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Biomedical subjects

Y Kikuchi

Publications and source records attributed to Y Kikuchi.

At least 721 records · Page 40Linked to original sources

[Inhibition of human ovarian cancer cell growth by prostaglandin D2].

The effects of prostaglandin D2 (PGD2) on human ovarian tumor growth were examined in vitro and in vivo by using a cell line, designated HR, derived from patients with serous cystadenocarcinoma of the ovary. The cell proliferation was dose-dependently inhibited by PGD2 between concentrations of 0.1 and 4.0 micrograms/ml after 24 hrs, 48 hrs and 72 hrs of contact time. Concentrations of PGD2 required for 50% inhibition of the cell proliferation were 2.0, 1.1 and 0.55 micrograms/ml with 24, 48 and 72 hrs of contact time, respectively. From the results of 51Cr-release assay, the inhibition of cell proliferation by PGD2 was considered to result from the direct cytotoxic effects. The incorporations of 3H-thymidine, 3H-uridine and 3H-valine were inhibited in a dose-dependent fashion with more than 1.0 micrograms/ml of PGD2. Tumor growth in nude mice treated with 0.3 mg/mouse PGD2 was significantly inhibited, compared to that of untreated nude mice. In untreated nude mice the tumor growth curve was parallel to the changes in the plasma alpha-hydroxybutyrate dehydrogenase (HBD). In both PGD2-treated groups with 0.1 mg/mouse and 0.3 mg/mouse, the HBD activity markedly decreased on the 14th and the 21st day after inoculation. The 50% survival time in untreated mouse, 0.1 mg/mouse and 0.3 mg/mouse PGD2-treated groups was 52 days, 55 days and 67 days, each respectively.

Adenocarcinoma, Mucinous↗

[Three cases of adenocarcinoma of the lower esophagus and cardia showing marked regression after radiotherapy with FT-207].

Three cases of adenocarcinoma of the lower esophagus and cardia which is considered to be difficult to control by radiotherapy alone, were given radical irradiation combined with FT-207 suppository. Dosages of radiation and FT-207 were 70 Gy/35 f and 1.5 g/day (1 case) or 1.0 g/day (2 cases), respectively. The treatment was successful locally; dysphagia was improved in all cases and 1 case has shown no recurrence for a period of two and a half years. Side effects were leukopenia and hemorrhagic esophagitis in the case given 1.5 g/day of FT-207, but these were cured by conservative therapy. These results emphasize that radiotherapy combined with anticancer drugs should be considered as a local therapy for inoperable adenocarcinoma of the lower esophagus and cardia.

Adenocarcinoma↗

Effects of naloxone on human ovarian cancer cell growth in vitro and in vivo.

The effects of naloxone on human ovarian cancer cell growth in vitro and in vivo were examined by using an established cell line, designated KF, derived from human ovarian carcinoma. When the KF cells were incubated in the presence of various concentrations of naloxone for 72 hr, the cell proliferation was inhibited in a dose-dependent manner in the concentration range of 30 to 120 microM naloxone. The growth-inhibitory effect of naloxone could not be detected by 51Cr-release assay or colony-forming assay. The inhibition of cell proliferation by naloxone resulted from the inhibitory effect on protein synthesis in the KF cells, as confirmed by a marked decrease of incorporation of [3H]valine. In order to determine the effect of naloxone on tumor growth in vivo, ip injections 3 times a week of 2.5 or 5.0 mg/kg naloxone were initiated either one week prior to tumor inoculation (pretreated groups) or one week after tumor inoculation (post-treated groups). Nude mice in the pretreated groups had significantly smaller tumor volumes than those in the untreated group as long as naloxone was administered. On the other hand, in the post-treated groups a significant growth retardation was observed 2 weeks after initiation of treatment with 2.5 mg/kg naloxone. In comparison to a median survival time of 38 days for untreated controls, the naloxone pre- and post-treated groups showed increases of 26-71% in median survival.

Animals↗

[An autopsy case of severe miliary tuberculosis in a patient with acute lymphatic leukemia (ALL)].

