Minoru Niimoto

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 < 0.05) and lymphatic invasion (P < 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P < 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.

Expression of epidermal growth factor, transforming growth factor-α and their receptor genes in human gastric carcinomas ; implication for autocrine growth

ABSTRACT The expressions of mRNA for epidermal growth factor (EGF), transforming growth factor‐α (TGF‐α) and EGF receptor (EGFR) genes were examined in 7 human gastric carcinoma cell lines and 15 gastric carcinoma tissues and the corresponding normal mucosas. All of the gastric carcinoma cell lines expressed mRNA for EGFR and TGF‐α genes. TMK‐1 and MKN‐28 cells also expressed EGF mRNA. Production of EGF, TGF‐α and EGFR protein by gastric carcinoma cell lines was also confirmed by EGF and TGF‐α specific monoclonal antibody binding. As for surgical specimens, EGFR and TGF‐α mRNA were detected at high levels in all the tumor tissues. Interestingly, EGF mRNA was detected in 5 (33.3%) of the 15 gastric carcinomas but it was not detected in normal tissues. Moreover, anti‐EGF and anti‐TGF‐α monoclonal antibodies inhibited the spontaneous 3H‐TdR uptake by gastric carcinoma cells. These results suggest that EGF and/or TGF‐α produced by tumor cells act as autocrine growth factors for gastric carcinomas.

Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years.

In order to evaluate the combination of immunochemotherapy with mitomycin C (MMC), futraful (FT) and PSK, as an adjuvant to surgery for curatively resected gastric cancer, a randomized controlled study by the sealed envelope method was performed with the participation of 97 hospitals in the Kyushu and Chugoku districts of Japan. The MMC+FT+ PSK group showed a significant increase in 5 year survival from the other groups (p<0.05). Moreover the survival rate was significantly higher in the MMC+FT+PSK group than in the MMC+FT group (p<0.01). According to the analysis on stratification, the MMC+FT+PSK group showed the best survival rate in cases with positive lymph node metastases, positive serosal invasion and positive lymph node metastases plus serosal invasion, and in cases of undifferentiated carcinoma by histological type and in those with a preoperative positive PPD reaction (p<0.01 or p<0.05). Thus, the combination of MMC, FT and PSK was indicated to be useful as an adjuvant immunochemotherapy for those patients with gastric cancer submitted to curative resection.

Post-operative long-term adjuvant immunochemotherapy with mitomycin-C, PSK and FT-207 in gastric cancer patients.

Long-term adjuvant immunochemotherapy carried out on the gastrectomized patients with stomach cancer was reported. The protocol comprises the administration of large-dose of Mitomycin-C (20+10) mg just after gastrectomy and the long-term administration of PSK, FT-207 or (PSK+FT-207). Almost no side effects were observed. According to the studies on the immunological parameters, the increased reactions in PPD skin test and lymphocyte blastogenesis induced by PHA and PWM were observed remarkably in group (P+F) 3 or 6 months after gastrectomy. As for the survival rate, group (P+F) showed the most preferable results at one year in stage IV, at two years in stage III and at three years in all the stages, respectively after gastrectomy.

Detection of androgen receptors in human esophageal cancer

The incidence of esophageal cancer is much higher in men than in women and the prognosis is generally worse in men than in women. This seems to depend on the difference in the hormonal environments of the patient. In this paper, androgen receptors (AR) were measured in 21 cases of human esophageal cancer. Of these, two cases of esophageal cancer xenografts implanted into nude mice were AR positive. In EH-1, an established cell line from human esophageal cancer, the number of binding sites was increased and tumor growth was enhanced by testosterone administration. On the other hand, the number of binding sites was decreased and tumor growth was suppressed by castration. The administration of estrogen, however, did not inhibit tumor growth.

