Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein.

Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.

Rescue Therapy for Helicobacter pylori Eradication: A Randomized Non-Inferiority Trial of Amoxicillin or Tetracycline in Bismuth Quadruple Therapy.

OBJECTIVES: To compare the efficacy and safety of bismuth-containing quadruple therapy with tetracycline or amoxicillin for rescue treatment of Helicobacter pylori. METHODS: The study was a non-inferiority trial of H. pylori eradication with at least two previous treatment failures. Subjects were randomized to receive 14-day therapy with b.i.d. lansoprazole 30 mg and bismuth 220 mg, plus metronidazole 400 mg q.i.d and amoxicillin 1 g t.i.d (amoxicillin group) or tetracycline 500 mg q.i.d (tetracycline group). Antimicrobial susceptibility was assessed by the agar-dilution method. Primary outcome was H. pylori eradication at 6 weeks after treatment. RESULTS: In all, 312 subjects were randomized, 13 were lost to follow-up; 29 violated the protocol. The intention-to-treat, per-protocol, and modified intention-to-treat eradication rates were (amoxicillin) 88.5% (138/156, 95% confidence interval (CI) 83.4-93.5%), 93.7% (133/142, 95% CI 89.7-97.7%), and 92.6% (138/149, 95% CI 88.4-96.8%). With tetracycline, they were 87.2% (136/156, 95% CI 81.9-92.4%), 95.3% (122/128, 95% CI 91.7-99.0%), and 90.7% (136/150, 95% CI 86.0-95.3%). Amoxicillin-, tetracycline-, and metronidazole-resistant rates were 8.3, 1.0, and 87.8%, respectively. Non-inferiority was confirmed (P<0.025). Metronidazole resistance did not affect the efficacy of either therapy. Compliance was greater and moderate and severe adverse events were less among those receiving amoxicillin than those receiving tetracycline. CONCLUSIONS: The novel bismuth-containing quadruple therapy with metronidazole and amoxicillin is an alternative to classical bismuth quadruple therapy for H. pylori rescue treatment as it provides similar eradication with superior safety and compliance.

Electronic transport properties of Ir-decorated graphene.

Graphene decorated with 5d transitional metal atoms is predicted to exhibit many intriguing properties; for example iridium adatoms are proposed to induce a substantial topological gap in graphene. We extensively investigated the conductivity of single-layer graphene decorated with iridium deposited in ultra-high vacuum at low temperature (7 K) as a function of Ir concentration, carrier density, temperature, and annealing conditions. Our results are consistent with the formation of Ir clusters of ~100 atoms at low temperature, with each cluster donating a single electronic charge to graphene. Annealing graphene increases the cluster size, reducing the doping and increasing the mobility. We do not observe any sign of an energy gap induced by spin-orbit coupling, possibly due to the clustering of Ir.

Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.

OBJECTIVE: To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. DESIGN: Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. RESULTS: Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. CONCLUSIONS: These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. TRIAL REGISTRATION NUMBER: NCT02175901.

Esaki Diodes in van der Waals Heterojunctions with Broken-Gap Energy Band Alignment.

van der Waals (vdW) heterojunctions composed of two-dimensional (2D) layered materials are emerging as a solid-state materials family that exhibits novel physics phenomena that can power a range of electronic and photonic applications. Here, we present the first demonstration of an important building block in vdW solids: room temperature Esaki tunnel diodes. The Esaki diodes were realized in vdW heterostructures made of black phosphorus (BP) and tin diselenide (SnSe2), two layered semiconductors that possess a broken-gap energy band offset. The presence of a thin insulating barrier between BP and SnSe2 enabled the observation of a prominent negative differential resistance (NDR) region in the forward-bias current-voltage characteristics, with a peak to valley ratio of 1.8 at 300 K and 2.8 at 80 K. A weak temperature dependence of the NDR indicates electron tunneling being the dominant transport mechanism, and a theoretical model shows excellent agreement with the experimental results. Furthermore, the broken-gap band alignment is confirmed by the junction photoresponse, and the phosphorus double planes in a single layer of BP are resolved in transmission electron microscopy (TEM) for the first time. Our results represent a significant advance in the fundamental understanding of vdW heterojunctions and broaden the potential applications of 2D layered materials.

