[Inhibitors of growth factor functions, possible antineoplastic agents].
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Biomedical subjects
M Toi
Publications and source records attributed to M Toi.
Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer.
Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.
Antigens, Neoplasm↗
Expression of human epidermal growth factor and its receptor in esophageal cancer.
The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer.
Carcinoma, Squamous Cell↗
Growth fractions of breast cancer in relation to epidermal growth factor receptor and estrogen receptor.
Growth fractions detected by a monoclonal antibody, Ki-67, were examined in 40 human breast cancer tissues and the results compared with the immunocytochemical reactivities of epidermal growth factor receptor (EGFR) and estrogen receptor (ER). The proportion of proliferating cells displaying Ki-67 positive staining was significantly higher in the EGFR positive tumors than in the EGFR negative tumors (p less than 0.01). The average percentage of Ki-67 positive cells in the EGFR positive tumors was 19.9 per cent, whereas that in the EGFR negative tumors was 8.0 per cent. By contrast, an inverse relationship between the proportion of proliferating cells and ER positive cells detected by anti-ER monoclonal antibody was observed. This data indicated the difference in growth fractions with relation to the EGFR and ER status of breast cancer.
Breast Neoplasms↗
Nuclear DNA content in breast carcinoma with special reference to the parameters of malignant potentiality.
Nuclear DNA ploidy pattern was examined in 22 breast carcinomas with a tumor mass of up to 2.2 cm and compared with the clinical and histological parameters of the malignant potentiality of breast carcinomas. The 22 carcinomas were divided into 11 aneuploid and 11 near-diploid carcinomas. It was found that the histological type, histological grade, nuclear grade, mitotic index and lymphatic invasion were either only slightly, or not correlated at all with the DNA ploidy pattern. Nevertheless, lymph node metastasis and negative estrogen receptor status was more frequently seen in the patients with aneuploid carcinoma than in those with near-diploid carcinoma.
Breast Neoplasms↗
Prospective randomized controlled study on bestatin in resectable gastric cancer--third report.
The efficacy of Bestatin as adjuvant immunochemotherapy for patients with resectable gastric cancer was investigated. Ninety-six patients with similar background factors were randomized into two groups; a control group and an experimental group, the patients in the experimental group receiving a daily oral dose of 60 mg Bestatin over a long period. All 96 patients were treated with a bolus intravenous injection of mitomycin C (MMC) plus oral administration of tegafur (FT-207, FT). The survival rate of the patients in the MMC + FT + Bestatin group was more favorable than that of the patients in the MMC + FT group, but the difference was not statistically significant. The survival rates of the MMC + FT + Bestatin group patients in the stratification of stage III + IV and positive histological serosal invasion, ps(+), were significantly superior to those of the MMC + FT group patients (Logrank test: p less than 0.05). Moreover, in patients with positive histological serosal invasion, the recurrence of peritoneal dissemination was significantly suppressed in the MMC + FT + Bestatin group.
Adjuvants, Immunologic↗
Antineoplastic effect of erbstatin on human mammary and esophageal tumors in athymic nude mice.
The growth of MCF-7, a human mammary carcinoma, in athymic nude mice was inhibited by intraperitoneal administration of erbstatin for 14 days in combination with an iron chelator, foroxymithine, which inhibits the decomposition of erbstatin. Another human mammary carcinoma, Br-10, was not affected. Foroxymithine alone had no anti-tumor activity. In four esophageal tumors, erbstatin retarded tumor growth. There were no side-effects in any erbstatin-treated group. Levels of epidermal growth factor receptors were not changed throughout treatment with erbstatin at any dose. Erbstatin, a tyrosine kinase inhibitor, may have an antineoplastic effect against human mammary and esophageal tumors.
Animals↗
[The expression of NCC-ST-439, a tumor marker, in human breast cancer patients].
