Nutritional effect of oral supplement enriched in beta-hydroxy-beta-methylbutyrate, glutamine and arginine on resting metabolic rate after laparoscopic gastric bypass

Background  

Weight regain that begins 12–18 months after laparoscopic gastric bypass has been attributed to changes in resting metabolic rate (RMR), which is largely determined by lean body mass (LBM). An oral supplement containing beta-hydroxy-beta-methylbutyrate, glutamine, and arginine (HMB/Glu/Arg) has helped to restore LBM in cachexia due to cancer and in critically ill trauma patients. The objective of this study was to evaluate the effect of oral HMB/Glu/Arg on LBM and RMR following laparoscopic gastric bypass (LGB).     

A common FGFR3 mutation functions as a diagnostic marker for achondroplasia-group disorders in the Japanese population

Recent DNA studies performed by several groups have detected mutations of the gene encoding fibroblast growth factor receptor 3 (FGFR3) in patients with achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia (TD). For this study, we analyzed theFGFR3 gene in 31 Japanese patients with typical ACH, four with HCH, three with a condition intermediate between ACH and HCH (ACH/HCH-intermediate), and one with TD. Of the 31 typical ACH patients, 29 showed a G1138 to A transition and the other two a G1138 to C transversion, both resulting in a common Gly380Arg substitution in the transmembrane domain of FGFR3. The one TD and the four HCH patients did not display any mutations in the transmembrane domain of FGFR3. Of the three ACH/HCH-intermediate cases, one patient showed the Gly380Arg substitution and one did not, and further analysis of the second patient revealed the presence of Asn540Lys substitution. The first patient was, therefore, genotypically diagnosed as ACH and the second as HCH. Peripheral blood leukocyte DNA analysis in the remaining ACH/HCH-intermediate patient indicated an unequal ratio of mutant to normal PCR products, possibly representing a somatic mosaic for the Gly380Arg mutation. Analysis of the common FGFR3 mutation thus appears to help in the molecular diagnosis of patients with achondroplasia-group disorders.     

TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring

Background

In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children.

Methods

The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels.

Results

There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism.

Conclusions

Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.     

Synergistical action of the β2 adrenoceptor and fatty acid binding protein 2 polymorphisms on the loss of glomerular filtration rate in Chinese patients with type 2 diabetic nephropathy

Purpose

Since altered sympathetic nerve activity and insulin resistance are implicated in the pathogenesis of type 2 diabetic nephropathy, we investigated the effect of polymorphic Arg16Gly and Gln27Glu in the β2 adrenoceptor gene and Ala54Thr in the fatty acid binding protein 2 gene on the estimated glomerular filtration rate (eGFR) in Chinese patients with the above disease.

Methods

A total of 552 diabetic subjects recruited from annual health examinations were studied. The eGFR was calculated from the Modification of Diet in Renal Disease equation for the Chinese. Plasma norepinephrine level and genotype were determined by high-performance liquid chromatography–tandem mass spectrometry and TaqMan method, respectively. Holter-derived heart rate viability (HRV) and the MRI-generated renal apparent diffusion coefficient (ADC) were evaluated.

Results

The Gly16Gly and Thr54Thr homozygotes had significantly higher microalbuminuria and lower eGFR against other genotypes in their individual polymorphism. Besides, the Gly16Gly variant exhibited markedly elevated norepinephrine level, whereas indicative of insulin resistance was increased in the Thr54Thr one. Multiple linear regression analysis further confirmed the independent genetic effect on the eGFR. Moreover, multifactor dimensionality reduction method detected a gene–gene synergistic action that subjects with the Gly16Gly/Thr54Thr genotype were exposed to higher risk of eGFR loss. Finally, these findings were accompanied by lower HRV and ADC, indicating sympathetically mediated hemodynamic changes.

Conclusions

By uncovering the genetic component of the coherent interplay between the elevated sympathetic nerve activity and metabolic disorders, our observations might promote the development of novel personalized prevention and management strategies against the diabetic nephropathy, especially in the genetically susceptible individuals.

     

Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

Summary

The P2X₇ receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X₇ receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X₇ receptor and the risk of osteoporosis.

Introduction

The purpose of this study was to determine whether genetic variation in the P2X₇ receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients.

Methods

Six hundred ninety women and 231 men aged ≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck.

Results

Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p?=?0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p?=?0.018 and p?=?0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40 % decrease in risk of a lower T-score value (OR?=?0.58 [95%CI, 0.33–1.00]).

Conclusion

Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment.     

PinX1 Inhibits Telomerase Activity in Gastric Cancer Cells Through Mad1/c-Myc Pathway

Introduction  

The aim of this study was to investigate the role of Mad1/c-Myc in telomerase regulation in gastric cancer cells in order to gain insight into telomerase activity and to evaluate PinX1 as a putative inhibitor of gastric cancer.     

