Biomedical subjects

S Yano

Publications and source records attributed to S Yano.

At least 127 records · Page 7Linked to original sources

PubMed2000

Morphological change in the MNNG-treated rat gastric mucosa.

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of the gastric mucosa from both MNNG-treated and control rats were histologically examined every 2 months, for 10 months. In 40% of the MNNG-treated rats, atrophy in the gastric mucosa was observed after 2 months, and regenerative epithelium was observed after 4 months, followed by adenomatous proliferation and disappearance of the tight junction electron microscopically after 6 months. A small intestinal cancer had developed in 2 rats at 6 months. While gastric cancer had developed in 3 rats at 8 months, and in one of these 3 rats, peritoneal dissemination was observed macroscopically and histologically. These results suggested that adenomatous proliferation and disappearance of the tight junction observed electron microscopically were characteristic pathological features of precancerous lesions in the stomach in MNNG-treated rat.

Animals↗

PubMed2000

Advanced gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion of 5-FU, MMC and peroral administration of 5-FU: a case report.

We have experienced a case of advanced gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion of 5-fluorouracil (5-FU), mitomycin C (MMC) and peroral administration of 5-FU. The patient was a 48-year-old male diagnosed as having advanced gastric cancer with multiple liver metastasis in the bilateral lobes of the liver. This patient was treated by intra-hepatic arterial infusion of 5-FU (250 mg/2 days x 8 doses), MMC (20 mg x 1 dose, 6 mg/2 weeks x 6 doses) and peroral administration of 5-FU (200 mg/day). At 14 weeks later, a CT revealed that the metastatic liver tumors had disappeared. However, at 7 months after the therapy, the patient eventually died of liver and brain metastasis. These results suggested that intra-hepatic arterial infusion of 5-FU and MMC was an effective therapy for metastatic tumors in the liver, but we need to perform intra-hepatic arterial infusion using a new prolonged regimen to treat the liver metastasis.

Administration, Oral↗

PubMed2000

Multiple carcinoids in the stomach with hypergastrinemia and type A gastritis: a case report.

We have experienced a case of the stomach with hypergastrinemia and type A gastritis with multiple carcinoids in a 37-year-old woman. An upper gastrointestinal series revealed multiple minute polyps in the upper body of the stomach. All polyps were diagnosed as carcinoid using endoscopic biopsies. She had neither symptom or signs of typical carcinoid disease. The serum gastrin level was as high as 725 pg/ml. Total gastrectomy was performed, and the diagnosis of multiple gastric carcinoids (sm, no) with type A gastritis was histologically confirmed. After the operation, the serum gastrin level returned to normal, and the patient has been doing well and is disease-free to date at 7 years after the operation. This case suggested that multiple gastric carcinoid lesions may be precipitated by chronic atrophic gastritis accompanying hypergastrinemia. In the treatment of multiple gastric carcinoids with type A gastritis, total gastrectomy with lymph node dissection should be standard operative procedure, in order to resect the fundic gland area completely which could be the origin of carcinoids and endocrine cell micronest.

Adult↗

PubMed2000

Primary gastric lymphoma: a clinicopathological study.

A retrospective study of 25 patients treated for primary gastric lymphoma was made to investigate a number of problems related to treatments and report the factors influencing prognosis. In the 5-year-survival rate according to Working Formulation classification, either survival rate of low-grade type or intermediate-grade type was higher than that of high-grade type. Both the 5-year-survival rate of cases without lymph node metastasis and that of cases that involved perigastric lymph nodes were higher than that of cases that involved distant gastric lymph nodes. Those surviving five years after perigastric lymph node metastasis had received D3 or D4 dissection and postoperative multicombined chemotherapy. Tumors invading only to the submucosal layer had received D2 dissection and were not treated by postoperative multicombined chemotherapy, and recurrence was not recognized in these cases. Of 9 cases infiltrating into the musclaris propria or serosa without lymph node metastasis, 8 cases were treated by postoperative multicombined chemotherapy and were alive without recurrence, but one case without postoperative multicombined chemotherapy died by recurrence. Therefore, adequate therapy for gastric lymphoma with infiltrating into submucosal layer is gastrectomy with D2 lymph node dissection, and postoperative multicombined chemotherapy is not necessary. The cases with perigastric lymph node metastasis, or the cases with invading from muscularis propria to serosa require D3 or D4 lymph node dissection with postoperative multicombined chemotherapy. But the cases with distant gastric lymph node metastasis or invading adjacent structure or high-grade type histologically (WF classification) require preoperative chemotherapy.

