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Biomedical subjects

Hiroyuki Kuramoto

Publications and source records attributed to Hiroyuki Kuramoto.

At least 19 recordsLinked to original sources
PubMed2006

Is peritoneal cytology a prognostic factor of endometrial cancer confined to the uterus?

OBJECTIVE: The goal of this study was to investigate whether intraoperative peritoneal cytology serves as a prognostic factor in patients with the endometrial cancer limited to the disease confined to the uterus. METHODS: From patients with endometrial cancer treated at 2 facilities between 1988 and 2001, 307 patients were selected for retrospective investigation. To be included in this study, patients required (1) full surgical staging including total abdominal hysterectomy/bilateral salpingo-oophorectomy/retroperitoneal lymph node dissection/peritoneal cytology, (2) negative nodes, (3) disease localized to the uterus and (4) endometrioid subtype. RESULTS: The median duration of the follow-up period was 61 months (25th to 75th percentiles: 45 to 92 months). Peritoneal cytology was positive in 32 patients (10.4%). The 5-year survival rate of peritoneal-cytology-positive patients was 87%, significantly lower than that (97%) of cytology-negative patients (P = 0.011). The relationship between the clinicopathological factors including peritoneal cytology and the prognosis was investigated by univariate analysis, and peritoneal cytology positivity, age of 60 years or older, histologic grade (Grades 2 and 3), myometrial invasion of 1/2 or more and vascular invasion were significant prognostic factors (P < 0.05 in all). On multivariate analysis of these factors, peritoneal cytology positivity and histologic grade (Grade 2 and 3) were independent prognostic factors (P < 0.05 each). CONCLUSIONS: For the patients with endometrial cancer limited to the disease confined to the uterus in which accurate staging including retroperitoneal lymph node dissection was performed, peritoneal cytology may be an important prognostic factor.

Adult↗
PubMed2005

High expression of skp2 correlates with poor prognosis in endometrial endometrioid adenocarcinoma.

PURPOSE: Skp2 interacts with the degradation of cyclin-dependent kinase inhibitor p27. This study aimed to investigate the correlation of skp2 expression with the expression of p27 and other cell cycle regulators, and clinicopathological parameters in endometrial endometrioid adenocarcinoma. METHODS: Tissue samples of 136 endometrioid adenocarcinomas, in addition to 20 endometrial hyperplasias and 20 normal endometria, were immunohistochemically stained for skp2. The expression was represented as a labeling index (LI), which indicates the percentage of positive nuclei. RESULTS: Skp2 staining was localized in the nuclei of the glandular cells of the proliferative phase endometrium, and endometrial hyperplasia and carcinoma cells. Skp2 expression was increased significantly in those of higher histological grade. The high level of skp2 expression was significantly correlated with the presence of lymph node metastasis and lymph-vascular space involvement. The LI of skp2 in endometrial carcinoma was significantly correlated with that of p27, Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p53 and PTEN. The high level of skp2 expression (LI> or =20%) was significantly correlated with the patients' poor survival. CONCLUSIONS: The skp2 level might have increased due to p27 accumulation and may be a good indicator of proliferative activity and poor prognosis.

Biomarkers, Tumor↗
PubMed2005

Cytologic scoring of endometrioid adenocarcinoma of the endometrium.

BACKGROUND: Endometrial carcinoma is one of the most frequent malignancies in the female genital tract, and its incidence has been increasing in Japan. Histologic grade is an important factor for organizing treatment strategies, including hormone therapy, and for predicting the prognosis of the patient. The objective of this study was to evaluate the applicability and usefulness of cytologic scoring in assessing the morphologic differentiation of endometrioid adenocarcinomas of the endometrium using endometrial smears. METHODS: Sixty-four endometrial cytologic samples of endometrioid adenocarcinomas of the endometrium were used in this study. All patients underwent endometrial cytology before hysterectomy, and the diagnosis was confirmed by histologic examination of the extirpated uterus. Each cytologic specimen was scored according to a scoring system established by the authors. The cytologic grade based on those estimated scores was compared with the histologic grade and clinicopathologic parameters, respectively. RESULTS: The cytologic grade (CG) was correlated positively with the histologic grade. A high cytologic score was correlated with p53 mutation and myometrial invasion and was correlated negatively with estrogen receptor and progesterone receptor status. The concordance rates of cytologic grade with well differentiated (Grade 1), moderately differentiated (Grade 2), and poorly differentiated (Grade 3) histologic grades were 83.3% (35 of 42 tumors), 9.1% (1 of 11 tumors), and 100% (11 of 11 tumors), respectively. The total concordance rate was 73.4% (47 of 64 tumors). The best cut-off value for distinguishing histologic Grade 1 from the others was a cytologic score of 17, representing a sensitivity of 83% and a specificity of 81%. For distinguishing histologic Grade 3 from the others, the best cut-off value was a cytologic score of 20, representing a sensitivity of 100% and a specificity of 83%. CONCLUSIONS: The cytologic scoring system studied for endometrioid adenocarcinoma was useful for predicting histologic grade and tumor malignant potential.

