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Biomedical subjects

J Amano

Publications and source records attributed to J Amano.

At least 37 records · Page 2Linked to original sources

Bifidobacterium longum as a delivery system for gene therapy of chemically induced rat mammary tumors.

A fundamental obstacle in cancer gene therapy is the specific targeting of therapy directly to a solid tumor, and no systemic delivery system yet exists. A strain of domestic bacteria, Bifidobacterium longum, which is nonpathogenic and anaerobic, selectively localized to and proliferated in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors after systemic application. We further ascertained the tumor specificity of genetically engineered, as well as wild-type, Bifidobacterium longum. This is the first demonstration that Bifidobacterium longum can be utilized as a specific gene delivery vector for gene therapy on solid breast tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Cavernous hemangioma of the liver with giant cyst formation: degeneration by apoptosis?

Cavernous hemangioma of the liver with cyst formation is a very rare condition. A case of cavernous hemangioma of the liver with unilocular giant cyst formation undergoing surgical removal is reported. Notably, the patient also had Budd-Chiari syndrome with an obstructing lesion in the inferior vena cava. The cystic degeneration of the hemangioma implied a relationship with apoptosis. This is the first reported case of Budd-Chiari syndrome caused by advanced cystic degeneration of hepatic cavernous hemangioma.

Angiography↗

Ulcer in the gastric tube for esophageal replacement: a comparison of 12 esophageal cancer patients with or without postoperative radiotherapy.

BACKGROUND AND AIMS: Ulcer in the gastric tube for esophageal replacement, which was caused by peptic factors or postoperative radiotherapy (Rx), are occasionally reported. The aim of this study was to clarify the clinicopathologic features of the ulcers in the gastric tube. METHODS: In 62 patients with a reconstructed gastric tube, after esophagectomy for esophageal cancer, esophagogastroduodenoscopy was performed. Ulcers of the gastric tube were detected in 12 patients: six with postoperative Rx and six without Rx. The 12 patients with gastric tube ulcers (GU-group) were reviewed and compared to the remaining 50 patients without ulcers of the gastric tube (Control-group). Clinicopathologic features of gastric tube ulcers were compared between the patients with and without Rx. RESULTS: There was no difference in any parameter between the patients of the GU- and Control-groups. Comparing the patients of the GU-group with and without Rx, the ulcers of the gastric tube in the patients without Rx were frequently located in the lower part of the gastric tube (P = 0.067), detected in a later period after surgery (P = 0.055), associated with cervical esophagitis (P = 0.03), and less associated with gastritis (P = 0.03). In three patients of the GU-group without Rx, Helicobacter pylori was detected in the gastric tube. Two of the three patients had a history of peptic ulcers before surgery, and had recurrence of the gastric tube ulcers. CONCLUSIONS: Gastric tube ulcers without postoperative Rx may have different characteristics compared to those induced by Rx.

Endoscopy, Digestive System↗

The rate of tumour growth does not distinguish between malignant and benign thyroid nodules.

OBJECTIVE: To clarify whether or not the rate of tumour growth is a useful measure for distinguishing papillary thyroid cancer from benign nodules. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: Fourteen patients with 27 nodules (<20 mm) followed up for 20 months or more. INTERVENTIONS: High resolution ultrasonography (US). MAIN OUTCOME MEASURE: Growth rate. RESULTS: There were 15 papillary thyroid cancers and 12 benign nodules. The median tumour diameters at the first and the last US examination were 9.0 mm (range 6-19) and 9.0 mm (range 5-21) in papillary thyroid cancers followed up for 37 months (range 21-85), and 11.5 mm (range 4-19) and 11.5 mm (range 5-23) in benign nodules followed up for 38 months (range 20-84), respectively. CONCLUSION: The rate of growth of thyroid nodules as documented by ultrasound did not prove to be useful in distinguishing between malignancy and benign disease of small thyroid nodules (<20 mm).

Adult↗

Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis.

