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Biomedical subjects

N Sakuragi

Publications and source records attributed to N Sakuragi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Bcl-2 expression and prognosis of patients with endometrial carcinoma.

Bcl-2 protein inhibits apoptosis, reduces the requirement for growth factors, and thereby extends the survival of cells. Recent findings of Bcl-2 in several solid tumors suggest that it might contribute to the genesis of some types of cancer. Over-expression of Bcl-2 might play a role in carcinogenesis and malignant progression of endometrial carcinoma. The aims of this study were to determine Bcl-2 expression in endometrial carcinoma in relation to other histopathologic prognostic factors, and to test its prognostic significance in patients with endometrial carcinoma. A total of 61 endometrioid-type endometrial carcinomas were immunohistochemically investigated for Bcl-2 expression on cryostat sections. Bcl-2 localization was observed in cytoplasm in 18 tumors, in nucleus in 27 tumors, or in both in 5 tumors. In 11 tumors, Bcl-2 was observed neither in cytoplasm nor in nucleus. There was not a statistically significant relationship between grade of tumor and Bcl-2 expression. Cytoplasmic Bcl-2 became less frequently expressed as the tumor invaded the myometrium deeper (p < 0.025). Retroperitoneal lymph-node dissection was performed in 57 patients. Multiple-regression analysis showed that lymph-vascular space invasion and nuclear expression of Bcl-2 were correlated to pelvic lymph-node metastasis (p < 0.0001 and < 0.05 respectively). Univariate Cox regression analysis revealed that nuclear Bcl-2 expression was associated with shorter survival (p < 0.05) than that of patients with cytoplasmic Bcl-2 expression. Pelvic node metastasis was a significant prognostic factor for patients who underwent systematic retroperitoneal lymph-node dissection. Cox multivariate-regression analysis revealed that pelvic node metastasis and cervical invasion were the most important prognostic factors in this series of patients. When the analysis was made after exclusion of pelvic node metastasis, histologic grade (hazard ratio = 2.4), cervical invasion (hazard ratio = 3.7) and nuclear Bcl-2 expression (hazard ratio = 11.5) were shown to be significant predictors of survival of the patients. These results indicate that aberrant Bcl-2 expression might be involved in malignant progression of endometrioid-type endometrial carcinoma. Site of Bcl-2 localization may be an important predictor of prognosis for patients with endometrioid-type endometrial carcinoma.

Adult↗
PubMed1998

High-dose-rate intracavitary irradiation using linear source arrangement for stage II and III squamous cell carcinoma of the uterine cervix.

PURPOSE: The purpose of this article is to evaluate fractionated high-dose-rate (HDR) intracavitary irradiation using linear source arrangement (LSA) for patients with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: The subjects consisted of 217 patients (71 patients with stage II and 146 with stage III disease) who received external beam therapy (EBT) followed by fractionated HDR intracavitary irradiation using LSA between January 1980 and June 1990. In EBT, 40 Gy in 20 fractions (40 Gy/20 Fr) or 39.6 Gy/22 Fr was delivered to the whole pelvis and an additional 10 Gy/5 Fr or 10.8 Gy/6 Fr was delivered to the parametrium. The intracavitary irradiation dose was 30 Gy/6 Fr or 35 Gy/7 Fr with a daily fraction size of 5 Gy and two fractions per week. During the intracavitary treatment, most patients were treated on an out-patient basis. RESULTS: Cause-specific 5-year survival rates were 77% for stage II and 50% for stage III. Pelvic failure rates were 13% for stage II and 36% for stage III. In multivariate analyses, improved cause-specific survival was significantly associated with stage II (P = 0.0003), higher pretreatment serum hemoglobin level (P = 0.0015), higher pretreatment serum total protein level (P = 0.0029), and shorter total treatment time (P = 0.0024). The rate of severe (grade 3 or 4) late complication was 2% for the rectum, 1% for the small intestine or sigmoid colon and 1% for the bladder. CONCLUSIONS: Fractionated HDR intracavitary irradiation using LSA is an effective treatment for patients with uterine cervical cancer without need for hospitalization.

