Takashi Aikou - Academia.edu (original) (raw)
Papers by Takashi Aikou
British journal of cancer, 2000
The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many ty... more The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application.
Esophagus, 2007
ABSTRACT A 62-year-old man was admitted to our hospital for dysphagia, leukocytosis, and pyrexia.... more ABSTRACT A 62-year-old man was admitted to our hospital for dysphagia, leukocytosis, and pyrexia. The serum level of granulocyte colony-stimulating factor (G-CSF) was high and immunostaining of a biopsy specimen of esophageal tumor using anti-granulocyte-macrophage colony-stimulating factor (anti-GM-CSF) antibody demonstrated GM-CSF expression in the cytoplasm of the tumor cells. After esophagectomy, the leukocyte count and serum G-CSF level normalized. Histologically, this tumor was diagnosed as a carcinosarcoma with two components: squamous cell carcinoma and sarcoma. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, tumor cells were positive for Ki-67, cyclin D1, p53, and epidermal growth factor receptor (EGFR), which were related to the acquisition of more aggressive tumor behavior. Although G-CSF-producing esophageal carcinosarcoma is very rare, we should consider such disease when a patient has symptoms of leukemia such as leukocytosis and high fever.
Human Cell
Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous me... more Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous metastases resulting in poor prognoses of the patients. We examined on whether E-cadherin is associated with these malignant behaviors of pancreatic carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1. Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a significant increase of invasiveness compared to those treated with the control oligonucleotide (P < 0.001), whereas the proliferation of JHP-1 cells was not affected by the presence of either E-cadherin antisense or control oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma cells induced the invasiveness into the basement membrane. These results suggest that the reduction in E-cadherin expression plays a key role not only in detachment of cell-cell adhesion but also in invasion and metastasis of pancreatic carcinoma cells.
Nippon Geka Gakkai zasshi
The first edition of the Guidelines for Treatment in Gastric Cancer (TGGC) was published in 2002 ... more The first edition of the Guidelines for Treatment in Gastric Cancer (TGGC) was published in 2002 and it was revised in 2004. Those were the first Japanese treatment guidelines for any type of cancer. Questionnaires were then sent to committee members of the Japanese Gastric Cancer Association. After the responses had been analyzed, problems and improvements in the TGGC were discussed in comparison with the guidelines for cancer treatment in other organs. Based on the questionnaire results, the TGGC have been used sufficiently in clinical practice to serve as a standardized guide for gastric cancer treatment, and thus the initial aims of standardization of treatment and a common understanding among physicians and patients were achieved. The following problems and areas for improvement were pointed out: 1) Some standard treatments are described in the clinical trial setting. 2) The renewal for chemotherapy is not performed on the basis of new evidence. 3) The announcement of time and ...
British journal of cancer, 1998
Midkine (MK) is a growth factor identified as a product of a retinoic acid-responsive gene. A tru... more Midkine (MK) is a growth factor identified as a product of a retinoic acid-responsive gene. A truncated form of MK mRNA, which lacks a sequence encoding the N-terminally located domain, was recently found in cancer cells. We investigated the expression of the truncated MK mRNA in specimens of 47 surgically removed human gastrointestinal organs using polymerase chain reaction. Truncated MK was not detected in all of the 46 corresponding non-cancerous regions. On the other hand, this short MK mRNA was expressed in the primary tumours in 12 of 16 gastric cancers, 8 of 13 colorectal carcinomas, five of nine hepatocellular carcinomas, two of two oesophageal carcinomas and one ampullary duodenal cancer. In addition, truncated MK was detectable in all of the 14 lymph node metastases but in none of three metastatic sites in the liver, suggesting that truncated MK mRNA could become a good marker of nodal metastases in gastrointestinal tract.
British journal of cancer, Jan 13, 2009
Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen acti... more Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen activation cascade and participates in extracellular matrix degradation, cell migration and invasion. We evaluated the expression level of uPAR mRNA and the presence of isolated tumour cells (ITCs) in bone marrow (BM) and peripheral blood (PB) in gastric cancer patients and clarified its clinical significance. We assessed specific uPAR mRNA expression by quantitative real-time reverse transcriptase- polymerase chain reaction (RT-PCR) in BM and PB in 846 gastric cancer patients as well as three epithelial cell markers, carcinoembryonic antigen (CEA), cytokeratin (CK)-19 and CK-7. The uPAR mRNA expression in bone marrow and peripheral blood expressed significantly higher than normal controls (P<0.0001). The uPAR mRNA in BM showed concordant expression with the depth of tumour invasion, distant metastasis, and the postoperative recurrence (P=0.015, 0.044 and 0.010, respectively); whereas in ...
