Search

Introduction: Asia-Pacific Colorectal Screening (APCS) score has been implemented for colorectal cancer screening in asymptomatic cohort in many regions. However, no study has validated its efficiency in Asian outpatients with mild-self-limited gastrointestinal symptoms yet. The purpose of this study was to validate its efficiency in asymptomatic subjects and outpatients in Ningxia. Methods: The records of 329 asymptomatic participants and 300 outpatients were collected and analyzed from database in the General Hospital of Ningxia Medical University from September 2017 to April 2018. These 2 main groups were divided into 3 tiers based on the scores calculated by the category of APCS score. The detection rates of advanced colorectal neoplasia (ACRN) were further compared according to histopathological classifications of tissues acquired during colonoscopy. Results: Among the 329 participants screened in the asymptomatic cohort, 78 subjects (23.7%) were in the low-risk (LR) tier, 187 subjects (56.8%) in the moderate-risk (MR) tier, and 64 subjects (19.5%) in the high-risk (HR) tier. The percentage of ACRN in the LR, MR, and HR groups was 1.3, 8.6, and 20.3%, respectively. In the 300 outpatient cohorts, 78 patients (26%) were in the LR tier, 140 patients (46.7%) in the MR tier, and 82 patients (27.3%) in the HR tier. The detection rates of ACRN in the LR, MR, and HR groups were 0, 10, and 39%, respectively. Conclusion: APCS score is an effective method for ACRN screening in asymptomatic and also the outpatient subjects. Individuals with HR scores should be given priority for colonoscopy.

Background The effectiveness in surveillance colonoscopy largely depends on the quality of bowel preparation. We aimed to investigate the quality of bowel preparation segmentally and its effect on Adenoma Detection Rate (ADR) and Advanced Adenoma Detection Rate (AADR) at corresponding bowel segments. Methods This is a single-centered and cross-sectional study. A consecutive of 5798 patients who underwent colonoscopy examination were included. Bowel preparation was evaluated based on Bowel Bubble Scale (BBS) in general and Boston Bowel Preparation Scale (BBPS) in each segment (right side, transverse and left side of colon) and total BBPS scores. The quality of bowel preparation was correlated with ADR and AADR. Results Four thousand nine hundred forty colonoscopies (14,820 bowel segments) were included in the final analysis. In which 30.9% scored 3, 57.5% scored 2, 11.2% scored 1 and 0.4% scored 0 on basis of BBPS. For each score, ADR were 10.8, 7.7, 4.9 and 3.2%, respectively; whereas AADR were 4.5, 2.8,1.8 and 1.6% (P

Sporadic tumors of the duodenal papilla are rare, with a prevalence of 0.04% to 0.12% in autopsies [1], most of which are adenomas histologically [2].

Background. Economic disparity contributes to the variation of intestinal obstruction (IO) etiologic spectrum. Clarifying the etiology distribution in local regions can help to unravel IO and promote early diagnosis, henceforth making sure standardized therapeutic interventions. Methods. Medical data of 4908 inpatients diagnosed with IO admitted to the General Hospital of Ningxia Medical University between January 2004 and December 2013 were recruited and analyzed retrospectively. The associated profiles included demographic features, clinical manifestations, and previous therapeutic operations. Results. 4908 cases of intestinal obstruction were identified during the period of study. It denoted that the hospitalization rate of IO has maintained upward momentum; the top four causes of IO were adhesion, tumor, intussusception, and hernias. These covered up nearly 80% of the total constitution. Among them, adhesive intestinal obstruction accounted for 45.17%, malignant bowel obstruction for 21.09%, intussusception for 8.72%, and hernia for 4.73%; abdominal surgery constituted for the majority (78.62%) of adhesive obstruction. The followed up analysis also found that appendectomy accounted for the biggest percentage, 28% of operation cases. Malignant bowel obstruction can have a rate of 96.43% in 1035 cases led by tumor lesions. Of which, the primary intestinal malignant tumor accounted for 68.64% and metastatic tumors for 31.36%. Nearly 50% occurred in the large intestine. The overall mortality of all 4908 cases was 4.7%. Conclusion. The hospitalizations of IO delineated an increasing trend. Adhesion was the main etiology in IO. The odds of malignant bowel obstruction was increasing in the proportion of IO. There were some differences towards the etiologic spectrum compared with western countries.

CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. The gastrin induced reduction in p27kip1 was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1.

This study retrospectively compared the safety and efficacy of two endoscopic techniques for treating newly diagnosed achalasia, pneumatic dilation (PD), and peroral endoscopic myotomy (POEM). Demographics, clinical and manometric data, and outcomes were collected from the medical records of patients who received POEM or PD as the primary therapy for achalasia at our hospital from January 2012 to August 2015. Of 72 patients, 32 and 40 received POEM and PD, respectively. The two groups had similar preoperative features. On short-term follow-up, improvements in high-resolution esophageal manometry and barium esophagogram parameters were similar. For PD, the success rates at 3, 6, 12, 24, and 36 months were 95, 88, 75, 72, and 60%, respectively. For POEM, these were 96, 96, 96, 93, and 93% (P = 0.013, log-rank test). On subgroup analysis, the success rate was higher with POEM than that with PD in all 3 manometric subtypes, but only that of type III was statistically significant. POEM required significantly longer operative time and hospitalization than did PD (P

Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls. Using a human-to-mouse approach, we next showed a similar enzymatic increase in two well-validated IBD murine models and evaluated the therapeutic effect of the potent FOLH1/ GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) (IC50 = 300 pM). In the dextran sodium sulfate (DSS) colitis model, 2-PMPA inhibited the GCPII activity in the colonic mucosa by over 90% and substantially reduced the disease activity. The significance of the target was confirmed in FOLH1-/- mice who exhibited resistance to DSS treatment. In the murine IL-10-/- model of spontaneous colitis, daily 2-PMPA treatment also significantly reduced both macroscopic and microscopic disease severity. These results provide the first evidence of FOLH1/GCPII enzymatic inhibition as a therapeutic option for IBD.

Introduction : The incidence of ulcerative colitis has increased tremendously over the past few decades, and caused much more attention in China. Several studies have revealed that both environmental and genetic factors play crucial roles in the formation and development of this disease. Among the environmental factors, the smoking condition is highly significant. Although current smoking has been associated with a protective effect on both the development and progression of ulcerative colitis (UC), the clinical characteristics of UC patients with current smoking in China is still unclear. Aim : To clarify the relationship between current smoking and the UC in the northwest of China, patients diagnosed with ulcerative colitis in the General Hospital of Ningxia Medical University from 2003.03 to 2012.09 were assessed. Material and methods : Data were collected about clinical features, cigarette smoking conditions, disease location, and therapeutic requirements. A total of 421 patients were included in this study, at diagnosis, 341 (81%) patients were non-smokers, and the current smokers amounted to 80 (19%). Results : As for disease location, there were no differences between the current smokers and non-smokers regarding proctitis and extensive colitis, but the current smokers had less left-sided colitis than non-smokers (p = 0.049). Based on the Modified Mayo score, heavier smokers had lower scores than other smokers and non-smokers. For the therapeutic requirements, current smokers needed fewer corticosteroids than non-smokers (p = 0.048). Conclusions : We found that current smoking is closely associated with a protective factor for UC.

Background In China, the incidence of Inflammatory bowel disease (IBD) has shown a significant growth trend. Analysis of the epidemiology, clinical manifestations, diagnostic means, and treatment of IBD will further improve the clinician's understanding of IBD, improve knowledge and further enable early diagnosis and standardized therapeutic management. The purpose of this study was to analyze the clinical characteristics of IBD inpatients in General Hospital of NingXia Medical University over a 12-year period to identify trends in clinical and epidemiological features, clinical manifestations, and treatment programs. Methods By excluding188 patients with incomplete information or incompatible with the 2012 Guidlines cases, we retrospectively analyzed the case records of 567 inpatients with a diagnosis of IBD admitted to the General Hospital of NingXia Medical University between January 2002 and December 2014. The clinical epidemiological features, clinical manifestations, diagnostic methods, and therapeutic status were analyzed. Results Over the study period, IBD hospitalization rates in 2002 and 2014 groups was 1.96 % and 4.05 %, increased 2.07 times. Of 567 cases of IBD, 483 (85.19 %) cases were categorized as ulcerative colitis (UC) and 84 as Crohn’s disease (CD) (14.81 %). Total male cases were 321 (56.61 %). Mean age of cases was 49.06 ± 14.92 years for UC and 44.84 ± 14.67 years for CD. The majority of UC was located in the colon, with a moderate level of disease activity. A combination of clinical manifestations and colonoscopy was mostly used to make a diagnosis; relatively the rate of pathological diagnosis was low, with a small proportion of patient’s diagnosed based on radiology. Treatment with SASP/5ASA and steroids was applied to the majority of inpatients and 47.83 % were treated with antibiotics; in contrast, only 1.86 % cases were treated with immunosuppressive therapy. Conclusions An increasing trend of admissions for IBD can be observed in our study; there are some differences in clinical features and treatment compared with Western countries, and further research into this is required.