Fourteen-day optimized levofloxacin-based therapy versus classical quadruple therapy for Helicobacter pylori treatment failures: a randomized clinical trial.

OBJECTIVE: To test the efficacy of lansoprazole, bismuth, levofloxacin, and amoxicillin therapy compared to bismuth metronidazole tetracycline (BMT) quadruple therapy for second-line treatment of Helicobacter pylori infection. METHODS: A total of 284 patients who failed prior H. pylori eradication were randomized to receive 14-day regimens containing lansoprazole 30 mg twice a day (b.i.d.), bismuth subcitrate 240 mg b.i.d., and either amoxcillin, 1 g b.i.d. and levofloxacin 500 mg once daily (qd) (levofloxacin/bismuth therapy) or metronidazole 400 mg four times daily (q.i.d.) and tetracycline, 500 mg q.i.d. (BMT quadruple therapy). Endoscopy and culture were performed before treatment. Antimicrobial susceptibility was by agar dilution. H. pylori status was determined 6 weeks after the end of therapy using a (13)C-urea breath test. RESULTS: The metronidazole, levofloxacin, tetracycline, and amoxicillin resistance rates were 85.3%, 40.2%, 1.1%, and 0.5%, respectively. The intention-to-treat and per-protocol (PP) eradication rates were 83% (95% confidence interval [CI]: 75.9-88.3%) and 88.1% (95% CI: 81.2-92.4%) (p = 0.22) for levofloxacin-bismuth (levo-bismuth) versus BMT quadruple, respectively, and PP rates were 85.4% (95% CI: 78.5-90.3%) and 90.6% (95% CI: 84.6-94.5%) (p = 0.18). Moderate and severe side effects were significantly higher with BMT quadruple than levo-bismuth (22.4% vs. 5%, p < 0.001) and higher in women (28.4%) than men (10.4%) in BMT quadruple therapy group (p = 0.015). CONCLUSION: Increasing fluoroquinolone resistance has undermined levo-bismuth quadruple therapy making BMT quadruple therapy a better choice empiric second-line therapy for H. pylori infection. However, compliance was significantly higher with levo-bismuth quadruple therapy, especially among women.

Inhibition of endothelial Slit2/Robo1 signaling by thalidomide restrains angiogenesis by blocking the PI3K/Akt pathway.

BACKGROUND: Thalidomide is effective in the treatment of angiodysplasia. The mechanisms underlying its activity may be associated with inhibition of angiogenic factors. It was recently shown that Slit2/Robo1 signaling plays a role in angiogenesis. PURPOSE: The aim of this study was to explore the expression and effects of Robo1 and Slit2 in angiodysplasia and to identify the possible therapeutic mechanisms of thalidomide. METHOD: Slit2 and Robo1 expression were analyzed in tissue samples and human umbilical vein endothelial cells (HUVECs) treated with thalidomide using a combination of laboratory assays that were able to detect functional activity. RESULTS: Slit2, Robo1 and vascular endothelial growth factor (VEGF) were strongly expressed in five angiodysplasia lesions out of seven cases, while expression was low in one out of seven normal tissues. Exposure of HUVECs to recombinant N-Slit2 resulted in an increase in VEGF levels and stimulated proliferation, migration and tube formation. These effects were blocked by an inhibitor of PI3K and thalidomide. CONCLUSIONS: Robo1 and Slit2 may have important roles in the formation of gastrointestinal vascular malformation. High concentrations of Slit2 increased the levels of VEGF in HUVECs via signaling through the PI3K/Akt pathway-an effect that could be inhibited by thalidomide.

