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Biomedical subjects

Kohji Miyazaki

Publications and source records attributed to Kohji Miyazaki.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effectiveness of antiadhesion barriers in preventing adhesion after myomectomy in patients with uterine leiomyoma.

BACKGROUND: Myomectomy often causes adhesion formation and decreases subsequent fertility. The purpose of the present study was to evaluate the effectiveness of several antiadhesion barrier materials in preventing adhesion after myomectomy. METHODS: We prospectively classified 63 women undergoing myomectomy alone into four groups according to the type of antiadhesion material used: Hyaluronic acid-carboxymethylcellulose film (Seprafilm) (n = 21, Group 1), Dextran 40 (10% Dextran 40 Low Injection) (n = 17, Group 2), factor 13 with fibrinogen (Beriplast) (n = 12, Group 3) and control (n = 13, Group 4). We performed early second-look laparoscopy after the seventh post-operative day in all patients and examined adhesion formation in the abdominal cavity. The incidence of adnexal adhesions was evaluated according to the American Fertility Association (AFS) adhesion score. RESULTS: The incidence of uterine adhesion was 14.3% in Group 1, 70.6% in Group 2, 75.0% in Group 3 and 76.9% in Group 4. Adhesion formation in Group 1 was significantly less than that in Group 2 (p = 0.0004), Group 3 (p = 0.0005) and Group 4 (p = 0.0003). The incidence of peritoneal adhesion was 14.3% in Group 1, 29.4% in Group 2, 41.6% in Group 3 and 69.2% in Group 4. Adhesion formation in Group 1 was significantly less than that in Group 4 (p = 0.001). AFS scores in Groups 1-4 were 0.38+/-1.02, 4.58 +/- 7.02, 0.83 +/- 1.99 and 8.53 +/- 8.79 (mean +/- S.D.), respectively. Group 1 had the lowest AFS score and the difference between Group 1 and Group 4 was significant (p < 0.0001). The AFS score in Group 3 was also significantly less than that of Group 4 (p = 0.0009). CONCLUSION: Seprafilm was highly effective and was superior to the other antiadhesion materials tested in preventing uterine adhesions after myomectomy.

Adult↗
PubMed2005

Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers.

BACKGROUND: We previously demonstrated in an immunohistochemical study that reduced expression of O(6)-methylguanine-DNA methyltransferase (MGMT) correlated with a poorer prognosis in patients with biliary tract cancers. The purpose of this study was to clarify how MGMT deficiency leads to a poor outcome in biliary tract cancer. Thus, we examined epigenetic (promoter methylation) and genetic (gene mutation) alterations in biliary tract cancer. METHODS: We examined 37 biliary tract cancer specimens from patients who underwent surgical resection. Promoter methylation was determined by one-step or two-step methylation-specific polymerase chain reaction. Gene mutation was identified by direct sequencing. The expression of MGMT protein in paraffin-embedded tissue was examined by immunohistochemistry. RESULTS: Frequencies of promoter methylation were 70% for p16/INK4a, 49% for MGMT, 46% for hMLH1, 41% for E-cadherin, and 32% for DAPK genes. MGMT methylation status was closely correlated with the MGMT protein expression determined by immunohistochemistry (P < .001). Although this was not statistically significant, biliary tract cancer tumors with MGMT methylation expressed multigene methylation more frequently than tumors without MGMT methylation (P = .071). A total of 33 mutations were identified in 4 cancer-related genes: p53, K-ras, beta-catenin, and p16/INK4a genes. The most common mutation was GC to AT transitions (58%), which were significantly associated with MGMT promoter methylation (P = .011). These findings suggest that loss of MGMT expression by promoter methylation results in accumulation of GC to AT gene mutations. CONCLUSIONS: Reduced MGMT expression may increase the malignant potential of biliary tract cancer through both epigenetic and genetic mechanisms.

Aged↗
PubMed2005

Expression of the type I interferon receptor and the interferon-induced Mx protein in human endometrium during the menstrual cycle.

