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Biomedical subjects

Yoshihiro Kikuchi

Publications and source records attributed to Yoshihiro Kikuchi.

At least 19 recordsLinked to original sources
PubMed2006

Clinical significance of immunocytochemistry for PIK3CA as a carcinogenesis-related marker on liquid-based cytology in cervical intraepithelial neoplasia.

The catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA) has been expected to play a role as an important oncogene in uterine cervical carcinoma, whose expression in non-invasive lesions has received considerable attention. We investigated the potential of PIK3CA as a carcinogenesis-related marker for early intraepithelial lesion of the uterine cervix in cytology samples. Seventy-four cases with abnormal cytology suggesting the existence of cervical intraepithelial neoplasia (CIN) lesions, whose findings were histologically confirmed, were selected; they consisted of 20 CIN1, 21 CIN2, and 33 CIN3, respectively. In addition, 17 normal cases, whose cervical cytology revealed no abnormality over three occasions, were selected. Liquid-based cytology specimens were applied for human papillomavirus (HPV) DNA typing and immunocytochemistry using three different antibodies for p16(INK4a), Ki-67 and PIK3CA, respectively. The fraction of immunopositive cells on the slides was calculated and expressed as mean numbers. Receiver operating characteristic (ROC) plots were generated to determine the diagnostic accuracy of each immunocytochemistry test. The mean number of immunopositive cells in the CIN3 group was significantly higher than other groups for all three antibodies. Among all groups, PIK3CA showed a superior specificity to distinguish CIN3 from other groups. Comparison of three markers by ROC curves also revealed that PIK3CA provided the best method for distinguishing CIN3. Thus, expression of PIK3CA was observed in liquid-based cytology in CIN lesions, which suggested its diagnostic significance in addition to the use of routine cervical cancer smear and the HPV screening program.

Biomarkers, Tumor↗
PubMed2005

Survey of human immunodeficiency virus (HIV)-seropositive patients with mycobacterial infection in Japan.

OBJECTIVE: To assess DNA polymorphisms in mycobacterial isolates obtained from human immunodeficiency virus (HIV)-seropositive patients with tuberculosis in Japan from 1996 to 2003. METHODS: Restriction fragment length polymorphisms (RFLP) from Mycobacterium tuberculosis and Mycobacterium avium isolates obtained from individual seropositive patients with tuberculosis (n=78) were analysed with the use of IS6110 and (CGG)(5) or IS1245 and IS1311, respectively, as markers. As a control, the same procedures were applied to isolates from HIV-seronegative tuberculosis patients (n=87). RESULTS: Of 86 mycobacterial strains, M. tuberculosis, M. avium and Mycobacterium chelonae were identified in 48 (55.8%), 36 (41.9%) and 2 (2.3%) isolates, respectively. The obtained RFLP patterns of M. tuberculosis isolates from both the HIV-seropositive and -seronegative groups were variable, suggesting no obvious clustering among the isolates. Similar results were obtained in isolates of M. avium. CONCLUSIONS: This is the first report on the molecular epidemiology of Mycobacterium spp. isolated from HIV-seropositive patients in Japan. The results indicate that no particular clones of M. tuberculosis or M. avium prevail in HIV-seropositive patients in Japan. Further monitoring of mycobacterial infection associated with HIV infection in Japan should be continued.

Adolescent↗
PubMed2005

Multidrug-resistant Pseudomonas aeruginosa strain that caused an outbreak in a neurosurgery ward and its aac(6')-Iae gene cassette encoding a novel aminoglycoside acetyltransferase.

