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Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 145 records · Page 8Linked to original sources

[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↗

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.

Adult↗

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.

Aged↗

The histological assessment and evaluation of a 4 day subrenal capsule assay by the percentage inhibition of DNA/protein.

A four day subrenal capsule assay was investigated in order to determine its ability to clinically predict tumor chemosensitivity. To establish more objective and accurate evaluation criteria, a histological assessment and measurement of the DNA and protein content of excised tumor implants was conducted in ddY mice. The histological studies provided qualitative results concerning the percentage of cancer cells in the xenograft, the number of mitoses, the amount of necrosis, and the extent of lymphocytic infiltration. The DNA content was measured by a modified version of the Schmidt-Thannhauser-Schneider method and the protein content was estimated using the Bio-Rad protein assay. The percentage of cancer cells in the xenograft correlated poorly with the relative increase in tumor size, weight and the percentage inhibition of DNA/protein (per cent DNA/protein), however, the per cent DNA/protein correlated well with the clinical effects in 85.7 per cent of the tumors studied. Moreover, the histological assessment information was only consistent with those results obtained for per cent DNA/protein in the control group.

Animals↗

Primary malignant melanoma of the esophagus--a case report.

An unusual case of primary esophageal melanoma is reported herein. A 68 year old man who had experienced occasional dysphagia for about one month without suffering any weight loss was admitted to our department. An esophagogram revealed two lobulated masses and esophagoscopy showed a pigmented tumor in one of the masses. Curative surgery was thus performed through a right thoracotomy. The macroscopic appearance of the resected specimen was very unusual and it was subsequently proven to be primary malignant melanoma of the esophagus by histological examination. Postoperatively, cyclophosphamide and interleukin-2 were administered intravenously, followed by lymphokine-activated killer therapy. However, multiple liver metastases were found on a CT scan, 3 months after the operation and he died about 1 month later. The operative indications for primary malignant melanoma of the esophagus are discussed in this report.

Aged↗

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↗

Blocking of lymphocyte surface binding sites for the soluble suppressor factor by protein-bound polysaccharide, PSK.

The ability of protein-bound polysaccharide (PSK) to block the suppressive activity of soluble suppressor factor (SSF) was investigated. The suppressive activity of SSF derived from U-937 cells on phytohemagglutinin (PHA)-induced lymphocyte proliferative (LP) response was significantly reduced in the presence of PSK. The release of SSF was not inhibited by the treatment of U-937 cells with PSK. The suppressive activity of SSF on LP response to PHA was significantly decreased by the pretreatment of responder lymphocytes with PSK. Studies to determine lymphocyte receptor activity were performed. PSK competed with wheat germ agglutinin (WGA) which recognized the same receptor as SSF on the surface of the lymphocyte. Neither PSK nor serum competed with anti-CD4 monoclonal antibody. Thus, PSK may inhibit SSF-mediated suppression by competing for specific binding sites on the surface of responder lymphocytes.

Antibodies, Monoclonal↗

[Submucosal injection of lipiodol-bleomycin in esophageal cancer].

Submucosal injection of Lipiodol-bleomycin (BLM) for esophageal cancer is complementary to CT scan in preoperative determination of the depth of the cancerous invasion in the esophageal wall. This procedure was performed not only for diagnosis but also as a preoperative therapy in 109 cases with esophageal cancer in Hiroshima University Hospital. The Lipiodol-BLM suspension was prepared by mixing 45 mg BLM and 5 ml Lipiodol on a clean bench. The mixture was usually injected into the submucosal layer of the esophagus using fiberscopy 12 days before the operation. BLM concentration was measured in the primary tumor, normal esophageal tissue around the tumor and regional lymph nodes in the specimen in 14 cases. As a result, a low level of BLM had been maintained in these tissues for a long time. The concentration of the primary tumor was 4 times higher than that of the normal esophageal tissue. In order to predict the side effects of BLM, such as pulmonary fibrosis, the change in serum BLM level was measured in 12 cases. Serum BLM decreased to an unmeasurable level 24 hours after the injection. Thus, the submucosal injection of lipiodol-BLM for esophageal cancer seems to be promising for a targeting cancer chemotherapy.

