Search

Background:Helicobacter pylori (Hp) infection and gastric atrophy are both risk factors for gastric cancer. Recently it has been found that X-ray examination for gastric cancer screening does not have much effect on the detection rate for gastric cancer in Japan. A candidate for a new mass screening for gastric cancer, the ABC method, using the combination assay of Hp and serum pepsinogen, was useful for identifying the development of gastric cancer in high-risk and low-risk populations. People with higher cancer risk are recommended to receive endoscopy. The ABC method was carried out as a gastric cancer mass-screening on the initiative of Nishitokyo Medical Association in Nishitokyo city from 2011. This paper reviewed the present status of gastric cancer screening using the ABC method, including the latest results of our ongoing screening. Summary: We report results for 36,627 individuals from 2011 to 2013. Among them, 16,965 received blood examination for the ABC method. Of those, 8,083 planned to undergo endoscopic examination according to stratification of the risk for the development of gastric cancer. In fact, a total of 2,911 individuals underwent endoscopic examination. Gastric cancer was detected in 65 patients, including 52 (80%) diagnosed with early gastric cancer. The ABC method was not organized screening but opportunistic screening. X-ray examination was the organized screening that was ongoing during the same period. Detection cost for 1 gastric cancer case using the ABC method was cheaper than the conventional X-ray screening method (¥1,267,452 vs. ¥2,807,763). Key Messages: Although further large epidemiological studies are required, the ABC method might be positioned as an effective mass screening for gastric cancer.

TiO2 films were deposited by DC magnetron sputtering under various discharge gas pressures and annealed at various temperatures. The structure of the films was investigated with focus on porosity, which was evaluated quantitatively by density and effective surface area. Furthermore, the H2 sensing property of the films was investigated at various operating temperatures in ambient air. As the pressure during deposition increased, pores developed between columnar grains. In the most porous film deposited at 12 Pa, the sidewalls of the columnar grains were mostly exposed. A dense film deposited under a low pressure showed sensitivity only at an operating temperature above 200°C. As the porosity increased, the sensing temperature decreased. A porous film annealed at 500°C showed a rather high sensitivity even at a low temperature of 100°C.

It is well known that cell-mediated immunity is suppressed in patients with neoplastic diseases. We have reported that soluble receptors for interleukin-2 (sIL-2R) and tumor necrosis factor (sTNF-R1) are elevated in the serum of patients with advanced colorectal cancer. The presence of these soluble receptors and immunosuppressive cytokines, including interleukin-10 (IL-10), might be important in the mechanisms of immunosuppression. cis-Diaminedichloroplatinum (cisplatin) has been reported to immunomodulate, especially when used in low dose in combination with 5-Fluorouracil (5-FU). In this study, cisplatin and UFT, a form of uracil and tegafur which is a prodrug of 5-FU, were administered with immunomodulator Polysaccharide K (PSK) to ten patients with colorectal cancer, who showed distant metastasis in the liver or lung, and the serum levels of sIL-2R and sTNF-R1 and the production of gamma-interferon (gamma-INF) and interleukin-10 by peripheral blood mononuclear cells were measured. The serum concentrations of sIL-2R and the production of IL-10 were reduced (p < 0.05) after 2 months of treatment. Thus, this combination appeared to have immunomodulative potential in patients with advanced colorectal cancer.

Background. The mechanisms leading to the development of cancer cachexia are still not well understood. Some important factors, including cytokines and growth factors, are involved, and recently, cytokines such as interleukin-1 and interleukin-6 have been reported to be involved as mediators of this disorder. Methods. In patients with colorectal cancer, serum concentrations of interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) and analyzed in relation to the patient's nutrition (in terms of albumin concentration [percentage of total protein] in the serum) and the tumor load. Results. The concentration of IL-1ra was significantly increased in cachectic patients compared with that in healthy volunteers and in the non-cachectic patients, and the concentration was correlated to the serum concentration of IL-6 and inversely correlated to the concentration of albumin (%). These concentrations, however, did not correlate to levels of tumor markers tested, ie, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9. Conclusion. It was shown that the serum concentration of IL-1ra was a useful indicator for cancer cachexia and hypoalbuminemia; IL-1ra seems to be produced by immune-regulating host cells rather than by neoplastic cells.

