Biomedical subjects

Y Maehara

Publications and source records attributed to Y Maehara.

At least 127 records · Page 7Linked to original sources

PubMed1996

Prediction of early and late recurrence after curative resection for gastric carcinoma.

BACKGROUND: Although several prognostic factors for patients with gastric carcinoma have been demonstrated, those predictive of early and late recurrences after surgery are still unclear. METHODS: Of 479 patients who underwent curative resection for gastric carcinoma from 1977 to 1987, 115 patients who died of recurrence were studied. RESULTS: The patients were divided into 2 groups: an early recurrence group that included 80 patients who died within 3 years after surgery, and a late recurrence group, that included 35 patients who died more than 3 years after surgery. Early recurrence was characterized by a large tumor (8.1 cm vs. 6.7 cm; P<0.05) and many involved lymph nodes (7.7 vs 4.4; P<0.01). However, the depth of invasion, as well as the level of positive lymph nodes were not different between the two groups. Multivariate analysis showed that tumor size and the number of positive lymph nodes independently influenced the survival period. CONCLUSIONS: Tumor size and the number of positive lymph nodes are the most important factors predicting the timing of recurrence after curative resection for gastric carcinoma.

Female↗

PubMed1996

Age-related characteristics of gastric carcinoma in young and elderly patients.

BACKGROUND: The clinicopathologic features of young and elderly patients with gastric carcinoma have been analyzed. METHODS: We analyzed the data from 174 patients with gastric carcinoma age 40 years and younger and from 356 patients with gastric carcinoma age 70 years and older who were surgically treated at the Department of Surgery II, Kyushu University, Japan. RESULTS: The rate of multiple gastric carcinomas was 2.9% (5/174) for the young patients and 13.2% (47/356) for the elderly. In subjects older than 70 years, male patients predominated, tumors were smaller, differentiated lesions more common, vascular involvement more frequent, tumors were less infiltrative, and the rate of liver metastasis was higher. For patients younger than age 40 years, undifferentiated type with infiltrative growth was frequent and the rate of liver metastasis was higher. There were no differences in the positive rate of p53 overexpression and the proliferating activity of the cancer cells determined by PCNA LI, between the young and elderly patients. The survival rate after curative resection was lower for the elderly compared with that for the young patients; hematogenous recurrence was higher in the former. CONCLUSIONS: The clinicopathological features of gastric carcinoma differed between the young and elderly patients, and these differences should be considered when age-oriented treatment is being designed.

Adult↗

PubMed1996

Transforming growth factor-beta 1 induces apoptosis in gastric cancer cells through a p53-independent pathway.

BACKGROUND: Apoptosis is induced by various anticancer agents or radiation through the tumor suppressor gene p53-dependent pathway and is also induced by other factors, including transforming growth factor-beta 1 (TGF-beta 1). In this study, the authors investigated whether TGF-beta 1 would induce apoptosis in gastrointestinal cancer cells, and its relation to the status of the p53 gene. METHODS: The induction of apoptosis by TGF-beta 1 was determined in 12 gastrointestinal cancer cell lines using DNA ladder formation. Status of the p53 gene was examined by sequencing of cDNA from p53 mRNA and expressions of TGF-beta 1 mRNA and TGF receptors I and II mRNAs were determined by Northern blot analysis and the reverse transcriptase-polymerase chain reaction analysis, respectively. RESULTS: Of 12 cell lines, wild-type p53 was present in 3 lines, point mutation was detected in 7 lines, and p53 mRNA was absent in 2 lines. TGF-beta 1 was expressed in all 12 lines, but both TGF receptors I and II were expressed in only 6 lines. Addition of TGF-beta 1 induced DNA ladder formation only in KATOIII cells, with deleted p53 mRNA, but expressed TGF receptors I and II. CONCLUSIONS: These findings show that TGF-beta 1 induces apoptosis in gastric cancer cells through TGF-beta receptors I and II and a p53-independent pathway.

Antineoplastic Agents↗

PubMed1996

Multidrug resistance-associated protein expression in clinical gastric carcinoma.

BACKGROUND: We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer. METHODS: In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was analyzed, and overexpression of the tumor suppressor gene p53 was investigated, immunohistochemically. RESULTS: Immunohistochemically detected MRP positive tumors were noted in 34 of 75 excised tumors (45%), and confirmed by RT-PCR. There was no significant relation between MRP expression and clinicopathologic features or prognosis. Positive p53 staining was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 negative ones (44%), and there was no significant correlation between MRP and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compared with MRP negative ones. A similar tendency was noted with VP-16. CONCLUSIONS: MRP expression relates to the chemosensitivity of tumor cells against some anticancer drugs and is independent of known factors related to the development, invasion, and metastasis of human gastric cancers.

