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T Aikou

Publications and source records attributed to T Aikou.

At least 55 records · Page 3Linked to original sources
PubMed2001

Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells.

Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. Although effective therapies exist for well differentiated tumors, the treatment options for poorly differentiated and anaplastic tumors are much less effective. In the present study we demonstrate that the thyroglobulin (Tg) promoter can be used to direct specific expression of either luciferase or thymidine kinase in thyroid cancer cells. Furthermore, using a putative enhancer element for the Tg gene, the activity of the Tg promoter in and its specificity for thyroid cells were enhanced. In transient transfectants or in stably transfected thyroid carcinoma cells, treatment with the histone deacetylase inhibitors, depsipeptide (FR9012228) and sodium butyrate, alone or in combination with 8-bromo-cAMP, resulted in further enhancement. In experiments in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the Tg promoter and the putative enhancer, HSV-TK expression and ganciclovir sensitivity were augmented. Similar results were obtained in two cell lines derived from a follicular thyroid carcinoma and in two anaplastic thyroid carcinoma cell lines. In summary, we report the construction of a suicide HSV-TK vector with preferential toxicity for thyroid cells. The results in anaplastic thyroid carcinoma cells suggest that it may be of use in the full spectrum of thyroid malignancies.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Low concentrations of the histone deacetylase inhibitor, depsipeptide (FR901228), increase expression of the Na(+)/I(-) symporter and iodine accumulation in poorly differentiated thyroid carcinoma cells.

Thyroid carcinoma accounts for the majority of deaths from endocrine cancers. A major cause of treatment failure is the inability to trap iodine. Chemotherapeutic agents with differentiating properties have been tried in an attempt to increase iodine uptake. We examined the ability of the novel histone deacetylase (HDAC) inhibitor, depsipeptide (FR901228), to modulate the expression of thyroid-specific genes. Four cell lines, two derived from follicular thyroid carcinomas (FTC 133 and FTC 236) and two derived from anaplastic thyroid carcinomas (SW-1736 and KAT-4) were used. In these four cell lines, a very low concentration of depsipeptide (1 ng/mL) increased histone acetylation and expression of both thyroglobulin and the Na(+)/I(-) symporter messenger RNAs. After 3 days, messenger RNA levels approached those of a normal thyroid control. Depsipeptide induced increases in (125)I accumulation indicated that a functional Na(+)/I(-) symporter protein was induced. Transient transfections indicate that the effects are mediated at least in part by a trans-activating factor. These in vitro results suggest that depsipeptide or other histone deacetylase inhibitors might be used clinically in thyroid carcinomas that are unable to trap iodine as an adjunct to radioiodine therapy.

Acetylation↗
PubMed2001

Preserved Smad4 expression in the transforming growth factor beta signaling pathway is a favorable prognostic factor in patients with advanced gastric cancer.

The signals of the transforming growth factor beta (TGF-beta) superfamily are conveyed through cell surface serine/threonine kinase receptors to the intracellular mediators known as Smads. Activation of Smads causes their translocation from the cytoplasm to the nucleus, where they function to control gene expression. The present study analyzed the expression of Smad4 and TGF-beta1 to determine their prognostic significance in advanced gastric cancer. Of 249 cases of advanced gastric cancer, 41 had invaded the muscular layer, 114 had invaded the subserosal layer, and 94 had invaded the serosa. Anti-Smad4 and TGF-beta1 antibodies were used for immunohistochemical staining. Reduced expression of Smad4 was 75.1%, whereas positive expression of TGF-beta1 was 39.6% in gastric cancer. Smad4 expression was related to the depth of tumor invasion (P < 0.05), and TGF-beta1 expression correlated with tumor gross type (P < 0.05). Postoperative survival analysis indicated that patients who had a tumor with reduced Smad4 expression had a poorer clinical outcome than those with preserved expression (P < 0.05). Furthermore, in patients with TGF-beta1-positive tumors, survival rate was significantly better in patients with preserved Smad4 expression than in those with reduced Smad4 expression (P < 0.05). According to multivariate analysis, Smad4 expression acted as an independent prognostic factor. Smad4 expression, particularly in the TGF-beta pathway, is an effective predictor of outcome for patients with advanced gastric cancer.

Adult↗
PubMed2001

Hand-assisted laparoscopic distal pancreatectomy with minilaparotomy for distal pancreatic cystadenoma.

Two patients with cystic tumors of the pancreas treated by laparoscopic distal pancreatectomy are presented. The first patient was a 34-year-old woman with a 6-cm cystadenoma of the tail of the pancreas treated with a complete laparoscopic distal pancreatectomy. After mobilization of the distal pancreas and spleen, the pancreas was transected proximally together with the splenic artery and vein using an endoscopic linear stapler. The second patient was a 71-year-old woman with a 6-cm cystadenoma of the body of the pancreas, treated by hand-assisted laparoscopic distal pancreatectomy with minilaparotomy because the tumor was adjacent to the portal vein and celiac axis. Using an upper median minilaparotomy, dissection of the gastrocolic ligament, division of the splenic artery, and transection and closure of the pancreas were performed. Division of the splenic vein and mobilization of the distal pancreas and spleen were performed via a hand-assisted laparoscopic approach. There were no postoperative complications (such as pancreatic fistulas) in either patient, and the postoperative courses were uneventful. The patients returned to normal activity within 1 week after the operation. Complete laparoscopic and hand-assisted laparoscopic distal pancreatectomy are preferable to conventional open surgery for benign tumors of the pancreas because of their less-invasive nature. Additionally, in tumors of the body of the pancreas, hand-assisted laparoscopic distal pancreatectomy might have the advantages of laparotomy and laparoscopy in terms of handling the splenic artery and vein just below the minilaparotomy site, suggesting an easier and safer procedure than complete laparoscopic distal pancreatectomy. Therefore, hand-assisted laparoscopic distal pancreatectomy can be recommended as a useful alternative to complete laparoscopic distal pancreatectomy for selected patients with benign tumors of the body and tail of the pancreas.

Adult↗
PubMed2001

Can sentinel node navigation surgery reduce the extent of lymph node dissection in gastric cancer?

Our group has conducted several studies of sentinel node navigation surgery (SNNS) for the management of early gastric cancer. To determine the distribution of nodal metastases and micrometastases, we used immunohistochemical staining with anticytokeratin antibody to examine 2605 lymph nodes obtained from 108 consecutive patients with submucosal gastric cancer. When nodes were negative by routine hematoxylin and eosin (H&E) examination, micrometastases were confined to one regional lymphatic pathway near the primary tumor; however, when nodes were H&E-positive, micrometastases were distributed more widely. The wide and complicated lymphatic stream from a gastric tumor contributed to the relatively high (23%) incidence of micrometastases and the frequent occurrence of skip metastasis. In another study, we used a combination of blue dye and radiopharmaceutical to perform SNNS in 18 patients with early gastric cancer. The rate of sentinel node detection was 94%, and the average number of sentinel nodes per patient was three. Technical issues included size of particles, method of injection, accuracy of frozen section examination, and standard criteria for defining a sentinel node. SNNS for gastric cancer is a promising technique; further study of various anatomic and pathologic factors will indicate whether it can be used to determine the extent of lymphadenectomy necessary in patients with early gastric cancer.

Coloring Agents↗
PubMed2001

[Survival benefits of and indications for extended surgery for advanced gastric cancer].

The surgical management of locally advanced gastric cancer remains controversial. It is also unclear whether the postoperative survival rate could be improved by extended lymph node dissection. The aim of this paper is to determine the survival benefit of and the indications for extended surgery. Lymph node metastasis in the paraaortic area frequently occurs in locally advanced cardiac cancer. In our previous studies, the paraaortic lymph nodes above and below the left renal vein were confirmed to be the terminal destination of lymphatic flow in the upper abdominal cavity. Paraaortic lymph node dissection is essential for curarive resection in some cases of advanced gastric cancer. The 5-year survival rate in patients who undergo paraaortic lymph node dissection is nearly 15% according to the literature. Patients with metastasis of the paraaortic lymph nodes on only one side and with fewer than four involved nodes clearly benefit from paraaortic lymph node dissection. It is indicated in cases with metastasis or suspected metastasis of the left or right cardiac lymph node or N2 lymph node station. There is little survival benefit from combined resection of involved organs (T4 disease) and it should only be performed in a select group of patients. Extended surgery for locally advanced gastric cancer, however, is feasible and has acceptable operative morbidity and mortality rates.

Gastrectomy↗
PubMed2000

PEA3 and AP-1 are required for constitutive IL-8 gene expression in hepatoma cells.