Relationship between β1‐adrenergic receptor polymorphisms and cardiovascular disease in patients with diabetic nephropathy

Aim: Activation of β1‐adrenergic receptor (β1AR) enhances contractility and heart rate. The polymorphism Arg389Gly in the β1AR gene was found to be functionally important in determining receptor activity. The relationship between this polymorphism and the risk of cardiovascular disease was investigated in Chinese subjects with overt diabetic nephropathy. Methods: A total of 219 type 2 diabetic subjects with nephropathy were recruited. Genotyping of the β1AR Arg389Gly polymorphism was determined. Patients were followed up to 96 months for the development of cardiovascular events. Results: There were 122, 86 and 11 patients with Arg/Arg, Arg/Gly and Gly/Gly genotype, respectively. At 96 months, the event‐free survival of primary composite cardiovascular end‐point was 33.0% and 44.3% for Gly⁺ and Gly^‐ groups, respectively (log–rank test, P = 0.105), while the event‐free survival for first ischaemic heart disease was 62.4% and 75.9%, respectively (log–rank test, P = 0.038). However, with multivariate analysis by the Cox proportional hazard model to adjust for confounders, only low‐density lipoprotein and baseline glomerular filtration rate were independent predictors of first ischaemic heart event. Conclusion: The β1AR Arg389Gly polymorphism is not an independent predictor of cardiovascular events in subjects with overt diabetic nephropathy.     

Analysis of S Gene Mutation of the Hepatitis B Virus in Adult Liver Transplant Recipients Showing Resistance to Hepatitis B Immunoglobulin Therapy

Background

A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160.

Methods

Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis.

Results

Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10⁶ copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy.

Conclusions

This study suggested that various mutations in the “a” determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory.     

Nicotine promotes cell migration through alpha7 nicotinic acetylcholine receptor in gastric cancer cells

Background  

The objective was to study the mechanism of nicotine-enhanced migration of gastric cancer cells. Long-term cigarette smoking increases the risk of gastric cancer mortality. Tobacco-specific mitogen, nicotine, was reported to correlate with cancer progression on gastric cancer. Since metastasis is the major cause of cancer death, the influence of nicotine on the migration of gastric cancer cells remains to be determined.     

Risk Factors of Survival and Surgical Treatment for Advanced Gastric Cancer with Large Tumor Size

Background  

The purpose of this study was to clarify the clinical significance of tumor size in advanced gastric cancer and to evaluate the risk factors of survival in advanced gastric cancer with large tumor size.     

Risk Factors for Metachronous Gastric Cancer in the Remnant Stomach After Early Cancer Surgery

Background  

Early gastric cancer patients have a good prognosis after radical resection. However, if the patients have a gastric remnant after the surgery, the risk of metachronous gastric cancer remains. The aim of this study was to clarify the risk factors for metachronous gastric cancer after partial gastrectomy for early gastric cancer.     

Gastric Cardia Carcinoma is Associated with the Promoter -77T>C Gene Polymorphism of X-Ray Cross-Complementing Group 1 (XRCC1)

Purpose  

X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the bas-excision repair pathway. Several single-nucleotide polymorphisms in the XRCC1 gene are identified and related with increased cancer risk development. In particular, the -77T>C polymorphism located on the promoter region relates with lung cancer risk development. The aim of this study is to analyze the -77T>C allelic frequencies in a population composed of 456 primary gastric cancer patients (GC) and 507 blood donor controls.     

Subclassification of Stage IV Gastric Cancer (IVa,IVb, and IVc) and Prognostic Significance of Substages

Background  

Although the prognosis of stage IV gastric cancer is poor, some patients with stage IV gastric cancer had a long-term survival after gastrectomy. The objective of this study was to subclassify stage IV gastric cancer according to survival differences, evaluate the prognosis by substage, and identify the factors associated with patient survival in each substage.     

Inpatient survival after gastrectomy for gastric cancer in the 21st century

Background

Surgical treatment for gastric cancer has evolved substantially. To understand how changes in patient- and hospital-level factors are associated with outcomes over the last decade, we examined a nationally representative sample.

Methods

Retrospective cross-sectional discharge data from the 2001–2010 Nationwide Inpatient Sample were analyzed using cross tabulation and multivariable regression modeling. Patients with a primary diagnosis of gastric cancer undergoing gastrectomy as primary procedure were included. We examined relationships between patient- and hospital-level factors, surgery type, and outcomes including in-hospital mortality and length of stay (LOS).

