Comparison of the efficacy between the dual therapy of tegoprazan and the quadruple therapy of tegoprazan: A randomized, controlled, multicenter study.

INTRODUCTION: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. METHODS: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multi-center, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. RESULTS: The intention-to-treat analysis revealed that H. pylori-eradication rates were 83.9% (95% confidence interval [CI] 78.2%-91.3%) and 81.4% (95% CI 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them (P = 0.606). The per-protocol analysis revealed that the H. pylori-eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively (P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs. 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs. 89.0%, P = 0.020). CONCLUSION: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: A multicenter randomized controlled trial in China.

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.

Prediction of Esophageal Stricture after Endoscopic Submucosal Dissection in Patients with Early Esophageal Cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) treatment of early esophageal cancer is effective and safe. It is currently the first-line treatment for early esophageal cancer. However, a common side effect is the development of esophageal strictures after ESD. This study was designed to identify the risk factors for esophageal stricture development and to predict its occurrence after ESD. METHODS: In this retrospective study, 150 consecutive patients with early esophageal cancer treated with ESD at Daping Hospital, Chongqing, were enrolled between January 2016 and December 2020. Data on patient demographics, esophageal tumor characteristics, procedure-related factors, and postoperative situations were collected. We identified independent risk factors of esophageal stricture formation using univariate analysis and multivariate logistic regression. The predictive probability was obtained after multivariate logistic analysis. In addition, patients were divided into six groups based on these risk factors and the rate of esophageal stricture in each group was analyzed. RESULTS: The postoperative esophageal stricture rate was 14% (21/150). Tumor location (OR = 5.655, 95% CI: 1.245-25.691, P = 0.025) and circumferential resection range (OR = 16.113, 95% CI: 4.294-60.466, P < 0.001) are independent risk factors for the development of esophageal strictures. According to predictive probability analysis and the rates of stricture in six groups, we developed a possible flow chart to predict stricture formation. CONCLUSIONS: Tumor location and circumferential resection range are reliable risk factors to predict the occurrence of esophageal strictures. Our prediction flow chart suggests that tumors with a circumferential resection range of 1/2-3/4 and located above the upper thoracic segment or a circumferential resection range of > 3/4 have a high risk of postoperative stricture. Thus, timely and effective preventive measures should be taken in these patients following ESD.

High-dose dual therapy versus culture-based susceptibility-guided therapy as a rescue regimen for Helicobacter pylori infection: a randomized controlled trial.

Background: Although the Maastricht VI/Florence consensus report recommended high-dose proton pump inhibitor-amoxicillin dual therapy as possible rescue therapy for Helicobacter pylori infection, clinical evidence of its efficacy was lacking. Objectives: To compare the efficacy, safety, patient compliance, and cost between high-dose dual therapy (HDDT) and culture-based susceptibility-guided therapy (CB-SGT) as a rescue regimen for H. pylori infection. Design: A single-center, open-label, randomized controlled clinical trial. Methods: In all, 146 patients with a history of eradication failure were enrolled and randomly assigned to receive HDDT or CB-SGT. HDDT consisted of esomeprazole 20 mg and amoxicillin 750 mg, both given four times per day (qid). CB-SGT consisted of esomeprazole 20 mg twice daily (bid), amoxicillin 1000 mg bid plus clarithromycin 500 mg bid, metronidazole 400 mg bid, or levofloxacin 500 mg daily (qd) for sensitive patients, in that order. For patients with triple resistance, a bismuth-containing regimen with a high dose of metronidazole was chosen, including esomeprazole 20 mg bid, bismuth 220 mg bid, amoxicillin 1000 mg bid, and metronidazole 400 mg qid. All regimens were given for 14 days. Results: The eradication H. pylori rates achieved with HDDT in the intention-to-treat (ITT), per-protocol, and modified ITT analyses were all 84.9% [62/73, 95% confidence interval (CI): 76.5-93.9%], compared with 83.6% (61/73, 95% CI: 74.9-92.3%), 84.7% (61/72, 95% CI: 76.2-93.2%), and 84.7% (61/72, 95% CI: 76.2-93.2%) with CB-SGT, respectively. For patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, the eradication rates of HDDT and CB-SGT were 90.70% (39/43, 95% CI: 77.86-97.41%) and 84.21% (32/38, 95% CI: 68.75-93.98%), respectively. The difference between groups was 6.49% (95% CI: -8.00% to 20.97%), and the non-inferiority p value was 0.0128. For patients with a treatment interval of more than 3 months, the eradication rates of the two regimens reached 88.71% (95% CI: 78.11-95.34%) and 71.97% (95% CI: 70.02-90.64%). The difference between groups was 6.74% (95% CI: -5.71% to 19.20%), with a non-inferiority p value of 0.0042. Patient adherence was high in both groups. The HDDT had a lower cost and rate of side effects (p < 0.001) compared with CB-SGT. Conclusions: HDDT can reach an eradication rate of 85% in treatment-experienced patients of H. pylori infection and 91% in patients with CYP2C19 polymorphisms of intermediate/poor metabolizers, with good compliance, lower side effects and costs, and less use of antibiotics. In conclusion, HDDT offers an effective rescue regimen for H. pylori infection. Registration: This clinical trial was registered at the Chinese Clinical Trail Registry (trail registration number: ChiCTR1900025044).