OBJECTIVE: To investigate the expression of the type I interferon receptor (IFNAR) and interferon-induced Mx protein (Mx) in normal human endometrium throughout the menstrual cycle. DESIGN: Prospective study. SETTING: Medical university in Japan. PATIENT(S): Thirty-seven normal endometrial tissues from fertile women who had undergone hysterectomies for reasons other than endometrial disease. INTERVENTION(S): IFNAR-1, IFNAR-2, MxA, and MxB gene expression was analyzed by reverse transcription-real-time quantitative polymerase chain reaction. Moreover, localization of IFNAR-1 and IFNAR-2 were studied by immunohistochemistry. MAIN OUTCOME MEASURE(S): Expression of IFNAR-1, IFNAR-2, MxA, and MxB. RESULT(S): Expression of IFNAR-2 gene was significantly increased in the menstrual and midsecretory phase as compared with in the proliferative phase. Immunohistochemistry for IFNAR-1 and IFNAR-2 revealed weak staining of glandular epithelium and weak staining of stromal cells during the proliferative phase. However, an intense immunohistochemical staining of IFNAR-2 was observed on the surface and basement membrane of glands in the secretory phase. There was no statistical difference between MxA and MxB gene expression throughout the menstrual cycle. CONCLUSION(S): Our results suggest that IFNAR and Mx are expressed in the human endometrium and that the expression of IFNAR is cyclically changed during the menstrual cycle.

Endometrium↗
PubMed2005

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a prognostic factor in human endometrial carcinoma.

OBJECTIVE: Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed in endometrial carcinoma. Our goal was to investigate if ATP7B is expressed in endometrial carcinoma and whether its expression correlates with prognosis. METHODS: We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 51 endometrial endometrioid adenocarcinomas. 27 of 51 patients were treated with cisplatin-based chemotherapy after surgery. RESULTS: Cytoplasmic staining of tumor cells was observed in 37.3% (19/51 cases) of the analyzed carcinomas and no staining was observed in adjacent non-neoplastic cells. ATP7B positivity in the degree of differentiation of G2 and G3 carcinoma was significantly higher than that of G1 carcinoma (P = 0.019). The patients with ATP7B-positive tumors had a worse prognosis than that with ATP7B-negative tumors in overall survival and disease-free survival, respectively (P < 0.01). CONCLUSIONS: These findings suggest that overexpression of ATP7B expression in endometrial carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. ATP7B expression could be considered as a prognostic factor in patients with endometrial carcinoma.

Adenocarcinoma↗
PubMed2005

Medium- to large-sized xylo-oligosaccharides are responsible for xylanase induction in Prevotella bryantii B14.

Experiments were done to define the nature of the xylan-derived induction signal for xylanase activity, and evaluate which xylanase genes among the three known ones (xynA, xynB and xynC) are induced by the presence of xylan in Prevotella bryantii B(1)4. During the later stages of exponential growth on glucose, addition of 0.05 % water-soluble xylan (WS-X) stimulated xylanase formation within 30 min. Xylose, xylobiose, xylotriose, xylotetraose, xylopentaose, arabinose and glucuronic acid all failed to induce the xylanase activity. An acid-ethanol-soluble fraction of WS-X (approximate degree of polymerization 30) enhanced the activity significantly, whereas the acid-ethanol-insoluble fraction had no effect, unless first digested by the cloned P. bryantii XynC xylanase. These results indicate that medium- to large-sized xylo-oligosaccharides are responsible for induction. The transcription of all three known xylanase genes from P. bryantii was upregulated coordinately by addition of WS-X. There have been relatively few investigations into the regulation of xylanase activity in bacteria, and it appears to be unique that medium- to large-sized xylo-oligosaccharides are responsible for induction.

Enzyme Induction↗
PubMed2005

Maternal thyroid function during pregnancy and puerperal period.