Cyclooxygenase-2 (COX-2), the key enzyme in prostaglandin synthesis, is often over-expressed in human gastric cancer. Recently, 15-hydroxyprostaglandin dehydrogenase [NAD+] (15-PGDH), the key enzyme in prostaglandin degradation, was found to be down-regulated in human gastric cancer tissues, but little is known about its role in gastric tumorigenesis. In this study, expression plasmids containing 15-PGDH siRNA were constructed and transfected into the gastric cancer cell line MKN45, which expresses endogenous 15-PGDH at a high level. The 15-PGDH gene was also transfected into the gastric cancer cell line SGC7901, which expresses endogenous 15-PGDH at a low level. When compared with the empty vector transfectant, MKN45 cells stably transfected with the 15-PGDH siRNA plasmid had a significantly increased proliferation rate. In contrast, SGC7901 cells stably transfected with the 15-PGDH cDNA had a significantly decreased growth rate. Furthermore, increased expression of 15-PGDH suppressed clone formation of gastric cancer cells in plate and soft agar colony formation assays in vitro and suppressed tumor formation in athymic nude mice in vivo. Stable silencing of 15-PGDH in gastric cancer cells also enhanced cell cycle entry in vitro. These results demonstrate for the first time that 15-PGDH acts as a tumor suppressor in human gastric cancer and provide further validation for 15-PGDH as a potential therapeutic target for human gastric cancer.

Background and aims HER2 , an oncogene, has been found to be over-expressed in 10–40% of human gastric carcinomas. The aims of this study were to investigate if a fusion protein consisting of anti-HER2 sFv and constitutively active caspase-3 was capable of inducing apoptosis in HER2-expressing human gastric cancer cells and blocking the growth of human gastric cancer xenografts in nude mice. Methods NIH3T3 cells stably transduced with the pcDNA3.1-HER-PE-CP3 recombinant plasmid containing a secretion signal, a single-chain anti-HER2 monoclonal antibody fragment, a Pseudomonas exotoxin A translocation domain and a constitutively active caspase-3 molecule were used to induce apoptosis in human gastric cancer cells both in vitro and in vivo. Immunofluorescence staining and western blotting were used to examine the expression of the recombinant protein HER-PE-CP3. Apoptosis was determined by flow cytometry and TUNEL assay. Results Co-cultivation of HER-PE-CP3/ NIH3T3 with human gastric cancer cells led to internalisation of HER-PE-CP3 and apoptosis in HER2-expressing human gastric cancer cells but not in HER2-negative cancer cells. Inoculation of HER-PE-CP3/NIH3T3 in nude mice resulted in potent inhibition of human gastric cancer xenografts and much prolonged survival time of the tumour-bearing mice compared with the control. Significantly more apoptotic cells were detected in xenografts in mice receiving HER-PE-CP3/NIH3T3 than in control mice. Conclusions The HER-PE-CP3 chimeric molecule could induce selective apoptosis and potent growth inhibition of HER2-positive human gastric cancer cells and might represent a novel HER2-directed treatment option for human gastric cancer.

