Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 73 records · Page 4Linked to original sources

PubMed2000

Frequency of microsatellite instability inBreast cancer determined by high-resolution fluorescent microsatellite analysis.

In breast cancer, the rates of positivity for microsatellite instability (MSI), vary greatly in the literature. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 75 patients with sporadic breast cancer. In this system, several devices were prepared to improve reproducibility of polymerase chain reaction products, migration accuracy of electrophoresis, and characteristics of the detection system. Precise and objective analyses of microsatellite alterations are made feasible using HRFMA. Seven of the 75 cases were judged to be positive for MSI, the rate of positivity being 9. 3%. This rate is relatively low compared to the data in the literature. All the microsatellite changes observed in this system can be classified into two types: type A with relatively small changes in microsatellite sequences observed in limited loci and type B with drastic and widely dispersed changes. The former was thought to be connected to abnormal activity in DNA mismatch repair (MMR). Among the 7 cases, 6 (8.0%) had type A alterations, which means that the tumors may have an abnormal MMR activity. Application of precise and objective systems for microsatellite analysis is expected to be clinically useful to detect patients at high risk for cancers.

Adult↗

PubMed2000

Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas.

The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein/multidrug resistance (MDR) 1 and MDR protein (MRP) 1, is often up-regulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. Five human MRP subfamily members (MRP2-6) with structural similarities to MRP1 have been identified. The relationships between MRP2-6 mRNA levels and drug resistance are not well understood. Data on 45 patients with colorectal cancer were analyzed. Of the ATP-binding cassette superfamily genes, we asked whether mRNA levels of MDR1, MRP1, MRP2, and MRP3 correlated with drug resistance to anticancer agents. For this analysis, we used quantitative reverse transcription-PCR, and the sensitivity to anticancer agents in surgically resected colon carcinomas was determined using the in vitro succinate dehydrogenase inhibition test. MDR1, MRP1, and MRP3 were highly expressed in normal colorectal mucosa, and the relative mRNA levels of MDR1, MRP1, and MRP3 in cancerous tissues compared with noncancerous tissues were decreased or unchanged. By contrast, MRP2 mRNA expression was low in normal colorectal mucosa and specifically increased in cancer regions compared with noncancerous regions. Of the anticancer agents prescribed for patients with colorectal cancers, including doxorubicin, mitomycin C, cisplatin, 5-fluorouracil, etoposide, and a camptothecin derivative, mRNA expression of MRP2 was significantly associated with resistance to cisplatin. MRP2 may be important for resistance to cisplatin treatment in colorectal cancer.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2000

[Risk of bradycardia after endoscopic electrocautery of the upper thoracic sympathetic ganglia].

We evaluated risk of bradycardia after endoscopic electrocautery of the upper thoracic sympathetic ganglia (ETS). Enrolled in this study were 24 patients. Bradycardia, defined as heart rate below 50 beats per min continuing for more than 5 min, was found in 12 patients (50%). All patients were divided into two groups; bradycardia group and non-bradycardia group. Age, sex, region of electrocautery, fentanyl dosage, and operation time were not different between the two groups. Power spectral analysis of heart rate variability revealed that sympathetic activity decreased after ETS. Multivariate analysis indicates that postoperative-minimal heart rate depends upon preoperative heart rate at rest. We conclude that careful monitoring after ETS is necessary in a patient with heart rate below 60 bpm preoperatively.

Aged↗

PubMed2000

[Pain management for patients with cancer--current problems in a pain clinic].

One hundred and twenty-three patients with early or advanced cancer who had been referred to our pain clinic were studied retrospectively to investigate current problems with pain management for cancer patients. Pain due to advanced cancer and prolonged post-thoracotomy pain were two major reasons for referral. It was found that 51.7% of the patients with advanced cancer had not been treated appropriately with the WHO protocol for cancer pain relief before referral; however, increased administration of morphine did not necessarily relieve cancer pain, and in fact decreased the QOL of some patients; and 47.7% of patients with cancer pain were effectively treated with nerve block therapy. The present investigation also indicates that many patients who had undergone thoracotomy suffered prolonged post thoracotomy pain. Although post-thoracotomy pain was refractory to NSAIDs, trigger point injections with or without intercostal nerve block were effective in 65.4% of such patients. We conclude that further propagation of the WHO protocol for cancer pain relief, appropriate use of nerve block and establishment of practical guidelines for multidisciplinary management of pain are mandatory for improving the QOL of patients with cancer.

