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Biomedical subjects

Tadaaki Maehara

Publications and source records attributed to Tadaaki Maehara.

At least 19 recordsLinked to original sources
PubMed2007

Significance of lymphatic invasion on regional lymph node metastasis in early gastric cancer using LYVE-1 immunohistochemical analysis.

It has been reported that lymphatic invasion is a predictor for lymph node metastasis in early gastric cancer (EGC); however, it has been impossible to differentiate between lymphatic invasion and blood vessel invasion using current staining techniques. We studied the significance of lymphatic invasion on regional lymph node metastasis in EGC by using human lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) antibody, specific to lymphatic vessels, and von Willebrand factor (vWF) antibody, specific to the blood vessels, to clearly distinguish these vascular tissues.EGC tissues were obtained from 66 node-positive and 66 node-negative subjects and were matched by age and sex. These tissues were immunostained with antibodies against LYVE-1 and vWF. Multivariate logistic regression analysis demonstrated that lymphatic invasion was a significant independent predictor for regional lymph node metastasis (odds ratio, 4.667; P = .0094), whereas blood vessel invasion was not. Thus, lymphatic invasion identified by LYVE-1 antibody could predict the existence of regional lymph node metastasis in EGC.

Biomarkers, Tumor↗
PubMed2006

Significance of thymidylate synthase gene expression level in patients with adenocarcinoma of the lung.

BACKGROUND: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis. High expression of TS is thought to be associated with poor prognosis in some kinds of cancers. However, this association has not been clarified for nonsmall cell lung carcinoma. In the current study, the authors investigated the clinicopathologic significance of TS mRNA levels and the correlation with cellular proliferation in patients with lung adenocarcinoma. METHODS: The expression levels of TS mRNA were measured in 47 lung adenocarcinoma tissues using the Taq-Man real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method and examined the clinicopathologic significance of TS expression. To clarify the correlation between TS expression level and cell proliferation, the Ki-67 labeling index was also examined using immunohistochemical staining. RESULTS: A positive correlation was observed between the expression levels of TS mRNA and stage of disease, lymph node metastasis, or tumor differentiation (P = .015). The higher expression group of TS mRNA showed a significantly poorer prognosis than the group with lower expression (P = .042). Moreover, there was a strong correlation noted between the expression levels of TS mRNA and the Ki-67 labeling index (P = .009). CONCLUSIONS: The results of the current study demonstrated that TS may be associated with stage of disease, lymph node metastasis, tumor differentiation, prognosis, and tumor cell proliferation. These results suggest that the expression levels of TS mRNA may be useful for predicting the malignant potential in patients with lung adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Controlled release of fibroblast growth factor-2 from an injectable 6-O-desulfated heparin hydrogel and subsequent effect on in vivo vascularization.

We prepared a 6-O-desulfated (DS-) heparin (Hep) hydrogel as an excellent carrier for the controlled release of Hep-binding growth factors, such as fibroblast growth factor (FGF)-2. This material, which is partially derived from photoreactive groups, such as cinnamate, is easily crosslinked upon ultraviolet light (UV)-irradiation, resulting in a water-insoluble, viscous, and injectable hydrogel. In the present study, we examined the capacity of 6-O-DS-Hep hydrogel to immobilize FGF-2, as well as the controlled release of FGF-2 molecules from this hydrogel in vitro and in vivo. Only 10% of FGF-2 was gradually released from the FGF-2-containing 6-O-DS-Hep hydrogel (photocrosslinked 6-O-DS-Hep (4%; w/w) hydrogel containing 50 microg/mL FGF-2) into PBS (phosphate-buffered saline) within first 7 days. The 6-O-DS-Hep hydrogel in vitro maintained the original form through 1 weeks incubation in PBS, but it was gradually fragmented and could not maintain the original form by 2-3 week-washing. When the FGF-2-containing 6-O-DS-Hep hydrogel was subcutaneously injected into the back of rats, significant neovascularization and fibrous tissue formation were induced near the injected site from day 3 after the injection. And, the hydrogel had been biodegraded and completely disappeared from the injected sites in vivo within about 15-20 days after the injection. These findings indicate a controlled release of biologically active FGF-2 molecules together with fragmentation and biodegradation of 6-O-DS-Hep hydrogel and the subsequent induction of neovascularization in vivo.