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP), a component of the ubiquitin-mediated proteolysis, could bind SKP1-CUL1-F box protein complex and participate in beta-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer and renal cancer. However, the role of CacyBP/SIP in pancreatic cancer progression still remains unclear. Therefore, the aim of the present study was to investigate the expression and clinical significance of CacyBP/SIP in pancreatic cancer.Immunohistochemistry was carried out on paraffin-embedded sections of pancreatic cancer and normal pancreatic tissues. In addition, Western blot and semiquantitative RT-PCR were carried out to analyze mRNA and protein expression of CacyBP/SIP in 8 pairs of freshly resected pancreatic cancer and their adjacent nontumorous tissue.CacyBP/SIP expression was significantly increased in pancreatic cancer tissue (28/68 or 41.2%) and correlated with differentiation degree, higher TNM (tumor, node, metastasis) stage and distance metastasis. Also, mRNA and protein expression of CacyBP/SIP were found to be at higher levels in almost all cancer tissues compared to adjacent tissues.CacyBP/SIP protein might play an important role in the process of pancreatic carcinogenesis and high-level CacyBP/SIP expression might be related to the malignant potential of pancreatic cancer.

Multidrug resistance (MDR) is a major impediment to the effective chemotherapy of many human malignancies. Although much effort has been devoted to develop new drugs for overcoming MDR, until now, still no useful method of reversing MDR, suitable for clinical use, has emerged from this large quantity of work. Some researchers have reported that proteasome inhibitors could induce apoptosis in a variety of cancer cells. In the present study, we found that, in vincristine-resistant human gastric cancer cell line SGC7901/VCR, proteasome inhibitor MG132 was an effective inducer of apoptosis, and also had the capacity of downregulating the expression of anti-apoptotic Bcl-2 and MDR1 (P-gp), by which MG132 resensitized tumor cells to the apoptosis induced by anticancer drugs. Data presented by drug sensitivity assay further demonstrated that MG132 could reverse the resistant phenotype of gastric cancer cells effectively through both enhancing drug-induced apoptosis and inhibiting P-gp. The further study of the effectiveness and safety of proteasome inhibitor in vivo may be helpful for developing a new possible strategy to treat gastric cancer MDR.

Osteopontin (OPN), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are overexpressed in various experimental models of malignancy. However, the correlation and role of the three molecules in gastric cancer is unclear. In the present study, we found that OPN, COX-2 and VEGF were overexpressed in 53 cancerous tissues with gastric cancer compared with 40 normal mucosa tissues by immunohistochemistry method. Moreover, the results indicated co-expression of OPN, COX-2, and VEGF in gastric cancer. Levels of OPN, COX-2, and VEGF were all significantly correlated with TNM stage, lymph node metastasis and distant metastasis (P0.05), while not related to prognosis of patients. In addition, individual levels of OPN, COX-2, and VEGF were all significantly correlated with microvessel density (MVD), valued by CD34 staining directly with r-values of 0.416, 0.400, and 0.566, respectively (P0.01). Both OPN and COX-2 levels showed a positive correlation with VEGF (P0.05). Meanwhile, expression of COX-2 is in relation to OPN (P0.01). Overall, survival for patients with high MVD was significantly lower than for patients with low MVD (P0.05). Our findings indicate that OPN, COX-2, and VEGF synergically promote angiogenesis and metastasis in gastric cancer. It may be an important and useful strategy to target these molecules for prevention and therapy of tumor.

Identifying an effective therapeutic target is pivotal in the treatment of gastric cancer. In this study, we investigated the expression of p75 neurotrophin receptor (p75NTR) in gastric cancer and the impact of its alteration on tumor growth. p75NTR expression was absent or significantly decreased in 212 cases of gastric cancers compared with the normal gastric mucosa (P < .05). Moreover, p75NTR expression was also lost or significantly decreased in various human gastric cancer cell lines. p75NTR inhibited in vitro growth activities and caused dramatic attenuation of tumor growth in animal models by induction of cell cycle arrest. Upregulation of p75NTR led to downregulation of cyclin A, cyclin D1, cyclin E, cyclin-dependent kinase 2, p-Rb, and PCNA, but to upregulation of Rb and p27 expressions. Conversely, downregulating p75NTR with specific siRNA yielded inverse results. The rescue of tumor cells from cell cycle progression by a death domain-deleted dominant-negative antagonist of p75NTR (Δp75NTR) showed that the death domain transduced antiproliferative activity in a ligandindependent manner and further demonstrated the inhibitive effect of p75NTR on growth in gastric cancer. Therefore, we provided evidence that p75NTR was a potential tumor suppressor and may be used as a therapeutic target for gastric cancer.

