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Daisuke Aoki

Publications and source records attributed to Daisuke Aoki.

At least 19 recordsLinked to original sources
PubMed2026

Survey on the current status of novel cancer drug therapies for gynecological cancers in Japan: a nationwide survey by the Japan Society of Obstetrics and Gynecology (JSOG).

OBJECTIVE: To characterize real-world implementation of novel therapies in gynecological oncology in Japan and identify actionable gaps through a nationwide survey. METHODS: A cross-sectional questionnaire was distributed to Japan Society of Obstetrics and Gynecology-affiliated institutions. The items covered institution characteristics; use of poly (ADP-ribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors (ICIs), kinase inhibitors, and antibody-based agents; local adverse event (AE) manuals; availability of expert panels and immune-related adverse event (irAE) teams; and perceptions of educational sufficiency. RESULTS: Valid responses were obtained from 245 institutions, spanning universities, cancer centers, and general hospitals. Most institutions reported the routine use of PARP inhibitors, ICIs, kinase inhibitors, and antibody drugs. However, only 40.4% of institutions had an in-hospital irAE management team, 57.1% had an AE/irAE manual, and 31.0% and 12.2% considered prior educational opportunities sufficient for physicians and nurses/other medical staff, respectively. High-volume institutions and academic centers were significantly more likely to have medical oncology support, expert-panel access, irAE teams, manuals, and higher self-rated evidence-based management capacity. The majority favored e-learning and society-led case conferences, and 76.3% supported the development of drug therapy subspecialties in gynecologic oncology. CONCLUSION: Innovative drug modalities are widely implemented across Japanese gynecological oncology services. However, critical gaps persist in multidisciplinary irAE management, standardized manuals, and practical education. Coordinated society-led programs to expand irAE teams, streamline companion diagnostics, disseminate ready-to-use algorithms, and provide credential-targeted training may enhance safety, equity, and evidence-concordant care nationwide.

Immune Checkpoint Inhibitors↗
PubMed2007

Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer.

The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanes in endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFR in 12.0% (6/50) of endometrial cancer specimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p<0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanes but became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFR also exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFR in endometrial cancer, and our results suggest that the methylation status of CHFR may be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.

Adult↗
PubMed2006

Systemic distribution and tissue localizations of human 17beta-hydroxysteroid dehydrogenase type 12.

The 17beta-hydroxysteroid dehydrogenases (HSDs) are enzymes that catalyze the reduction of 17-ketosteroids or the oxidation of 17beta-hydroxysteroids. 17beta-HSD type 12, the most recently cloned member of this gene family, was classified into the 17beta-HSD family based on sequence homology, rather than steroid catalyzing activity. Meanwhile, it has been reported that 17beta-HSD type 12 may be involved in fatty acid synthesis. To better understand the role of 17beta-HSD type 12 in lipid metabolism, we determined the detailed systemic distribution and tissue localizations of 17beta-HSD type 12, which, due partly to the lack of antibodies, had not yet been studied. We carried out these investigations by quantitative reverse transcription (RT)-PCR, Northern blot analysis, and immunohistochemistry, using an antibody against 17beta-HSD type 12 that we have generated. 17beta-HSD type 12 is highly expressed in organs related to lipid metabolism such as liver, kidney, heart and skeletal muscle. 17beta-HSD type 12 is also detected in endocrine-related organs such as pancreas, pituitary gland, adrenal gland, testis and placenta, and in the gastrointestinal tract, which point to the possible involvement of 17beta-HSD type 12 in the regulation of lipid biosynthesis and steroid metabolism. These results support previous reports and solidify the possibility that 17beta-HSD type 12 may play critical roles in the physiological processes, such as fatty acid synthesis, in addition to the steroid metabolism.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

Proliferative activity of early ovarian clear cell adenocarcinoma depends on association with endometriosis.

OBJECTIVE: To investigate differences in the biological characteristics of ovarian clear cell adenocarcinoma based on the presence/absence of endometriosis and tumor proliferative activity. METHODS: Stage I ovarian clear cell adenocarcinoma patients were divided into groups with and without endometriosis, and immunohistochemical expression of proliferating cell nuclear antigen was determined in surgical specimens. Then xenograft models of human ovarian clear cell adenocarcinoma with or without human ectopic endometrium were created in severe combined immunodeficiency mice, and tumor growth was assessed from the wet weight and the bromodeoxyuridine uptake. Furthermore, a xenograft model of human endometriosis was made with or without ovarian clear cell adenocarcinoma and cytokine production was investigated. RESULTS: The proliferating cell nuclear antigen labeling index was significantly lower in the tumors of patients with endometriosis compared to the tumors of patients without endometriosis. In tumor-bearing mice, the tumor weight and bromodeoxyuridine uptake were both significantly lower when ovarian clear cell adenocarcinoma was associated with endometriosis than in its absence. Release of transforming growth factor-beta1 and interleukin-6 from the ectopic human endometrium was greater in the presence of clear cell adenocarcinoma than without it, and transforming growth factor-beta1 levels showed a significant difference. CONCLUSION: The proliferative activity of early ovarian clear cell adenocarcinoma seems to depend on the association of this cancer with endometriosis. When endometriosis is associated with ovarian clear cell adenocarcinoma, there is a change of its cytokine production that may inhibit tumor growth.

