DNA methylation plays a significant role in gastric carcinogenesis. The CpG island methylator phenotype (CIMP) characterizes distinct subtypes of gastric cancer (GC) and the relationship between ...specific methylation patterns and clinicopathological features has been evaluated. Altered DNA methylation is also observed in Helicobacter pylori-infected gastric mucosa, and its potential utility for GC risk estimation has been suggested. The ability to detect small amounts of methylated DNA among tissues allows us to use DNA methylation as a molecular biomarker in GC in a variety of samples, including serum, plasma and gastric washes. The DNA methylation status of nontargeted tissue, particularly blood, has been associated with predisposition to GC. We focus on the recent development of DNA methylation-based biomarkers in GC.
Exosome Research and Co-culture Study Shimasaki, Takeo; Yamamoto, Satoko; Arisawa, Tomiyasu
Biological & pharmaceutical bulletin,
09/2018, Volume:
41, Issue:
9
Journal Article
Peer reviewed
Open access
In biological systems, extracellular vesicles including exosomes have recently been revealed to play a significant role in the communication between various cells, and the number of papers on this ...subject has dramatically increased. In current conventional exosome studies, the standard research method is to use liquid biopsies to analyze extracts of various disease exosomes. However, exosomes are only one of many key players in natural cellular interactions. Reproducing the phenomena occurring in vivo and investigating the interactions are required in order to examine their role fully. For exosome research, an alternative to the liquid biopsy method for observing natural interactions is the co-culturing technique. It does not require an exosome extraction procedure, and while the technique has been used in many studies thus far, its application to exosome research has been limited. However, the use of co-culturing technologies is necessary to examine the essential interactions of exosomes. An overview of exosome research methodologies and co-culturing systems is thus provided here.
Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis ...to steatohepatitis,liver cirrhosis,and hepatocellular carcinoma.Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis,a small percentage of individuals will develop progressive liver disease.Notably,both ALD and NAFLD are frequently accompanied by extrahepatic complications,including cardiovascular disease and malignancy.The survival of patients with ALD and NAFLD depends on various disease-associated conditions.This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology,the factors associated with disease susceptibility and progression,and the predictors and characteristics of outcomes.A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.
Liver cirrhosis(LC)patients often have protein-energy malnutrition(PEM)and decreased physical activity.These conditions often lead to sarcopenia,which is the loss of skeletal muscle volume and ...increased muscle weakness.Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients.Nutrition and exercise management can improve PEM and sarcopenia in those patients.Nutrition management includes sufficient dietary intake and improved nutrient metabolism.With the current high prevalence of obesity,the number of obese LC patients has increased,and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients.Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients.Exercise management can increase skeletal muscle volume and strength and improve insulin resistance;however,nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients.The establishment of optimal exercise regimens for LC patients is currently required.In this review,we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.
Background
Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a ...disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time.
Method
Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment.
Results and Conclusion
These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.
Toll like receptors (TLR) play important roles in the signaling of many pathogen‐related molecules and endogenous proteins associated with immune activation. The –196 to –174del polymorphism affects ...the TLR2 gene and alters its promoter activity. We investigated the influence of the TLR2–196 to –174del polymorphism on the occurrence of non‐cardiac gastric cancer (NCGC) in a Japanese population. The study was carried out with 289 patients with NCGC, 309 non‐cancer patients with abdominal discomfort and 146 healthy controls. The –196 to –174del TLR2 polymorphism was investigated using the allele‐specific polymerase chain reaction method in all of the subjects. The –196 to –174del/del genotype of TLR2 showed a significantly higher frequency in NCGC patients than in healthy controls (adjusted odds ratio OR = 6.06; 95% confidence interval CI = 1.86–19.72). Similarly, the frequency of the –196 to –174del/del genotype was significantly higher among NCGC patients than in non‐cancer patients (adjusted OR = 2.02; 95% CI = 1.22–3.34). The same genotype was associated with an increased risk of both intestinal (OR = 2.00, 95% CI = 1.12–3.60) and diffuse‐type (OR = 2.05; 95% CI = 1.11–3.79) histopathology. There were no significant associations between TLR2 genotypes and tumor stage and anatomical location. Our data suggest that the –196 to –174del/del genotype of TLR2 may increase the risk of gastric cancer in the Japanese population. (Cancer Sci 2007; 98: 1790–1794)
Background Magnifying narrow-band imaging (NBI) endoscopy clearly visualizes superficial gastric mucosal patterns and capillary patterns. Objective To investigate gastric mucosal patterns by using ...magnifying NBI endoscopy and identify any relationship between those patterns and Helicobacter pylori –induced gastritis. Design Gastric mucosal patterns seen with magnifying NBI in uninvolved gastric corpus were divided into the following categories: normal—small, round pits with regular subepithelial capillary networks; type 1—slightly enlarged, round pits with unclear or irregular subepithelial capillary networks; type 2—obviously enlarged, oval or prolonged pits with increased density of irregular vessels; and type 3—well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. Setting Department of Gastroenterology, Fujita Health University. Patients This study involved 106 participants undergoing upper endoscopy. Results H pylori infection–positive ratios of normal and types 1, 2, and 3 patterns were 7.5%, 92.9%, 94.5%, and 66.7%, respectively. Sensitivity and specificity for types 1 + 2 + 3 for detection of H pylori positivity and type 3 for detection of intestinal metaplasia were 95.2%, 82.2%, 73.3%, and 95.6%, respectively. Development of mucosal patterns from normal to types 1, 2, and 3 was correlated with all histological parameters ( P < .0001), lower pepsinogen I/II ratios ( P < .0001), and degree of endoscopic atrophy ( P < .0001). Sensitivity and specificity of type 3 for the prediction of severe histological atrophy was also better than those of serum pepsinogen level and standard endoscopy. Limitations Only 1 endoscopist performed endoscopic procedures, and interobserver agreement could not be assessed. Conclusions Magnifying NBI endoscopy is useful for predicting H pylori infection and the histological severity of gastritis and is valuable for predicting gastric atrophy in the entire stomach.
We herein report the case of a 79-year-old patient with unresectable stage III non-small cell lung cancer who developed immune-related hepatitis caused by durvalumab administration. Durvalumab was ...administered at 10 mg/kg every two weeks after the treatment with carboplatin (AUC2), paclitaxel (35 mg/m2), and 60 Gy radiation. At the day 208 in which the 14th durvalumab administration was scheduled, the patient was urgently hospitalized due to CTCAE Grade 4 hepatic dysfunction detected during the an outpatient blood sampling test. He was diagnosed with immune-related hepatitis and started on methylprednisolone 60 mg/day. After 51 days, his liver dysfunction improved and he was discharged.
Liver cirrhosis(LC)is a critical stage of chronic liver disease,including that caused by hepatitis C virus(HCV).In the absence of antiviral therapy,67%-91%of patients with HCV-related LC patients die ...of liver-related causes,including hepatocellular carcinoma(HCC)and liver failure.Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin,which induces a sustained virological response(SVR)in 25%of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3.SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation,HCC,and mortality.More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy,with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50%of patients with HCV genotype 1 LC.Branched-chain amino acid supplementation,improvement of insulin resistance,and the use ofβ-blockers for portal hypertension may also reduce liverrelated complications.Here,we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC.
PDF