British journal of cancer, Jan 22, 2008
Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expres... more Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial g...
British journal of cancer, Jan 6, 2007
Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene.... more Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P=0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P=0.0073). Multivariate analysis reveal...
British journal of cancer, Jan 19, 2005
The monoclonal antibody D2-40 is a specific lymphatic endothelial markers and D2-40 staining have... more The monoclonal antibody D2-40 is a specific lymphatic endothelial markers and D2-40 staining have been applicable to evaluate lymphatic invasion in various malignant neoplasms. In the present study, we investigated lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in all dissected lymph nodes obtained from 80 patients with node-negative gastric cancer, and analysed the relationship between micrometastasis and clinicopathological findings including lymphatic invasion of the resected primary tumour using D2-40 immunohistochemical staining. The incidence of micrometastasis determined by IHC and RT-PCR was 11.3% (nine out of 80) and 31.3% (25 out of 80), respectively. Although haematoxylin-eosin (HE) staining revealed lymphatic invasion in 11.3% (nine out of 80) of patients, D2-40 staining uncovered new invasion in 23.8% (19 out of 80) of patients. In the diagnosis of HE and D2-40 staining, the incidence of m...
Nihon Geka Gakkai zasshi, 2005
British journal of cancer, Jan 31, 2005
The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA da... more The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA damage. In the present study, we analysed the expression of some p53 family proteins and their responses to chemoradiation therapy (CRT) in cases of oesophageal squamous cell carcinoma (ESCC). We immunohistochemically investigated the relationship between p53, p53R2, and p21 expression in biopsy specimens of untreated primary tumours and their clinical and histological responses to CRT in 62 patients with ESCC. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The rates of clinical and histological responses (complete or partial) to CRT were 71.0% (clinical) and 52.8% (histological). The rate of positive expression was 43.5% for p53, 37.1% for p53R2, and 54.8% for p21 expression. Statistically significant correlations were found between p53 or p53R2 expression and favourable response to CRT (P=0.0001 or 0.041 clinical, P=0.016 or 0.0018 histological,...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 1999
BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The ... more BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The purpose of this study was to investigate the incidence and significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in these critical lymph nodes.METHODS: A total of 2339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically, using cytokeratin antibody.RESULTS: Lymph node metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine histological examination. MM or TCM was immunohistochemically detected in 45 of the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n = 10). The 5-year-survival rate in the paraaortic node-negative group and cytokeratin-positive group was significantly higher that that of the hematoxilin and eosin-positive group. The total number of lymph node metastases by hematoxylin and eosin staining and the pathological lymp...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2001
No reports have, to date, focused on the relationship between preoperative determination of the d... more No reports have, to date, focused on the relationship between preoperative determination of the depth of invasion and lymph node metastasis. The present study, under the leadership of the Japanese Gastric Cancer Association, was designed to form a basis for decision making in limited treatment for early gastric cancer (EGC). From eight major hospitals in Japan, 2672 gastric cancers whose preoperative depth of invasion was mucosal(M-cancer), and 6209 EGCs, consisting of 3584 mucosal(m-) and 2625 submucosal(sm-) cancers, were collected by questionnaire. All registered patients underwent gastrectomy with D1 or more extensive lymphadenectomy between 1985 and 1998. The accuracy of preoperative diagnosis of depth of invasion of M-cancers was 80.2% (2144/2672). However, of the total of 2432 M-cancers in which no nodal involvement was observed intraoperatively (N0), histological examination of the resected specimens confirmed that lymph node metastasis was absent in 2353 (96.8%). The freque...
Cancer research, 2000
We developed a novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidiny... more 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.
