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Biomedical subjects

Y Nio

Publications and source records attributed to Y Nio.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mechanisms of cytotoxic effects of heavy water (deuterium oxide: D2O) on cancer cells.

Heavy water (deuterium oxide: D2O) contains a neutron and a proton in its hydrogen atoms and shows a variety of biologic activities different from normal light water. In the present study the cytotoxic and cytostatic activity of D2O was assessed using a BALB/c-3T3 fibroblast cell line and four human digestive organ cancer cell lines, i.e. HepG2 hepatic, Panc-1 pancreatic, KATO-3 gastric and Colo205 colonic cancer cell lines. Against four cancer cell lines, D2O showed significant cytotoxic and cytostatic effects in a MTT assay and a Trypan blue dye exclusion assay, at concentrations higher than 30% D2O. These effects were time and dose dependent, and the IC50 after 72 h of culture ranged from 20 to 30% D2O in the Trypan blue dye exclusion assay and from 30 to 50% D2O in the MTT assay. By contrast, IC50 for the 3T3 fibroblast cell line after 72 h of culture was about 15% in the Trypan blue dye exclusion assay and 50% inhibition was not achieved in the MTT assay. Furthermore, D2O was found to significantly inhibit the invasion of tumor cells in a Matrigel invasion chamber assay at concentrations higher than 10% D2O. Incubation with D2O resulted in enlargement of cells, nuclear pyknosis and vacuolization, and immunostaining studies demonstrated that D2O treatment resulted in an increase in nuclear nick-end-labeling, which indicates DNA fragmentation, in KATO-3 and HepG2 cell lines. Furthermore, the nucleic acids and protein synthesis inhibition assay suggested that the inhibition of DNA synthesis may be one of the mechanisms responsible for the antitumor effects of D2O. Furthermore, oral administration of D2O resulted in a significant inhibition of the growth of Panc-1 tumor xenografted s.c. in nude mice, but survival was not prolonged. In conclusion, D2O has cytotoxic and cytostatic activities against human digestive organ cancer cell lines, and D2O may be a potential anticancer agent.

3T3 Cells↗
PubMed1998

Comparative study of p53 expression in primary invasive ductal carcinoma of the pancreas between Chinese and Japanese.

Previous studies reported different frequencies of p53 expression between Japanese and Americans or Europeans. The present study was designed to clarify whether there is a significant difference in p53 expression and its clinical implications between Chinese and Japanese patients with primary invasive ductal carcinoma (IDC) of the pancreas. p53 expression was studied in 39 Chinese and 47 Japanese patients, and immunostaining with the SAB method was performed using anti-p53 monoclonal antibody (DO-1) in formalin-fixed and paraffin-embedded specimens. Clinical data were analyzed according to the International Union Against Cancer classification. p53 expression was seen in 71.8% of Chinese and in 48.9% of Japanese patients with IDCs of the pancreas (p < 0.05). The Chinese patients were significantly younger than the Japanese ones (p < 0.05), but there were no significant correlations between p53 immunoreactivity and age, gender, stage, and histopathological grade in separate analyses of the Chinese and Japanese patients. A comparison between them showed that in patients younger than 55 and 65 years old, the incidence of p53 expression was markedly lower in Japanese than in Chinese (p < 0.05). In Japanese patients, those with a p53-positive pancreatic cancer had a significantly lower survival rate than those with a p53-negative tumor, but there was no correlation between p53 expression and the prognosis of Chinese patients. The frequency of p53 expression in IDC of the pancreas is higher in Chinese than in Japanese patients, and the effect of p53 expression on prognosis is different between Chinese and Japanese patients.

Aged↗
PubMed1998

The correlation between coronary stenosis index and flow-mediated dilation of the brachial artery.