Humans↗

PubMed2000

Histopathological study of venous aneurysms in patients with dural arteriovenous fistulas.

OBJECT: Of all intracranial dural arteriovenous fistulas (DAVFs), those with cortical venous drainage associated with cortical venous ectasia or varices are predisposed to an aggressive course and produce progressive neurological symptoms or hemorrhages. The authors undertook a histological examination of venous aneurysms and arterialized veins in the proximity of these aneurysms that had been surgically removed in patients with DAVFs. METHODS: Surgical specimens were obtained in eight patients. The excised venous aneurysms and the arterialized veins in their proximity were stained using hematoxylin and eosin, van Gieson's elastic, and Masson's trichrome stain. Immunostaining was also performed for alpha smooth-muscle actin, desmin, and factor VIII antigen. Five of the patients had presented with venous hypertension, and three had intracranial hemorrhages. The arterialized vein obtained in the proximity of the venous aneurysm exhibited local irregular intimal thickening; the internal elastic lamina (IEL) was grossly preserved. All venous aneurysms in patients with venous hypertension manifested medial thickening and local intimal thickening with loss of IEL; the thickness of the wall was relatively uniform. In contrast, the wall thickness of venous aneurysms in patients with hemorrhage was extremely irregular and there was no clear delineation between the media and the intima. In media with complete disappearance of IEL, there was scant muscle tissue. CONCLUSIONS: Degenerative changes in venous aneurysms in patients with hemorrhage were much greater than in patients with venous hypertension, possibly because hemorrhages result from a more complicated interplay of anatomical, hemodynamic, and degenerative factors.

Aged↗

PubMed2000

Human interferon-gamma enhances expression of ganglioside GM2 on human lung cancer cells and their susceptibility for antiganglioside GM2 monoclonal antibody-dependent cellular cytotoxicity.

Interferons are known to modulate several cellular functions by the induction of various proteins. In this study, we demonstrated that human interferon-gamma (HuIFN-gamma) enhanced the expression of ganglioside GM2 (GM2), which is a kind of tumor-associated antigen substantially expressed in human lung cancer and that human lung cancer cells expressing GM2 became more susceptible to anti-GM2 monoclonal antibody (mAb)-dependent tumor cell killing mediated by human effector cells after HuIFN-gamma treatment. GM2 expression on human lung cancer cells treated with or without HuIFN-gamma was measured by flow cytometry. The antibody-dependent cellular cytotoxicity (ADCC) activity was assessed by 4-h 51Cr release assay. HuIFN-gamma enhanced GM2 expression on human small-cell lung cancer (SCLC), SBC-3, and human non-small-cell lung cancer (NSCLC), A549 cells in a dose-dependent manner. The optimal concentration of HulIFN-gamma was 1,000 U/ml. The effect of HulFN-gamma reached maximum after 4 days of culture. HulFN-gamma did not have any effect to enhance the expression of other gangliosides in SBC-3 cells. No other cytokines used in this study modulated GM2 expression in SBC-3 cells. Anti-GM2 mAb-dependent ADCC activities induced by lymphocytes and monocytes were more potent against IFN-gamma-treated SBC-3 and A549 cells than nontreated cells. Taken together, HulFN-gamma combined with anti-GM2 mAb may be useful for immunotherapy against GM2-positive human lung cancer.

Antibodies, Monoclonal↗

PubMed2000

Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer patients with bone metastases.

Animals↗

PubMed2000

Site-specific expression of transferrin receptor by human colon cancer cells directly correlates with eradication by antitransferrin recombinant immunotoxin.