Adult↗
PubMed1997

A clinical and pathologic study on para-aortic lymph node metastasis in endometrial carcinoma.

BACKGROUND: Recent studies have shown that poor survival for patients with early endometrial cancer was related to the extrapelvic spread of the cancer. The purpose of this study was to evaluate the correlation between para-aortic lymph node (PAN) metastasis and histopathologic findings and to assess the clinical utility of identifying PAN metastasis of endometrial carcinoma. METHODS: The correlation of para-aortic lymph node metastasis to the clinical stages of endometrial carcinoma (FIGO, 1982), histopathologic findings, and prognosis were investigated in 200 patients with endometrial carcinoma, who were treated by radical operations, including systematic retroperitoneal lymphadenectomies, between July 1982 and February 1996. RESULTS: Of these, para-aortic lymph node (PAN) metastasis was seen in 18 (9.0%) and pelvic lymph node (PLN) metastasis in 40 (20.0%). The incidence of PAN metastasis according to clinical stages Ia, Ib, II, and III were 2.5%, 8.5%, 15.7%, and 33.3%, respectively. The incidence of metastasis was significantly higher in stage II than in stage Ia (P < 0.05), and in stage III than in stage Ia (P < 0.01). PAN metastasis occurred significantly more frequently in the first of each of the following groups: invasion of > 1/2 of the myometrium (15.7%) vs. invasion of < 1/2 of the myometrium (3.6%) (P < 0.01), the group with cervical invasion (23.5%) vs. the group without (4.0%) (P < 0.0001), the group with lymph-vascular space involvement (17.2%) vs. the group without (1.0%) (P < 0.0005), and PLN-metastasis-positive group (40.0%) vs. the negative group (1.3%) (P < 0.0001). Multivariate analysis showed a significant correlation between PAN and PLN metastases (P < 0.0005). Positive PAN metastasis is not related to multiple PLN metastasis (bilateral PLN metastasis and the number of PLN metastatic groups). However, a correlation was seen between PAN metastasis and common iliac node metastasis. The prognosis was significantly poorer (P < 0.05) for patients with both PLN and PAN metastases than for those with PLN metastasis alone. CONCLUSIONS: The results of the present study suggest that PAN metastasis may occur as a consequence of PLN metastasis or the two may occur simultaneously as PLN metastasis and also that careful examination of PAN metastasis is necessary to determine the prognosis.

Adenocarcinoma↗
PubMed1997

Importance of the transitional zone between the cervical stroma and the parametrium in the treatment of cervical carcinoma.

OBJECTIVES: Parametrial invasion is an important risk factor in cervical carcinoma. Because the vessels of the parametrium start in the zone between the cervical compact stromal layer and the parametrium, which we have defined as the parametrial initial zone (PIZ) or transitional zone, the invasion of a carcinoma into this part of the cervix is also important. Our objectives in this study were find a characteristic index of the transitional zone and to clarify the relationship between a transitional-zone invasion and the prognosis in a case. METHODS: Thirty-three cases of carcinoma in situ were available to use for the morphological examination of the cervix. The cervix was divided into 8-12 sections. In each section, the outer diameters of the short axis of the arteries were measured with a light microscope and a micrometer. Using the arterial diameter as the characteristic index of the transitional zone, we performed epidemiological studies on 312 patients with clinical Stage Ib-III squamous-cell carcinoma of uterine cervix. RESULTS: The arteries with an axis exceeding 300 microns were concentrated in the transitional zone at a rate of 94.6%. Therefore, arteries of this size are used as the characteristic index of the transitional zone. Patients with invasion to transitional zone only had lymph node metastasis at the rate of 28.1%, compared with 0% for patients who had no permeation to the zone (p < 0.001). The 5-year survival rate of patients with invasion to the transitional zone only was 87.3%, which is significantly lower than those without invasion (99.2%) (p < 0.01). CONCLUSIONS: Measuring the short axis (300 microns < or = ) of the artery is the best method by which to pinpoint the transitional zone. The invasion of a carcinoma into the transitional zone in the cervix should be treated as a parametrial involvement.