We examined the relationship between flow-mediated dilation (FMD) of the brachial artery and the extent and severity of coronary artery disease (CAD). Using high-resolution ultrasonography, we measured FMD and nitroglycerin-induced brachial artery dilation. We studied 121 patients (77 men, 44 women; mean age 64+/-11 years, range 25-79 years) who underwent coronary arteriography. The extent and severity of CAD were assessed by the coronary stenosis index (CSI). The adjusted FMD correlated inversely with CSI (rs=-0.63, p<0.0001). Multivariate analysis demonstrated that the adjusted FMD was an independent predictor of CSI. The adjusted FMD was 10.2+/-4.8% in patients without CAD (n=32), 7.7+/-6.0% in patients with single-vessel disease (n=31), 5.2+/-5.5% in patients with double-vessel disease (n=29), and 2.0+/-3.9% in patients with triple-vessel disease (n=29). The adjusted FMD was significantly lower in the double- (p<0.01) and triple-vessel (p<0.0001) disease groups than in patients without CAD. The adjusted FMD was significantly lower in the triple-vessel disease group than in the single-vessel disease group (p<0.001). Based on our results, as coronary atherosclerosis becomes more severe, the adjusted brachial artery FMD becomes more severely impaired.

Adult↗
PubMed1997

Experimental investigation of the role of the splenic vein in gastric venous obstruction after pylorus-preserving pancreatoduodenectomy in the dog.

CONCLUSION: This study showed that the splenic vein (SV) plays a major role in maintaining gastric blood flow after ligature of peripyloric vessels in the dog. Therefore, SV preservation or alternative venous drainage may be recommended to maintain sufficient gastric blood flow in pylorus-preserving pancreatoduodenectomy (PPPD). BACKGROUND: In PPPD, we often encounter the problem of gastric venous drainage obstruction, if the splenic-portal vein confluence needs to be resected. This study investigated significance of venous drainage via the left gastric and splenic veins in gastric tissue blood flow. METHODS: In seven mongrel dogs, gastric tissue blood flow was measured by both laser Doppler flowmetry (LDF) in the antrum and hydrogen gas clearance (HGC) in the antrum and body. Blood flow was measured after the following treatments: 1. No treatment; 2. Duodenal transection; 3. Ligature of the right gastric and gastroepiploic arteries and veins; 4. Transient obstruction of the left gastric vein (LGV); 5. Transient obstruction of the SV with the LGV open; and 6. Obstruction of both the LGV and the SV. RESULTS: As judged by LDF, treatments 2, 3, and 4 did not decrease blood flow, but treatments 5 and 6 significantly decreased it compared with both treatments 1 and 3. By HGC, changes in the antrum and the body were parallel. Duodenal transection did not, but treatments 3 and 4 did decrease blood flow compared with no treatment. Obstruction of the left gastric vein did not, but treatments 5 and 6 did significantly decrease it compared with treatment 3.

Animals↗
PubMed1997

A quinolinone derivative, vesnarinone (OPC-8212), significantly inhibits the in vitro and in vivo growth of human pancreatic cancer cell lines.

A quinolinone derivative, vesnarinone, has been used as a cardiotonic agent. Previous studies have demonstrated that vesnarinone has potent antitumor activity. The present study was designed to assess the antitumor effects of vesnarinone on human pancreatic cancer cell lines in vitro and in vivo. The in vitro effects of vesnarinone on the human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were assessed by the MTT assay, the Trypan blue dye exclusion test and the Matrigel invasion chamber assay. The inhibition of in vivo tumor growth was evaluated on two human pancreatic cancer xenografts (BxPC-3 and SPa-1) transplanted s.c. into nude mice. The dose of vesnarinone for 50% inhibition of cell growth in a 7 day culture ranged between 10 and 20 micrograms/ml as verified by the Trypan blue dye exclusion test. The dose for 50% cytotoxicity after a 3 day culture in the MTT assay was 32 micrograms/ml for PANC-1 and 30 micrograms/ml for BxPC-3, but 50% cytotoxicity for MIA PaCa-2 was not achieved by the maximal dose of vesnarinone (50 micrograms/ml). Nomalsky optic microscopy and acridine orange staining demonstrated the vacuolization and crater-like changes in the cell nucleus after vesnarinone treatment. Moreover, staining of an apoptosis marker (Le(y) protein) and nick end-labeling increased. Vesnarinone also inhibited cancer invasion in the Matrigel invasion chamber assay. In vivo, BxPC-3 and SPa-1 were s.c. transplanted into the nude mice, and vesnarinone (5 or 50 mg/kg) was daily administered orally for 21 days. In both lines, vesnarinone at 50 mg/kg achieved significant inhibition. The present study suggests that vesnarinone may be a new therapeutic agent for pancreatic cancer.