We characterized multidrug-resistant Pseudomonas aeruginosa strains isolated from patients involved in an outbreak of catheter-associated urinary tract infections that occurred in a neurosurgery ward of a hospital in Sendai, Japan. Pulsed-field gel electrophoresis of SpeI-, XbaI-, or HpaI-digested genomic DNAs from the isolates revealed that clonal expansion of a P. aeruginosa strain designated IMCJ2.S1 had occurred in the ward. This strain possessed broad-spectrum resistance to aminoglycosides, beta-lactams, fluoroquinolones, tetracyclines, sulfonamides, and chlorhexidine. Strain IMCJ2.S1 showed a level of resistance to some kinds of disinfectants similar to that of a control strain of P. aeruginosa, ATCC 27853. IMCJ2.S1 contained a novel class 1 integron, In113, in the chromosome but not on a plasmid. In113 contains an array of three gene cassettes of bla(IMP-1), a novel aminoglycoside resistance gene, and the aadA1 gene. The aminoglycoside resistance gene, designated aac(6')-Iae, encoded a 183-amino-acid protein that shared 57.1% identity with AAC(6')-Iq. Recombinant AAC(6')-Iae protein showed aminoglycoside 6'-N-acetyltransferase activity by thin-layer chromatography. Escherichia coli expressing exogenous aac(6')-Iae showed resistance to amikacin, dibekacin, isepamicin, kanamycin, netilmicin, sisomicin, and tobramycin but not to arbekacin, gentamicins, or streptomycin. Alterations of gyrA and parC at the amino acid sequence level were detected in IMCJ2.S1, suggesting that such mutations confer the resistance to fluoroquinolones observed for this strain. These results indicate that P. aeruginosa IMCJ2.S1 has developed multidrug resistance by acquiring resistance determinants, including a novel member of the aac(6')-I family and mutations in drug resistance genes.

Acetyltransferases↗
PubMed2005

Application of expression genomics for predicting treatment response in cancer.

During tumor progression, multiple genetic changes in the genome vastly alter the transcriptomes of cancers. Some of these changes, including the mutations of various growth regulatory genes as well as alterations in the transcription of a large number of genes, may lead to resistance to treatment. Therefore, capturing such genomic information of the tumors would enable a physician to decide on the course of treatment options clinically available. Currently, it is still not feasible to identify all the genetic mutations that have occurred in a patient's cancer genome. However, the advent of DNA microarray coupled with the completion of the human genome sequence and the identification of all its genes, have made possible genome-wide gene expression profiling of the cancer genome. In this review, we will focus on the application of expression genomics for identifying signature gene expression profiles in primary cancers to predict response to either radio- or chemotherapy. We envision that transcription profiling of the cancer genomes ultimately will not only reveal how altered gene expression results in resistance to treatment, but also be exploited for predicting and personalizing cancer therapy.

Animals↗
PubMed2005

Cerebral edema on MRI in severe preeclamptic women developing eclampsia.

OBJECTIVE: The aim of this study is to identify suitable applications for cerebral MR (magnetic resonance) scanning in cases of severe preeclampsia and eclampsia through comparison of clinical course and easily accessible parameters. METHODS: From January 2001 to December 2003, cerebral MR scans were performed on 43 women with severe preeclampsia; of those 41 were enrolled in data analyses. Twenty clinical parameters, including age, body mass index, blood pressure, liver and renal function, and coagulation status, were compared for each patient. Data were analyzed using the SPSS program on a VAX main frame. RESULTS: Among 41 severe preeclamptic women, abnormal MR images were observed in 11 cases including six with systemic seizures. Predictive accuracy of eclampsia with abnormal cerebral MR imaging was 84.9% (P=0.00001), while only 14.3% of severe preeclampsia cases had been diagnosed radiologically. Statistical analysis suggests diastolic BP and serum AST as predictive parameters for abnormal MR images with 82.9% predictive accuracy (P=0.0007). CONCLUSIONS: Cerebral edema can be observed in preeclamptic patients developing eclampsia. Rapid delivery is indicated when diastolic BP and AST are elevated. MR scanning is useful when delivery is delayed due to fetal immaturityin cases of severe preeclampsia.

Acute Disease↗
PubMed2005

Treatment options in the management of ovarian cancer.

The standard regimen used as primary chemotherapy of ovarian cancer is combination chemotherapy using paclitaxel and carboplatin. The main objective of first-line chemotherapy is to induce complete response. Although most cases respond to the initial chemotherapy, many cases relapse within 3 years. Such relapsed and persistent cases become resistant to first-line chemotherapy and require second-line chemotherapy. Objectives of such a second-line chemotherapy are to obtain disease palliation to cease disease progression. Meanwhile, consolidation or maintenance chemotherapy may be added to prevent or inhibit disease relapse for patients with advanced disease after induction of complete remission by a primary chemotherapy. When the unresectable tumour is presumed by primary surgery, neoadjuvant chemotherapy may be selected. Recently, conventional cytotoxic anticancer drugs containing paclitaxel have been shown to be capable of inhibiting angiogenesis. The notion of 'redefining' chemotherapeutic drugs has been recognised; thus, continuous low-dose chemotherapy -- so-called metronomic chemotherapy -- has been approved as a new concept. Many new molecular-targeted therapies became available for clinical cancer therapy. The explosion of new molecular targets and the development and application of many powerful technologies should accelerate the discovery of innovative molecular therapeutics. Understanding the molecular mechanisms will help to clarify the pathways in ovarian cancer development and help to identify new therapeutic and diagnostic targets. These are exciting times for new drug development and the treatment of cancer. Cautious optimism should prevail for all investigators involved in translating these exciting new biological findings into new pharmacological agents for treatment of cancer.