Adult↗
PubMed1997

Lectin affinity electrophoresis in a yolk sac tumour in the vagina with yolk sac tumour-type glycoform of alpha fetoprotein.

AIMS: To investigate a potential diagnostic use of alpha fetoprotein (alpha FP) isoform analysis by lectin affinity electrophoresis to distinguish between endodermal sinus tumours arising in the vagina in infants from those at other sites. METHODS: alpha FP in the serum of a patient with a vaginal endodermal sinus tumour was analysed for its isoforms by lectin affinity electrophoresis. The isoforms were compared with that of cord serum, sera of hepatoid adenocarcinoma of the uterus, and endodermal sinus tumour of the ovary. RESULTS: The isoforms of alpha FP obtained by lectin affinity electrophoresis in the serum of the patient with vaginal endodermal sinus tumour differed from the isoforms of alpha FP in the cord serum of normal neonates, and sera of patients with hepatoid adenocarcinoma of the uterus or endodermal sinus tumour of the ovary. CONCLUSIONS: Endodermal sinus tumour arising in the vagina could be distinguished from that in the ovary by the lectin affinity electrophoresis, and a potential diagnostic use of alpha FP isoform analysis by the lectin affinity electrophoresis for the detection of the endodermal sinus tumour in infants was demonstrated.

Diagnosis, Differential↗
PubMed1996

Serum and tissue measurements of CA72-4 in patients with endometrial carcinoma.

AIMS: To evaluate the clinical usefulness of CA72-4 as a serum tumour marker for endometrial carcinoma and to investigate its immunohistochemical localisation in endometrial carcinoma cells. METHODS: Serum concentrations of CA72-4 were determined in 72 patients with endometrial carcinoma. Immunohistochemical localisation of CA72-4 was investigated using the streptavidin-biotin method, using monoclonal antibodies B72.3 and CC49. RESULTS: Serum CA72-4 was increased above the cut off value in 31.9% of the patients with endometrial carcinoma. Serum CA72-4 positivity was correlated with depth of myometrial invasion, adnexal metastasis, lymphovascular space involvement, and pelvic and para-aortic lymph node metastasis. Multivariate analysis showed a significant correlation between serum CA72-4 positivity and adnexal metastasis. The serum concentrations of CA125 and CA19-9, which could be tumour markers for endometrial carcinoma, were measured at the same time. In seven of 72 patients increased concentrations of serum CA72-4 were found while those for CA125 and CA19-9 were within the normal ranges; in four of the seven patients the disease had spread beyond the uterus. Immunohistochemical positivity for CA72-4 antigen was 76.9% and occurred in the tumour cell membrane and cytoplasm. There was no significant difference in immunohistochemical positivity between patients with increased CA72-4 and those with normal CA72-4 values. CONCLUSIONS: The measurement of serum concentrations of CA 72-4 could be useful for predicting and monitoring the progress of disease-for example, extracorporeal spread.

Adult↗
PubMed1996

[An analysis of pelvic and para-aortic lymph node metastasis in ovarian carcinoma by systematic retroperitoneal lymph node dissection].

We performed a systematic retroperitoneal lymph node dissection (RPLND) on 137 patients with primary ovarian carcinoma, of whom 97 had undergone RPLND during the primary surgery before chemotherapy and 40 had undergone RPLND during the secondary cytoreductive surgery after preoperative chemotherapy. The tentative staging of the ovarian carcinoma used in this study was determined according to the FIGO criteria without considering the pathologic findings of retroperitoneal lymph nodes. Nodal metastasis was seen in 21.9% (30/137) of them. Thirteen had positive pelvic lymph nodes (PLN) but no positive para-aortic nodes (PAN). Eleven had both positive PLN and positive PAN. Six had positive PAN but no positive PLN. The PAN was the most frequent site of metastasis (17/137). Next were the common iliac, obturator, and lateral group of deep inguinal nodes. Solitary metastasis in the patients who had undergone RPLND during the primary surgery was seen in a PAN and a common iliac node. Among 24 patients with PLN metastasis, there was a significant (p < 0.05) difference in the number of positive PLN between the patients with PAN metastasis (5.27 +/- 3.00) and the patients without PAN metastasis (2.62 +/- 1.66). These results indicate that the PAN and common iliac nodes are the most important site of nodal metastasis in ovarian carcinoma. The metastasis to PLN such as obturator node and internal iliac node seems to occur independently of the PAN metastasis, and the PAN metastasis occurs not only through the direct route but also as a consequence of extension of PLN metastases. Systematic retroperitoneal lymph node exploration therefore seems to be necessary to clarify the lymph node status.

