Novel combined endoscopic and laparoscopic surgery for advanced T2 gastric cancer: Two case reports.

BACKGROUND: The standard treatment for advanced T2 gastric cancer (GC) is laparoscopic or surgical gastrectomy (either partial or total) and D2 lymphadenectomy. A novel combined endoscopic and laparoscopic surgery (NCELS) has recently been proposed as a better option for T2 GC. Here we describe two case studies demonstrating the efficacy and safety of NCELS. CASE SUMMARY: Two T2 GC cases were both resected by endoscopic submucosal dissection and full-thickness resection and laparoscopic lymph nodes dissection. This method has the advantage of being more precise and minimally invasive compared to current methods. The treatment of these 2 patients was safe and effective with no complications. These cases were followed up for nearly 4 years without recurrence or metastasis. CONCLUSION: This novel method provides a minimally invasive treatment option for T2 GC, and its potential indications, effectiveness and safety needs to be further evaluated in controlled studies.

Effects of Autologous Platelet-Rich Plasma on Healing of Peptic Ulcers: A Randomized Controlled Trial.

Purpose: Peptic ulcer is a multifactorial and complex disease and affects a wide range of people worldwide. We provided a novel therapeutic approach for peptic ulcer and observed its effect. Methods: Peptic ulcer patients were enrolled from 2016 to 2017 in Chongqing and randomly assigned to two groups: a control group that used only rabeprazole and a platelet-rich plasma (PRP) group that received a combination therapy of autologous PRP (aPRP) and rabeprazole. The therapeutic effect was assessed via the ulcer size and symptom score. Results: A total of 27 patients were included (12 patients in the control group and 15 patients in the PRP group) in this study. Our results showed that all participants have healed in 30 days, and there was no significant difference in healing time between the PRP group and the control group in different independent variables. However, regression analysis revealed that the healing time was 6.99 days shorter in the PRP group than that in the control group, and patients with higher symptom scores in the initial examination need more time to heal during treatment. Endoscopic results showed that the repaired ulcer in the PRP group was more similar to the normal gastric mucosa tissue than that the control group. Conclusion: This study showed an encouraging preliminary result that aPRP has a positive result in patients with peptic ulcer and seems to be a better choice for refractory peptic ulcer treatment. Although further follow-up studies are needed to determine the duration of efficacy of aPRP, the approach will be helpful in improving the clinical treatment of peptic ulcer.

Long-term outcomes of endoscopic treatment for colorectal laterally spreading tumor: a large-scale multicenter retrospective study from China.

BACKGROUND: Laterally spreading tumor (LST) is a type of precancerous lesion of colorectal cancer with high malignant potential. The present study aimed to evaluate long-term outcomes of endoscopic treatment for LST in Chinese patients. METHODS: This study was a retrospective review of data collected from 653 included patients with LST from six regional representative hospitals in China between January 2007 and January 2017. Demographic characteristics, endoscopic features of LST, operation-related data, and follow-up results were collected and analyzed. RESULTS: LST-granular type (LST-G, 80.3%) was much more common than LST-non-grandular type (LST-NG, 19.7%). The overall submucosal invasion rate of all LSTs was 6.1% and the submucosal invasion rate of LST-NG was significantly higher than that of LST-G (6.79% vs. 3.87%, p = 0.000). The en bloc resection rate of ESD and EMR treatment was 96% and 93.7%, respectively, with pathologic R0 resection rate of 90.1% and 82.8%. After an average duration of follow-up about 34.52 ± 11.76 months, the recurrence rate of ESD was 3.47%, and the recurrence rate of EMR was 8.8% after an average follow-up of about 38.44 ± 4.42 months. However, the recurrence rate of ESD was much lower than piecemeal EMR for LST (3.47% vs. 8.62%, p = 0.017). Retroflexion-assisted technique applied for resection of rectal LST was associated with a significantly shortened operating time (85.40 min vs. 174.18 min, p = 0.002). CONCLUSION: Endoscopic resection is a safe and efficient modality for the treatment of colorectal LST with a relatively low recurrence rate and shortened operating time with the use of retroflexion.

