TNFAIP6 promotes invasion and metastasis of gastric cancer and indicates poor prognosis of patients.

TNFα-stimulated gene-6 (TNFAIP6) plays an important role in the prognosis of many tumors. Our objective was to investigate the clinical and prognostic value of TNFAIP6 expression in gastric cancer (GC) patients. Here, we investigated the expression of TNFAIP6 in GC tissues using western blotting and immunohistochemistry and the association between TNFAIP6 expression and the prognosis and clinicopathological parameters of GC patients. Our results revealed that the expression of TNFAIP6 was higher in GC tissue than in normal gastric tissue, and the levels were positively correlated with the depth of tumor invasion (P = 0.010), tumors with lymph node metastasis (P = 0.000) and TNM stage (P = 0.003) of GC patients. Moreover, the results revealed that patients with high TNFAIP6 expression exhibited poorer overall survival than those with low TNFAIP6 expression (P = 0.037). Additionally, knockdown of TNFAIP6 inhibited the proliferation, invasion and metastasis of GC cells in vitro. High TNFAIP6 expression was associated with the depth of tumor invasion, lymph node metastasis, TNM stage and poor prognosis of GC patients, suggesting that TNFAIP6 may serve as a novel indicator of the prognosis and as a treatment target of GC.

Potential antigen candidates for subunit vaccine development against Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a resident bacterium in the stomach that accounts for 75% cases of gastric cancer. In this review, we comprehensively studied published papers on H. pylori vaccines using Google Scholar and NCBI databases to gather information about vaccines against H. pylori. Considering the pivotal roles of the enzyme urease (in production of NH3 and neutralization of the acidic medium of the stomach), cytotoxin-associated gene A, and vacuolating cytotoxin A proteins in H. pylori infection, they could be the best candidates for the construction of recombinant vaccines. The outer membrane porins (Hop), blood group antigen-binding adhesin (BabA), sialic acid-binding adhesin (SabA), and outer inflammatory protein A, play significant roles in binding of bacterium to human gastric tissues, and because binding is the first step in bacterial fixation and colonization, these antigens also can be considered as suitable candidates for designing vaccines. Likely, other significant bacterial antigens, such as NapA (chemotactic factor for recruitment of human neutrophils and monocytes to the site of infection), duodenal ulcer promoting protein A (to promote duodenal ulcer), and Hsp60 (as a molecular chaperon for activation of urease enzyme), can be used in the construction of subunit vaccines. New vaccines in use currently, such as DNA vaccines and subunit vaccines, can efficiently replace the dead and attenuated vaccines. Nonetheless, the results show that urease enzyme is most used compared with bacterial components in the designing and construction of recombinant vaccines. The BabA and SabA antigens belong to the outer membrane porins family in H. pylori and are required for binding and fixation of the bacterium to the human gastric tissues.

Downregulation of microRNA-193-3p inhibits tumor proliferation migration and chemoresistance in human gastric cancer by regulating PTEN gene.

In this study, we investigated the functional mechanisms of microRNA-193-3p (miR-193-3p) in human gastric cancer. Quantitative RT-PCR (qRT-PCR) was used to assess whether miR-193-3p was aberrantly expressed in gastric cancer cells and clinical samples from gastric cancer patients. Gastric cancer cell line AGS and MKN-45 cells were stably transduced with lentivirus to downregulate endogenous miR-193-3p. The modulation of miR-193-3p downregulation on gastric cancer proliferation, migration, chemo-drug responses, and tumor explant were assessed by MTT, wound-healing, 5-FU chemoresistance and in vivo tumorigenicity assays, respectively. Downstream target of miR-193-3p, phosphatase and tensin homolog (PTEN) in gastric cancer, was assessed by dual-luciferase reporter assay, qRT-PCR, and western blot. PTEN was knocked down by siRNA in AGS and MKN-45 cells to assess its direct impact on miR-193-3p modulation in gastric cancer. MiR-193-3p was aberrantly upregulated in both gastric cell lines and human gastric tumors. In AGS and MKN-45 cells, miR-193-3p downregulation reduced cancer proliferation, migration and 5-FU chemoresistance in vitro, and tumorigenicity in vivo. PTEN was confirmed to be targeted by miR-193-3p in gastric cancer. PTEN inhibition in AGS and MKN-45 cells directly reversed the anti-tumor modulations of miR-193-3p downregulation on gastric cancer proliferation, migration, and 5-FU chemoresistance. We presented clear evidence showing miR-193-3p played critical role in regulating human gastric cancer through direct targeting on PTEN gene.

Previous Exposure to the Fish Parasite Anisakis as a Potential Risk Factor for Gastric or Colon Adenocarcinoma.

Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis spp. larvae. High rates of parasitization of fish worldwide make Anisakis a serious health hazard. In fact, anisakiasis is a growing disease in countries such as Spain, Italy, and Japan, where consumption of raw/marinated fish is high. Some parasitic infections have been recognized as a causative factor for human cancer. Suggested mechanisms include chronic inflammation elicited by the parasite, and a possible tumorigenic effect from certain parasitic secretions. Anisakis can produce persistent local inflammation and granuloma, and larvae have been incidentally found in gastrointestinal (GI) tumors. Our aim was to discover possible differences in the prevalence of unnoticed or asymptomatic previous Anisakis infection in GI cancer patients compared with healthy individuals. Serum levels of specific antibodies against Anisakis antigens were used as a reliable marker of previous contact with their larvae. Ninety-four participants without a previous history of Anisakis infection were prospectively allocated into 1 of 2 groups: 47 patients with GI cancer and 47 controls. Specific IgE, IgA1, and IgG1 against the Anisakis recombinant antigens Ani s 1, Ani s 5, Ani s 9, and Ani s 10 were determined by an ELISA assay. The ratio of positivity to sIgA1, rAni s 1, or rAni s 5 was significantly higher in the cancer patients than in the controls (38.30% vs 6.38%, P < 0.001) and (42.55% vs 10.64%, P < 0.001, respectively). When disaggregated by type of tumor, the patients with gastric cancer showed a higher proportion of positive results for sIgA1 to rAni s 1 (P < 0.001), whereas a higher proportion of colon cancer patients were shown to be positive for sIgA1 to both rAni s 1 (P < 0.05) and rAni s 5 (P < 0.01). Earlier Anisakis infection might be a risk factor for the development of stomach or colon cancer.

An anisakis larva attached to early gastric cancer: report of a case.

Gastrointestinal anisakidosis is a nematode infection caused by the ingestion of larvae-infected raw or undercooked fish. The Japanese like to eat raw or undercooked fish, so gastric anisakiasis is a common disease in Japan. However, reports of anisakiasis with gastrointestinal cancer are rare. A 63-year-old Japanese male was diagnosed with a small early gastric cancerous lesion associated with gastric anisakiasis. From our experience and based on a review of the literature, the attachment of an anisakis larva to early gastric cancer is not considered accidental.

RhoGDI2 is associated with HGF-mediated tumor invasion through VEGF in stomach cancer.

RhoGDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of tumor metastasis; however, its role in cancer remains controversial. The aims of this study were to analyze RhoGDI2 in gastric cancer growth and metastasis, and to determine its possible signaling pathway. The level of expression of RhoGDI2 was further confirmed by real time RT-RCR and Western blot analysis. Transfection of cells with RhoGDI2 shRNA resulted in no effects of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with RhoGDI2 shRNA, compared with control cells, were able to invade across a Matrigel membrane barrier. The role of RhoGDI2 in the level of HGF-induced up-regulation of vascular endothelial growth factor (VEGF) was measured by knockdown of RhoGDI2 with RhoGDI2 shRNA and a chromatic immuno-precipitation assay. The levels of RhoGDI2 and VEGF were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up-regulation of VEGF was repressed by RhoGDI2 knockdown. HGF-induced upregulation of phosphorylated ERK and P38 levels was inhibited in RhoGDI2 knockdown cells. HGF enhanced the binding activity of RhoGDI2 to the VEGF promoter in control cells, but not in RhoGDI2-shRNA cells. Findings of this study also showed a statistically significant difference in the mean RhoGDI2 level before and after surgery (p < 0.01) and the mean level of RhoGDI2 before surgery showed a statistically significant difference depending on lymphatic, neural invasion and stage (p < 0.05). In conclusion, RhoGDI2 might play an important role in up-regulation of VEGF induced by HGF and contributes to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.

Low-positive antibody titer against Helicobacter pylori cytotoxin-associated gene A (CagA) may predict future gastric cancer better than simple seropositivity against H. pylori CagA or against H. pylori.

BACKGROUND: To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer. METHODS: A nested case-control study was done in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose. RESULTS: H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers. CONCLUSIONS: A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction.

Giardia lamblia trophozoites in gastric biopsies.

