Expression of the mdr1 gene in bone and soft tissue sarcomas of adult patients

Stein, Ulf; Wunderlich, V.; Haensch, Wolfgang; Schmidt-Peter, P

doi:10.1016/0959-8049(93)90457-q

Cited by 39 publications

(23 citation statements)

References 10 publications

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“…However a positive correlation with cellularity was found. Spindle-cell tumors, such as leiomyosarcoma and malignant neurogenic tumor, showed a higher frequency of P-gp expression in the current cases, which confirmed the previous study showing the expression of P-gp at the mRNA level: 66 % among all soft-tissue sarcomas, 100 % in leiomyosarcomas, and 88 % in neurofibrosarcomas (Stein et al 1993). By contrast, the frequency rate of P-gp expression was low (29 %:4/14) in the myxoid and epithelioid tumors.…”

Section: Discussionsupporting

confidence: 94%

P-glycoprotein expression in soft-tissue sarcomas

Nakanishi

Myoui

Ochi

et al. 1997

J Cancer Res Clin Oncol

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Multidrug resistance (MDR) is an important problem in chemotherapy for neoplastic disease. In humans. MDR is mainly mediated by P-glycoprotein (P-gp) a product of the MDRI gene, which acts as a transmembrane protein pump and eliminates chemotherapeutic agents from the cells. Expression of P-gp was immunohistochemically studied by using two monoclonal antibodies, JSB-1 and C-219, on paraffin-embedded sections from 55 patients with soft-tissue sarcoma. The histological diagnosis of tumors was malignant fibrous histiocytoma in 24 cases, liposarcoma in 9, synovial sarcoma in 7, malignant neurogenic tumors in 6, leiomyosarcoma in 5, others in 4. The histological grade was determined on the basis of criteria previously proposed by us. Out of 55 cases, 34 (62%) were positive for P-gp expression. There was a significant difference in P-gp expression between high-grade (90%) and intermediate and low-grade tumors (46%) (P < 0.005). Tumors expressing P-gp had a less favorable prognosis than P-gp-negative tumors in the high- and intermediate-grade tumors. The current study demonstrated that the estimation of P-gp expression could be used to select appropriate therapeutic modalities.

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Section: Discussionsupporting

confidence: 94%

P-glycoprotein expression in soft-tissue sarcomas

Nakanishi

Myoui

Ochi

et al. 1997

J Cancer Res Clin Oncol

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“…Other authors have examined the validity of assays with rhodamine 123 accumulation or ef¯ux with or without PSC 833 to get an impression of functional resistance in tumor cells. These methods enable Stein et al [25] examined Pgp expression in bone and soft tissue sarcomas of adult patients in relapse and noted a 52% positivity rate among all chemotherapy-treated patients. In our study, 50% of the tumors expressed more Pgp in relapse than at diagnosis, and 30% expressed less.…”

Section: Discussionmentioning

confidence: 98%

Effect of P-Glycoprotein Expression on Outcome in the Ewing Family of Tumors

Perri

Fogel

Mor

et al. 2001

Pediatric Hematology and Oncology

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This study was designed to determine the prognostic significance of multidrug resistance, mediated by P-glycoprotein (Pgp) expression, in Ewing sarcoma. The clinical and laboratory features, treatment protocol, and outcome of 75 patients with Ewing sarcoma or peripheral neuroectodermal tumor treated between 1972 and 1997 were reviewed. Pgp expression was tested with the monoclonal antibody JSB-1. Thirty-four (64%) of the 53 tissue samples from untreated patients stained positive for Pgp. Progression-free and overall survival were 44 and 59%, respectively, in patients with negative findings, and 28 and 41% in those with positive findings; neither difference was significant. Of the 12 relapsed patients, 6 (50%) expressed more Pgp after chemotherapy than at diagnosis and 4 (33%) expressed less. Within these subgroups, 5 out of 6 and 3 out of 4 died from the disease. No correlation was found between Pgp and known prognostic factors of Ewing tumors. Pgp expression is probably an intrinsic factor of Ewing tumors but has no correlation to prognosis.