ATP-Binding Cassette Transporters↗

PubMed1996

Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.

BACKGROUND: Several studies have proven the usefulness of microvessel quantification as a prognostic factor for patients with various malignant tumors. The aim of this paper was to clarify the relationship between microvessel density (MVD) as a parameter of tumor angiogenesis and liver metastasis in colorectal cancer. METHODS: A total of 175 patients with advanced colorectal cancer were evaluated (58 with concurrent liver metastases). Microvessel quantification was performed immunohistochemically, using monoclonal antibodies against endothelial protein Factor VIII-related antigen (F8RA) and against endothelial surface marker CD34. Finally, the relationship between MVD and liver metastasis was analyzed. RESULTS: A significant correlation was observed between MVD for F8RA and MVD for CD34 (n = 175, r = 0.9560, P = 0.0001). MVD in the tumors stained for F8RA ranged from 15.2 to 78.6 microvessels per x 200 field (mean 32.8 +/- 11.7), while the tumors with liver metastatic disease compared with the tumors without liver metastasis (F8RA; mean 36.1 +/- 11.3 vs. 31.2 +/- 11.5, P = 0.0090; CD34; mean 64.4 +/- 20.4 vs. 52.0 +/- 19.4, P = 0.0010). CONCLUSIONS: Microvessel quantification within a colorectal tumor using immunohistochemical staining methods has shown a significant correlation between MVD and liver metastasis. Tumors with a greater MVD may thus have a greater hematogenous metastatic propensity.

Aged↗

PubMed1996

Postoperative chemotherapy for colorectal cancer by combining 5-fluorouracil infusion and 1-hexylcarbamoyl-5-fluorouracil administration after curative resection.

BACKGROUND: Colorectal cancer is one of the major malignant diseases and, recently, its incidence appears to be increasing. Surgical resectability is an important prognostic determinant; however, recurrent tumors are commonly noted, even after apparently curative surgery. Because such metastatic disease cannot be cured, better adjuvant therapies are urgently called for. METHODS: We studied the effect of postoperative chemotherapy using 5-fluorouracil (5-FU) infusions and 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration for curatively resected Stage II to IV colorectal cancer. This study was prospectively randomized and controlled and 251 (93.3%) of 269 patients were determined to be candidates for statistical assessment. The inductive regimen for Group A included a total of 6 5-FU intravenous injections, 10 mg/kg, on postoperative days 0, 1, 2, 7, 8, and 9. For maintenance therapy, Group A also received oral HCFU, 300 mg daily for 52 weeks beginning 2 weeks after surgery. The regimen for Group B included only 5-FU injections of Group A. RESULTS: There were no differences in the prognostic factors or doses of 5-FU between Groups A and B. In addition, no difference was observed in the toxicity rate between the two groups. Group A, with 5-FU infusions plus oral HCFU administration, produced a reduction in the recurrence rate and a prolongation of the survival time for patients with rectal cancer. In a retrospective analysis, this protocol was also effective for patients with Stage III to IV, wall invasion-positive, and lymph node metastasis-positive colorectal cancers. CONCLUSIONS: This study suggests that the combination of 5-FU infusions and the continuous oral administration of HCFU is a reasonable therapeutic approach for patients with surgically resected colorectal cancer and a high risk of recurrence.

Adult↗

PubMed1996

Flavone acetic acid increases the cytotoxicity of mitomycin C when combined with hyperthermia.