Carcinoma, Endometrioid↗
PubMed2004

Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma.

The progesterone receptor (PR) has two isoforms, A and B, among which PR-B is mainly involved in regulating proliferation of the uterine endometrium. In this study, immunohistochemical analysis was carried out to investigate the correlation of PR-A and -B expressions with cell cycle-regulatory proteins and clinicopathological parameters in endometrial adenocarcinoma. One hundred and forty-one endometrioid adenocarcinomas [76 with well-differentiated (G1), 35 with moderately differentiated (G2) and 30 with poorly differentiated (G3)] were used. Specimens of formalin-fixed and paraffin-embedded tissue were immunohistochemically stained using the high polymer method (HISTOFINE, NICHIREI). The percentage of positive nuclei of tumor cells observed in three high power fields was expressed as a labeling index (LI). PR-B expression significantly occurred more frequently in G1. It was inversely correlated with p53 gene mutation and p53 over expression, and also with clinicopathological variables, including myometrial and lymph-vascular space invasion and the FIGO stage. Patients with negative PR-B had a poorer prognosis than positive cases. PR-A expression was also significantly higher in G1 and was inversely correlated with Ki-67 expression and myometrial invasion, but not with prognosis. PR-A and -B expressions were significantly correlated with biologically malignant potential. Especially, PR-B expression is useful as a prognostic indicator of endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Phase II trial of 3-h infusion of paclitaxel in patients with adenocarcinoma of endometrium: Japanese Multicenter Study Group.

OBJECTIVE: We assessed the antineoplastic effect and adverse reactions of paclitaxel monotherapy with paclitaxel 210 mg/m(2) given every 3 weeks by 3-h infusion on patients with endometrial cancer given as a 3-h infusion. METHODS: This study was a multi-center, open-label phase II clinical trial of paclitaxel 210 mg/m(2) given every 3 weeks by 3-h infusion. Patients with advanced or recurrent endometrial cancer were enrolled. The primary endpoint for efficacy was tumor response rate. The secondary endpoints were duration of response and adverse drug reactions. RESULTS: Among 23 patients evaluated for efficacy, partial remission (PR) was achieved in 7, no change (NC) in 10, progressive disease (PD) in 5, and not estimable (NE) in 1. The overall response rate was 30.4% (7/23 cases). In seven PR cases, median duration of response was 130 days (100-245 days). Subjective or objective symptoms > or =grade 3 included febrile neutropenia and constipation in 8.7% (2/23 cases) each; and nausea, vomiting, fatigue, pain, urinary tract infection, lowered oxygen saturation, anorexia, arthralgia, myalgia, neuropathy, weight loss, dyspnea, and need for red cell transfusion in 4.3% (1/23) each. Laboratory test abnormalities > or =grade 3 included neutropenia (78.3%, 18/23), leucopenia (47.8%, 11/23), lowered hemoglobin (13.0%, 3/23), decreased potassium (8.7%, 2/23), and decreased sodium (4.3%, 1/23). All adverse reactions were successfully managed by prolonging treatment interval, dose reduction, interrupting administration, discontinuation, and administration of G-CSF. CONCLUSION: Three-hour intravenous infusion of paclitaxel 210 mg/m(2) is useful for endometrial cancer. Antineoplastic effect was achieved and adverse reactions were clinically manageable.

