Extrapancreatic solid pseudopapillary neoplasm followed by multiple metastases: Case report.

Solid pseudopapillary neoplasm (SPN), also known as Gruber-Frantz tumor, is a rare form of neoplasm that almost exclusively occurs in the pancreas and in young females. While the potential of malignancy is low for SPN, these tumors can mimic other diseases and require a meticulous investigation and a standard treatment by total surgical resection. We present an unusual case of SPN arising in the mesentery of a 40-year-old man with subsequent multiple metastases. Histopathological examination showed similar properties of the mesenteric neoplasm to those of SPN in pancreas. Although the mass was surgically removed, the patient died of recurrent disease 4 years after the initial presentation. We speculate that SPN originates from pancreatic progenitor cells. Further histopathological analyses are required for the prediction of SPN recurrence after resection.

EMT and acquisition of stem cell-like properties are involved in spontaneous formation of tumorigenic hybrids between lung cancer and bone marrow-derived mesenchymal stem cells.

The most deadly phase in cancer progression is metastatic conversion. Epithelial-to-mesenchymal transition (EMT) is a key process by which cancer cells acquire invasive and metastatic phenotypes. In order to spawn macroscopic metastases, disseminated cancer cells would seem to require self-renewal capability. However, the underlying mechanism defining these processes is poorly understood. One possible mechanism underlying metastasis is fusion between myeloid cells and cancer cells. In this study, we found that spontaneously-formed tumorigenic hybrids between bone marrow-derived mesenchymal stem cells (MSCs) and three different non-small cell lung cancer (NSCLC) cell lines contributed to highly malignant subpopulations with both EMT and stem cell-like properties. Hybrids lost their epithelial morphology and assumed a fibroblast-like appearance. Up-regulation of vimentin, α-smooth muscle actin (α-SMA), and fibronectin, and down-regulation of E-cadherin and pancytokeratin were observed in tumorigenic hybrids. These cells also exhibited increased expression of the stem cell marker prominin-1 (CD133) and over-expression of transcription factors OCT4, Nanog, BMI1, Notch1, ALDH1 as well as Sox2, all genes responsible for regulating and maintaining the stem cell phenotype. In addition, in spontaneously-formed tumorigenic hybrids, increased pneumosphere-forming capacity and tumor-forming ability in NOD/SCID mice were detectable. Thus, cell fusion between lung cancer cells and MSCs provides a nonmutational mechanism that could contribute to aberrant gene expression patterns and give rise to highly malignant subpopulations both capable of EMT and with properties of cancer stem cells (CSCs).

[The relationship between waist to stature ratio and hypertension, diabetes, and dyslipidemia in Qingdao].

OBJECTIVE: To evaluate the relationship between waist to stature ratio (WSR) and hypertension, diabetes, dyslipidemia in Qingdao. METHODS: Data were collected from a 2001 - 2007 Qingdao area diabetes survey, population-based cross-sectional study, and 30 712 Chinese adults aged>18 years old were enrolled. Correlation analysis of BMI, WSR, hip circumference, waist circumference, waist to hip ratio (WHR) with blood glucose, blood pressure, blood lipid were conducted. ROC curve analysis in diabetes, hypertension, dyslipidemia and multivariate logistic regression analysis were also conducted. RESULTS: Anthropometric indicators were related with hypertension, diabetes and dyslipidemia in both men and women. Comparing with other anthropometric indicators, WSR was found to have the largest area under the ROC curve and the best cut-off point of WSR was 0.52. Multivariate logistic regression analysis showed that, after controlling age, disease history, physical activity, sex, the diabetes hypertension and dyslipidemia risk OR of WSR ≥ 0.52 were largest. CONCLUSIONS: Anthropometric indicators intimately related with cardiovascular risk factors in Qingdao region, and may predict and evaluate the risk of cardiovascular disease. WSR may be the best index for predicting cardiovascular risk factors in Qingdao area. The optimal WSR cut off point for identifying cardiovascular risk factors clustering is 0.52.

The combined treatment of praziquantel with osteopontin immunoneutralization reduces liver damage in Schistosoma japonicum-infected mice.