Flavone acetic acid (FAA, NSC 347512) is known to selectively reduce tumor blood flow. Taking advantage of this pharmacodynamic effect, we have previously shown that FAA in combination with hyperthermia (HT) can produce a marked improvement in antitumor response in mice. In the present study, we investigated whether FAA could increase the cytotoxicity of mitomycin C (MMC), a bioreductive drug with selective cytotoxicity against hypoxic cells, under either normothermic or hyperthermic conditions. In vitro, the cytotoxicity of MMC against B16 melanoma cells was not enhanced with exposure to FAA at concentrations less than 100 microgram/ml, even when combined with HT (43 degrees C, 60 min). The cytotoxicity of MMC (1 microgram/ml) at pH 6.5, however, was enhanced by exposure of cells to hypoxia in combination with HT. In vivo, the tumor growth time, calculated as the time required to double the initial tumor volume, was 5.2, 6.8, 8.5, and 15.0 days with FAA (150 mg/kg) alone, MMC (4 mg/kg) alone, FAA + MMC, or FAA + MMC + HT (43 degrees C, 15 min) treatment groups, respectively. Antitumor response obtained in animals treated with FAA plus MMC with HT was clearly better than that obtained in any of the other groups. Scheduling of FAA, MMC, and HT was found to be important in producing optimal antitumor response. Administration of MMC (4 mg/kg) prior to FAA (150 mg/kg) and subsequent HT treatment was superior to administration of FAA before MMC. In an attempt to explain these findings, the influence of FAA on blood flow in skeletal muscle and in tumor was examined using a laser blood flowmeter. FAA administration to mice produced a 75% reduction in blood flow to the tumor for up to 2 h but had no detectable effect on normal skeletal blood flow. Our current explanation of the increased antitumor response achieved with the combination of MMC, FAA, and HT is as follows. The FAA-mediated decrease in blood flow to the tumor, when combined with HT, may produce sufficiently hypoxic conditions to significantly increase the antitumor efficacy of the bioreductive drug, MMC. We believe that clinical testing of this combined drug treatment with hyperthermia is warranted.

Animals↗

PubMed1996

Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence.

BACKGROUND: Even after curative resection of an early gastric cancer, some patients die of a recurrence. It is our view that patients with early gastric cancer who died of their disease had occult micrometastases in perigastric lymph nodes at the time of the original diagnosis. In an attempt to identify these micrometastases, lymph nodes dissected from early gastric cancer lesions were stained after operation with monoclonal antibody against cytokeratin, an essential constituent of the cytoskeleton of epithelial cells. METHODS: The 420 dissected lymph nodes from 34 patients with node-negative early gastric cancer who died of a recurrence were examined for the presence of tumor cells. We used immunocytochemical techniques and an antiserum to epithelial membrane antigen. The monoclonal antibody CAM 5.2 recognizes cytokeratin polypeptides (human cytokeratin numbers 8 and 18) commonly present in epithelial cells. Clinicopathologic characteristics and prognosis were determined for patients with cytokeratin-positive cells in the lymph nodes. RESULTS. Of 420 lymph nodes, 15 (3.6%) nodes and 23.5% (8 of 34) of the patients presented with cytokeratin-positive cells at the time of primary operation. The presence of cytokeratin positivity was not related to various clinicopathologic factors. The histologic stage of eight cytokeratin-positive cases was upstaged by the group of cytokeratin-positive lymph nodes from stage I to three of stage II, four of stage III, and one of stage IV, hematogenous recurrences were common, and the prognosis was poorer. CONCLUSIONS: Immunohistochemical techniques aid in identifying micrometastatic disease in lymph nodes missed in routine hematoxylin-eosin staining. Cytokeratin staining of the dissected lymph nodes is recommended to precisely determine tumor stage and prognosis for patients with early gastric cancer.

Adult↗

PubMed1996

Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis of gastric cancer.

Direct evidence of tumour seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap since it is a feature of epithelial cells that would not normally be present in bone marrow. The bone marrow of 46 patients with primary gastric cancer was examined for tumour cells, using immunocytochemical techniques and antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. The monoclonal antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no. 18) commonly present in epithelial cells. The expression of tumour-suppressor genes p53 and RB for the primary lesion was also determined using the monoclonal antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the time of primary surgery. The positive findings were related to the undifferentiated tissue type and to the prominent depth of invasion, but not to other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of invasion was limited to the mucosa. The metastatic potential to bone marrow did not relate to expressions of p53 and RB genes, or to the proliferating activity of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in bone marrow are indicative of the general disseminative capability of an individual tumour, this technique may be useful for identifying patients at high risk of metastasis from a gastric tumour.

Antibodies, Monoclonal↗

PubMed1996

Recurrences and related characteristics of gastric cancer.

We analysed data on 1117 patients with gastric cancer who were treated by curative resection. Attention was focused on invasion and a recurrence of the cancer. Based on a univariate analysis, death following a recurrence and prognosis were related to age of the patients, size of the tumour, tumour location, tumour tissue differentiation, growth pattern, depth of invasion, lymphatic and vascular invasion and lymph node metastasis. In proportion to the growth potential, determined by the level of proliferating cell nuclear antigen (PCNA) labelling, the death related to a recurrence was increased and the prognosis was poorer. Multivariate analysis showed that the three factors of serosal invasion, PCNA labelling index and lymph node dissection were independent prognostic factors. When sites of recurrence were analysed regarding each depth of invasion, haematogenous recurrence, in particular in the liver, occurred even in cases of an early invasion and many types of recurrences, including peritoneal recurrence, were noted in patients with an advanced state of invasion.