It has been noted that hypothyroidism in pregnant women can adversely affect the children's subsequent psychoneurotic development. Also, transient elevation of serum free thyroxine is occasionally seen in the first trimester of normal pregnancy. However, normal thyroid function during pregnancy and the puerperal period has not been clearly defined in Japan. The aim of this study was to assess maternal thyroid function during pregnancy and puerperal period in Japan. The concentrations of thyroid stimulating hormone (TSH), free triiodo-thyronine (free T(3)), free thyroxine (free T(4)) and thyroid binding capacity (TBC) of 522 normal pregnant and puerperal women (119 in the first trimester; 132 in the second trimester; 135 in the third trimester and 136 in the early puerperium) were measured by electrochemiluminescence immunoassay. We compared the measured data with those of healthy nonpregnant control. Twenty-six (21.8%) of 119 women in the first trimester had lower TSH levels and 23 (16.9%) of 136 women in the early puerperium had higher TSH levels than the normal range of healthy nonpregnant controls. Free T(3) gradually decreased during pregnancy, although it remained within the normal control range. Eight (6.7%) of 119 women in the first trimester had high free T(4) levels, which gradually decreased during pregnancy. Sixty (44.4%) of 135 women in the third trimester had low free T(4) levels. The values of TBC in the second trimester increased compared with the first trimester and did not change in the third trimester and decreased after delivery. There were no correlations between maternal TSH and levels of thyroid hormones (free T(3) or free T(4)), except for TSH and free T(4) in the first trimester. In conclusion, we showed that maternal thyroid function, especially TSH and free T(4), changed during the course of pregnancy. In assessing the thyroid function associated with pregnancy, one needs to keep in mind the tendency toward low free T(4) levels in the third trimester and high TSH levels in the early puerperal period.

Female↗
PubMed2005

Cisplatin represses transcriptional activity from the minimal promoter of the O6-methylguanine methyltransferase gene and increases sensitivity of human gallbladder cancer cells to 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-2-chloroethyl)-3-nitrosourea.

O(6)-methylguanine methyltransferase (MGMT) repairs O(6)-alkylguanine in cellular DNA introduced by the clinically used alkylating drug 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Thus, cancer cells with MGMT expression are resistant to ACNU treatment. Cisplatin has been reported to suppress MGMT expression; however, the molecular mechanism by which cisplatin reduces MGMT expression remains to be elucidated. Using gallbladder cancer cells (KMG-C) expressing MGMT, we analyzed whether a low dose of cisplatin suppresses MGMT expression, followed by an enhanced drug effect of ACNU in vitro and in vivo. We also investigated the promoter region critical for the transcriptional repression of MGMT gene by cisplatin using 5 deletion mutants in reporter promoter assays. In RT-PCR analysis, the expression of MGMT mRNA in KMG-C cells was dose- and time-dependently repressed. Drug sensitivity to ACNU was increased 2-fold by pretreatment with cisplatin, compared with only ACNU treatment, in MTT assays as well as tumor-bearing nude mice. Although the 5'-flanking region is deleted as far as -69 bp upstream of the transcription start site, cisplatin dose dependently inhibited luciferase activity. However, cisplatin did not cause such repression when 59 bp region from -69 to -10 bp was deleted. We confirmed that cisplatin enhanced sensitivity to ACNU in KMG-C cells expressing MGMT both in vitro and in vivo. Furthermore, a low dose of cisplatin repressed the transcription of the MGMT promoter. The 59 bp region in the MGMT promoter was crucial for repression by cisplatin. These results might form the basis of a chemotherapeutic strategy involving alkylating agents via prior cisplatin-induced biochemical modulation.

Antineoplastic Agents↗
PubMed2005

[Surgical strategy based on the spread mode of gallbladder carcinoma].