We have investigated the roles of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. The up-regulation of DARPP-32 was found to significantly enhance the sensitivity of cells of human adriamycin (ADR)-resistant gastric adenocarcinoma cell line SGC7901/ADR to vincristine, ADR, 5-fludrouracil and cisplatin. The results of an in vivo drug sensitivity assay confirmed that DARPP-32 may play a specific role in the MDR of gastric cancer. DARPP-32 significantly down-regulated the expression of P-glycoprotein and zinc ribbon domain-containing 1 (ZNRD1), but did not alter the expression of MDR-associated protein or glutathione-S-transferase. The up-regulation of ZNRD1 significantly inhibited the drug sensitivity of gastric cancer cells over-expressing DARPP-32, indicating that ZNRD1 may be important in the DARPP-32-mediated MDR of gastric cancer. DARPP-32 was also able to significantly decrease the anti-apoptotic activity of SGC7901/ADR cells. Further study of the biological functions of DARPP-32 may be helpful for understanding the mechanisms of MDR of gastric cancer cells and developing possible strategies to treat gastric cancer.

The p75 neurotrophin receptor (p75NTR) is a focus for study at present. However, its function in gastric cancer was not elucidated. Here, we investigated its relation with metastasis of gastric cancer. By immunohistochemistry, we found that the positive rate of p75NTR expression in metastatic gastric cancer was 15.09% (16 of 106), which was lower compared with nonmetastatic gastric cancer (64.15%; 68 of 106). The average staining score in nonmetastatic gastric cancer was significantly higher than in metastatic gastric cancer (1.21 ± 0.35 versus 0.23 ± 0.18; P < 0.01). p75NTR protein level was also lowly expressed in the highly liver-metastatic gastric cancer cell line XGC9811-L compared with other gastric cancer cell lines by Western blotting. It could also significantly inhibit the in vitro adhesive, invasive, and migratory and in vivo metastatic abilities of gastric cancer cell lines SGC7901 and MKN45 by reducing urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 proteins and by increasing tissue inhibitor of matrix metalloproteinase (TIMP)-1 protein. Further studies showed that p75NTR could suppress the nuclear factor-κB (NF-κB) signal. SN50, a specific inhibitor of NF-κB, which could inhibit in vitro invasive and migratory abilities of gastric cancer cells, reduced expression of uPA and MMP9 proteins and increased expression of TIMP1 protein. Taken together, p75NTR had the function of inhibiting the invasive and metastatic abilities of gastric cancer cells, which was mediated, at least partially, by down-regulation of uPA and MMP9 proteins and up-regulation of TIMP1 protein via the NF-κB signal transduction pathway. Our studies suggested that p75NTR may be used as a new potential therapeutic target in metastatic gastric cancer. (Mol Cancer Res 2007;5(5):423–30)

Peritoneal dissemination in gastric cancer is the most frequent cause of the noncurative resection and recurrence after curative resection. We, therefore, evaluated the feasibility of a peptide, which was obtained by screening a random phage display library, in the treatment of peritoneal metastases of gastric cancer. In this study, a novel cell line, GC9811-P, with a high potential peritoneal metastasis of gastric cancer derived from its parental cell line, GC9811, was established. Using a phage display library, we isolated a specific peptide that selectively bound to GC9811-P cells rather than its parental GC9811cells. The isolated phage-displaying peptide, SMSIASPYIALE (named peptide PIII), was obtained after four rounds of selection, showing a tendency to preferentially bind to GC9811-P cells compared with a panel of other gastric cancer cell lines, and preferentially accumulate in peritoneal metastasis tumor tissue in comparison with control organs, peritoneum, liver, pancreas, spleen, lung, and kidney. Further study showed that synthetic peptide PIII could significantly inhibit adhesive and invasional ability of GC9811-P cells and could effectively block the corresponding phage binding to the GC9811-P cells, whereas, exposure of the cells to various concentrations of peptide PIII showed no obvious cell growth inhibition. Furthermore, a highly reproducible animal experimental model of gastric cancer with peritoneal dissemination was established in nude mice by injecting a suspension of the cell line into the gastric wall of nude mice. Animals intraperitoneally treated with peptide PIII in this model or another animal model of gastric cancer with peritoneal dissemination established using MKN45 cells showed suppressed tumor metastasis to peritoneum and significantly prolonged survival. In conclusion, the selected peptide PIII was a biologically active peptide and could effectively inhibit peritoneal dissemination of gastric cancer.

