The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Rik J Scheper - One of the best experts on this subject based on the ideXlab platform.
-
Detection of the Mr 110,000 Lung Resistance-related protein LRP/MVP with monoclonal antibodies
Journal of Histochemistry and Cytochemistry, 2001Co-Authors: Anouk B Schroeijers, Adriana C. L. M. Pijnenborg, Ciro Abbondanza, Erik A.c. Wiemer, George L. Scheffer, Anneke W. Reurs, Rik J ScheperAbstract:The Mr 110,000 Lung Resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug Resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.
-
Lung Resistance-related protein/major vault protein and vaults in multidrug-resistant cancer.
Current opinion in oncology, 2000Co-Authors: George L. Scheffer, Anouk B Schroeijers, Erik A.c. Wiemer, Miguel A. Izquierdo, Rik J ScheperAbstract:Tumor cells that are insensitive to anticancer drugs frequently have a multidrug-resistant (MDR) phenotype. Proteins that can be involved in this phenomenon are transport-associated proteins such as P-glycoprotein, multidrug-Resistance protein 1, breast cancer Resistance protein, and Lung Resistance-related protein (LRP). LRP was identified as the major vault protein (MVP), the main component of multimeric vault particles. With the recent identification of the two minor vault proteins as telomerase-associated protein (TEP1) and vault-poly (ADP-ribose) polymerase (VPARP), and with high-resolution three-dimensional imaging, the composition of vaults is almost unraveled. Although the first direct evidence for a causal relationship between LRP/MVP expression and drug Resistance has been obtained, many functional aspects of vaults in normal physiology and in MDR still need to be clarified. The current clinical data on LRP/MVP detection indicate that LRP/MVP expression can be of high clinical value to predict the response to chemotherapy of several tumor types.
-
The Lung Resistance protein (LRP) predicts poor outcome in acute myeloid leukemia.
Advances in experimental medicine and biology, 1999Co-Authors: Robert Pirker, Rik J Scheper, Gudrun Pohl, R.w. Suchomel, Thomas Stranzl, Ulrich Jäger, Klaus Geissler, Klaus Lechner, Martin FilipitsAbstract:To determine the clinical significance of the Lung Resistance protein (LRP) in acute myeloid leukemia (AML), we have studied LRP expression of leukemic blasts and its association with clinical outcome in patients with de novo AML. LRP expression of leukemic blasts was determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 out of 86 (36%) patients and correlated with white blood cell count (p = 0.01). The complete remission rate of induction chemotherapy was 72% for all treated patients (n = 82). The complete remission rate was 81% for patients without LRP expression but only 55% for patients with LRP expression (p = 0.01). Overall survival and disease-free survival were estimated according to Kaplan-Meier in 82 and 59 patients, respectively. At a median follow-up of 16 months, median overall survival was 17 months for LRP-negative patients but only 8 months for LRP-positive patients (p = 0.006). Disease-free survival was 9 months for LRP-negative patients and 6 months for LRP-positive patients (p = 0.078). Thus LRP predicts for poor outcome indicating that the LRP gene is a clinically relevant drug Resistance gene in AML.
-
Lung Resistance protein (LRP) expression in human normal tissues in comparison with that of MDR1 and MRP
Cancer letters, 1997Co-Authors: Isamu Sugawara, Rik J Scheper, Shin-ichi Akiyama, Shinji ItoyamaAbstract:MDR1 (P-glycoprotein), multidrug Resistance-associated protein (MRP) and Lung Resistance protein (LRP) are associated with multidrug Resistance in various cancer cells. It is known that P-glycoprotein and MRP are also expressed in several normal tissues. However, the exact location of LRP in normal tissues is still unclear. In order to obtain more insight into the physiological role of LRP, its expression in human normal tissues was examined by an immunohistochemical technique, using one monoclonal antibody, LRP-56. Reverse transcriptase-polymerase chain reaction (RT-PCR) was also utilized for several cell lines and fresh-frozen tissues. P-glycoprotein was found to be expressed in the kidney, adrenal, brain vessels, muscle, Lung, pancreas, liver, intestine, placenta and testis. MRP was expressed in the kidney, adrenal, Lung, pancreas, muscle, intestine, thyroid and prostate, and its distribution mostly overlapped with that of P-glycoprotein. Interestingly, MRP was not expressed in the liver. LRP at 110 kDa was expressed in the kidney, adrenal, heart, Lung, muscle, thyroid, prostate, bone marrow and testis. These findings suggest that LRP as well as P-glycoprotein and MRP plays distinct roles in the physiology of various organs.
-
overexpression of the major vault transporter protein Lung Resistance protein predicts treatment outcome in acute myeloid leukemia
Blood, 1996Co-Authors: Alan F List, George L. Scheffer, C Spier, Thomas M Grogan, Cynthia Johnson, Denise J Roe, John P Greer, Steven N Wolff, Henricus J Broxterman, Rik J ScheperAbstract:The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (Lung-Resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.
