Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease

BACKGROUND/AIMS: This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). METHODS: Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. RESULTS: Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 µg/mL (160/80 mg group) and 7.5-9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. CONCLUSIONS: Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.

Early hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: the risk factors and long-time survival / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To identify the risk factors of early post-TIPS hepatic encephalopathy (HE) and the long-time survival of patients with or without early post-TIPS HE.</p><p><b>METHODS</b>Consecutive cirrhotic patients who underwent TIPS for variceal rebleeding or refractory ascites in our center from January 2003 to December 2008 were included in this study. More than 60 clinical characteristics were enrolled in univariate analysis and logistic regression analysis to define the risk factors of HE in 3 months after TIPS procedure (early post-TIPS HE). The long-time survival of patients with or without early post-TIPS HE was compared by Cox regression with several covariates.</p><p><b>RESULTS</b>According to our inclusion criteria, 190 patients were included. The median follow-up was 30.5 months. Lower serum concentration of fibrinogen and higher Child-Pugh score were the independent risk factors for suffering early post-TIPS HE. Patients without early post-TIPS HE after TIPS showed better prognosis than those with early post-TIPS HE after TIPS (P = 0.044).</p><p><b>CONCLUSION</b>Patients with lower serum fibrinogen and higher Child-Pugh score before TIPS might be more probably attacked by early post-TIPS HE which indicated worse long-term survival.</p>

Challenge and exploration of army medical college graduate education in the context of internationalization / 中华医学教育探索杂志

In the context of internationalization of education,the military graduate education concepts and models also come to change,and opportunities and challenges coexist.In this article,the challenges and problems of army medical college graduate education were mentioned and analyzed,and the exploration and attempt of graduate education in the process of international were summarized.

Screening of specific binding peptide targeting blood vessel of human esophageal cancer in vivo in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer.</p><p><b>METHODS</b>The phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced. During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues. Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and VIII-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test.</p><p><b>RESULTS</b>The number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P < 0.01 in tumor and spleen, P < 0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or VIII-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by analyzing the homology of these peptide sequences. The staining distribution of phage with the sequence of PNPNNST was similar to that of the blood vessel marker factor VIII-related antigen staining. After sequencing, each phage with the selected peptide of PNPNNST with 1.0 × 10(11) pfu/ml was injected intravenously into mice. The homing ability to tumor vessel of these 9 kinds of peptides in the xenograft was higher than control tissues (lung and spleen).</p><p><b>CONCLUSION</b>Nine peptides obtained from in vivo screening homed to the blood vessel of human esophageal cancer, and the two motifs of YSXNXW and PXNXXN are the possible biochemical recognition units binding to vascular endothelial cells of esophageal cancer.</p>

Expression of heme oxygenase-1 in peritoneal metastasis of gastric cancer and its significance HUI / 中华消化杂志

Objective To investigate the expression and significance of heme oxygenase-1(HO-1) in gastric adenocarcinoma and its peritoneal metastatic tissues, as well as drug-resistant cell strains. Methods The expression of HO-1 in patients with (n=68) or without (n=46) peritoneal metastasis of gastric adenocarinoma was examined. The expression of HO-1 in cancerous tissue, peritoneal metastatic foci, and normal peritoneum was detected by immunohistochemistry. The expression of HO-1 protein in metastatic foci and drug-resistant cell strains was measured by Western blotting. Results The positive expression of HO-1 was 39.7% (27/68) in gastric adenocarcinoma tissues with metastasis and 41.2% (28/68) in peritoneal metastatic tissues, which was significantly higher than that in normal peritoneum (0%,0/68,P<0.01) and gastric adenocarcinoma tissues without metastasis (21.7%, 10/46, P<0.05). The Western blot study showed that the HO-1 expression in metastatic tissues was higher than that in normal peritoneum (P<0.05). The expression of HO-1 protein was markedly increased in GC9811-P drug-resistant cell strains compared with its parental cell strains (P<0.05). Conclusions The increased expression of HO-1 may be involved in the peritoneal metastasis of gastric adenocarcinoma, and related to the malignant potential. The underlying signal pathways in neopastic epithelium may also be related to the multi-drug resistance.