Bleomycin↗

[Clinical efficacy of LAK cell adoptive immunotherapy in advanced cancer patients].

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange was investigated as protocol 1 in 24 patients with advanced cancer. For the development of protocol 1, AIT in combination with plasma exchange, OK-432, interleukin-2 (IL-2) and cyclophosphamide was performed as protocol 2, in which LAK cells, OK-432 and IL-2 were administered through the catheter located in the hepatic or bronchial artery. The clinical efficacy of protocol 1 was found in patients with pleural effusion and metastasis to the lung or liver and resulted in 4 partial responses (20%) and 1 minor response of 20 evaluable cases. On the other hand, that of protocol 2 did 1 partial response (20%) in 5 cases. In vitro cytotoxic activity against either Daudi or K 562 tumor cells of peripheral blood lymphocytes from patient given intraaorta administration of OK-432 and IL-2 was tended to increase to be higher than that from nontreated patients. Postoperative immunodepression in esophageal cancer was blocked by AIT, suggesting the usefulness of AIT as a postoperative adjuvant immunotherapy. Thus, target organ of AIT should be limited for better therapeutic effect and the superiority of local AIT in combination with biological response modifiers may be indicated.

Aged↗

[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↗

[Surgical stress and immunosuppression in cancer patients].

The immunosuppression caused by surgical stress in cancer therapy may affect the prognosis of patients by enhancing the residual tumors. An investigation of changes of lymphocyte subsets and suppressor cell activity during the postoperative course was performed for the analysis of the immunosuppression caused by the surgical stress in patients with gastrointestinal cancer. In patients undergoing the surgical stress of total gastrectomy or esophageal resection, CD4+2H4- (helper T) and CD8+CD11-(cytotoxic T) cells significantly depressed on day 1 after operation and remained until day 7. In these patients, CD4+2H4+ (suppressor inducer T) cells significantly increased from just after the operation, remained to increase until day 1 after operation and recovered to the preoperative level thereafter. Concanavalin A-induced suppressor cell activity peaked on day 4 and decreased thereafter. However, in patients with benign disease, decreases of helper and cytotoxic T cells were found to a slight degree. The population of lymphocytes with surface receptors for a soluble suppressor factor significantly increased on day 1 after operation in patients receiving esophageal resection and continued to increase until day 30. In patients with preoperative treatment of PSK and cyclophosphamide, the decreases in helper and cytotoxic T cells and the increase in suppressor inducer T cells were significantly blocked during the postoperative course. Thus, these results indicate that extensive surgical stress such as total gastrectomy and esophageal resection may be attributable to the immunosuppression produced by the induction of suppressor cells, and the necessity of pre- and post- operative immunotherapies may be indicated for a better prognosis.

Esophageal Neoplasms↗

[Evaluation and problems of second-look operations in resectable gastric cancer].

During the period from June 1973 to December 1985, one thousand and ninety-seven patients with primary gastric cancer have been operated on in our Dept. of Surgery. Of the 1097 gastric cancer patients, 59 were reoperated and evaluated for chemotherapeutic effects. The cases were 21/548 (3.83%) for absolute curatively resection, 16/202 (7.92%) for relative curatively resection, 9/64 (14.0%) for relatively noncurative resection and 13/283 (4.59%) for absolutely noncurative resection, respectively, The median survival period from primary gastrectomy to second look operation was less than 2 years, and the prognoses were not very good. The factors of relaparotomy were peritoneal dissemination 44/59 (78.6%), invasion to contiguous structures, lymph node metastases and liver metastasis. Those with local recurrence or remnant stomach cancer could be resected in 5 cases, and one patient was well more than 2 years following surgery. The reoperation procedures were reconstruction of artificial anus, intestinal anastomosis or intestinal fistula. Some 7 of 59 patients were found to be entirely beyond surgical aid at the second look operation and were administered large-dose OK-432 or ADM patch method. These methods are suggested for their usefulness for peritoneal dissemination.