Interleukin-8 (IL-8) mRNA was constitutively expressed in human hepatoma cell line, HepG2 and in human hepatocellular carcinoma (HCC), which often form hypervascular tumors. The sequence 5'-AGGAAG-3' at -137 to -132 bp of IL-8 promoter was shown to be polyomavirus enhancer A binding protein-3 (PEA3) binding site, which can cooperate with activator protein-1 (AP-1). Both PEA3 and AP-1 are essential for constitutive IL-8 expression in HepG2 cells, determined by promoter assays. Moreover, PEA3 and IL-8 proteins coexisted in HCC tissues, but not in uninvolved liver tissues. It is possible PEA3 may have important roles in tumor progression and in angiogenesis in HCC.

Base Sequence↗
PubMed2000

Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in the patients with esophageal carcinoma.

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Aged↗
PubMed2000

Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer.

Intratumoral natural killer cells (NKC) and dendritic cells (DC) may affect the clinical features of various gastrointestinal cancers. However, the relationship between intratumoral NKC and DC remains unclear. We examined 169 patients with gastric cancer who underwent gastrectomy at Kagoshima University Hospital. Immunohistochemical staining of CD57 and S-100-protein was performed to evaluate NKC and DC infiltration, respectively. A total of 25 areas containing pericancerous tissue were selected for determining the number of NKC and DC under high power microscopy (x400). Patients were classified into two groups according to NKC and DC population. Intratumoral lymphocytic infiltration was also calculated in 15 areas with a high power (x400) objective. The degree of NKC and DC infiltration was gradually decreased according to the progression of nodal involvement. Patients with many NKC infiltration had a lower positivity of lymph node metastasis and lymphatic invasion than patients with little NKC infiltration. DC infiltration was also negatively correlated with depth of invasion, lymph node metastasis and curativity. DC infiltration was positively correlated with lymphocytic infiltration (P=0.01. r=0.6). The 5-year survival rates of patients with many NKC infiltration and patients with DC many infiltration were 75 and 78%, respectively, both of which were significantly better than that of patients with little NKC and DC infiltration (P<0.05). NKC may be activated without DC or intratumoral lymphocytes. Intratumoral NKC may act as an independent immunologic effector against tumor cells, unlike DC.

CD57 Antigens↗
PubMed2000

Apoptosis and cell proliferation in esophageal sqamous cell carcinoma treated by chemotherapy.

The p53 gene is associated with G1 arrest during the cell cycle and with apoptosis. To evaluate the preoperative chemotherapeutic effect in esophageal squamous cell carcinoma, we retrospectively investigated the apoptotic index (AI) and Ki-67 labeling index (Ki-67LI) in relation to the expression of p53. Thirty patients with esophageal carcinoma who had received chemotherapy prior to surgery were examined using the terminal deoxynucleotidyl-transferase-mediated in-situ end-labeling (TUNEL) method for evaluating AI and immunohistochemical staining with anti Ki-67 and anti p53 antibody for evaluating Ki-67LI and p53 expression, respectively. The histological response rate of chemotherapy was 20.0%. A significant correlation between p53-negative expression and response to chemotherapy was found (P<0. 01). The AIs and Ki-67LIs in p53-negative tumors with ineffective responses to chemotherapy were significantly higher than those in p53-positive tumors with ineffective responses (P<0.05). The AIs and Ki-67LIs were significantly lower in p53-negative tumors with effective responses to chemotherapy than those in p53-negative tumors with ineffective responses (P<0.05 and P<0.01, respectively). Furthermore, significant correlations were found between AIs and Ki-67LIs in p53 negative tumors (r=0.60, P<0.05). In esophageal carcinoma, p53-negative tumors with highly proliferative cells might be susceptible to apoptosis induced by chemotherapy.

Adult↗
PubMed2000

Suppression of metastasis by thymidine phosphorylase inhibitor.

We developed a novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI), that is about 1000-fold more active than 6-amino-5-chlorouracil, one of the most potent TP inhibitors. TPI inhibited the high chemotactic motility and basement membrane invasion of KB/TP cells, a TP-positive clone transfected with Rous sarcoma virus (RSV)/TP, to the levels seen in KB/CV cells, a control clone transfected with RSV. In nude mice, oral administration of TPI suppressed not only macroscopic liver metastases of highly metastatic KB/TP cells but also the level of human beta-globin as a molecular marker of micrometastases in the livers of the mice. These findings demonstrate that TP plays a key role in the invasiveness and metastasis of TP-expressing solid tumors and suggest that TPI might be a novel antimetastatic agent for blood-borne metastasis.

