Katsumasa Kuroi

Relationship of the distribution of leu-2+ cells with suppressor cell activities in the spleen and lymphnodes from gastric cancer

Tissue distributions of Leu-2+ cells in the spleen and draining lymphnodes in cases of clinical gastric cancer were investigated, with special reference to suppressor cell function. Significantly higher Concanavalin-A (Con-A) induced suppressor cell activities were evident in spleen cells (SCs), as compared with peripheral blood lymphocytes (PBLs). As for the tissue distribution, the proportion of Leu-2+ (cytotoxic/suppressor) cells within Leu-1+ cells was higher in the spleen than in the lymphnodes without metastasis. On the other hand, in lymphnodes with metastasis, the enhanced spontaneous suppressor cell activity was noted. In addition, the proportion of Leu-2+ cells within Leu-1+ cells was the greatest in the lymphnodes with metastasis, among the lymphoid organs tested. In lymphnodes without metastasis, lower suppressor cell activities were noted, and numerous Leu-3+ (helper/inducer) cells were present, while Leu-2+ cells were less frequent. NK cell activity against K-562 cells was enhanced by elimination of Leu-2+/OKT-8+ cells with complement-mediated lysis. These results suggest that Leu-2+ cells located in the spleen and lymphnodes with metastasis may predominantly act as suppressor cells and interact with effector cells.

Effects of intraperitoneal administration of OK-432 for patients with advanced cancer.

The effects of intraperitoneal administration of OK-432 on tumor cells in ascites, in relation to the infiltration of effector cells and on the immune reponses of the host, particularly, with regard to immune suppressive mechanisms, were investigated in 25 patients with cancerous ascites. The effects of OK-432 depended on frequency of the repeated and continuous administrations through a tube placed in the peritoneum during laparotomy. Infiltrations of neutrophils and lymphocytes were observed in the ascites within a short period after the administration and monocyte infiltration followed. Disappearance of tumor cells correlated well with the infiltration of these cells. No marked changes in the proliferative responses of peripheral blood lymphocytes were noted and decreases in serum inhibitory factor levels in sera were observed in patients given larger doses of OK-432. A marked reduction in Concanavalin-A-induced suppressor cell activities was observed after OK-432 administration. OK-432 administration probably leads to a disappearance of tumor cells by enhancing peritoneal effector cell activities and by inhibiting the induction of suppressor cell activities, in a dose dependent manner.

A role of VLA‐6 laminin receptor in invasion of breast carcinoma

The integrin VLA‐6 as a laminin receptor and laminin as a ligand for laminin receptor were detected immunohisto‐chemically in normal, benign tumor and carcinoma tissues of the breast. Epithelial cells of both normal breast and benign tumor were in almost all cases strongly immuno‐reactive for VLA‐6 in the plasma membrane. Carcinoma cells in 34 of 70 cases (49%) with an invasive component were not immunoreactive for VLA‐6, and no carcinoma ceils showed strong positivity. Although carcinoma cells in only four of 51 cases (8%) with intraductal components were negative for VLA‐6, 37 cases (72%) showed weak expression of VLA‐6 and 10 cases (20%) showed strong expression of VLA‐6. A concordant expression of VLA‐6 on carcinoma cells and laminin around carcinoma cell nests with an invasive component was observed, and VLA‐6 expression in carcinoma cells was correlated to tubular formation in carcinoma cell nests as an indicator of differentiation. These findings suggest that loss of VLA‐6 plays a role in the invasion of breast carcinoma, and that VLA‐6 laminin receptor and laminin may contribute to tubular differentiation of breast carcinoma cells.

Myxoma of the breast: Report of a case with unique histological and immunohistochemical appearances

A case of myxoma of the breast is reported. The patient, a 19 year old Japanese woman, showed a lump in the left breast which had enlarged gradually over 3 years. A tumor measuring 5 × 5 × 4.5 cm was located mainly in the mammary parenchyma, but partially involved the overlying subcutaneous tissue. Histologically the tumor was multinodular and each nodule consisted of an abundant myxoid substance with a few spindle or stellate mesenchymal cells. The presence of hyaluronic acid was observed in the myxoid area, and a few constituent cells showed Immunoreactivitiesfor S‐100 protein and α1‐antichymotrypsin. Electron microscopic studies revealed that some constituent cells looked like undifferentiated mesenchymal cells, while others showed a differentiation similar to fibroblast or histiocyte. These findings suggest that the constituent cells might derive from totlpotential primitive mesenchymal cells.

Primary squamous cell carcinoma of the breast after cured Hodgkin's disease

An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkins disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkins disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkins disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkins disease. The risk of patients treated for Hodgkins disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case.

Interference of the induction of suppressor cells by a streptococcal preparation, OK-432 through the blocking of suppressor inducer T-cells

The effect of OK-432 on suppressor inducer T cells in the generation of suppressor cells was investigated to determine its mechanism of action as an immunopotentiating agent. Suppressor cell activities induced by sera from patients with advanced cancer (stage III, IV or recurrence) were found to be as high as those induced by Con-A. Suppressor activity induced by Con-A or serum from cancer patients resided in CD8+ T cells, although CD4+ T-cells were required for the induction of suppressor cells. Significant increases in the CD4+2H4+ T cell population after stimulation with either Con-A or sera from the advanced cancer patients were observed when compared with stimulation by normal serum. Stimulation with Con-A induced suppressor cells as well as a significant increase of CD4+2H4+ T-cells. The presence of OK-432 during the generation of suppressor cells, however, significantly reduced the suppressor activity and apparently blocked the increase of CD4+2H4+ T-cells. Thus, it is suggested that OK-432 may interfere with the induction of suppressor cells through the blocking of CD4+2H4+ suppressor inducer T-cells.

Multicentric breast carcinoma: Evaluation of clinicopathological and immunohistochemical characteristics

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In7 (3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.

A combination therapy with mitomycin c, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy for advanced breast cancer refractory to combination chemotherapy of cyclophosphamide, doxorubicin and 5 fluorouracil

Thirty-two patients with advanced breast cancer refractory to combination chemotherapy with cyclophosphamide (CPA), doxorubicin (ADR) and 5-fluorouracil (5-FU) (CAF) were treated with the combination of mitomycin C, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy. Observed responses included 6 patients (18.7%) with complete response (CR) and 7 (21.9%) with partial response (PR). Two (50%) out of 4 patients who had bone pain due to bone metastasis noted pain relief. CR or PR were obtained in 4 out of 12 patients who had not responded to the previous CAF therapy. While grade III myelosuppression was observed in 3 patients, other adverse effects were minimal. It is suggested that this combination therapy may be recommended for advanced breast cancer patients as a second therapy.

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL byin vitro additional OK432, interleukin 2 or γ-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmentedin vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432. An increase in CD4+2H4+ cells and a decrease in CD4+2H4− cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.