Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, recent advances in the clinical therapy of osteosarcoma, including results from the European Osteosarcoma Intergroup trial demonstrating the efficacy of a short intensive two drug protocol are discussed as well the evolving role of ifosfamide. Biologically, the area of interest on chromosome 3q, which may contain an osteosarcoma tumor suppressor gene, is being narrowed, and several promising new therapeutic approaches including tumor vaccine have been explored. In chondrosarcoma research, abnormalities in hereditary multiple exostoses genes, which encode protein products essential for normal cartilage development, and a potential mechanism for the characteristic chemotherapy resistance of cartilaginous tumors (overexpression of P-glycoprotein) have been described. Surgical advances include testing of total en bloc spondylectomy for vertebral tumors as well as a noninvasively extendable long bone endoprosthesis. Finally, new insights in diagnostic imaging, including the evolving role of 201Tl, 99mTc-MIBI (methoxyisobutylisonitrile), and newer variations on magnetic resonance imaging are reviewed.
 ...
PMID:Osteosarcoma and other bone cancers. 970

Chondrosarcomas are alleged to be resistant to chemotherapy. A retrospective review of our experience primarily with dedifferentiated chondrosarcomas treated with chemotherapy was performed to reevaluate the efficacy of chemotherapy for this tumor. There were 18 patients: 14 stage IIB and four stage III. Seventeen patients had dedifferentiated chondrosarcoma. The median age at diagnosis was 57 years. Fourteen of the patients underwent wide excision of the tumor, two underwent amputation, and two had no surgery. The femur and the pelvis were the most common locations of the primary tumor. Chemotherapy for 11 of the patients consisted of cisplatin and doxorubicin. Survival was analyzed with the Kaplan-Meier method; the median survival was 12 months. The hypothesis that chondrosarcomas express P-glycoprotein was tested. Expression of P-glycoprotein was evaluated by immunostaining with use of the C494 and C219 antibodies on 41 benign and malignant cartilage tumors, six of which were from the patients in the chemotherapy group. Immunostaining revealed that 37 of 41 cartilage tumors expressed P-glycoprotein. The rate of survival of patients with high-grade chondrosarcoma treated with chemotherapy is poor. P-glycoprotein expression is common in benign and malignant cartilage lesions. The lack of response to chemotherapy may be related to the expression of P-glycoprotein.
 ...
PMID:Chemotherapy and P-glycoprotein expression in chondrosarcoma. 982 Feb 82

We report on two chondrosarcoma cell lines, FS and AQ, that may be used as models of multidrug resistance in chondrosarcoma. Multidrug resistance-1 expression was assayed with reverse transcription-polymerase chain reaction. Immunostaining for the multidrug resistance-1 product, P-glycoprotein, was performed with the monoclonal antibody C494. Intracellular levels of doxorubicin were measured by fluorescent emission at 590 nm after 1 hour of incubation with the agent and again after 1, 2, and 4-hour washout periods. Chemosensitivity was assayed by staining micropellet cultures of AQ and FS cells with fluorescein acetate before and after the cells were exposed to varying doses of doxorubicin for 48 hours. Cytotoxicity was assessed by comparison of computer-processed images before and after treatment. The FS cell line was positive for multidrug resistance-1 expression, stained heavily for P-glycoprotein, and had significantly lower intracellular levels of doxorubicin than the AQ cell line, which was negative for multidrug resistance-1 and P-glycoprotein. Chemosensitivity testing showed that the FS cell line was significantly more resistant to doxorubicin than was the AQ cell line at all doses tested. Our results show that multidrug resistance-1 expression in a human chondrosarcoma cell line results in resistance to doxorubicin in vitro.
 ...
PMID:Multidrug resistance-1 and p-glycoprotein in human chondrosarcoma cell lines: expression correlates with decreased intracellular doxorubicin and in vitro chemoresistance. 1063 61

A human chondrosarcoma cell line, CS-1, was treated successively with increasing concentrations of the marine chemotherapeutic Ecteinascidin-743 (ET-743), yielding a variant cell line displaying a significant degree of resistance to the cytotoxic action of this drug. Various experiments were performed to discern molecular aberrations between the parent and resistant cell line, and also identify potential molecular markers indicative of drug resistance. Although no significant differences in the levels of membrane transporters such as P-glycoprotein or multidrug resistance protein 1 (MRP1) were detected, the cell migratory ability of the ET-743-resistant cell variant was reduced, as was its attachment capability to gelatin-coated cell culture dishes. Staining of the actin-containing cytoskeleton with fluorescent-labeled phalloidin revealed marked differences in the cytoskeleton architecture between the parent and ET-743-resistant CS-1 cell lines. Comparison of serum-free conditioned medium from both cell lines showed conspicuous differences in the levels of several proteins, including a quartet of high molecular weight proteins (> or =140 kDa). The protein sequences of two of these high molecular weight proteins, present at significantly higher concentrations in conditioned medium obtained from the parent cell line, corresponded to subunits of types I and IV collagen. Analysis of type I collagen alpha1 chain mRNA revealed a significantly lower level in the ET-743-resistant CS-1 cell line. Thus, prolonged exposure to ET-743 may cause changes in cell function through cytoskeleton rearrangement and/or modulation of collagen levels.
 ...
PMID:Ecteinascidin-743 drug resistance in sarcoma cells: transcriptional and cellular alterations. 1463 96

Heat shock proteins (HSPs) are involved in tumour immunity, and are correlated with survival and drug resistance in numerous types of cancer. The present study investigated the expression of HSPs and multiple drug resistance (MDR) in human chondrosarcoma. HSP and P-glycoprotein (the MDR1 gene product) expression was evaluated by immunohistochemical analysis of paraffin-embedded sections obtained from 37 patients with chondrosarcoma (19 male and 18 female; aged 33-85 years; mean age, 48.5 years). HSP73 and 90 were significantly overexpressed in patients with local recurrence: HSP73 was expressed in 7/7 patients (100%) with local recurrence and 9/18 patients (50%) without recurrence (P<0.02), while HSP90 was expressed in all patients with recurrence but only 8/18 (44%) without recurrence (P<0.02). A marked association was also identified between HSP expression and survival. HSP72 and 73 were significantly overexpressed in tumours from patients who succumbed to the disease (all positive for HSP72 and 73; P<0.05). No differences were observed between HSP27, 73 or 90-positive or -negative tumours according to age or gender. In addition, HSP72 expression was correlated with differentiation of the tumours (P<0.02). These results indicate that HSP72, 73 and 90 may function as novel prognostic markers for chondrosarcoma, and initiate further studies regarding the use of such markers for the identification of patients with poor prognosis.
 ...
PMID:Recurrence rate and progression of chondrosarcoma is correlated with heat shock protein expression. 2687 Feb 41