Adult↗

PubMed1996

Argyrophilic nucleolar organizer region in endoscopically obtained biopsy tissue: a useful predictor of nodal metastasis and prognosis in carcinoma of the stomach.

BACKGROUND: Argyrophilic nucleolar organizer region (AgNOR) staining is a simple and economical technique for investigating proliferative activity. We examined AgNOR measured in biopsy specimens of carcinoma of the stomach in humans. STUDY DESIGN: Argyrophilic nucleolar organizer region staining was done on 76 biopsy specimens and corresponding resected cancer tissues. All estimations were made at the invasive tumor margin. RESULTS: Of the 76 cases, intratumoral heterogeneity of AgNOR count (more than 1.0 difference) between superficial and deep layers was recognized in six (7.9 percent) cases, all of which were advanced. In biopsy specimens, the AgNOR count ranged from 1.68 to 7.74 (mean, 3.79). A significant correlation was found between AgNOR counts of biopsied materials and those of resected specimens, both in early and advanced cases. Tumors with a high AgNOR count (greater than or equal to 3.79) were more likely to be of a larger size (p < 0.01), to have metastasized to lymph nodes (p < 0.01), and to be associated with a lower survival rate (p < 0.05) compared to tumors with low AgNOR counts. CONCLUSIONS: Estimating the AgNOR count in endoscopically biopsied specimens at the margin of invasive gastric carcinoma is useful for assessing nodal metastasis and clinical prognosis. These preoperative estimates may aid in tailoring the operative procedure and administrating adjuvant therapy.

Adult↗

PubMed1996

[Advances in the treatment of colorectal cancer].

Colorectal cancer is one of the most serious diseases of our time. Recent progress in its treatment is reviewed in this paper. There are many approaches for treating colorectal cancer; extended surgery to function-preserving surgery. The aim of surgical treatment is to excise the tumor completely, so extended surgery has been performed for curative resection of colorectal cancer. However, the quality of life (QOL) of the patients has been extremely impaired. In recent years, surgical treatments for avoiding colostomy, and urinary and sexual difficulties have been widely carried out, and QOL of the patients could be maintained in the postoperative period. Stage-oriented therapy is accepted as the concept of surgical treatment of colorectal cancer. For further improving the clinical results of colorectal cancer, we advocated "type-oriented therapy" which is based on the biological characteristics of colorectal cancer, by determining i.e., p53 abnormalities of cancer cells, serum p53 antibodies, micrometastasis in the bone marrow and/or sensitivity to anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Growth pattern and p53 overexpression in patients with early gastric cancer.

BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects well biologic characteristics of the tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with a superficially spreading (Super) type. Abnormality of the p53 suppressor gene plays an important role in alteration of cells leading to development of cancer. p53 point mutations are present even in an early stage of carcinoma. METHOD: In 159 patients with early gastric carcinoma, overexpression of p53 was studied immunohistochemically, using a monoclonal antibody (PAb 1801), and the relationship between growth pattern and p53 overexpression was analyzed. RESULTS: Early gastric carcinoma was grouped into 43 of the Super type, 37 of the expansively penetrating growth (Pen-A) type, 16 of the infiltratively penetrating growth (Pen-B) type, and 63 of the Small mucosal type limited to the mucosal layer. The Pen-A type tumors were characterized by the highest incidence of p53 positive expression and poorest postoperative course. Between the Pen-A type and the Super type, there were significant differences in the incidence of the p53 positive expression (43% vs. 16%), the frequency of recurrence (16% vs. 7%), and disease free interval (574 days vs. 2926 days). CONCLUSION: The authors' observations show that the p53 gene plays an important role in expansion of gastric carcinoma, even in the early stages.

Gene Expression↗

PubMed1995

Gastric carcinoma in patients over 70 years of age.

The clinicopathological features and prognosis of gastric cancer in 344 patients aged 70 years or older who underwent gastrectomy between 1965 and 1990 were determined. Over the years the mean size of the tumour decreased, differentiated tumour tissue was more common, depth of penetration was less prominent, lymphatic and vascular involvement was less frequent, and the rate of lymph node metastasis and peritoneal dissemination decreased. Extensive lymph node dissection was more frequently carried out and the rate of curative resection rose. Survival rates improved with early detection of gastric cancer and there was no increase in operative morbidity and mortality rates. As age alone is not a contraindication to surgery for patients with gastric carcinoma, early detection of the lesion and surgical treatment are expected to increase the survival of elderly patients with this malignancy.