Identification of Lesional Tissues and Nonlesional Tissues in Early Gastric Cancer Endoscopic Submucosal Dissection Specimens Using a Fiber Optic Raman System.

AIM: To identify lesional and nonlesional tissues from early gastric cancer (EGC) patients by Raman spectroscopy to build a diagnostic model and effectively diagnose EGC. METHOD: Specimens were collected by endoscopic submucosal dissection from 13 patients with EGC, and 55 sets of standard Raman spectral data (each integrated 10 times) were obtained using the fiber optic Raman system; there were 33 sets of lesional tissue data, including 18 sets of high-grade intraepithelial neoplasia (HGIN) data and 15 sets of adenocarcinoma data, and 22 sets of nonlesional tissue data. After the preprocessing steps, the average Raman spectrum was obtained. RESULTS: The nonlesional tissues showed peaks at 891 cm-1, 1103 cm-1, 1417 cm-1, 1206 cm-1, 1234 cm-1, 1479 cm-1, 1560 cm-1, and 1678 cm-1. Compared with the peaks corresponding to nonlesional tissues, the peaks of the lesional tissues shifted by different magnitudes, and a new characteristic peak at 1324 cm-1 was observed. Comparing the peak intensity ratio and the integral energy ratio of the lesional tissues with those of the nonlesional tissues revealed a significant difference between the two groups (independent-samplest-test, P < 0.05). Considering the peak intensity ratio of I1560 cm-1/I1103 cm-1 as a diagnostic indicator, the accuracy, sensitivity, and specificity of diagnosing EGC were 98.8%, 93.9%, and 91.9%, respectively. Considering the integral energy ratio (noncontinuous frequency band and continuous frequency band) as a diagnostic indicator, the accuracy, sensitivity, and specificity of diagnosing EGC were 99.2-99.6%, 93.9-97.0%, and 95.5%, respectively. CONCLUSIONS: The integral energy ratio of the Raman spectrum could be considered an effective indicator for the diagnosis of EGC.

Role of Kruppel-Like Factor 5 in Deoxycholic Acid-Mediated Intestinal Transdifferentiation of Esophageal Squamous Epithelium.

Barrett's esophagus (BE) is an acquired condition in which normal squamous epithelium is replaced with metaplastic columnar epithelium as a consequence of gastroesophageal reflux disease. BE is known as a precursor of esophageal adenocarcinoma. Currently, the molecular mechanism underlying epithelial metaplasia in BE patients remains unknown. Therefore, we investigated the role of Krüppel-like factor 5 (KLF5) signaling in the initiation of BE-associated metaplasia. Sprague-Dawley (SD) rats were used to create a surgical model of bile reflux injury. Immunohistochemistry was performed to analyze human and mouse esophageal specimens. Human esophageal squamous epithelial (HET-1A) cells were treated with bile acid and used in transfection experiments. Quantitative real-time PCR and western blot analysis were performed to detect the expression of KLF5, CDX2, MUC2 and villin. Epithelial tissue from both the rat BE model and human BE patients strongly expressed KLF5, CDX2, MUC2, and villin. Bile acid treatment also increased the expression of KLF5, CDX2, MUC2 and villin in esophageal epithelial cells in a time-dependent manner. Moreover, siRNA-mediated knockdown of KLF5 blocked the expression of CDX2, MUC2 and villin, but transfection of a KLF5 expression vector into esophageal epithelial cells promoted their transdifferentiation into columnar-like cells, as demonstrated by increased expression of the intestinal markers CDX2, MUC2 and villin. Thus, in addition to its function as a transcription factor, KLF5 may be linked to an increased risk of BE development.

Consensus on the digestive endoscopic tunnel technique.

With the digestive endoscopic tunnel technique (DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria (MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal (GI) tract. At present, the tunnel technique application range covers the following: (1) Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis; (2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and (3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment. The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism, and significance of DETT, prevention of infection and concepts of DETT-associated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract (indications and contraindications, procedures, pre- and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

Evaluation of the diagnostic potential of ex vivo Raman spectroscopy in gastric cancers: fingerprint versus high wavenumber.

