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  • 1
    ISSN: 1573-7276
    Keywords: cAMP ; colon cancer ; DLD-1 ; phosphodiesterase ; rolipram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate mechanisms for regulation of intracellular cAMP involved in cancer cell invasion, phosphodiesterase (PDE) activity in a colon cancer cell line, DLD-1, was studied. Activities of PDE 2, 4, and 5 were detected in DLD-1 cells by pharmacological approach. Specific and cell permeable inhibitors for those PDEs were used to determine which PDE is responsible for cAMP turnover involved in cancer cell motility. Treatment of DLD-1 cells with rolipram and Ro-20-1724, inhibitors for PDE 4, elevated intracellular cAMP contents three to five times of control. EHNA, an inhibitor for PDE 2, and zaprinast, an inhibitor for PDE 5, did not affect cAMP levels. To assess cellular motility, we utilized chemotaxis assay. EHNA and zaprinast did not suppress serum-induced chemotaxis. In contrast, rolipram and Ro-20-1724, suppressed chemotaxis in a dose dependent fashion. These suggest that PDE 4 plays a critical role in regulating intracellular cAMP levels of colon cancer cells and is involved in cancer invasion. PDE 4 can be a novel target of anti-invasion drug.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-3305
    Keywords: Key words: second malignancy, adjuvant chemotherapy, stomach cancer, 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. Although many trials have been conducted to evaluate the feasibility and effectiveness of adjuvant chemotherapy (ACT) for patients with stomach cancer, the benefits of ACT remain unclear. Moreover, some authors have reported that ACT increased the incidence of second malignancy. The risk of second malignancy was evaluated in patients who underwent treatment for stomach cancer in the past 20 years at Osaka Medical Center for Cancer and Cardiovascular Diseases. Methods. The study population consisted of 1925 patients who underwent gastrectomies for stomach cancer between the years 1978 and 1992 and who received follow-up examinations to check for second malignancies. They included 1114 patients who underwent surgery only (group A) and 811 who underwent surgery and received chemotherapy (group B). The observed incidence of second malignancy (O) was compared with the expected incidence (E), calculated by the person-year method, using data from the Cancer Registry in Osaka. Results. The average follow-up period was 7.99 years. The total number of patients with a second malignancy was 127 (men, 97; women, 30); 72 patients had the second malignancy in digestive organs; 27 in respiratory organs; and 28 in other organs. The relative risks of a second malignancy in group A and B patients were 1.05 and 1.02 (differences between the two groups were not significant). The relative risks of a second malignancy in patients who received ACT with 5-fluorouracil, Tegafur and Uracil, and FT207 were 0.79, 1.01, and 1.06, respectively (differences between the groups were not significant). Conclusion. The risk of second malignancy after chemotherapy for stomach cancer was not high in comparison with the expected incidence. Adjuvant chemotherapy did not increase the risk of a second malignancy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7276
    Keywords: cell motility ; cilostazol ; colon cancer ; invasion ; phosphodiesterase type III
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metastasis of cancer cells is initiated by the cellular migration into extracellular matrix and surrounding vessels. We previously showed that elevation of cAMP levels in cancer cells suppressed trans-cellular migration in vitro. Drugs that can elevate cAMP levels in cancer cells effectively may be applied to prevent metastasis in cancer patients. Cilostazol, an oral anti-platelet drug, is a specific cAMP phosphodiesterase type III inhibitor and has been clinically used to treat thrombosis patients. In chemotaxis assay, cellular migration of human colon cancer cells, DLD-1, was induced by 10 μg/ml of soluble fibronectin or 10% of fetal bovine serum (FBS). Treatment with cilostazol (50 μM) suppressed 92.3% or 84.6% of the migration in control cells, respectively. When DLD-1 cells were stimulated by soluble fibronectin in phagokinetic assay, migration assessed by the area of gold particle phagocytosis track was induced and cilostazol also decreased 67.3% of the cellular migration in control cells. Furthermore, in the trans-cellular migration assay, cilostazol suppressed cancer cell invasion induced by FBS. Thus, cilostazol can suppress colon cancer cell motility and might be effective as an anti-metastasis drug for cancer patients.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7276
    Keywords: apigenin ; azoxymethane ; bombesin ; cancer metastasis ; intestinal cancer ; MMP-9 ; MAPK