Adenocarcinoma, Clear Cell↗
PubMed2006

Evaluation of super-high-dose steroid therapy for sudden sensorineural hearing loss.

OBJECTIVE: To determine the efficacy of a high-dose steroid regimen for patients with sudden sensorineural hearing loss (SSNHL) and to evaluate the relationship between outcome and initial steroid dose. STUDY DESIGN AND SETTING: We conducted a retrospective study of 112 patients presenting to Saitama Medical Center. Patients received tapering courses of hydrocortisone (HC) with an initial dose of either 1200 mg or 600 mg. RESULTS: More than 87% of patients had recovery of hearing. When hearing stabilized, there were no significant differences between the 1200 mg and 600 mg groups in terms of hearing outcome (P>0.05). However, at completion of treatment, the 1200 mg group exhibited significantly superior complete recovery rate and improvement rate (P<0.05). CONCLUSION: Application of our treatment protocol of a tapered course of 1200 mg HC significantly and rapidly improves recovery outcomes in patients of SSNHL. EBM RATING: C-4.

Acute Disease↗
PubMed2006

DNA sequencing and transcriptional analysis of the kasugamycin biosynthetic gene cluster from Streptomyces kasugaensis M338-M1.

Streptomyces kasugaensis M338-M1 produces the aminoglycoside antibiotic kasugamycin (KSM). We previously cloned, sequenced and characterized the KSM acetyltransferase, transporter, and some of the biosynthetic genes from this strain. To identify other potential genes in a chromosome walk experiment, a 6.8-kb EcoRI-PstI region immediately downstream from the KSM transporter genes was sequenced. Five open reading frames (designated as kasN, kasO, kasP, kasQ, kasR) and the 5' region of kasA were found in this region. The genes are apparently co-transcribed as bicistrons, all of which are co-directional except for the kasPQ transcript. Homology analysis of the deduced products of kasN, kasP, kasQ and kasR revealed similarities with known enzymes: KasN, D-amino acid oxidase from Pseudomonas aeruginosa (35% identity); KasP, F420-dependent H4MPT reductase from Streptomyces lavendulae (33% identity); KasQ, UDP-N-acetylglucosamine 2-epimerase from Streptomyces verticillus (45% identity); and KasR, NDP-hexose 3,4-dehydratase from Streptomyces cyanogenus (38% identity); respectively. A gel retardation assay showed that KasT, a putative pathway-specific regulator for this gene cluster, bound to the upstream region of kasN and to the intergenic region of kasQ-kasR, suggesting that the expression of these operons is under the control of the regulator protein.

Amino Acid Sequence↗
PubMed2006

Lactation and risk of endometrial cancer in Japan: a case-control study.

The incidence of endometrial cancer is rapidly increasing in Japan. Although the risk factors in European populations have been well described, there are few epidemiologic studies regarding risk factors for endometrial cancer in Japanese women. This hospital-based case-control study among Japanese women was carried out from 1998 to 2000. The cases were selected from women with endometrial cancer (n =155), and the controls selected from women attending the university gynecological outpatient clinic for cervical cancer screening (n = 96). Subjects were interviewed to ascertain breast feeding practices, contraceptive usage, as well as potential risk factors for endometrial cancer. We observed a lower risk of endometrial cancer associated with oral contraceptive (OC) and a higher risk associated with higher body mass index (BMI), and older ages at first and last delivery. Gravidity reduced odds ratio (OR) for endometrial cancer to 0.34 (95% confidence interval [CI] 0.13-0.92). Compared with parous women who had never breastfed, the multivariate OR for women with a history of breastfeeding was 0.37 (95% CI, 0.17-0.82). Additionally, a greater lapse of time since breastfeeding increased OR for endometrial cancer by over three times. In conclusion, the present study has indicated that breastfeeding reduces the risk of endometrial cancer in Japanese women.

Adult↗
PubMed2006

[Clinical study on deep neck infection].