Human pathology, 2000
Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important rol... more Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion and in cell-matrix interaction. We have examined the expression of galectin-3 in normal, adenomatous, and malignant thyroid tissues and also in metastatic lesions. Galectin-3 was rarely expressed in normal thyroid tissue but was abundant in the cytoplasm of the neoplastic lesions. Among neoplastic lesions, galectin-3 was expressed to a greater extent in follicular carcinomas than in follicular adenomas and was present in greater amounts in papillary carcinomas than in follicular adenomas or carcinomas. Primary lesions of papillary carcinoma with metastasis contained significantly higher concentrations of galectin-3 than tumors of this type without metastases. However, the expression of galectin-3 was significantly decreased in metastatic lesions in the lymph nodes compared with their primary lesions. From these results, we assumed that galectin-3 works in differen...
Surgery, 1998
This study was undertaken to evaluate the response to therapy aimed at achieving supranormal card... more This study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index > than 4.5 L/min/m2, oxygen delivery > 600 ml/min/m2, and oxygen consumption > 170 ml/min/m2) in patients with cirrhosis who have undergone partial hepatectomy and to assess the relationship between those parameters and outcome. Thirty-four consecutive patients underwent elective hepatectomy for hepatocellular carcinoma. The postoperative outcomes and hemodynamic and oxygen transport values in 16 patients (group S) who maintained supranormal values were compared with those in 18 patients (group N) treated to maintain normal hemodynamic values. Patients in group S received volume expansion and then, if necessary, dobutamine (3 to 15 micrograms/kg/min) to increase cardiac index, oxygen delivery, and oxygen comsumption simultaneously during the first 12 hours. The hemodynamic targets were reached by 56% of patients in group S during...
Gastric Cancer, 1998
BACKGROUND: To elucidate the role that cyclin E overexpression plays in the progression of early ... more BACKGROUND: To elucidate the role that cyclin E overexpression plays in the progression of early gastric cancer, we examined the expression of cyclin E and p53, as abnormal p53 expression is linked with cyclin E overexpression in exerting adverse affects on the cell cycle.METHODS: Specimens from 108 early gastric cancers were stained by an immunohistochemical method, using anti-cyclin E and anti- p53 antibodies.RESULTS: The positivity rate of cyclin E expression in early gastric cancer was 33% (36/108). Cyclin E-positive tumors invaded more deeply ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.05), infiltrated lymphatic vessels more frequently ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.01), showed a higher incidence of differentiated cancer ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.01), and more often expressed p53 ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.01) than cyclin E-negative tumors. Differentiated cancers showing coexpression of cyclin E and p53 were more likely to metastasize to the lymph nodes.CONCLUSIONS: Overexpression of cyclin E may promote the progression of early gastric cancer.
International Journal of Oncology, 2006
Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuv... more Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuvant chemotherapy gives a better chance of survival, we attempted to develop a chemosensitivity prediction model to improve individual responses to therapy. Comprehensive gene expression analyses (cDNA and oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell carcinoma cell lines were performed to distinguish candidate marker genes whose expression levels reproducibly correlated with cellular drug sensitivities. After confirmation with real-time RT-PCR, we performed multiple regression analyses to develop drugsensitivity prediction formulae using the quantified expression data of selected marker genes. Using the same sets of genes, we also constructed prediction models for individual clinical responses to 5-FU-based chemotherapy using 18 cases. We selected 5 better marker genes, known as drug sensitivity determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5-FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based adjuvant chemotherapies in terms of overall and disease-free survivals. Our selected genes are likely to be effective drug-sensitivity markers and formulae using the 9 novel genes would provide advantages in prediction.
World Journal of Surgery, 2003
The purpose of this retrospective study was to analyze the distribution of lymph node metastases,... more The purpose of this retrospective study was to analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion. A total of 118 patients with submucosal gastric cancer were enrolled in this study. The distribution of lymph node metastases was examined according to tumor location. Immunohistochemical examination using anti-cytokeratin antibody was performed to examine nodal micrometastases in 118 patients. Lymph node metastasis was found in 19.5% (23/118) of the patients. Significant differences were found for tumor size and depth, lymphatic invasion, and venous invasion for patients with and without nodal metastasis. The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was 24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor. When planning minimally invasive treatment for submucosal gastric cancer, it is important to understand the distribution of lymph node metastasis, including micrometastasis, according to tumor location.