Tumor growth, progression and metastasis are critically dependent on blood supply, which has received increased attention as a potential target of new anticancer therapies. Antiangiogenic therapy to limit and even reverse the growth of tumors is under investigation and showing promise. Moreover, tumor vascular express specific surface proteins (“vascular zip codes”), not present in resting blood vessels of normal tissues, are suitable for targeting purposes. The specific “vascular zip codes” can be identified by screening phage-displayed peptide library in vivo. This technology is simple but powerful, providing the advantages of selectivity of action plus improved accessibility and efficacy. To date, a variety of tumor-homing peptides have been isolated in this method, and most of the peptides have been used for targeting devices to concentrate drugs and other therapeutic materials to tumors. Such a targeting strategy can decrease toxicity and increase the therapeutic efficacy of the drug.

Objective Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is a target protein of the S100A6, which is a member of the S100 family. It has been shown that CacyBP/SIP plays important roles in cell cycle progression, differentiation, and carcinogenesis. The purpose of this study was to explore the correlation of CacyBP/SIP expression and clinical significance in breast cancer. Methods Immunohistochemistry was performed to detect the CacyBP/SIP expression in 79 pairs of breast cancer tissues and adjacent nontumor tissues. Western blot analysis and semiquantitative RT-PCR were used to measure CacyBP/SIP protein and mRNA levels in three pairs of fresh breast cancer tissues and adjacent nontumor tissues. The clinical data were collected by telephone follow-up for 5 years. Results CacyBP/SIP mRNA and protein levels in breast cancer tissues were significantly higher compared with adjacent nontumor tissues. Poor cellular differentiation, lymph node invasion, and clinicopathological staging in breast cancer were associated with CacyBP/SIP expression. Other factors, such as age, menses, and tumor size, were not related to CacyBP/SIP expression. The up-regulation of CacyBP/SIP expression also was shown to increase recurrence and metastasis of breast cancer and to correlate with short overall survival rate. Conclusions CacyBP/SIP expression is evident in more advanced clinical progression of breast cancer, and it might be a biomarker for poor prognosis and a potential therapeutic target in breast cancer.

10 páginas, 6 figuras, 2 tablas., MC3 is a colorectal cancer (CRC)-specific mAb previously prepared in our laboratory that can detect CRC with high sensitivity and specificity. However, the target antigen for MC3 had not been identified due to technological limitations. In the present study, immunocytochemistry and immunohistochemistry revealed the expression patterns of MC3 antigen (MC3-Ag) in colon cancer cell lines and CRC tissues. Western blotting analysis showed that the MC3 antibody reproducibly recognized two ∼30 kDa proteins in the total cell lysates of human colon carcinoma cell lines SW480 and HT-29. Using a proteomic approach, we identified two MC3 immunoreactive spots as two isoforms of thioredoxin-like 2 (Txl-2) protein. Further paired immunostaining showed that Txl-2 had the same expression profile as probed by the MC3 antibody. Western blotting also showed that both antibodies could detect the same two bands, further verifying that Txl-2 is the antigen of MC3 antibody. Additionally, tissue arrays revealed the expression patterns of Txl-2 in various normal and cancer tissues. Further analysis showed that Txl-2 mRNA was elevated in 18 cases of CRC tissues compared to paracancerous tissues and adjacent normal tissues., This work was supported by grants from National Natural Science Foundation of China (No. 30672399) and National High Technology Research and Development Program of China (No. 2006AA02A253).