SHARPIN stabilizes ß-catenin through a linear ubiquitination-independent manner to support gastric tumorigenesis.

BACKGROUND: Aberrant activation of Wnt/ß-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/ß-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity. METHODS: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/ß-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of ß-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo. RESULTS: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with ß-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase ß-Trcp1 for ß-catenin binding, thereby decreasing ß-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner ß-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with ß-catenin expression levels. CONCLUSIONS: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/ß-catenin signaling via SHARPIN-mediated stabilization of ß-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive ß-catenin signaling in a subset of human gastric cancers.

BRD4 Promotes Gastric Cancer Progression and Metastasis through Acetylation-Dependent Stabilization of Snail.

Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells in vitro and their dissemination at distal organs in vivo. Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and ß-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors. SIGNIFICANCE: These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4869/F1.large.jpg.

Eradication Efficacy of Modified Dual Therapy Compared with Bismuth-Containing Quadruple Therapy as a First-Line Treatment of Helicobacter pylori.

OBJECTIVES: This study assessed the effectiveness, adverse events, patient adherence, and costs of modified dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori infection in Chinese patients. We also sought to determine whether modified dual therapy could be used as an alternative first-line treatment for H. pylori infection. METHODS: A total of 232 H. pylori-infected, treatment-naive patients were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day modified dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the 2 groups. RESULTS: The modified dual therapy group achieved eradication rates of 87.9%, 91.1%, and 91.1% as determined by the intention-to-treat, per-protocol, and modified intention-to-treat analyses, respectively. The eradication rates were similar compared with the bismuth-containing quadruple therapy group: 89.7%, 91.2%, and 90.4%. In addition, modified dual therapy ameliorated variations in the CYP2C19, IL-1B-511, and H. pylori VacA genotypes. There were no significant differences in the compliance rates between the 2 groups. The modified dual therapy group exhibited significantly less overall side effects compared with the bismuth-containing quadruple therapy group (P < 0.001). Furthermore, the cost of medications in the modified dual therapy was lower compared with that in the bismuth-containing quadruple therapy. CONCLUSIONS: Modified dual therapy at high dose and administration frequency is equally effective and safer and less costly compared with bismuth-containing quadruple therapy.

A salivary effector enables whitefly to feed on host plants by eliciting salicylic acid-signaling pathway.