Animals↗
PubMed2006

Chitosan hydrogel as a drug delivery carrier to control angiogenesis.

An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO(4)-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.

Animals↗
PubMed2006

Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth.

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted in an insoluble hydrogel like a soft rubber within 30 sec of ultraviolet light (UV)-irradiation. The photocrosslinked chitosan hydrogel showed strong sealing strength and potential use as a new tissue adhesive in surgical application. Paclitaxel, which is an anti-tumor reagent and a vascularization-inhibitor, retained in the photocrosslinked chitosan hydrogel, and were gradually released from the photocrosslinked chitosan hydrogel in vivo upon the degradation of the hydrogel. The paclitaxel-incorporated photocrosslinked chitosan hydrogels effectively inhibited tumor growth and angiogenesis in mice. On the other hand, the fibroblast growth factor (FGF)-2 molecules also retained in both the photocrosslinked chitosan and an injectable chitosan/IO(4)-heparin hydrogels, and were gradually released from the hydrogels upon their in vivo biodegradations. The activity of FGF-2 in the hydrogels was stable for long time (more than 14 days). The controlled release of biologically active FGF-2 molecules from the hydrogels caused an induction of the angiogenesis and, possibly, collateral circulation occurred in the healing-impaired diabetic (db/db) mice and the ischemic limbs of rats. The purpose of this review is to describe the effectiveness of the chitosan hydrogels (photocrosslinkable chitosan hydrogel and chitosan/IO(4)-heparin hydrogel) as a local drug delivery carrier for FGF-2 and paclitaxel to control wound repair, tumor growth, and angiogenesis. It is thus proposed that the chitosan hydrogels may be a promising new local carrier for drugs such as FGF-2 and paclitaxel.

Animals↗
PubMed2006

[A case of gastric cancer with peritoneal dissemination who achieved five-year survival by successive treatments with TS-1 alone and in combination with other drugs].

The patient was a 65-year-old male with gastric cancer. Peritoneal disseminations were detected during distal gastrectomy. CDDP and mitomycin C were administered into the peritoneal cavity. Administration of TS-1 was begun and continued without adverse effects. After 33 months, a high dose of CDDP was administered twice in combination with TS-1, because elevation of serum CEA levels and paraortic lymphnode swelling were observed for the first time. A partial response was obtained, but an elevation of CEA was seen again in three months. We then tried weekly administration of paclitaxel, and a complete response was achieved in three months. After three months'rest from chemotherapy, a third regrowth of the tumor was observed. Paclitaxel was ineffective, and so we opted for weekly administration of low-dose CDDP combined with TS-1, which led to the third recovery. Biweekly administration of CPT-11 combined with TS-1 followed the low-dose CDDP and was successfully continued five years after the surgery. The treatment course in this patient was fully suggestive for patients with advanced or recurrent gastric cancer because the use of newly available chemotherapeutic agents in turn was effective at each recurrence of the tumor and achieved five-year survival with minimal hospitalization.

Aged↗
PubMed2005

Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its subsequent effect on subcutaneous tumor growth in mice.

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth.

Animals↗
PubMed2005

Efficacy of photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2 in a rabbit model of chronic myocardial infarction.

BACKGROUND: Therapeutic angiogenesis in ischemic myocardium has been shown to be an effective strategy to improve regional blood flow and myocardial function. However, no effective delivery system for growth factor administration is yet known to induce important therapeutic angiogenic responses in ischemic myocardium. MATERIALS AND METHODS: FGF-2-incorporated chitosan (FGF-2/chitosan) hydrogels were immobilized on the surface of ischemic myocardium of rabbit models of chronic myocardial infarction by UV-irradiation. After 4 weeks, cardiac functional analyses by noradrenalin challenge and histopathological analyses were performed to evaluate the efficacy of a controlled release of FGF-2 from FGF-2/chitosan hydrogel immobilized on the surface of ischemic myocardium. RESULTS: Significant improvement by application of FGF-2/chitosan hydrogels was found in systolic pressure at the left ventricle, +dp/dt maximum, and -dp/dt maximum during noradrenalin challenge at a dose of 1 microg/kg/min. Histological observations showed that a significantly larger amount of viable myocardium and CD 31 immunostained blood vessels were found in the FGF-2/chitosan hydrogel-applied group than only the chitosan-applied and control groups. CONCLUSIONS: These preliminary results indicate that the controlled release of biologically active FGF-2 molecules from FGF-2/chitosan hydrogel induces angiogenesis and possibly collateral circulation in ischemic myocardium, thereby protecting the myocardium.

