Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer.
Mol Cancer Ther
; 7(8): 2464-75, 2008 Aug.
Article
en En
| MEDLINE
| ID: mdl-18723492
ABSTRACT
Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Because as yet no treatments are available that produce a substantial survival benefit for this fatal neoplasia, new therapeutic concepts are urgently required to support cancer standard treatment. In search of tumor-associated gangliosides with therapeutic background, we probed a random collection of cancerous and adjacent normal postoperative tissue samples from 38 patients for the expression of CD75s- and iso-CD75s-gangliosides. We exhaustively analyzed the expression of CD75s-1-ganglioside (IV(6)Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1-ganglioside (IV(3)Neu5Ac-nLc4Cer) by means of immunohistology of cryosections and semiquantitative TLC of tissue lipid extracts combined with mass spectrometry. CD75s-1- and iso-CD75s-1-ganglioside showed an elevated expression in 42% and 66% of the tumors, respectively, indicating a significant association with neoplastic transformation (P = 0.001). Thus, increased expression of CD75s-1- and iso-CD75s-1-gangliosides renders these cell surface molecules promising candidates for oncologic applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (grade >2) suggesting this ganglioside as a potential marker for poor differentiation. The CD75s-specific antitumor drug rViscumin, which represents the recombinant counterpart of the ribosome-inactivating lectin viscumin, has successfully passed clinical phase I trials and provides an opportunity for treating pancreatic cancer. Consequently, if an enhanced expression is existent in malignant tissues, we propose the targeting of CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant treatment of pancreatic malignancies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Sialiltransferasas
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Toxinas Biológicas
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Adenocarcinoma
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Biomarcadores de Tumor
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Proteínas Inactivadoras de Ribosomas Tipo 2
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Gangliósidos
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Antineoplásicos
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Asunto de la revista:
ANTINEOPLASICOS
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania