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Biomedical subjects

R Kudo

Publications and source records attributed to R Kudo.

At least 91 records · Page 5Linked to original sources
PubMed1996

Simultaneous intra- and extra-uterine pregnancy with ovarian hyperstimulation syndrome after induction of ovulation: a case report.

We present a case of polycystic ovary syndrome (PCOS) that developed simultaneous intra- and extra-uterine pregnancy with ovarian hyperstimulation syndrome (OHSS) after induction of ovulation with pure FSH-HCG. At 9 weeks of pregnancy, the bilateral tubal pregnancy caused an imminent spontaneous abortion, and both Fallopian tubes were resected. After the laparotomy, the pregnancy progressed without problems until 31 weeks and 5 days of pregnancy, when signs of spontaneous abortion appeared, and healthy twin female babies were delivered by cesarean section. The incidence of heterotopic pregnancy is increasing in cases in which inducers of ovulation or ART, such as IVF-ET and GIFT, have been employed. One must be well aware that the danger of heterotopic pregnancy following induction of ovulation is imminent, particularly in cases with risk factors of multiple and/or extra-uterine pregnancy, such as PCOS, a history of tubal restoration, and sexually transmitted disease(s).

Adult↗
PubMed1996

Interaction between cell-surface-expressed 70-kilodalton heat shock protein-like antigen and CD3(+)4(-)8(-) killer T cells.

The 70-kilodalton heat shock proteins may be expressed on the cell surface by an unknown mechanism and may interact with CD3+4-8- T cell receptor-alpha beta-killer (DNT) cells. In this interaction, certain cellular nascent or mutant peptides may be important (the complexes of 70-kilodalton heat shock protein and cellular peptides directly interact with DNT cells). The results imply that the interaction between 70 kilodalton heat shock proteins and DNT cells may also work in graft rejection. By using antibodies that react with the cell surface-expressed 70-kilodalton heat shock proteins, one may overcome graft rejection.

Animals↗
PubMed1996

[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion].

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adult↗
PubMed1996

[Expression of the small molecular weight matrix metalloproteinase in adenomyosis of the mouse uterus].

The etiology and the pathogenesis of adenomyosis, which is a benign disease featuring ectopic proliferation and invasion of the endometrial stromas and glands into the myometrium, as seen with malignant tumor cells, are still unknown. Adenomyosis induced in mice by intrauterine pituitary isografts was analyzed to study the relationship between adenomyosis and matrix metalloproteinase. Under zymography, adenomyosis showed a gelatiolytic band of 20-30kDa, which was inhibited by EDTA. We then compared matrix metalloproteinase, which is a small protein, with the known pump-1 (MMP7) utilizing RT-PCR and southern blotting hybridization. The PCR product from pump-1 mRNA was clearly detected in both adenomyosis and normal uterus, as in postpartum uterus and kidney in which pump-1 is expressed. These results were confirmed by southern blotting hybridization, and closely resembled the results obtained with RT-PCR. Our study suggests that the small molecular weight matrix metalloproteinase, which is virtually identical to pump-1, may play important roles in adenomyosis at the level of gene transcription, activation, inhibition or otherwise.

Animals↗
PubMed1996

[Experimental studies on the cell adhesion molecule E-cadherin and in vitro invasion of endometrial carcinoma cell lines].

The enhancement of the in vitro invasive ability and the morphological changes caused by anti-E-cadherin antibody HECD-1 were investigated by in vitro invasion assay and electron microscopy in three human endometrial carcinoma cell lines. The cell lines were NUE-1 (E-cadherin negative and high in vitro invasive ability), HEC-1BE and HEC-108 (E-cadherin positive and low in vitro invasive ability). In NUE-1 invasive ability was not enhanced by HECD-1, but in HEC-1BE and HEC-108 invasive ability was enhanced to 223 +/- 41.2% and 307 +/- 173% by 5 micrograms/ml HECD-1. Morphologically NUE-1 invaded the extracellular matrix (Matrigel) with a long micro villis. But in HEC-1BE and HEC-108 the villis did not invade the Matrigel, the whole cell invaded it. Together with HECD-1, HEC-1BE and HEC-108 were changed to become similar to the NUE-1 cell line with high invasive ability and the micro villis invaded the Matrigel.

Adenocarcinoma↗
PubMed1995

High incidence of point mutation in K-ras codon 12 in carcinoma of the fallopian tube.