Aged↗

PubMed2000

Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph node metastasis.

Endoscopic mucosal resection, which has been widely accepted for the treatment of intramucosal gastric carcinoma (IMGC) because of the minimal invasiveness of the procedure and the sustained quality of life it provides, can only be used on the premise that the carcinoma has no lymph node metastasis. We evaluated the clinicopathological and biological features of IMGC with lymph node metastases in relation to matrix metalloproteinase (MMP) expression. Fifteen cases of lymph node metastasis-positive [n(+)] IMGC and 59 cases of lymph node metastatic-negative [n(-)] IMGC were obtained. The expression of MMP-2 and MMP-9 was investigated with immunohistochemical methods. Clinicopathologically, n(+)-IMGCs were more likely to be of a larger size, to be of poorly differentiated adenocarcinoma, to have had lymphatic permeation [ly(+)], and to have ulcerations within the lesion compared to n(-)-IMGCs. The incidence of the positive expression of MMP-9 in n(+)-IMGCs (67%) or ly(+)-IMGCs (86%) was significantly higher than that in n(-)-IMGCs (32%) or ly(-)-IMGCs (34%). Even in IMGCs, carcinoma cells may produce MMPs that can degrade the basement membrane, allowing them to permeate the lymph capillary. Ulcerations within the lesion may also facilitate the interchange of lymphatic flow between the mucosa and the submucosa, promoting the development of lymph node metastases.

Carcinoma↗

PubMed2000

Application of quantitative RT-PCR using "TaqMan" technology to evaluate the expression of CK 18 mRNA in various cell lines.

Reverse transcriptase polymerase chain reaction (RT-PCR) is often used for sensitive detection of micrometastasis in peripheral blood, lymph nodes and bone marrow. While the utility of this method has been documented, it also has limitations in the detection of micrometastasis. The mRNA of target genes can be detected in healthy donors or in samples used for negative control, therefore the non-quantitativeness of conventional RT-PCR has been called into question. We analyzed the expression level of cytokeratin (CK) 18 mRNA in established esophageal and gastrointestinal carcinoma cell lines and non-epithelial cells, using quantitative RT-PCR, based on real time 'TaqMan TM' technology. CK 18 mRNA is more highly expressed in carcinoma cells than in non-epithelial cells. However, the expression level in non-epithelial cells was easily detected using conventional RT-PCR and agarose gel electrophoresis. In an analysis of CK 18 mRNA expression in peripheral venous blood in 13 healthy volunteers, we found that CK 18 mRNA was much less expressed than in cancer cell lines. However, the expression in all samples was at a level which was also detected using conventional RT-PCR. It would thus seem that not only qualitative, but also quantitative analysis, of the target mRNA is important to detect micrometastasis. Quantitative RT-PCR methods will make comparisons of the possible differences in expression levels of the target gene. For clinical applications, much further study is needed.

Adult↗

PubMed1999

Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer.

p33(ING1) is a novel growth inhibitor candidate for a tumor suppressor gene. p33(ING1) cooperates with p53 and negatively regulates cell growth by activating transcription from the p21/WAF1 promoter even though it has no significant sequence similarity to p53. We first compared p33(ING1) expression in human gastric cancers and matched normal tissues using quantitative RT-PCR and real time 'Taqman TM' technology. A significant decrease in p33(ING1) expression was evident in 15 of 20 gastric cancers. In immunohistochemical analysis, p53 protein expression was detected in 4 of 20 (20%) tumors, and 12 of 15 (80%) tumors with decreasing p33(ING1) expression in RT-PCR had the wild type p53. When we examined the sequence of p33(ING1) in 12 gastrointestinal carcinoma cell lines, we found mutation in only one cell line, HCT116. Our findings are interpreted to mean that p33(ING1) may function as a tumor suppressor in gastric carcinogenesis, even though the gene is preserved in the majority of gastrointestinal carcinomas. It should be noted that expression of p33 decreased in many cancer patients, and the biological effects of p33(ING1) and p53 are interrelated and require the activity of both genes.