Cancer recurs even from early stage of gallbladder cancer if the bile spills over during surgery. The most important point to determine the surgical strategy for gallbladder cancer is the spread mode For pT1b gallbladder cancer, cholecystectomy in the entire layer and regional lymphadenectomy are necessary. Even for pT2 cancer the same surgery is sufficient if the invasion into the subserosal layer is minimal. However, anatomic hepatectomy of S4a + 5 and extrahepatic bile duct resection combined with D2 + paraaortic lymphadenectomy is the fundamental procedure for apparent pT2 or more advanced cancers. If massive direct hepatic invasion is present, central hepatectomy or extended right hepatectomy is indicated. If the right Glissonian triad is involved, right extended hepatectomy is mandatory but the addition of pancreatoduodenectomy must be carefully considered to avoid surgical risk. The presence of liver metasis, jaundice, apparent paraaortic lymph node metastasis, and involvement of the major vessels are not indications for surgery.

Bile Ducts, Extrahepatic↗
PubMed2005

Deficient MGMT and proficient hMLH1 expression renders gallbladder carcinoma cells sensitive to alkylating agents through G2-M cell cycle arrest.

The aim of this study was to assess whether combined evaluation of O6-methylguanine methyltransferase (MGMT) and hMLH1 status determines sensitivity to monofuntional alkylating agents such as N-methyl-N-nitrosourea (MNU) and dacarbazine (DTIC) against gallbladder carcinoma cells. The molecular mechanism behind MGMT and hMLH1 status affecting the cell cycle was also addressed. Using 5 gallbladder cancer carcinoma lines and 1 colon carcinoma cell line (SW48), MGMT and hMLH1 expression was analyzed using RT-PCR and Western blotting. MGMT and hMLH1 status in the 6 cell lines was compared with drug sensitivity to MNU. As a result, cell lines that were MGMT-/hMLH1+ had the highest sensitivity to MNU, compared with MGMT+/hMLH1+ and MGMT-/hMLH1- cells. In flow cytometric analysis, G2-M cell cycle arrest was specifically observed in GB-d1 cells with MGMT-/hMLH1+ and expression of cyclin A and Cdc2 in GB-d1 cells was significantly reduced by MNU treatment, but not observed in KMG-C cells with MGMT+/hMLH1+. Finally, we assessed the in vitro and in vivo effect of the clinically used alkylating agent DTIC in these cells. The highest sensitivity to DTIC was also observed in MGMT-/hMLH1+. In conclusion, MNU suppressed cell proliferation of MGMT-/hMLH1+ gallbladder carcinoma cells by arresting the cell cycle at the G2-M phase, accompanied by down-regulation of cyclin A and Cdc2. These results indicated that expression of MGMT and hMLH1 could be used to select candidates for alkylating agent chemotherapy against gallbladder carcinoma.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Allelic loss of the DNA repair gene OGG1 against oxidative damage in esophageal squamous cell carcinoma.

Esophageal tissue often undergoes oxidative damage from exposure to cigarettes and alcohol. The OGG1 gene plays a major role in maintaining genetic integrity by removing 8-oxoguanine (8-oxoG) in cellular DNA by way of the base excision repair pathway. The OGG1 gene is located at 3p26.2 of the human chromosome. Although deletion in the 3p region is frequently found in cases of esophageal cancer, few reports have focused on the allelic loss of the OGG1 gene. Using 24 samples of surgically-resected esophageal cancer tissue, we assessed the allelic loss of the OGG1 gene with a set of three microsatellite markers that flank the OGG1 gene. We compared the loss of homozygosity status for the OGG1 gene with clinicopathologic factors, as well as OGG1 expression and accumulation of 8-oxoG, which was estimated in an immunohistochemical study. Of 24 cases, 20 were suitable for determining OGG1 allelic loss. Allelic loss of OGG1 was observed in 6 of 20 (30%) cases. An inverse correlation between OGG1 allelic loss and OGG1 expression was weakly observed (p=0.051). In contrast, OGG1 allelic loss showed a positive correlation with 8-oxoG accumulation, although the correlation was not statistically significant (0.095). OGG1 allelic loss was observed in 30% of patients in our study, a lower frequency than that reported in other malignancies, and correlated with reduced OGG1 expression and 8-oxoG accumulation. These findings suggest that attenuated OGG1 expression contributes to 8-oxoG accumulation under oxidative stress, resulting in cancer development in the esophagus. Thus, OGG1 allelic loss is related to carcinogenesis by oxidative stress rather than cancer progression in esophageal cancer.