World Journal of Surgery, 2005
The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increas... more The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increased. The purpose of this study was to analyze clinicopathologic findings for MPC and for only esophageal cancer (OEC). Of 157 patients with MPCs, 60 had synchronous cancer and 97 metachronous cancer. Another 42 patients had antecedent esophageal cancer (AEC), and 55 patients had subsequent esophageal cancer (SEC). We retrospectively analyzed the clincopathologic findings for patients in these categories. The incidence of early-stage carcinoma was higher in patients with MPCs than in those with an OEC. Of patients with MPCs, those with metachronous cancer had a higher rate of earlystage carcinoma than those with synchronous cancer. The 5-year survival rates were not significantly different for MPC and OEC patients. Patients with metachronous cancer had a significantly better prognosis than those with synchronous cancer (p = 0.017); and in the metachronous cancer group the prognosis was significantly better for patients with AEC than for those with SEC (p = 0.0005). Meticulous follow-up after treatment of a first cancer should be required to detect other early-stage carcinomas.
British journal of cancer, 2000
The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many ty... more The level of expression of midkine (MK), a heparin-binding growth factor, is increased in many types of human carcinomas. An enzyme-linked immunoassay, which utilizes a combination of rabbit and chicken antibodies revealed that serum MK level in the controls (n = 135) was 0.154 +/- 0.076 (mean +/- SD) ng ml(-1)with an apparent cut-off value as 0.5 ng ml(-1). Serum MK level was significantly elevated in the cancer patients (n = 150) (P< 0.001); 87% of the patients showed levels of more than 0.5 ng ml(-1). All ten types of cancer examined showed a similar profile of serum MK level. There was no or weak correlation between C-reactive protein level, a marker of inflammation, and serum MK level. Furthermore, in case of gastric carcinoma and lung carcinoma, patients with stage I carcinoma already showed elevated serum MK levels. The present results indicated that serum MK could serve as a general tumour marker with a good potential for clinical application.
Esophagus, 2007
ABSTRACT A 62-year-old man was admitted to our hospital for dysphagia, leukocytosis, and pyrexia.... more ABSTRACT A 62-year-old man was admitted to our hospital for dysphagia, leukocytosis, and pyrexia. The serum level of granulocyte colony-stimulating factor (G-CSF) was high and immunostaining of a biopsy specimen of esophageal tumor using anti-granulocyte-macrophage colony-stimulating factor (anti-GM-CSF) antibody demonstrated GM-CSF expression in the cytoplasm of the tumor cells. After esophagectomy, the leukocyte count and serum G-CSF level normalized. Histologically, this tumor was diagnosed as a carcinosarcoma with two components: squamous cell carcinoma and sarcoma. Tumor cells were also positive for G-CSF receptor, suggesting autocrine growth regulation by G-CSF. Moreover, tumor cells were positive for Ki-67, cyclin D1, p53, and epidermal growth factor receptor (EGFR), which were related to the acquisition of more aggressive tumor behavior. Although G-CSF-producing esophageal carcinosarcoma is very rare, we should consider such disease when a patient has symptoms of leukemia such as leukocytosis and high fever.
Human Cell
Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous me... more Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or hematogenous metastases resulting in poor prognoses of the patients. We examined on whether E-cadherin is associated with these malignant behaviors of pancreatic carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1. Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a significant increase of invasiveness compared to those treated with the control oligonucleotide (P < 0.001), whereas the proliferation of JHP-1 cells was not affected by the presence of either E-cadherin antisense or control oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma cells induced the invasiveness into the basement membrane. These results suggest that the reduction in E-cadherin expression plays a key role not only in detachment of cell-cell adhesion but also in invasion and metastasis of pancreatic carcinoma cells.
Nippon Geka Gakkai zasshi
The first edition of the Guidelines for Treatment in Gastric Cancer (TGGC) was published in 2002 ... more The first edition of the Guidelines for Treatment in Gastric Cancer (TGGC) was published in 2002 and it was revised in 2004. Those were the first Japanese treatment guidelines for any type of cancer. Questionnaires were then sent to committee members of the Japanese Gastric Cancer Association. After the responses had been analyzed, problems and improvements in the TGGC were discussed in comparison with the guidelines for cancer treatment in other organs. Based on the questionnaire results, the TGGC have been used sufficiently in clinical practice to serve as a standardized guide for gastric cancer treatment, and thus the initial aims of standardization of treatment and a common understanding among physicians and patients were achieved. The following problems and areas for improvement were pointed out: 1) Some standard treatments are described in the clinical trial setting. 2) The renewal for chemotherapy is not performed on the basis of new evidence. 3) The announcement of time and ...