Adenocarcinoma↗

PubMed1999

Intratumoral neovascularization and growth pattern in early gastric carcinoma.

BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects biologic characteristics of the tumor. The authors investigated the microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), and growth patterns in early gastric carcinoma. METHODS: Ninety-four tissue specimens resected from patients with early gastric carcinoma invading the submucosal layer were examined. Microvessel quantification was performed immunohistochemically using a monoclonal antibody against factor VIII-related antigen. VEGF expression was studied using an anti-VEGF polyclonal antibody. Growth patterns were defined as follows: Pen A type: expansively penetrating growth; Pen B type: infiltratively penetrating growth; Super type: superficially spreading growth. RESULTS: The mean MVD was 16.9 (range, 5.2-43.0). MVD was significantly higher in tumors with venous invasion (P<0.01), lymphatic vessel invasion (P<0.05), and lymph node metastases (P<0.05) compared with MVD in tumors without venous or lymphatic vessel invasion or lymph node metastases. The VEGF-positive rate of Pen A type tumors was 66.7% (18 of 27), that Pen B type was 10.0% (1 of 10), that of Super type was 19.4% (6 of 31), and that of the unclassified type was 15.4% (4 of 26). The VEGF-positive rate in patients with Pen A type tumors was significantly higher than that in patients with the other three growth patterns(P<0.01). MVD in patients with Pen A type tumors (25.9+/-9.2) was significantly higher than that in patients with Super type tumors (12.6+/-5.4) (P<0.01). Patients with Pen A type tumors had a poorer prognosis than patients whose tumors had other growth patterns (P<0.05). According to multivariate analysis, VEGF expression and lymphatic vessel invasion were significant prognostic factors. CONCLUSIONS: Pen A type gastric carcinoma tends to secrete VEGF, thus inducing tumor angiogenesis and resulting in venous invasion. Intensive follow-up is necessary for patients with Pen A type tumors, because this tumor type has a greater propensity for hematogenous metastasis.

Aged↗

PubMed1999

Temperature-Responsiveness of A-B-A Block Telomers at Solid-Liquid Interfaces.

Macroinitiators were prepared by coupling disuccinimidyl ester of 4,4'-azobis(cyanovaleric acid) with poly(N-isopropylacrylamide) (PIPA), which had an amino group at its end. Styrene was telomerized with the initiators in THF. When the styrene content in the A-B-A block telomer obtained (PIPA-b-PSt-b-PIPA) was high, the telomer formed an irreversible aggregation resulting in microspheres, whereas the telomer with a much shorter styrene block could be dispersed monomolecularly. The telomers dispersed in water were aggregated by raising the temperature above 32 degrees C due to a coil-globule transition of PIPA moieties. The PIPA-b-PSt-b-PIPA could be strongly adsorbed to polystyrene (PSt) solid surfaces to form a layer, and the PSt blocks might lay on the PSt surface and the PIPA blocks might direct to the solution phase. The contact angle of air bubbles on the surface of telomer-coated PSt in the air-in-water system was dependent on temperature; that is, with the increase in temperature the contact angle of air bubbles largely decreased and leveled off above the coil-globule transition temperature (Tc). Correspondingly, the amount of protein Concanavalin A adsorbed to the telomer layer deposited on the PSt surface increased gradually with an increase in temperature and leveled off above the Tc. These phenomena were attributed to the changes in hydrophobicity of the telomer layer below and above the Tc. The usefulness of macroinitiators in preparing various kinds of block telomers which have responsiveness to external stimuli was strongly suggested. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Mutated gene-specific phenotypes of dinucleotide repeat instability in human colorectal carcinoma cell lines deficient in DNA mismatch repair.