OBJECTIVES: Although the incidence of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) infection is higher than in patients with hepatitis B virus (HBV)-related HCC in Japan, the long-term prognosis and prognostic factors of HCV-related HCC after hepatic resection are poorly understood. METHODS: The surgical outcome of HCV-related HCC in 172 consecutive patients who underwent hepatic resection between 1989 and 1997 was retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The overall incidence of postoperative complications was 23.2%, and 11 patients among that group had hospital deaths (6.4%) including 9 (5.2%) operative deaths. The mean and median overall survivals including hospital death after surgery were 41 months and 33 months, respectively. The 3-, 5-, and 7-yr overall survival rates after hepatic resection were 63%, 52%, and 47%, respectively. The 3-, 5-, and 7-yr disease-free survival rates after hepatic resection were 33%, 20%, and 15%, respectively. Multivariate analysis revealed that serum alpha-fetoprotein (AFP) of > or = 1000 ng/ml and the presence of vascular invasion were independent unfavorable prognostic factors affecting overall survival and that AFP of > or = 1000 ng/ml was an independently significant factor of poor disease-free survival. CONCLUSIONS: We found the postresection survival of patients with HCV-related HCC should be stratified by the high value of AFP and the presence of vascular invasion. AFP may be the most powerful predictor of the long-term prognosis and recurrence in such patients.

Aged↗

Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus.

OBJECTIVE: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC). METHODS: Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis. RESULTS: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. CONCLUSION: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

Apoptosis↗

Tranilast inhibits cardiac allograft vasculopathy in association with p21(Waf1/Cip1) expression on neointimal cells in murine cardiac transplantation model.

Cardiac allograft vasculopathy is a major complication after cardiac transplantation, often limiting long-term recipient survival. N-(3,4-Dimethoxycinnamoyl)anthranilic acid (tranilast) inhibits cyclin-dependent kinase activity through p21(Waf1/Cip1) induction and arrests vascular smooth muscle cell proliferation in vitro. We tested a hypothesis that tranilast inhibits the vasculopathy characterized by diffuse intimal thickening in a murine heart transplantation model. Hearts from DBA/2 mice were heterotopically transplanted into B10.D2 mice as allografts. Oral administration of tranilast started 3 days before transplantation at doses of 550 or 1040 mg/kg per day until the animals were killed. Cardiac allograft vasculopathy was defined as luminal stenosis caused by neointimal formation. The percentage of luminal stenosis and cardiac rejection were analyzed 14 and 28 days after transplantation. Tranilast administration was associated with a marked reduction in luminal occlusion but with no significant effect on cardiac rejection. Immunohistochemical study of the tranilast-treated graft coronary arteries revealed enhancement of p21(Waf1/Cip1) and decreased expression of proliferating cell nuclear antigen in the neointima. The significant reduction in allograft vasculopathy concomitant with the enhancement of p21(Waf1/Cip1) indicates that tranilast has an antiproliferative effect that could be applicable to clinical treatment of cardiac allograft vasculopathy.

Animals↗

Pulmonary epithelioid hemangioendothelioma coexistent with pulmonary metastasis of thyroid cancer.

We report a 45-year-old man with epithelioid hemangioendothelioma (EH) and simultaneous pulmonary metastasis of thyroid cancer in his lung. Thyroid cancer, and multiple small nodules in both lungs were noted. He underwent total thyroidectomy followed by radiotherapy with 131I. However, 131I scintigraphy showed poor uptake of radionuclide in the nodules, and the size of the nodules remained unchanged. The diagnostic thoracoscopic biopsy showed two types of nodules, some were positive for thyroglobulin and cytokeratin, and others were reactive for factor VIII. The former nodules were diagnosed as pulmonary metastases of thyroid cancer, and the latter EH.

Adenocarcinoma, Papillary↗

[Clinical study of operated nine thymic carcinomas].

Nine cases of thymic carcinoma (5 males and 4 females) were operated in our hospital between 1990 and 1998. These cases included 4 squamous cell carcinomas, 2 small cell carcinomas, 2 undifferentiated carcinomas and one adenocarcinoma. Preoperative chemotherapy were performed in 3 cases. All cases underwent median-sternotomy followed by mediastinal irradiation, 4 had total resection of the tumor, 2 had subtotal resection and 3 had exploratory thoracotomy followed by mediastinal irradiation. Adjuvant chemotherapy were administered in 4 cases and re-operation were performed in 2 cases. We applied Masaoka's clinical staging for thymoma, nine cases consisted of 6 stage III cases, 2 stage IV b cases and one stage IV a case. Within 2 years after operation, 3 cases (two complete resection cases and one exploratory thoracotomy case) were died of the carcinoma. However, two cases of squamous cell carcinoma have been alive more than 5 years after surgery followed by chemoradiation. The remaining 4 patients are alive either with or without the carcinoma after 7 to 28 months after operation. Thymic carcinoma is not so common mediastinal tumor but is expected to increase in the future. The treatment of thymic carcinoma remains a controversial matter and the survival is poor compared with invasive thymoma, but multimodal-therapy would contribute to improvement of the results in treatment for thymic carcinoma especially in squamous cell carcinoma.

