Biomedical subjects

Kohji Miyazaki

Publications and source records attributed to Kohji Miyazaki.

At least 73 records · Page 4Linked to original sources

PubMed2003

Allelotypes as potential prognostic markers in ovarian carcinoma treated with cisplatin-based chemotherapy.

We analyzed a series of ovarian carcinomas from patients treated with cisplatin-based chemotherapy for loss of heterozygosity (LOH) to determine the relationship between microsatellite alteration and prognosis. Patients with tumors that had lost alleles at loci 3p14-21, 12qter, or 17p13.3 showed significantly reduced survival compared to patients with tumors that retained both alleles at those loci. The 5-year mortality rates for patients exhibiting allele loss and patients with allele retention were 50 and 41%, respectively, for the 3p14-21 locus (P=0.0023); 57 and 24%, respectively, for 12qter (P=0.0256); and 55 and 40%, respectively, for 17p13.3 (P=0.0489). A statistically significant difference was also observed with respect to fractional allelic loss (FAL), which was a significant indicator for disease recurrence (P=0.0227). The prognosis of patients with high FAL values were significantly worse compared to those with low FAL values (P=0.0306). Our results suggested that LOH at loci 3p14-21, 12qter, or 17p13.3 was a significant predictor of poor survival in ovarian carcinomas treated with cisplatin-based chemotherapy. Furthermore, the association of FAL value with therapy response indicated that ovarian carcinomas with high levels of chromosomal alteration may be more resistant to this type of chemotherapy.

Alleles↗

PubMed2003

[A case of para-aortic lymph node recurrence of gallbladder cancer completely responding to single drug (UFT) chemotherapy].

A 67-year-old man with gallbladder cancer was treated by cholecystectomy and extrahepatic bile duct resection with regional lymph node dissection. At 10 months after surgery, CT demonstrated para-aortic lymph node recurrence. Single drug chemotherapy of UFT at 400 mg was started. After one month, the lymph node recurrence could not be detected by CT. UFT may be the primary candidate for chemotherapy for lymph node recurrence of gallbladder cancer.

Adenocarcinoma↗

PubMed2002

Copper-transporting P-type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian carcinoma: comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP.

Intrinsic or acquired resistance to chemotherapy is the major obstacle to overcome in the treatment of patients with solid carcinoma. Cisplatin is one of the most effective chemotherapeutic agents for treating ovarian carcinoma. Recently, copper-transporting P-type adenosine triphosphatase (ATP7B) has been demonstrated as one of the genes responsible for cisplatin resistance in vitro. We hypothesized that the expression of ATP7B gene increases resistance to cisplatin in ovarian carcinoma and a priori knowledge of its expression is important for the choice of therapy. The aim of our study was to assess the role of ATP7B gene in ovarian carcinoma and compare its expression with those of multidrug resistance-related transporters such as MDR1, MRP1, MRP2, LRP and BCRP genes. The transporters' gene expression profiles from 82 patients treated with cisplatin-based chemotherapy after surgery were assessed by RT-PCR. We did not observe any significant correlation between ATP7B gene expression and those of MDR1, MRP1, MRP2, LRP or BCRP. The expression level of ATP7B gene was significantly increased (p < 0.05) in patients with moderately-/poorly-differentiated ovarian carcinomas treated with cisplatin-based chemotherapy, thus ATP7B may serve as an independent prognostic factor in these patients. In contrast, the expression level of MDR1, MRP1, MRP2, LRP and BCRP genes were not prognostic indicators of disease. These findings suggest that ATP7B gene may be considered as a novel chemoresistance marker and that inhibitor(s) of ATP7B might be useful, in patients with ovarian carcinoma treated with cisplatin-based chemotherapy.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2002

Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes.