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of a naturally occurring flavonoid apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 μg/kg body weight) every other day, and from week 16, s.c. injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression. Our findings indicate that apigenin inhibits cancer metastasis through inhibition of phosphorylation of MAPK.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1436-2813
    Keywords: multiple malignant neoplasms ; Bowen's disease ; arsenic ingestion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report describes the successful treatment of quadruple cancer including Bowen's disease in a 71-year-old man who had been given injections of salvarsan, an arsenic compound, for syphilis more than 40 years earlier. Resection of a skin lesion on his chest subsequently confirmed a diagnosis of Bowen's disease, 3 years after which he was operated on for concurrent gastric cancer and sigmoid colon cancer. A fourth cancer was discovered on his left vocal cord 2 weeks after this operation; it was resected 2 years later. A discussion of multiple malignant neoplasms and the possible relationship between arsenic and cancer is presented following this case report.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1534-4681
    Keywords: Early gastric cancer ; Limited operation ; Nerve preservation ; Segmental resection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Endoscopic resection for treatment of early gastric cancer (EGC) is widely performed. Recently, however, surgeons began performing a limited operation for EGC when endoscopic resection was not indicated. This report discusses the surgical technique and the results of the limited operation, which is generally referred to as “segmental resection” (SR). Methods: Since 1990, a total of 50 patients with intramucosal invasive EGC of the middle stomach underwent SR. The procedure included a limited gastrectomy, limited lymph node dissection, and preservation of the vagal nerve. We examined the surgical risk, postoperative complications, and patient survival rates and compared the results for the SR-treated patients (group A) with results for patients with EGC who underwent subtotal gastrectomy and systemic lymph node dissection (group B). Results: Blood loss was less in group A (239±180 ml) than in group B (342±176 ml) (P〈.05). The incidence of postoperative complications was also lower in group A (2.0%) than in group B (14.0%) (P〈.05). The incidence of postoperative cholelithiasis was lower in group A (4.0%) than in group B (18.0%) (P〈.05). All patients in both groups are alive without recurrence. Conclusions: Compared with distal gastrectomy, SR for EGC of the middle stomach decreased the surgical risk and postoperative complications without increasing the recurrence rate.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 57 (1995), S. 120-126 
    ISSN: 0730-2312
    Keywords: protein phosphatase ; calyculin A ; platelet ; talin ; phosphorylation ; phosphoamino acid analysis ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Calyculin A and okadaic acid, potent and cell permeable inhibitors of type 1 and type 2A protein phosphatases, inhibit platelet aggregation and secretion. However, the relationship between phosphatase inhibition and inhibition of platelet function is not well understood. We found that in unstimulated platelets, talin (P235) was phosphorylated at threonine residues by calyculin A. Furthermore, the extent of talin phosphorylation by calyculin A was closely correlated with its inhibition of thrombin-induced platelet aggregation. Since the binding of talin to platelet glycoprotein IIb/IIIa complex has been shown to be affected by its phosphorylation, these results suggest that type 1 and/or type 2A protein phosphatases may play a role in the regulation of membrane-cytoskeleton interaction through dephosphorylation of talin.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 63 (1996), S. 311-319 
    ISSN: 0730-2312
    Keywords: protein phosphatase 2A ; endothelial cells ; cyclic strain ; proliferation ; okadaic acid ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We previously proposed that activation of protein kinase C is a key mechanism for control of cell growth enhanced by cyclic strain [Rosales and Sumpio (1992): Surgery 112:459-466]. Here we examined protein phosphatase 1 and 2A activity in bovine aortic endothelial cells exposed to cyclic strain. Protein phosphatase 2A activity in the cytosol was decreased by 36.1% in response to cyclic strain for 60 min, whereas the activity in the membrane did not change. Treatment with low concentration (0.1 nM) of okadaic acid enhanced proliferation of both static and stretched endothelial cells in 10% fetal bovine serum. These data suggest that protein phosphatase 2A acts as a growth suppressor and cyclic strain may enhance cellular proliferation by inhibiting protein phosphatase 2A as well as stimulating protein kinase C. © 1996 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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