Expression of MDR1 and GST-π in human soft tissue sarcomas: Relation to drug resistance and biological aggressiveness

Toffoli, Giuseppe; Frustaci, S.; Tumiotto, Loretta; Talamini, Renato; Gherlinzoni, F.; Picci, Piero; Boiocchi, Mauro

doi:10.1093/oxfordjournals.annonc.a058073

Cited by 45 publications

(16 citation statements)

References 24 publications

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“…Three of these six reports study P-gp expression only by Western blotting or immunohistochemistry (Gerlach et al, 1987;Chan et al, 1990;Schlaifer et al, 1990), and three study MDR1 mRNA expression only by slot or dot blot hybridisation (Goldstein et al, 1989;Tawa et al, 1990;Toffoli et al, 1992). Our results do not agree with the findings of these other authors: they observed a more frequent overexpression of the MDR1 gene in the tumour samples they studied.…”

Section: Resultscontrasting

confidence: 77%

“…At present there are only six reports reporting MDR1 expression in human sarcomas, and findings are conflicting (Gerlach et al, 1987;Goldstein et al, 1989;Chan et al, 1990;Tawa et al, 1990;Schlaifer et al, 1990;Toffoli et al, 1992). Three of these six reports study P-gp expression only by Western blotting or immunohistochemistry (Gerlach et al, 1987;Chan et al, 1990;Schlaifer et al, 1990), and three study MDR1 mRNA expression only by slot or dot blot hybridisation (Goldstein et al, 1989;Tawa et al, 1990;Toffoli et al, 1992).…”

Section: Resultsmentioning

confidence: 99%

“…Our results do not agree with the findings of these other authors: they observed a more frequent overexpression of the MDR1 gene in the tumour samples they studied. Table II (Toffoli et al, 1992), important discrepancies still remain which could be explained by the fact that we did not use the same probe nor apply the same dilutions of total RNA samples, and did not use the same cell line for positive control. So it is very difficult to compare these different results, and discrepancies are obvious.…”

Section: Resultsmentioning

confidence: 99%

“…It would be advisable to study the same samples with the same methods, and for different investigators to study simultaneously MDR1 mRNA/P-glycoprotein expression. However, all investigators agree on the fact that the constitutive expression of the MDR1 gene has no effect on the primary response in untreated sarcomas (Chan et al, 1990;Toffoli et al, 1992). The acquisition of high MDR1 mRNA/P-gp expression would be predictive of further response to chemotherapy in the course of the disease after drug treatment.…”

Section: Resultsmentioning

confidence: 99%

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Expression of MDR1/P glycoprotein in human sarcomas

Vergier

Cany²,

Bonnet³

et al. 1993

Br J Cancer

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Summary Conflicting reports of MDR1 gene expression in human tumours are observed according to whether studies are performed at the mRNA or P-glycoprotein level. We have investigated this expression in 22 clinically drug-resistant sarcomas at the mRNA level by Northern blot (NB), Dot blot (DB), in situ hybridisation (ISH), and at the protein level by immunohistochemistry (IHC) using three monoclonal antibodies (MoAbs): C219, JSB1, MRK16. Increased MDR1 mRNA expression was detected by NB, DB, and ISH in 1/22 sarcoma (an Ewing's sarcoma). ISH was perfectly correlated with DB hybridisation and confirmed the expression of tumoral cells alone. Specific staining of 100% of tumoral cells was obtained with the three MoAbs in the same sarcoma. Expression in tumoral cells of 12 other sarcomas was detected with MRK16, and positive staining of stromal cells with both C219 (1/22) and MRK16 (8/22) was observed. This study confirms that MDR1 overexpression occurs in human sarcomas but is not the principal mechanism of drug-resistance. Furthermore, positivity with one antibody does not necessarily imply the presence of P glycoprotein (P-gp) and a disparity may exist between the levels of P-gp and its mRNA in the same sample. So care must be taken in interpreting results and more sensitive techniques such as the polymerase chain reaction (PCR) could prove useful.

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Section: Resultscontrasting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Expression of MDR1/P glycoprotein in human sarcomas

Vergier

Cany²,

Bonnet³

et al. 1993

Br J Cancer

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“…In breast cancer, as for other cancers, colon, stomach, pancreas, bladder, lung, head and neck, ovary, and cervix, the expression of GST pi is highly increased as compared to benign tissues (Niitsu et al, 1989;Randall et al, 1990;Kantor et al, 1991;Satta et al, 1992;Toffoli et al, 1992;Green et al, 1993;Inoue et al, 1995;Bentz et al, 2000;Tratche et al, 2002;Simic et al, 2005;Arai et al, 2006). Of particular interest, Hafez et al have showed that GSTP1 gene has been highly hypermethylated in TNBC cases as compared to non-TNBC cases.…”

Section: Genetic Aspects Of Tnbcmentioning

confidence: 99%

Recent Progress in Triple Negative Breast Cancer Research

Mouh¹,

Mzibri²,

Slaoui³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Triple-negative breast cancer (TNBC) is defined as a type of breast carcinoma that is negative for expression of oestrogene and progesterone hormone receptors (ER, PR) and HER2. This form of breast cancer is marked by its aggressiveness, low survival rate and lack of specific therapies. Recently, important molecular characteristics of TNBC have been highlighted and led to the identification of some biomarkers that could be used in diagnosis, as therapeutic targets or to assess the prognosis. In this review, we summarize recent progress in TNBC research focusing on the genetic and epigenetic alterations of TNBC and the potential use of these biomarkers in the targeted therapy for better management of TNBC.

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Flow cytometric analysis of P-glycoprotein expression and drug efflux in human soft tissue and bone sarcomas

et al. 1997

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Twenty‐two fresh surgical specimens of human sarcomas (soft tissue and bone) from 20 patients were analyzed by flow cytometry for the expression of drug resistance‐related P‐glycoprotein (P‐gp) and cellular daunorubicin (DNR) accumulation with or without the presence of DNR efflux blockers. Single‐cell suspensions prepared from the tumor specimens were analyzed by dual‐color flow cytometry after reaction with MRK‐16 (anti‐P‐gp) and anti‐CD45 (pan‐leukocyte) antibodies. MRK‐16 reactivity of tumor cells was evaluated after exclusion of CD45‐positive cells by electronic gates. Parallel samples were incubated with DNR alone or in combination with DNR efflux blockers, verapamil (VPL), or dipyridamole (DPD) for determination of cellular DNR accumulation and the effect of the efflux blockers. Extensive heterogeneity was observed in both P‐gp expression and DNR accumulation of the tumor specimens examined. Eight of the 22 tumor specimens had significant numbers of P‐gp‐positive cells. In three of the eight P‐gp‐positive tumors, cellular DNR accumulation was significantly increased by co‐incubation with the efflux blockers VPL or DPD. These results indicate that both quantitative and functional analysis of P‐gp expression may be essential in determining the cellular drug resistance phenotype of tumor cells and its correlation with therapeutic outcome. Cytometry 30:197–203, 1997. © 1997 Wiley‐Liss, Inc.

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Expression of MDR1 and GST-π in human soft tissue sarcomas: Relation to drug resistance and biological aggressiveness

Cited by 45 publications

References 24 publications

Expression of MDR1/P glycoprotein in human sarcomas

Expression of MDR1/P glycoprotein in human sarcomas

Recent Progress in Triple Negative Breast Cancer Research

Flow cytometric analysis of P-glycoprotein expression and drug efflux in human soft tissue and bone sarcomas

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