Angiogenesis Inhibitors↗
PubMed2004

Extracellular cAMP-dependent protein kinase (ECPKA) in melanoma.

Melanoma is one of the fastest rising malignancies in the United States. When detected early, primary melanomas are curable through surgery. However, despite significant improvements in diagnosis and surgical, local and systemic therapy, mortality rate in metastatic melanoma remains high. Furthermore, genetic alterations associated with the development and stepwise progression of melanoma, are still unclear. Previous reports show that the catalytic kinase subunit of the cAMP-dependent protein kinase is secreted by tumor cells and can be detected in the serum of cancer patients. We examine in this report the clinical significance of this secreted C subunit kinase termed extracellular protein kinase (ECPKA) in melanoma patients. Our results showed the presence of ECPKA activity in the serum of melanoma patients and correlate with the appearance and size of the tumor. Most importantly, surgical removal of melanoma causes a precipitous decrease in ECPKA activity in the sera of patients, suggesting that ECPKA may be a novel predictive marker in melanoma.

Cyclic AMP-Dependent Protein Kinases↗
PubMed2004

The effect of single weekly paclitaxel in heavily pretreated patients with recurrent or persistent advanced ovarian cancer.

OBJECTIVES: We have reported that single weekly paclitaxel has moderate activity in heavily pretreated ovarian cancer patients and is associated with a favorable toxicity profile. The purpose of this study was to reconfirm the effect of weekly paclitaxel in more number of cases. METHODS: Although 39 patients were enrolled, 37 patients with recurrent or persistent ovarian cancer previously treated with between one and three chemotherapeutic regimens containing platinum were eligible. Patients had measurable or assessable disease defined by clinical exam, radiographic studies, or serum CA 125. One cycle of treatment consisted of paclitaxel 80 mg/m2/week in 1-h infusion, 3 weeks on, 1 week off, and repeated at least twice. Two patients were withdrawn because of refusal of further treatment for neuropathy after the first cycle. Clinical responses were defined by established criteria. RESULTS: Thirty-seven patients were included in this intent-to-treat study. The overall clinical response rate was 45.9% (5 complete responses, 12 partial responses). The clinical response rate in patients with measurable tumor was 25.0% (2 complete responses, 1 partial response), while that in patients without measurable tumor and with assessable CA 125 levels was 56.0% (3 complete responses, 11 partial responses). Clinical response rate in patients with chemotherapy-free interval more than 6 months had about twice higher than that in patients with chemotherapy-free interval less than 6 months. The clinical response rate by number of prior regimens revealed that as number of prior regimens increases, the response rate decreases. CONCLUSION: Weekly paclitaxel has significant antitumor activity in heavily pretreated patients with recurrent or persistent ovarian carcinoma and warrants as second or third line chemotherapy in such setting.

Adult↗
PubMed2004

Chronic administration of single weekly paclitaxel in heavily pretreated ovarian cancer patients.