Specific anti-gastric cancer effects of a recombinant plasmid expressing nonstructural protein 1 of parvovirus H1.

OBJECTIVE: To investigate the responsiveness of gastric tumor cells to the nonstructural protein (NS)1 of parvovirus H1, which has a preferential lytic growth cycle in cancer cells. METHODS: This study was carried out in Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai, China from 2009 to 2012. An NS1-expressing plasmid was introduced into gastric cell lines or nude mice bearing tumor grafts. Expression was monitored by tracking fluorescence tag and specific transcription. Tumor growth suppression was measured, and cell cycle dyshomeostasis was verified by flow cytometry. Cell cycle regulators' level was measured on both the transcription and protein level. RESULTS: Gastric cancer cells were efficiently suppressed in vitro, or in the xenograft mice model. The NS1 dependent tumor suppression was specific since plasmid-driven NS1 expression in some normal tissues, in particular, the lungs was not accompanied by adverse side effects. The NS1 expression was found to stall gastric cancer cells in the G0/G1 stage with accumulation of cycle regulator p21. CONCLUSION: The NS1 expression can suppress gastric cancer cell growth both in vitro and in xenograft model, probably through induction of the cell cycle regulator p21. These results support further development of the parvoviral NS1 protein as an anti-cancer effector.

Low-dose azathioprine is effective in maintaining remission among Chinese patients with Crohn's disease.

BACKGROUND: Azathiopurine (AZA) is efficacious for maintenance remission of Crohn's disease (CD) at the standard dose of 2.0-2.5 mg/kg for Caucasian. It has been reported that the lower dose (1.0-2.0 mg/kg) in some Asian countries was as effective as the standard dose. In the present study we analyzed the efficacy of <1.0 mg/kg AZA in maintaining remission for Chinese patients. METHODS: The clinical data of all CD patients were reviewed from 1993 to December 2012. The patients who initiated AZA treatment and were followed for ≥ 2 years with complete medical data were included. We divided the patients into two groups according to their initial dose: <1.0 mg/kg group and 1.0-2.0 mg/kg group. RESULTS: Among 77 patients, 39 (50.6%) started treatment with <1.0 mg/kg AZA and 38 (49.4%) with 1.0-2.0 mg/kg. The mean dose of <1.0 mg/kg group remained under 1.0 mg/kg at 6, 12 and 24 months, even if the doses were adjusted according to efficacy and tolerance. The remission rate in patients of <1.0 mg/kg group was significantly higher than that in those of 1.0-2.0 mg/kg group (P = 0.025). A dose of <1.0 mg/kg AZA was more commonly associated with male gender, older age, heavier body weight and L1 location. Adverse events were observed in 21 of 77 patients (27.3%) and no significant difference in occurrence of adverse events or leucopenia between two groups. CONCLUSIONS: <1.0 mg/kg AZA was effective as 1.0-2.0 mg/kg in maintaining remission among Chinese patients with CD.

Effect of fluoroquinolone resistance on 14-day levofloxacin triple and triple plus bismuth quadruple therapy.

