AIM To study the activation of CTLs against gastric cancer cells induced by FasL/B7-l (FB-ll)genes modified tumor cells, and to explore whether co-expression of FasL and B7-1 in SGC-7901 tumor cells could initiate an synergistic antitumor effect. METHODS FasL and B7-1 genes were transfected into human SGC-7901 gastric cancer cells with adenovirus vectors. The positive clones were selected by G418. FasL and B7-1 were detected by Flow cytometry and RT-PCR .The abdominal infiltrating lymphocytes and sensitized spleen cells were obtained from the mice who were immunized with SGC-7901/FB-11 or wild type SGC-7901 cells intraperitoneally, and the cytotoxicity of these CTLs against tumor cells was determined by MTT assay. RESULTS Flow cytometry and RT-PCR showed that FasL and B7-1 were highly expressed. FasL + /B7 - ¿SGC-7901 cells (SGC-7901/FB-11) were inoculated subcutaneously in the dorsal skin of C57BL/6 mice and then they decreased their tumorigenicity greatly (p < 0.01). The SGC-7901/FB-11 cell-sensitized mice obtained the protective immune activity against the rechallenge of wild type SGC-7901 cells (p < 0.05). It was showed that the cytotoxicity of CTLs induced by SGC-7901/FB-11 cells against SGC-7901 was significantly higher than that of CTLs activated by wild-type SGC-7901 cells (p < 0.05). CONCLUSION The results suggest that the FasL and B7-1 can effectively promote the activity of CTLs against gastric cancer cells. And FasL/B7-l molecules play an important role in CTL cytotoxicity function as well. After introduced into SGC-7901 cells, Ad-B7-1 shows enhanced therapeutic efficiency for SGC-7901 cells when combined with Ad-FasL.
Most clinicians dread seeing the patient presenting with a primary complaint of a burning pain on one or more oral mucosal surfaces. Unlike most other clinical conditions presenting in a dental office, burning mouth syndrome is poorly understood with few evidence based remedies. More recently, advances have been made towards clarifying the possible etiology of the disorder and testing the possible therapeutic modalities available. This article attempts to summarize the ＂state of the art＂ today.
Most clinicians dread seeing the patient presenting with a primary complaint of a burning pain on one or more oral mucosal surfaces. Unlike most other clinical conditions presenting in a dental office, burning mouth syndrome is poorly understood with few evidence based remedies. More recently, advances have been made towards clarifying the possible etiology of the disorder and testing the possible therapeutic modalities available. This article attempts to summarize the "state of the art" today.
Context.-The histopathologic criteria for idiopathic pulmonary fibrosis were revised in the American Thoracic Society/European Respiratory Society/Japan Respiratory Society/Latin American Thoracic Association guidelines in 2011. However, the evidence of diagnosis based on the guidelines needs further investigation. Objective.-To examine whether the revised histopathologic criteria for idiopathic pulmonary fibrosis improved interobserver agreement among pathologists and the predicted prognosis in patients with interstitial pneumonia. Design.-Twenty, consecutive, surgical lung-biopsy specimens from cases of interstitial pneumonia were examined for histologic patterns by 11 pathologists without knowledge of clinical and radiologic data. Diagnosis was based on American Thoracic Society/European Respiratory Society guidelines of 2002 and 2011. Pathologists were grouped by cluster analysis, and interobserver agreement and associa-tion to the patient prognosis were compared with the diagnoses for each cluster. Results.-The generalized j coefficient of diagnosis for all pathologists was 0.23. If the diagnoses were divided into 2 groups: usual interstitial pneumonia (UIP)/probable UIP (the UIP group) or possible/not UIP (the non-UIP group), according to the 2011 guidelines, the j improved to 0.37. The pathologists were subdivided into 2 clusters in which 1 showed an association between UIP group diagnosis and patient prognosis (P < .05). Conclusions.-Agreement about pathologic diagnosis of interstitial pneumonia is low; however, results after division into UIP and non-UIP groups provided favorable agreement. The cluster analysis revealed 1 of the 2 clusters providing high interobserver agreement and prediction of patient prognosis.
Background Agenesis of the dorsal pancreas is a very rare congenital pancreatic malformation and is associated with some other diseases. Methods A PubMed search revealed 53 cases of agenesis of the dorsal pancreas. Results In 28 patients with this congenital malformation hyperglycemia was demonstrated, 27 had abdominal pain, 16 had pancreatitis, 14 had an enlarged or prominent pancreatic head visible on computed tomography, and in a few cases, polysplenia, which may occur with various congenital anomalies of visceral organs, was described. Conclusions Difficulties involved in obtaining a firm diagnosis have led to a variety of terms being used to describe this congenital disease. Diagnosis of agenesis of the dorsal pancreas is inconclusive without demonstration of the absence of the dorsal pancreatic duct. Here we describe the embryological development of the pancreas, the so-far known cases of agenesis of the dorsal pancreas with associated medical problems, and the diagnostic measures to find the right conclusions.