Animals↗
PubMed2000

The cooperative role of p27 with cyclin E in the prognosis of advanced gastric carcinoma.

BACKGROUND: Cyclin E and p27 play opposing roles in the cell cycle. This study investigated the protein expression of p27 with cyclin E in the progression and prognosis of gastric carcinoma. METHODS: Of 241 patients with advanced gastric carcinoma, 38 had muscular layer invasion, 113 had subserosal layer invasion, and 90 had serosal invasion. Anti-p27 and cyclin E antibodies were used for immunohistochemical staining. RESULTS: Positive expression of p27 and cyclin E was 32.4% and 38.2%, respectively. Both p27 and cyclin E expression were related to histology of tumors but not to depth of invasion, lymph node metastasis, or stage grouping. A positive correlation was observed between p27 and cyclin E expression (P < 0. 05). Tumors were divided into two groups according to the expression of cyclin E. Within the cyclin E positive tumors, the five-year survival rate was higher in patients with a p27 positive tumor than in those with a p27 negative tumor (P < 0.05). Patients with cyclin E positive tumors showing low expression of p27 had a poor prognosis. In cyclin E negative group tumors, no significant differences were observed irrespective of p27 expression. CONCLUSIONS: Reduced p27 expression is a negative prognostic factor for patients with cyclin E positive tumors.

Adult↗
PubMed2000

Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma.

The lymph nodes of 59 patients with pN0 esophageal squamous cell carcinomas were examined immunohistochemically using cytokeratin (CK) antibody. Primary tumors were immunostained with cyclin D1 (CD1) and E-cadherin (E-cad) antibody. Lymph node micrometastasis (MM) was found in 39 (55.5%) patients. Tumor recurrence was found in 17 patients and all but one of them had MM. The 5-year survival rate was significantly poorer in patients with MM than in those without MM. Almost all patients with positive CD1 and negative E-cad expression had MM. The examination of CD1 and E-cad expression in primary tumors may be useful for predicting MM.

Adult↗
PubMed2000

Expression of thrombomodulin in squamous cell carcinoma of the lung: its relationship to lymph node metastasis and prognosis of the patients.

Thrombomodulin (TM) is a type of thrombin receptor that was identified originally on the endothelium and acts as a natural anticoagulant through converting thrombin from a procoagulant protease to an anticoagulant. We reported previously that TM was also expressed in the squamous epithelium mainly at the intercellular bridges. In this study, we examined TM expression in the primary lesions of 81 patients with squamous cell carcinomas (SCCs) of the lung and in the lymph node metastatic lesions of 39 patients using immunohistochemical methods. The carcinoma tissues expressed TM mainly at the cell-cell boundaries and also in the cytoplasm. When TM expression was compared between the primary and metastatic lesions in the 39 patients who had lymph node metastasis, 26 (67%) showed decreased TM expression, 13 (33%) showed no change, and none (0%) showed an increase in the metastatic lesions. Wilcoxon's signed-rank test indicated that tumor cells that were positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.0001). The present study also showed that the patients with TM-negative expression in the primary tumors showed significantly poorer survival than those with TM-positive expression, mainly due to distant metastases of poorly-differentiated SCCs with negative TM expression in the primary tumors. These results indicate that the reduction of TM expression seems to play an important role in the metastatic process of lung SCCs.

Adult↗
PubMed2000

p21 expression is a prognostic factor in patients with p53-negative gastric cancer.

The expression of p21 and p53 proteins was analyzed by immunohistochemistry in 256 patients with advanced gastric cancer. The results showed that strong, weak and negative expression of p21 were detected in 22.2 (57/256), 68.0 (174/256) and 9.8% (25/256) of the patients, respectively. p53 expression was found in 28.9% (74/256). The expression of p21 was not associated with clinicopathological features. In p53 negative tumors, p21 expression was associated with the survival of patients who underwent curative operations (P = 0.007). The 5-year survival rates were 20.1, 36.6 and 59.8% in patients with p21-negative, -weakly positive and -strongly positive tumors, respectively. In contrast, in p53-positive tumors, prognosis did not differ in spite of p21 expression. Multivariate analysis showed that p21 expression was an independent factor in patients with p53-negative tumors. These results indicate that examination of p21 expression in p53 negative tumors will be useful for estimating the prognosis of patients with advanced gastric cancer.