Deep neck infection (DNI) remains an emergent and life-threatening otolaryngologic disease. We examined 69 patients, 52 men and 17 women, with DNI, who were treated in our hospital between January 1995 and December 2004. The mean age of the patients with DNI was 50.0 years and the peak incidence was in the sixth decade. Twenty patients suffered from diabetes mellitus (DM). The primary DNI lesion was found in the tonsils in 34 cases, the oral cavity in 16 cases, and the pharynx in 12 cases, respectivelys. Among the 69 patients with DNI, the infection remained in the suprahyoid region in 31 cases, but it extended to the infrahyoid region in 33 cases and to the mediastinum in 5 cases. The titer of C-reacting protein (CRP) and the duration of admission were considered as parameters of the severity of DNI. CRP was significantly higher in elderly patients, in patients with DM, and in patients whose infection extended to the infrahyoid region and to the mediastinum, however, significant difference was not found between men and women, or among the types of primary DNI lesions. Moreover, the duration of admission was significantly longer in elderly patients, in patients with DM, and in patients with infrahyoid and mediastinal DNI, whereas no significant differences were found between men and women or among the types of primary lesions. Therefore, age, DM, and the extension of DNI are considered to be important factors which determining the severity of DNI.

Abscess↗
PubMed2006

Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer.

Human papillomavirus (HPV) 18 is related not only to squamous cell carcinoma of the cervix, but also to adenocarcinoma and small cell carcinoma of the cervix, in which prognosis is known to be poor. Small interfering RNA (siRNA) that targets HPV18 E6 and E7 was tested in HPV18-positive cell lines to investigate its effect and investigate its mechanism of action. Nude mice were also tested in a combination of siRNA and atelocollagen to determine whether it might be useful as a new molecule-targeting therapy for cervical cancer. siRNAs targeting HPV18 E6 and E7 were transfected into cervical cancer cells in vitro and they were investigated for cell growth inhibition, expression of E6 and E7 mRNA, expression of retinoblastoma protein, and senescence-associated beta-galactosidase staining. Sequence-specific siRNA inhibited cell growth. Decreased expression of E6 and E7 mRNA followed with E7 protein was observed in the transfected cells, but the expression of retinoblastoma protein and the beta-galactosidase staining increased, suggesting cell growth inhibitory effect through senescence. Treatment of xenografts established from SKG-II cells with siRNA specific for E6 and E7 obviously suppressed tumor growth in vivo. These results indicate that atelocollagen-mediated delivery of siRNA HPV18 E6 and E7 can be used as a novel therapeutic approach for cervical cancer.

Animals↗
PubMed2006

Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer.

Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLH1 and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.

DNA Methylation↗
PubMed2005

Identification of tissue-specific vasculogenic cells originating from murine uterus.

Endometrium is a highly regenerative adult tissue that undergoes repeated degeneration and regeneration following menarche. Therefore, it is believed that endometrium contains stem and/or progenitor cells in order to compensate for the regeneration of tissue components. We report here that stem-like cells having vasculogenic potential are present in the uterus. Enzymatically extracted cells from murine uteri were characterized and fractionated into four subpopulations by flowcytometry; CD34(+)/45(-) (Ut-34), CD34(-)/45(-) (Ut-DN) and the remaining CD45(+) cell fractions (CD34(+)/45(+) and CD34(-)/45(+) cells). The Ut-34 and Ut-DN fractions were mostly negative for putative endothelial cell (EC) markers, such as CD31, Flk-1, c-kit and VE-cadherin, although the Ut-DN fraction contained 2.8% CD31(+) cells. Ut-DN cells were further divided into CD31(+) and CD31(-) fractions. Three cell populations were obtained from green fluorescence protein (GFP) transgenic mice and were transplanted into injured wild-type mouse skeletal muscle. At 4 weeks after cell transplantation, donor-derived vascular smooth muscle and ECs were observed in the injured recipient muscle. A similar trend was observed in the Ut-34 group, but differentiation into vascular smooth muscle was predominant. In contrast, the Ut-DN/31(+) cell-transplanted group showed preferential differentiation into vascular ECs, thus suggesting that they were relatively committed preexisting ECs. These characteristics were also seen in vitro, in clonal cell cultures. Interestingly, donor derived Ut-DN/31(+), Ut-DN/31(-) and Ut-34 cells could not be identified after bone marrow (BM) transplantation, thus confirming that they are not derived from BM. It therefore appeared that tissue-specific vasculogenic cells are present in the murine uterus and that they exhibit vascular formation, even in different tissue microenvironments.

Animals↗
PubMed2005

Intermittent pneumatic compression for prevention of pulmonary thromboembolism after gynecologic surgery.

BACKGROUND: To investigate the incidence of pulmonary embolism and risk factors for this condition after obstetric and gynecologic surgery, as well as the efficacy of intermittent pneumatic compression. METHODS: A total of 6,218 patients operated at Keio University Hospital excluding obstetric or infertility-related surgery and uterine cervical conization were evaluated retrospectively to determine the preventive effect of intermittent pneumatic compression on postoperative pulmonary embolism. RESULTS: Pulmonary embolism occurred in 42 patients (0.68%). Multivariate analysis showed that malignancy, blood transfusion, and a body mass index > or =25 kg/m2 or > or =28 kg/m2 were independent risk factors for postoperative pulmonary embolism. A significantly lower incidence of pulmonary embolism occurred in patients receiving pneumatic compression postoperatively versus those without it. Among gynecologic malignancies, endometrial cancer was a significant risk factor for pulmonary embolism. CONCLUSION: Preventive measures, including intermittent pneumatic compression, should be taken to avoid postoperative pulmonary thromboembolism in the gynecology field.