The expression and serum level of NCC-ST-439, a tumor marker, has been investigated in 20 primary and 28 recurrent breast cancer patients, and the positive rate was found to amount to 21.1% in primary cases and 42.9% in recurrent cases, respectively, thereby indicating a positive correlation between the expression of NCC-ST-439 and the progression of the diseases. The accordance rate between NCC-ST-439 and CEA was 64.6%; in contrast, the rate between NCC-ST-439 and CA 15-3 was 82.1%, suggesting a difference in specificity against tumor between NCC-ST-439 and CEA. The change in the serum level of NCC-ST-439 in recurrent cases clearly correlated with the effectiveness of the therapy. These findings suggest that measurement of the NCC-ST-439 level, especially in combination with the CEA level, may be useful for the early detection and the monitoring of relapses in breast cancer patients.
Antigens, Tumor-Associated, Carbohydrate↗
Immunocytochemical and biochemical analysis of epidermal growth factor receptor expression in human breast cancer tissues: relationship to estrogen receptor and lymphatic invasion.
Expression of epidermal growth factor receptor (EGFR) and estrogen receptor (ER) was examined by an immunocytochemical assay (ICA) using serial cross-sections of human breast cancer tissues. Immunocytochemical results were compared with those obtained by biochemical competitive binding assay and with histological lymphatic invasion. EGFR was evaluated as positive in 17 (34.0%) out of 50 primary tumors by ICA. A significant inverse relationship of the proportion of stained cells between EGFR and ER was demonstrated. In more than one-half of the tumors that were positive for both EGFR and ER, these 2 receptors were inversely stained in relation to the distribution. In ER-negative cells, EGFR expression was more marked than in ER-positive cells. Biochemical data confirmed the immunocytochemical results, pointing to an inverse relationship between EGFR and ER content. EGFR status correlated well with the degree of lymphatic invasion but not with the number of lymph nodes with metastases.
Breast Neoplasms↗
The acceptable delay between biopsy and radical mastectomy in breast cancer patients.
The effects on the prognosis of breast cancer, of the delay between biopsy and radical mastectomy were studied in 394 patients. No delay had been experienced by 148 cases (no delay group), no biopsy had been performed in 166 cases (no biopsy group) and 80 cases had experienced a delay of 1 day or longer after having had a biopsy taken at a different institution (delay group). The recurrence rate of the no delay group was 10.8 per cent (16/148), whereas that of the delay group was 18.8 per cent (15/80). The relapse free survival rate of the no delay group was superior to that of the delay group (Kaplan Meier's method: p less than 0.05). The delay group was further divided into two groups according to the duration of delay, namely: a group whose delay was less than 7 days and another whose delay was longer than 8 days. There was no significant difference between the relapse free survival rates of the no delay group and the less than 7 days group, however, a significant difference was observed between the no delay group and the longer than 8 days delay group (p less than 0.05). The acceptable delay between biopsy and radical mastectomy may therefore be concluded as less than 7 days.
Biopsy↗
The discrepancy between immunocytochemical and biochemical assay of estrogen receptor in breast cancer patients treated by endocrine therapy.
Estrogen receptor (ER) expression was investigated by ER-immunocytochemical assay (ICA) and the dextran coated charcoal (DCC) method in 10 recurrent or primary-advanced breast cancer patients treated with endocrine or chemo-endocrine therapy. In 6 of these 10 patients, ER was examined both before and after treatments by the 2 methods. ER contents measured by the DCC method were found to be decreased after treatments, however, no change in the immunoreactivities of ER-ICA was observed. In the remaining 4 patients, the ER of new lesions refractory to endocrine or chemo-endocrine therapy was examined. ER status was determined as negative in 3 of the 4 patients by the DCC method, whereas by ER-ICA, the proportion of ER stained cells was about 70 per cent, those cells being diffusely distributed in the section. A discrepancy between ER-ICA and the DCC method was thus demonstrated in breast cancer patients treated by endocrine therapy.
Adrenalectomy↗
Involvement of the nipple in early carcinoma of the breast.