OBJECTIVE: Levofloxacin has been proposed to replace clarithromycin for Helicobacter pylori treatment. Seven- and 10-day fluoroquinolone triple therapies have generally failed to achieve cure rates of ≥90%, whereas 14-day therapy has achieved 95% success. The aim was to assess the efficacy and effect of fluoroquinolone resistance on 14-day levofloxacin-containing triple therapy with or without the addition of bismuth. DESIGN: Helicobacter pylori-positive patients with functional dyspepsia or healed peptic ulcers were randomized to receive lansoprazole 30 mg b.i.d., amoxicillin 1000 mg b.i.d., and levofloxacin 500 mg daily with (B-LAL) or without (LAL) bismuth potassium citrate 220 mg b.i.d. for 14 days. Eradication was assessed by ¹³C-urea breath testing 4 weeks after completing treatment. Antimicrobial susceptibility was by the agar dilution method. Success was defined as PP success ≥90%. RESULTS: A total of 152 of 161 patients (81 LAL and 80 B-LAL) enrolled completed treatment. The PP rates were 94.6% (70/74; 95% CI, 86.9-97.9%) with B-LAL and 85.9% (95% CI, 76.5-91.9%) with LAL (p = .07); the ITT eradication rates were 87.5% (95% CI, 78.5-93.1%) with B-LAL and 82.7% (95% CI, 73-89.4%) with LAL (p = .39). Levofloxacin resistance was present in 30.3%. Treatment success was excellent with susceptible strains (97.5%) versus resistant strains (70.6%) for B-LAL and 97.3% versus 37.5% for LAL, respectively. CONCLUSIONS: Fourteen-day fluoroquinolone therapy was highly effective when fluoroquinolone resistance rates are <12%. The addition of bismuth maintained effectiveness with fluoroquinolone resistance as high as 25%.

Efficacy of bismuth-containing quadruple therapies for clarithromycin-, metronidazole-, and fluoroquinolone-resistant Helicobacter pylori infections in a prospective study.

BACKGROUND & AIMS: We assessed the efficacy and safety of 4 bismuth-containing quadruple regimens as empiric therapies for Helicobacter pylori infections in patients who did not respond to previous treatment. METHODS: We performed a prospective single-center study of 424 patients with H pylori infection that was not eradicated by previous therapies. Patients were assigned randomly to groups given lansoprazole (30 mg twice daily) and bismuth potassium citrate (220 mg twice daily), along with 500 mg tetracycline and 400 mg metronidazole 4 times daily (LBTM), 500 mg tetracycline and 100 mg furazolidone 3 times daily (LBTF), 1000 mg amoxicillin 3 times and 500 mg tetracycline 4 times daily (LBAT), or 1000 mg amoxicillin and 100 mg furazolidone 3 times daily (LBAF). Eradication was assessed by a (13)C-urea breath test. Antimicrobial susceptibility was assessed in 188 patients by the agar dilution method. RESULTS: Per-protocol rates of H pylori eradication were greater than 90% for all regimens: 93.1% for LBTM (95% confidence interval [CI], 88.1%-98.0%), 96.1% for LBTF (95% CI, 92.4%-99.8%), 94.6% for LBAT (95% CI, 90.0%-99.2%), and 99.0% for LBAF (95% CI, 97.0%-100%). The intention-to-treat response rates were 87.9% for LBTM (95% CI, 81.7%-94.0%), 91.7% for LBTF (95% CI, 87.1%-96.3%), 83.8% for LBAT (95% CI, 76.8%-90.9%), and 95.2% for LBAF (95% CI, 91.1%-99.3%). Significantly more patients had infections eradicated by furazolidone-containing regimens than nonfurazolidone regimens (P = .01). Side effects occurred in 33.6% of subjects and occurred significantly more frequently in the LBTM group than the other 3 groups (vs LBTF, P = .006; vs LBAT, P = .003; vs LBAF, P = .02). Metronidazole resistance was 96.8%; no isolates were resistant to amoxicillin, tetracycline, or furazolidone. CONCLUSIONS: Four bismuth-containing quadruple therapies achieved greater than 90% eradication of H pylori in patients who did not respond to previous treatment, including patients with metronidazole resistance. For patients allergic to penicillin, tetracycline and either metronidazole- or furazolidone-containing regimens are recommended. ClincialTrials.gov number, NCT01668927.

[Clinical observation of fluorescence endoscopy in medical diagnosis].