A 58-year-old Japanese man being diagnosed as having ALL suffered from continuous fever and dysfunction of the liver and kidneys despite being in a state of haematological remission. Further clinical investigations, however had not been able to find the causes of his condition before his death. The autopsy revealed severe miliary tuberculosis affecting many organs including the heart, lungs, liver, spleen, kidneys, thyroid gland, pancreas, bone marrow, and central nervous system, which is compatible with multiple organ failures. Recent pharmacological advances have increased the usage of many kinds of antineoplastic drugs, and this has resulted in increased chances of opportunistic infections by various microorganisms in the course of treatment. The present case implies the significance of the reactivation of tuberculosis in the secondary immunodeficient syndrome (SIDS).

Humans↗

[Effects of cimetidine and PSK on interleukin-2 production by PBL in patients with advanced ovarian carcinoma during the course of chemotherapy].

The present study was designed to elucidate the effect of cimetidine and PSK on T-cell subsets, interleukin-2 (IL-2) production and its receptor in peripheral blood lymphocytes (PBL) from patients with advanced ovarian carcinoma during the course of chemotherapy. Preoperative levels of OKT 4/8 cell ratio and IL-2 production in PBL from patients with advanced ovarian carcinoma were significantly lower than those with benign ovarian tumor. When a combination chemotherapy which consisted of cisplatin, adriamycin and cyclophosphamide was given to these ovarian cancer patients, the OKT 4/8 cell ratio was significantly increased while the IL-2 production was markedly inhibited. When PSK and cimetidine were combined with the combination chemotherapy, the inhibition of IL-2 production was reduced. When treatment with PSK or cimetidine was initiated after completion of the combination chemotherapy, the OKT 4/8 cell ratio was significantly elevated on 30 days and 60 days, compared to 7 days after the completion of chemotherapy. The depressed IL-2 production after completion of the combination chemotherapy was increased to about 8 times by cimetidine and about 2.5 times by PSK on 60 days after completion of chemotherapy. On the other hand, the IL-2 receptor remained unchanged even if PSK or cimetidine was administered.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of carcinoma in situ of the renal pelvis].

A case of carcinoma in situ of the renal pelvis in a 70-year-old female is reported. The patient was admitted with the complaints of macrohematuria and left back pain. Urine cytology, which was carried out three times using urine samples collected directly from the urinary bladder proved to be negative. Drip infusion pyelography (DIP) and retrograde pyelography (RP) disclosed stenosis of the left ureter at the level of L3-L4. Selective renal angiography revealed no abnormalities. Based on the DIP and RP findings, the diagnosis of tumor in the left ureter was made, and left total nephroureterectomy with partial cystectomy was performed. The removed kidney showed signs of mild hydronephrosis but no tumor was found macroscopically. The stenosed site of the ureter had scar-like tissue. Microscopic examination revealed that the stenosed ureter consisted of nonspecific granulation tissue but the mucosa of the renal pelvis showed grade III transitional epithelial cell carcinoma, At 24 months after operation, there is no evidence of tumor recurrence, and urine cytology is also negative.

Aged↗

Generation of cytotoxic T lymphocytes from thymocyte precursors to trinitrophenyl-modified self antigens. II. Establishment of a T cell hybrid clone constitutively producing killer-helper factor(s) (KHF) and functional analysis of released KHF.