We determined the efficacy of HB21(Fv)PE40, a single-chain immunotoxin made by fusing the variable regions of a monoclonal antibody directed at the human transferrin receptor (TfR) with a truncated mutant of Pseudomonas exotoxin (PE), against metastatic human colon carcinoma KM12L4 cells growing in the liver or subcutis of nude mice. Organ-specific modulation of TfR expression was examined by immunohistochemistry and flow cytometry using anti-human CD71 antibody. KM12L4 cells expressed human TfR and were lysed in vitro by HB21(Fv)PE40 but not LMB-7 (a control immunotoxin specific for a Lewis Y-related carbohydrate antigen). KM12L4 cells growing in the liver expressed higher levels of TfR than cells growing s.c. Systemic administration of HB21(Fv)PE40 eliminated KM12L4 liver metastasis, whereas administration of LMB-7 did not. Treatment of mice with HB21(Fv)PE40 only delayed the growth of s.c. tumors. KM12L4 cells recovered from liver metastases, expressed higher levels of TfR, and were more sensitive to lysis by HB21(Fv)PE40 than KM12L4 cells recovered from s.c. tumors. Indeed, collectively, the data show that the expression level of the TfR by human colon cancer cells is modulated by the organ microenvironment which can be advantageous for the use of therapeutic immunotoxins.

Animals↗

PubMed2000

[A case of recurrent pancreatic cancer brought into a complete response by a multimodal treatment with intraarterial chemotherapy and radiotherapy].

We achieved a complete response of recurrent pancreatic cancer using a multimodal treatment with intravenous, oral and intraarterial chemotherapies and radiotherapy. A 55-year-old female patient had a recurrent pancreatic cancer, which had invaded the portal vein, 2 years after pancreatoduodenectomy. Angiography demonstrated prominent stenosis of the portal vein, which was enlarged by the insertion of a metalic stent to maintain blood flow to the liver. Chemotherapy included intravenous mitomycin C, 5-FU and 4'-epirubicin (EPI), oral UFT and cyclophosphamide, and intraarterial cisplatin, 5-FU and EPI through a catheter inserted into the celiac artery. Furthermore, the patient received a total of 50 Gy radiotherapy. Four months after the initiation of therapy, a computed tomography image demonstrated a complete disappearance of the recurrent tumor and a prominent decrease in the serum CA19-9 level. At present, 11 months have passed after the initiation of therapy, and she has been followed at our outpatient department without any symptoms of recurrence.

Adenocarcinoma↗

PubMed2000

Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma.

Because routine histopathological examination of primary non-small cell lung cancer does not predict disease outcome, we correlated disease outcome with the expression level of multiple genes that regulate distinct steps of the metastatic process in 60 formalin-fixed, paraffin-embedded, archival specimens of stage I lung carcinoma from patients undergoing curative surgery at the M. D. Anderson Cancer Center. The expression of E-cadherin (related to cell cohesion), type IV collagenase [matrix metalloproteinase (MMP)-2 and MMP-9, related to invasion], and three angiogenic molecules, basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8, were examined by a colorimetric in situ mRNA hybridization technique. The expression levels of the individual genes analyzed by a Cox univariate analysis were not prognostic. In contrast, the ratio between expression of type IV collagenases (mean of the expression of MMP-2 and MMP-9) and E-cadherin, the MMP:E-cadherin ratio (measured at the periphery of each tumor), was significantly higher in patients with recurrent disease than in patients who remained disease free (P = 0.00003). Longer overall survival and reduced disease recurrence rates were significantly associated with a lower MMP:E-cadherin ratio (<2) by a Kaplan-Meier survival analysis (P = 0.0002 and P = 0.0001, respectively). Multiple covariate analyses of overall and disease-free survival also concluded that the MMP:E-cadherin ratio was a significant prognostic factor when corrected for age (P = 0.0001). Determination of this gene expression ratio in individual human lung cancers might therefore be used to direct tailored treatment for individual patients with resectable lung cancer.

Adult↗

PubMed2000

Treatment for malignant pleural effusion of human lung adenocarcinoma by inhibition of vascular endothelial growth factor receptor tyrosine kinase phosphorylation.