Adenocarcinoma↗
PubMed2004

Expression of tumor suppressor gene product p14ARF in endometrioid adenocarcinoma of the uterine corpus.

p14 activates p53 by inhibiting MDM2 expression and arrests the cell cycle in G1 and G2/M. Abnormal p14 expression has been reported in various human cancers. This study investigated p14 expression in endometrioid adenocarcinoma of the uterine corpus in an attempt to clarify its correlation with other cell cycle-regulators and clinicopathologic parameters. The specimen studied consisted of 124 endometrioid adenocarcinomas, 20 normal endometria, and 20 endometrial hyperplasias. Immunohistochemical staining of formalin-fixed and paraffin-embedded tissues was performed using a Catalyzed Signal Amplification System. Cells with >5% positive staining were classified as positive for p14. A staining score of 1 was adopted when the percentage of positive nuclei was <5%, a score of 2 when it was 5 to 50%, and a score of 3 when it was >50%. In normal endometrium, the frequency of positive staining in the proliferative phase and secretory phase was 50% (4/8) and 58.3% (7/12), with staining scores of 1.8+/-0.9 and 1.6+/-0.5, respectively. The frequency of staining in simple hyperplasia (SH), complex hyperplasia (CH), and complex atypical hyperplasia (CAH) was 88.9% (8/9), 25% (1/4), and 42.9% (3/7), respectively; the staining scores were 1.9+/-0.3, 1.3+/-0.5, and 1.4+/-0.5, respectively. Among endometrioid adenocarcinomas, the frequency of staining of well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) adenocarcinomas was 69% (49/71), 64% (16/25), and 42.9% (12/28) respectively, with staining scores of 2.1+/-0.8, 2+/-0.9, and 1.8+/-1, respectively. Thus expression levels of p14 were higher in G1 tumors than in normal endometria or endometrial hyperplasias, and the frequency of its staining in endometrioid carcinomas was inversely correlated with histologic grade. The staining score for endometrioid adenocarcinomas also was inversely correlated with the labeling index (LI) of Ki-67, but not with that of cyclin A, cyclin D1, cyclin E, cdk2, p27, p53, or other clinicopathologic parameters. In conclusion, p14 expression correlated with histologic grade and Ki-67, but not other prognostic factors in endometrioid adenocarcinoma. Long-term follow-up studies are needed to analyze the significance of p14 expression in these tumors.

Adult↗
PubMed2003

Antitumor effects of a soluble insulin-like growth factor I receptor in human ovarian cancer cells: advantage of recombinant protein administration in vivo.

Antitumor effects of a soluble form dominant negative of the type I insulin-like growth factor receptor (IGF-IR) designated as 486/STOP were evaluated in CaOV-3 human ovarian cancer cells by establishing stable transformants overexpressing 486/STOP and by administration of 486/STOP recombinant protein. Expression of 486/STOP was detected from total cell lysates, as well as conditioned media collected from stable transformants. In stable transformants, growth in monolayer was slightly retarded, and anchorage-independent growth in vitro and tumorigenicity in vivo were markedly inhibited. Addition of conditioned media from 486/STOP cells inhibited anchorage-independent growth of parental cells. Although tumorigenicity of parental cells in vivo was abrogated when they were cocultured in monolayer with 486/STOP cells over 48 h before injection to nude mice, coinjection of parental cells and 486/STOP cells without preculture was not successful. In contrast, administration of 486/STOP partially purified recombinant protein inhibited tumorigenicity of parental cells in vivo. Because 486/STOP cells result in massive apoptosis in vivo within 48 h, usage of a recombinant protein has a great advantage to use its unique bystander effect in vivo for clinical application.

Animals↗
PubMed2003

Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas, squamous cell carcinomas, and small cell carcinomas.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated. METHODS: Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs). RESULTS: Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%). CONCLUSIONS: Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background.

Adenocarcinoma↗
PubMed2003

Up-regulation and nuclear localization of beta-catenin in endometrial carcinoma in response to progesterone therapy.

Ovarian hormones are considered to be capable of regulating expression of beta-catenins. A possible role of beta-catenin in alteration of cell morphology has been proposed, but little is known about beta-catenin expression during changes in the tumor morphology of endometrial carcinomas induced by progesterone therapy. To clarify changes in expression of beta-catenin and their relation to morphological alteration, expression of hormone receptors and several cell kinetic markers, sequential biopsy and hysterectomy specimens of 23 endometrial carcinoma and 6 complex hyperplasia with atypia (atypical hyperplasia) cases receiving progesterone therapy were investigated. In vitro assay was also conducted using two endometrial carcinoma cell lines (HEC265 and Ishikawa) expressing progesterone receptors (PRs). An increase of nuclear beta-catenin accumulation was evident during progesterone therapy in endometrial carcinomas and atypical hyperplasias. The nuclear labeling indices were significantly associated with gene mutations and alteration in morphological features in response to progesterone, independently of the status of Ki-67, p21WAF1 and p27Kip1, and hormone receptors. In HEC265 having a beta-catenin gene mutation (A32V), cytoplasmic beta-catenin levels were elevated by progesterone treatment, linked to down-regulation of PR expression, but such changes were relatively minor in Ishikawa without the gene alterations. These findings demonstrate a possible role of progesterone in regulation of beta-catenin expression in endometrial tumors. Moreover, nuclear beta-catenin accumulation, like gene abnormalities, is associated with the alteration of tumor morphology due to progesterone, indicating that beta-catenin may be a clinically useful marker of hormone therapeutic effects.