TK is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis. What roles TK may play in epithelial ovarian cancer and the relationships between TK and the other pyrimidine pathway enzymes remain unclear. We examined TK1 gene expression by RT-PCR and related it to gene expression of TS, TP and DPD in 69 samples from epithelial ovarian cancer, 8 low-malignant-potential tumors, 16 benign ovarian tumors and 34 normal ovaries. Additionally, cytosolic and serum TK activities were determined by radioenzymatic assay. TK1 gene expression, the ratio of TK1 to TS gene expression, that of TK1 to TP and that of TK1 to DPD were significantly higher in epithelial ovarian cancer than in normal ovaries. In epithelial ovarian cancer, TK1 gene expression correlated with cytosolic and serum TK activities, TS and TP gene expression and the ratio of TP to DPD gene expression. Patients with high-TK1 gene expression had a significantly poorer survival than those with low TK1 gene expression. Combined analysis demonstrated that the relative risk of cancer death for tumors with high TK1, high TS and high TP gene expression was greater than that for tumors with high TK1 gene expression alone. TK1 gene expression together with TS, TP and DPD gene expression may play important roles in influencing the malignant behavior of epithelial ovarian cancer. Combination therapy including TK inhibitor is a possible therapeutic intervention in patients with epithelial ovarian cancer.

Aged↗

PubMed2002

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) gene expression in human ovarian carcinoma.

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) that regulates genes involved in response to hypoxia and promotes neo-angiogenesis, is a transcriptional factor for vascular endothelial cell growth factor (VEGF). The aim of this study was to examine the expression of HIF-1 alpha and VEGF gene expressions and their relation to angiogenesis, clinicopathologic variables and survival in the patient with human ovarian carcinoma. We retrospectively analyzed HIF-1 alpha and VEGF gene expression levels using reverse transcriptase polymerase chain reaction (RT-PCR) in 60 ovarian carcinomas. Intratumoral microvessel density (IMD) was assessed by immunostaining endothelial cells, using anti-CD 31 antibody in frozen sections. The relationships between the expression level of these genes, IMD and clinicopathologic variables were evaluated by Student's t-test and chi-square tests. Survival analysis was performed by Kaplan-Meier curves. HIF-1 alpha or VEGF gene expression level was independent of age, clinical stage and histological subtype besides grade of tumor. There was no relationship between HIF-1 alpha or VEGF gene expression level and IMD in all carcinomas (R=0.118 and 0.224, respectively). In addition, a weak association between HIF-1 alpha and VEGF gene expression level was observed (R=0.300, P=0.020). The association between VEGF gene expression and IMD was observed (R=0.501, P=0.016). However, no association between IMD and HIF-1 alpha gene expression was observed. Further, both HIF-1 alpha and VEGF gene expression levels had no effect on survival in the patient with ovarian carcinoma. These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of some type of ovarian carcinoma, but the expression levels of both genes have no effect on survival in the patients with ovarian carcinoma.

Adult↗

PubMed2002

Deficient expression of O(6)-methylguanine-DNA methyltransferase combined with mismatch-repair proteins hMLH1 and hMSH2 is related to poor prognosis in human biliary tract carcinoma.

BACKGROUND: O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that transfers methyl groups from O(6)-methylguanine to itself. Alkylation of DNA at the O(6) position of guanine is an important step in the induction of mutations in the organism by alkylating agents. The O(6)-methyl G:T mismatch is recognized by the mismatch-repair (MMR) pathway. The biliary duct is highly exposed to alkylating agents because of its anatomical location. METHODS: We examined 39 surgically resected gallbladder carcinomas and 35 extrahepatic bile duct carcinomas and evaluated the expression of MGMT and MMR protein (hMLH1 and hMSH2) by immunohistochemical staining. RESULTS: MGMT-negative staining was detected in 59.0% of gallbladder carcinoma specimens and 60.0% of extrahepatic bile duct carcinoma specimens. In gallbladder carcinoma, hMLH1- and hMSH2-negative staining was observed in 51.3% and 59.0%, respectively, whereas in extrahepatic bile duct carcinoma, the respective values were 57.1% and 65.7%. MGMT-negative staining correlated with hepatic invasion in gallbladder carcinoma and with poor prognosis in both types of tumor. Furthermore, a combined MGMT and MMR status was shown to be a more significant prognostic biomarker in both tumor types. CONCLUSIONS: Combined MGMT and MMR is a possible prognostic marker that probably reflects an accumulation of genetic mutations.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Focal pancreatic hemorrhage mimicking pancreas carcinoma with lymph node metastasis.