It's difficult to diagnose precancerous lesion and early cancer for a long time, because both of them haven't typical morphological characteristics. As a novel diagnostic modality, fluorescence endoscopy can accurately reflect minimal changes in human's tissue, thus making a meaningful progress for cancer diagnosing. 200 patients were examined by fluorescence endoscopy to evaluate the diagnostic value. The overall accuracy, sensitivity and specificity for detecting malignant gastrointestinal tumor was 94.0%, 94.6% and 93.5%, respectively. Thus, fluorescence endoscopy can be used to diagnose malignant gastrointestinal tumors with high validity and reliability, and is advantageous over conventional white light endoscopy especially in detecting the atypical and suspicious lesions. Furthermore, fluorescence endoscopy can also guide target biopsy, is significant to improve the early cancer detection rate, has a broad development prospect.

Predictive value of neutrophil infiltration as a marker of Helicobacter pylori infection.

AIM: To evaluate the predictive value of neutrophil infiltration as a marker of Helicobacter pylori (H. pylori) infection. METHODS: A total of 315 patients with dyspepsia symptoms who underwent upper gastrointestinal endoscopy were enrolled in this study. Biopsies were evaluated using the updated Sydney system. The medication history of all patients in the preceding 4 wk was recorded. The diagnosis of H. pylori infection was based on (13)C-urea breath test at least 4 wk after withdrawal of antisecretory drugs, antibiotics and related drugs. For the patients with subtotal gastrectomy, the diagnosis of H. pylori infection was based on anti-H. pylori immunoglobulin G (IgG) antibody. Serum anti-H. pylori IgG antibody was measured by enzyme-linked immunosorbent assays (Biohit, Finland). RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of neutrophil infiltration in the diagnosis of H. pylori infection were 92.3%, 83.5%, 77.4% and 94.7%, respectively. Neutrophil infiltration of gastric mucosa in the histological analysis was strongly associated with H. pylori infection (77.4% vs 5.3% in the neutrophil infiltration negative group, P = 0.000). Moderate neutrophil infiltration was more frequent in H. pylori infection when compared to mild infiltration (81.8% and 75%, respectively), but did not reach statistical significance. For those patients with negative rapid urease test, H. pylori was detected in 73.2% of patients with positive neutrophil infiltration on histology. In patients with subtotal gastrectomy, the diagnostic accuracy of neutrophil infiltration in H. pylori infection was 50%. CONCLUSION: Neutrophil infiltration is closely associated with H. pylori and may be recognized as a sign of this infection.

[The potential pathogenesis of gastrointestinal vascular malformation and the potential mechanism of thalidomide in the treatment of gastrointestinal vascular malformation].

OBJECTIVE: To study the pathogenesis of gastrointestinal vascular malformation (GIVM) and the potential mechanism of thalidomide in the treatment of gastrointestinal bleeding due to GIVM. METHODS: We collected the surgical intestinal specimens from 10 patients who suffered from massive hemorrhage of gastrointestinal tract owning to GIVM and the normal intestinal mucosa around the lesions, as well as normal intestinal mucosa from healthy subjects. Immunohistochemical (IHC) staining was carried out to investigate the differences of angiopoietin 2 (Ang2), Notch1 and delta like ligand 4 (Dll4) in the above three intestinal mucosa to find the relationship with the pathogenesis of GIVM. Human umbilical vein endothelial cells (HUVECs) were cultured with 0, 25, 50, 100 and 200 mg/L thalidomide for 24 or 48 hours to observe their mRNA and protein expressions of Ang2, Notch1, Dll4 by real-time PCR and Western blot. RESULTS: By IHC staining, more expressions of Ang2, Notch1 and Dll4 in the lesions were detected than those in the normal intestinal mucosa around the lesions and the normal intestinal mucosa in healthy people. The expressions of Ang2, Notch1 and Dll4 were significantly correlated (P = 0.016, r = 0.732), and the expressions of Notch1 and Dll4 were absolutely correlated (P = 0.000, r = 1.000). Real-time PCR and Western blot showed that thalidomide could down-regulate the expressions of them, which were in a concentration-dependent manner. CONCLUSION: Ang2, Notch1 and Dll4 may correlate with the pathogenesis of GIVM, while thalidomide can concentration-dependently down-regulate the expression of Ang2, Notch1 and Dll4, which may be one of the mechanism that thalidomide play a therapeutic role in GIVM.