BACKGROUND: Adenocarcinoma of the fallopian tube is a rare tumor with a poor prognosis. Whether these carcinomas possess any genetic changes that contribute to their malignant behavior is unknown and to date few studies regarding the molecular pathogenesis of these tumors have been reported. In adenocarcinoma of the endometrium, mutations in the first exon of K-ras, although relatively infrequent, were observed to be an independent risk factor for poor clinical outcome. METHODS: Eight patients with adenocarcinoma of the fallopian tube were examined for mutations in the 12th codon of K-ras. DNA was obtained from single sections of paraffin embedded tumor tissue and the first exon of K-ras was amplified by the polymerase chain reaction. Point mutations were assayed using a nonradioactive restriction fragment length polymorphism technique. RESULTS: The eight patients in this study varied in clinical stage from I-IV and were all treated with surgery and chemotherapy. Six of eight of the patients died and one of the surviving patients had metastases in the vertebrae. K-ras point mutations were detected at codon 12 in seven of the eight tumors (87.5%). CONCLUSIONS: K-ras mutations occurred with high frequency in this series of eight patients with fallopian tube carcinoma, suggesting that mutations of this protooncogene could play an important role in the molecular pathogenesis of this lesion.

Adenocarcinoma↗
PubMed1995

Microsatellite instability in endometrial carcinomas: frequent replication errors in tumors of early onset and/or of poorly differentiated type.

Endometrial and ovarian carcinomas are common among women belonging to hereditary nonpolyposis colorectal carcinoma (HNPCC) families; tumors developing in them are characterized by genetic instability due to an inherited dysfunction of the DNA-mismatch-repair system. To clarify the role of similar genetic factors in sporadic forms of gynecological tumors, we examined 77 endometrial and 68 ovarian carcinomas for replication error (RER) at five microsatellite loci. RER-positive phenotypes at two or more microsatellite loci were observed in 18 of the endometrial carcinomas, but in only two of the ovarian carcinomas. Among the patients with endometrial carcinomas, the frequency of RER tended to be higher in those under age 50 than in those over age 60. Furthermore, RER was significantly more frequent in poorly differentiated than in well-differentiated tumors (P = 0.008, Fisher's exact test). These data suggest that genetic factors characterized by RER are likely to play an important role in some endometrial carcinomas, particularly those of early onset and/or of the poorly differentiated type.

Age of Onset↗
PubMed1995

Activation of phospholipase D by prostaglandin F2 alpha in rat luteal cells and effects of inhibitors of arachidonic acid metabolism.

In rat luteal cells labeled with [3H]oleic acid, PGF2 alpha-stimulated phospholipase D (PLD) activation was investigated. The PLD activity was detected by measuring the accumulation of [3H]phosphatidylethanol (PtdEt) in the presence of ethanol. PGF2 alpha stimulated PtdEt accumulation at concentrations of more than 100 nM in the presence of ethanol. However, PtdEt accumulation did not change in the absence of ethanol. PGF2 alpha (1 microM) increased PtdEt accumulation after 1 min, and the accumulation reached a plateau by 2-3 min. These results indicate that PGF2 alpha activates PLD in rat luteal cells. U-73122, a phospholipase C (PLC) inhibitor, and staurosporine, a protein kinase C (PKC) inhibitor, did not inhibit PGF2 alpha-stimulated [3H]PtdEt accumulation. These results suggest that PGF2 alpha-induced PLD activation is different from PLC-PKC systems. We reported previously that PGF2 alpha stimulated the release of arachidonic acid. The effects of indomethacin, nordihydroguaiaretic acid (NDGA), and 5,8,11,14-eicosatetraynoic acid (ETYA), inhibitors of arachidonic acid metabolism, on PGF2 alpha-stimulated PtdEt accumulation were examined. Pretreatment with indomethacin enhanced PGF2 alpha-induced PtdEt accumulation. In contrast, pretreatment with NDGA and ETYA inhibited PGF2 alpha-induced PtdEt accumulation. It is suggested that PGF2 alpha-stimulated PLD activation is mediated via lipoxygenase products.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1995

[Experimental and clinical study on chemotherapy for cervical adenocarcinoma].