Screening and identification of phage-displayed polypeptides specifically binding to human gastric cancer with high metastatic potential to peritoneum / 中华肿瘤杂志

<p><b>OBJECTIVE</b>By means of phage-display technique, to screen polypeptides that specifically bind to human gastric cancer with high metastatic potential to peritoneum.</p><p><b>METHODS</b>Two human gastric cancer cell lines were used: GC9811-P with high metastatic potential to peritoneum and its wild type parental GC9811, to carry out subtractive screening with a phage display-12 peptide library.</p><p><b>RESULTS</b>After three rounds of screening, 40 phage clones bond to GC9811-P cells were randomly selected. When injected into the peritoneal cavity of nude mice, 6 of the 40 clones did not bind to mouse peritoneum as examined by immunohistochemical staining. They were considered to be capable of binding specifically to GC9811-P cells. Sequence analysis revealed two different exogenous peptides: TLNINRLILPRT and SMSI(X)SPYI(XXX).</p><p><b>CONCLUSION</b>Two peptides have been obtained that specifically bind to a gastric cancer cell variant GC9811-P, which easily disseminates to the peritoneum. Whether or not they could block GC9811-P metastasis to peritoneum in vivo remains to be determined.</p>

Effect of human angiopoietin-1 on tumorigenesis and angiogenesis of gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the role of human angiopoietin-1 (Ang1) in tumorigenesis and angiogenesis of human gastric cancer cell line SGC7901 in nude mice.</p><p><b>METHODS</b>Recombinant human Ang1 sense or antisense eukaryotic expression vectors were constructed, and transfected by lipofectin into human gastric cancer line SGC7901. Stable transfectants were obtained respectively, namely 7Ang1+ for sense, 7Ang1- for antisense, and 7901P for empty vector transfected cells. Semiquantitative PCR and Western blot were employed to testify the transfection efficiency. Cell growth curve and cell cycle were observed by MTT assays or flow cytometry. In in vivo study, growth of SGC7901 xeno-transplant was observed in BALB/c nude mice. Microvessel density (MVD) was analyzed by immunohistochemistry for Factor VIII staining.</p><p><b>RESULTS</b>Stably transfected cell lines were established and decreased expression of Ang1 protein and mRNA in the antisense transfected SGC7901 cells was achieved. Tumorigenesis of 7Ang1- cells on day 30 days was significantly inhibited with decreased MVD as compared to that in 7901P and 7Ang1+ cells (P < 0.01).</p><p><b>CONCLUSION</b>Angiopoietin-1 plays an important role in tumorigenesis and angiogenesis of gastric cancer which can be partially abrogated by antisense technique.</p>

Osteopontin expression and its relation to invasion and metastases in gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation between expression of the osteopontin (OPN) and invasion and metastases in gastric cancer.</p><p><b>METHODS</b>The expression of OPN, NF-kappaB p65 and matrix metallo-proteinase 9 (MMP-9) was detected by immunohistochemistry in non-cancer gastric tissue (n = 12 cases) and gastric cancer tissue (n = 72 cases).</p><p><b>RESULTS</b>(1) OPN, NF-kappaB p65 and MMP-9 were not expressed in 12 non-cancer gastric tissue samples(group A). Their expression rates were 43.3%, 40.0% and 46.7% respectively in 30 gastric cancer samples without lymph nodes metastasis (group B), but they increased to 76.9%, 73.1% and 80.8% in 26 gastric cancer samples with lymph nodes metastases (group C), and 87.5%, 81.3% and 93.8% respectively in 16 gastric cancer samples with lymph node and distant metastases (group D). (2) There were statistically significant differences in their expressions between group D and group B (P(a) = 0.004, P(c) = 0.007, P(e) = 0.002), and between group C and group B (P(b) = 0.011, P(d) = 0.013, P(f) = 0.009). (3) Despite some differences in positive expression rates, correlations existed between OPN and NF-kappaB p65, and between NF-kappaB p65 and MMP-9 (P(1) = 0.042, P(2) = 0.013; r(1)= 0.67, r(2)= 0.72).</p><p><b>CONCLUSION</b>Osteopondin espression is closely related to the invasion and metastases of gastric cancer. It may upregulate the expression of metastasis-related molecule MMP-9 by activating NF-kappaB pathway.</p>