Carcinoma, Squamous Cell↗
PubMed2004

Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer.

The putative tumor suppressor CDKN1C is an imprinted gene at 11p15.5, a well-known imprinted region often deleted in tumors. The absence of somatic mutations and the frequent diminished expression in tumors would suggest that CDKN1C expression is regulated epigenetically. It has been, however, controversial whether the diminution is caused by imprinting disruption of the CDKN1C/LIT1 domain or by promoter hypermethylation of CDKN1C itself. To clarify this, we investigated the CpG methylation index of the CDKN1C promoter and the differentially methylated region of the LIT1 CpG island (differentially methylated region (DMR)-LIT1), an imprinting control region of the domain, and CDKN1C expression in esophageal cancer cell lines. CDKN1C expression was diminished in 10 of 17 lines and statistically correlated with the loss of methylation at DMR-LIT1 in all but three. However, there was no statistical correlation between CDKN1C promoter MI and CDKN1C expression. Furthermore, loss of CpG methylation was associated with loss of histone H3 lysine 9 (H3K9) methylation at DMR-LIT1. Histone modifications at CDKN1C promoter were not correlated with CDKN1C expression. The data suggested that the diminished CDKN1C expression is associated with the loss of methylation of CpG and H3K9 at DMR-LIT1, not by its own promoter CpG methylation, and is involved in esophageal cancer, implying that DMR-LIT1 epigenetically regulates CDKN1C expression not through histone modifications at CDKN1C promoter, but through that of DMR-LIT1.

Cell Line, Tumor↗
PubMed2004

Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy.

PURPOSE: A major obstacle in the treatment of ovarian carcinoma is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Cu-transporting ATPase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed. Our goal was to investigate ATP7B expression in ovarian carcinoma and whether its expression correlates with prognosis and reduced responsiveness to cisplatin treatment. EXPERIMENTAL DESIGN: We retrospectively examined the expression of ATP7B and p53 in primary ovarian carcinoma and its association with chemotherapeutic effect. Tissues were surgically removed from 104 ovarian carcinomas patients who received cisplatin-based chemotherapy. We performed immunohistochemical analysis of ATP7B and p53 using a monoclonal antibody against ATP7B and DO7 antibody against p53 protein in 104 ovarian carcinomas and adjacent nonneoplastic tissues. The significance of ATP7B and p53 in the prognosis of patients with ovarian carcinomas was also examined in the survival analysis of mortality follow-up data covering the period between 1988 and 2001. Furthermore, mutation analysis at the six Cu-binding domain and ATP-binding domain, which may be important for cisplatin transport, were performed using single-strand conformational polymorphism after reverse transcriptase-PCR. RESULTS: A variable degree of cytoplasmic staining of ATP7B in tumor cells was observed in 34.6% (36 of 104 cases) of the analyzed carcinomas. ATP7B expression was not observed in adjacent nonneoplastic tissues. ATP7B positivity in poorly/moderately differentiated carcinoma was significantly higher than that in low malignant potential tumor/well-differentiated carcinoma (P = 0.0276). Patients with ATP7B-positive tumors had a significantly inferior response to chemotherapy compared with the patients with ATP7B-negative tumors (P = 0.025). The multivariate Cox regression analysis revealed that ATP7B expression (hazard ratio, 1.8; 95% confidence interval, 1.0-3.2, P = 0.048), as well as International Federation of Gynecologists and Obstetricians stage (hazard ratio, 2.0; 95% confidence interval, 1.1-3.6, P = 0.018), was prognostic for poor disease outcome after adjustment for p53 expression, grade, and residual tumor. p53 expression was detected in 31.5% (26/104 cases). No mutation was observed on the six Cu-binding domain or ATP-binding domain in human ovarian carcinomas expressing ATP7B gene. CONCLUSIONS: This study demonstrates that overexpression of ATP7B in ovarian carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, ATP7B expression may be considered as a predictive marker of chemoresistance for cisplatin-based chemotherapy in patients with ovarian carcinoma. We further predict that drugs targeting ATP7B might be useful in combination with cisplatin-based regimen for the improvement of patients with ovarian carcinoma.

