Foundation for Promotion of Cancer Research

Early diagnosis of premalignant gastric condition, such as chronic atrophic gastritis and intestinal metaplasia, allow us to assess and stratify the risk of gastric cancer. Gastric mucosal cleaning, mucosal exploration, photo-documentation, and advanced technologies like optical enhancement, electron chromoendoscopy and magnification endoscopy improve lesion detection rates. This study compares the detection rate of premalignant gastric lesions between biopsies guided Electron chromoendoscopy combined with optical enhancement and magnification endoscopy versus random biopsies (Sydney Protocol) with optical enhancement. This is a prospective, observational, blinded comparative study. Outpatients were divided into two groups: group 1 (162 patients), biopsies were performed either under Electron chromoendoscopy combined magnification endoscopy guidance; and group 2 (160 patients), biopsies were performed under blinded mapping (updated Sydney system) with optical enhancement. The following clinical outcomes were assessed in each group: age, gender, adequate gastric clearance rate, gastric atrophy rate, intestinal metaplasia rate. A total of 322 patients were randomized, where 76 were excluded from the study. Detection rate for Intestinal metaplasia was significantly higher with Electron chromoendoscopy combined with optical enhancement and magnification endoscopy (37.6% versus 23.7%; p < 0.0001). Extensive Intestinal metaplasia was significantly more prevalent with Electron chromoendoscopy combined magnification endoscopy compared to mapping with optical enhancement (p = 0.029; p = 0.048, respectively). Electron chromoendoscopy combined with optical enhancement and magnification endoscopy demonstrated a comparative superiority over Sydney System random biopsy protocol in the identification of patients with premalignant gastric conditions. By enabling more precise endoscopic targeting, directed biopsies help reduce sampling error; however, in high-risk populations, a complementary approach integrating both targeted and systematic random biopsies remains advisable to optimize diagnostic accuracy.

Nitric oxide synthase (NOS) activity was induced in the cytosol of A-172 cells by treatment with lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma. A 130-kDa human inducible NOS (iNOS) protein was detected with anti-rat iNOS antibody by western blot analysis. Northern blot analysis showed that the iNOS mRNA was approximately 4.5 kb, using a cDNA fragment for human iNOS, isolated from stimulated A-172 cells by reverse transcriptase-PCR, as a probe. The mRNA was induced by interferon-gamma at a trace level, and its expression was synergistically enhanced by simultaneous addition of lipopolysaccharide, tumor necrosis factor-alpha, and, to a larger extent, interleukin-1 beta. The mRNA expression was blocked by coincubation with actinomycin D or cycloheximide. Furthermore, by transfecting the mouse iNOS gene promoter into A-172 cells, transcriptional activation of the iNOS gene was detected in these cells upon stimulation with lipopolysaccharide and cytokines. The pattern of promoter activation correlated well with that of iNOS mRNA expression upon stimulation. These data indicate that expression of iNOS is transcriptionally regulated in A-172 cells. This process requires de novo protein synthesis with a mechanism similar to that in place in mouse macrophages.

KW‐2189, a novel antitumor antibiotic belonging to the duocarmycins, possesses marked DNA‐binding activity upon activation by carboxyl esterase to its active form, DU‐86. Three duocarmycins, KW‐2189, DU‐86 and duocarmycin SA, were active against the cisplatin (CDDP)‐resistant human non‐small cell lung cancer cell lines PC‐9/CDDP and PC‐14/CDDP, and the multidrug‐resistant human small cell lung cancer cell line H69/VP. However, HAC2/0.1, a CDDP‐resistant human ovarian cancer cell line which is also resistant to CPT‐11 because of decreased intracellular activation of CPT‐11, was about 12.8‐fold more resistant to KW‐2189. HAC2/0.1 was not resistant to other duocarmycins as compared to its parental cell line, HAC2. There was no difference between HAC2 and HAC2/0.1 with regard to the intracellular accumulation of KW‐2189. Addition of 130 mU/ml of carboxyl esterase to the culture medium did not influence the sensitivity of HAC2 cells to KW‐2189. However, the sensitivity of HAC2/0.1 cells to KW‐2189 was enhanced to the level of HAC2. These results suggest that HAC2/0.1 is less potent than HAC2 in activating KW‐2189. The carboxyl esterase activity of whole‐cell and microsomal extracts from HAC2/0.1 was approximately 60% of that from HAC2. The cell‐free experiment revealed that KW‐2189 bound to DNA more efficiently in the presence of HAC2 than HAC2/0.1 cell extract. It was concluded that decreased intracellular carboxyl esterase activity in HAC2/0.1 cells caused decreased intracellular conversion of KW‐2189 to its active form, thus producing resistance to KW‐2189. The decreased conversion of CPT‐11 to SN‐38 in HAC2/0.1 cells might be explained by decreased carboxyl esterase activity.