Journal Article↗
PubMed2005

Paraneoplastic cerebellar degeneration with fallopian tube adenocarcinoma.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is rarely caused by fallopian tube adenocarcinoma. CASE: We present a patient with PCD and fallopian tube cancer. Anti-Yo antibody, one of an anti-neuronal antibody, was positive in serum and cerebrospinal fluid. She was also positive for HLA A24, which is common in patients with PCD. Radical surgery did not significantly ameliorate her neurological impairment, although the dysarthria improved slightly. CONCLUSION: This case highlights the importance of detecting the underlying malignancy in patients with subacute neurological impairment and shows that fallopian tube cancer can potentially cause PCD.

Adenocarcinoma↗
PubMed2005

Clinical characteristics of prognostic factors in poorly differentiated (G3) endometrioid adenocarcinoma in Japan.

BACKGROUND: It has been reported that prognosis is less favorable in poorly (G3) differentiated endometrioid adenocarcinoma than in well (G1) or moderately (G2) differentiated endometrioid adenocarcinoma. The goal of this study is therefore to analyze the prognosis of G3 endometrioid adenocarcinoma and various factors that may predict a favorable prognosis. METHOD: This study included 699 Japanese cases of endometrioid adenocarcinoma at the International Federation of Gynaecology and Obstetrics (FIGO) surgical stages I-IV (including 74 G3 cases). We investigated the G1-G3 survival rates of endometrioid adenocarcinoma cases and the G2 and G3 disease-free periods. We also examined the clinicopathological characteristics of G3 endometrioid adenocarcinoma. RESULT: The prognosis was poor in stages III and IV in G3 and in G2 cases, but recurrence was observed more frequently in G3 cases than in G2 cases. Adnexal metastasis and high pre-surgery CA602 values showed significantly low P-values for survival. CONCLUSIONS: We suggest that the risk of late recurrence is higher in G3 than in G2 cases. The absence of adnexal metastasis and low pre-surgery CA19-9 values may suggest a relatively favorable prognosis in G3 endometrioid adenocarcinoma.

Adult↗
PubMed2005

Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer.

AIM: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed. METHODS: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent. RESULTS: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P < 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%). CONCLUSION: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.

Adenocarcinoma↗
PubMed2005

Establishment and characterization of the RMG-V cell line from human ovarian clear cell adenocarcinoma.

A cell line, designated as RMG-V, was established from a patient with clear cell adenocarcinoma of the ovary. The cell line has grown without interruption and has been propagated continuously by serial passaging (more than 36 times) over 5 years. The cells are spindle-shaped, display neoplastic and pleomorphic features, and grow in a jigsaw puzzle-like arrangement while forming monolayers without contact inhibition. These cells proliferate rapidly, and the population doubling time is about 15.5 hours. The number of chromosomes ranges between 77 and 85, with a modal number of 83.

Adenocarcinoma, Clear Cell↗
PubMed2005

Loss of integrin alpha3 expression associated with acquisition of invasive potential by ovarian clear cell adenocarcinoma cells.

Among various types of surface epithelial ovarian carcinoma, clear cell adenocarcinoma often has a particularly poor prognosis even when diagnosed in stage I. It is resistant to existing anticancer drugs and appears to have different biological properties to other histological types of ovarian cancer. The present study was conducted using cell lines derived from ovarian clear cell adenocarcinoma in order to identify genes associated with the acquisition of malignant potential by this type of cancer. Two cell lines derived from ovarian clear cell adenocarcinoma (RMG-I and RMG-V), with different levels of invasive potential in an invasion assay, were used. DNA fragments were extracted from the band showing differences in the level of expression by RT-PCR with fluorescent differential display. A total of 56 different DNA base sequences were determined by direct sequencing. Primers were established using these base sequences and the level of expression in each cancer cell line was determined by real-time PCR. Integrin a3, the gene of which is present on chromosome 17q, was identified. It was also detected by a microarray analysis as one of the molecules showing a different level of expression between the two cell lines. Then the pattern of integrin a3 expression was investigated using immunocytochemical staining, and was found to differ between the two cell lines. The findings obtained using these cell lines derived from ovarian clear cell adenocarcinoma indicate that integrin alpha3 may associated with the acquisition of malignant potential by clear cell adenocarcinoma.

Adenocarcinoma, Clear Cell↗