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.

Share This

Department of Neurology and Neuromuscular Disorders, Oita University Faculty of Medicine.

A 76-year-old woman developed weakness and sensory loss in the lower limbs and urinary disturbance in four days. She had a history of operation for the ascending colon cancer and lung metastasis one year ago. Neurological examination revealed flaccid paraplegia, absent Achilles tendon reflex, severe disturbance of superficial and deep sensation below the L3 level, and vesicorectal abnormality. Magnetic resonance imaging (MRI) studies showed an intramedullary T1-iso, T2-low lesion with Gd-DTPA contrast enhancement in conus medullaris at LI level. The laboratory examination revealed the elevated level of serum FDP. D-dimer and TAT. She was diagnosed as hematomyelia, which may be caused by the activation of coagulation and fibrinolysis system. We suggested that the ascending colon cancer and lung metastasis may contribute to the coagulation-fibrinolysis abnormality.

Share This

Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan, akio.saiura@jfcr.or.jp.

PURPOSE: Surgical indications for colon cancer directly invading the pancreas head are controversial. METHODS: Between 1957 and 2007, a total of 12 patients (8 men) underwent pancreaticoduodenectomy combined with right hemicolectomy for colon cancer involving the pancreas head. RESULTS: Mean age was 58 (range, 34-77) years. Fistula formation was observed in five patients (41 percent) preoperatively. Tumor involvement was duodenum only (n = 4), duodenum/pancreas (n = 3), stomach/pancreas (n = 1), duodenum/stomach (n = 2), duodenum/liver (n = 1), and pancreas only (n = 1). Only one postoperative death was encountered. Histologic examination showed malignant invasion to the pancreas head in nine cases (75 percent). Overall one-year, three-year and, five-year survival rates after surgery were 75, 66, and 55 percent, respectively. Five patients (41 percent) survived for more than ten 10 years. CONCLUSIONS: Pancreaticoduodenectomy for advanced colon cancer invading the pancreas or duodenum provides favorable long-term survival.

Share This

Center of Experimental Medicine, Wuhan First Hospital, Wuhan City, People’s Republic of China.

Human colon cancer is the leading cause of cancer death in both men and women worldwide. The c-Myc gene is frequently deregulated and overexpressed in this malignancy, and strategies designed to inhibit c-Myc expression in cancer cells may have considerable therapeutic value. We design and use short hairpin RNA (shRNA) to inhibit c-Myc expression in Colo 320 cells and validat its effect on cell proliferation. In this study, four c-Myc-shRNA expression vectors were constructed and introduced into Colo 320 cells, and the cell cycle and apoptotic cells were analyzed by flow cytometry. The effects of c-Myc silencing on tumor-cell growth was assessed by the soft agar assay and by DNA synthesis experiments. Expression of c-Myc was also assessed by real-time reverse transcription polymerase chain reaction and Western blot analysis. Upon transient transfection with plasmid-encoding shRNA, it was found that expression of c-Myc decreased in shRNA-transfected cells, and the downregulation of c-Myc inhibited cell growth and induced apoptosis in Colo 320 cells. c-Myc downregulation also increased cell population in the G0-G1 phase. In conclusion, our findings demonstrate that shRNA can inhibit the DNA replication and induce apoptosis in Colo 320 cells effectively and, therefore, could be used as a new potential anticancer tool for the therapy of human colon cancer.

Share This

Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O.B. 63, 00014 Helsinki, Finland. tatiana.petrova@helsinki.fi

The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc(min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.

Share This