The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells

Zheng, Min; Wang, Hao; Zhang, Hao-Bo; Ou, Qishui; Shen, Baihua; Li, Ningli; Yu, Bo

doi:10.1007/s004320050286

Cited by 23 publications

(13 citation statements)

References 20 publications

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“…Immunostaining does not necessarily distinguish the accumulation of abnormal p53 protein due to gene mutation from the overexpression of normal protein (Lenz, Hayashi et al, 1998, Momand, ANNALS OF Cancer Research andTherapy Zambetti et al, 1992). In fact, it has been reported that mutation or disruption of the p53 gene is associated with low chemosensitivity to 5-FU (Bunz, Hwang et al, 1999, Zheng, Wang et al, 1999. p53-independent regulation of apoptosis in colorectal cancers has been shown in the previous in vitro studies (Bracey, Miller et al, 1995).…”

Section: Discussionmentioning

confidence: 90%

“…p53 protein normally functions as either an initiator of repair of the damaged sense DNA or a trigger of the apoptotic pathway if a sufficient level of damage takes place within the cell (Harwood, Frazier et al, 1996, Leonard, Canman et al, 1995. Inactivation or mutation of the p53 gene is allegedly associated with the enhancement of cellular resistance to DNA-damaging agents (Benhattar, Cerottini et al, 1996, Bunz, Hwang et al, 1999, Lowe, Schmitt et al, 1993, Zheng, Wang et al, 1999. It has been suggested that the p53 gene assay can be employed to predict the responsiveness of cancer to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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IMMUNOHISTOCHEMICAL DEMONSTRATION OF THYMIDYLATE SYNTHASE (TS), p53 PROTEIN AND BCL-XL PROTEIN IN COLORECTAL CANCER WITH PREOPERATIVE PERORAL CHEMOTHERAPY

Kamoshida

Matsuoka

Matsuyama

et al. 2003

ACRT

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of apoptosis, p53 protein, selection of patients, thymidylate synthase (TS). AbstractHigh expression of thymidylate synthase (TS), p53 protein and bcl-XL protein has been suggested to be associated with chemoresistance of colorectal malignancies. The significance of TS, p53 protein and bcl-XL protein as predictive parameters of effects of 5-fluorouracil (5-FU)-based chemotherapy on colorectal cancers was evaluated.Immunoperoxidase staining of TS, p53 protein and bcl-XL protein was performed on formalin-fixed, paraffin-embedded, 1opsied and resected specimens from 37 patients with advanced colorectal cancers, preoperatively treated with 5-FU derivatives per os. When more than one third of the cancer cells were stained, the lesions were considered high for antigen expression. High TS expression in the resected tumors was seen in 23 (74%) of 31 histologic non-responders but none in six responders. TS expression in preoperative biopsies and resected specimens was concordant in 80% of cases when two or more biopsy specimens were available.The rate of high TS expression was comparable in the control non-treated group. There was no difference between chemotherapeutic effects and the expression of p53 protein or bcl-XL protein.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

IMMUNOHISTOCHEMICAL DEMONSTRATION OF THYMIDYLATE SYNTHASE (TS), p53 PROTEIN AND BCL-XL PROTEIN IN COLORECTAL CANCER WITH PREOPERATIVE PERORAL CHEMOTHERAPY

Kamoshida

Matsuoka

Matsuyama

et al. 2003

ACRT

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“…Clinical studies have revealed higher resistance to fluoropyrimidine therapy of tumors expressing p53 mutants (Benhattar et al, 1996;Cabelguenne et al, 2000;Zheng et al, 1999). In several cases such effects of p53 mutants were attributed to dominant-negative suppression of the wild type p53 activity that resulted in abrogation of p53-induced apoptosis (Bunz et al, 1999), and an increase in activity of the MDR1 gene (Bottini et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil

et al. 2002

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“…[160][161][162][163][164][165][166][167][168] Here, we will only briefly report on the putative role of p53 with respect to 5-FU efficacy, as this relationship has been most extensively studied. Mutations in the p53 gene and p53 overexpression have been associated with 5-FU chemoresistance both in vitro [169][170][171] and in vivo in colorectal, 124,[172][173][174][175] head and neck, 176,177 and breast cancer. 178 However, results in some other studies are less unequivocal.…”

Section: Jg Maring Et Almentioning

confidence: 99%

Genetic factors influencing Pyrimidine-antagonist chemotherapy

et al. 2005

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Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of these pyrimidine prodrugs into active compounds. Interindividual variation in the activity of metabolising enzymes can affect the extent of prodrug activation and, as a result, act on the efficacy of chemotherapy treatment. Genetic factors at least partly explain interindividual variation in antitumour efficacy and toxicity of pyrimidine antagonists. In this review, proteins relevant for the efficacy and toxicity of pyrimidine antagonists will be summarised. In addition, the role of germline polymorphisms, tumourspecific somatic mutations and protein expression levels in the metabolic pathways and clinical pharmacology of these drugs are described. Germline polymorphisms of uridine monophosphate kinase (UMPK), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and methylene tetrahydrofolate reductase (MTHFR) and gene expression levels of OPRT, UMPK, TS, DPD, uridine phosphorylase, uridine kinase, thymidine phosphorylase, thymidine kinase, deoxyuridine triphosphate nucleotide hydrolase are discussed in relation to 5-FU efficacy. Cytidine deaminase (CDD) and 5 0 -nucleotidase (5NT) gene polymorphisms and CDD, 5NT, deoxycytidine kinase and MRP5 gene expression levels and their potential relation to dFdC and ara-C cytotoxicity are reviewed.

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The influence of the p53 gene on the in vitro chemosensitivity of colorectal cancer cells

Abstract: Routine assessment of p53 status may be helpful in selecting patients with the wildtype p53 gene, who have a predictably better response to chemotherapy.

Cited by 23 publications

References 20 publications

IMMUNOHISTOCHEMICAL DEMONSTRATION OF THYMIDYLATE SYNTHASE (TS), p53 PROTEIN AND BCL-XL PROTEIN IN COLORECTAL CANCER WITH PREOPERATIVE PERORAL CHEMOTHERAPY

IMMUNOHISTOCHEMICAL DEMONSTRATION OF THYMIDYLATE SYNTHASE (TS), p53 PROTEIN AND BCL-XL PROTEIN IN COLORECTAL CANCER WITH PREOPERATIVE PERORAL CHEMOTHERAPY

Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil

Genetic factors influencing Pyrimidine-antagonist chemotherapy

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