Ovarian cancer patients with paclitaxel-resistance have been reported to respond to a weekly schedule of the same drug. In this report, two cases with long progression free interval by weekly paclitaxel (T) are presented. Case 1. A 41-year-old Japanese woman, gravida 2, para 0, was referred to our hospital in September 16, 1998, because of abdominal mass accompanying large amount of ascites with elevated CA125 (8400 U/ml) and CA19-9 (770 U/ml). Exploratory laparotomy (tumor biopsy plus partial omentectomy) was performed September 21, 1998. After the surgery, the tumor was diagnosed as serous cystadenocarcinoma of the ovary (stage IV) and 6 cycles of treatment consisting of cyclophosphamide, adriamycin and cisplatin (CAP) were performed. The CA 125 level (8400 U/ml) rapidly declined to 150 U/ml by this CAP therapy. After second cytoreductive surgery (SRS) (total hysterectomy and bilateral salpingo-oophorectomy), residual tumor was less than 2 cm. Although 7 cycles of CAP was added, ascites and elevation of CA 125 (5100 U/ml) were observed. Therefore, treatment with single weekly T was performed and CA 125 levels remained between 70-90 U/ml during 13 cycles of this therapy (progression free interval; more than 1 year). Thereafter, she is alive with disease and followed-up. Case 2. A 48-year-old Japanese woman, gravida 3, para 2, was referred to our hospital in July 22, 1998, because of abdominal swelling and pain. Computing tomography (CT) and magnetic resonance imaging (MRI) revealed large amount of ascite and pelvic mass (9 x 7 x 7 cm), and low density area (3 x 3 cm) suggesting metastasis in right lobe of liver. Serum CA 125 level elevated to 5100 U/ml. Bilateral salpingo-oophorectomy and infracolic omentectomy were performed on August 5, 1998. The tumor was diagnosed as endometrioid adenocarcinoma of the ovary, stage IV and chemotherapy with CAP was initiated on September 5, 1998. After 6 cycles of CAP, SRS was performed. After SRS, 3 cycles of CAP were added and changed to weekly T because of damage of renal function. The CA 125 level returned within normal range during weekly T. Total 13 cycles of weekly T were performed and progression free interval was about 18 months. Thereafter, she received treatments with gamma knife and CAP for brain metastasis. She is alive without disease and followed-up. Side effects by weekly T were mild and tolerable despite of long term treatment. In addition, weekly T can be safely used in outpatient setting and even in patients with poor performance status (PS), and warrant long time to progression.

Adult↗
PubMed2004

[The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in paclitaxel combination chemotherapy for epithelial ovarian carcinoma].

Shakuyaku-Kanzo-to was first medicated for muscular pain which was called Komuragaeri, and it has been reported that it is effective for peripheral nerve dysfunction such as arthralgia and numbness. Recently, Paclitaxel (T) and Carboplatin (J) combination chemotherapy (TJ chemotherapy) has been a standard first-line chemotherapy for epithelial ovarian carcinoma. For the arthralgia and muscular pain occurring in TJ chemotherapy, non-steroid-anti-inflammatory drugs (NSAIDs), Vitamin B12 (VB12) and Shakuyaku-Kanzo-to are the major medications. In this study, we examined twenty-one cases in which arthralgia and muscular pain occurred in TJ chemotherapy (including 16 cases as first-line chemotherapy). In all cases, patients took 7.5 g of Shakuyaku-Kanzo-to orally per day for eight days. We investigated the efficacy of Shakuyaku-Kanzo-to retrospectively with the following results. In nine cases (43%), Shakuyaku-Kanzo-to was effective in reducing pain. Especially in TJ chemotherapy as first-line chemotherapy, Shakuyaku-Kanzo-to was even more effective in reducing pain. We suggested that Paclitaxel combination chemotherapy with Shakuyaku-Kanzo-to taken orally is a more safe and tolerable way to reduce pain in epithelial ovarian carcinoma.

Adult↗
PubMed2004

Amplicon profiling reveals cytoplasmic overexpression of MUC1 protein as an indicator of resistance to platinum-based chemotherapy in patients with ovarian cancer.

Chromosomal gains of 1q21-q22 and 13q12-q14 were closely related with the chemoresistance of patients with ovarian cancer in our previous CGH (comparative genomic hybridization) study. We conducted the present study to determine the amplified genes on chromosome 1q. Comparisons of relative copy numbers of clinically platinum-sensitive ovarian tumors (CR-group, n=14) and platinum-resistant tumors (PD-group, n=14) were carried out using real-time PCR from ten different gene loci on chromosome 1q. Increased copy numbers were frequently observed in PD-group tumors, especially in the region between WI-8123 and MUC1. Relative copy number of MUC1 over 1.5 was observed in 13 (92%) of 14 PD-group tumors and 3 (21%) of 14 CR-group tumors (p<0.05). Moreover, cytoplasmic expressions of MUC1 protein were significantly higher in PD-group than those in CR-group (p<0.01). We concluded that the cytoplasmic overexpression of MUC1 might be an indicator of resistance to platinum-based chemotherapy and a prognostic marker in ovarian cancer.

Aged↗
PubMed2004

[Clinical study on the efficacy of weekly paclitaxel administration for platinum-resistant epithelial ovarian carcinoma].