Cancerous involvement of the nipple and subareolar tissue (nipple and areolar complex, NAC) was confirmed histopathologically in 24 of 65 patients with gross tumors measuring 2.5 centimeters or less. Erosion of the nipple as a clinical manifestation of involvement of NAC was seen in only two patients. The other 22 were all subclinical. The histologic form of involvement of NAC included intraductal-1 in 19 patients, stromal in one patient, lymphatic in two patients and intraductal-1 as well as stromal in two. Stepcut and serial observation of the whole breast suggested that both intraductal spread and stromal invasion of carcinoma were continuous processes from the underlying tumor. Involvement of NAC was more frequent if the patient was aged 50 years or less and if the proximity of the tumor to the nipple was less than 4 centimeters, regardless of the size of the tumor.
Adult↗
[Expression of the epidermal growth factor receptor in esophageal cancer].
The level of epidermal growth factor receptor (EGF-R) has been measured by a competitive binding assay in 45 human esophageal cancer tissues. The EGF-R level in the esophageal cancer tissue was found to be significantly higher than in specimens of gastric or colonic cancer. No correlation was observed, however between the EGF-R level and the pathological findings, such as the depth of the tumoral invasion, the degree of lymph node metastasis, and the histologic staging. Even so, the prognosis of the patients with a high level of EGF-R of more than 50 fmol/mg of protein was significantly worse than those with a low level of EGF-R and less than 50 fmol/mg of protein (p less than 0.01). Further, according to an immunohistochemical assay using anti EGF-R monoclonal antibody, EGF-R was focally stained in the basal cells and in the parabasal cells of normal esophageal mucossa, but was diffuse in almost all tumor cells of ane esophageal cancer. Thus, a good relationship with the quantitative level of EGF-R and its immunoreactivities was demonstrated, indications that EGF-R plays an important role in tumor progression and appears to be a useful prognostic factor in cases of esophageal cancer.
Binding, Competitive↗
[Combination chemotherapy of CPM-MTX-5-FU in non-resectable and recurrent cancer patients].
Fifty-two non-resectable and recurrent cancer patients with prior treatment, were entered in this study; 1 esophageal, 33 gastric, 1 duodenal, 4 colorectal, 2 pancreatic, 2 bile duct, and 9 breast cancer. The protocol of this therapy was as follows: On day 1, 500 mg/body cyclophosphamide (CPM) was administered by drip infusion, and on day 2, 200 mg/m2 methotrexate (MTX) was infused intravenously for 30 min; immediately after, 500 mg/body 5-fluorouracil (5-FU) was injected by bolus infusion for 5-10 min. On day 3, 24 hours after MTX administration, leucovorin rescue was added. This combination chemotherapy was repeated every two weeks. As a result, 35 of 52 patients were evaluable and the response rate (CR + PR) was investigated; 2/21 (9.5%) for gastric, 2/7 (28.6%) for breast, and 0% for miscellaneous. As complications for side effect, general fatigue, anorexia, nausea, vomiting and stomatitis were observed symptomatically, and leukopenia and thrombocytopenia were recognized in laboratory data as dose limiting factors.
Anorexia↗
Immunocytochemical study on the variation in estrogen receptors of primary and nodal metastases of breast cancer.
The variation in estrogen receptors (ER) between primary and regional nodal metastatic lesions was examined by an estrogen receptor immunocytochemical assay (ER-ICA) in 25 mammary carcinoma patients. The ER status was evaluated in terms of the percentage of ER positive stained cells, staining intensity and distribution of those stained cells. The overall ER status was consistent in both sites, however, the percentage of ER positive cells and the staining intensity were not always consistent. A decrease in the percentage of ER positive cells and staining intensity was demonstrated in the nodal metastatic lesions of 4 and 3 cases out of a total 14 ER positive cases, respectively. The mean percentage of ER positive cells in the nodal metastatic lesions was 57 per cent compared with 73 per cent in primary lesions. Thus, a tendency of both the percentage of ER positive cells and the staining intensity to decrease in nodal metastases as when compared with primary lesions in breast cancer was demonstrated.