Calcyclin-binding protein (CacyBP)/Siah-1 interacting protein (SIP), a component of ubiquitin-mediated proteolysis, could bind the Skp1-Cul1-F box protein complex. Although CacyBP/SIP was implicated in p53-induced β-catenin degradation, its exact function was still unknown. Our previous studies showed that CacyBP/SIP could modulate the multidrug-resistant phenotype of gastric cancer cells and was highly expressed in gastric cancer tissues compared with that in non-cancerous tissues. In this study, CacyBP/SIP protein expression profile in a broad range of human normal tissues and carcinomas was analyzed by immunohistochemistry staining with anti-CacyBP/SIP monoclonal antibody first produced in our laboratory. CacyBP/SIP was generally localized in the cytoplasm/nucleus. Positive staining of CacyBP/SIP was found in brain, heart, lymph node, and esophagus. Weak staining was shown in the rectum and kidney. No CacyBP/SIP was detected in other normal tissues. However, CacyBP/SIP was ubiquitously detected in all kinds of tumor tissues and was highly expressed in nasopharyngeal carcinoma, osteogenic sarcoma, and pancreatic cancer. To our knowledge, this is the first study on the CacyBP/SIP expression pattern in a broad range of human normal and tumor tissues. The data presented should serve as a useful reference for other investigators in future studies of CacyBP/SIP functions. Hopefully, this knowledge will lead to discovery of more roles of CacyBP/SIP in tumorigenesis. (J Histochem Cytochem 56:765–772, 2008)

To explore the proteins regulated by cyclooxygenase-2 (COX-2) in gastric cancer, the expression plasmid of COX-2siRNA was constructed and transfected into gastric cancer cell line SGC7901. Then, two-dimensional electrophoresis and the PDQuest software analysis were applied to discover the differentially expressed proteins. The differential protein spots were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Fourteen differentially expressed proteins between the two cell lines were identified. 15-Hydroxyprostaglandin dehydrogenase [NAD(+)] (15-PGDH), a key enzyme in prostaglandin degradation, was identified as an upregulated protein in SGC7901 cells transfected with the COX-2siRNA plasmid. To further explore whether the 15-PGDH is regulated by COX-2, western blotting and immunocytochemical assay were performed to detect the expression of 15-PGDH in different cell lines with different expression level of COX-2. The results showed that the expression of 15-PGDH was upregulated (128.57%) as COX-2 was suppressed by small interfering RNA and downregulated (51.72%) as COX-2 was enhanced by COX-2 cDNA transfection in gastric cancer cells. In tissue specimens with gastric cancer, there was a decreased expression of 15-PGDH and an increased expression of COX-2 simultaneously. A significantly negative correlation of 15-PGDH expression was found to COX-2 level, tumor differentiation, tumor, lymph node, metastasis (TNM) staging and lymph node metastasis of gastric cancer. All the results suggest that 15-PGDH is downregulated by COX-2 in human gastric cancer and may contribute to the carcinogenesis and development of human gastric cancer in combination with COX-2.

The aim of this study was to establish an orthotopic implantation model with high metastasis of gastric cancer to the peritoneum which is more faithful to clinical metastasis. A human gastric carcinoma cell line, GC9811, was injected as a single-cell suspension into the stomach of nude mice. The cells from some peritoneum metastatic foci were expanded in vitro and subsequently implanted to the stomach wall of nude mice. By repeating the in vivo stepwise selection method for four rounds and cloning culture, we obtained a cell line designated GC9811-P, which developed peritoneal metastasis in 13 of 13 (100%) of mice, compared with only 20% of those implanted with parental GC9811. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. Tumor cell growth of GC9811-P in vitro was faster than that of GC9811. Motility assays demonstrated higher motility of GC9811-P than of GC9811. The adhesive ability of GC9811-P cells to laminin was lower than that of GC9811 cells, whereas the ability of GC9811-P cells to adhere to fibronectin was significantly higher than that of parental cells. Differences between GC9811-P and their parental GC9811 cells were found in expression levels of various molecules by flow cytometric and western blot. The findings indicated that up-regulation in the expressions of CD155, VEGF, syndecan-1, and syndecan-2 or down-regulation in the expressions of IL-6 and E-cadherin play an important role in the peritoneal metastasis of human gastric carcinoma cells. The high-metastatic cell line appears to be useful for investigating the mechanisms of peritoneal metastasis and preventing peritoneal metastasis of human gastric cancer.