Adenocarcinoma↗
PubMed1997

5-Fluorouracil + cisplatin + mitomycin C is a relatively most effective combination against xenograft lines of human colorectal cancer.

5-Fluorouracil (5-FU) has been an accepted effective against colorectal cancer, but combination regimens resulted in a lesser effect than 5-FU alone. The present study was designed to evaluate the efficiency of various combination chemotherapies, including 5-FU, on human colorectal cancer xenograft lines (CC-KK and RC-TK), which had been passed by transplantation in nude mice. Eight anticancer agents [5-FU, mitomycin C (MMC), adriamycin (ADR), 4'-epirubicin (EPIR), carboquone (CQ), cisplatin, carboplatin and etoposide (VP-16)] and their combinations were evaluated at 2-4 times the clinical dose. When the agents were administered singly, 5-FU, EPIR and CQ were effective against CC-KK, and 5-FU, MMC, EPIR, ADR, CQ and carboplatin were effective against RC-TK. Of the two-agent combinations including 5-FU, cisplatin + 5-FU was the most effective against both CC-KK and RC-TK. However, of the three-agent combinations, only cisplatin + 5-FU + MMC was more effective against both lines than cisplatin + 5-FU. These results suggest that cisplatin + 5-FU + MMC may be the most useful regimen against colorectal cancers in clinical application.

Adenocarcinoma↗
PubMed1997

[Newly-developing therapies of pancreatic cancer--immunotherapy, gene therapy, differentiation therapy, endocrine therapy and others].

Pancreatic cancer is extremely resistant to various cancer therapies, however, variety of new therapies for pancreatic cancer have been investigated: (1) immunotherapy including cytokines like TNF, adoptive immunotherapy with lymphokine-activated killer cells or cytotoxic T-lymphocytes, and tumor vaccines using mutated Ki-ras oncoprotein or irradiated tumor cells which were transfected by cytokine genes; (2) gene therapy including transfer of cytokine genes or antisense Ki-ras oncogene, and a combination of gene transfer of herpes simplex virus thymidine kinase and subsequent administration of ganciclovir; (3) differentiation therapy including a quinolinone derivative, vesnarinone; (4) endocrine therapy including cholecystokinin-receptor antagonist, CR1505 or L364,718; (5) heavy water, and etc. All of these therapies will be applied for the treatment of pancreatic cancer in the near future.

Animals↗
PubMed1997

Deuterium oxide (heavy water) accelerates actin assembly in vitro and changes microfilament distribution in cultured cells.

While deuterium oxide (D2O) is known to produce various biological effects in living animals and cultured cells, the detailed mechanisms by which it does so remain unclear. The present study was designed to assess the effects of D2O on microfilaments (MFs) via fluorescence staining of BALB 3T3 cells and in vitro actin polymerization studies. After BALB 3T3 cells had been exposed to a concentration of more than 30% D2O for several hours, stress fibers in the peripheral region became thick and distinct, while the quantity of perinuclear MFs was drastically reduced. This effect was transient and returned to the original distribution within 12 h. Cytoplasmic F-actin (FA) also increased transiently coincident with the enhancement of stress fibers. The pattern of cell locomotion became simpler, and total locomotor activity was suppressed in a D2O concentration-dependent manner. Analysis of in vitro studies demonstrated that, when purified G-actin was polymerized in D2O at a concentration greater than 10%, the rate of actin polymerization was accelerated, whereas the total amount of polymerized actin at the steady state in D2O was the same as that in H2O controls. A gelation assay and transmission electron microscopy (TEM) showed that the network of crosslinked FA with alpha-actinin became denser in 30% D2O than in H2O. These findings concerning actin polymerization and FA gelation suggest that the alteration of stress fibers in cultured cells is caused by a direct effect of D2O on cellular MF dynamics.