T cell hybridoma lines were constructed by fusion of Mycobacterium tuberculosis-primed and boosted BALB/c T cells with the AKR-derived T lymphoma cell line BW5147. Certain of the hybridomas prepared in this manner secreted constitutively into their culture supernatants biologically active molecules that displayed precursors of cytotoxic T cell activating properties characteristic of killer-helper factor (KHF). Cell surface analysis revealed that the hybridomas were indeed somatic cell hybrids between the two respective partner cells used for fusion. KHF properties of these hybridoma supernatants were verified by their capacity to stimulate peanut agglutinin-binding (PNA+) C3H/He thymocytes to respond in vitro to 2,4,6-trinitrophenyl(TNP)-modified syngeneic stimulator cells in conjunction with suboptimal doses (10 U/ml) of interleukin 2 (IL 2) for the generation of H-2-restricted, TNP-reactive cytotoxic T cells. The biologically active molecules secreted by a T cell hybrid clone (2Y4) were, like conventional KHF, distinct from IL 1, IL 2, or immune interferon (IFN-gamma). The partially purified KHF derived from 2Y4 cells shows activity at apparent m.w. range of 34,000 to 60,000 on gel permeation, and is relatively homogeneous with respect to isoelectric point, which was approximately 4.5 to 4.7. The partially purified 2Y4-KHF is able to augment proliferation of as well as the expression of IL 2 receptors on PNA+ thymocytes in conjunction with IL 2. Finally, addition of 2Y4-KHF on day 0, followed by the addition of IL 2 on day 2 for 7 days of culture was effective in generating potent CTL responses, whereas addition of IL 2 on day 0, followed by the addition of 2Y4-KHF on day 2 to the culture was ineffective.

Animals↗

Generation of cytotoxic T lymphocytes from thymocyte precursors to trinitrophenyl-modified self antigens. I. Requirement of both killer-helper factor(s) and interleukin 2 for CTL generation from a subpopulation of thymocytes.

The requirement for signals in the induction of cytotoxic T lymphocytes (CTL) from thymocyte precursors has been investigated. Either unfractionated or peanut agglutinin-binding (PNA+) C3H/He thymocytes were stimulated with mitomycin C(MMC)-treated, 2,4,6-trinitrophenyl(TNP)-modified syngeneic spleen cells in the presence of a variety of lymphokine preparations. Cellfree supernatant (CFS) from purified protein derivatives(PPD-CFS) stimulated Mycobacterium tuberculosis (Tbc)-primed cells, or partially purified interleukin 2 (IL 2) mediated strong cytotoxic responses in unfractionated thymocytes, whereas only PPD-CFS at final concentrations beyond 30% was active for CTL generation in PNA+ thymocytes. Neither IL 2 at concentrations of below 60 U/ml nor a low concentration of PPD-CFS (at final below 10%) had such a capacity. The addition of monoclonal anti-IL 2 receptor antibody completely blocked CTL generation induced by PPD-CFS in PNA+ thymocytes. In contrast, anti-immune interferon (IFN-gamma) antibody showed a marginal effect. PPD-CFS (10%) and IL 2 (10 U/ml) could synergistically trigger PNA+ thymocytes to induce CTL generation. These results suggested that both IL 2 and "helper" factors other than IL 2 are required for CTL generation from PNA+ thymocytes. We refer to these kinds of helper factors as killer helper factors (KHF). Partially purified IL 2-free KHF show two peaks of activities at apparent m.w. 14,000 to 34,000 and 44,000 to 90,000, and are heterogeneous with respect to isoelectric point, which is between 4.5 and 5.1. Cultures that received TNP-modified syngeneic cells and KHF on day 0 and IL 2 on day 2 generated potent CTL responses, whereas the addition of IL 2 on day 0 followed by the addition of KHF on day 2 to the culture was ineffective, suggesting that KHF is required in the early phase of the culture to achieve optimal CTL responses.

Animals↗

Monitoring by alpha-hydroxybutyrate dehydrogenase of human ovarian carcinoma grown in nude mice.

In order to establish that the tumor burden in nude mice bearing a xenografted human ovarian tumor can be assessed by measuring plasma levels of alpha-hydroxybutyrate dehydrogenase (HBD) (E.C. 1.1.1.30), the plasma HBD and the tumor volume were measured every week after inoculation of a human ovarian carcinoma cell line designated HR. About 3 weeks after tumor inoculation, all nude mice had a palpable tumor while elevated levels of HBD were observed in a half of the mice at that time. Thereafter the HBD levels rose with increasing tumor volume. There was a quantitative linear relationship between the tumor weight and HBD activity per mouse. When 40 micrograms of cisplatin (about 2 mg/kg) was administered i.p. every week for 5 weeks 2 weeks after inoculation, plasma levels of HBD were significantly decreased on day 27 compared to those in untreated nude mice. Decreases in the HBD levels during treatment with cisplatin occurred 7 days prior to changes in tumor volumes. Further, removal of local tumor mass resulted in a marked decrease in HBD levels on day 1 after surgery and the HBD levels in nude mice which had no recurrent tumor fell into the normal range 8 days after surgery.