Phloem-feeding insects feed on plant phloem using their stylets. While ingesting phloem sap, these insects secrete saliva to circumvent plant defenses. Previous studies have shown that, to facilitate their feeding, many phloem-feeding insects can elicit the salicylic acid- (SA-) signaling pathway and thus suppress effective jasmonic acid defenses. However, the molecular basis for the regulation of the plant's defense by phloem-feeding insects remains largely unknown. Here, we show that Bt56, a whitefly-secreted low molecular weight salivary protein, is highly expressed in the whitefly primary salivary gland and is delivered into host plants during feeding. Overexpression of the Bt56 gene in planta promotes susceptibility of tobacco to the whitefly and elicits the SA-signaling pathway. In contrast, silencing the whitefly Bt56 gene significantly decreases whitefly performance on host plants and interrupts whitefly phloem feeding with whiteflies losing the ability to activate the SA pathway. Protein-protein interaction assays show that the Bt56 protein directly interacts with a tobacco KNOTTED 1-like homeobox transcription factor that decreases whitefly performance and suppresses whitefly-induced SA accumulation. The Bt56 orthologous genes are highly conserved but differentially expressed in different species of whiteflies. In conclusion, Bt56 is a key salivary effector that promotes whitefly performance by eliciting salicylic acid-signaling pathway.

Epigenetic restriction of Hippo signaling by MORC2 underlies stemness of hepatocellular carcinoma cells.

The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC). We identify a member of the microrchidia (MORC) protein family, MORC2, as an inhibitor of the Hippo pathway by controlling upstream Hippo regulators, neurofibromatosis 2 (NF2) and kidney and brain protein (KIBRA). Mechanistically, MORC2 forms a complex with DNA methyltransferase 3A (DNMT3A) at the promoters of NF2 and KIBRA, leading to their DNA hyper-methylation and transcriptional repression. As a result, NF2 and KIBRA are crucial targets of MORC2 to regulate confluence-induced activation of Hippo signaling and contact inhibition of cell growth under both physiological and pathological conditions. The MORC2-NF2/KIBRA axis is critical for maintaining self-renewal, sorafenib resistance, and oncogenicity of HCC cells in vitro and in nude mice. Furthermore, MORC2 expression is elevated in HCC tissues, associated with stem-like properties of cancer cells, and disease progression in patients. Collectively, MORC2 promotes cancer stemness and tumorigenesis by facilitating DNA methylation-dependent silencing of Hippo signaling and could be a potential molecular target for cancer therapeutics.

Digenic mutations involving both the BSND and GJB2 genes detected in Bartter syndrome type IV.

Bartter syndrome type IV, characterized by salt-losing nephropathies and sensorineural deafness, is caused by mutations of BSND or simultaneous mutations of both CLCNKA and CLCNKB. GJB2 is the primary causative gene for non-syndromic sensorineural deafness and associated with several syndromic sensorineural deafness. Owing to the rarity of Bartter syndrome, only a few mutations have been reported in the abovementioned causative genes. To investigate the underlying mutations in a Chinese patient with Bartter syndrome type IV, genetic analysis of BSND, CLCNKA, CLCNKB and GJB2 were performed by polymerase chain reaction and direct sequencing. Finally, double homozygous mutations c.22C > T (p.Arg8Trp) and c.127G > A (Val43Ile) were detected in exon 1 of BSND. Intriguingly, compound heterozygous mutations c.235delC (p.Leu79CysfsX3) and c.109G > A (p.Val37Ile) were also revealed in exon 2 of GJB2 in the same patient. No pathogenic mutations were found in CLCNKA and CLCNKB. Our results indicated that the homozygous mutation c.22C > T was the key genetic reason for the proband, and a digenic effect of BSND and GJB2 might contributed to sensorineural deafness. To our knowledge, it was the first report showing that the GJB2 gene mutations were detected in Bartter syndrome.

RING finger proteins are involved in the progression of barrett esophagus to esophageal adenocarcinoma: a preliminary study.

BACKGROUND/AIMS: To investigate the differential expression of RING finger (RNF) proteins in Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: The differential expression of RNFs in normal esophagus (NE), BE, and EAC was screened using microarray assay. Real-time quantitative polymerase chain reaction (PCR), tissue micro-array assay, and Western blot analysis were independently performed to detect the mRNA and protein expression of screened RNFs. RESULTS: The expression of nine RNFs in the BE or EAC was 2-fold higher than those in NE. Among these proteins, the RNF32 and RNF121 expression in BE was 20.3-fold and 16.4-fold higher, respectively, than that in NE, and the expression of RNF24, RNF130, RNF141, RNF139, RNF11, RNF14, and RNF159 was upregulated more than 2-fold compared with NE. The expression of nine RNFs was not only upregulated in the EAC but was also positively related to the RNF expression in BE. The PCR results also indicated increased expression of these RNFs in BE and EAC compared to NE. Furthermore, the mRNA expression of all RNFs, except for RNF141 in EAC, was dramatically higher than those in the BE. Similar results were also obtained from the Western blot analysis. CONCLUSIONS: A total of nine RNFs play critical roles in the progression of BE to EAC.