3T3 Cells↗
PubMed1996

Cis-diamminedichloroplatinum(II) augments expression of tumor-associated antigens on human gastric cancer cell line KATO-3 and increases susceptibility and binding of tumor cells to various cytotoxic effector cells.

Previous studies have demonstrated the immunomodulatory effects of cisplatin under certain conditions. The present study was designed to clarify whether cisplatin modulates the expression of surface antigens, especially human leukocyte antigen (HLA), on human tumor cell lines and/or augments the susceptibility and binding of tumor cells to cytotoxic effector cells. A human gastric cancer cell line, KATO-3, was employed. The expression of HLA and other tumor-associated antigens was analyzed by flow cytometry using FITC-conjugated monoclonal antibodies. The cytotoxicity of effector cells was determined by 51Cr release assay. The expression of HLA class I antigen, beta2-microglobulin, leukocyte function-associated antigen-1, and AC-81 adenocarcinoma-associated antigen on KATO-3 increased after exposure to cisplatin at 10 micrograms/ml for 3-6 hr; augmentation of HLA class I subtypes -B2 and -B27 was particularly prominent. Furthermore, the susceptibility and binding of KATO-3 to both lymphokine-activated killer cells and KATO-3-specific cytotoxic T lymphocytes significantly increased after cisplatin treatment. Cisplatin may modulate the expression of tumor-associated antigens on some human tumor cells. Tumor regression by cisplatin administration may depend on its direct cytotoxicity as well as on its modulating effects on the expression of tumor-associated antigens, subsequently leading to the activation of the immune surveillance system against the tumor.

Adjuvants, Immunologic↗
PubMed1996

Role of endogenous hypergastrinemia in regenerating endocrine pancreas after partial pancreatectomy.

We studied the possible role of endogenous gastrin in the regenerating pancreas. Male Wistar rats underwent sham operation or 90% partial pancreatectomy (Px). Lansoprazole (30 mg/kg body wt), a proton pump inhibitor (PPI), was given p.o. for 3 weeks after surgery. Plasma glucose levels were higher in Px rats than in shams. Lansoprazole lowered plasma glucose levels in the Px rats. In addition, integrated insulin secretion during an oral glucose tolerance test (2 g/kg body wt) was significantly (p < 0.01) higher in lansoprazole-treated Px rats than in control Px rats, while lansoprazole did not affect insulin secretion in shams. Fasting serum gastrin levels were higher (p < 0.01) in lansoprazole-treated animals than in controls both in sham rats and in Px rats. Furthermore, lansoprazole increased the pancreas weight per body weight and elevated the insulin content of the pancreas in Px rats. These results suggest that endogenous hypergastrinemia has a trophic effect on endocrine pancreas during regenerating processes and that administration of PPI may be clinically beneficial to the remnant pancreas after pancreatectomy if the whole stomach is preserved.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Clinicopathological significance of Ki-ras point mutation and p21 expression in benign and malignant exocrine tumors of the human pancreas.

