Forskolin and phorbol ester have opposite effects on the expression of mucin-associated sialyl-Lewisa in pancreatic cancer cells

Yamashita, Yoshito; Ho, Jenny J. L.; Farrelly, Ellyn; Hirakawa, Kosei; Sowa, Michio; Kim, Y.S.

doi:10.1016/s0959-8049(99)00238-5

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…Forskolin is known to up-regulate cAMP and enhance kinase activity and exert its influence via ion channels , while Ecay et al report on the wortmannin inhibition of forskolin-stimulated chloride secretion. Similarly, the results of Yamashita et al show that forskolin and phorbol esters have opposite effects on the expression of mucin-associated sialyl-Lewis(a) in pancreatic cancer cells. Thus, exploration of coclustered compounds may further illuminate known mechanistic pathways involved in cancer chemotherapy and reveal previously unknown molecular interactions.…”

Section: Region P: Cellular Regulation and Apoptosismentioning

confidence: 68%

Mining the National Cancer Institute's Tumor-Screening Database: Identification of Compounds with Similar Cellular Activities

et al. 2002

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In an effort to enhance access to information available in the National Cancer Institute's (NCI) anticancer drug-screening database, a new suite of Internet accessible (http://spheroid. ncifcrf.gov) computational tools has been assembled for self-organizing map-based (SOM) cluster analysis and data visualization. A range of analysis questions were initially addressed to evaluate improvements in SOM cluster quality based on the data-conditioning procedures of Z-score normalization, capping, and treatment of missing data as well as completeness of drug cell-screening data. These studies established a foundation for SOM cluster analysis of the complete set of NCI's publicly available antitumor drug-screening data. This analysis identified relationships between chemotypes of screened agents and their effect on four major classes of cellular activities: mitosis, nucleic acid synthesis, membrane transport and integrity, and phosphatase- and kinase-mediated cell cycle regulation. Validations of these cellular activities, obtained from literature sources, found (i) strong evidence supporting within cluster memberships and shared cellular activity, (ii) indications of compound selectivity between various types of cellular activity, and (iii) strengths and weaknesses of the NCI's antitumor drug screen data for assigning compounds to these classes of cellular activity. Subsequent analyses of averaged responses within these tumor panel types find a strong dependence on chemotype for coherence among cellular response patterns. The advantages of a global analysis of the complete screening data set are discussed.

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Section: Region P: Cellular Regulation and Apoptosismentioning

confidence: 68%

Mining the National Cancer Institute's Tumor-Screening Database: Identification of Compounds with Similar Cellular Activities

et al. 2002

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“…In one study on colon cancer patients immunoscintigraphy with a "cocktail" of antibodies reactive with both sialyl-Tn and CEA detected 16 of 19 confirmed lesions as compared to only 9 of 19 lesion detected by CT scan [109]. Recently we observed that forskolin, an activator of adenyl cyclase, increased expression and release of MUC1 associated sialyl-Lewis a [65]. Several means have been investigated to upregulate antigen expression, i.e., increase the number of cells expressing antigen or the level of antigen expressed per cell.…”

Section: E Therapymentioning

confidence: 99%

“…The ability of pancreatic cancer cells to adhere to Eselectin was dependent upon the level of sialyl-Lewis a on their surface [63]. Blocking cell surface sialyl-Lewis a with antibodies such as 19-9 [63] or SPan-1 [65] reduced E-selectin binding but antibodies against sialyl-Lewis x did not. When cell surface levels of sialyl-Lewis a were reduced by an inhibitor of O-linked glycosylation E-selectin binding was also reduced [63].…”

Section: C2 Suppression Of Immune Responsementioning

confidence: 99%

Mucins in the Diagnosis and Therapy of Pancreatic Cancer

Ho¹

2000

CPD

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Mucins are large glycoproteins that form a protective layer along the lumens of the organs of the gastrointestinal and reproductive tracts. Frequently in tumors of the pancreas there are changes in the structure of mucin carbohydrates and/or levels of apomucin types. Originally mucins were of interest clinically because diagnostic tests could be based on their levels in circulation. More recently mucin directed monoclonal antibodies have been used to target tumors with cytotoxic agents. There is now a considerable literature on the development of mucin-based vaccines. Both monoclonal antibodies and vaccines could be powerful tools to specifically target tumor cells in distant metastases. Gene therapy based upon the MUC1 gene promoter is being investigated to target therapeutic genes to MUC1 expressing cells. The carbohydrates of mucins on the surface of tumor cells have been reported to inhibit cells of the immune system. These carbohydrates also act as ligands during the process of tumor cell metastasis. Another approach to therapy is to block interactions between the ligands and their receptors.

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MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis

2010

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Apomucins play important biological roles in cell-cell and cell-extracellular matrix interactions, in cell signaling, and in biological properties of cancer cells. Their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins, gel-forming components of viscoelastic mucus gels protecting the epithelia, includes mucins MUC2 and MUC6. Their principle function is to contribute in mucus formation by forming a tridimensional network via oligomerization domains to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and MUC6 in patients with gastric carcinoma. MUC2 and MUC6 expressions were detected immunohistochemically in gastric cancer biopsies using specific monoclonal antibodies. The results showed that in our gastric carcinoma cases, MUC2 expression was detected in 78.6% of cases. MUC2 expression is increased from well differentiated to moderately differentiated to poorly differentiated gastric adenocarcinoma. On the other hand, MUC6 was detected in 32% of cases. The expression of MUC2 is increasing, which is accompanied by an altered expression of MUC6 in gastric cancer. Therefore, it is concluded that the expression pattern of secreted mucins including MUC2 and MUC6 is altered apparently in gastric carcinoma.

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Forskolin and phorbol ester have opposite effects on the expression of mucin-associated sialyl-Lewisa in pancreatic cancer cells

Cited by 7 publications

References 14 publications

Mining the National Cancer Institute's Tumor-Screening Database: Identification of Compounds with Similar Cellular Activities

Mining the National Cancer Institute's Tumor-Screening Database: Identification of Compounds with Similar Cellular Activities

Mucins in the Diagnosis and Therapy of Pancreatic Cancer

MUC2 and MUC6 apomucins expression in human gastric neoplasm: an immunohistochemical analysis

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