The aim of this study was to apply Raman spectroscopy in the high wavenumber (HW) region (2800 to 3000??cm?1) for ex vivo detection of gastric cancer and compare its diagnostic potential with that of the fingerprint (FP) region (800 to 1800??cm?1). Raman spectra were collected in the FP and HW regions to differentiate between normal mucosa (n=38) and gastric cancer (n=37). The distinctive Raman spectral differences between normal and cancer tissues are observed at 853, 879, 1157, 1319, 1338, 1448, and 2932??cm?1 and are primarily related to proteins, lipids, nucleic acids, collagen, and carotenoids in the tissue. In FP and HW Raman spectroscopy for diagnosis of gastric cancer, multivariate diagnostic algorithms based on partial-least-squares discriminant analysis, together with leave-one-sample-out cross validation, yielded diagnostic sensitivities of 94.59% and 81.08%, and specificities of 86.84% and 71.05%, respectively. Receiver operating characteristic analysis further confirmed that the FP region model performance is superior to that of the HW region model. Better differentiation between normal and gastric cancer tissues can be achieved using FP Raman spectroscopy and PLS-DA techniques, but the complementary natures of the FP and HW regions make both of them useful in diagnosis of gastric cancer.

H. pylori infection is related to mitochondrial microsatellite instability in gastric carcinogenesis.

BACHGROUND: To assess the correlation of H. pylori infection with mitochondrial microsatellite instability (mtMSI) and IL-8 in gastric carcinogenesis. METHODS: H. pylori infection was evaluated through histology and a urease breath test; mtMSI was measured using PCR-single strand conformation polymorphism (PCR-SSCP); IL-8 was analyzed with ELISA methods. RESULTS: The detection rate of mtMSI was significantly higher in specimens with H. pylori infection than in those without H. pylori infection (P < 0.05). The levels of IL-8 were significantly higher in specimens with mtMSI than in those without mtMSI (P < 0.01).An association of mtMSI with the intestinal histological type was found (P < 0.05). Increased IL-8 levels induced by H. pylori were related to the invasion, lymphnode spreading and clinical stage of gastric cancer (P < 0.05). CONCLUSIONS: H. pylori infection is related to mitochondrial microsatellite instability in the early steps of gastric cancer development. IL-8 may play a role in the development of mtMSI induced by H. pylori. Our results support a role for mtMSI in different mechanisms of gastric carcinogenesis.

Prevalence, histologic and clinical characteristics of heterotopic gastric mucosa in Chinese patients.

AIM: To determine the prevalence, demographic, clinical and histopathologic features of heterotopic gastric mucosa (HGM) in Chinese patients. METHODS: Patients referred to three endoscopy units were enrolled in this study. The macroscopic characteristics of HGM were documented. Biopsies were obtained and observed using hematoxylin and eosin staining. Helicobacter pylori colonization was examined by Whartin-Starry staining. RESULTS: HGM was observed in 420 Chinese patients, yielding a prevalence of 0.4%. The majority of patients had a single patch (300/420; 71.4%), while the remainder had two (84/420; 20%) or multiple patches (36/420; 8.6%). The size of the patches and the distance from the patch to the frontal incisor teeth varied significantly. The large majority of HGM patches were flat (393/420; 93.6%), whereas the remaining patches were slightly elevated. The primary histological characteristic was fundic-type (216/420; 51.4%) within the HGM patch, and antral- (43/420; 10.2%) and transitional-type (65/420; 15.5%) mucosa were also observed. The prevalence of intestinal metaplasia was 3.1% (13/420) and the prevalence of dysplasia was 1.4% (6/420), indicating the necessity for endoscopic follow-up in patients with HGM. Esophageal and extraesophageal complaints were also observed in patients with HGM. Dysphagia and epigastric discomfort (odds ratios: 6.836 and 115.826, respectively; Ps < 0.05) were independent risk factors for HGM. CONCLUSION: Clinical complaints should be considered to improve the detection rate of HMG. The prevalence of intestinal metaplasia and dysplasia also indicates a need for endoscopic follow-up.

Effects of lentiviral vector-mediated TRADD expression on the inhibition of hypertrophic scar formation.