Chronic atrophic gastritis is a progressive disease: analysis of medical reports from Shanghai (1985-2009).

INTRODUCTION: We aimed to examine the turnover of chronic atrophic gastritis (CAG) pathologically and endoscopically and explore its potential causes. METHODS: A retrospective analysis was conducted of prospective data collected from 1,592 patients who underwent gastroscopy three times or more during the period 1985-2009 at Renji Hospital, Shanghai, China. Pathological and endoscopic findings were analysed. Data collected included gender, age, length of follow-up period, family history, past medical history, history of Helicobacter (H.) pylori infection, drug history for the use of proton pump inhibitors (PPIs), antacids and non-steroidal anti-inflammatory drugs [NSAIDs], and lifestyle history, including the patients' eating habits. RESULTS: 23 (1.44%) patients presented with gastric cancers resulting from CAG and 349 (21.92%) patients had dysplasia. Pathological and endoscopic findings suggested that the proportion of patients with worsening gastric mucosa during the atrophic and intestinal metaplasia (IM) phases was over 35% with increasing age. Gastric mucosa was found to be pathologically aggravated by carbonated drinks and fast food, and pathologically degenerated by H. pylori infection. Smoking deteriorated the gastric mucosa. Side dishes of vegetables may benefit the gastric mucosa even in the atrophic and IM phases. CONCLUSION: Our findings support the consensus that CAG is a progressive disease. Potential factors that were found to affect the state of the gastric mucosa in our patient group were gender, H. pylori infection, use of PPIs or NSAIDs, and intake of vegetable side dishes, spicy food, carbonated drinks and fast food.

Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide.

BACKGROUND AND AIM: The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia-inducible factor-1α (HIF-1α) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters. METHODS: Immunohistochemistry was performed to visualize VEGF in angiodysplasia lesions. HUVEC were incubated under hypoxic conditions or in the presence of bFGF. Effects of exposure to thalidomide were studied. Cell growth was assessed in methylthiazolyte-trazolium assays. Enzyme-linked immunosorbent assays and real-time polymerase chain reaction were performed to assess the expression of VEGF at protein and mRNA levels. Western blot was performed to detect the expression of HIF-1α under hypoxic conditions. RESULTS: VEGF was strongly expressed in 75% of patients with angiodysplasia lesions, as compared to expression in patients without angiodysplasia lesions. VEGF was also induced in HUVEC under hypoxic conditions (P < 0.05). bFGF was found to stimulate the proliferation of HUVEC and enhance the expression of VEGF. Thalidomide suppressed bFGF-induced proliferation significantly and decreased VEGF expression, both at the protein and mRNA levels. Thalidomide also inhibited HIF-1α in a dose-dependent manner (P < 0.05). CONCLUSIONS: VEGF may play an important role in the pathogenesis of angiodysplasia. Thalidomide can suppress VEGF, either induced by HIF-1α or bFGF.

Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation.

BACKGROUND & AIMS: Patients with recurrent bleeding from gastrointestinal vascular malformations are a challenge to treat. We investigated the long-term efficacy and safety of thalidomide for refractory bleeding from gastrointestinal vascular malformations in an open-label, randomized study. METHODS: Eligible patients were randomly assigned to groups that were given either 100 mg thalidomide (n = 28) or 400 mg iron (n = 27, controls), daily for 4 months; patients were followed for at least 1 year (mean, 39 months). Bleeding was defined by a positive result from an immunoassay fecal occult blood test. The primary end point was the effective response rate, defined as the proportion of patients in whom bleeding episodes had decreased by ≥ 50% in the first year of the follow-up period. The secondary end points included the rates of cessation of bleeding, blood transfusion, overall hospitalization, and hospitalization for bleeding. We also quantified yearly bleeding episodes, bleeding duration, levels of hemoglobin, and yearly requirements for transfusions of red cells, numbers of hospitalizations for bleeding, and hospital stays. Plasma levels of vascular endothelial growth factor were measured in the group given thalidomide. RESULTS: Rates of response in the thalidomide and control groups were 71.4% and 3.7%, respectively (P < .001). All secondary end points differed significantly different between groups; thalidomide was more effective. No severe adverse effects were observed, although minor side effects were common among patients in the thalidomide group. Levels of vascular endothelial growth factor were significantly reduced by thalidomide (P < .001). CONCLUSIONS: Thalidomide is an effective and relatively safe treatment for patients with refractory bleeding from gastrointestinal vascular malformations. Mechanisms of thalidomide activity might involve vascular endothelial growth factor.