A 67-year-old man was referred to our department because of a mass in the pancreas tail. Pancreatic tail cancer with lymph node metastasis was diagnosed, based on various radiological findings. Computed tomography (CT) revealed a slightly enhanced tumor mass around the celiac plexus, and endoscopic retrograde pancreatography (ERP) showed complete obstruction of the main pancreatic duct at the tail, although magnetic resonance imaging (MRI) demonstrated no elevation of the mean pixel value of the tumor after gadolinium (Gd) injection, and tumor markers of pancreas cancer were within normal limits. At surgery, the mass around the celiac plexus was found to be blood coagulation, and the pancreas tail tumor was found to be a focal hematoma in the pancreas. Pathologically, the hematoma was not encapsulated, and it was diagnosed as hemorrhage in the pancreas parenchyma. Both hemorrhagic lesions were suspected to have developed respectively. It is difficult to distinguish pancreas hemorrhage from carcinoma in the pancreas with chronic pancreatitis, especially when the hemorrhage is small in size and there are other extrapancreatic hemorrhagic lesions. For such diagnosis, the superiority of MRI with Gd injection is indicated.

Aged↗

PubMed2002

Benign nonepithelial fibroma in the pancreas.

This is, to our knowledge, the first report of a fibroma originating in the pancreas in which preoperative imaging findings or explicit descriptions of histopathologic observations are clearly described. A 64-year-old man was referred to our hospital for further evaluation of a pancreatic mass. Clinical examination and laboratory analysis revealed no abnormal findings, except for mild elevation of serum trypsin (550 ng/ml). Abdominal ultrasonogram, computed tomographic scan, magnetic resonance imaging, and angiography demonstrated a well-demarcated circular mass in the tail of the pancreas. A laparotomy was performed on April 26, 1995. The tumor was observed to be tan-colored and smooth, and was localized in the front of the pancreas tail, suggesting that it had arisen from the pancreatic capsule. The patient underwent enucleation of the tumor. The resected tumor presented macroscopically as a fibrous nodule measuring 5.5 x 6.0 cm. The pathological diagnosis was fibroma. Immunohistochemically, spindle cells were positive for vimentin and negative for alpha-smooth muscle actin, desmin, S-100, and neuron-specific enolase.

Fibroma↗

PubMed2002

Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase.

Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing production of angiogenic factors. These mechanisms require clarification in endometrial cancer. COX-2 expression was examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal endometrium in various phases. We investigated the relationship between COX-2 expression and clinicopathologic variables, microvessel count, and expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but not in stromal cells. COX-2 expression in epithelial cells was significantly greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than in normal endometrium in any phase (n = 53). Although COX-2 did not correlate with any conventional clinicopathologic factor in patients with endometrial cancer, COX-2 expression was associated with high microvessel count, VEGF expression, and TP expression. By combined analysis of COX-2, VEGF, and TP, tumors with high expression of at least one factor had a significantly higher microvessel count than tumors expressing little of the three factors. We confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression significantly correlated with VEGF mRNA expression in these tumors. COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a useful therapeutic intervention in endometrial cancer.

Cyclooxygenase 2↗

PubMed2002

Differential regulation of pituitary hormone secretion and gene expression by thyrotropin-releasing hormone. A role for mitogen-activated protein kinase signaling cascade in rat pituitary GH3 cells.