Adenosine Triphosphatases↗
PubMed2004

Comparison of multivisceral resection and standard operation for locally advanced colorectal cancer: analysis of prognostic factors for short-term and long-term outcome.

PURPOSE: The aim of the present study is to clarify the characteristics of multivisceral resection and to discuss strategies for improving the overall outcome of multivisceral resection for locally advanced colorectal cancer. METHODS: The study included 323 patients who electively underwent curative surgery for pT3-pT4 colorectal carcinoma without distant metastasis. We evaluated the short-term and long-term outcome of multivisceral resection relative to that of the standard operation by means of multivariate analysis of the prognostic factors. RESULTS: Of 323 patients, 53 (16.4 percent) received multivisceral resection because of adhesion to other organs. Multivisceral resection was significantly associated with tumor size, depth of invasion, operative blood loss, operation time, and blood transfusion (all: P < 0.0001). Overall morbidity rates were 49.1 percent after multivisceral resection vs. 17.8 percent after the standard operation (P < 0.0001), and postoperative mortality rate was 0 percent in both groups (not significant). Only multivisceral resection (odds ratio, 2.725; 95 percent confidence interval, 1.125-6.623; P = 0.0264) was an independent factor for overall postoperative complications. The survival rate of patients after multivisceral resection was similar to that after the standard operation (5-year rate, 76.6 percent vs. 79.5 percent, P = 0.9347). Lymph node metastasis (hazard ratio, 2.510; 95 percent confidence interval, 1.460-4.315; P = 0.0009) and blood transfusion (hazard ratio, 2.353; 95 percent confidence interval, 1.185-4.651; P = 0.0145) were independently associated with patient survival. CONCLUSIONS: For locally advanced colorectal cancer, the long-term outcome after multivisceral resection is comparable to that after the standard operation. However, it should be recognized that multivisceral resection is associated with higher postoperative morbidity. In addition, a reduction in the incidence of blood transfusion may contribute to improving patient survival.

Aged↗
PubMed2004

Expression of the angopoietin-1, angopoietin-2, Tie2, and vascular endothelial growth factor gene in epithelial ovarian cancer.

OBJECTIVES: Angiopoietin/Tie2 system with vascular endothelial growth factor (VEFG) is known to be important for the initiation of angiogenesis in tumors. The aim was to evaluate whether angiopoietin/Tie2 system with VEFG affects prognosis in patients of epithelial ovarian cancer. METHODS: Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie2, and VEGF gene expression were analyzed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 85 epithelial ovarian cancer surgical specimens. These gene expressions were correlated with clinical-pathological parameters, microvessel density (MVD), and patients' survival. RESULTS: Ang-1/Ang-2 gene expression ratio, VEGF, and Tie2 gene expression significantly associated with MVD, respectively (P < 0.0001, P = 0.024, P = 0.005). The patients with low Ang-1/Ang-2 gene expression ratio and high VEGF gene expression were found to have a significantly higher MVD when compared to others (P = 0.0003). Moreover, there was a significant difference between the values of MVD in patients with low Ang-1/Ang-2 gene expression ratio and high VEGF and high Tie2 gene expression and those in others (P = 0.0025). FIGO stage (P = 0.014), residual disease (P = 0.042), histological grade (P = 0.028), Ang-1/Ang-2 gene expression ratio (P = 0.010), and combination of Ang-1/Ang-2 gene expression ratio and VEGF gene expression (P = 0.019), were found to be significantly associated with a poor prognosis in univariate Cox regression analysis. Multivariate Cox regression analysis revealed that FIGO stage is an independent prognostic factor (P = 0.035). Low Ang-1/Ang-2 gene expression ratio had a tendency to be an independent prognostic factor (P = 0.061). CONCLUSIONS: Angiogenesis occurred by angiopoietin/Tie2 system in concert with VEGF in epithelial ovarian cancer did not affect patients' survival. However, gene expression of Ang-1 and Ang-2 might present a pertinent diagnostic tool to select a high-risk group of patients independent of clinical-pathological parameters and a new insight to understand the biology of epithelial ovarian cancer.