Mutations in DNA mismatch repair (MMR) genes in hereditary non-polyposis colon cancer (HNPCC) patients revealed the importance of MMR deficiency as a risk for carcinogenesis. Since diverse mutations occur in several MMR genes, the instability of repeat sequences dispersed in the genome, which are also governed by the MMR system, is a well used marker. However, the relationship between repeat sequence instability and MMR gene mutation in human cells has not been well defined mainly because precise systems to analyse repeat sequences have not been available. Using our newly developed system, we analysed alteration of dinucleotide repeats in human cell lines which harbour mutations in MMR genes. Among 24 subclones of DLD-1 cells (hMSH6-) only one had a dinucleotide repeat alteration in only one microsatellite locus, while LoVo cells (hMSH2-/hMSH6-) exhibited marked dinucleotide repeat instability (DRI). HCT116 cells, a hMLH1-mutant, showed an ultimate DRI phenotype. Interestingly, SW48 cells lacking hMLH1 expression also demonstrated DRI, albeit the extent of diversity being significantly lower than HCT116. These data suggest that the DRI phenotype in human cells is highly dependent on mutated MMR genes and on forms of mutation. The results of DRI analyses used to detect MMR-deficiency should be interpreted with caution.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Clinical implications of serum anti-p53 antibodies for patients with gastric carcinoma.

BACKGROUND: Mutations of p53 can lead to the production of anti-p53 antibodies in sera of cancer patients. Before this study, the value of preoperative serum anti-p53 antibodies in determining the prognoses of patients with gastric carcinoma had yet to be determined. METHODS: The authors used a highly specific enzyme-linked immunosorbent assay (ELISA) kit (Pharma Cell, France) to determine the preoperative presence of serum anti-p53 antibodies in 120 patients with gastric carcinoma. The relation between the positivity of serum anti-p53 antibodies and p53 abnormal staining of gastric carcinoma tissues was examined. Clinicopathologic characteristics and prognoses of these patients were given attention. RESULTS: Anti-p53 antibodies were detected in 19.2%(23 of 120) of these patients with gastric carcinoma. Among those who were positive for anti-p53 antibodies, female patients were predominant, the depth of invasion was greater, and liver metastasis was present, as compared with those who were negative for anti-p53 antibodies. Regarding other factors, there were no differences between those who were positive or negative for anti-p53 antibodies. Gastric carcinoma tissues had a 60.9% (14 of 23) positivity rate of p53 staining with anti-p53 antibodies and a 33.0% (32 of 97) negativity rate, and this difference was statistically significant (P < 0.05). The survival time of patients with anti-p53 antibodies in their sera was shorter than that of subjects with sera negative for anti-p53 antibodies (P < 0.05). The presence of anti-p53 antibodies was not an independent prognostic factor in multivariate analysis. CONCLUSIONS: Serum assay of anti-p53 antibodies is a rapid and readily facilitated test for predicting tumor advancement, depth of invasion, and liver metastasis, and it will show a poorer prognosis for surgically treated patients with gastric carcinoma.

Antibodies, Monoclonal↗

PubMed1999

The p53 tumor suppressor gene in anticancer agent-induced apoptosis and chemosensitivity of human gastrointestinal cancer cell lines.