The aim of this study was to evaluate the therapeutic effects of osteopontin neutralization treatment on schistosome-induced liver injury in BALB/C mice. We randomly divided 100 BALB/C mice into groups A, B, C, D and group E. Mice in all groups except group A were abdominally infected with schistosomal cercariae to induce a schistosomal hepatopathological model. Mice in group C, D and group E were respectively administered with praziquantel, praziquantel plus colchicine and praziquantel plus neutralizing osteopontin antibody. We extracted mouse liver tissues at 3 and 9 weeks after the 'stool-eggs-positive' day, observed liver histopathological changes by haematoxylin-eosin and Masson trichrome staining and detected the expression of osteopontin, alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-ß1) by immunohistochemistry, RT-PCR and Western blot. We found that praziquantel plus neutralizing osteopontin antibody treatment significantly decreased the granuloma dimension, the percentage of collagen and the expression of osteopontin, α-SMA and TGF-ß1 compared to praziquantel plus colchicine treatment in both the acute and chronic stage of schistosomal liver damage (P<0·05). So we believe that the combined regimen of osteopontin immunoneutralization and anti-helminthic treatment can reduce the granulomatous response and liver fibrosis during the schistosomal hepatopathologic course.

[Efficacy of bismuth-based quadruple therapy as first-line treatment for Helicobacter pylori infection].

OBJECTIVE: To evaluate the efficacy of bismuth-based quadruple therapy as the first-line treatment for H.pylori infection. METHODS: A total of 136 patients with H.pylori related peptic ulcer or chronic gastritis were randomized into two groups: 67 patients in bismuth-based quadruple group received esomeprazole 20 mg, clarithromycin 0.5 g,amoxicillin 1.0 g,and bismuth potassium citrate 220 mg for 7 d; 69 patients in standard triple group received esomeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1.0 g for 7 d. Outcome of eradication therapy was assessed by (14)C-UBT. On ITT and PP analysis, calculating the cost-effectiveness ratio (C/E) and the incremental cost-effectiveness ratio (delta C/delta E). RESULT: On ITT and PP analysis, the eradication rates of the quadruple therapy group were 82.09% and 88.71%, and those of the triple therapy group were 66.67% and 73.02% (P<0.05). The cost-effectiveness ratio of two groups was 4.15 and 4.82; The incremental cost-effectiveness ratio of quadruple therapy group was 1.02 as against triple therapy group. CONCLUSION: Compared to the standard triple therapy regimen, the bismuth-containing quadruple therapy regimen has higher eradication rate and cost-effectiveness, which can be recommended as the fist-line treatment for H.pylori infection.

[H.pylori in patients with cirrhosis and liver cirrhosis with hepatocellular carcinoma].

OBJECTIVE: To understand the prevalence of H.pylori infection in patients with cirrhosis, and liver cirrhosis with hepatocellular carcinoma(HCC), and to investigate the relationship between H.pylori infection and liver cirrhosis, and liver cirrhosis with hepatocellular carcinoma in patients. METHODS: Serum anti-H.pylori antibodies IgG (HpIgG) was measured by dot immunogold filtration assay (DIGFA) in 101 liver cirrhosis and 42 liver cirrhosis with hepatoma patients and alpha-fetopro-tei(AFP)was determined by chemiluminescence. RESULTS: HpIgG seroprevalence was 42.57% (43/101) in the liver cirrhosis patients, and 69.05% (29/42) in the liver cirrhosis with the HCC patients. HpIgG seropositivity in the liver cirrhosis with the HCC patients was higher than in those without HCC. HpIgG seropositivity in the HBV positive patients was higher than in the HBV negative patients (chi2=4.164, P=0.041). HpIgG seropositivity in the AFP abnormal patients was higher than in the AFP normal patients (chi2=4.695, P=0.030). CONCLUSION: H.pylori may be a risk factor in patients with cirrhosis and HCC.

Tissue specific expression of suicide genes delivered by nanoparticles inhibits gastric carcinoma growth.

