, anticoagulation user, without DAPT, and events of myocardial infarction (MI), ischemic stroke, major bleeding, and heart failure within 3-month of enrollment. Primary outcomes were 1-year all-cause mortality, recurrent MI, major bleeding, and gastrointestinal bleeding.
A total of 150,887 patients with AMI retrieved. After exclusion criteria and propensity score-matching, 914 cirrhotic and 3,656 non-cirrhotic patients with AMI on DAPT were studied. During 1-year follow-up, there was significantly increased mortality in cirrhotic patients compared to non-cirrhotic patients (HR = 1.49, 95% CI = 1.28-1.74). There was significantly decreased recurrent MI in cirrhotic patients compared to non-cirrhotic patients (subdistribution HR SHR = 0.71, 95% CI = 0.54-0.92). However, non-significantly increased major bleeding (SHR = 1.23, 95% CI = 0.87-1.73) and significantly increased gastrointestinal bleeding (SHR = 1.49, 95% CI = 1.31-1.70).
In cirrhotic patients with AMI, DAPT offers benefit with decreased recurrent MI at the expense of increased gastrointestinal bleeding.
BACKGROUNDAn increased amount of Fusobacterium nucleatum (F. nucleatum) is frequently detected in the gastric cancer-associated microbiota of the Taiwanese population. F. nucleatum is known to exert ...cytotoxic effects and play a role in the progression of colorectal cancer, though the impact of F. nucleatum colonization on gastric cancer cells and patient prognosis has not yet been examined. AIMTo identify F. nucleatum-dependent molecular pathways in gastric cancer cells and to determine the impact of F. nucleatum on survival in gastric cancer. METHODSCoculture of F. nucleatum with a gastric cancer cell line was performed, and changes in gene expression were investigated. Genes with significant changes in expression were identified by RNA sequencing. Pathway analysis was carried out to determine deregulated cellular functions. A cohort of gastric cancer patients undergoing gastrectomy was recruited, and nested polymerase chain reaction was performed to detect the presence of F. nucleatum in resected cancer tissues. Statistical analysis was performed to determine whether F. nucleatum colonization affects patient survival. RESULTSRNA sequencing and subsequent pathway analysis revealed a drastic interferon response induced by a high colonization load. This response peaked within 24 h and subsided after 72 h of incubation. In contrast, deregulation of actin and its regulators was observed during prolonged incubation under a low colonization load, likely altering the mobility of gastric cancer cells. According to the clinical specimen analysis, approximately one-third of the gastric cancer patients were positive for F. nucleatum, and statistical analysis indicated that the risk for colonization increases in late-stage cancer patients. Survival analysis demonstrated that F. nucleatum colonization was associated with poorer outcomes among patients also positive for Helicobacter pylori (H. pylori). CONCLUSIONF. nucleatum colonization leads to deregulation of actin dynamics and likely changes cancer cell mobility. Cohort analysis demonstrated that F. nucleatum colonization leads to poorer prognosis in H. pylori-positive patients with late-stage gastric cancer. Hence, combined colonization of F. nucleatum and H. pylori is a predictive biomarker for poorer survival in late-stage gastric cancer patients treated with gastrectomy.
Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC), and all liver study societies recommend HCC surveillance in patients with cirrhosis. However, no ideal modality for HCC ...surveillance has been determined. The aim of this study is to assess the effectiveness of α-fetoprotein (AFP) measurement in HCC surveillance.
In this retrospective analysis, all patients with cirrhosis, who received HCC surveillance through ultrasound (US) and AFP measurement between January 2002 and July 2010, were followed up until June 2013. The performance effectiveness of surveillance using AFP, US, or both in HCC detection was compared.
Overall, 1,597 patients were followed for a median duration of 4.75 (range 1.42-12) years. Over the 8563.25-person-year follow-up period, 363 patients (22.7%) developed HCCs. For HCC detection, the area under the receiver operator characteristic curve of surveillance AFP was 0.844 (95% confidence interval: 0.820-0.868, P<0.001). When the traditional cutoff value of 20 ng/ml was used, the sensitivity and specificity of AFP were 52.9% and 93.3%, respectively. US exhibited a sensitivity and specificity of 92.0% and 74.2%, respectively. A combination of US and AFP exhibited a sensitivity and specificity of 99.2% and 68.3%, respectively. By using cut-off at 20 ng/ml and AFP level increase ≥2 × from its nadir during the previous 1 year, the combination of US and AFP yielded a sensitivity of 99.2% and an improved specificity of 71.5%.
The complementary use of AFP and US improved the effectiveness of HCC surveillance in patients with cirrhosis.
Gastric cancer is a leading cause of cancer worldwide. Our previous studies showed that aberrant activation of JAK/STAT3 signaling confer epigenetically silences STAT3 target genes in gastric cancer. ...To further investigate the clinical significance of this phenomenon, we performed Illumina 850K methylation microarray analysis in AGS gastric cancer cells, and cells depleted of STAT3. Integrative computational analysis identified SPG20 as a putative STAT3 epigenetic target, showing promoter hypomethylation in STAT3-depleted AGS cells. Bisulphite pyrosequencing and qRT-PCR confirmed that SPG20 is epigenetically silenced by promoter hypermethylation in a panel of gastric cancer cell lines including AGS cells, but not in immortalized gastric epithelial GES cells. Expression of SPG20 could be restored by the treatment with a DNMT inhibitor, further suggesting that SPG20 is epigenetically silenced by promoter methylation. Clinically, a progressive increase in SPG20 methylation was observed in tissues samples from gastritis (n = 34), to intestinal metaplasia (IM, n = 33), to gastric cancer (n = 53). Importantly, SPG20 methylation could be detected in cell-free DNA isolated from serum samples of gastritis, IM and gastric cancer patients, having a progressive similar to tissues. Taken together, SPG20, a potential STAT3 target, is frequently methylated in gastric cancer, representing a novel noninvasive biomarker for early detection of this deadly disease.
Gastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate. Approximately 40% of patients are refractory to chemotherapy. Currently, the anti-HER2 therapy is the only ...clinically employed targeted therapy. However, only 7% patients in Taiwan are HER2-positive. Identifying candidate target genes will facilitate the development of adjuvant targeted therapy to increase the efficacy of gastric cancer treatment.
Clinical specimens were analyzed by targeted RNA sequencing to assess the expression levels of target genes. Statistical significance of differential expression and correlation between specimens was evaluated. The correlation with patient survival was analyzed as well. In vitro cell mobility was determined using wound-healing and transwell mobility assays.
Expression of BMP1, COL1A1, STAT3, SOX2, FOXA2, and GATA6 was progressively dysregulated through the stages of gastric oncogenesis. The expression profile of these six genes forms an ubiquitously biomarker signature that is sufficient to differentiate cancer from non-cancerous specimens. High expression status of BMP1 correlates with poor long-term survival of late-stage patients. In vitro, suppression of BMP1 inhibits the mobility of the gastric cancer cell lines, indicating a role of BMP1 in metastasis.
BMP1 is upregulated in gastric cancer and is correlated with poor patient survival. Suppression of BMP1 reduced gastric cancer mobility in vitro. Our finding suggests that anti-BMP1 therapy will likely augment the efficacy of standard chemotherapy and improve the treatment outcome.
PDF