We examined the possible involvement of mitogen-activated protein (MAP) kinase activation in the secretory process and gene expression of prolactin and growth hormone. Thyrotropin-releasing hormone (TRH) rapidly stimulated the secretion of both prolactin and growth hormone from GH3 cells. Secretion induced by TRH was not inhibited by 50 microM PD098059, but was completely inhibited by 1 microM wortmannin and 10 microM KN93, suggesting that MAP kinase does not mediate the secretory process. Stimulation of GH3 cells with TRH significantly increased the mRNA level of prolactin, whereas expression of growth hormone mRNA was largely attenuated. The increase in prolactin mRNA stimulated by TRH was inhibited by addition of PD098059, and the decrease in growth hormone mRNA was also inhibited by PD098059. Transfection of the cells with a pFC-MEKK vector (a constitutively active MAP kinase kinase kinase), significantly increased the synthesis of prolactin and decreased the synthesis of growth hormone. These data taken together indicate that MAP kinase mediates TRH-induced regulation of prolactin and growth hormone gene expression. Reporter gene assays showed that prolactin promoter activity was increased by TRH and was completely inhibited by addition of PD098059, but that the promoter activity of growth hormone was unchanged by TRH. These results suggest that TRH stimulates both prolactin and growth hormone secretion, but that the gene expressions of prolactin and growth hormone are differentially regulated by TRH and are mediated by different mechanisms.

Animals↗

PubMed2002

Regulation of gonadotropin alpha subunit gene expression by dopamine D(2) receptor agonist in clonal mouse gonadotroph alphaT3-1 cells.

Pituitary prolactin biosynthesis is negatively regulated by hypothalamic dopamine through D(2) receptors in pituitary lactotrophs, but little is known about the direct effect of dopamine on gonadotrophs. In this study, the clonal gonadotroph-derived cell line, alphaT3-1, was used to examine whether gene expression of the pituitary gonadotropin alpha subunit, stimulated with GnRH or pituitary adenylate cyclase-activating polypeptide (PACAP), was controlled by dopamine D(2) receptor. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated the presence of dopamine D(2) receptors in alphaT3-1 cells. Both GnRH and PACAP increased alpha subunit gene expression. GnRH-induced alpha subunit gene expression was not affected by quinpirol, a specific dopamine D(2) receptor agonist. In contrast, PACAP-induced gene expression was significantly lower in the presence of quinpirol. The roles of extracellular signal-regulated kinase (ERK) and cAMP in the expression of the alpha subunit gene were examined. GnRH activated ERK, but PACAP did not, and the activation was not inhibited by quinpirol. GnRH-induced alpha subunit gene expression was completely inhibited by an ERK inhibitor, PD098059. Cyclic AMP accumulation in alphaT3-1 cells was increased by treatment with PACAP, and quinpirol inhibited this effect. GnRH did not affect cAMP production in these cells. These results suggest that in alphaT3-1 cells, dopamine D(2) receptors negatively regulate pituitary alpha subunit gene expression in association with the cAMP-dependent pathway, but not with the ERK pathway.

Animals↗

PubMed2002

Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer.

OBJECTIVE: The recent discovery of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) has provided novel and important insights into the molecular mechanisms of blood vessel formation. Ang1 and Ang2 bind with similar affinity to the endothelial cell tyrosine kinase receptor Tie2. Our purpose was to assess the potential role of the Ang/Tie2 system in physiological and pathological angiogenesis in the ovary. METHODS: Ang1, Ang2, and Tie2 gene expression in 14 normal ovaries with corpus luteum (CL) and in 19 cases of ovarian cancer were analyzed by polymerase chain reaction of RNA after reverse transcription. The level of each gene expression was presented by the relative yield of each gene to the beta(2)-microglobulin gene, respectively. Furthermore, cellular distribution of Ang1 and Ang2 mRNA was examined by in situ hybridization, and localization of Tie2 was studied by immunochemistry. RESULTS: The Ang1, Ang2, and Tie2 gene expression in normal ovary with CL ranged from 0.18 to 1.06 (median 0.54), 0.31-2.64 (median 1.01), and 0.10-0.47 (median 0.20), respectively. The expression of these same genes in ovarian cancer ranged from 0.06 to 0.75 (median 0.14), 0.69-1.59 (median 1.12), and 0.04-0.35 (median 0.15), respectively. Ang1 gene expression in normal ovary with CL was significantly higher than that in ovarian cancer (p = 0.0004). The gene expression levels of Ang2 and Tie2 were statistically the same in both groups. There was a significant correlation between Ang1 gene expression and Tie2 gene expression in normal ovary with CL (r = 0.619, p = 0.018). No such significant correlation was found in ovarian cancer. Moreover, Ang2 gene expression showed no significant correlation with the Tie2 gene expression either in normal ovary with CL or in ovarian cancer. Transcripts for Ang1 were observed in CL cells and endothelial cells around CL, and in tumor cells and endothelial cells at the periphery of tumor invasion. Ang2 transcripts were expressed in the same patterns. Tie2 expression was positive primarily in the endothelial cells around CL and in those at the periphery of tumor invasion. CONCLUSION: Our results indicate that there is a difference in the Ang/Tie2 gene expression between physiological and pathological angiogenesis in the ovary. This finding may aid in the development of new therapeutic interventions for ovarian cancer.