The tumor necrosis factor receptor-associated death domain protein (TRADD) regulates cell proliferation and apoptosis via tumor necrosis factor alpha (TNF-α)-mediated signaling pathways. Low levels of TRADD expression may result in the excessive proliferation of hypertrophic scar fibroblasts (HSFb). This study investigated the effects of a lentiviral vector carrying the human tradd gene on the proliferation, apoptosis and type I collagen synthesis of HSFb and embryonic fibroblasts (EFb) and further explored the resulting effects on hypertrophic scars (HS). We utilized cytoimmunofluorescence and Western blotting to confirm the expression of TRADD in HSFb and EFb. A PLVX-TRADD-EGFP lentivirus was prepared and transfected into EFb and HSFb, and then the expression of a TRADD-GFP-FLAG fusion protein was detected in HSFb and EFb. After stimulation with 10 ng/mL TNF-α, cell proliferation, apoptosis, and the synthesis of type I collagen were assessed. Our results show that the expression level of TRADD was significantly lower in HSFb than in EFb. A biologically active PLVX-TRADD-EGFP lentivirus was constructed and transfected into HSFb and EFb. The TRADD-GFP-FLAG fusion protein was effectively expressed in HSFb and EFb. Either alone or in combination with 10 ng/mL TNF-α, the PLVX-TRADD-EGFP lentivirus inhibited proliferation, caused a G2/M phase arrest, induced the appearance of a sub-G1 apoptotic peak and inhibited the secretion of type I collagen by HSFb without significantly affecting EFb. These results suggest that the low expression of TRADD in HSFb is a principal reason for their excessive proliferation. The transfection of a PLVX-TRADD-EGFP lentivirus led to the normal expression of TRADD in HSFb. When combined with 10 ng/mL TNF-α, a PLVX-TRADD-EGFP lentivirus transfection could inhibit cell proliferation, promote apoptosis, and reduce the secretion of type I collagen in HSFb, thereby reducing HS formation.

Endoscopic classification can predict the infiltrative growth patterns of early-stage esophageal cancer: a retrospective study of 133 patients at a single academic tertiary care center.

The relationships between two endoscopic classification systems (type I and II) and the infiltrative growth patterns (INF) of early esophageal cancers were evaluated. Among type I carcinomas, the INFs were mainly INFb in the polypoid and mixed types, INFa in the superficial type, and INFc in the excavated type. Among type II carcinomas, INFa was the main pattern in the surface-propagating type, whereas INFb was observed in the intraluminal, bilateral, and mixed types. INFb and INFc were observed in the intramural type. Our results indicate that the superficial and surface-propagating types had the weakest infiltrative potential, whereas the excavated and intramural types had the highest infiltrative potential.

Raman spectroscopy analysis of the biochemical characteristics of molecules associated with the malignant transformation of gastric mucosa.

OBJECTIVE: The purpose of this study was to comparatively analyze the signature Raman spectra of genomic DNA, nuclei, and tissue of normal gastric mucosa and gastric cancer and to investigate the biochemical transformation of molecules associated with gastric mucosa malignancy. METHOD: Genomic DNA, nuclei, and tissue from normal gastric mucosa and gastric cancer were analyzed by Raman spectroscopy. RESULTS: 1) The Raman spectrum of gastric cancer genomic DNA showed that two peaks appeared, one at approximately 1090 cm-1 with a higher intensity than the peak at 1050 cm-1 in the spectrum. Characteristic peaks appeared at 950 cm-1, 1010 cm-1, and 1100-1600 cm-1. 2) Using a hematoxylin and eosin (H&E)-stained section, the intensity of the characteristic peak of nucleic acids at 1085 cm-1 was increased and shifted to 1088 cm-1 in cancer cells. The relative intensity of the characteristic peaks of nucleoproteins at 755 cm-1 and 1607 cm-1 was significantly increased in cancer cells compared with normal cells. 3) Compared with normal tissues, the peak representing PO2- symmetric stretching vibration shifted from 1088 cm-1 to 1083 cm-1 in cancer tissue, and the characteristic peak for collagen at 938 cm-1 shifted to 944 cm-1. In addition, an extra characteristic peak indicating C = C stretching vibration appeared at 1379 cm-1 in the lipid spectrum in cancer tissue. CONCLUSIONS: The position, intensity, and shape of peaks in the Raman spectra of DNA, nuclei, and tissue from gastric cancer were significantly different compared with those of normal cells. These results indicate that the DNA phosphate backbone becomes unstable in cancer cells and might be broken; the relative content of histones is increased and stable; the relative collagen content is reduced, facilitating cancer cell metastasis; and the relative content of unsaturated fatty acids is increased, increasing the mobility of the plasma membrane of cancer cells.