Active Transport, Cell Nucleus↗
PubMed2003

[Tumor markers in gynecological and breast cancer].

Serum tumor markers are useful in diagnosis and follow-up for patients with gynecological malignancy or breast cancer. In epithelial ovarian cancer, CA125 has been identified as the most sensitive marker. Unfortunately, CA125 detection in the serum of patients with minimal malignant tumor has not been possible. Many nonmalignant conditions including endometriosis, menstruation and massive ascites may elevate the CA125, and almost 50% of patients with clear cell adenocarcinoma do not show CA125 elevated above 100 U/ml. To improve sensitivity and specificity in the diagnosis of ovarian cancer, the use of multiple tumor markers and the simultaneous use of image diagnosis should be employed. The value of tumor markers in the screening for cervical cancer and endometrial cancer has received little attention. However, the utility of serum SCC as a marker for monitoring cervical squamous cell carcinoma has been established. Since hCG is produced by gestational trophoblastic neoplasia and is a sensitive marker of trophoblastic cells in the body, patients with choriocarcinoma or invasive mole must be followed closely for this parameter. The improvement of the hCG detection technique has reduced the mortality rate from trophoblastic neoplasia. In breast cancer, many markers including CEA and CA15-3 are used, and they are reported to be useful as markers for monitoring.

Biomarkers, Tumor↗
PubMed2002

Involvement of microsatellite instability in lymph node metastasis of endometrial carcinoma.

We evaluated microsatellite instability (MSI) in primary lesions and lymph node metastatic lesions in 66 patients with endometrial carcinoma (FIGO stage IIIC) accompanied by lymph node metastasis. DNA was extracted from paraffin-embedded tissue of both the primary and lymph node metastatic lesions of endometrial carcinoma, and MSI was evaluated using microsatellite markers at five loci. Microsatellite instability was positive in the primary lesion in 27 patients (41%). All patients with MSI-positive primary lesions also showed MSI-positive in lymph node metastatic lesions. Of the other 39 patients with MSI-negative primary lesions, 4 showed MSI-positive in lymph node metastatic lesions. As the result of individual identification by polymerase chain reaction (PCR) using short tandem repeat loci in these 4 patients, PCR profiles of primary and metastatic lesions matched with those of normal controls in all 4 patients. Therefore, it was confirmed that both primary and metastatic lesions developed from the same individual. These results suggest that MSI is also involved in lymph node metastasis in the development and/or progression of endometrial carcinoma in some patients.

Adult↗
PubMed2002

[The effect of L-Glutamine and Shakuyaku-Kanzo-to for paclitaxel-induced myalgia/arthralgia].

Myalgia/arthralgia is a crucial side effect of paclitaxel, and may become the major dose-limiting side effect. However, this is a situation where there is little effective preventive treatment. L-Glutamine was reported as a neuroprotective agent for vincristine-induced neurotoxicity. In Japan, there have been reports on steroid and Shakuyaku-Kanzou-to (a herbal medicine) for paclitaxel-induced myalgia/arthralgia. This study aimed to compare the effect of L-Glutamine and Shakuyaku-Kanzou-to, and to discuss the validity of these agents for the paclitaxel-induced myalgia/arthralgia. Our results suggested that Shakuyaku-Kanzou-to showed no remarkable effects against paclitaxel-induced myalgia/arthralgia as had been reported before; however, both L-Glutamine and Shakuyaku-Kanzou-to decreased the duration of grade 2 toxicity (CALGB Expanded Common Toxicity Criteria) in comparison with those who were not treated. L-Glutamine and Shakuyaku-Kanzou-to might therefore a preventive effect against moderate or severer myalgia/arthralgia during paclitaxel-treated chemotherapy. Further trials are needed to confirm the value of these drugs.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Comparative image analysis of cells in voided and catheterized urine.