To assess the prevalence of gastric giardiasis in gastric biopsies of patients with carcinoma stomach and in patients taking treatment for duodenal ulcer. Gastric biopsy specimens from 54 patients of carcinoma stomach and 100 antral biopsies from patients taking treatment for duodenal ulcer were included in the study. Sections were stained with haematoxylin and eosin, methylene blue and May Grunwald-Giemsa stains and examined for presence of Giardia lamblia trophozoites. Eight out of 54 (14.9%) biopsies of gastric carcinoma patients harboured trophozoites of Giardia lamblia. Associated H. pylori infection was present in all biopsies (8/8; 100%). Atrophy and intestinal metaplasia was present in 62.5% (5/8) and 25% (2/8) cases respectively. Sections from seven out of 35 patients (20%) taking treatment for duodenal ulcer showed presence of G. lamblia. H. pylori infection, gastritis and atrophy were found in 85.7% (6/7), 71.4% (5/7) and 28.6% (2/7) cases respectively. First gastric biopsy in these patients was negative for G. lamblia but 2nd and 3rd biopsies were positive. A careful search for G. lamblia trophozoites should be made while examining the gastric biopsies, especially in patients with carcinoma stomach, intestinal metaplasia, atrophic gastritis and those taking treatment for duodenal ulcer. This may help in indirect diagnosis of clinically unsuspected cases of intestinal giardiasis and may explain persistence of vague upper gastrointestinal tract (UGIT) symptoms despite clearance of H. pylori in patients on anti-ulcer therapy.

Toxoplasma infection and cell free extract of the parasites are able to reverse multidrug resistance of mouse lymphoma and human gastric cancer cells in vitro.

A large number of compounds are known to reduce the ATP-dependent efflux pump activity of multidrug resistant (mdr) tumor cells. Here we report that an infection of cancer cells with T. gondii reduced the multidrug resistance of the tumour cells against cytostatic drugs. Two mouse lymphoma cell lines (Mdr L 5718 and Par 5718) were infected with Toxoplasma gondii in vitro and the reduction of efflux pump activity of the cells was measured. The drug accumulation (Rhodamin-123) was increased in the infected mdr cell lines compared with non- infected mdr-cells, and no effect was shown after infection of the parental cell line. The same effect was also achieved by incubation of Mdr-tumor cells with cell lysate of Toxoplasma gondii. Mdr-1-gene expression was reduced in the infected cell lines 48 hours after infection. Co-cultivation of Toxoplasma gondii with mdr cell lines separated by a microfilter from tumor cells was performed, but this cocultivation did not change the mdr efflux activity. The effect of Toxoplasma gondii infection on the efflux pump activity and mdr-1 gene expression was also examined in the human gastric cancer cells. A sensitization of resistant gastric cancer cells was also achieved by parasite infection. This phenomenon is an evidence that a reduction of resistance in tumor cells can be achieved by a natural parasite infection. It is as yet unclear whether an active infection or another substance of T. gondii is responsible for this phenomenon.

[Apropos of 1 case of hepatogastric fascioliasis in Cape Verde]. / A propos d'un cas de fasciolose hépato-gastrique en provenance du Cap-Vert.

The authors report a case of Fascioliasis sp. distomiasis with a double hepatic and gastric location primitively associated with a gastric cancer metastazed to the liver. The parasitic origin of the lesions suspected from the histological specimen of the gastric biopsy (the presence of eggs) was confirmed by serology with the presence of the arc 2 specific to immunoelectrophoretic analysis, while the parasitological examination of the stools was always negative. The patient grew well after a day's cure of triclabendazole (375 mg x 2). Although the ectopic locations of Fascioliasis are classic, they are usually in the abdominal wall, less frequently in the gastric or colic wall. The fact that the contamination originated on the Cape Verde is indiscutable, since the patient had never left the island. It is the 5th case described in medical literature, thus confirming the presence of Fasciola hepatica (or gigantica) on the islands of the Cape Verde, whose population is of both Portuguese and African origin and has kept the eating habits of the former colonial power (Portugal is a zone of high endemicity for human fascioliasis). It would be interesting to look for Limnaea and contaminated bovine on the Cape Verde islands.

The morphogenesis of a papillomatous gastric polyp in the crab-eating monkey (Macaca fascicularis).

The histopathology of gastric papillomas in 17 crab-eating monkeys from Indonesia and Malaysia was investigated. The changes in the affected mucosa consisted of papillomatous proliferation with accidental heterotopia, desquamation or necrosis of the epithelium associated with eggs or adults of the small nematode Nochtia nochti, inflammatory cell infiltration and haemorrhage or oedema and fibrosis. The primary pathogenic effect of this parasite was due to its irritant action on the gastric mucosa. Hyper-regeneration, with a downward shift of the proliferating zone in the gastric gland and an inflammatory process, appeared to play a significant role in the morphogenesis of this lesion. It is concluded that the gastric papilloma associated with Nochtia nochti in the monkey is a parasitic inflammatory polyp.