Knockdown of nucleostemin can inhibit the proliferation of esophageal carcinoma cells in vitro through upregulating p21.

BACKGROUND/AIMS: Esophageal squamous cell carcinoma is a common digestive tract cancer with poor prognosis. Nucleostemin is a nucleolar protein expressed in stem and cancer cells, involved in the regulation of cell proliferation. p21 plays an important role in negative regulation of the cell-cycle. We investigated the role of nucleostemin through regulating p21 expression in the occurrence and progression of human esophageal carcinoma. METHODOLOGY: The expression of nucleostemin and p21 protein and of nucleostemin was knocked-down by means of RNA interference (RNAi) in Eca109 cells. Then, mRNA and protein expressions of nucleostemin and p21 were determined by reverse transcriptase polymerase chain reaction and Western blotting, respectively. In addition, the effect of nucleostemin RNAi on cell proliferation and cell cycle distribution of Eca109 cells were observed. RESULTS: Nucleostemin was high expressed, but p21 was low expressed in esophageal carcinoma tissues while increased level of nucleostemin protein was associated with reduced p21. inhibition of nucleostemin resulted in an increased expression of p21 and inhibition of cell proliferation, cause G1/G0 phase cells increased and S-phase cells reduced greatly in Eca109 cells. CONCLUSION: Silence of nucleostemin inhibit cell proliferation through up-regulating p21 expression and nucleostemin may be involved in the pathogenesis of esophageal squamous cell carcinoma.

Plastic tube-assisted gastroscopic removal of embedded esophageal metal stents: a case report.

A patient with stent embedding after placement of an esophageal stent for an esophagobronchial fistula was treated with an ST-E plastic tube inserted into the esophagus to the upper end of the stent using gastroscopy. The gastroscope was guided into the esophagus through the ST-E tube, and an alligator forceps was inserted into the esophagus through the ST-E tube alongside the gastroscope. Under gastroscopy, the stent wire was grasped with the forceps and pulled into the ST-E tube. When resistance was met during withdrawal, the gastroscope was guided further to the esophageal section where the stent was embedded. Biopsy forceps were guided through a biopsy hole in the gastroscope to the embedded stent to remove silicone membranes and connection threads linking the Z-shaped wire mesh. While the lower section of the Z-shaped stent was fixed by the biopsy forceps, the alligator forceps were used to pull the upper section of the metal wire until the Z-shaped metal loops elongated. The wire mesh of the stent was then removed in stages through the ST-E tube. Care was taken to avoid bleeding and perforation. Under the assistance of an ST-E plastic tube, an embedded esophageal metal stent was successfully removed with no bleeding or perforation. The patient experienced an uneventful recovery after surgery. Plastic tube-assisted gastroscopic removal of embedded metal stents can be minimally invasive, safe, and effective.

Ad-KDRscFv:sTRAIL displays a synergistic antitumor effect without obvious cytotoxicity to normal tissues.