Aged↗

PubMed1995

Macroscopically node-negative but histologically node-positive gastric carcinoma.

The features of macroscopically node-negative but histologically node-positive (N(-) n(+)) tumours were examined in 521 patients undergoing curative surgery for gastric carcinoma. Of 240 histologically node-positive tumours, 62 (26 per cent) were N(-) n(+). The 10-year survival rate of patients with N(-) n(+) tumour at 66 per cent was worse than that of those with histologically node-negative tumour (91 per cent) (P < 0.01) but better than that of patients with macroscopically and histologically node-positive tumour (40 per cent) (P < 0.01). N(-) n(+) tumour was characterized by size less than 5 cm (47 per cent), invasion not beyond the muscularis propria (53 per cent), lymph node metastasis limited to group 1 nodes (76 per cent), number of positive nodes fewer than seven (90 per cent) and disease of stage II (52 per cent). The survival of patients with N(-) n(+) tumour was determined by the number of positive nodes and stage of disease. N(-) n(+) tumours are associated with a better outcome, owing to less progressive disease, and the number of positive nodes is a prognostic indicator.

Adenocarcinoma↗

PubMed1995

Surgical treatment of patients with gastric carcinoma and duodenal invasion.

We retrospectively examined the extent of invasion of gastric cancer with duodenal involvement in order to design pertinent surgical procedures that may lead to a better prognosis. Examinations were made on excised tissues from 650 patients who underwent gastrectomy for adenocarcinoma in the gastric antrum. In 95 patients, the cancer cells extended to beyond the pyloric ring. Spread into the duodenum was limited to within 2 cm in 76% of the patients and to within 3 cm in 81%. In addition to high rates of metastasis in group 1 and 2 lymph nodes, some group 3 lymph nodes also were involved, and more frequently so in cases with duodenal invasion than in those without such invasion (P < 0.01). The 5-year survival rate for patients with duodenal invasion was 35.4% when a curative resection was done. For patients with advanced adenocarcinoma with duodenal invasion, gastrectomy with resection of 3-4 cm of the duodenum and dissection of group 1, 2, and 3 lymph nodes were recommended.

Adenocarcinoma↗

PubMed1995

Macroscopic intraoperative diagnosis of serosal invasion and clinical outcome of gastric cancer: risk of underestimation.

Data on 715 Japanese patients with gastric cancer were studied retrospectively with regard to the relationship between macroscopic and microscopic diagnoses of serosal invasion and clinicopathological factors affecting the accuracy of the macroscopic diagnosis. Although there was no macroscopic evidence of serosal invasion intraoperatively (S0 or S1), there was histological evidence of cancer cells on the serosal surface in 69 patients (9.7%). In these serosal invasion-positive cases, the tumors were larger; were located more commonly in the upper third, lesser and greater curvatures of the stomach; were Borrmann type 3 or type 4 tumors, and of an undifferentiated histologic type with an infiltrative growth pattern more commonly, and had more extensive lymphatic and vascular vessel invasion and lymph node metastasis (P < 0.01). Total gastrectomy was done more often for the serosal invasion-positive group, but the extent of lymph node dissection was comparable. Cases of a noncurative resection because of a positive surgical margin were more frequent in the serosal invasion-positive group (8/69 vs. 14/646, P < 0.01), and most had undifferentiated and infiltrative cancers. The 10-year survival rates were 49.2% and 85.5% for patients with and without serosa invasion, respectively. These findings clearly show that the serosal surface, especially in cases of the undifferentiated or infiltrative type of gastric cancer, must be closely inspected intraoperatively.

Aged↗

PubMed1995

Absorption cytometric DNA analysis of sections of gastric carcinomas and a comparison with cytofluorometry of single-cell suspensions and flow cytometry.

Measurements were made of cellular deoxyribonucleic acid (DNA) content in paraffin-embedded materials from 44 gastric carcinomas, using three different methods; static cytometric light absorbance technique using tissue sections (SCM-abs), static cytometric fluorescence technique using single-cell suspensions (SCM-flu), and flow cytometry (FCM). The DNA ploidy determined by SCM-abs was grouped into low or high ploidy according to dispersion on the DNA histogram, and the DNA ploidy determined by SCM-flu and FCM was grouped into diploidy or aneuploidy, according to the peak DNA value. Accord between SCM-abs and SCM-flu or between SCM-abs and FCM was confirmed when low ploidy by SCM-abs showed diploidy by SCM-flu or FCM and high ploidy by SCM-abs showed aneuploidy by SCM-flu or FCM. An incomplete but good accord of DNA ploidy was obtained with these methods.

Absorption↗