Adenocarcinoma↗

[A case of primary leiomyosarcoma of the pulmonary artery].

A 74-year-old woman was admitted to our hospital because of right chest pain. The chest radiograph showed right hilar pulmonary artery dilatation. A mass exhibiting low intensity in T1-weighted images and high intensity in T2-weighted images was disclosed in the right pulmonary artery. Because of its clinical course and the MRI findings, the mass was thought to be tumorous tissue, and so pneumonectomy was performed. Leiomyosarcoma was diagnosed from the histological findings. Primary artery sarcoma is rare and the prognosis is considered to be extremely poor. The patient was successfully treated and had a good clinical outcome.

Aged↗

Gene therapy for attenuating cardiac allograft arteriopathy using ex vivo E2F decoy transfection by HVJ-AVE-liposome method in mice and nonhuman primates.

Cardiac allograft arteriopathy, which limits the long-term survival of recipients, is characterized by diffuse intimal thickening composed of proliferative smooth muscle cells. The transcription factor E2F plays a pivotal role in the coordinated transcription of cell-cycle regulatory genes. To test the hypothesis that double-stranded DNA with specific affinity for E2F (E2F decoy) is effective in preventing intimal hyperplasia, we performed ex vivo single intraluminal delivery of E2F decoy into cardiac allografts of mice and Japanese monkeys using the hemagglutinating virus of Japan (HVJ) artificial viral envelope-liposome method. In murine models, antisense cyclin-dependent kinase 2 (cdk2) kinase oligodeoxynucleotide (ODN) and no transfers were performed to compare the effects. Severe intimal thickening was observed, and multiple cell-cycle regulatory genes were enhanced in untreated allografts. E2F decoy prevented neointimal formation and suppressed these genes for up to 8 weeks, whereas antisense cdk2 kinase ODN had limited effects. In primate models, E2F decoy dramatically prevented neointimal thickening and suppressed multiple cell-cycle regulatory genes, whereas intimal thickening developed in the nontransfected or mismatch decoy-transfected allografts. Gel mobility shift assay proved the specific effects of E2F decoy, and reverse transcriptase-polymerase chain reaction documented that neither complication nor dissemination of HVJ into other organs was observed. We demonstrate that ex vivo gene delivery to allografts is a potent strategy to modify allograft gene expression, resulting in prevention of graft arteriopathy without systemic adverse effects.

Animals↗

Prevention of cardiac allograft arteriosclerosis using antisense proliferating-cell nuclear antigen oligonucleotide.

Cardiac allograft arteriosclerosis limits long-term survival of recipients and is characterized by intimal thickening comprised of proliferative smooth muscle cells. Proliferating-cell nuclear antigen (PCNA) plays a pivotal role in the cell cycle regulatory genes involved in smooth muscle cell proliferation. To test the hypothesis that antisense PCNA oligodeoxynucleotide (ODN) can prevent allograft arterial intimal hyperplasia, we performed single intraluminal delivery of the antisense or sense PCNA ODN or no transfer into murine cardiac allografts. DBA/2 murine hearts were transfected and transplanted into B10.D2 mice; the allografts were harvested 4 weeks later. Severe intimal thickening with enhanced expression of PCNA was observed in untransfected and sense PCNA ODN-treated allografts, whereas antisense PCNA ODN prevented neointimal formation.

Animals↗

Urinary bladder injury during inguinal herniorrhaphy in a renal transplant patient: report of a case.

The urinary bladder was injured in a renal transplant patient during inguinal herniorrhaphy. The bladder was mistakenly identified as an internal inguinal hernia. The protuberant bladder from the thin muscle layers was caused by a previous renal transplantation. The defect in the bladder was sutured by absorbable suture material, and the posterior wall of the inguinal canal was reinforced by artificial mesh. Surgeons performing inguinal herniorrhaphy on the grafted side in a renal transplant patient should thus be warned not to injure the bladder during the operation.

Adult↗

Altered expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in acutely rejected myocardium and coronary arteriosclerosis in cardiac allografts of nonhuman primates.