Results

A total of 67,327 patients with gastric cancer undergoing gastrectomy nationwide with complete information were included. Compared with patients treated in 2001, patients in 2010 were younger, more likely admitted electively, treated in a teaching hospital, or at an urban center. There was no difference in the type of procedure performed over time. Factors associated with an increased risk of in-hospital mortality included older age, male gender, and nonelective admission (P < 0.05). In multivariable analysis, patients undergoing gastrectomy in 2010 demonstrated 40% lower odds of in-hospital mortality (odds ratio, 0.60; P = 0.008). Overall mean LOS was 13.9 d (standard error, 0.1) without change over time. Factors associated with longer LOS included procedure type, hospital location, nonelective admission, and comorbid disease (all P < 0.05).

Conclusions

The adjusted odds of in-hospital mortality among surgically treated patients with gastric cancer decreased >40% between 2001 and 2010. Further research is warranted to determine if these findings are due to better patient selection, regionalization of care, or improvement of in-hospital quality of care.     

Clinical outcome and management of ureteral obstruction secondary to gastric cancer

Background  

The clinical outcome of ureteral obstruction secondary to gastric cancer remains unclear. The present study was designed to evaluate the clinical outcome and predictive factors of survival in patients with ureteral obstruction secondary to gastric cancer.     

Low Prognostic Implication of Fibroblast Growth Factor Family Activation in Triple-negative Breast Cancer Subsets

Background

Despite a greater understanding of the molecular heterogeneity of breast cancer, current therapeutic strategies still cannot overcome the relatively poor prognosis of triple-negative breast cancer (TNBC). Deregulation of fibroblast growth factor (FGF) signaling has been found in breast cancer, and blocking this pathway has been suggested as a potential therapeutic target. We therefore evaluated the expression and copy number changes of FGF family members in TNBC.

Methods

We retrospectively evaluated 148 primary TNBC in 2009 for FGFR1, FGFR2, and FGF2 expression by immunohistochemistry. FGFR1 and FGFR2 gene copy numbers were analyzed by fluorescence in situ hybridization. The Cancer Genome Atlas (TCGA) data was used to study correlations between gene expression and amplification or methylation of FGFR1, FGFR2, and FGF2 in basal-like TNBC.

Results

FGFR1, FGFR2, and FGF2 expression were found in 16.2 % (24 of 148), 12.8 % (19 of 148), and 12.8 % (19 of 148) of TNBCs, respectively. FGFR1 gene amplification was observed in 4.1 % (6 of 145), and FGFR1 high polysomy was detected in 6.9 % (10 of 145) of the cases examined. FGFR2 gene amplification and high polysomy were identified in 4.7 % (6 of 129 cases) and 0.8 % (1 of 129 cases), respectively. FGF2 expression was found to be associated with basal-like TNBC. The expression of FGF family members and FGFR1 or FGFR2 gene amplification did not affect patient survival. TCGA data revealed that promoter methylation of the 3 genes was significantly associated with mRNA expression.

Conclusions

Even though the implications for patient outcomes are not significant, subsets of TNBCs harbor FGFR1 or FGFR2 gene amplification and FGFR1, FGFR2, or FGF2 protein overexpression.     

Survival Benefit of Non-curative Gastrectomy for Gastric Cancer Patients with Synchronous Distant Metastasis

Background  

The prognosis for gastric cancer patients with distant metastasis is very poor. The purpose of this study was to evaluate the survival benefit of non-curative gastrectomy for gastric cancer patients with synchronous distant metastasis.     

The Combined Expression of Metaplasia Biomarkers Predicts the Prognosis Of Gastric Cancer

Background  

Our previous study indicated that gene expression profiling of intestinal metaplasia (IM) or spasmolytic polypeptide-expressing metaplasia (SPEM) can identify useful prognostic markers of early-stage gastric cancer, and seven metaplasia biomarkers (MUC13, CDH17, OLFM4, KRT20, LGALS4, MUC5AC, and REG4) were selectively expressed in 17–50% of gastric cancer tissues. We investigated whether the combined expression of these metaplasia biomarkers could predict the prognosis of advanced stage gastric cancer.     

Investigation of the recurrence patterns of gastric cancer following a curative resection

Purpose  

The goal of this study was to investigate the recurrence patterns of gastric cancer and determine the predictive information of recurrence patterns of gastric cancer following a curative resection.     

The Clinical Significance of Vimentin-Expressing Gastric Cancer Cells in Bone Marrow

Background  

Expression of the mesenchymal marker gene vimentin (VIM) in gastric cancer is associated with a more aggressive form of the disease and poor prognosis. Because epithelial mesenchymal transition (EMT) plays a critical role in the progression of gastric cancer, VIM expression was examined in the bone marrow (BM) of gastric cancer patients.