Urinary gonadotropin peptide as acute phase reactant: transient elevation after operation for digestive diseases. (17/1704)

OBJECTIVE: In order to characterize urinary gonadotropin peptide (UGP) as an acute phase reactant, we focused on the UGP levels after surgical operation. DESIGN: Fifty cases of gastrointestinal cancer, 4 cases of cancers of other organs and 13 cases of benign digestive diseases were enrolled into this study. METHODS: UGP levels were measured using an enzyme immunoassay before and after surgery. RESULTS: Fifty-four (80.6%) of the 67 cases studied showed transient elevations of UGP. Both urinary interleukin (IL)-6 and LH levels were also increased transiently in 49 cases (73.1%). All of these three factors were increased in 38 cases (56.7%), and in 32 (84.2%) of these 38 cases, the order of peak appearance was as follows: IL-6, LH, and UGP. The UGP levels in the group of total gastrectomy were significantly higher than those in the group of partial gastrectomy. CONCLUSIONS: These results suggest that UGP shows a transient peak after surgery, correlating with levels of cytokines such as IL-6. UGP may be an acute phase reactant, and its levels are correlated with the grade of surgical stress.  (+info)

Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. (18/1704)

The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastrointestinal cancer (e.g., APC, K-ras, and p53) are less frequently mutated in near-diploid MMP gastrointestinal tumors. These tumors accumulate mutations in other genes, such as DNA mismatch repair hMSH3 and hMSH6, transforming growth factor-beta type II receptor, and BAX. All these genes carry, within their coding sequences, mononucleotide repeats that are preferred targets for the MMP. Endometrial carcinoma is the most common type of extracolonic neoplasia in the hereditary nonpolyposis colorectal cancer syndrome, but the spectrum of its target cancer genes is not well characterized. Here, we report that endometrial cancer of the MMP also accumulates mutations in genes that are typically mutated in gastrointestinal cancer of the mutator pathway, including BAX (55%), hMSH3 (28%), and hMSH6 (17%). We also report the detection of frameshift mutations in caspase-5, a member of the caspase family of proteases that has an (A)10 repeat within its coding region, in MMP tumors of the endometrium, colon, and stomach (28, 62, and 44%, respectively). We therefore suggest caspase-5 as a new target gene in the microsatellite mutator pathway for cancer.  (+info)

Current concepts in gastrointestinal photodynamic therapy. (19/1704)

OBJECTIVE: To review current concepts of photodynamic therapy (PDT) applied to the treatment of tumors of the gastrointestinal tract. SUMMARY BACKGROUND DATA: PDT initially involves the uptake or production of a photosensitive compound by tumor cells. Subsequent activation of the photoreactive compound by a specific wavelength of light results in cell death, either directly or as a result of vascular compromise and/or apoptosis. METHODS: The authors selectively review current concepts relating to photosensitization, photoactivation, time of PDT application, tissue selectivity, sites of photodynamic action, PDT effects on normal tissue, limitations of PDT, toxicity of photosensitizers, application of principles of PDT to tumor detection, and current applications of PDT to tumors of the gastrointestinal tract. RESULTS: PDT is clearly effective for small cancers, but it is not yet clear in which cases such treatment is more effective than other currently acceptable approaches. The major side effect of PDT is cutaneous photosensitization. The major limitation of PDT is depth of tumor kill. As data from current and future clinical trials become available, a clearer perspective of where PDT fits in the treatment of cancers will be gained. Many issues regarding pharmacokinetic data of photosensitizers, newer technology involved in light sources, optimal treatment regimens that take advantage of the pharmacophysiology of photoablation, and light dosimetry still require solution. One can foresee application of differing sensitizers and light sources depending on the specific clinical situation. As technologic advances occur, interstitial PDT may have significant application. CONCLUSIONS: PDT has a potentially important role either as a primary or adjuvant mode of treatment of tumors of the gastrointestinal tract.  (+info)

Frequent mutation of bcl-6 proto-oncogene in high grade, but not low grade, MALT lymphomas of the gastrointestinal tract. (20/1704)

BACKGROUND AND OBJECTIVE: Knowledge regarding the molecular pathogenesis and histogenesis of gastrointestinal mucosa-associated lymphoid tissue non-Hodgkin's lymphomas (MALT-NHL) is limited. Mutations of BCL-6, a zinc finger transcription factor implicated in lymphoid development, occur frequently in lymphomas and represent a histogenetic marker of B-cell transit through the germinal center. The distribution of BCL-6 mutations in gastrointestinal MALT-NHL was analyzed in this study. DESIGN AND METHODS: This study was based on 26 gastrointestinal MALT-NHL, including 16 cases of low grade histology and 10 cases of high grade histology. Mutations of BCL-6 were investigated by a combination of polymerase chain reaction-single strand conformation polymorphism and DNA direct sequencing analysis. RESULTS: Mutations of BCL-6 occurred in 6/10 high grade MALT-NHL, whereas they were absent from all low grade cases tested (n = 16; p = 0.001). MALT-NHL harboring BCL-6 mutations included 5 cases of gastric MALT-NHL and 1 case of jejunal MALT-NHL. Mutations were predominantly represented by single nucleotide substitutions which were multiple in most cases. All sequence alterations were unique to individual cases of gastrointestinal MALT-NHL. INTERPRETATION AND CONCLUSIONS: Mutations of BCL-6 occur frequently in high grade gastrointestinal MALT-NHL and display characteristics similar to those of BCL-6 mutations harbored by other B-cell lymphomas. The association of high grade MALT-NHL with BCL-6 mutations corroborates their histogenetic derivation from germinal center-related B-cells and may be of potential pathogenetic relevance for these disorders.  (+info)