Animals↗
PubMed2005

Rabbit model of airway stenosis induced by scraping of the tracheal mucosa.

BACKGROUND: Prolonged endotracheal intubation in children often induces intractable airway stenosis. The aim of the present study was to establish a new model of airway stenosis for developing an effective method of treatment. MATERIAL AND METHODS: The rabbit trachea was annularly incised, and the tracheal mucosa was scraped with a nylon brush. The trachea was then closed. Nine days after scraping, the trachea was microscopically examined. RESULTS: All of the examined rabbits showed tracheal stenosis, ranging from 22% to 82% in diameter and from 48% to 97% in cross-sectional area. The stenotic lesion was confined within the scraped region, not including the sutured region. Histologic examination showed inflammation in the stenotic lesion with submucosal hyperplasia caused by proliferation of fibroblasts and thickening of collagen fibers. CONCLUSION: This method can be easily carried out and assures induction of airway stenosis. This model may be useful for developing methods for treating airway stenosis in the early stage.

Animals↗
PubMed2005

Expression of hypoxia-inducible factor-1alpha in esophageal squamous cell carcinoma.

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF-1alpha, a subunit of HIF-1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF-1alpha expression in esophageal squamous cell carcinoma. In 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF-1alpha protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF-1alpha messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase-polymerase chain reaction [RT-PCR]). A positive HIF-1alpha protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the 'high score' group for HIF-1alpha protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF-1alpha protein was found to have a significant effect on disease-free survival rate in our univariate analysis, but no effect on overall survival rate. In RT-PCR, HIF-1alpha mRNA scores correlated significantly with scores for HIF-1alpha protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF-1alpha protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma.

Adult↗
PubMed2004

A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma, based on correlation of fluorescence in situ hybridization and immunohistochemical measurements.

Amplification of the epidermal growth factor receptor (EGFR) and/or c-erbB-2 oncogenes and overexpression of their proteins are detected in 30% of gastric carcinomas, but there are few reports regarding the correlation between gene amplification and protein overexpression. We examined the correlation between amplification of the EGFR and c-erbB-2 genes, detected using fluorescence in situ hybridization, and overexpression of their proteins, detected using immunohistochemistry, in formalin-fixed tissue sections of 54 surgically resected gastric carcinomas. A mean EGFR copy number per nucleus of four or more and an EGFR/chromosome 7 centromere (CEP7) ratio of 1.7 or more were each detected in 4 specimens (7%). The sensitivity and specificity of both criteria for EGFR protein overexpression were 75% and 92%, respectively. A mean c-erbB-2 copy number per nucleus of 7.0 or more and a c-erbB-2/chromosome 17 centromere (CEP17) ratio of 2.0 or more were detected in six (11%) and eight (15%) specimens, respectively. The sensitivity and specificity of the former criterion to c-erbB-2 overexpression were 83% and 98%, respectively, while those of the latter were 63% and 98%. A mean EGFR gene copy number of 4.0 or more and/or an EGFR/CEP7 ratio of 1.7 and a mean c-erbB-2 gene copy number of 7.0 or more and/or a c-erbB-2/CEP17 ratio of 2.0 or more would be useful in defining increased EGFR and c-erbB-2 gene copy numbers, respectively, in gastric carcinomas.

Adenocarcinoma↗
PubMed2004

A new mouse model for renal lesions produced by intravenous injection of diphtheria toxin A-chain expression plasmid.

