Department of Medical Oncology, Hospital Universitario Puerta de Hierro, E-28035 Madrid, Spain.

Little is yet known about the origin and protective mechanism of free nucleic acids in plasma. We investigated the possibility of these free nucleic acids being particle associated. Plasma samples from colon cancer patients and cell culture media were subjected to various antibody incubations, ultracentrifugation, and RNA extraction protocols for total RNA, epithelial RNA, and mRNA. Flow cytometry using a Ber-EP4 antibody and confocal laser microscopy after staining with propidium iodide were also performed. mRNA levels of the LISCH7 and SDHA genes were determined in cells and in culture media. Ber-EP4 antibody and polystyrene beads coated with oligo dT sequences were employed. We observed that, after incubation, total RNA and mRNA were always detected after membrane digestion, and that epithelial RNA was detected before this procedure. In ultracentrifugation, mRNA was caught in the supernatant only if a former lysis mediated or in the pellet if there was no previous digestion. Flow cytometry determinations showed that antibody-coated microbeads keep acellular structures bearing epithelial antigens apart. Confocal laser microscopy made 1- to 2-mum-diameter particles perceptible in the vicinity of magnetic polystyrene beads. Relevant differences were observed between mRNA of cells and culture media, as there was a considerable difference in LISCH7 mRNA levels between HT29 and IMR90 cell co-cultures and their culture media. Our results support the view that extracellular RNA found in plasma from cancer patients circulates in association with or is protected in a multiparticle complex, and that an active release mechanism by tumor cells may be a possible origin.

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jiang.jdong@163.com.

Forty-six new compounds were synthesized on the basis of our knowledge of the 3-haloacylamino benzoylurea (HBU) series. Structure-activity relationship (SAR) analysis indicates that (i) the configuration of the chiral center in 1 (JIMB01) is not indispensable for the activity, (ii) the phenyl ring is essential, and (iii) a substitution at the 6-position of the phenyl ring with a halogen enhances the activity. Among the analogues, 11e and 14b bearing 6-fluoro substitution showed potent activities against nine human tumor cell lines, including CEM (leukemia), Daudi (lymphoma), MCF-7 (breast cancer), Bel-7402 (hepatoma), DU-145 (prostate cancer), PC-3 (prostate cancer), DND-1A(melanoma), LOVO (colon cancer), and MIA Paca (pancreatic cancer) with IC 50 values between 0.01 and 0.30 microM. 14b inhibited human hepatocarcinoma by 86% in volume in nude mice. The mechanism of 14b is to inhibit microtubule assembly, followed by the M-phase arrest, bcl-2 inactivation, and then apoptosis. We consider 14b promising for further anticancer investigation.

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Division of Medical Oncology A, Department of Medicine, National Tumor Institute, Naples, Italy.

Capecitabine, an oral prodrug of fluorouracil (5FU), has shown efficacy in terms of progression-free and overall survival at least equivalent to standard folinic acid (leucovorin)-modulated intravenous 5FU bolus regimens in patients with metastatic colorectal cancer. Moreover, capecitabine has demonstrated a better tolerability profile, producing a significantly lower occurrence of severe stomatitis than 5FU plus folinic acid regimens, making this drug particularly attractive for treating elderly patients. In addition, capecitabine can be combined with other active drugs such as irinotecan or oxaliplatin. Indeed, the combination of capecitabine plus oxaliplatin (XELOX regimen) now represents a new standard of care for the metastatic disease and is also under evaluation in the adjuvant setting. The combination of new biological drugs, such as bevacizumab, with the XELOX regimen was shown to further prolong the time to progression of metastatic disease, and might reduce the risk of recurrence for those with resected colon cancer with poor risk factors. Cost-effectiveness analyses have demonstrated that, despite higher acquisition costs, capecitabine appears to be more cost effective than standard treatments for the management of colorectal cancer patients.

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Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.

BACKGROUND: We developed and evaluated the clinical usefulness of a scoring system that subclassified type VI: pit patterns. METHODS: We studied 119 colon cancer lesions (pTis, n = 26; pT1, n = 93) and 22 tubular adenoma lesions with severe atypia in which a type VI: pit pattern was visible under a stereomicroscope. Four type VI: pit pattern formation appearances (existing pits, marginal irregularities of the gland duct, narrowing of the gland duct lumen, and unclear outline of the gland duct) were defined, and the relationship between each appearance and the invasive depth of the cancer was evaluated. RESULTS: When the four type VI: pit pattern appearances were considered in a logistic regression analysis, the odds of a more invasive submucosal cancer were significantly increased by the appearance of marginal irregularities, a narrowed lumen, and an unclear outline. In the logistic regression analysis results, when 0.63 was used as the cutoff score for prediction of a more invasive submucosal cancer, 80 cases in the less invasive group were classified correctly (specificity, 1.0), whereas 53 (86.9%) of the 61 cases in the more invasive group were classified correctly (sensitivity, 0.869). CONCLUSIONS: It is important first to understand the usability and limitations of objective scoring of type V pit pattern findings and then to apply this score to the determination of cancer depth in order to accurately identify lesions suitable for endoscopic treatment.

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Department of Surgery, Aristotelian University, 15 Fitziou Street, N751, Panorama, Thessaloniki, 55236, Greece, costasspanos@hotmail.com.

PURPOSE: It is estimated that the incidence of cancer in women aged 40 years or less is 8%. Females under the age of 40 are in their childbearing years. In the Western world, colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract. It is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the USA. The incidence of CRC in patients under 40 is 3-6%. Over the past decades, there has been a significant improvement in survival rates due to progress in cancer treatment, including CRC. This has been achieved with advances in adjuvant chemotherapeutic regimens. In the case of locally advanced rectal cancer, radiation therapy is also used. Treatment for CRC may have adverse effects on female fertility. The purpose of this paper is to discuss the effects of treatment of CRC on female fertility as well as the options for fertility preservation. MATERIALS AND METHODS: A review of relevant English language articles was performed on the basis of a MEDLINE search of the keywords: female, fertility, fecundity, colon, rectal cancer, fertility preservation, chemotherapy, and radiation. RESULTS: Surgical resection for colon cancer possibly has no effect on female fertility. Resection below the peritoneal reflection may adversely affect fertility, based on lower fertility and fecundity rates associated with pelvic surgery for ulcerative colitis and familial adenomatous polyposis. Standard 5-FU-based chemotherapy may not have significant effects. The advent of oxaliplatin in adjuvant chemotherapy may be more harmful. Adjuvant and neoadjuvant radiation therapy may cause premature ovarian failure using current dosing schedules. The effect of pregnancy and female hormones on the incidence, progression, and recurrence of CRC remains unclear. Established methods for fertility preservation include ovarian transposition and embryo cryopreservation. Oocyte cryopreservation has yielded inferior results. An investigational fertility preservation method is ovarian tissue cryopreservation, with promising results. Ovarian suppression and the use of apoptotic inhibitors are also investigational at present. CONCLUSION: Young female patients need to be informed about the effects of treatment on fertility and options for fertility preservation. A multidisciplinary approach for appropriate consultation of these patients is mandatory.

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