British journal of cancer, 1998
Midkine (MK) is a growth factor identified as a product of a retinoic acid-responsive gene. A tru... more Midkine (MK) is a growth factor identified as a product of a retinoic acid-responsive gene. A truncated form of MK mRNA, which lacks a sequence encoding the N-terminally located domain, was recently found in cancer cells. We investigated the expression of the truncated MK mRNA in specimens of 47 surgically removed human gastrointestinal organs using polymerase chain reaction. Truncated MK was not detected in all of the 46 corresponding non-cancerous regions. On the other hand, this short MK mRNA was expressed in the primary tumours in 12 of 16 gastric cancers, 8 of 13 colorectal carcinomas, five of nine hepatocellular carcinomas, two of two oesophageal carcinomas and one ampullary duodenal cancer. In addition, truncated MK was detectable in all of the 14 lymph node metastases but in none of three metastatic sites in the liver, suggesting that truncated MK mRNA could become a good marker of nodal metastases in gastrointestinal tract.
British journal of cancer, Jan 13, 2009
Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen acti... more Urokinase-type plasminogen activator receptor (uPAR) plays a central role in the plasminogen activation cascade and participates in extracellular matrix degradation, cell migration and invasion. We evaluated the expression level of uPAR mRNA and the presence of isolated tumour cells (ITCs) in bone marrow (BM) and peripheral blood (PB) in gastric cancer patients and clarified its clinical significance. We assessed specific uPAR mRNA expression by quantitative real-time reverse transcriptase- polymerase chain reaction (RT-PCR) in BM and PB in 846 gastric cancer patients as well as three epithelial cell markers, carcinoembryonic antigen (CEA), cytokeratin (CK)-19 and CK-7. The uPAR mRNA expression in bone marrow and peripheral blood expressed significantly higher than normal controls (P<0.0001). The uPAR mRNA in BM showed concordant expression with the depth of tumour invasion, distant metastasis, and the postoperative recurrence (P=0.015, 0.044 and 0.010, respectively); whereas in ...
British journal of cancer, Jan 22, 2008
Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expres... more Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial g...
British journal of cancer, Jan 6, 2007
Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene.... more Midkine (MK) is a heparin-binding growth factor and a product of a retinoic acid-responsive gene. Midkine is overexpressed in many carcinomas and thought to play an important role in carcinogenesis. However, no studies have been focussed on the role of MK in pancreatic carcinoma. This study sought to evaluate the clinical significance of MK expression in pancreatic head carcinoma, including the relationship between immunohistochemical expression and clinicopathologic factors such as prognosis. Immunohistochemical expression of MK and CD34 was evaluated in pancreatic head carcinoma specimens from 75 patients who underwent surgical resection. Midkine was expressed in 53.3% of patients. Midkine expression was significantly correlated with venous invasion, microvessel density, and liver metastasis (P=0.0063, 0.0025, and 0.0153, respectively). The 5-year survival rate was significantly lower for patients positive for MK vs patients negative for MK (P=0.0073). Multivariate analysis reveal...
British journal of cancer, Jan 19, 2005
The monoclonal antibody D2-40 is a specific lymphatic endothelial markers and D2-40 staining have... more The monoclonal antibody D2-40 is a specific lymphatic endothelial markers and D2-40 staining have been applicable to evaluate lymphatic invasion in various malignant neoplasms. In the present study, we investigated lymph node micrometastasis determined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in all dissected lymph nodes obtained from 80 patients with node-negative gastric cancer, and analysed the relationship between micrometastasis and clinicopathological findings including lymphatic invasion of the resected primary tumour using D2-40 immunohistochemical staining. The incidence of micrometastasis determined by IHC and RT-PCR was 11.3% (nine out of 80) and 31.3% (25 out of 80), respectively. Although haematoxylin-eosin (HE) staining revealed lymphatic invasion in 11.3% (nine out of 80) of patients, D2-40 staining uncovered new invasion in 23.8% (19 out of 80) of patients. In the diagnosis of HE and D2-40 staining, the incidence of m...