CONCLUSION: The present study suggests that Ki-ras point mutations may play an important role in the early stages of tumorigenesis and that a double mutation has a stronger detrimental effect than a single mutation on the survival after pancreatectomy. BACKGROUND: Previous studies have suggested the important role of Ki-ras point mutations in ras gene codon 12 in the tumorigenesis of pancreatic cancer, but their clinicopathological significance is still unclear. The present study was designed to assess the clinicopathological significance of Ki-ras point mutations, and p21 expression in malignant and benign diseases of the pancreas. METHODS: Oligonucleotide dot-blot hybridization for Ki-ras point mutations in codon 12 and immunohistochemical staining for p21 expression were applied. Cases included 44 primary and 15 metastatic lesions of pancreatic cancer, and 17 benign pancreatic diseases. RESULTS: Ki-ras point mutations and p21 expression were detected in 43 and 19 primary lesions, 9 and 6 metastatic lesions, and four and five benign diseases, respectively. The patients with a single mutation had a better survival after pancreatectomy than those with a double mutation. The patients with a p21(+) GAT mutation showed the worst survival after pancreatectomy compared with other categories of patients.

Adult↗
PubMed1996

[Two operated cases of synchronous double cancer of the lung and digestive tract in patients over 80 years old and genetical diagnosis].

Synchronous double cancer of the lung and gastrointestinal organ was successfully resected by an one-step approach in two aged patients over 80 years. An 81-year-old man was clinically diagnosed as having a right lung cancer (S3) along with a sigmoid colon cancer. The pathological cell types of these cancers were squamous cell carcinoma and adenocarcinoma respectively. Right upper lobectomy and sigmoidectomy were performed at the same time because he had no risks for the operation. An-80-year-old woman was diagnosed as having a left lung cancer (S8-9) along with a stomach cancer. The cell types of these cancers were both highly differentiated adenocarcinoma. Left lower lobectomy and subtotal gastrectomy were performed at the same time, too. We limited lymph nodes dissection to shorten the operation time and no postoperative complications occurred in both patients. It is suggested that simultaneous operation for double cancer in aged patients can be safely performed in selected cases. In the latter patient, pathological cell type of the lung cancer was similar to that of stomach cancer. So we applied polymerase chain reaction (PCR) for making a diagnosis of double cancer postoperatively, and it was proved that the lung and gastric cancers were different from each other in genetical natures. Application of the genetical technique to clinical field which greatly contribute to making a diagnosis of double cancer is expected.

Adenocarcinoma↗
PubMed1996

[Application for therapeutic use of deuterium oxide (D2O) against human pancreatic cancer].

This study was designed to assess the possibility of D2O as a therapeutic agent against human pancreatic cancer. We examined the effect of D2O on growth and invasion of human pancreatic cancer cells (Panc-1, MIA PaCa-2, BxPC-3) by using MTT assay and nude mice, on which human pancreas cancer cells were transplanted. In vitro growth of the three lines was significantly inhibited by D2O in a dose dependent manner, especially at more than a 10% concentration. Growth of Panc-1, which was transplanted in nude mice, was also inhibited by continuous oral intake of 30% D2O. Furthermore, the effect of D2O on cancer invasiveness was assessed by Matrigel invasion chamber assay. BxPC-3, which is the most adherent of the three lines, significantly reduced its invasiveness in more than 30% D2O media. In addition, the present study also demonstrated the inhibition of cancer cell locomotion by D2O in phagocytokinetic analysis. In conclusion, D2O may be applied for the therapeutic use against pancreatic cancer.

Animals↗
PubMed1995

Characterization of glucocorticoid response element of rat angiotensin II type 1A receptor gene.

The responsiveness of the rat angiotensin II type 1a and type 1b receptor (AT1a-R and AT1b-R) genes to glucocorticoid was examined in rat vascular smooth muscle cells (VSMCs) and the glucocorticoid response element (GRE) of the AT1a-R gene was characterized. Glucocorticoid induced an increase in AT1a-R mRNA levels, whereas AT1b-R mRNA levels were unaffected. The nuclear run-off assay indicated that the transcription of the AT1a-R gene, but not that of the AT1b-R gene, was increased by glucocorticoid. The mRNA stability of AT1a-R was unchanged by glucocorticoid. Promoter/chrolamphenicol acetyltransferase reporter analysis demonstrated that the 5'-flanking region of the AT1a-R gene was functional in rat VSMCs and established that the GRE motif between -770 to -756 could confer glucocorticoid responsiveness on the AT1a-R gene.