54 patients had liver metastases from colorectal cancer. Microwave Coagulo-necrotic therapy (MCN) for liver metastases from colorectal cancer was performed in 25 patients. The patients with a MCN for liver metastases had a three-year survival rate of 46.6%. The patients of liver metastases with chemotherapy by intrahepatic infusion and with systematic chemotherapy by p.o. had each a three-year survival rate of 0% and 9.6%. For nonresectable liver metastases (H2, H3), a three-year survival rate of MCN and chemotherapy was each 39% and 0%. We propose that MCN should be selected for cases of nonresectable liver metastases from colorectal cancer.

PURPOSE: This study was designed to evaluate and to compare the outcome of anal fistula surgery using techniques involving minimal sphincter damage (sphincter-preserving) and conventional laying open techniques. PATIENTS AND METHODS: From January 1987 to December 1993, 2,242 patients with anal fistulas were treated surgically, of whom 1,070 had sphincter-preserving operations. These included 530 patients with low intersphincteric fistulas (II L), 116 patients with high intersphincteric fistulas (II H), 73 patients with combined high and low intersphincteric fistulas, 239 patients with transphincteric fistulas (III), and 112 patients with supralevator fistulas (IV). The open method of fistula surgery was used in 1,172 patients. RESULTS: Of 1,070 sphincter-preserving operations, delayed healing occurred in 49 patients (4.6 percent) and recurrent fistula occurred in 32 patients (3 percent). By using the open method in 1,172 patients, delayed healing occurred in 10 patients (0.9 percent) and recurrence of fistula occurred in 23 patients (2 percent). Failure rates increased with increasing depth and complexity of the fistula. CONCLUSION: Sphincter function is better with sphincter-preserving fistula surgery than with the open method, although healing was delayed more commonly in sphincter-preserving operations that with the open methods, and fistula recurrence was similar with the two methods. Choice of operation depends on depth of fistula, outcome by manometry, and history of former operations.

The substrate specificity of β1,4-N-acetylgalactosaminyltransferase has been analyzed using a fusion enzyme which consisted of the catalytic domain of the enzyme and the IgG binding domain of protein A, and also by extracts from cDNA transfectants. Both enzyme sources were capable of producing not only GM2 and GD2, but also asialo-GM2, GalNAc-sialylparagloboside, and GalNAc-GD1a from appropriate acceptors, although the efficiencies were at most 1-3% of those of GM2/GD2. The biological significance of these low specificities was studied with transient and stable transfectant cells. From the results of transient expression of the cDNA, asialo-GM2 expression appeared to inversely correlate with GM3 synthase levels in those lines. Consequently, GM2 seemed to be preferentially synthesized when both GM3 and lactosylceramide are available, and asialo-GM2 is synthesized in the absence of GM3 synthesis. However, the results of double immunostaining of CHO transfectants with anti-GM2 and anti-asialo-GM2 antibodies indicated that another factor may be involved in asialo-GM2 synthesis. From the in vitro assay using mixed acceptors, it was concluded that the presence of certain levels of GM2 might enhance the asialo-GM2 synthesis. These results suggest that even acceptors showing low efficiencies in vitro might be used in certain cells depending on the availability of precursors, expression levels of other gangliosides, as well as the kinetic properties of the enzyme, and the compartmentation of the glycosylation machineries in the cells.

It has been reported that multicentricity of pancreatic carcinomas extending beyond the pancreatic duct occur in 15% to 40% of patients. This has been difficult to confirm, however, with currently available histologic techniques. Mutations in the Kirsten (Ki)-ras oncogene, which can be detected frequently in pancreatic carcinomas using the polymerase chain reaction (PCR), may serve as a potential clonal marker of the cancer cells. Fifty-three patients with a histopathologic diagnosis of pancreatic carcinoma were selected for the determination of certain Ki-ras mutations through PCR. The authors identified mutations in the Ki-ras codon 12 in 46 of 53 tumors. Two of these 46 tumors had two different mutations to aspartic acid (GAT) and to valine (GTT) in Ki-ras codon 12. Another isolate had an additional mutation in Ki-ras codon 13. The detection of different mutations in the same tumor suggests that there may be multicentricity in pancreatic carcinomas and that its frequency may be as low as 6% of the carcinomas. These results imply that total pancreatectomy for eliminating tumor recurrence due to multicentricity may not be warranted.