Aorta↗
PubMed1995

Malignant trophoblastic neoplasms with different modes of origin.

The genetic origin of 24 trophoblastic neoplasms was determined using PCR polymorphisms. Based on pregnancy history, these tumors included nine postmolar trophoblastic tumors, 12 tumors preceded by live birth or abortion, and three nongestational tumors. Androgenetic origin was defined in eight post-molar trophoblastic tumors, and the remaining one might have arisen from a normal fertilization. Six tumors retained genetic features carried by the homozygous complete mole. Two tumors showed PCR polymorphism compatible with that of the heterozygous complete mole. All 12 tumors in the second class had alleles of both paternal and maternal contribution. However, discordance of sex between the antecedent pregnancy product and the tumor was recognized in three choriocarcinomas. The absence of paternal contribution suggested a parthenogenetic origin of three nongestational choriocarcinomas. The findings that PCR polymorphisms were either homozygous in certain loci or heterozygous in others may mean that the tumor was derived from a germ cell after meiosis I. As a result, at least three subtypes with different modes of origin were demonstrated in the 24 trophoblastic tumors. These findings underscore the importance of precise genetic marker analyses in a large series to clearly identify clinical and biologic characteristics of each subset of tumors.

Base Sequence↗
PubMed1995

Therapeutic efficacy of 5-fluorouracil prodrugs using endogenous serum proteins as drug carriers: a new strategy in drug delivery system.

To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology.

Animals↗
PubMed1995

[Abnormal E-cadherin expression as a risk factor for deep myometrial invasion and lymph node metastasis in endometrial carcinoma].

We examined expression of E-cadherin cell-cell adhesion molecule, which is supposed to have invasion-suppressing activity, in 53 cases with endometrial carcinoma. Fresh frozen sections were immunostained with a mouse monoclonal antibody to human E-cadherin (HECD-1). E-cadherin expression was inversely correlated with grade of tumor (p = 0.0267), depth of myometrial invasion (p = 0.0146) and pelvic and paraaortic node metastases (p = 0.0184 and p = 0.0419, respectively). Multivariate analysis revealed that among histologic grade, nuclear grade, and E-cadherin expression, E-cadherin expression was most strongly correlated with depth of myometrial invasion (p = 0.0491). These results suggest that decreased expression of E-cadherin facilitates invasion of endometrial carcinoma.

Cadherins↗
PubMed1994

Production of monoclonal antibodies recognizing cancer-associated antigens expressed on mucin-type sugar chains.

To obtain monoclonal antibodies directed to mucin-type sugar chains, mice were immunized with bovine submaxillary mucin (BSM) that had been conjugated with ovalbumin. Conjugation of BSM with ovalbumin enhanced the antigenicity of BSM to about five to ten times that of intact BSM and resulted in the establishment of ten hybridomas, all of which secreted monoclonal antibodies toward BSM. Most of the antibodies secreted by these hybridomas did not react with glycolipids but did react with glycoproteins. Several antibodies lost their reactivity when sialic acid residues were removed from BSM, indicating that these antibodies recognize carbohydrate moieties of mucins. Immunohistochemical studies revealed that three of the antibodies recognized human ovarian cancer-associated carbohydrate antigens. In addition, one of these three antibodies reacted with a human cultured colonic cancer cell line. The protocol described in this paper was effective in producing monoclonal antibodies that recognize mucin-carbohydrates and some of the generated antibodies can be applied to the detection of cancers.

