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K Kuroi

Publications and source records attributed to K Kuroi.

At least 37 records · Page 2Linked to original sources

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 immunohistochemically 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 immunoreactive 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 cells 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.

Breast Diseases↗

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 x 5 x 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 immunoreactivities for S-100 protein and alpha 1-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 totipotential primitive mesenchymal cells.

Adult↗

Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer patients.

The expression of c-erbB-2 oncoprotein and epidermal growth factor receptor (EGFR) was examined by immunocytochemical and radioreceptor assays in 115 patients with primary breast cancer. In 48 of 115 patients (42%), the assays were found to be positive for the expression of c-erbB-2 oncoprotein, and, in 44 of 115 (35%) patients, the assays were positive for the expression of EGFR. There was no correlation between the expression of c-erbB-2 oncoprotein and EGFR. Clinical survey demonstrated that both c-erbB-2 oncoprotein expression and EGFR expression have independent prognostic values. Furthermore, when patients were divided into three groups on the basis of the expression of both c-erbB-2 oncoprotein and EGFR, those who were found to be positive for the expression of both c-erbB-2 oncoprotein and EGFR showed a worse prognosis than other groups. These results suggest that the combination of the expression of both c-erbB-2 oncoprotein and EGFR may be important in selecting patients who have a poor prognosis.

Biomarkers, Tumor↗

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 by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in 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.

Administration, Oral↗

[Prognostic significance of expression of c-ERBB-2 oncoprotein in breast cancer patients].

The c-erbB-2 oncogene, is a member of tyrosine kinase oncogene family and expected to play a role in the regulation of cell growth. In the present study, prognostic significance of the expression of c-erbB-2 oncoprotein was investigated by immunocytochemical assay with 130 primary breast cancer patients. The positive expression of c-erbB-2 oncoprotein was found in 53 out of 130 patients (40.8%). There was no significant correlation between expression of c-erbB-2 oncoprotein and conventional prognostic factors, estrogen receptor (ER), axillary lymph node metastasis and epidermal growth factor receptor (EGFR). Relapse free survival rate of the patients with positive c-erbB-2 expression was significantly worse than those with negative at 49 month after operation. Similar result was found in overall survival rate but the difference was not significant. Furthermore, when patients were stratified by regional nodal status, in the patients with lymph node metastasis, the prognosis of the patients with positive c-erbB-2 expression was significantly worse than those with negative, while no significant difference was found in the patients without lymph node metastasis. These results suggest that c-erbB-2 oncoprotein may act as a prognostic factor independently, predicting the prognosis of breast cancer patients.

Adult↗

[LAK cell adoptive immunotherapy and its problems].

Clinical efficacy of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT) in combination with plasma exchange and interleukin (IL-2) was investigated in 24 patients with advanced cancer. Partial response (PR) was found in 4 patients (20%), including 1 primary liver tumor, 1 metastatic lung tumor from renal cancer and 2 malignant pleural effusions from gastric and lung cancer. Based on these results new AIT in combination with plasma exchange, OK-432, IL-2 and cyclophosphamide was designed to target liver and lung tumors, in which LAK cells and other drugs were administered through the catheter located in the feeding artery of the tumor. Out of ten patients treated, 1 (10%) with metastatic liver tumor from gallbladder cancer was evaluated as PR. It is suggested that a strategy to enhance tumor accumulation and recognition of LAK cells should be attempted for development of gastrointestinal cancer therapy with AIT.

Aged↗

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.

Antibodies, Monoclonal↗

Lymphocyte subpopulations in peripheral blood and the spleen from gastric cancer patients.

Lymphocyte subpopulations in peripheral blood and the spleen from gastric cancer patients were identified by either single or two color analysis with fluorescence activated cell sorter-IV (FACS-IV) using monoclonal antibodies. The absolute and percentages of CD3+ (mature T) cells and CD4+ (helper/inducer T) cells in peripheral blood from the advanced cancer patients were significantly lower than those from normal healthy controls. In peripheral blood, a significant decrease of CD4+ cells was due to the decrease of CD4+ CD45RA+ (suppressor inducer T) cells, while CD8+ CD11b+ (suppressor T) cells tended to increase with progress of the disease. CD4+ CD45RA+ cells located more predominantly in peripheral blood and spleen than in the splenic vein, while CD8+ CD11b+ cells were more predominant in the splenic vein.