Antibodies, Monoclonal↗
[Effects of high-dose medroxyprogesterone acetate in advanced breast cancer, with special reference to prior endocrine therapy and hormone receptors].
Forty-six patients with advanced breast cancer were treated orally with high-dose medroxyprogesterone acetate (MPA), and a 28% (2 CRs, 11 PRs) response rate was obtained. The patient groups that showed a favorable response to MPA were as follows: patients in a postmenopausal state, with soft tissue or bone metastases, with slow-growing tumors, without prior therapy or with good response to prior endocrine therapy, and with positive estrogen (ER)- and/or progesterone (PgR) receptors. Six of 10 patients who had responded to prior endocrine therapy responded to MPA, while only 2 of 23 who had not responded to prior endocrine therapy showed a good response to MPA. There was a significant difference in response to MPA between patients with positive ER or PgR and those with negative ER or PgR tumors. The ER detected in primary or initially relapsed tumors correlated well with the effects of MPA given as a 2nd-line endocrine therapy for advanced breast cancer. The possible roles of MPA in the treatment of advanced breast cancer were discussed.
Administration, Oral↗
[Comparative study on estrogen receptor, epidermal growth factor and epidermal growth factor receptor using immunocytochemical and biochemical assays in breast cancer].
Estrogen receptor (ER), epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were examined by immunocytochemical and biochemical assays in 86 breast carcinomas. The following results were obtained. 1. ER was stained in cellular nuclei by immunocytochemical assay using anti-ER monoclonal antibody. ER positive stained tumor cells were distributed in the various patterns. 2. Immunocytochemical analysis of ER was evaluated with the percentage of ER positive cells and the staining intensity. ER values between immunocytochemical and biochemical assays accorded in 79 out of 86 cases (91.9%). Significant correlation was obtained in both assays (p less than 0.01). A high tendency of the percentage of ER positive cells was demonstrated in PgR positive cases. 3. EGFR was evaluated as positive in 12 out of 38 cases (31.6%) by immunocytochemical assay and in 13 out of 38 (34.4%) by biochemical competitive binding assay using 125I labeled EGF, respectively. A significant inverse relationship was obtained between ER and EGFR values (p less than 0.05). 4. EGF was evaluated as positive in 22 out of 38 cases by immunocytochemical assay. EGF expression was observed in all EGFR positive tumors. Compared with ER and EGF staining, the percentage of ER positive cells was higher in EGF negative tumors than in EGF positive ones (p less than 0.05).
Breast Neoplasms↗
[Comparative study of estrogen receptor assays between immunocytochemical assay using monoclonal antibody and the dextran- coated charcoal method].
Estrogen receptor (ER) was measured by the estrogen receptor-immunocytochemical assay (ER-ICA) using monoclonal antibody in 36 mammary carcinomas. Simultaneously, ER and progesterone receptor (PgR) were measured by the dextran coated charcoal (DCC) method. In ER-ICA, tumor cells with estrogen receptors were histologically observed. The proportion of ER-positive tumor cells among tumor tissues and the levels of staining intensity were also examined. Results were compared to those obtained by the dextran coated charcoal (DCC) method. Tumors were evaluated as ER-ICA-positive when they contained more than 10% ER-positive cells. ER at a level of more than 5.0 fmol/mg protein was evaluated ER-positive and PgR at more than 5.0 fmol/mg protein as PgR-positive by the DCC method. Twenty-one out of 24 ER-ICA-positive tumors were ER-positive by the DCC method, and 11 out of 12 ER-ICA-negative tumors were ER-negative by the DCC method. Correlation of ER-ICA and ER by the DCC method was 88.9%. There were 11 PgR-positive tumors, and all were included among ER-ICA-positive tumors which had a high proportion of ER-positive cells and high staining intensities.
Antibodies, Monoclonal↗