Angiotensin II↗
PubMed1995

Anticancer chemosensitivity changes between the original and recurrent tumors after successful chemotherapy selected according to the sensitivity assay.

OBJECTIVE: The authors compare and characterize the changes in chemosensitivity between the original tumors before chemotherapy and recurrent tumors after responses. SUMMARY BACKGROUND DATA: The drug resistance in clinical chemotherapy appears to be different from that in experimental chemotherapy, and the profile and mechanisms of clinical drug resistance in recurrent tumors, especially after successful chemotherapy has scarcely been studied. METHODS: Applied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors was assessed. Responses were defined according to the standard criteria, and successful chemotherapy indicates complete response (CR) or partial response (PR) for solid tumors and complete disappearance for malignant effusion. RESULTS: In 37 patients, the effectiveness of four agents were compared between before chemotherapy and after recurrence, and the response lasted between 2 and 26 months (mean +/- SD, 7.7 +/- 5.5). The results suggest that locally recurred tumors may become resistant to the agents previously administered; by contrast, distantly recurred tumors may not necessarily become resistant to the agents administered. The recurrent tumors are suggested to be sensitive to the agents as follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion, ADR. Twenty-three of 37 recurrent tumors were re-treated with chemotherapies selected according to the sensitivity assay, singly or in combination with a biologic response modifier (BRM)--a streptococcal preparation, OK-432, or interferon-alpha. Responses were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent effusions. Responses were seen only when the patients were treated with a combination of chemotherapy and BRM. CONCLUSION: There may be a notable differences in the basic biologic characteristics of tumor cells with respect to local versus distant recurrences, and between effusion versus solid recurrences. Various approaches, including a combination of chemotherapy and BRM, therefore, may have to be applied to overcome these drug resistances in practical chemotherapies for recurrent tumors.

Antineoplastic Agents↗
PubMed1995

Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.

Increasing evidence suggests that angiotensin II (AngII) acts as a modulator for ventricular remodeling after myocardial infarction. Using competitive reverse-transcriptase polymerase chain reaction, nuclear runoff, and binding assays, we examined the regulation of AngII type 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in the infarcted rat heart as well as the effects of AngII receptor antagonists. AT1a-R mRNA levels were increased in the infarcted (4.2-fold) and noninfarcted portions (2.2-fold) of the myocardium 7 d after myocardial infarction as compared with those in sham-operated controls, whereas AT1b-R mRNA levels were unchanged. The amount of detectable AT2-R mRNA increased in infarcted (3.1-fold) and noninfarcted (1.9-fold) portions relative to that in the control. The transcription rates for AT1a-R and AT2-R genes, determined by means of a nuclear runoff assay, were significantly increased in the infarcted heart. The AngII receptor numbers were elevated (from 12 to 35 fmol/mg protein) in the infarcted myocardium in which the increases in AT1-R and AT2-R were 3.2- and 2.3-fold, respectively, while the receptor affinity was unchanged. Therapy with AT1-R antagonist for 7 d reduced the increase in AT1-R and AT2-R expressions in the infarcted heart together with a decrease in blood pressure, whereas therapy with an AT2-R antagonist did not affect mRNA levels and blood pressure. Neither AT1-R nor AT2-R antagonists affected the infarct sizes. These results demonstrated that myocardial infarction causes an increase in the gene transcription and protein expression of cardiac AT1a-R and AT2-R, whereas the AT1b-R gene is unaffected, and that therapy with an AT1-R antagonist, but not with an AT2-R antagonist, is effective in reducing the increased expression of AngII receptor subtypes induced by myocardial infarction.

Angiotensin Receptor Antagonists↗