Animals↗

The inhibitory effect of tranexamic acid on human ovarian carcinoma cell grown in vitro and in vivo.

Effects of tranexamic acid on tumor growth were examined by using five kinds of human cultured cell lines derived from ovarian malignant tissues. An optimum inhibitory effect on cell proliferation was observed at a concentration of 10 mg/ml tranexamic acid, while replication of a clear cell carcinoma cell line (OK) was not inhibited by any concentration of tranexamic acid used in the present study. Exposure of a cystadenocarcinoma cell line (HR) to 10 mg/ml tranexamic acid for 2 hr resulted in significant growth retardation of tumors formed in nude mice. Further, tranexamic acid seemed to change the morphology of the ovarian carcinoma cells to enlarged cells with abundant cytoplasm. These results suggest that fibrinolytic factors are associated with growth of the tumor and tranexamic acid is useful as an adjuvant therapy for ovarian carcinoma.

Adenocarcinoma↗

Human leucocyte antigen and coronary artery spasm.

To elucidate possible genetic links in the pathogenesis of coronary artery spasm, we investigated the frequencies of human leucocyte antigen in 37 patients with variant angina and 236 unrelated healthy controls. We found no significant differences in human leucocyte antigen frequencies between the patients and the controls. These results may suggest that genetic factors in linkage disequilibrium with human leucocyte antigen may not be involved in the pathogenesis of coronary artery spasm.

Angina Pectoris, Variant↗

Augmented natural killer activity in ovarian cancer patients treated with cimetidine.

The effect of cimetidine on natural killer (NK) activity of peripheral blood lymphocytes (PBL) was studied in 37 post-operative patients with ovarian cancer. There was no significant difference in the NK activities between normal healthy women and patients with no residual tumor after surgery, while those in patients with large residual tumor after surgery were suppressed to less than a half of those in normal healthy women. Cimetidine augmented the NK activities in patients with no residual tumor but not in normal healthy women. Particularly, the NK activities in patients with low baseline NK status before cimetidine treatment was markedly enhanced. Furthermore, the NK boosting by cimetidine was more effective in patients with large residual tumor than in patients with no residual tumor. The NK activity in PBL from such patients was also enhanced by in vitro exposure to cimetidine. These findings suggest that cimetidine may be used as an immunorestorative-therapy for ovarian cancer patients with depressed NK activity.

Adult↗

Effects of oral diltiazem on ventricular premature contractions.

The effects of oral diltiazem (90-180 mg/day for four weeks) on ventricular premature contractions (VPCs) were studied in 16 patients with frequent VPCs using 24-hour ambulatory ECG recordings. VPC frequency was evaluated as a function of underlying heart rate. Plots of VPC frequency vs. heart rate were made at 1-beat/min intervals for all heart rates recorded for at least five minutes during 24 hours. Patterns of correlation between VPC frequency and heart rate observed before diltiazem therapy included: 1) a relatively linear increase in VPCs with heart rate (positive correlation) in ten patients, 2) a linear decrease (negative correlation) in one patient, and 3) an increase at low heart rates and a decrease at high heart rates (bidirectional correlation) in five patients. Diltiazem significantly reduced the mean VPC frequency per 24 hours for patients with a positive correlation, but induced no significant change for patients with a negative or a bidirectional correlation. At the 65% level of VPC reduction, diltiazem was effective in eight of ten patients with a positive correlation but was not effective in the six patients with other correlations (p less than 0.01). These results suggest that an evaluation of VPC frequency as a function of heart rate predicts the response of VPCs to diltiazem.

Administration, Oral↗