OBJECTIVE: To objectively evaluate the difference in cytologic findings between specimens of voided and catheterized urine by using a comparative image analysis device, CAS200. STUDY DESIGN: Cells in voided and catheterized urine from 13 patients with transitional cell carcinoma (TCC), including 3 with grade 1, 6 with grade 2 and 4 with grade 3, were compared cytologically. The cellular area, nuclear area, nuclear/cytoplasmic ratio and nuclear density of both types of cytologic specimen were measured using CAS200. RESULTS: Cell area and nuclear area of grade 1 TCCs were significantly greater in voided urine than in catheterized urine. In contrast, cell area and nuclear area of grade 3 TCCs were significantly smaller in voided urine than in catheterized urine (P < .01), and nuclear density of grade 3 TCCs was higher in the latter than in the former. CONCLUSION: The cellular findings in voided urine were different from those in catheterized urine from the same patient. Thus, the method selected for obtaining urine specimens will affect the findings in urinary cytology.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Aspiration cytology of malignant fibrous histiocytoma after radiation therapy for carcinoma of the uterine cervix: a case report.

BACKGROUND: Cytologic reports on malignant fibrous histiocytoma (MFH) following radiation therapy for carcinoma of the uterine cervix are very rare. CASE: A 59-year-old woman presented with slowly increasing pain in the left hip joint. Eight years earlier, she had received radiotherapy at a dosage of 5,000 cGy to the whole pelvis for carcinoma of the uterine cervix. An osteolytic lesion of the pelvic bone was revealed on computed tomography, and a hard tumor was palpable in the left pelvic cavity. Fine needle aspiration (FNA) of the tumor via the left vaginal wall obtained 0.5 mL of yellow fluid consisting of markedly anaplastic and pleomorphic giant cells. Frequent multinucleation and mitoses were observed, although no atypical spindle cells were observed. Immunocytochemistry disclosed vimentin reactivity. An open biopsy of the tumor revealed the histologic and immunohistochemical features of MFH arising in the pelvic cavity. CONCLUSION: FNA of the pelvic lesion via the vaginal wall revealed an MFH in the radiation therapy field. This is one of the few reports dealing with FNA cytology of a postradiation sarcoma in the pelvic cavity.

Biopsy, Fine-Needle↗
PubMedDate not supplied

Clinicopathologic relevance of asymptomatic endometrial carcinoma.

OBJECTIVE: To assess whether screening asymptomatic women is significant for early detection of endometrial carcinoma. STUDY DESIGN: We compared the clinicopathologic findings and prognoses of 21 asymptomatic patients with 427 symptomatic patients with endometrial carcinoma. RESULTS: The incidence of asymptomatic endometrial carcinoma was 4.7%. Nineteen of 21 asymptomatic patients with endometrial carcinoma were found by cytologic screening for endometrial cancer. There was a statistical difference in the histopathology and depth of myometrial invasion between the asymptomatic and symptomatic groups. However, no statistical differences were found in tumor grade, lymph node metastasis, adnexal metastasis, cervical invasion, peritoneal cytology, surgical stage and patient age. Univariate analysis showed that the presence or absence of symptoms was not related to survival. CONCLUSION: The detection of asymptomatic endometrial carcinoma is not related to a reduced mortality rate. Screening asymptomatic women for endometrial carcinoma is not recommended.

Adult↗
PubMedDate not supplied

Effectiveness of mass screening for endometrial cancer.

OBJECTIVE: To investigate the effectiveness of mass screening for endometrial cancer using Endocyte (Laboratoire CCD, Paris, France) endometrial smears. STUDY DESIGN: The study subjects were consecutive patients with documented endometrial cancer diagnosed between January 1, 1989, and December 31, 1997, at 22 hospitals in Japan. One hundred twenty-six cases were detected by mass screening and 1,069 diagnosed in outpatient clinics. We compared the stage of cancer at diagnosis and survival rate of patients in the two groups. RESULTS: Early stage was significantly more frequent in the screening group (P < .001); stage I comprised 88.1% of the screening group as compared with 65.3% of the outpatient group. Well-differentiated adenocarcinoma was significantly more frequent in the screening group (P < .01); grade 1 constituted 74.7% of the screening group as compared with 61.0% of the outpatient group. The five-year survival rate was significantly higher in the screening group than in the outpatient group (94.0% vs. 84.3%, P = .041). The crude hazard ratio (HR) of dying of endometrial cancer for the screening group as compared to the outpatient group was .47 (95% CI .22-.99, P = .048). HR became .96 (95% CI .45-2.08, P = .925) after adjustment for age, study area and cancer stage. CONCLUSION: The results suggest that an endometrial cancer screening program would lead to early detection and improved survival among women with endometrial cancer.

Adult↗