Antibodies, Monoclonal↗

[Intra-arterial infusion chemotherapy in non-resectable pancreatic cancer using angiotensin-II and implantable drug delivery system].

Over the past 6 years, we have treated 25 cases of pancreatic cancer, 6 cases of cholangioma in pancreas-head and 3 cases of cancer in duodenal papilla (2 cases Stage I, 5 cases stage II, 2 cases stage III, 25 cases stage IV). Twelve cases (10 unresectable cases, 1 hepatic metastasis case, 1 recurrent case) were treated with intra-arterial infusion chemotherapy using implantable Drug Delivery System, combined with angiotensin-II to increase the concentration of anti-cancer agents in cancer tissue. Twenty-four cases (70%) died in less than one year, so operation is not effective except for curative resection of cholangioma and duodenal papilla cancer. But exploratory laparotomy or inoperable cases given intermittent transcatheter arterial infusion chemotherapy (5-FU + ADM + MMC + angiotensin-II), showed favorable results (decrease of tumor size and pain in 2 cases; recanalization of obstruction in choledochus of 1 case). Especially trans-femoral or left subclavian arterial catheterization proved to be effective therapy for possibly giant or recurrent inoperable pancreatic cancer and hepatic metastasis. Using the drug delivery system, the technical approach to arterial infusion therapy and angiography has been readily undertaken. Quality of life has been improved, and course observation of the patient has been possible by imaging diagnosis and multidisciplinary treatment for advanced pancreatic cancer.

Adenoma, Bile Duct↗

Role of the spleen in immunosuppression of gastric cancer: predominance of suppressor precursor and suppressor inducer T cells in the recirculating spleen cells.

In order to analyse the role of the spleen on immunosuppression of gastric cancer, T cell phenotypes in the spleen cells (SC) were investigated by two colour fluorescence flow cytometry, with reference to their suppressor cell activity. Suppressor T cell phenotypes of CD4+2H4+ cells (suppressor/inducer T cells) and CD8+CD11+ (suppressor T cells) were distributed predominantly in SCs from patients with gastric cancer, while they were distributed scarcely in those with liver cirrhosis. Moreover, CD4+2H4+ cells and CD8+CD11+ cells were found predominantly in SCs and splenic vein lymphocytes (SVL) respectively. Among SCs, a significantly higher proportion of CD4+2H4+ cells was found in the recirculating SCs, but fewer were found in the residual SCs. Higher activity of Concanavalin-A induced suppressor cells was found in the former and that of spontaneously activated suppressor cells was found in the latter. These results suggest the suppressor precursor and suppressor/inducer T cells might distribute predominantly in the cells recirculating from the spleen, and that suppressor cells might be matured during the migration from the spleen.

Adult↗

Relationship of the distribution of Leu-2+ cells with suppressor cell activities in the spleen and lymph-nodes from gastric cancer.

Tissue distributions of Leu-2+ cells in the spleen and draining lymph-nodes 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 lymph-nodes without metastasis. On the other hand, in lymph-nodes 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 lymph-nodes with metastasis, among the lymphoid organs tested. In lymph-nodes 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 lymph-nodes with metastasis may predominantly act as suppressor cells and interact with effector cells.

Adult↗

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 responses 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.

Ascites↗

[Clinical studies on plasma exchange in advanced cancer patients with special reference to the postcentrifugal filter].

Plasma exchange was undertaken to remove the immunosuppressive factors in 25 advanced cancer patients who did not respond to immunochemotherapy. In the present studies, a postcentrifugal filter was tried, and the filtrated autologous plasma was replaced in 10 patients replaced by about 1000 ml in eight and by about 1600 ml in two. The improvement of subjective symptoms and reduction of tumors were observed in 15 (60%) and seven (28%) patients, respectively. It was suggested that immunosuppressive factors of a large molecular size could be selectively removed by the postcentrifugal filter.

Adult↗

[The role of the spleen in immunosuppression and the effects of splenectomy on prognosis in gastric cancer patients].

