Shoshichi Takeuchi

Clinical evaluation of schizophyllan combined with irradiation in patients with cervical cancer: A randomized controlled study

To evaluate the clinical effects of the anti‐tumor polysaccharide Schizophyllan (SPG), a randomized study was done on 220 patients with Stage II or Stage III cervical cancer who had been given irradiation, concomitantly. The tumor‐reducing effect of SPG was significant in patients in either stage. The time to recurrence was longer in SPG‐dosed patients with Stage II cancer, compared with findings in the control group. There was no significant difference in the time to recurrence in patients with Stage III cancer between the SPG and control groups. When comparing the 48‐month survival curve, the survival time of patients with Stage II cancer in the SPG group was significantly longer than in the control group. However, there was no significant difference in the survival rate of patients with Stage III cancer between the SPG‐ dosed and control groups.

Analysis of Th1 and Th2 cytokine production by peripheral blood mononuclear cells as a parameter of immunological dysfunction in advanced cancer patients

Purpose: The presence of immunological dysfunction has not been well demonstrated in cancer patients. Recent studies have revealed that the immune response can be classified into types 1 and 2, and in the present work the immunological function of patients was studied from the perspective of these two types of response. Methods: Types 1 and 2 immune response were evaluated by monitoring the production of various cytokines by peripheral blood mononuclear cells from 38 patients with advanced cancer of various organs and 20 healthy subjects. The usual immunological parameters, differential cell leukocyte counts, the level of T cell subsets (CD4 and CD8) and natural killer activity were also examined. Results: The production of interleukin-2 (IL-2), interferon γ, IL-10, IL-12 and tumor necrosis factor α was found to be significantly lower in the patients (75 ± 57, 171 ± 205, 40 ± 34, 8 ± 8, 1450 ± 1010 pg/ml) than in healthy subjects (143 ± 99, 422 ± 296, 64 ± 34, 16 ± 10, 2550 ± 950 pg/ml); however, the mean level of IL-4 in the patients seemed to be higher. The correlations between different cytokine levels suggested that they were produced differently. Lymphocyte counts were significantly lower in patients, but there was no difference in the other usual immunological parameters. Conclusions: Patients with advanced cancer are deficient in monocytes and the type 1 immune response. The measurement of various cytokines reported in this study provides a more sensitive and valuable tool for evaluating the function of cell-mediated immunity in cancer patients than do the usual tests.

Phase II Study of Irinotecan and Cisplatin as First-Line Chemotherapy in Advanced or Recurrent Cervical Cancer

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m2) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m2 i.v.) on day 1 over 90 min. The patients’ median age was 57 years (range 35–75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41–74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16–62 days). The median survival was 27.7+ months (range, 6.4–52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.

Result of Immunotherapy on Patients With Unexplained Recurrent Abortion: A Beneficial Treatment for Patients With Negative Blocking Antibodies

ABSTRACT: Thirty‐nine unexplained recurrent aborters underwent vaccination using husbands lymphocytes according to the previously reported protocol. No mixed lymphocyte culture reaction‐blocking antibodies (MLR‐BAbs) were observed in these patients prior to vaccination. Of 35 newly pregnant patients after vaccination(s), pregnancy successfully continued in 28 (80.0%) and have already been terminated with a liveborn offspring. Pregnancy outcome was also analyzed in unexplained recurrent aborters who revealed positive MLR‐BAbs without immunotherapy. In this group, out of eight pregnancies in seven patients, five (62.5%) continued beyond their critical period of 14 wks of gestation. Three infants born from these pregnancies, however, presented severe abnormalities. Furthermore, outcome of 14 pregnancies in 12 unexplained recurrent aborters with negative MLR‐BAbs was analyzed since they had become pregnant without immunotherapy; pregnancy was successfully continued in only four cases (28.6%). Thus, vaccination using husbands lymphocytes on unexplained recurrent aborters with negative MLR‐BAbs is suggested to be effective. In addition, it is suggested that immunotherapy for patients with positive MLR‐BAbs should be carefully followed.

