Adenovirus-mediated expression of pig α(1, 3) galactosyltransferase reconstructs Gal a(1, 3) Gal epitope on the surface of human tumor cells

Xing, Li; Xia, Guo Hong; Fei, Jian; Huang, Feizhou; Guo, Li

doi:10.1038/sj.cr.7290076

Cited by 10 publications

(7 citation statements)

References 17 publications

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“…No difference was observed in the growth of the human pancreatic tumoral cells expressing the αGal epitope compared to control cell clones. This observation was supported by Xing et al 54. who showed that the expression of αGal epitope on tumoral cells did not modify the cell growth in vitro .…”

Section: Discussionsupporting

confidence: 54%

Candidemia in women with breast carcinoma treated with high‐dose chemotherapy and autologous bone marrow transplantation

Gottfreðsson

Vredenburgh

et al. 2003

Cancer

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This work builds on our prior results to develop novel control structure design principles for integrated plants featuring multiple time scale dynamics. Specifically, the concept of self‐optimizing control can be used to identify the variables that must be controlled to achieve acceptable economic performance during plant operation. This approach does not, however, provide guidelines on control structure design and control loop tuning; a detailed controllability and dynamic analysis is generally needed to this end. In this work, we employ a singular perturbation‐based framework, which accounts for the time scale separation present in the open loop dynamics of integrated plants, to identify the available controlled and manipulated variables in each time scale. The resulting controller design procedure thus accounts for both economic optimality and dynamic performance. The developed concepts are subsequently successfully applied on a reactor‐separator process with recycle and purge. © 2008 American Institute of Chemical Engineers AIChE J, 2008

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Section: Discussionsupporting

confidence: 54%

Candidemia in women with breast carcinoma treated with high‐dose chemotherapy and autologous bone marrow transplantation

Gottfreðsson

Vredenburgh

et al. 2003

Cancer

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“…No difference was observed in the growth of the human pancreatic tumoral cells expressing the ␣Gal epitope compared to control cell clones. This observation was supported by Xing et al 54 who showed that the expression of ␣Gal epitope on tumoral cells did not modify the cell growth in vitro. Therefore, the expression of ␣Gal epitope at the surface of tumoral cells could alter greatly cell-to-cell and cell-to-substratum interactions, 5,6 cellular motility and tumor progression.…”

Section: Discussionsupporting

confidence: 52%

Decrease of human pancreatic cancer cell tumorigenicity by α1,3galactosyltransferase gene transfer

Aubert

Crotté

Bernard

et al. 2003

Intl Journal of Cancer

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The enzyme ␣1,3galactosyltransferase synthesizes the ␣Gal epitope, a carbohydrate structure (Gal␣1,3Gal␤1,4GlcNAc-R), on glycoconjugates in lower mammals. The enzyme is absent in humans but large amounts of natural antibodies that recognize ␣Gal epitopes are present in human serum. It is likely that these antibodies contribute to the host defense and participate in the hyperacute rejection of xenograft. Previous studies indicated that the glycosyltransferase gene transfer into tumoral cells can modify the structure of glycoconjugates at the cell surface and, as a consequence, modulates the metastatic and tumorigenic behaviors of these cells. The aim of our study was to determine whether the expression of ␣Gal epitope can modify the tumorigenicity of human pancreatic cancer cells In the past decades, the incidence of pancreatic cancer has been increasing and it is now the fourth-leading cause of cancer-related deaths in the United States and Western countries. 1,2 This cancer is extremely aggressive and very resistant to current treatments including surgery. 3 Diagnosis in most patients occurs once the tumor has spread over into lymph nodes or formed distant metastases. 4 The molecular mechanism regulating pancreatic tumor cell invasion, metastasis and tumor progression still remains poorly understood. Several studies, however, reported that aberrant glycosylation of glycosphingolipids and glycoproteins expressed in tumor cells has been implicated in metastatic and tumorigenic behaviors of these cells. 5,6 The most common alterations are modifications of ABH, Lewis and blood group-related antigens. Lewis b, Lewis y, H-type and T antigens were expressed in normal pancreas whereas Lewis x, sialyl-Lewis x, sialyl-Lewis a and sialyl-Tn antigens were principally detected in pancreatic cancer tissues. 7-11 Sialyl-Lewis a antigens expressed preferentially at the surface of circulating adenocarcinoma cells are recognized by selectins located on endothelial cell membrane and thus, may play an important role in the metastasis formation consecutive to pancreatic adenocarcinoma. [12][13][14][15] The mechanism by which these antigens arise is not well understood but may involve changes in the activity of glycosyltransferases. In particular, a substantial decrease of ␣1,2fuco-syltransferase activity and an enhanced ␣1,4fucosyltransferase activity have been observed in tumoral pancreatic cell lines compared to normal tissue. 16 This balance can favor the expression of sialyl-Lewis x and sialyl-Lewis a antigens. We have shown recently that the restoration of ␣1,2fucosyltransferase FUT1 expression or the invalidation of ␣1,3/1,4fucosyltransferase FUT3 in human pancreatic tumor cells resulted in the decrease of sialylLewis antigen expression associated with an in vivo decrease in metastatic properties in nude mice. 17,18 These tumor-associated carbohydrate antigens represent potential targets for diagnosis, imaging and new therapeutic treatments such as gene therapy and immune therapy.In this context, the carbohydrate epitope Gal␣...