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis.

PURPOSE: The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC. METHODS: All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials. RESULTS: Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60-5.18) and remission rate (OR, 2.04; 95% CI, 1.36-3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44-31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22-29.90). The incidence of mild-moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04-0.60). Few severe adverse events were observed. CONCLUSIONS: Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

Frequent down-regulation of hABH2 in gastric cancer and its involvement in growth of cancer cells.

BACKGROUND AND AIM: Methyl or 1, N(6) -ethenoadenine base lesions are frequent and highly-mutagenic or -carcinogenic events in mammalian DNA. Human AlkB homologue-2 (hABH2), a homologue of the Escherichia coli AlkB protein, has been found to be the principal dioxygenase for the repair of these lesions. Mounting evidence indicates that impaired DNA repair contributes to gastric cancer induction and progression. Whether hABH2 is involved in this malignancy is unknown. The present study was aimed to investigate the expression profile of hABH2 in gastric cancer and the effect of hABH2 on cancer cell growth. METHODS: The expression of hABH2 in 35 pair-matched gastric neoplastic and adjacent non-neoplastic tissues, and in five gastric cancer cell lines, was examined by real-time polymerase chain reaction (PCR), immunohistochemistry, or Western blot. The cell growth was determined using cell-counting kit-8 assay. The apoptosis or cell-cycle analysis was determined using flow cytometry. RESULTS: The hABH2 expression was downregulated in 68% (24/35) of primary gastric cancers, as determined by real-time PCR; the hABH2 expression was also substantially decreased in gastric cancer cell lines. Immunohistochemical or Western blot analysis further confirmed the downregulation of hABH2 expression in gastric cancers. The overexpression of hABH2 significantly inhibited the proliferation of gastric cancer cells, and induced G(1) arrest of the cell cycle, while hABH2 knockdown promoted cell growth and cell-cycle progression of gastric cancer cells. CONCLUSIONS: These results suggest that hABH2 is downregulated in a subset of gastric cancers, and might be involved in the molecular mechanism of gastric cancer through inhibiting the proliferation of gastric cancer cells.

Resistance of Helicobacter pylori to antibiotics from 2000 to 2009 in Shanghai.

AIM: To investigate the resistance of Helicobacter pylori (H. pylori) to 6 commonly used antibiotics from 2000 to 2009 in Shanghai. METHODS: A total of 293 H. pylori strains were collected from 2000 to 2009 in Shanghai and tested for their susceptibility to metronidazole, clarithromycin, amoxicillin, furazolidone, levofloxacin and tetracycline using agar dilution. RESULTS: The resistant rates of H. pylori to clarithromycin (8.6%, 9.0% and 20.7%) and levofloxacin (10.3%, 24.0% and 32.5%) increased from 2000 to 2009 in Shanghai. The resistant rate of H. pylori to metronidazole remained stable (40%-50%). Only one strain of H. pylori isolated in 2005 was resistant to tetracycline. All strains were sensitive to amoxicillin and furazolidone. The resistant rate of H. pylori to antibiotics was not related with the sex, age and clinical outcome of patients. CONCLUSION: Resistance of H. pylori to antibiotics plays an important role in making treatment strategies against H. pylori-associated diseases.