Adult↗

PubMedDate not supplied

Induction of thymidine phosphorylase expression by Taxol does not enhance Furtulon sensitivity in a cisplatin-resistant human ovarian carcinoma cell line.

OBJECTIVE: Thymidine phosphorylase (TP) can metabolize the prodrug 5'-deoxy-5-fluorouridine (Furtulon) to 5-fluorouracil (5-FU) and 5'-deoxy-D-ribose-1-phosphate. Furthermore, TP may enhance the toxicity of the active drug 5-FU by the transfer of 2'-deoxyribose 1-phosphate, so producing 5-fluoro-2'-deoxyuridine. This product can form 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) through the action of thymidine kinase, and FdUMP in turn can inhibit thymidylate synthase (TS), leading to reduced thymidylate formation and subsequent inhibition of DNA synthesis. The aim of this study was to determine whether the expression of TP is associated with the sensitivity to Furtulon, using a single-cell clone of the human ovarian carcinoma cell line, KF-28, and KFr13, a cisplatin-resistant subline derived from KF28 cells. Next, if lower TP expression correlated with decreased sensitivity to Furtulon, we planned to investigate the possibility that increased TP expression induced by Paclitaxel (Taxol) exposure might increase the sensitivity to Furtulon. MATERIALS AND METHODS: Cell growth was evaluated by MTT assay. TP and TS expression were assessed by RT-PCR and Western blot analysis. RESULTS: Cell growth was significantly inhibited compared to the control at 10 (p < 0.0001), 100 (p < 0.0001) and 1000 microM (p < 0.0001) of Furtulon after 24 hours Furtulon treatment in KF28. However, cell growth was significantly inhibited only at 1000 microM (p < 0.0001), in KFr13. The expression of TP was observed only in KF28 in our PCR condition. Next, Western blot analysis confirmed that TP protein levels in KF28 were markedly elevated compared to those in KFr13. TP gene expression emerged at 72, 96 and 120 hours after 0.5 nM Taxol (about twenty percent of IC50; 2.61 +/- 0.06 nM) exposure to KFr13 in our PCR condition. The level of TP gene expression was the highest at 120 hours Taxol exposure. Similarly, Western blot analysis showed that the TP protein level of KFr13 cells 120 hours after Taxol exposure (KFr13/120 hours Taxol exposure) was elevated compared to the control. Cell growth did not significantly differ between KFr13 and KFr13/120 hours Taxol exposure cells. KFr13 and KFr13/120 hours Taxol exposure cells were incubated with 0-1000 microM Furtulon for 24 hours-168 hours. Furtulon sensitivity of KFr13/120 hours Taxol exposure cells was not found to be significantly enhanced compared to that of KFr13 cells at any of the indicated times. The level of TS gene expression assessed by RT-PCR in KFr13 and KFr13/120 hours Taxol exposure cells was significantly lower than that in KF28 cells (p < 0.001). Moreover, higher protein level expression of TS was noted in KF28 cells compared to KFr13 or KFr13/120 hours Taxol exposure cells. CONCLUSION: Our results suggest that lower expression of TP is not a critical determinant in the development of resistance to Furtulon in the cisplatin-resistant human ovarian carcinoma cell line, KFr13. The clinical relevance of these observation remains to be established.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Serum endostatin levels in patients with epithelial ovarian cancer.