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“…Similarly, it was reported that 98 % of α-gal-positive MC38 colon carcinoma cells were killed by media containing human serum [ 16 ]. However, Li et al reported that there is no significant difference in susceptibility to lysis at various concentrations of human serum in three tested human tumor cell lines expressing gal epitope compared with their corresponding parental cells [ 40 ]. Consistent with this report, we incubated SKOV3-gal cells with different dilutions of serum obtained from ovarian cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Epithelial ovarian cancer stem-like cells expressing α-gal epitopes increase the immunogenicity of tumor associated antigens

et al. 2015

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BackgroundAs ovarian cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and chemo-resistance, new stratagems that selectively target ovarian CSCs are critically significant. Our previous work have demonstrated that ovarian cancer spheroid cells are tumorigenic and chemo-resistant, and have the properties of ovarian CSCs. Herein, we hypothesized that expressing α-gal epitopes on ovarian spheroid cells may help eliminate CSCs and improve the outcome of therapeutic intervention for ovarian cancer patients.MethodsLentivirus-mediated transfer of a pig α(1,3)galactosyltransferase [α1,3GT] enzyme gene into human ovarian cell line SKOV3 cells formed α-gal epitope-expressing cells (SKOV3-gal cells), and then these cells were maintained in a serum-free culture system to form SKOV3-gal spheroid cells. Efficacy of this cell vaccine was demonstrated in α1,3GT knockout mice (α1,3GT KO mice).ResultsThe antibody titers to α-gal epitopes measured by ELISA were significantly increased in α1,3GT KO mice after immunization with SKOV3-gal spheroid cells. Furthermore, compared with the non-immunized KO mice, the SKOV3 tumors grafted under renal capsules of KO mice immunized with SKOV3-gal spheroid cells grew slower and began to shrink on day 12. Western blot analysis also showed that immunized KO mice can produce effective antibody against certain tumor associated antigens (TAAs) derived from both SKOV3 cells and SKOV3 spheroid cells. The TAAs were further investigated by mass spectrometry and RNA interference (RNAi) technology. The results suggested that antibodies responding to protein c-erbB-2 may be raised in the sera of the mice after immunization with SKOV3-gal spheroid cells. Ultimately, vaccination with SKOV3-gal spheroid cells induced more CD3 + CD4 + T cells in the spleen of immunized mice than non-immunized KO mice.ConclusionsThe results suggest that vaccination using ovarian cancer stem-like cells engineered to express α-gal epitopes may be a novel strategy for treatment of ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1973-7) contains supplementary material, which is available to authorized users.

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Adenovirus-mediated expression of pig α(1, 3) galactosyltransferase reconstructs Gal a(1, 3) Gal epitope on the surface of human tumor cells

Cited by 10 publications

References 17 publications

Candidemia in women with breast carcinoma treated with high‐dose chemotherapy and autologous bone marrow transplantation

Candidemia in women with breast carcinoma treated with high‐dose chemotherapy and autologous bone marrow transplantation

Decrease of human pancreatic cancer cell tumorigenicity by α1,3galactosyltransferase gene transfer

Epithelial ovarian cancer stem-like cells expressing α-gal epitopes increase the immunogenicity of tumor associated antigens

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