Antineoplastic Agents↗

[Clinical efficacy of intratumoral administration of BRM in advanced cancer and their mechanism of actions].

The clinical efficacy of intratumoral (IT) administration of BRM in 157 patients with unresectable or recurrent tumors was investigated, and the infiltration of lymphocyte subsets into tumor tissues after IT administration of BRM was immunohistologically examined, to analyse its action mechanism. BRMs used in this study were OK-432, tumor necrosing factor (TNF), whole peptide glucagon (WPG), interferon (IFN)-alpha, IFN-beta, IFN-gamma and interleukin-2 (IL-2). Among them, one hundred thirty-one patients were evaluable for clinical effects, and the therapeutic response rate (CR + PR) was determined in 11/131 (8.4%). Higher therapeutic responses were found in the patients with esophageal cancer, pancreatic cancer and breast cancer, respectively. As for the relationship between the clinical efficacy of IT administration of BRM and the injected sites, the injection into metastatic lesions was more effective than that into the primary or local recurrence. A increase of lymphocyte infiltration after IT BRM immunotherapy and a variety of lymphocyte subsets in tumor tissue injected with any BRMs were found immunohistologically. These results suggest that IT BRM immunotherapy may be effective for the control of tumor growth locally through host-mediated action.

Adjuvants, Immunologic↗

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↗

The regulation of natural killer cell activity by splenic nonspecific suppressor cells and its modification in cancer patients.

Spleen cells (SC), splenic venous blood lymphocytes (SVL) and peripheral blood lymphocytes (PBL) from gastric and esophageal cancer patients were simultaneously tested for natural killer (NK) and nonspecific suppressor (Ts) cell activities. Furthermore, the influence of Ts activity on the augmentation of NK activity by a biological response modifier (BRM) was also investigated. Positive Ts activities were frequently detected in the SC, SVL and PBL of advanced cancer patients. The NK activities of SC and SVL were maintained even in advanced cancer patients, though significantly depressed NK activities were observed in the PBL of advanced cases. Cancer patient SC, SVL and PBL with positive Ts activity showed low NK activities. Moreover, the NK activities of SVL and PBL were low in the patients with positive Ts activity in SC. The NK activity of normal control PBL was strongly augmented by interleukin 2, interferon and OK-432. These BRMs exhibited comparable capacities to augment the NK activities of SC, SVL and PBL with negative Ts activity in cancer patients, however, the effects of these agents seemed to be low in cells with a positive Ts activity. These results suggested that NK activity might be regulated by nonspecific suppressor cells and the presence of suppressor cells might affect the augmentation of NK activity through BRM in circulating blood lymphocytes and also in spleen cells.

Adult↗

The clinical efficacy of intratumoral OK-432 administration in advanced cancer patients.

The clinical efficacy of intratumoral (IT) OK-432 immunotherapy in advanced cancer patients was investigated. Furthermore, the infiltration of lymphocyte subsets into the tumor tissues after the IT administration of OK-432 was also immunohistologically examined in order to analyze the mechanism of action of OK-432 immunotherapy. Forty-four patients with advanced cancer were treated with IT OK-432 immunotherapy. Ten KE (1 mg) of OK-432 was given either daily or on every second day and repeated as often as possible, the mean frequency of OK-432 injections being 18.1 +/- 14.5 times, ranging between 5 and 25 administrations. Thirty-one of the 44 patients were evaluable, 3 of whom (9.7 per cent) developed a partial response and 5 (16.1 per cent) a minor response. Intratumoral OK-432 immunotherapy, however, did not necessarily prolong the survival time. Leu 1, 3 and 7 reactive cells infiltrated into the tumor tissues treated by OK-432 injection, more frequently, when compared with cells which had been treated by recombinant TNF injection. Thus, it was suggested that IT OK-432 immunotherapy might be effective for the local control of tumor growth through the host mediated action, and that, in combination with systemic therapy, may enhance the clinical effects and prolong the survival time in advanced cancer patients.

Adult↗