Reconstruction of full-thickness chest wall defects using rectus abdominis musculocutaneous flap: A report of fifteen cases

In 15 patients chest walls were excised because of recurrent breast cancer, radiation ulcer, or rib tumor. In most cases the full-thickness defect of the chest wall was about 10 × 10 cm. Reconstruction was performed using only a rectus abdominis musculocutaneous flap. No patient developed circulation problems in the flap or severe flail chest, and we had successful results in all our cases. These results show that the rectus abdominis musculocutaneous flap is quite effective and safe to use in the reconstruction of chest wall defects.

Lymphocyte responsiveness to phytohemagglutinin (PHA) and serum inhibitory effect in patients with gastric cancer

The in vitro lymphocyte response to PHA was determined in patients with gastric cancer in various stages prior to the sugical treatment. The lymphocyte responsiveness in the presence of homologous pooled AB serum in patients of stages II, III and IV were markedly reduced as compared with that in healthy controls (stages II, III; p<0.05, stage IV; p<0.01). Inhibition of normal lymphocyte responsiveness to PHA by serum from patients in stages III and IV were statistically significant as compared with that in stage I (stage III; p<0.05, stage IV; p<0.01). Serum inhibitory effect on the normal lymphocyte responsiveness was significant only in the advanced stage. It was concluded that the suppression of the immune response in the early stage of gastric cancer was mainly due to the impairment of lymphocyte itself, which advanced with the progress of the stage and was modified by the serum inhibitory effect in advanced stages. In patients with advanced cancer, the higher was the lymphocyte responsiveness to PHA and PWM prior to the initial treatment, the more effective was the immunotherapy. This shows that the indication of the immunotherapy in patients with advanced cancer could be initiated. Furthermore, the correlation between the lymphocyte responsiveness to PHA and the clinical results of immunotherapy was discussed.

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 (Chisquare test, p<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<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<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.

Bypass operation for advanced esophageal cancer —An analysis of 93 cases—

From 1973 to 1987, 235 patients with esophageal squamous cell carcinoma were treated at Hiroshima University. Of these patients, 121 (51.5 per cent) were submitted to esophagectomy, 93 (39.6 per cent) to bypass surgery and 21 (8.9 per cent) to either exploratory or no surgery. In this report, the 93 cases who underwent bypass surgery were analysed. Ten patients died within thirty days after their operation (10.8 per cent) and there were 33 cases of hospital death (35.5 per cent). Following the bypass surgery, 49 (59.0 per cent) cases were able to tolerate over 50 per cent of their normal oral intake and 22 cases (26.5 per cent) were able to tolerate between 25 per cent and 50 per cent. For twelve cases (14.6 per cent), however, oral ingestion proved impossible up until the time of death due to such complications as leakage. The overall survival rates were 44.3 per cent at 6 months, 12.7 per cent at 1 year and 2.8 per cent at 5 years, respectively. Two cases survived for over 5 years. Hyperthermia was applied in combination with chemotherapy from 1981, however, no case survived for over one year without radiation therapy. Recently, radiation plus hyperthermia is being performed in combination with immunochemotherapy.

Mitomycin C plus carmofur (HCFU) adjuvant chemotherapy for noncuratively resected cases of colorectal carcinoma (interim report).

In order to examine the efficacy of adjuvant chemotherapy employing Mitomycin C (MMC) and carmofur (HCFU) for patients with noncuratively resected colorectal carcinoma, a cooperative study was performed by 54 institutions in the Kyushu and Chugoku areas in Japan. The prospective randomized controlled study consisted of two groups, one receiving only MMC and the other receiving MMC as well as HCFU. Out of an original total of 200, 170 cases were evaluable. Concerning the 30-month survival rate, a better result was observed in the MMC+HCFU group than in the MMC only group (Z-test: p<0.05). Significantly better survival rates were obtained in those cases with disseminating peritoneal metastasis, hepatic metastasis and Stage V cancer in the MMC+HCFU group as when compared with the MMC only group (generalized Wilcoxon test: p<0.05). No significant side effects due to the combined administration of HCFU were recognized. The combined administration of MMC and HCFU were recognized. The combined administration of MMC and HCFU was suggested to be a safe and effective adjuvant chemotherapy in noncuratively resected cases of colorectal carcinoma.