Authors’ Affiliation: Department of Cell and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China.

PURPOSE: The purpose of the present study was to screen the autoantibody signature of colon cancers to develop serum markers for colon cancer detection. EXPERIMENTAL DESIGN: A phage cDNA expression library of colon cancer was built. The library was sequentially screened by a pool of 10 colon cancer sera, goat antihuman IgG, and a pool of two healthy sera to identify phage-expressed antigens recognized by tumor-associated antibodies. The clones picked out by these screening were subjected to a training set with 24 colon cancer sera and 24 healthy sera. The antigen combination, which got the most satisfactory classification, was tested by an independent set of 24 colon cancer sera with equal number of sera from normal donors. The carcinoembryonic antigen (CEA) level of these sera was detected for the additional classification analysis with or without the antigen combination. RESULTS: A cDNA expression library consisting of 2 x 10(6) primary clones was prepared. After three turns of screening, 24 antigens recognized by tumor-associated antibodies were picked out for serum marker identification. The training set showed that a six-marker combination got the most satisfactory classification in a logistic regression model; leave-one-out validation achieved 91.7% sensitivity and 91.7% specificity. In a testing set with this marker panel, we correctly predicted 85% of the samples. Although according to CEA level alone, we correctly predicted 75% of the samples with 42% of cancer patients misclassified. When CEA was combined with the six markers, the sensitivity and specificity increased to 91.7% and 95.8%, respectively. The six antigen sequences in the phage display system are relatively short peptides. Only two of them showed homology to known protein sequences. CONCLUSIONS: Autoantibodies against phage-expressed antigens derived from colon cancer tissues could be used as serum markers for the detection of colon cancer.

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Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

Six new sesquiterpenes, 10-hydroxy-epiaplysin (1), 10-hydroxy-aplysin (2), 10-hydroxy-debromoepiaplysin (3), aplysin-9-ene (4), epiaplysinol (5) and debromoepiaplysinol (6), together with 13 known compounds (7-19), have been isolated from the red alga Laurencia tristicha. The structures of 1-6 were determined by spectroscopic methods including IR, EI-MS, HREI-MS, and 1D and 2D NMR techniques. All compounds were obtained from this species for the first time and were tested for cytotoxic activities against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), hepatoma (Bel 7402), colon cancer (HCT-8) and HeLa cell lines. Compound 6 showed selective cytotoxicity against HeLa cell line with IC(50) 15.5 muM, cholest-5-en-3beta,7alpha-diol (14) was toxic to all tested cell lines with IC(50) values of 16.8, 5.1, 0.5, 0.5, and 0.3 muM, respectively, and other compounds were inactive (IC(50)>10 mug/ml).

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Tohoku Pharmaceutical University.

A novel human cytochrome P450, designated CYP2W1, has recently been identified and is found to be present mainly in tumor cells, particularly in colon cancer cells. In the present study, we report the first systematic investigation of polymorphisms in the human CYP2W1 gene. Based on denaturing high performance liquid chromatography analyses of polymerase chain reaction products, we analyzed 9 exons and exon-intron junctions of the gene in DNA samples from 200 Japanese subjects and identified 6 single nucleotide polymorphisms (SNP). Three of the novel nonsynonymous SNPs were as follows: 173A>C (Glu58Ala) in exon 1, 5432G>A (Val432Ile) and 5584G>C (Gln482His) in exon 9. Two previously known nonsynonymous SNPs, i.e., 2008G>A (Ala181Thr) in exon 4 and 5601C>T (Pro488Leu) in exon 9, were also found. On haplotype analyses, in addition to the wild-type CYP2W1*1A (frequency: 0.295) allele, other alleles, namely, CYP2W1*1B (0.318), CYP2W1*2 (0.005), CYP2W1*3 (0.005), CYP2W1*4 (0.008), CYP2W1*5 (0.003), and CYP2W1*6 (0.368), were also characterized. The most common allele CYP2W1*6 exhibited the amino acid substitution Pro488Leu. These results were in good agreement with the expected genotype distributions that were calculated using the Hardy-Weinberg equation. The data on variant alleles and comprehensive haplotype structures would be useful for predicting the metabolic phenotypes of CYP2W1 substrates in the Japanese population.

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aLarnaca General Hospital, Larnaca, Cyprus bAreteeio Hospital, University of Athens, Athens, Greece.

A 52-year-old Cypriot woman was admitted to the surgical department of Larnaca General Hospital complaining of diarrhea and pain in the right upper and lower quadrants, which was reproduced by clinical examination. A palpable mass was also felt in the region. The white blood cell count was 8420/mul: 73.9% neutrophils, 13.3% lymphocytes and 6.9% eosinophils. Erythrocyte sedimentation rate was 80 mm/h. Parasitic examination of the stools was negative. A colonoscopy located a small mass near the ileoceacal valvule, which was sent for a biopsy. A barium enema and computed tomography scan revealed the same lesion to have expanded into the ascending colon. Despite negative biopsy reports, other findings suggestive of colon cancer prompted us to perform a right hemicolectomy and ileotransverse end to side anastomosis. The mass was found to be expanding into the surrounding fat tissue and into the regional lymph notes. Surprisingly, histological examination of the mass revealed visceral larva migrans, owing to ascaris Toxocara canis or Toxocara cati.

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Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612.

Recently, we identified a nucleoside analog named ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide), which has the properties of a general transcriptional inhibitor. Here, we report the characterization of ARC on a panel of colorectal cancer (CRC) cell lines. Cell death induced by ARC in CRC cells was accompanied by caspase-3 cleavage and correlated with the downregulation of antiapoptotic proteins, survivin and Mcl-1 and with the inhibition of Akt phosphorylation. At the same time, colon cancer cell lines were resistant to the well-known nucleoside analog DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole), which failed to downregulate Mcl-1 or survivin. Overall, ARC could represent an attractive candidate for anti-cancer drug development that targets multiple survival pathways in colon cancer cells. (c) 2007 Wiley-Liss, Inc.

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