The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. (21/1704)

Both DR4 and DR5 have recently been identified as membrane death receptors that are activated by their ligand TRAIL to engage the intracellular apoptotic machinery. TRID (also named as TRAIL-R3) is an antagonist decoy receptor and lacks the cytoplasmic death domain. TRID protects from TRAIL-induced apoptosis by competing with DR4 and DR5 for binding to TRAIL. TRID has been shown to be overexpressed in normal human tissues but not in malignantly transformed cell lines. DR5 is a p53-regulated gene and we have recently reported that DR5 expression is induced in response to genotoxic stress in both a p53-dependent and independent manner (Sheikh et al., 1998). In the current study, we demonstrate that TRID gene expression is also induced by the genotoxic agents ionizing radiation and methyl methanesulfonate (MMS) in predominantly p53 wild-type cells, whereas UV-irradiation does not induce TRID gene expression. Consistent with these results, exogenous wild-type p53 also upregulates the expression of endogenous TRID in p53-null cells. Thus, TRID appears to be a p53 target gene that is regulated by genotoxic stress in a p53-dependent manner. Using primary gastrointestinal tract (GIT) tumors and their matching normal tissue, we also demonstrate for the first time that TRID expression is enhanced in primary tumors of the GIT. It is, therefore, possible that TRID overexpressing GIT tumors may gain a selective growth advantage by escaping from TRAIL-induced apoptosis.  (+info)

Treatment of malignant pericardial effusion with 32P-colloid. (22/1704)

Malignant pericardial effusion is usually treated only when signs of cardiac tamponade develop. Several methods of treatment have been reported with an overall response rate of approximately 75%. Since our initial study using intrapericardial 32P-colloid instillation as a treatment modality for pericardial effusion demonstrated a significant higher response rate, this study was conducted to further evaluate the efficacy of intrapericardial 32P-colloid in terms of response rates and duration of remissions. Intrapericardial instillation of 185-370 MBq (5-10 mCi) 32P-colloid in 36 patients with malignant pericardial effusion resulted in a complete remission rate of 94.5% (34 patients) whereas two patients did not respond to treatment due to a foudroyant formation of pericardial fluid. The median duration time was 8 months. No side-effects were observed. These results suggest that intrapericardial instillation of 32P-colloid is a simple, reliable and safe treatment strategy for patients with malignant pericardial effusions. Therefore, since further evidence is provided that 32P-colloid is significantly more effective than external radiation or non-radioactive sclerosing agents, this treatment modality should be considered for the management of malignant pericardial effusion.  (+info)

Does cimetidine improve prospects for cancer patients?. A reappraisal of the evidence to date. (23/1704)

BACKGROUND: Evidence first appeared in 1988 that cimetidine as an adjuvant may improve the survival of severely ill gastro-intestinal cancer patients when given peri- or postoperatively. Since then, several studies have appeared which suggest an anticancer activity for cimetidine, although few attempts have been made to corroborate their findings in large, placebo-controlled, double-blind studies. METHOD: We reviewed the literature concerning cimetidine's potential anticancer activity, particularly with regard to gastro-intestinal cancers. RESULTS: Most studies suggest that cimetidine may improve the outcome in cancer patients by a three-pronged mechanism involving (1) inhibition of cancer cell proliferation; (2) stimulation of the lymphocyte activity by inhibition of T cell suppressor function, and (3) inhibition of histamine's activity as a growth factor in tumours. CONCLUSION: Bearing in mind the experimental evidence, as well as the potential and excellent safety profile of cimetidine, more studies are required and justified to clarify cimetidine's protherapeutic activity.  (+info)

Chromosome breakage at sites of oncogenes in a population accidentally exposed to radioactive chemical pollution. (24/1704)

The purpose of the present study was to investigate the level of aberrations at fragile sites of chromosomes in peripheral blood lymphocytes of the population of an area polluted with radionuclides, following an accident at the Siberian Chemical Plant. We carried out the micronucleus test to screen people with radiation-related cytogenetic effects. Of the 1246 inhabitants of the settlement of Samus examined, 148 showed a significantly increased frequency of micronucleated erythrocytes and were selected for chromosome analysis as a radiation-exposed group. Additional analysis was carried out on 40 patients with gastric cancer and atrophic gastritis with stage II-III epithelial dysplasia. Eighty six individuals from a non-polluted area were used as a control group. Chromosomal breaks and exchanges occurred preferentially in chromosomes 3 and 6 among radiation-exposed persons and patients. The regions 3p14-25 and 6p23 were damaged most often. There was a tendency to preferential involvement of q21-25 of chromosome 6 in patients with gastric cancer and atrophic gastritis. Specific damage at certain chromosome sites was observed in the radiation-exposed population as well as in patients with gastric cancer. Most often this damage was located near oncogene loci, which could imply that chromosome damage induced by radiation is likely to be a predisposing factor to the expression of oncogenes and malignant transformation of cells in exposed individuals.  (+info)