To elucidate the role of the spleen on the immunosuppression in gastric cancer patients, mechanism of the induction of suppressor cells in the spleen was investigated. Studies of tissue distribution of T cells using monoclonal antibodies revealed that spleen contained much higher proportion of OKT8 reactive T cells as compared with those in regional lymphnodes without metastasis. Lymphocytes released from the spleen during perfusion were taken to be representative of recirculating lymphocytes. Suppressor precursor cells were found to exist predominantly in perfusate from the spleen, while spontaneously activated suppressor cells were in the residual lymphocytes in the spleen after perfusion. Culture supernatants from splenic adherent cells induced suppressor cell activities as well as sera from splenic venous blood. These results suggest that suppressor precursor cells which could be mobilized slowly was more comparable to splenic lymphocytes and might be matured by factors released from splenic adherent cells, partly moving into peripheral blood. Furthermore, the effect of splenectomy on the prognosis of gastric cancer patients was investigated in randomized controlled trial. The patients who underwent total gastrectomy and had main location of the tumor on lesser curvature region were divided into two groups at random; splenectomy (+) and splenectomy (-) groups. A suggestive prolongation of survival time was observed in splenectomy (+) group. Thus, spleen seem to contribute to the immunosuppression in gastric cancer patients and splenectomy may lead to better prognosis.

Adult↗

Circulating angiogenesis regulators in cancer patients.

BACKGROUND/AIMS: To date, numerous studies have demonstrated that several angiogenesis regulators circulate in the blood and may function as endocrine factors in cancer patients. This review aims to give a comprehensive insight into the possible clinical value of circulating angiogenesis regulators, mainly basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF), angiogenin, pleiotrophin, thrombospondin (TSP) and endostatin (ES) in cancer patients. METHODS: A computerized (MEDLINE) and a manual search based on the reference lists of the publications were performed to identify articles published on this topic. RESULTS: In a detailed literature search, approximately 100 publications were found up to the end of 1999. Circulating angiogenic factors such as bFGF, VEGF, HGF and angiogenin have been evaluated not only as diagnostic and/or prognostic factors but also as predictive factors in cancer patients. On the other hand, little is known about the clinical significance of negative regulators. Neither the source nor the mechanism of protein externalization has been clarified in detail. CONCLUSIONS: Although there are no known factors with established clinical utility, circulating angiogenesis regulators may be useful in several situations. They could be used to determine the risk of developing cancer, to screen for early detection, to distinguish benign from malignant disease, and to distinguish between different types of malignancies. In patients with established malignancies such factors might be used to determine prognosis, to predict the response to therapy, and to monitor the clinical course. Further investigations are warranted to assess the specific utility of each factor.

Biomarkers, Tumor↗

Homology of partial primary sequences between alpha-enolase and a suppressive lymphokine from human T cells.

A relationship is described between TS--a human suppressive lymphokine produced by hybridoma T cells--and alpha-enolase from the U937 monocyte human cell line. A strong homology (92%) was observed by comparing the internal amino acid sequences of 6 TS peptides, corresponding to 52 residues, with the complete sequence of alpha-enolase. The molecular masses of these two molecules were found to be of about 47 kDa and both were detected with the same monoclonal antibody to TS. In contrast, no immunosuppressive activity was detected with the purified enolase fraction, whereas TS did not show any enolase activity. A suppressive monokine secreted by U937 cells was found to be unrelated with TS. Theses results suggest that the TS immunosuppressive factor despite its absence of enzyme activity, belongs to the enolase family.

Amino Acid Sequence↗

Circulating levels of endostatin in cancer patients.

Endostatin is a negative regulator of angiogenesis. We examined plasma endostatin levels (PESLs) in cancer patients and healthy controls. PESLs were detected by competitive enzyme immunoassay in 147 patients with primary breast cancer, 44 patients with other histological types of cancer, 26 patients with recurrent breast cancer, 17 patients with benign breast disease and 221 healthy controls. PESLs were elevated in those patients with cancer or benign breast disease. In patients with primary breast cancer, significantly higher PESLs were found in post-menopausal patients than in pre-menopausal patients (p<0.01), although there were no differences in the other clinicopathological characteristics evaluated. PESLs in primary breast cancer patients did not change after surgery, but they increased after administration of the adjuvant tamoxifen. When we applied an age-matched cut-off value as a mean of the values for the female controls, we found that node-negative breast cancer patients with high PESLs had a significantly more favorable relapse-free survival time than those with low PESLs (p<0.05, log-rank test). Our data demonstrate that PESLs are detectable in healthy controls, and that cancer patients have elevated PESLs. A larger study is warranted to clarify the clinical significance of circulating endostatin.

Adult↗