A semiquantitative estimation of human T-lymphotropic virus type I (HTLV-I) integration by peripheral blood mononuclear cells (PBMC) was performed. Genomic DNA samples derived from 134 HTLV-I carriers were subjected to 40 or 60 cycles of the polymerase chain reaction to amplify the pol region of HTLV-I. The HTLV-I genome was detected by dot hybridization using a 32P-labeled oligonucleotide probe for the pol region. The radioactivity of hybridized dot membranes was then counted with an RI Imaging System (Ambis Inc, San Diego, CA) and the HTLV-I genome dose was determined by comparison with standard curve for serially diluted HTLV-I genome-positive DNA. A wide range of variation of HTLV-I genome integration was observed. When the integrated genome dose was calculated as the number of HTLV-I copies per 100 PBMC, 7 carriers (5%) had more than 10 copies, 56 (42%) had 1 to 10 copies, 46 (34%) had 0.1 to 1 copy, and 24 (18%) had less than 0.1 copy. In one sample, the HTLV-I genome was undetectable, which may indicate that the integrated genome was present at less than 0.01 copies per 100 PBMC. Age- or sex-related variations in the distribution of individuals with different HTLV-I genome were rather limited. However, carriers with a high level of the HTLV-I genome were always more than 30 years old and were predominantly male (six of seven).

Adult T-cell leukemia (ATL) cells have been shown to express the receptor for IL-2 by studies using anti-CD25 monoclonal antibody, but these cells usually show no or only a weak proliferative response to IL-2. In the present study, we established thirteen IL-2-dependent T-cell lines from four ATL patients. Examination of the clonalities of these cell lines by the rearrangement profiles of the TCR β-chain gene and the integration sites of the HTLV-I proviral genome, revealed that two cell lines (KK-1 and KK-5) were of real ATL cell origin. The others were of normal T-cell origin and had been established by infection with HTLV-I. The KK-1 and KK-5 cell lines were derived from a single ATL patient (KK). Interestingly, these cells showed different phenotypic features from the majority of original leukemia cells (CD3 ± CD4 + CD8 − ). The KK-1 cell line acquired CD8 antigen expression and became double-positive (CD3 ± CD4 + CD8 + ), while the KK-5 cell line prominently expressed CD3 antigen (CD3 + CD4 + CD8 − ). These results indicate that the phenotypic feature of ATL cells are not fixed, but can change in vitro as has occasionally been observed in vivo .

Point mutations of c‐ras genes at codons 12, 13 and 61 were analyzed in 26 cases of bladder cancer and 16 cases of kidney cancer. DNA prepared from either frozen tissues or 10% formalin‐fixed, paraffin‐embedded tissues were amplified by means of polymerase chain reaction methods, and mutations were analyzed by dot blot hybridization assays with oligonucleotide probes. In three cases of bladder cancer c‐ras mutations were found, at codons 13 and 61 of c‐Ha‐ras and at codon 61 of c‐Ki‐ras, while no mutation was found in kidney cancer. No mutation was found in normal bladder epithelial tissues from the same patients. Our findings, taken together, may indicate relative scarcity of c‐ras mutations in these types of human cancer. The results of dot blot hybridization assays and DNA sequencing showed a G‐to‐C transition of the first nucleotide at codon 13 of c‐Ha‐ras. This is the first time that such a point mutation has been detected in human cancer tissues.

Point mutations at codons 12 and 13 of c-Ki-ras gene were analyzed in human pancreatic cancer. DNAs obtained from sample tissues were amplified by means of polymerase chain reaction and were analyzed by dot blot hybridization assays with oligonucleotide probes appropriate for detecting mutations at these codons. Out of 38 evaluated cases, point mutations at codon 12 were found in 35 cases; these mutations resulted in changes of the coded amino acid to aspartic acid in 24 cases, to valine in 9 cases, to arginine in 2 cases and to cysteine in one case. In one case, a glycine-to-aspartic acid mutation was found at codon 13. In two cases, two distinct mutations were simultaneously present. The frequency pattern of mutations at codon 12 was somewhat different from those given in two previous reports on the similar analysis of pancreatic cancers in European countries. This may indicate the presence of possible genetic or non-genetic factors in determining preferential mutational patterns at these particular codons.