Malignant pleural effusion (PE) is associated with advanced human lung cancer. We found recently, using a nude mouse model, that vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is responsible for PE induced by non-small cell human lung carcinoma cells. The purpose of this study was to determine the therapeutic potential of a VEGF/VPF receptor tyrosine kinase phosphorylation inhibitor, PTK 787, against PE formed by human lung adenocarcinoma (PC14PE6) cells. PTK 787 did not affect the in vitro proliferation of PC14PE6 cells, whereas it specifically inhibited proliferation of human dermal microvascular endothelial cells stimulated by VEGF/VPF. A specific platelet-derived growth factor receptor tyrosine kinase inhibitor, CGP57148 (used as a control because PTK 787 also inhibits platelet-derived growth factor receptor tyrosine kinases), had no effect on proliferation of PC14PE6 or human dermal microvascular endothelial cells. i.v. injection of PC14PE6 cells into nude mice produced lung lesions and a large volume of PE containing a high level of VEGF/VPF. Oral treatment with CGP57148 had no effect on PE or lung metastasis. In contrast, oral treatment with PTK 787 significantly reduced the formation of PE but not the number of lung lesions. Furthermore, treatment with PTK 787 significantly suppressed vascular hyperpermeability of PE-bearing mice but did not affect the VEGF/VPF level in PE or expression of VEGF/VPF protein and mRNA in the lung tumors of PC14PE6 cells in vivo. These findings indicate that PTK 787 reduced PE formation mainly by inhibiting vascular permeability, suggesting that this VEGF/VPF receptor tyrosine kinase inhibitor could be useful for the control of malignant PE.

Adenocarcinoma↗

PubMed2000

[Limited-form Wegener's granulomatosis without anti-neutrophil cytoplasmic antibody].

A 78-year-old woman was admitted because of dry cough and weight loss. A computed tomographic (CT) scan of the thorax showed multiple masses in both lungs with and without cavitation. No other organ lesions were detected. The patient was seronegative for antineutrophil cytoplasmic antibody (ANCA) and a routine sputum culture was normal. Because specimens from transbronchial and CT-guided transluminal lung biopsies disclosed non-specific granuloma with necrosis, an excisional biopsy of the mass by video-assisted thoracoscopic surgery was performed. The specimens contained geographic basophilic necrosis with palisading histiocytes, giant cells, and neutrophils. A limited form of Wegener's granulomatosis was diagnosed on the basis of the clinical and pathological features and effects of treatment.

Aged↗

PubMed2000

Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer.

Interleukin 8 (IL-8) is mitogenic and chemotactic for endothelial cells. Within a neoplasm, IL-8 is secreted by inflammatory and neoplastic cells. The highly metastatic PC-3M-LN4 cell line overexpresses IL-8 relative to the poorly metastatic PC-3P cell line. We evaluated whether IL-8 expression by human prostate cancer growing within the prostate of athymic nude mice regulates tumor angiogenesis, growth, and metastasis. PC-3P cells were transfected with the full-length sense IL-8 cDNA, whereas PC-3M-LN4 cells were transfected with the full-sequence antisense IL-8 cDNA. Control cells were transfected with the neomycin resistance gene (Neo). In vitro, sense-transfected PC-3P cells overexpressed IL-8-specific mRNA and protein, which resulted in up-regulation of matrix metalloproteinase 9 (MMP-9) mRNA, and collagenase activity, resulting in increased invasion through Matrigel. After antisense transfection of the PC-3M-LN4 cells, IL-8 and MMP-9 expression, collagenase activity, and invasion were markedly reduced relative to controls. After orthotopic implantation, the sense-transfected PC-3P cells were highly tumorigenic and metastatic, with significantly increased neovascularity and IL-8 expression compared with either PC-3P cells or controls. Antisense transfection significantly reduced the expression of IL-8 and MMP-9 and tumor-induced neovascularity, resulting in inhibition of tumorigenicity and metastasis. These results demonstrate that IL-8 expression regulates angiogenesis in prostate cancer, in part by induction of MMP-9 expression, and subsequently regulates the growth and metastasis of human prostate cancer.

Androgens↗

PubMed2000

[Causative agents for lung carcinogenesis].

Lung cancer is a leading cause of malignancy-related death in Japan, and its incidence is still rising steeply. Various factors, including cigarette smoking, asbestos, and diet, have been reported to correlate with the development of lung cancer. Of these factors, cigarette smoking is believed as the major carcinogen for lung cancer. Recent studies indicate that cigarette smoke carcinogens cause genetic damages at both oncogenes(K-ras) and tumor suppressor genes(p53) of lung cancer, and hence initiate and promote the development of lung cancer. This article reviews recent advances in the molecular mechanisms of lung cancer carcinogenesis.

Air Pollution↗

PubMed2000

[Erdheim-Chester disease presenting with pulmonary lesion].