PURPOSE: While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the chemosensitivity of these lines was determined. METHODS: Twelve gastrointestinal cancer cell lines were examined for the presence of either a wild-type or mutant p53 gene by direct sequencing. We also determined whether or not cell killing would occur when the cell lines were exposed to anticancer drugs. The sensitivity to the anticancer agents was determined based on colony formation. RESULTS: All 12 gastrointestinal cancer cell lines carried either a wild-type or mutant p53 gene. Three lines, MKN45, MKN74 and COLO320, carried the wild-type p53 gene, and nine carried the mutant p53 gene. When three lines were exposed to the anticancer agents etoposide, doxorubicin (DXR) or 5-fluorouracil (5-FU), cell death ensued. In these cells, the population of cells in G1 phase increased after exposure to high-dose anticancer agents, but cells in G2 phase increased when exposed to low-dose anticancer agents. Our observations support the concept that cells carrying the wild-type p53 gene tend to be sensitive to etoposide and DXR and, in particular, deletion of the p53 function results in a greater resistance to anticancer agents. CONCLUSION: Based on our findings, human gastrointestinal cancer-related cell death apparently occurs via a p53-dependent pathway. A relationship was observed between the induction of cell death and chemosensitivity.

Antineoplastic Agents↗

PubMed1999

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

Adult↗

PubMed1999

Prognostic value of p53 protein expression for patients with gastric cancer--a multivariate analysis.

Mutations in the p53 gene, one of the most common genetic alterations in human cancer, are implicated in tumorigenesis and tumour progression. Although p53 protein expression appears to be correlated to prognosis in patients with malignancy, its prognostic role in gastric cancer has remained controversial. We examined the clinical significance of p53 overexpression in 427 patients with gastric cancer, using multivariate analysis. Tumour sections of gastric cancer tissues from these 427 Japanese patients were stained immunohistochemically with monoclonal antibody PAb1801. The presence of p53 expression was statistically compared with clinicopathological features and post-operative survival, using univariate and multivariate analyses. p53 expression was detected in 38.6% (165 out of 427) of these gastric cancers and immunoreactivity was not observed in normal mucosa adjacent to the tumour. A higher rate of p53 detection was observed among large tumours and in those with a prominent depth of invasion, lymphatic and vascular invasion and lymph node involvement. Prognosis was significantly worse for patients with p53-positive-staining tumours. The 5-year survival rate was 62.5% for patients with p53-negative tumours and 43.3% for those with positive malignancies. p53 expression was a significant prognostic factor for node-positive gastric cancers in subjects undergoing treatment with curative resection, as assessed by Cox regression analysis. Thus, the expression of p53 was closely related to the potential for tumour advance and a poorer post-operative prognosis for patients with gastric cancer.

Analysis of Variance↗

PubMed1999

Recurrences and relation to tumor growth potential and local immune response in node-negative advanced gastric cancer.

Biological characteristics and the prognosis for subjects with node-negative advanced gastric cancer have been given little attention in related literature. We analyzed data on 112 patients with serosally invasive gastric cancer who were lymph node metastasis-negative; all had been surgically treated in the Department of Surgery II, Kyushu University Hospital, between 1970 and 1992. Recurrences and relation to the growth potential of the tumor and local immune response were examined. Thirty patients died with a recurrence of the gastric cancer, and in these patients, the tumor was larger, the whole stomach was more frequently involved and infiltrative growth was more common, compared to findings in patients who were recurrence-free. Peritoneal recurrence was evident in half the number of patients and the 5-year survival rate was 74. 5%. Tumor growth potential was evaluated, based on the level of proliferating cell nuclear antigen (PCNA) of the primary tumor and on dendritic cell infiltration into the tumor, determined as a level of local immune function of the host. Higher growth potential and lower immune levels were more frequent in patients with recurrences. Multivariate analysis revealed that tumor size and PCNA labeling index were significant prognostic factors for node-negative gastric cancers. In a subset of advanced gastric cancers, there was no apparent distinct lymph node metastasis and the prognosis was better. However, cancer cells with a higher growth potential and a lower immune response in the host can biologically amplify and mainly infiltrate the gastric wall, extend to the serosa and disseminate transserosally into the peritoneum.

Aged↗

PubMed1999

An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group.