We examined the effectiveness of 5 anticancer agents in nude mice transplanted with 4 kinds of uterine cervical adenocarcinoma. MMC, CDDP, ACM, ACD and VP-16 were selected. The therapeutic effects were assessed in terms of growth inhibition rates and histological effects in the transplanted tumors of nude mice. From this study, the following results were obtained: In single agent administration, MMC was effective in all tumors, and CDDP was effective in 3 kinds of tumors as indicated by the results showing growth inhibition rates. Histological findings for the agents did not correlate with therapeutic findings. In combined administration, MMC + CDDP was the most effective as indicated by the results showing growth inhibition rates; this combination showed an additive effect and MMC and CDDP were considered to be key drugs for treating cervical adenocarcinoma. On the basis of these results, we used combination chemotherapy with MMC, CDDP and ACM (PAM regimen) in high risk and advanced patients. We found an improved prognosis in advanced patients. There were one complete response and three partial responses in 7 advanced cases including one suffering recurrence. The combination therapy including MMC, CDDP and ACM was found to be effective against cervical adenocarcinoma.

Aclarubicin↗
PubMed1995

[Is CA125 useful in the management of recurrence of endometrial carcinoma?].

It has been considered that there is no useful serum tumor marker to diagnose endometrial cancer. But recently several reports describe how the serum CA125 value decreases in patients who have received bilateral oophorectomy and in postmenopausal women. In this study, we therefore determined a new cutoff level for serum CA125 and examined the usefulness of serum CA125 in the assessment of recurrence in 42 endometrial cancer cases. These cases were divided into 3 groups: one of 22 low risk cases, 10 moderate risk cases and 10 high risk cases cased by prognosis 1) In the low risk group, 5 cases had a higher serum CA125 level within 1 month after operation than before. 2) In 151 measurements, the mean CA125 value was 9.7 +/- 3.6U/ml, so we considered that 17 U/ml is the cutoff value for determining recurrence. 3) In the low risk group, the CA125 value was either lower than 17U/ml or it has not continued to increase. 4) We divided the high risk group into 3 subgroups into those who had died within 6 months, those who died within 13-14 months and those who died 2-5 years after the initial treatment. In the group who died 13-14 months after the initial treatment, the seurm CA125 level had continued to be high and there was no change in the value after the initial treatment. In the group who died 2-5 years after the initial treatment, the mean +/- S.D. for serum CA125 was 157.3 +/- 158.3U/ml, the maximum was 377U/ml and the minimum was 28U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Antioxidant enzyme activities and oxidative stress in human breast cancer.

We have analysed products of lipid peroxidation reactions and activities of antioxidant enzymes in cancerous breast tissue and in corresponding reference tissue. In addition, the serum lipid peroxidation and peroxyl-radical-trapping capacity of breast cancer patients were compared to those of healthy subjects. A total of 23 patients with breast cancer participated in this study. In the cancerous tissue, catalase activity was lower than in the reference tissue, while the activities of superoxide dismutase, glutathione peroxidase and the hexose monophosphate shunt were elevated. The content of thiobarbituric-acid-reactive material was slightly lower in the cancerous tissues, but the levels in serum were found to be elevated in patients with breast cancer. The amounts of conjugated diene double bonds were essentially equal both in the cancerous and in the reference tissue. Moreover, in breast cancer patients the serum levels of diene conjugation and the peroxyl-radical-scavenging capacity did not differ from those measured in healthy subjects. This study indicates that the antioxidant defence system is altered in cancerous breast tissues, but does not support the hypothesis suggesting that formation of lipid peroxides in the tumour tissue itself is of primary importance in the carcinogenesis.

Antioxidants↗
PubMed1994

1C5 antigen: cancer-associated protein expressed by cervical adenocarcinomas and beta-casein.

The monoclonal antibody 1C5 reacts with an antigenic determinant present in 90% of the cases of adenocarcinoma of the uterine cervix. The antigen defined by the 1C5 antibody exhibits immunological characteristics similar to those of skim milk (bovine buttermilk). 1C5-defined antigen obtained from tumor extract and skim milk binds specifically to wheat germ agglutinin (WGA) lectin. The 1C5-defined antigenic activity of a WGA lectin-bound fraction was eluted at 0.7-0.8 M NaCl off a Mono Q column. Use of an inhibition assay and a dot immunobinding assay revealed that the antigenic epitope defined by the 1C5 MoAb from skim milk exists within the first 28 amino acids of the beta-casein peptide.

Adenocarcinoma↗
PubMed1994

[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group].

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed1994

[The factors involved in invasive ability of endometrial carcinoma cells].

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.

Cadherins↗