Nihon Geka Gakkai zasshi, 2005
British journal of cancer, Jan 31, 2005
The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA da... more The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA damage. In the present study, we analysed the expression of some p53 family proteins and their responses to chemoradiation therapy (CRT) in cases of oesophageal squamous cell carcinoma (ESCC). We immunohistochemically investigated the relationship between p53, p53R2, and p21 expression in biopsy specimens of untreated primary tumours and their clinical and histological responses to CRT in 62 patients with ESCC. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The rates of clinical and histological responses (complete or partial) to CRT were 71.0% (clinical) and 52.8% (histological). The rate of positive expression was 43.5% for p53, 37.1% for p53R2, and 54.8% for p21 expression. Statistically significant correlations were found between p53 or p53R2 expression and favourable response to CRT (P=0.0001 or 0.041 clinical, P=0.016 or 0.0018 histological,...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 1999
BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The ... more BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The purpose of this study was to investigate the incidence and significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in these critical lymph nodes.METHODS: A total of 2339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically, using cytokeratin antibody.RESULTS: Lymph node metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine histological examination. MM or TCM was immunohistochemically detected in 45 of the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n = 10). The 5-year-survival rate in the paraaortic node-negative group and cytokeratin-positive group was significantly higher that that of the hematoxilin and eosin-positive group. The total number of lymph node metastases by hematoxylin and eosin staining and the pathological lymp...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2001
No reports have, to date, focused on the relationship between preoperative determination of the d... more No reports have, to date, focused on the relationship between preoperative determination of the depth of invasion and lymph node metastasis. The present study, under the leadership of the Japanese Gastric Cancer Association, was designed to form a basis for decision making in limited treatment for early gastric cancer (EGC). From eight major hospitals in Japan, 2672 gastric cancers whose preoperative depth of invasion was mucosal(M-cancer), and 6209 EGCs, consisting of 3584 mucosal(m-) and 2625 submucosal(sm-) cancers, were collected by questionnaire. All registered patients underwent gastrectomy with D1 or more extensive lymphadenectomy between 1985 and 1998. The accuracy of preoperative diagnosis of depth of invasion of M-cancers was 80.2% (2144/2672). However, of the total of 2432 M-cancers in which no nodal involvement was observed intraoperatively (N0), histological examination of the resected specimens confirmed that lymph node metastasis was absent in 2353 (96.8%). The freque...
Cancer research, 2000
We developed a novel inhibitor of thymidine phosphorylase (TP), 5-chloro-6-[1-(2-iminopyrrolidiny... more 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.
Human pathology, 2000
Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important rol... more Galectin-3 is a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion and in cell-matrix interaction. We have examined the expression of galectin-3 in normal, adenomatous, and malignant thyroid tissues and also in metastatic lesions. Galectin-3 was rarely expressed in normal thyroid tissue but was abundant in the cytoplasm of the neoplastic lesions. Among neoplastic lesions, galectin-3 was expressed to a greater extent in follicular carcinomas than in follicular adenomas and was present in greater amounts in papillary carcinomas than in follicular adenomas or carcinomas. Primary lesions of papillary carcinoma with metastasis contained significantly higher concentrations of galectin-3 than tumors of this type without metastases. However, the expression of galectin-3 was significantly decreased in metastatic lesions in the lymph nodes compared with their primary lesions. From these results, we assumed that galectin-3 works in differen...
Surgery, 1998
This study was undertaken to evaluate the response to therapy aimed at achieving supranormal card... more This study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport variables (cardiac index > than 4.5 L/min/m2, oxygen delivery > 600 ml/min/m2, and oxygen consumption > 170 ml/min/m2) in patients with cirrhosis who have undergone partial hepatectomy and to assess the relationship between those parameters and outcome. Thirty-four consecutive patients underwent elective hepatectomy for hepatocellular carcinoma. The postoperative outcomes and hemodynamic and oxygen transport values in 16 patients (group S) who maintained supranormal values were compared with those in 18 patients (group N) treated to maintain normal hemodynamic values. Patients in group S received volume expansion and then, if necessary, dobutamine (3 to 15 micrograms/kg/min) to increase cardiac index, oxygen delivery, and oxygen comsumption simultaneously during the first 12 hours. The hemodynamic targets were reached by 56% of patients in group S during...