OBJECTIVE: Endostatin, a 20-kDa C-terminal fragment of collagen XVIII, specifically inhibits endothelial proliferation and potently inhibits angiogenesis and tumor growth. The aim of this study was to assess the prognostic potentials of serum endostatin levels in epithelial ovarian cancer. MATERIALS AND METHODS: The preoperative serum levels of endostatin in 61 cases of epithelial ovarian cancer (29 serous, 13 mucinous, 13 endometrioid, 5 clear cell and 1 Brenner cell) were analyzed using a competitive enzyme immunoassay. With regard to staging, 23 cases had stage I disease, 6 had stage II disease, 28 had stage III disease and 4 had stage IV disease. RESULTS: Serum levels were compared with levels from 22 age-matched healthy volunteer blood donors. The median serum levels were 18.5 ng/ml (range, 6.3-50.3 ng/ml) in patients with epithelial ovarian cancer and 18.4 ng/ml (range, 8.4-27.0 ng/ml) in controls. No significant difference was noted between the two groups. No clinicopathological features (e.g., patients' age at diagnosis, stage of disease, histological subtype and grade) were significantly associated with serum endostatin levels. Survival data were available for all patients. Multivariate Cox regression analysis revealed that FIGO stage III-IV (p = 0.015) and serum endostatin levels (> 2 standard deviations above the control mean; 27.7 ng/ml) (p = 0.035) are independent prognostic factors. CONCLUSION: Elevated serum levels of this endogenous inhibitor of angiogenesis may be a pertinent prognostic indicator for patients with epithelial ovarian cancer. It is anticipated that this finding may aid the development of a new therapeutic strategy for epithelial ovarian cancer.

Adult↗

PubMedDate not supplied

Induction of thymidine phosphorylase expression and enhancement of Furtulon sensitivity by Taxol in a human ovarian carcinoma cell line.

OBJECTIVE: Thymidine phosphorylase (TP) is one of the enzymes involved in the salvage pathways of nucleotide synthesis. The enzyme converts thymidine to thymine and 2'-deoxyribose-1-phosphate and can also metabolize the prodrug 5'-deoxy-5-fluorouridine (Furtulon) to 5-fluorouracil and 5'-deoxy-D-ribose-1-phosphate. The aim of this study was to determine whether Paclitaxel (Taxol) induces TP expression and whether increased TP expression is further sensitized to Furtulon, using a human ovarian carcinoma cell line. MATERIAL AND METHODS: KF 28, a single-cell clone of a human ovarian carcinoma cell line, was used. TP expression was assessed by RT-PCR and Western blot analysis. Cell growth was evaluated by MTT assay. RESULTS: The concentration of Taxol that inhibited the growth of cells to the level of 50% of the control growth was 4.65 +/- 0.35 nM. TP gene expression was significantly increased at 72 hours 1 nM Taxol exposure compared to the control by RT-PCR (p = 0.020). Western blot analysis confirmed that the TP protein level was elevated compared to the control at 72 hours 1 nM Taxol exposure. Cell growth did not significantly differ between the control and 72 hours 1 nM Taxol exposure groups (p = 0.917). After 48 hours treatment with Furtulon followed by 72 hours 1 nM Taxol exposure, cell growth was dose-dependently inhibited in Taxol-treated cells (p = 0.022), but not in non-Taxol-treated cells (p = 0.082). CONCLUSION: Our results show that a low concentration of Taxol is a candidate for increasing TP expression in a human ovarian carcinoma cell line, and that cells with an elevated level of TP expression can be further sensitized to Furtulon. This information might be valuable in the development of new therapeutic interventions for epithelial ovarian cancer.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

The proliferative activity of ovarian tumors of low malignant potential differs from that of ovarian carcinoma.