Immunohistochemical localization of HLA antigens and placental proteins (αhCG, βhCG CTP, hPL and SP1 in villous and extravillous trophoblast in normal human pregnancy: a distinctive pathway of differentiation of extravillous trophoblast

Abstract Immunohistochemical localization of HLA antigens and plancental proteins (αhCG, βhCG CTP, hPL and SP 1 ) in villous and extravillous trophoblast at various stages of normal human gestation were studied, using hysterectomy specimens. In the chorionic villi, the capacity for synthesizing placental proteins seemed to develop in parallel with the morphological change from mononuclear cells to multinucleated syncytiotrophoblast and no villous trophoblast expressed HLA antigens. In contrast, extravillous trophoblast, including the multinucleated trophoblastic cells at the deciduomuscular junction, expressed HLA-A, -B, and -C, and their capacity for synthesizing placental proteins did not seem to correspond with the degree of morphological change: the location of αhCG, βhCG CTP and SP 1 was restricted to mononuclear trophoblast in the superficial decidua, while hPL was present extensively in extravillous trophoblast. These findings strongly suggest that extravillous trophoblast possesses many distinctive biological features and differentiates in an independent manner. Mononuclear trophoblast forming the cell columns was also positive for HLA-A, -B, and -C, and no placental protein was demonstrated in these cells; this, together with previous morphological observations, may indicate the germinative nature of these cells.

Immunology of Spontaneous Abortion and Hydatidiform Mole

ABSTRACT: Our study of the sequence of morphological events leading to the formation of hydatidiform mole (HM) led us to this study. Our object in this paper is to present evidence supporting our 1971 hypothesis with results obtained by various immunological methods in our laboratory, and to propose the importance of an immunoregulatory mechanism by blocking antibody (BA).

Cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19‐9 in ovarian tumors

The authors studied data of combination assays of tumor markers, because simultaneous elevation of different types of tumor markers in the serum was puzzling. They interpreted such phenomena regarding cancer antigen 125, carcinoembryonic antigen, and carbohydrate determinant 19‐9 in ovarian tumors. the tissue expression of the antigens was compared with preoperative serum levels. Several different factors were found to cause the simultaneous elevation of two or three of these markers in the serum. Furthermore, even when the levels of some of the tumor markers were raised in the serum, the ovarian tumor did not always produce the marker by itself. This study indicates that immunohistochemical identification of a marker in tumor tissue is prerequisite to the use of that marker in the serum to monitor disease status.

Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate.

Following a previous report [1] we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan.Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.

Irinotecan (CPT-11) and Cisplatin as First-Line Chemotherapy for Advanced Ovarian Cancer

Objective: To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer. Methods: Twenty-six patients with previously untreated advanced epithelial ovarian cancer were enrolled in this study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1. Cycles were repeated every 28 days for at least two cycles. The median patient age was 55 years (range, 37–75), and the median performance status was 1. Results: Objective responses were recorded in 19 of 25 eligible patients (76%; 95% confidence interval, 55–91%). Complete responses were obtained in 2 patients (8%), and partial response in 17 patients (68%). Stable disease was recorded in 2 patients (8%) and progressive disease in 2 (8%). The median time to response was 62 days (range, 28–234 days). The median survival time for all 25 patients was 30.9+ months (range, 4.1–60.0+ months). The major toxic effects were leukopenia, neutropenia, and diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea occurred in 17 (68%), 20 (83.3%), and 5 patients (20%), respectively. Thrombocytopenia was less common. No treatment-related deaths occurred. Conclusion: The combination of CPT-11 and cisplatin showed significant activity in chemotherapy-naive patients with advanced ovarian cancer. Neutropenia was the dose-limiting adverse effect, whereas diarrhea was mainly mild to moderate.

Reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) on human tissue sections: analysis of their usefulness as a histological trophoblast marker in normal pregnancy and trophoblastic disease

In normal and molar pregnancy, a morphological discrimination between nonvillous trophoblasts which lie scattered in the placental bed and surrounding maternal cells is considered to be difficult. We examined the reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) against cytokeratin by an immunoperoxidase technique and analyzed their usefulness as a histological trophoblast marker. Materials were taken from 42 uteri with normal pregnancy, 7 uteri with hydatidiform mole, 2 uteri with gestational choriocarcinoma, 1 fallopian tube with nongestational choriocarcinoma, 5 delivered term placentae of normal pregnancy, and 5 nongestational uteri. The reactivities of Troma 1 on frozen sections and those of CAM 5.2 on paraffin sections were identical. They reacted with surface epithelium and gland epithelium in the nongestational uterine corpus. In the implantation site of normal and molar pregnancy, they reacted with villous and nonvillous trophoblasts as well as endometrial gland epithelium. In gestational and nongestational choriocarcinoma, they reacted with carcinoma cells specifically. Since the histological detection of gland epithelium may not be difficult, it was concluded that the two antibodies were very beneficial as a histological marker for trophoblasts in normal pregnancy and trophoblastic disease.