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are important in any process of tissue remodeling. However, there is no report evaluating their expression in cardiac allografts in human or non-human primates. Heterotopic cardiac transplantation was performed on Japanese monkeys. Subjects were treated with chimeric anti-human lymphocyte function-associated antigen-1 monoclonal antibody for 2 weeks. Heart grafts were harvested at days 1-95 (n = 7). Native monkey hearts were used as controls (n = 2). We examined expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 using immunohistochemistry and in situ reverse transcriptase polymerase chain reaction (RT-PCR). In the myocardium, the expression of MMP-2 was increased in the spindle-shaped cells of acutely rejected myocardial interstitium and prior to the presence of mononuclear cell infiltration at days 1-41. TIMP-1 and 2 expression was enhanced in association with the progression of fibrosis at days 40-95. In the coronary arteries of chronically rejected allografts, enhanced MMP and decreased TIMP expression was observed in both thickened intima and media at days 40-95. The medial MMP mRNA expression was observed before the development of intimal thickening occurred at days 7-28. MMPs are critical for the progression of acute and chronic rejection, and TIMP predominance plays important roles in fibrosis in association with acute rejection. Expression of MMPs and TIMPs is a sensitive indicator of acute and chronic cardiac rejection.

Acute Disease↗

Four resections for hepatic metastasis from gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis.

In a patient with gastric cancer (GC) associated with one synchronous and three metachronous hepatic metastases (HM), who underwent four hepatectomies, we carried out histochemical investigations regarding cell proliferation, apoptosis, and angiogenesis in the GC and HM. Tissue samples were taken from the primary GC and four HM. Ki-67 immunostaining was performed to evaluate cell proliferation and determine the labeling index (Ki-67 LI; ie, the percentage of cancer cells with nuclei stained for Ki-67). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) was performed to evaluate apoptosis and determine the apoptotic index (ie, the percentage of TUNEL-positive cells), and immunostaining for factor VIII-related antigen was performed to evaluate angiogenesis and measure microvessel density (MVD). The Ki-67 LI was 43.2% in the primary GC and 39.9% in the synchronous HM, and the LI increased with the number of resections of metachronous HM. The apoptotic index was 3.36% in the primary GC, and 5.30% in the synchronous HM, and the index decreased after further resections of the metachronous HM. The MVD was 35 in the primary GC, and 22 in the synchronous HM, and it increased with the number of resections of metachronous HM. The primary GC in this patient may have strongly influenced the growth of HM through effects on cell proliferation, apoptosis, and angiogenesis.

Adenocarcinoma↗

The likely transformation of papillary thyroid carcinoma into anaplastic carcinoma during postoperative radioactive iodine-131 therapy: report of a case.

We report herein a case of papillary carcinoma which appeared to transform into anaplastic carcinoma during postoperative radioactive iodine-131 (131I) therapy. A 67-year-old man who was diagnosed as having papillary thyroid carcinoma with bilateral neck lymph node involvement and multiple lung metastases underwent total thyroidectomy prior to 131I therapy. Immediately after a second course of 131I therapy, the patient complained of right neck pain and swelling, and a biopsy of the swollen neck lymph node was taken. Histologic examination of this biopsy specimen revealed anaplastic carcinoma. With p53 immunohistochemical staining, both the primary tumor and the biopsy specimen were positive. We speculate that first, some DNA damage in tumor cells was induced by the initial 131I therapy, but neither DNA repair nor cell apoptosis occurred because the p53 gene was already mutated; then further DNA damage was induced by the second 131I therapy, leading to anaplastic transformation.

Aged↗

Solitary brain metastasis from papillary thyroid carcinoma in a patient with depression: report of a case.

Papillary carcinoma of the thyroid is a common thyroid malignancy with a relatively good prognosis. However, distant metastases may develop and become threatening, particularly to older patients, in a more aggressive manner. We report herein the clinical, radiological, and pathological findings of a patient with papillary thyroid carcinoma who had a solitary cerebral metastasis. The patient had been suffering from depression and had already undergone a hemithyroidectomy for primary thyroid carcinoma, and was known to have metastatic thyroid carcinoma of the lungs and bone. After the removal of the remnant thyroid gland prior to radioiodine (131I) therapy, he developed additional problems related to depression. Electroencephalography played an important role in identifying suspected brain metastasis and computed tomography demonstrated a space-occupying lesion in the left cerebral hemisphere. Consequently, an early removal of intracranial mass could be performed without any further life-threatening complications. Moreover, after removal of the brain mass the patient's depression improved immediately without the use of any antidepressants. This case report indicates the possibility that a patient's depression might be associated with brain metastasis from papillary thyroid carcinoma, and also suggests that an early diagnosis with the appropriate surgical management of a brain metastasis followed by radioiodine therapy could be valuable for achieving a prolonged disease-free period.

Bone Neoplasms↗