AIM: To investigate the antitumor activities and safety of Ad-KDRscFv, Ad-sTRAIL (114-281) and Ad-KDRscFv:sTRAIL in vivo and in vitro. METHODS: Recombinant replication-defective adenovirus vectors encoding either the extracellular domain (114-281 aa) of TRAIL, the KDRscFv (single chain antibody (scFv) against human vascular endothelial growth factor (VEGF) receptor KDR) or the fusion gene of KDRscFv:sTRAIL were constructed and transfected into HEK 293 cells for virus packaging. The recombinant virus particles were then infected human tumor cell lines of liver cancer (HepG2), gastric cancer (SGC-7901), colorectal cancer (SW480) and normal human liver cell line (LO2) to investigate the antitumor activities. Nude mice of the subcutaneous tumor models were established with HepG2 cells and were randomly divided into different groups to investigate the therapeutic effect and safety of these adenovirus particles on hepatocellular carcinoma. The expression of foreign proteins and the effect on microvascular number were also evaluated. RESULTS: All three adenovirus particles could induce apoptosis of cancer cells lines HepG2, SGC-7901 and SW480, but had no obvious lethal effect on LO2 cells. Ad-KDRscFv:sTRAIL showed the strongest tumoricidal effect. After intratumoral injection with these adenovirus particles on nude mice model, all the three adenoviruses could inhibit the tumor growth and angiogenesis, and the expression of foreign proteins (sTRAIL, KDRscFv and KDRscFv:sTRAIL fusion protein) was restricted to liver and tumor tissues. In coincidence with the result in vitro, Ad-KDRscFv:sTRAIL also had the strongest antitumor activity in vivo. No obvious pathological changes were detected in vivo. CONCLUSIONS: Replication-defective recombinant adenovirus of Ad-KDRscFv, Ad-sTRAIL and Ad-KDRscFv:sTRAIL all had tumoricidal activities and Ad-KDRscFv:sTRAIL showed the strongest effect. All three adenoviruses had no obvious toxicity to normal cells and tissues in vitro and in vivo.

A new endoscopic classification system of early-stage esophageal carcinoma and its usefulness in assessing the infiltration depth of esophageal carcinoma.

The growth pattern, height, and depth of early esophageal carcinoma were observed under gastroscopy and endoscopic ultrasonography. The infiltration depth of carcinomas was determined pathologically. Early esophageal carcinomas were classified into five types by endoscopy: surface propagating growth, intraluminal growth, intramural growth, bilateral growth, and mixed growth. Intramucosal and submucosal carcinomas were differentiated on the basis of the different types, height of intraluminal growth and bilateral growth, and depth of intramural growth type. The accuracy of differentiate diagnosis was 87.2%. Our results indicate that this new endoscopic classification system can accurately differentiate intramucosal and submucosal infiltration of early-stage esophageal carcinomas.

Evaluation of double vital staining with lugol's iodine and methylene blue in diagnosing superficial esophageal lesions.

OBJECTIVE: To evaluate the accuracy of double vital staining with lugol's iodine and methylene blue in the diagnosis of superficial esophageal lesions. METHODS: Doubtful superficial esophageal lesions identified with conventional endoscope were sprayed with 3% lugol's iodine and 0.5% methylene blue in order and observed in detail after each staining. Depending on the mucosal staining, biopsy specimen was obtained and underwent pathological examination. RESULTS: Using conventional endoscope, we found 356 lesions in 297 patients, among which 179 were esophageal squamous cell carcinoma and precancerous lesions (CAPs) (including 71 early esophageal squamous cell carcinoma, 23 esophageal high-grade intraepithelial neoplasias, 85 esophageal low-grade intraepithelial neoplasias) and 177 were non-cancer non-precancerous lesions (NCNPs) (i.e. esophagitis and esophageal squamous cell hyperplasia). Most of CAPs were lightly stained or unstained, while NCNPs were hyperstained after lugol's iodine stained. The specificity, sensitivity, positive predictive value, negative predictive value and accuracy of lugol's lightly stained and unstained for identifying CAPs were 34.5%, 100%, 60.7%, 100% and 67.4%, respectively. Most of CAPs were lightly stained or hyperstained, while NCNPs were unstained after double vital staining. The specificity, sensitivity, positive predictive value, negative predictive value and accuracy of double vital staining lightly stained and hyperstained for identifying CAPs were 97.7%, 100%, 97.8%, 100% and 98.9%, respectively. The accuracy of double vital staining for identifying CAPs was higher than that of lugol's iodine stained (p = 0.000). CONCLUSION: The double staining with lugol's iodine and methylene blue significantly improves the detection and diagnosis of early esophageal squamous cell CAPs.

RNA interference-mediated hTERT inhibition enhances TRAIL-induced apoptosis in resistant hepatocellular carcinoma cells.