Developing an efficient and safe strategy to introduce a therapeutic gene into targeting cells in vivo is a key issue in cancer gene therapy nowadays. Novel non-viral gene carriers, such as nanoparticles, have been shown to be able to deliver DNA into cancer cells efficiently. Suicide gene therapy has been demonstrated to be effective in inhibiting tumor growth, however, the lack of tumor specificity limits its application in clinic. Developing a targeting system for suicide gene is an attractive strategy in cancer gene therapy. In this study, the CMV enhancer and carcinoembryonic antigen (CEA) promoter was fused to a chimeric suicide gene yCDglyTK. This construct was delivered into SGC7901 gastric cancer cells using calcium phosphate nanoparticles (CPNPs). The expression of yCDglyTK in SGC7901 cells was confirmed by RT-PCR and western blot. Immunofluorescence experiments showed that yCDglyTK is only expressed in CEA-positive cancer cells, but not in CEA-negative cells. The expression of yCDglyTK induced cancer cell death following the addition of the prodrug 5-FC, and also elicit "bystander effect" to kill the neighboring cells. Intratumoral injection of CPNP-yCDglyTK complex followed by administration of 5-FC produced marked regression in gastric cancer xenografts. Taken together, our study suggests that the combination of calcium phosphate nanoparticles and suicide gene therapy represents a novel approach for targeting gastric cancer gene therapy.

Effect of indomethacin on cell cycle proteins in colon cancer cell lines.

AIM: To study the effect of indomethacin (IN) on human colon cancer cell line SW480 with p53 mutant and SW480 transfected wild-type p53 (wtp53/SW480) in vitro and investigate molecular mechanism of anti-tumor effect of IN on colon cancer. METHODS: SW480 cells and wtp53/SW480 cells were treated with different concentrations of IN respectively, the expressions of CDK2, CDK4 and p21WAF1/CIP1 protein were detected by Western blotting. RESULTS: IN gradually down-regulated the expression of CDK2, CDK4 protein of wtp53/SW480 cells in a dose-dependent manner, and inhibitory effect reached the maximum level at 600 micromol/L; IN up-regulated the expression of p21 WAF1/CIP1 protein in a dose-dependent manner at a certain concentration range, and the expression reached the maximum level at 400 micromol/L, and returned to the base level at 600 micromol/L. The expression of CDK2, CDK4 and p21WAF1/CIP1 protein of SW480 cells did not change. CONCLUSION: IN exerts antitumor effect partly through down regulation of the expression of CDK2, CDK4 protein and up regulation of the expression of p21WAF1/PIC1.

Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenoma-carcinoma sequence.

AIM: To investigate the expression of inducible nitric oxide synthase (iNOS) in aberrant crypt foci (ACF) -adenoma-carcinoma sequence and its relation with tumor cell apoptosis, proliferation and angiogenesis. METHODS: The expression of iNOS, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) in different stages of colorectal cancer were studied by immunohistochemical method from 30 normal tissues, 30 nonhyperplastic ACF, 30 hyperplastic ACF, 30 dysplastic ACF, 30 adenomas and 60 carcinomas. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of iNOS significantly increased in the transition from hyperplastic ACF to dysplastic ACF. This transition was associated with a significant decrease in the apoptotic index (AI) (0.73+/-0.37 vs 0.61+/-0.35, P<0.05) and significant increases in the PCNA labeling index (LI) (27.3+/-2.80 vs 40.3+/-3.11, P<0.01) and microvessel density (MVD) (55+/-11.5 vs 70+/-13.2, P<0.01). The expression of iNOS was in low levels and positively correlated with PCNA-LI (r=0.812, P<0.01) and MVD (r=0.863, P<0.01) during transition from normal mucosa to nonhyperplastic ACF and hyperplastic ACF. The expression of iNOS was in high levels and positively correlated with AI (r=0.901, P<0.01) after transition from hyperplastic ACF to dysplastic ACF, adenoma and carcinoma. CONCLUSION: The results suggest that the transition from hyperplastic ACF to dysplastic ACF may be a crucial step in the ACF-adenoma-carcinoma sequence, in which iNOS plays an important role by regulating tumor cell apoptosis, proliferation and angiogenesis.