BACKGROUND: Various animal models of renal failure have been produced and used to investigate mechanisms underlying renal disease and develop therapeutic drugs. Most methods available to produce such models appear to involve subtotal nephrectomy or intravenous administration of antibodies raised against basement membrane of glomeruli. In this study, we developed a novel method to produce mouse models of renal failure by intravenous injection of a plasmid carrying a toxic gene such as diphtheria toxin A-chain (DT-A) gene. DT-A is known to kill cells by inhibiting protein synthesis. METHODS: An expression plasmid carrying the cytomegalovirus enhancer/chicken beta-actin promoter linked to a DT-A gene was mixed with lipid (FuGENE trade mark 6) and the resulting complexes were intravenously injected into adult male B6C3F1 mice every day for up to 6 days. After final injection, the kidneys of these mice were sampled on day 4 and weeks 3 and 5. RESULTS: H-E staining of the kidney specimens sampled on day 4 revealed remarkable alterations in glomerular compartments, as exemplified by mesangial cell proliferation and formation of extensive deposits in glomerular basement membrane. At weeks 3 and 5, gradual recovery of these tissues was observed. These mice exhibited proteinuria and disease resembling sub-acute glomerulonephritis. CONCLUSIONS: Repeated intravenous injections of DT-A expression plasmid DNA/lipid complex caused temporary abnormalities mainly in glomeruli of mouse kidney. The disease in these mice resembles sub-acute glomerulonephritis. These DT-A gene-incorporated mice will be useful as animal models in the fields of nephrology and regenerative medicine.

Actins↗
PubMed2004

Acinar cell carcinoma of the pancreas eroding the pylorus and duodenal bulb.

A 74-year-old woman presented at the National Defense Medical College Hospital in April 2001 with a chief complaint of upper abdominal pain. She had been diagnosed as having adenocarcinoma on the basis of results of examination of a biopsy specimen taken from an ulcer of the duodenal bulb at a local hospital. On admission, she showed no jaundice, but a hard mass, about 10 cm in diameter, was palpated in the right upper quadrant. Laboratory data showed high levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. Abdominal computed tomography (CT) and angiography demonstrated a giant enhanced mass in a pattern of eccentric gradation extending to the pylorus, duodenal bulb, and pancreatic head. She underwent pancreatoduodenectomy with combined resection of the transverse colon. The histologic diagnosis was acinar cell carcinoma (ACC), originating in the pancreatic head and extending to the stomach, duodenum, and transverse colon, without any lymph node involvement. In most reported cases of ACC, the preoperative diagnosis was a pancreatic mass or endocrine tumor of the pancreas. The correct diagnosis in those cases was made by postoperative or postmortem pathological examination. If criteria for detecting the slight differences between ACC and endocrine tumors on some images were to be established, the diagnostic skill for ACC would improve dramatically.

Aged↗
PubMed2004

Efficacy of endoventricular circular patch plasty: will this procedure improve the prognosis of patients with ischemic cardiomyopathy?

OBJECTIVES: We report hemodynamic and clinical results of our series of endoventricular circular patch plasty (Dor operation) and consider some advantages of this procedure for patients with ischemic cardiomyopathy. METHODS: Between 1996 and 2001, 23 consecutive patients with left ventricular aneurysm and/ or ischemic cardiomyopathy after myocardial infarction who underwent Dor operation were included in this study. Hemodynamic and clinical results of Dor operation were analyzed periodically. Patients were divided into two groups according to the extent of asynergy, more than 60% or not, i.e., an ischemic cardiomyopathy group (ICM group) or a simple left ventricular aneurysm group (sLVA group). RESULTS: Hospital mortality was 4.4%. Postoperative New York Heart Association functional class was improved in all survivors to class I or II. Postoperative ejection fraction (EF) increased and postoperative left ventricular (LV) volume decreased in all survivors. In both groups, early and 1 year postoperative EF increased significantly. Additionally, end-diastolic and end-systolic volumes decreased significantly in the early postoperative period. Postoperative LV volume had re-enlarged in the cases in which preoperative left ventricular end-systolic volume index was more than 90 mL/m2, though left ventricular ejection fraction was maintained or rather improved at 1 year postoperatively. The survival rates after 3 years of the operation in the sLVA and ICM groups were 85.7% and 81.3%. CONCLUSION: Though patients with ischemic cardiomyopathy with severe LV dysfunction may benefit the most from Dor operation, postoperative LV re-dilatation may deteriorate late mortality. At operation, whether optimal LV size and shape can be reconstructed and the timing of operation are the important issues because they affect prognoses.