5-Fluorouracil (5-FU) or a 5-FU derivative 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) has been widely prescribed for patients with gastrointestinal cancer. However, the phosphorylation of 5-FU in the digestive tract causes gastrointestinal toxicities. 5-FU is also rapidly degraded to alpha-fluoro-beta-alanine after contact with dihydropyrimidine dehydrogenase (DPDase) which is mainly present in the liver. Therefore, to overcome these metabolic events, S-1, an antitumor agent was developed, based on the biochemical modulation of FT by 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo), in a molar ratio of 1:0.4:1. The antineoplastic effect of S-1, was examined in Japanese patients with advanced gastric (G) or colorectal (C) cancer in a multicenter early phase II study involving 24 centers throughout Japan. The patients were prescribed a minimum of 2 courses of S-1 orally, with each course consisting of 75 or 50 mg (in terms of FT) twice a day for 28 days followed by withdrawal for 2 weeks. Thirty-one patients with G and 31 C were entered into this study. The clinical response and extent of toxicity were evaluated in G 28 and C 30 cases, respectively. Nine (32.1%) G patients and 14 (46.7%) C patients had been treated previously with other anticancer drugs. In G patients, there was a 53.6% (15/28) and in C patients a 16.7% (5/30) response rate (90% confidence interval G 38.4-68.1% and C 8.4-30.5%) with 15 (53.6%) (G) and 5 (16.7%) (C) partial responses (PR), and these responses persisted for 79 days (G) and 120 days (C) (median value). In particular, the response rate for the primary lesion was 27.8% (5/18) (G) and 33.3% (1/3) (C). No change (NC) in the disease was observed in 4 (14.3%) (G) and 13 (43.3%) (C) patients, and in 6 (21. 4%) (G) and 7 (23.3%) (C) the disease progressed (PD). At the time of analysis, the median survival was 298 days (G) and 358 days (C). Major adverse effects consisted of gastrointestinal symptoms and myelosuppression while toxicities of grade 3 or more occurred in 35. 7% (10/28) (G) and 33.3% (10/30) (C). Based on these data, S-1 is considered to have positive effects in patients with advanced gastrointestinal cancer.

Adult↗

PubMed1999

Role of transforming growth factor-beta 1 in invasion and metastasis in gastric carcinoma.

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is a major modulator of cellular proliferation and extracellular matrix formation. We determined the role of TGF-beta1 in invasion and metastasis in gastric cancer. MATERIALS AND METHODS: We detected TGF-beta1 expression in primary and lymph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-beta1 levels in the peripheral vein and in the tumor drainage vein were assayed. RESULTS: In the cytoplasm of cancer cells, TGF- beta1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was confirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-beta1-negative primary tumor, metastatic lymph nodes were positive for TGF-beta1 staining in 32 cases (54.2%). Positive staining of TGF-beta1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growth, and lymph node metastasis. Multivariate analysis showed that the expression of TGF-beta1 was an independent risk factor for serosal invasion and infiltrative growth of the tumor. The plasma level of TGF-beta1 did not differ between TGF-beta1-negative and -positive groups. There were also no differences in plasma TGF-beta1 levels among each tumor stage, between the peripheral and the tumor drainage veins, and between preoperative and postoperative testings. CONCLUSION: Transforming growth factor-beta1 is closely related to the invasion and metastasis of gastric cancer, and production of TGF-beta1 in the tumor does not contribute to the total amount of TGF-beta1 in the blood circulation. We interpret our observations to mean that in a tumor microenvironment, TGF-beta1 alters the biologic behavior of the tumor.

Aged↗

PubMed1999

[Clinical evaluation of S-1, a new anticancer agent, in patients with advanced gastrointestinal cancer. S-1 Cooperative Gastrointestinal Study Group].

In developing a new anticancer agent, it is most important to balance the antitumor activity and toxicity of the agent. S-1 was designed to achieve high activity and low toxicity. In it tegafur, a prodrug of 5-FU, is combined with two classes of modulators. CDHP, an inhibitor of 5-FU degradation in the liver, and Oxo, an inhibitor of 5-FU phosphoribosylation in the digestive tract. In both early and late Phase II studies, S-1 was effective against advanced or recurrent gastrointestinal cancer. Toxicities were generally mild, and there were no toxic deaths.

Administration, Oral↗