Adenocarcinoma↗
PubMed1994

Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion.

Decreased E-cadherin expression in tumor cells has been suggested to promote tumor invasiveness. We examined E-cadherin expression in 30 cases of endometrial carcinoma by immunohistochemistry using a monoclonal antibody to E-cadherin and investigated its correlation with other histopathologic features of the tumor. We observed that: (1) E-cadherin expression decreased with loss of differentiation (P < 0.05); (2) E-cadherin expression was inversely correlated with depth of myometrial invasion (P < 0.05); (3) decreased E-cadherin expression was correlated with paraaortic node metastasis (P < 0.01); and (4) multivariate analysis comparing the depth of myometrial invasion to the pattern of E-cadherin expression, histologic grade, nuclear grade, and lymph-vascular space invasion showed that the depth of myometrial invasion was most strongly correlated with decreased E-cadherin expression (P < 0.005). These findings seem to be consistent with the concept that the dissociation of cancer cells due to decreased expression of E-cadherin facilitates invasion of tumor cells.

Analysis of Variance↗
PubMed1994

A comparison between the preoperative and operative findings of peritoneal cytology in patients with endometrial cancer.

Laparoscopy and hysteroscopy were simultaneously performed to examine the intraperitoneal and intrauterine spread of endometrial cancer prior to surgery. Peritoneal cytology (PC) was examined before and after hysteroscopy and at the time of laparotomy. To elucidate the mechanisms by which endometrial cancer cells spread into the peritoneal cavity, the changes in PC in sequential samples and the association between PC and other prognostic factors were examined. 1) Of the patients who had negative PC before hysteroscopy, 3 patients exhibited positive PC from their operation materials (12.5%). It was suggested that leakage of endometrial cancer cells into the peritoneal cavity was induced by hysteroscopy in 2 patients and by endometrial biopsy in one patient. 2) Of those patients with no intraperitoneal lesions, 3 patients had positive PC in the prehysteroscopy samples (11.1%). A statistically significant association was found between pelvic node metastasis and positive PC in the prehysteroscopy samples.

Endometrial Neoplasms↗
PubMed1993

Chicken sterol carrier protein 2/sterol carrier protein x: cDNA cloning reveals evolutionary conservation of structure and regulated expression.

The chicken is a useful model for studies of lipid biochemistry because of the profound changes in lipid metabolism during development and the marked effects of estrogen on its lipids. Here we report the cloning of a cDNA encoding chicken sterol carrier protein 2 (SCP2)/sterol carrier protein x (SCPx), proteins that are believed to play key roles in intracellular lipid movement and metabolism. The 2.4-kb clone, isolated from a liver cDNA library by homology screening with a rat SCP2 cDNA, encodes a 58-kDa polypeptide, SCPx, which encompasses the sequence for SCP2 at its C-terminus. Comparison of the deduced amino acid sequence of the chicken protein with those of mammals revealed conservation of structure from an evolutionary standpoint. Like the other vertebrate SCPx proteins, the chicken protein contains a conserved Arg-Gly-Asp sequence and a cysteine residue in the N-terminus that aligns with the active site cysteine of Escherichia coli 3-ketoacyl-CoA thiolase, a protein that was previously shown to be homologous to vertebrate SCPx. Northern blot analysis of poly(A)+ RNA from different chicken tissues revealed two mRNA species, one of 2.5 kb, encoding SCPx, and one of 1.4 kb, presumably encoding SCP2. High levels of the 2.5 and 1.4-kb mRNAs were found in liver, intestine, and ovarian granulosa cells, consistent with a role for these proteins in lipid metabolism. There was no change in the 2.5-kb mRNA in chicken liver with development (Day 20 embryo to 4 weeks posthatch), but there was a 10-fold increase in the 1.4-kb mRNA by 1 week posthatch. Treatment of roosters with a single injection of estradiol (25 mg/kg) caused a twofold increase in the 2.5-kb mRNA in liver at 6 h after estradiol administration, reaching a maximum fourfold increase at 48 h, while the 1.4-kb mRNA increased twofold at 48 h. The two SCP2/SCPx mRNAs were most abundant in granulosa cells from small follicles. A reduction in SCP2/SCPx gene expression was observed with follicular maturation, correlating with falling estrogen production. In summary, we have documented (i) marked conservation of SCP2/SCPx structure across species and (ii) developmental and hormonal regulation of the mRNAs which encode proteins thought to be involved in lipid metabolism.