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“…Experimentally, many candidate MDR-modifying agents have been found, [4][5][6][7][8][9][10] but only a few have clinical potential, for example, verapamil, 4) FK506 5) and MS-209. 6,8) Those agents can modify the MDR associated with P-glycoprotein, [15][16][17][18] but not other drug resistances associated with the MRP/GS-X pump or glutathione. 19,20) Recently, we have found that AO with PDT has a strong cytocidal effect on the chemosensitive mouse osteosarcoma cell line, MOS.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic Inactivation with Acridine Orange on a Multidrug‐resistant Mouse Osteosarcoma Cell Line

Kusuzaki

Minami

Takeshita

et al. 2000

Japanese Journal of Cancer Research

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Overcoming multidrug resistance (MDR) is an urgent issue to improve the prognosis of osteosarcoma patients. In this study, we undertook to clarify the effect of photodynamic therapy (PDT) with acridine orange (AO) on the MDR mouse osteosarcoma (MOS/ADR1) cell line, by comparing the outcome with the effect on a chemosensitive osteosarcoma (MOS) cell line. Cultured cells of MOS and MOS/ADR1 cell lines were exposed to AO at various concentrations for various times, followed by long-or short-term (10 or 1 min) illumination with blue light (466.5 nm) for excitation. Key words: Multidrug resistance -Osteosarcoma -Acridine orange -Photodynamic therapyThere is no doubt that chemotherapy is the most important treatment for improving the prognosis of patients with osteosarcoma. However, about 30% of these patients have been found to be resistant to chemotherapy.1-3) Therefore, overcoming multidrug resistance (MDR) is an urgent issue in the management of osteosarcomas. There have been many studies conducted on the modification of MDR in various tumor cell lines, [4][5][6][7][8][9][10] but none is clinically applicable at present. Recently, we have found that photodynamic therapy (PDT) with acridine orange (AO) has a strong cytocidal effect on a chemosensitive mouse osteosarcoma cell line. We conducted the present study to clarify the effect of PDT with AO (AO-PDT) on an MDR mouse osteosarcoma cell line, in comparison with the effect on the chemosensitive cell line. MATERIALS AND METHODS AO-PDT with mouse osteosarcoma cellsThe MDR mouse osteosarcoma cell line (MOS/ADR1) 11) was used in this study. This cell line was established from a radiationinduced mouse osteosarcoma cell line (MOS) 12) by single cell culture after exposure to six-pulsed, stepwise increments of doxorubicin (DOX) concentration ranging from 0.01 to 1 µg/ml. The MOS cells were chemosensitive to most anticancer agents, but the MOS/ADR1 cells showed a classical MDR phenotype with overexpression of P-glycoprotein; they were resistant to DOX, vincristine, vinblastine, etoposide, mitomycin C, and actinomycin D. 11)DOX binding assay demonstrated that more than 90% of the MOS/ADR1 cells were negative for nuclear DOX fluorescence. 11)We cultured 2×10 5 MOS/ADR1 cells and MOS cells in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal calf serum (FCS) at 37°C under a 5% CO 2 atmosphere, using 6-well plates. At 24 h, in a preconfluent cell growth condition, the medium of the wells was replaced with 0.025, 0.05, 0.1, 1.0, or 2.0 µg/ml AO containing DMEM. After 15-min exposure to AO, 1400 lx blue light selected through an interference filter (466.5 nm) from a 150-W halogen lamp source (Nikon Fibertrans 2; Nikon, Tokyo) was employed to illuminate the cell surface, to excite AO bound to the cells, using a double fiber tube system (PDT with AO: AO-PDT). This blue light has low energy and does not generate heat. In the continuous AO exposure study, after illumination for 10 min, both tumor cell groups were further cultured in an AO-containing medium. In the fl...

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Expression of the mdr1 gene in bone and soft tissue sarcomas of adult patients

Cited by 39 publications

References 10 publications

P-glycoprotein expression in soft-tissue sarcomas

P-glycoprotein expression in soft-tissue sarcomas

Effect of P-Glycoprotein Expression on Outcome in the Ewing Family of Tumors

Photodynamic Inactivation with Acridine Orange on a Multidrug‐resistant Mouse Osteosarcoma Cell Line

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