Evaluate the possible value of FasL in gastric cancer gene therapy by investigating the effects of FasL expression on human gastric cancer cell line.An adenoviral vector encoding the full-length human FasL cDNA was constructed and used to infect a human gastric cancer (SGC-7901) cell line. FasL expression was confirmed by X-gal staining, flow cytometric analysis and RT-PCR. The effect of FasL on cell proliferation was determined by clonogenic assay, cytotoxicity was detected by MTT assay, and cell viability was measured by trypan blue exclusion. The therapeutic efficiency of Ad-FasL in in vivo was investigated with a xenograft tumor model in nude mice.SGC-7901 cells infected with Ad-FasL showed increased expression of FasL, resulting in significantly decreased cell growth and colony-forming activity when compared with control adenovirus-infected cells. The cytotoxicity of anti-Fas antibody (CH-11) in gastric cancer cells was stronger than that of ActD (91plusmn8 vs 60plusmn5, P<0.01), and the cytotoxicity of Ad-FasL was stronger than that of CH-11 (60plusmn5 vs 50plusmn2, P<0.05). In addition, G 1 -phase arrest (67.75plusmn0.39 vs 58.03plusmn2.16, P<0.05) and apoptosis were observed in Ad-FasL-infected SGC-7901 cells, and the growth of SGC-7901 xenografts in nude mice was retarded after intra-tumoral injection with Ad-FasL (54% vs 0%, P<0.0001).Infection of human gastric carcinoma cells with Ad-FasL induces apoptosis, indicating that this target gene might be of potential value in gene therapy for gastric cancer.
Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair (MMR) genes. During the last decades, there have been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention, chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such asMLH1,MSH2,MSH6, andMLH3, other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor β receptor 2, and alanine aminopeptidase, metastasis-associated protein 2, adenomatosis polyposis coli down-regulated 1, and hepatic and glial cell adhesion molecule have also been implicated in Chinese Lynch syndrome. Most Chinese researchers focused on the clinicopathologic features of Lynch syndrome, and it is noticeable that the most frequent extracolonic tumor in northeast China is lung cancer, which is different from other areas in China. The Chinese diagnostic criteria for Lynch syndrome have been established to identify gene mutation or methylation. With regard to chemoprevention, celecoxib may be effective to prevent polyps relapse in Lynch syndrome carriers. Additionally, a colonoscopy-based surveillance strategy for the prevention and early detection of neoplasms in Lynch-syndrome carriers has been proposed.
A pancreatic pseudocyst (PPC) is typically a complication of acute and chronic pancreatitis, trauma or pancreatic duct obstruction. The diagnosis of PPC can be made if an acute fluid collection persists for 4 to 6 wk and is enveloped by a distinct wall. Most PPCs regress spontaneously and require no treatment, whereas some may persist and progress until complications occur. The decision whether to treat a patient who has a PPC, as well as when and with what treatment modalities, is a difficult one. PPCs can be treated with a variety of methods: percutaneous catheter drainage (PCD), endoscopic transpapillary or transmural drainage, laparoscopic surgery, or open pseudocystoenterostomy. The recent trend in the management of symptomatic PPC has moved toward less invasive approaches such as endoscopic- and image-guided PCD. The endoscopic approach is suitable because most PPCs lie adjacent to the stomach. The major advantage of the endoscopic approach is that it creates a permanent pseudocysto-gastric track with no spillage of pancreatic enzymes. However, given the drainage problems, the monitoring, catheter manipulation and the analysis of cystic content are very difficult or impossible to perform endoscopically, unlike in the PCD approach. Several conditions must be met to achieve the complete obliteration of the cyst cavity.
Gastroparesis has traditionally been a largely medically managed disease with refractory symptoms typically falling under the umbrella of the surgical domain. Surgical options include, but are not limited to, gastrostomy, jejunostomy, pyloromyotomy, or pyloroplasty, and the Food and Drug Administration approved gastric electrical stimulation implantation. Endoscopic management of gastroparesis most commonly involves intrapyloric botulinum toxin injection; however, there exists a variety of endoscopic approaches on the horizon that have the potential to radically shift standard of care. Endoscopic management of gastroparesis seeks to treat delayed gastric emptying with a less invasive approach compared to the surgical approach. This review will serve to highlight such innovative and potentially transformative, endoscopic interventions available to gastroenterologists in the management of gastroparesis.
Diabetogenic traits in patients undergoing liver transplantation (LT) are exacerbated intraoperatively by exogenous causes, such as surgical stress, steroids, blood transfusions, and catecholamines, which lead to intraoperative hyperglycemia. In contrast to the strict glucose control performed in the intensive care unit, no systematic protocol has been developed for glucose management during LT. Intraoperative blood glucose concentrations typically exceed 200 mg/dL in LT, and extreme hyperglycemia (> 300 mg/dL) is common during the neohepatic phase. Only a few retrospective studies have examined the relationship between intraoperative hyperglycemia and post-transplant complications, with reports of infectious complications or mortality. However, no prospective studies have been conducted regarding the influence of intraoperative hyperglycemia in LT on post-transplant outcome. In addition to absolute blood glucose values, the temporal patterns in blood glucose levels during LT may serve as prognostic features. Persistent neohepatic hyperglycemia (without a decline) throughout LT is a useful indicator of early graft dysfunction. Moreover, intraoperative variability in glucose levels may predict the need for reoperation for hemorrhage after LT. Thus, there is an urgent need for guidelines for glucose control in these patients, as well as prospective studies on the impact of glucose control on various post-transplant complications. This report highlights some of the recent studies related to perioperative blood glucose management focused on LT and liver disease.
Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above.
Generally, proton-pump inhibitors (PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury. Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth (SIBO) compared to patients who lack the aforementioned conditions. Furthermore, there is insufficient evidence that these conditions induceClostridium difficileinfection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and autoimmune diseases. When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation,etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.