Amino Acid Sequence↗
PubMed1993

D21S418E identifies a cAMP-regulated gene located on chromosome 21q22.3 that is expressed in placental syncytiotrophoblast and choriocarcinoma cells.

A partial cDNA (D21S418E) whose nucleotide sequence has no significant homologies with known mammalian DNA sequences was isolated from a human placental library. The cDNA hybridized with a 10-kb transcript present in term placenta. Messages of 10 and 7.5 kb were induced in BeWo and JEG-3 choriocarcinoma cells by treatment with 8-Br-cAMP. The mRNA was not detected in human brain, liver, lung, kidney, pancreas, heart, skeletal muscle, or myometrium. The D21S418E locus was assigned to a 3.5-Mb region of chromosome 21q22.3.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Sterol carrier protein 2: a role in steroid hormone synthesis?

The intracellular movement of cholesterol is an important regulated step in the process of steroidogenesis. However, the molecular mechanisms by which cholesterol is translocated to key organelles, including the mitochondria, remains poorly understood. Lipid transfer proteins may have an important function in this process. One candidate lipid transfer protein is sterol carrier protein 2 (SCP2). This 13.2 kDa protein enhances the movement of cholesterol between vesicles and isolated mitochondria. It also stimulates mitochondrial pregnenolone synthesis. When introduced into intact cells, anti-SCP2 antibodies reduce steroid secretion. Moreover, expression of SCP2 in COS cells engineered to produce progestins increases steroid formation. SCP2 is abundant in steroidogenic glands and the pattern of SCP2 gene expression is consistent with a role for the protein in hormone synthesis: SCP2 transcripts are more prominent in the most steroidogenic compartments of the ovary and tropic hormones that stimulate steroidogenesis increase SCP2 gene expression. Other evidence that suggests that SCP2 plays important roles in cellular function includes a remarkable conservation of primary structure across species. The mechanisms by which SCP2 promotes intracellular sterol movement have not been elucidated. The protein appears to bind sterols and is synthesized with a 20 amino acid N-terminal "pro-" sequence that may serve to target SCP2 to mitochondria. In addition, the C-terminus of SCP2 contains a peroxisome-targeting sequence. SCP2 is derived from a large gene that encodes transcripts that are translated into larger proteins of 30 and 58 kDa. The 58 kDa protein, which has some structural homologies with thiolases, seems to be specifically targeted to peroxisomes whereas SCP2 has a broader subcellular distribution. The significance of the peroxisome association of SCP2 and steroidogenesis has not been disclosed. However, diseases of peroxisome function, including adrenoleukodystrophy and Zellweger syndrome, have notable deficits in steroid and bile acid metabolism, thus linking peroxisomes and steroidogenesis. SCP2 is deficient in fibroblasts of patients with these diseases.

Animals↗
PubMed1992

The physiological role of estradiol 17-sulfate during pregnancy.

To clarify the physiological role of estradiol 17-sulfate (ES) during pregnancy, experiments were conducted and the following results were obtained: (1) serum or urinary ES levels rose as a function of gestational age; (2) placental microsomes showed fairly high 2- and 4-hydroxylase activity for ES; and (3) the catechol products, 2- and 4-hydroxy-ES, had a strong inhibitory effect upon the in vitro production of lipid peroxides. These results suggest that ES acts as a precursor to the catechol metabolites which maintain normal gestation. This is coincident with the negative correlation of serum levels in ES and lipid peroxides observed in late pregnancy.

Chromatography, High Pressure Liquid↗