A 3-methylcholanthrene-induced fibrosarcoma cell line of BALB/c origin, CMS5j, was co-transfected with cDNA for the p40 and p35 subunits of interleukin-12 (IL-12). Injection of transfected cells producing 5 x 10(3) U IL-12/10(6) cells/ml/day in nude mice with an established fibrosarcoma at a contralateral site efficiently eliminated tumor growth in the early phase (injection on day 0 or 4) but not later (day 8). This effect could be abrogated by simultaneous i.v. injection of antibodies against NK1.1 or ASGM1 (asialoGM1 = ganglio-N-tetraosyl-ceramide), which indicates that natural killer (NK) cells play a major role in tumor eradication or suppression when stimulated by IL-12. In wild-type mice, application of IL-12-secreting CMS5j cells abrogated growth of tumors established 8 days before but not earlier. Based on our experiments with antibody blocking in vivo, all CD4+, CD8+ and ASGM1+ cells are involved in tumor rejection. However, in our system, CD4+ cells or CD8+ cells alone, but not ASGM1+ cells alone, also could lead to tumor rejection. IL-12-engineered fibrosarcoma cells may constitute an efficient and safe system for immunotherapy of cancer.

The prevalence of Kirsten (Ki)-ras gene mutations was studied in 105 paraffin-embedded tissues obtained from 40 patients with pancreatic cancer, 48 with bile duct carcinoma (19 distal, 6 middle, and 23 proximal), 16 with ampullary carcinoma and 1 with duodenal cancer, by in vitro amplification of target sequences by the polymerase chain reaction (PCR). With regard to pancreatic cancers, the authors' data confirm the very high frequency (88.6%) of Ki-ras gene mutations occurring at codon 12. Five pancreatic carcinomas did not contain the Ki-ras mutation and included rare types of histopathology. By histologic review after the examination of Ki-ras mutations through PCR, the diagnosis of four patients could be legitimately revised from other periampullary carcinoma to pancreatic carcinoma. In the ampullary carcinoma, the prevalence of mutations in Ki-ras codon 12 was 13.3%. Although there was a large difference in incidence of mutations between distal and middle or proximal bile duct carcinoma, the prevalence of mutations in bile duct carcinoma was limited to 19.6%. Unlike other approaches to diagnose periampullary carcinoma, detection of a mutation in Ki-ras codon 12 by PCR may distinguish pancreatic carcinoma from other periampullary carcinomas that have better prognoses.

GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids expressed in some normal tissues such as brain and in various tumors such as neuroblastomas, astrocytomas, and malignant melanomas. We used a eukaryotic cell transient expression system to isolate cDNA clones that determine GM2 expression. We developed a new cell line from murine melanoma line B16 by transfecting with the polyoma T antigen gene that was suitable for this purpose. Two cDNA clones, both of which have a continuous open reading frame of 1683 base pairs, were isolated. Although the cloned cDNAs had no primary sequence similarity to reported glycosyltransferases, the deduced amino acid sequence predicted a type II transmembrane protein with an overall structure similar to other glycosyltransferases. The cDNA clones, when stably transfected, determined the expression of GM2 in B16 cells and GM2 and GD2 in the human melanoma line MeWo. Northern blot analysis revealed two transcripts in all cells that expressed either GM2 or GD2 or both. These findings indicate that the cDNAs catalyze the transfer of GalNAc onto GM3 and GD3 by a beta 1,4 linkage, resulting in the synthesis of GM2 and GD2, respectively. Namely they suggest that these cDNAs derive from the UDP-GalNAc: GM3/GD3 beta 1,4 N-acetylgalactosaminyltransferase (EC 2.4.1.92) gene.

Twenty-three cases of non-Hodgkin's lymphoma (NHL) were analyzed for expression of ras genes by in situ hybridization utilizing biotinylated DNA probes. Increased expression of Ki-ras, Ha-ras and N-ras genes was observed in 12 cases, 6 cases and 1 case of NHL, respectively. Genomic DNA extracted from these 23 cases of NHL was region-specifically amplified by means of polymerase chain reaction to examine the presence of point mutations at the 12th, 13th and 61st codons of Ki-, Ha- and N-ras genes. Dot hybridization assays with appropriate oligonucleotide probes showed no evidence of point mutation in any case of NHL examined. These results indicate that increased expression of ras genes in NHL is not associated with ras gene activation by point mutation.