A 49-year-old man first visited our hospital in 1991 for further examination of abnormal pulmonary shadows. A chest radiograph and computed tomographic (CT) scan showed diffuse reticular shadows in both lung fields. The findings from a transbronchial lung biopsy specimen were not conclusive. Although there was little change in the abnormal pulmonary shadows, the patient's lung functions gradually deteriorated, indicating an obstructive defect. The patient was admitted in 1998 with the chief complaint of increasing dyspnea on exertion. A thoracoscopic lung biopsy specimen revealed proliferation of histiocytes with fibrosis in the pleura and perivascular interstitium. Immunohistochemically, the histiocytic cells were CD68-positive, alpha 1-antichymotripsin-positive, S100 protein-negative, and CD1a-negative. A bone scintigram and magnetic resonance images showed symmetrical diametaphyseal bone lesions in the distal femurs and the proximal tibiae; however, the epiphyses were spared. These findings were consistent with Erdheim-Chester disease. This is the first reported case of Erdheim-Chester disease with pulmonary involvement in Japan.

Antigens, CD↗

PubMed2000

[The role of daunorubicin in induction therapy for adult acute myeloid leukemia].

The relationship between the total dose of daunorubicin (DNR) in induction therapy and the treatment outcome were evaluated based upon individualized doses of DNR during induction therapy for patients with acute myeloid leukemia(AML). Ninety-two previously untreated adult AML patients admitted to our hospital were analyzed for the dose of DNR required for complete remission (CR), the CR rate, disease-free survival (DFS) and overall survival (OS). The induction therapy consisted of DNR (40 mg/m2/d, i.v., from D 1 until the marrow was hypoplastic), Ara-C, prednisolone, and/or 6-thioguanine. Eighty-three out of 92 patients were assessable. Sixty-three patients entered CR (76%), of whom 52 attained CR with the first course of induction therapy. The 10-year DFS and OS rates were 31.2% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120-480 mg/m2), which was not influenced by initial WBC count, or FAB type. These results indicate that when the dose is linked to the observed tumor response, the optimal dose of DNR in the induction therapy is around 280 mg/m2 (40 mg/m2 x 7 times), which is higher than the conventional dose of 40-60 mg/m2 for 3 days. The higher dose of DNR in the induction therapy for adult AML should be selected when the feasibility of a new drug is evaluated in a randomized trial.

Adolescent↗

PubMed2000

[Two-step tuberculin skin testing in our hospital employees].

To evaluate the baseline values of tuberculin reaction, two-step tuberculin skin testing was carried out in 365 employees of our hospital. We defined strongly response group when the size of erythema showed more than 30 mm or who showed strongly positive reaction. Two-step tuberculin skin testing was carried out in 165 hospital employees excluding those who were defined as the strongly response group in the first testing. 80 hospital employees (48.5%) became strongly response group by the second tuberculin skin testing. Altogether, 76.7% of all employees were strongly response group either by the first time or the second tuberculin skin testing. The size of erythema and that of induration showed 13.2 +/- 12.6 mm (mean +/- SD), 6.9 +/- 9.2 mm increase, respectively, in the two-step tuberculin skin testing, so-called Booster phenomenon. We could not know the true tuberculin reaction status by the single tuberculin skin testing. Therefore, two-step tuberculin skin testing is important as one of an infection prevention countermeasures in the hospital workers.

Adult↗

PubMed2000

[A case of transient cortical blindness complicated by Henoch-Schönlein purpura with bronchiectasis].

A 19-year-old woman had been treated for bronchiectasis since she was born. In October 1995, she was diagnosed as Henoch-Schönlein purpura (HSP) and HSP nephritis with the findings as follows; palpable petechial rash of legs, abdominal pain, arthralgias, and proteinuria. The administration of oral prednisolone was started, the clinical symptoms except for proteinuria was disappeared. However, nephrotic syndrome was continued despite the therapy of intravenous methylprednisolone pulse, various immunosuppressive drugs and warfarin. In February 1998, she was admitted to our hospital because of pneumonia. Several days later, her pneumonia improved on treatment with antibiotics, but she suddenly developed transient cortical blindness and acute renal failure. A provisional diagnosis of hypertensive encephalopathy and cerebral edema related to vasculitis was made, and she was treated with nifedipine, Glycelo, and high dose immunoglobulin. After the treatment, her vision and renal function had improved. She is a rare case associated with transient cortical blindness, bronchiectasis, and HSP.

Adult↗