Gastric Cancer, 1998
BACKGROUND: To elucidate the role that cyclin E overexpression plays in the progression of early ... more BACKGROUND: To elucidate the role that cyclin E overexpression plays in the progression of early gastric cancer, we examined the expression of cyclin E and p53, as abnormal p53 expression is linked with cyclin E overexpression in exerting adverse affects on the cell cycle.METHODS: Specimens from 108 early gastric cancers were stained by an immunohistochemical method, using anti-cyclin E and anti- p53 antibodies.RESULTS: The positivity rate of cyclin E expression in early gastric cancer was 33% (36/108). Cyclin E-positive tumors invaded more deeply ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.05), infiltrated lymphatic vessels more frequently ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.01), showed a higher incidence of differentiated cancer ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.01), and more often expressed p53 ( P &amp;amp;amp;amp;amp;amp;amp;lt; 0.01) than cyclin E-negative tumors. Differentiated cancers showing coexpression of cyclin E and p53 were more likely to metastasize to the lymph nodes.CONCLUSIONS: Overexpression of cyclin E may promote the progression of early gastric cancer.
International Journal of Oncology, 2006
Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuv... more Esophageal cancer is a highly lethal disease and the optimal therapy remains unclear. Since adjuvant chemotherapy gives a better chance of survival, we attempted to develop a chemosensitivity prediction model to improve individual responses to therapy. Comprehensive gene expression analyses (cDNA and oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell carcinoma cell lines were performed to distinguish candidate marker genes whose expression levels reproducibly correlated with cellular drug sensitivities. After confirmation with real-time RT-PCR, we performed multiple regression analyses to develop drugsensitivity prediction formulae using the quantified expression data of selected marker genes. Using the same sets of genes, we also constructed prediction models for individual clinical responses to 5-FU-based chemotherapy using 18 cases. We selected 5 better marker genes, known as drug sensitivity determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5-FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based adjuvant chemotherapies in terms of overall and disease-free survivals. Our selected genes are likely to be effective drug-sensitivity markers and formulae using the 9 novel genes would provide advantages in prediction.
World Journal of Surgery, 2003
The purpose of this retrospective study was to analyze the distribution of lymph node metastases,... more The purpose of this retrospective study was to analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion. A total of 118 patients with submucosal gastric cancer were enrolled in this study. The distribution of lymph node metastases was examined according to tumor location. Immunohistochemical examination using anti-cytokeratin antibody was performed to examine nodal micrometastases in 118 patients. Lymph node metastasis was found in 19.5% (23/118) of the patients. Significant differences were found for tumor size and depth, lymphatic invasion, and venous invasion for patients with and without nodal metastasis. The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was 24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor. When planning minimally invasive treatment for submucosal gastric cancer, it is important to understand the distribution of lymph node metastasis, including micrometastasis, according to tumor location.
World Journal of Surgery, 2005
The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increas... more The incidence of multiple primary carcinomas (MPCs) associated with esophageal cancer has increased. The purpose of this study was to analyze clinicopathologic findings for MPC and for only esophageal cancer (OEC). Of 157 patients with MPCs, 60 had synchronous cancer and 97 metachronous cancer. Another 42 patients had antecedent esophageal cancer (AEC), and 55 patients had subsequent esophageal cancer (SEC). We retrospectively analyzed the clincopathologic findings for patients in these categories. The incidence of early-stage carcinoma was higher in patients with MPCs than in those with an OEC. Of patients with MPCs, those with metachronous cancer had a higher rate of earlystage carcinoma than those with synchronous cancer. The 5-year survival rates were not significantly different for MPC and OEC patients. Patients with metachronous cancer had a significantly better prognosis than those with synchronous cancer (p = 0.017); and in the metachronous cancer group the prognosis was significantly better for patients with AEC than for those with SEC (p = 0.0005). Meticulous follow-up after treatment of a first cancer should be required to detect other early-stage carcinomas.