Angiopoietin-1↗
PubMed2004

[A case of liver metastatic recurrence of bile duct cancer completely responding to single drug, UFT, chemotherapy].

A 72-year-old man with common bile duct cancer was treated by pylorus preserving pancreatoduodenectomy with D3 lymph node dissection and preventive radiotherapy at hepaticojejunostomy. At 4 months after surgery, CT demonstrated multiple liver metastatic tumors. Single drug chemotherapy, UFT 600 mg, was started. After 6 months, the liver metastatic tumor could not be seen by CT. UFT may be a first candidate for chemotherapy for recurrence of bile duct cancer.

Adenocarcinoma↗
PubMed2004

Gallbladder cancers rarely overexpress HER-2/neu, demonstrated by Hercep test.

c-erbB-2, proto-oncogene is amplified and overexpressed in a number of human adenocarcinomas. Overexpression of c-erbB-2 is indicated as a worse prognostic factor and associated with neoplastic progression in various organs. To investigate the therapeutic effect of Trastuzumab in gallbladder cancer, we studied HER-2/neu expression in 43 primary tumors, 12 metastatic lymph nodes and two liver metastasis, using the Hercep test. Among primary tumors, strong (3+) immunohistochemical intensity was found in two cases (4.7%), weak (2+) in two (4.7%) and negative (1+) (2.3%) in one case. This positivity rate was distinctly lower than those in previous reports. There was no tendency between clinicopathologic characteristics and HER-2 positivity in the primary gallbladder. Among 12 metastatic lymph nodes, only one specimen showed 2+ positivity where the primary lesion revealed 3+ intensity of HER-2. In two liver metastatic lesions, the expression of HER-2 was not found. Our study implied that Trastzumab may not contribute to improvement in treatment of gallbladder cancer. However, there may be a therapeutic possibility for cases with lymph node recurrence overexpressing c-erbB-2.

Adenocarcinoma↗
PubMed2004

Loss of estrogen receptor beta expression at cancer front correlates with tumor progression and poor prognosis of gallbladder cancer.

Gallbladder carcinoma is a relatively rare malignancy with an extremely poor patient prognosis. This malignancy occurs more frequently in women than men, yet expression of the estrogen receptor (ER) family has not been studied. We applied an immunohistochemical technique to examine the expression of ERalpha and ERbeta in gallbladder carcinoma tissues and then compared their expression status with several clinicopathological factors. We examined 26 gallbladder adenocarcinoma specimens and 11 non-cancerous regions using ERalpha and ERbeta antibodies. Expression of the ER isoforms in the cancer specimens was further evaluated at the central area and at the invasive front. ERbeta was expressed in most specimens including cancer and normal region, however ERbeta expression significantly differed between non-cancerous and cancerous regions. Moreover, negative expression of ERbeta at the invasive front was significantly associated with malignant properties of the primary tumor such as lymph node metastasis, advanced stage, lower differentiation of histologic type, lymphatic invasion and a poor prognosis of the patients. In conclusion, evaluation of ERbeta expression at cancer front may be an important factor in identifying a highly malignant group of gallbladder carcinoma.

Adenocarcinoma↗