OBJECTIVE: Recently, paclitaxel (T) and carboplatin (J) combination chemotherapy has been a standard first-line chemotherapy for epithelial ovarian cancer and has improved its prognosis. But we have many chemoresistant cases, and we examined the efficacy of weekly, single-agent, paclitaxel administration. METHODS: Seven cases were included in this study. In all cases weekly paclitaxel administration (weekly-T chemotherapy) was performed because of the resistance to pre-treated platinum-based chemotherapy. In all cases the clinical stage was III c, and the histologic types consisted of four serous adenocarcinomas and three clear cell carcinomas. The number of courses and regimens in pre-treated chemotherapy was 8 to 16 (median 9) and 1 to 3 (median 2). Performance status (PS) was more than 2 in four cases. During weekly-T chemotherapy, 80 mg/m2 of paclitaxel was intravenously administered weekyl for 1-hour three times over two weeks, and next administration was performed two weeks later. 2 to 7 (mean 3.9) courses of weekly-T chemotherapy were performed in this study. RESULTS: The treatment outcomes of weekly-T chemotherapy were 2 partial remission (PR), 3 no change (NC) and 2 progressive disease (PD). Though peripheral neuropathy occurred in five cases (71%), the drug for neuropathy needed to be administered in only one case (14%). While the toxicity of hemoglobin was worse than grade 3 in 13 courses (48%), hematological and non-hematological toxicity was mild. CONCLUSION: The findings suggested that weekly-T chemotherapy was effective for heavily treated ovarian cancer patients in terms of both toxicity and quality of life (QOL).

Adult↗
PubMed2004

Successful management of cervical pregnancy by selective uterine artery embolization: a case report.

BACKGROUND: Cervical pregnancy is potentially associated with life-threatening hemorrhage and often requires hysterectomy to stop the bleeding. Conservative management is becoming more common as treatment of cervical pregnancy. CASE: A case of cervical pregnancy presented with a severe vaginal hemorrhage at 6 weeks' gestation. The patient was conservatively managed with selective bilateral uterine artery embolization (UAE). The vaginal bleeding stopped completely after UAE. The clinical course was uneventful and serum human chorionic gonadotropin decreased immediately. The cervical mass gradually shrank and disappeared on the 31st day after UAE. UAE. CONCLUSION: This was the second case of cervical pregnancy successfully treated with only UAE.

Adult↗
PubMed2003

Immunological and endocrinological studies on lymphocyte subpopulation and medical treatment for infertility in patients with endometriosis.

We investigated the relationship between interleukin-6 (IL-6) levels and subset profiles of T lymphocyte (T-cell) and macrophage in peritoneal fluid (PF) with or without endometriosis (EM). IL-6 levels in PF with EM were significantly higher than those without EM. IL-6 producing cells with EM were analyzed in each activated mature T-cell (CD3+CD69+) and macrophage (CD14+) were 0.5 and 3.5%, respectively, whereas it was mostly negative in those without EM. Cytotoxic T-cell (CD8+CD11b-) profiles in PF with EM were also quiet different from those without EM. Cellular immunity in the peripheral blood did not change during the course of IVF-ET cycles, although plasma levels of ovarian steroid hormones significantly increased comparing with that in normal ovarian cycles. Cytotoxic T-cell type 1 (Tc1) profiles might be useful predictive values in the pregnancy outcome for infertile patients with EM.

Ascitic Fluid↗
PubMed2003

Malignant mixed Mullerian tumor of the uterine corpus with alpha-fetoprotein-producing hepatoid adenocarcinoma component.

OBJECTIVES: Hepatoid adenocarcinoma is a rare tumor and has the histological coexistence of well-differentiated adenocarcinoma and nests of hepatoid cells with immunoreactivity for alpha-fetoprotein (AFP). A case of hepatoid adenocarcinoma in malignant mixed Mullerian tumor of the uterus is presented with a review of the literature. CASE: The patient is a 63-year-old woman who complained of abnormal genital bleeding. Serum AFP concentration was 5060 ng/ml. Histologically, the tumor was composed of endometrioid adenocarcinoma, neoplastic hepatoid cells, and sarcoma component including leiomyosarcoma and rhabdomyosarcoma. After operation followed by six courses of platinum-based chemotherapy, serum levels of AFP dropped into normal range. CONCLUSIONS: This is, to our knowledge, the first report of malignant mixed Mullerian tumor of the uterus with an AFP-producing hepatoid adenocarcinoma component.

Carcinoma, Hepatocellular↗