TRAIL has been reported to induce apoptosis in a variety of tumor cell types including hepato-cellular carcinoma (HCC) cell lines. However, considerable numbers of HCC cells, especially some highly malignant tumors, show resistance to TRAIL-induced apoptosis. The molecular mechanisms that regulate sensitivity versus resistance of tumor cells to TRAIL-induced apoptosis remain poorly defined. It has been shown that human telomerase catalytic subunit (hTERT) is overexpressed in human HCCs. In this study, we investigated the effects and the mechanisms of hTERT RNAi on the TRAIL-induced apoptosis of HCC cells that exhibit resistance to TRAIL. Our results indicate that hTERT RNAi sensitizes TRAIL-resistant HCC cells to TRAIL-induced apoptosis. hTERT RNAi-mediated sensitization to TRAIL-induced apoptosis is accompanied up-regulation of procaspases-8 and -9, inhibition of telomerase activity and loss of telomere length. Our results suggest that hTERT RNAi overcame the resistance of the HCC cells against TRAIL, at least in part, via the mitochondrial type II apoptosis pathway and telomerase-dependent pathway.

Dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress in rats.

AIM: To investigate the dynamic functional and ultrastructural changes of gastric parietal cells induced by water immersion-restraint stress (WRS) in rats. METHODS: WRS model of Sprague-Dawley (SD) rats was established. Fifty-six male SD rats were randomly divided into control group, stress group and post-stress group. The stress group was divided into 1, 2 and 4 h stress subgroups. The post-stress group was divided into 24, 48 and 72 h subgroups. The pH value of gastric juice, ulcer index (UI) of gastric mucosa and H(+), K(+)-ATPase activity of gastric parietal cells were measured. Ultrastructural change of parietal cells was observed under transmission electron microscope (TEM). RESULTS: The pH value of gastric juice decreased time-dependently in stress group and increased in post-stress group. The H(+), K(+)-ATPase activity of gastric parietal cells and the UI of gastric mucosa increased time-dependently in stress group and decreased in post-stress group. Compared to control group, the pH value decreased remarkably (P = 0.0001), the UI and H(+), K(+)-ATPase activity increased significantly (P = 0.0001, P = 0.0174) in 4 h stress subgroup. UI was positively related with stress time (r = 0.9876, P < 0.01) but negatively with pH value (r = -0.8724, P < 0.05). The parietal cells became active in stress group, especially in 4 h stress subgroup, in which plenty of intracellular canalicular and mitochondria were observed under TEM. In post-stress group, the parietal cells recovered to resting state. CONCLUSION: The acid secretion of parietal cells is consistent with their ultrastructural changes during the development and healing of stress ulcer induced by WRS and the degree of gastric mucosal lesions, suggesting gastric acid play an important role in the development of stress ulcer and is closely related with the recovery of gastric mucosal lesions induced by WRS.

Mutation and methylation of hMLH1 in gastric carcinomas with microsatellite instability.

AIM: To appraise the correlation of mutation and methylation of hMSH1 with microsatellite instability (MSI) in gastric cancers. METHODS: Mutation of hMLH1 was detected by Two-dimensional electrophoresis (Two-D) and DNA sequencing; Methylation of hMLH1 promoter was measured with methylation-specific PCR; MSI was analyzed by PCR-based methods. RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for mutation and methylation of hMLH1 promoter and MSI. Three mutations were found, two of them were caused by a single bp substitution and one was caused by a 2 bp substitution, which displayed similar Two-D band pattern. Methylation of hMLH1 promoter was detected in 11(16.2 %) gastric cancer. By using five MSI markers, MSI in at least one locus was detected in 17/68(25 %) of the tumors analyzed. Three hMLH1 mutations were all detected in MSI-H (>=2 loci, n=8), but no mutation was found in MSI-L (only one locus, n=9) or MSS (tumor lacking MSI or stable, n=51). Methylation frequency of hMLH1 in MSI-H (87.5 %, 7/8) was significantly higher than that in MSI-L (11.1 %, 1/9) or MSS (5.9 %, 3/51) (P<0.01-0.001), but no difference was found between MSI-L and MSS (P>0.05). CONCLUSION: Both mutation and methylation of hMLH1 are involved in the MSI pathway but not related to the LOH pathway in gastric carcinogenesis.