Summary: Background: Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.Aim: To evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long‐term follow‐up.Methods: 598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori‐negative (n = 65), H. pylori non‐eradicated (n = 91), and H. pylori‐eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification.Results: Histological follow‐up was performed regularly at 1, 2, 3‐4 and ≥5 years, with mean follow‐up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori‐eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori‐eradicated and H. pylori‐negative groups disappeared from 1‐year follow‐up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori‐eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori‐eradicated and H. pylori‐negative groups disappeared from ≥5 years of follow‐up in the antrum and from 3 years of follow‐up in the corpus.Conclusion: H. pylori eradication may be a preventative strategy for intestinal‐type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.
Personalized cancer therapy is based on a patient's tumor lineage, histopathology, expression analyses, and/or tumor DNA or RNA analysis. Here, we aim to develop an in vitro functional assay of a patient's living cancer cells that could complement these approaches. We present methods for developing cell cultures from tumor biopsies and identify the types of samples and culture conditions associated with higher efficiency of model establishment. Toward the application of patient-derived cell cultures for personalized care, we established an immunofluorescence-based functional assay that quantifies cancer cell responses to targeted therapy in mixed cell cultures. Assaying patient-derived lung cancer cultures with this method showed promise in modeling patient response for diagnostic use. This platform should allow for the development of co-clinical trial studies to prospectively test the value of drug profiling on tumor-biopsy-derived cultures to direct patient care.
The frequent outbreaks of human trichinellosis globally underscore the need to develop effective vaccine. We hypothesized that a novel vaccine could improve vaccine efficacy against Trichinella spiralis. In this study, we developed virus-like particles (VLPs) containing the 53 KDa excretory/secretory (ES) protein of T. spiralis and the influenza matrix protein 1 (M1) as a core protein, and investigated the protective efficacy of the VLPs alone or with cholera toxin (CT) in a mouse model. Intramuscular immunization induced T. spiralis-specific IgG, IgG1 and IgG2a antibody responses before and after challenge infections in the sera. These antibody responses were significantly enhanced in mice immunized with adjuvanted VLPs. Upon challenge infection, vaccinated mice showed significantly reduced worm burden in the diaphragm. Protective immune responses and efficacy of protection were significantly improved by immunization with VLPs together with CT adjuvant. Our results are informative for a better understanding of the protective immunity induced by T. spiralis VLPs, and will provide insight into designing safe and effective vaccines.
17 November 2017 in Nephrology Dialysis Transplantation
Intravenous (IV) iron can modulate fibroblast growth factor 23 (FGF23) concentrations and cause transient but significant hypophosphataemia. However, it is unknown what other markers might be involved, especially in different patient groups. This study aimed to determine changes in bone and haematinic biomarkers following IV ferric carboxymaltose (FCM) and to identify risk factors for hypophosphataemia in pregnant subjects and those with chronic kidney disease (CKD). Changes in bone [serum FGF23, fractional excretion of phosphate urinary fractional excretion of phosphate (FEPi), serum phosphate and serum vitamin D derivatives] and haematinic [plasma hepcidin, serum ferritin and transferrin saturation (TSAT)] biomarkers after 1 g of IV FCM were followed in iron-deficient pregnant and CKD patients and compared with controls (estimated glomerular filtration rate > 60 mL/min/1.73 m2). Data were collected at baseline and up to 42 days after infusion. Risk factors for post-FCM hypophosphataemia were also assessed. Sixty-five subjects completed the study (control, n = 20; pregnant, n = 20; CKD, n = 25). A uniform but variable increase across groups was seen in intact FGF23 (peak Day 2), whereas c-terminal FGF23 varied markedly. Trough serum phosphate timed with the peak FEPi at Day 7, recovering by Day 21 in the pregnant group and Day 42 in other groups. Independent predictors of a low phosphate nadir included baseline phosphate, FEPi and weight-adjusted FCM dose. All groups showed an early and marked increase in plasma hepcidin (peak Day 2), serum ferritin and TSAT (peak Day 7 for both). Changes in bone and haematinic biomarkers differ between patient groups following IV FCM. For patients with lower serum phosphate concentrations, limiting the dose and measuring levels 7 days after administration may mitigate clinically significant hypophosphataemia.
Rhoptry organelle proteins (ROPs) secreted by Toxoplasma gondii (T. gondii) play a critical role during parasite invasion into host cells. In this study, virus-like particles (VLPs) vaccines containing ROP4 and/or ROP13 together with influenza M1 were generated. ROP4+ROP13 VLPs were produced by combining ROP4 VLPs with ROP13 VLPs, and ROP(4 + 13) VLPs by co-infecting insect cells with recombinant baculovirus expressing ROP4 or ROP13. Mice intranasally immunized with ROP(4 + 13) VLPs showed significantly higher levels of IgG, IgG1, IgG2a and IgA antibody responses in sera compared to ROP4+ROP13VLPs. Upon challenge infection by oral route, mice immunized with ROP(4 + 13) VLPs elicited higher levels of IgG and IgA antibody responses in fecal, urine, intestine and vaginal samples as well as CD4+ T, CD8+ T cells, and germinal center B cell responses compared to other type of vaccines, ROP4 VLPs, ROP13 VLPs, and ROP4+ROP13 VLPs. ROP(4 + 13) VLPs vaccination showed a significant decrease in the size and number of cyst in the brain and less body weight loss compared to combination ROP4+ROP13 VLPs upon challenge infection with T. gondii ME49. These results indicated that the ROP(4 + 13) VLPs vaccination provided enhanced protection against T. gondii infection compared to ROP4+ROP13 VLPs, providing an important insight into vaccine design strategy for T. gondii VLPs vaccines.