Identification and functional analysis of a novel mutation in the SOX10 gene associated with Waardenburg syndrome type IV.

Waardenburg syndrome type IV (WS4) is a rare genetic disorder, characterized by auditory-pigmentary abnormalities and Hirschsprung disease. Mutations of the EDNRB gene, EDN3 gene, or SOX10 gene are responsible for WS4. In the present study, we reported a case of a Chinese patient with clinical features of WS4. In addition, the three genes mentioned above were sequenced in order to identify whether mutations are responsible for the case. We revealed a novel nonsense mutation, c.1063C>T (p.Q355*), in the last coding exon of SOX10. The same mutation was not found in three unaffected family members or 100 unrelated controls. Then, the function and mechanism of the mutation were investigated in vitro. We found both wild-type (WT) and mutant SOX10 p.Q355* were detected at the expected size and their expression levels are equivalent. The mutant protein also localized in the nucleus and retained the DNA-binding activity as WT counterpart; however, it lost its transactivation capability on the MITF promoter and acted as a dominant-negative repressor impairing function of the WT SOX10.

[Preparation and optimum process of walnut peel activated carbon by zinc chloride as activating agent].

Walnut peel as raw material, zinc chloride was used as activating agent for preparation walnut peel activated carbon in the muffle furnace in this experiment, using orthogonal design. Yield, the specific surface area and iodine number of walnut peel activated carbon were determined at all designed experimental conditions and the optimum technological condition of preparation was obtained. By analysis of aperture, infrared spectra and the content of acidic group in surface with Boehm, walnut peel activated carbon of prepared at the optimum condition was characterized. The results showed the optimum technological parameters of preparation: activation temperature (600 °C), activation time (1 h), the concentration of zinc chloride (50%), the particle size (60 mesh). The specific surface area of walnut peel activated carbon obtained at optimum condition was mounting to 1258.05 m2 · g(-1), the ratio of medium porous 32.18%. Therefore, walnut peel can be used in the preparation of the high-quality activated carbon of large surface area. Agricultural wastes, as walnut peel, not only were implemented recycle, but also didn't make any pollution. Meanwhile, a cheap adsorbent was provided and it was of great significance to open a new source of activated carbon.

Transoralgastric gastroscopic debridement for peripancreatic abscess: a special case report.

Transoralgastric debridement for pancreatic abscess is one of the successful applications of NOTES in clinical practice. We present a case report as follows: a 71-year-old female was hospitalized due to acute biliary pancreatitis. Three weeks after onset, the secondary abdominal CT showed a peripancreatic abscess. A passageway between the gastric wall and the abscess was made with a high-frequency puncher under the guidance of an ultrasonic gastroscope and then a gastroscope was directly inserted into the abscess, and a large amount of solid necrotic tissue was taken out with foreign body forceps and snare under the direct vision of a gastroscope. Then a 8.5F double-J stent and a nasobiliary drainage tube were inserted. After three times of intra-abdominal abscess debridement and repeated rinsing with an antibiotic solution, abdominal CT revealed the intra-abdominal abscess nearly disappeared and the patient discharged from hospital.

Osteopontin expression in nasopharyngeal carcinoma: its relevance to the clinical stage of the disease.