Ovarian tumors of low malignant potential (LMPs) are intermediate between adenomas and ovarian carcinomas (OCs); however, whether an LMP is a precursor of OC or is a unique type of tumor that will not progress to OC is still controversial. To gain better insight into the relationship between LMP and OC, we compared proliferative and apoptotic activity and tumor size in 50 cases of LMP and 27 cases of OC. We employed immunohistochemical staining with Ki-67 and apoptotic labeling was based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The average tumor size observed in mucinous LMP was significantly larger than that in mucinous OC (p = 0.014). In contrast, there was no difference in tumor size between serous OC and serous LMP. The average Ki-67 labeling index (LI) in mucinous OC was significantly higher than that in mucinous LMP (p = 0.028). There was no difference between serous OC and serous LMP in the Ki-67 LI. There was also no difference in apoptotic indeed (AI) between OC and LMP, irrespective of histological subtype. A significant positive relationship between the Ki-67 LI and tumor size was observed in mucinous LMP (R = 0.516, p = 0.0003). Interestingly, the Ki-67 LI was inversely correlated with tumor size in mucinous OC (R = 0.570, p = 0.0317). Significant positive correlations between Ki-67 LI and tumor size were observed in both serous LMP and serous OC (R = 0.707, p = 0.0488, R = 0.789, p = 0.0168, respectively). No association was seen between AI and tumor size in LMP and OC, irrespective of histological subtype. The different associations between proliferative activity and tumor size in the mucinous subtype of LMP and OC suggest that mucinous LMPs may not be precursors of mucinous OCs. In contrast, the similar associations of proliferative activity with tumor size in the serous subtype of LMP and OC suggest that serous LMPs may be precursors of serous OCs.

Adenocarcinoma, Mucinous↗

PubMedDate not supplied

Modification of lymph node dissection for colon cancer by clinical diagnosis.

BACKGROUND/AIMS: Less invasive procedures for colon cancer that are available now increase the needs of modified lymph node dissection. The aim of the present study is to establish oncologically safe criteria for modifying lymph node dissection for colon cancer by clinical diagnosis. METHODOLOGY: We evaluated the central extent of lymph node metastasis in 276 patients who underwent curative surgery for colon cancer according to clinicopathologic factors and analyzed the accuracy of clinical assessment of the factors. RESULTS: Only the degree in depth of invasion determined the maximum extent of lymph node metastasis. None of pTis-pT2 tumors showed metastasis to nodes along the main vessels including apical nodes, demonstrating that patients with pTis-pT2, but not pT3-pT4, tumors could be candidates for modified lymph node dissection. While the accuracy in clinical assessment of depth for pTis, pT1, and pT2 tumors was only 59.1%, 73.7%, and 53.6%, respectively, none of the clinically assessed as Tis or T1 tumors was finally diagnosed as a pT3-pT4 tumor. On the other hand, 30.8% of T2 tumors were revealed to be pT3 tumors. CONCLUSIONS: Modification of lymph node dissection by clinical diagnosis should be performed for Tis-T1 but not for T2-T4 tumors when bowel resection is performed.

Aged↗

PubMedDate not supplied

The effect of o6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) status on the sensitivity to alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea(ACNU) in gallbladder carcinoma cells.

The aim of this study was to correlate O6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) expression in gallbladder carcinoma cells with drug sensitivity to the bifunctional alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Using 5 gallbladder carcinoma cell lines and 1 colon carcinoma cell line (SW48), the MGMT and hMLH1 status was assessed both by RT-PCR and Western blot analyses. Sensitivity to ACNU was estimated by the MTT assay. MGMT+/hMLH1+ status was revealed in 2 gallbladder carcinoma cells, MGMT-/hMLH1+ in another 3 gallbladder carcinomas and MGMT-/hMLH1- in SW48. MGMT-/hMLH1+ and MGMT-/hMLH1- cells were more sensitive to ACNU compared with MGMT+/hMLH1+ cells. These results indicate that MGMT, but not hMLH1, expression is an important determinant for drug sensitivity to ACNU in gallbladder carcinoma cells. The drug effect of ACNU, which depends on the MGMT status, was verified using xenograft tumors grown in nude mice. Furthermore, the apoptotic index of MGMT- GB-dl xenografts was significantly increased by ACNU treatment, compared with that of MGMT+ KMG-C. In conclusion, the sensitivity to ACNU was not associated with hMLH1 status, but was found to depend only on the MGMT status. ACNU might be a useful chemotherapeutic agent for MGMT- gallbladder carcinoma, which is associated with poor patient outcome.

Adaptor Proteins, Signal Transducing↗