Adult↗
PubMed2000

Prognostic value of intratumoral natural killer cells in gastric carcinoma.

BACKGROUND: Natural killer (NK) cells are a group of effector cells that act nonspecifically against tumor cells. The correlation between intratumoral NK cell infiltration and clinicopathologic features remains unclear. METHODS: The authors selected 146 patients with gastric carcinoma who underwent gastrectomy at Kagoshima University Hospital between 1985-1995. Immunohistochemical staining with the CD57 antibody was performed for the evaluation of NK cell infiltration. A total of 25 areas containing CD57 positive cells were selected and the number of NK cells were counted (magnification, x200). The patients were divided into 2 groups: patients with a high level of NK infiltration (n = 39) (>25 NK cells/25 high-power fields [HPF]) and patients with a low level of NK infiltration (n = 107) (<25 NK cells/25 HPF). Intratumoral lymphocytic infiltration also was counted in 25 areas at a magnification of x200. Patients were classified into a high infiltrating lymphocyte (IL) group (n = 69) (>150 cells/HPF) and a low IL group (n = 77) (<150 cells/HPF). The Kaplan-Meier curve was used to analyze surgical outcome. Multivariate analyses were performed to evaluate prognostic factors. RESULTS: Patients with a high level of NK infiltration had a higher rate of early gastric carcinoma, fewer metastases to the lymph nodes (P < 0.01), and less lymphatic invasion (P < 0.05) than patients with a low level of NK infiltration. NK cell infiltration also was found to correlate with depth of invasion, clinical stage, and venous invasion. There was no correlation between NK cells and lymphocytic infiltration (P = 0.07; correlation coefficient = 0.15). The 5-year survival rate of patients with a high rate of NK infiltration was 78%, which was significantly better than that of patients with a low level of NK infiltration (P < 0.01). Multivariate analysis did not show NK cell infiltration to be a significant prognostic factor. Combination analysis of the number of NK cells and lymphocytic infiltration was shown to be an independent prognostic factor (P = 0.02; hazard ratio = 1.32). CONCLUSIONS: Patients with a high level of NK infiltration were found to have a better prognosis than those with a low level of NK infiltration. Combination analysis with lymphocytic infiltration may provide useful information regarding the immunologic condition of patients with gastric carcinoma.

Adult↗
PubMed2000

Length and quality of survival following external beam radiotherapy combined with expandable metallic stent for unresectable hilar cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Hilar cholangiocarcinoma is a morbid disease with a poor prognosis because resection cannot be performed in many cases. The purpose of this study was to evaluate whether external beam radiotherapy (RT) combined with expandable metallic biliary stent (EMS) affects the length and quality of survival of patients with unresectable hilar cholangiocarcinomas. METHODS: Fifty-one patients with unresectable hilar cholangiocarcinoma were retrospectively reviewed. Thirty patients received external beam radiotherapy combined with EMS (EMS+RT group), 10 patients were treated with EMS alone (EMS group), and the remaining 11 patients underwent percutaneous transhepatic biliary drainage alone (PTBD group). The length and quality of survival were analyzed and compared among the three groups. RESULTS: The mean survival of 6.4 months in the EMS group was significantly longer than that of 4.4 months in the PTBD group (P < 0.05). The EMS+RT group with a mean survival of 10.6 months had a significantly longer survival than the EMS group (P < 0.05). The average of the monthly Karnofsky scores of 74.9 in the EMS+RT group and 68.1 in the EMS group, as a parameter of quality of survival, was significantly higher than that of 57.7 in the PTBD group (P < 0.01). The number of hospital days per month of survival was significantly smaller in the EMS+RT and EMS groups than in the PTBD group (10.4, 14.2 vs. 27.3 days; P < 0.001). The EMS+RT group had a longer stent patency than the EMS group (mean: 9.8 vs. 3.7 months; P < 0.001). CONCLUSIONS: These results indicate that external radiotherapy combined with metallic biliary endoprosthesis can increase the length and quality of survival and consequently provide a definite palliative benefit for patients with unresectable hilar cholangiocarcinoma.

Adult↗