PURPOSE: To investigate osteopontin (OPN) expression in human nasopharyngeal carcinoma (NPC) and evaluate its clinical significance in the disease. MATERIALS AND METHODS: The expression of OPN mRNA in 44 frozen NPC tissue and 15 normal nasopharyngeal epithelium tissue (NNET) samples was examined by semi-quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). OPN protein expression in 67 paraffin-embedded NPC tissue and 21 NNET samples was detected by immunohistochemistry (IHC). In addition, OPN expression was investigated in 12 paired NPC and para-carcinoma tissue (PCT) samples by western blotting (WB). The association between the expression of OPN and the clinicopathologic parameters of NPC was evaluated. RESULTS: Three different methods all showed that the expression of OPN mRNA or protein in NPC was significantly higher than in NNET or PCT (P = 0.000, 0.001, 0.000, respectively). After an examination by IHC, 88.1% (59/67) of NPC samples showed strong or moderate positive OPN staining and 28.6% (6/21) of NNET samples displayed a weak positive OPN staining. The staining of OPN in tumor cells was mainly localized to the cytoplasm. OPN expression in NPC was not related to patient age or sex (P > 0.05), but was significantly related to tumor size, regional lymph nodal metastasis, and NPC clinical stages (P < 0.05). CONCLUSIONS: Our study demonstrated that OPN mRNA and protein overexpression in NPC may be important in the pathogenesis of the disease. It was strongly related to T stage, N stage and clinical stages of NPC, suggesting that OPN may be involved in NPC metastasis and progression.

PinX1 gene transfection enhances the sensitivity of gastric carcinoma cell line to 5-fluorouracil.

BACKGROUND/AIMS: Since telomeres and telomerase play crucial roles in maintaining cell immortalization and cancer progression, they may be targets for anticancer treatment. PinX1 is a potent telomerase inhibitor, and a putative tumor suppressor. The use of PinX1 to treat cancers has not been reported yet. METHODOLOGY: In order to use PinX1 in gene therapy for gastric carcinoma, we transfected PinX1 gene into the gastric carcinoma line MKN28 using the eukaryotic expression vector pIRES2-EGFP. PinX1-expressing, drug-resistant clones were screened with G418 and used in the study. RESULTS: MKN28 cells transfected with PinX1 gene grew more slowly than the cells not transfected or transfected with void vectors (p<0.05). The IC50 value decreased markedly in cells transfected with PinX1 gene. PinX1 gene transfection enhanced the sensitivity of MKN28 cells to 5-fluorouracil (p<0.05). CONCLUSIONS: PinX1 may be used in gene therapy for gastric carcinoma.

Bone morphogenetic protein-4-induced epithelial-mesenchymal transition and invasiveness through Smad1-mediated signal pathway in squamous cell carcinoma of the head and neck.

BACKGROUND AND AIMS: Bone morphogenetic proteins (BMPs) have recently been shown to be involved in the genesis and progression of a wide variety of carcinomas. The present study was undertaken to estimate the effect of BMP-4 on squamous cell carcinoma of the head and neck (SCCHN) in tissue and cell levels. METHODS: In this study, immunohistochemistry, Western blotting and RT-PCR were utilized to detect the expression of BMP-4, Smad1 and phosphorylated Smad1 in SCCHN tissues or SCCHN cell lines. Those three proteins in tissues were further correlated with prognosis of SCCHN by Kaplan-Meier analysis. The epithelial-mesenchymal transition (EMT)-associated changes in SCCHN cells were detected after stimulation by human BMP-4 recombinant protein and knockdown of Smad1 gene. Meanwhile, the effect on invasiveness and migration was evaluated by invasion and scratch assays, respectively. RESULTS: BMP-4 and p-Smad1 protein were overexpressed in SCCHN tissues with cervical lymph node metastasis, which was significantly higher than those without metastasis. The expression of BMP-4 and p-Smad1 protein was negatively correlated with the prognosis of SCCHN. BMP-4 promoted the invasiveness and migration through EMT, which was demonstrated by morphological alterations, loss of E-cadherin, increase of vimentin and activation of the Smad1 signal pathway. Knockdown of Smad1 expression suppressed BMP-4 induced EMT in both cell lines and weakened the invasiveness and migration of Tu686 and Tu212 in vitro. CONCLUSIONS: Our results demonstrate that BMP-4 protein may contribute to the malignant metastasis of SCCHN, which presents as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.