Aged↗
PubMed2004

Inhibition of vascular prosthetic graft infection using a photocrosslinkable chitosan hydrogel.

BACKGROUND: Despite improvements in surgical techniques and antimicrobial therapies, prosthetic aortic graft infections remain a clinical problem. It is well known that chitosan has strong antibacterial activities to a wide variety of bacteria including Staphylococcus aureus, epidermidis and Escherichia coli (E. coli). The antibacterial activity by adhering a photocrosslinkable chitosan hydrogel to Dacron grafts was investigated in vitro and in vivo using a rabbit model. MATERIALS AND METHODS: The photocrosslinkable chitosan hydrogel (50microl) coated grafts (3 x 2mm fragments) were evaluated on a resistance against E. coliin vitro. The graft infections in vivo were also initiated through implantation of a Dacron graft fragment into the infrarenal aorta of a rabbit, followed by a topical inoculation with 10(6) colony-forming units of E. coli. The graft infection was allowed to develop over the following 1 week. RESULTS: The photocrosslinkable chitosan hydrogel-coated grafts exhibited a resistance against E. coliin vitro. Furthermore, application of 0.1ml photocrosslinkable chitosan hydrogel on the Dacron implant in vivo substantially inhibited graft infection with E. coli. CONCLUSIONS: These preliminary results suggested the potential use of a photocrosslinkable chitosan hydrogel in directing graft infection prophylaxis.

Animals↗
PubMed2004

A new rabbit model of myocardial infarction without endotracheal intubation.

INTRODUCTION: When establishing a myocardial infarction model in rabbits, artificial ventilation under endotracheal intubation is required to prevent pulmonary collapse caused by pneumothorax. However, it is difficult to carry out endotracheal intubation due to the rabbit anatomy. We therefore attempted to develop a myocardial infarction model in rabbits without endotracheal intubation. MATERIALS AND METHODS: A facial oxygen mask with a flow rate of 200 mL/min was placed on anesthetized rabbits (n = 17). The sternum was carefully incised along the midline to avoid injury to the parietal pleura. The major branch of the left coronary artery was then ligated and the surgical wound was closed. To investigate the effects of the surgical procedure on physiological parameters, blood pressure and blood gas were measured during the same procedure using 10 other rabbits. RESULTS: During the surgery, PaO(2) and PaCO(2) were stable at approximately 230 and 50 mm Hg, respectively. In addition, the animals did not experience severe ventilatory impairment. Four weeks after the myocardial ischemia, the overall mortality rate was 29.4% (5/17). All of the surviving animals showed Q-waves on ECG and myocardial infarction upon histological examination. CONCLUSIONS: Our new method established a chronic rabbit model of myocardial infarction without the need for endotracheal intubation.

Animals↗
PubMed2004

Vascularization in vivo caused by the controlled release of fibroblast growth factor-2 from an injectable chitosan/non-anticoagulant heparin hydrogel.

Addition of various heparinoids to the lactose-introduced, water-soluble chitosan (CH-LA) aqueous solution produces an injectable chitosan/heparinoid hydrogel. In the present work, we examined the capability of the chitosan/non-anticoagulant heparin (periodate-oxidized (IO(4)-) heparin) hydrogel to immobilize fibroblast growth factor (FGF)-2, as well as the controlled release of FGF-2 molecules from the hydrogel in vitro and in vivo. The hydrogel was biodegraded in about 20 days after subcutaneous injection into the back of a mouse. When the FGF-2-incorporated hydrogel was subcutaneously injected into the back of both mice and rats, a significant neovascularization and fibrous tissue formation were induced near the injected site. These results indicate that the controlled release of biologically active FGF-2 molecules is caused by biodegradation of the hydrogel, and that subsequent induction of the vascularization occurs.

Animals↗