Michael J. Bishop - One of the best experts on this subject based on the ideXlab platform.
-
the effect of isoflurane halothane sevoflurane and thiopental nitrous oxide on respiratory system Resistance after tracheal intubation
Anesthesiology, 1997Co-Authors: Alec G Rooke, Jongho Choi, Michael J. BishopAbstract:Background:After tracheal intubation, Lung Resistance and therefore respiratory system Resistance (Rrs) routinely increase, sometimes to the point of clinical bronchospasm. Volatile anesthetics generally have been considered to be effective bronchodilators, although there are few human data comparin
-
Effect of prophylactic bronchodilator treatment on Lung Resistance after tracheal intubation.
Anesthesiology, 1994Co-Authors: Hae-keum Kil, G. Alec Rooke, Margaret A. Ryan-dykes, Michael J. BishopAbstract:BACKGROUND After induction of anesthesia, Lung Resistance increases. We hypothesized that prophylactic bronchodilator treatment before tracheal intubation would result in a lower Lung Resistance after placement of the endotracheal tube. METHODS Forty-two adult patients were randomized to receive one of three inhaled medications 1 h before surgery. All patients first underwent pulmonary function tests. Patients then received either inhaled albuterol (360 micrograms) (n = 12), inhaled ipratropium bromide (72 micrograms) (n = 15) or a placebo inhalation (n = 15). Two, 5, and 15 min after tracheal intubation, Lung Resistance was measured using the method of von Neergard and Wirtz. RESULTS Patients who received either bronchodilator had significantly lower Lung Resistance after intubation than those receiving placebo. At 2 min, Lung Resistances were 12.7 +/- 1.4 cmH2O.l-1.s-1 (mean +/- SEM) for the placebo group, 6.4 +/- 3.1 cmH2O.l-1.s-1 for the ipratropium-treated group (P < 0.05 vs. placebo), and 7.2 +/- 0.8 cmH2O.l-1.s-1 for the albuterol-treated group (P < 0.05 vs. placebo). The differences in Lung Resistance persisted through the final measurement at 15 min. Three of fifteen placebo-treated patients developed audible wheezing whereas no patients developed wheezing in either bronchodilator-treated group (P < 0.05 by Fisher's exact test). Although smokers and nonsmokers in the placebo group developed similar Resistances after intubation, bronchodilator treatment resulted in lower Resistance in nonsmokers than in smokers (P < 0.05). CONCLUSIONS Prophylactic treatment with either an inhaled beta 2-adrenergic agonist or an inhaled cholinergic antagonist produced lower Lung Resistance after intubation when compared with an inhaled placebo medication. The effect was more pronounced in nonsmokers than in smokers.
George L. Scheffer - One of the best experts on this subject based on the ideXlab platform.
-
Detection of the Mr 110,000 Lung Resistance-related protein LRP/MVP with monoclonal antibodies
Journal of Histochemistry and Cytochemistry, 2001Co-Authors: Anouk B Schroeijers, Adriana C. L. M. Pijnenborg, Ciro Abbondanza, Erik A.c. Wiemer, George L. Scheffer, Anneke W. Reurs, Rik J ScheperAbstract:The Mr 110,000 Lung Resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug Resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.
-
Lung Resistance-related protein/major vault protein and vaults in multidrug-resistant cancer.
Current opinion in oncology, 2000Co-Authors: George L. Scheffer, Anouk B Schroeijers, Erik A.c. Wiemer, Miguel A. Izquierdo, Rik J ScheperAbstract:Tumor cells that are insensitive to anticancer drugs frequently have a multidrug-resistant (MDR) phenotype. Proteins that can be involved in this phenomenon are transport-associated proteins such as P-glycoprotein, multidrug-Resistance protein 1, breast cancer Resistance protein, and Lung Resistance-related protein (LRP). LRP was identified as the major vault protein (MVP), the main component of multimeric vault particles. With the recent identification of the two minor vault proteins as telomerase-associated protein (TEP1) and vault-poly (ADP-ribose) polymerase (VPARP), and with high-resolution three-dimensional imaging, the composition of vaults is almost unraveled. Although the first direct evidence for a causal relationship between LRP/MVP expression and drug Resistance has been obtained, many functional aspects of vaults in normal physiology and in MDR still need to be clarified. The current clinical data on LRP/MVP detection indicate that LRP/MVP expression can be of high clinical value to predict the response to chemotherapy of several tumor types.
-
overexpression of the major vault transporter protein Lung Resistance protein predicts treatment outcome in acute myeloid leukemia
Blood, 1996Co-Authors: Alan F List, George L. Scheffer, C Spier, Thomas M Grogan, Cynthia Johnson, Denise J Roe, John P Greer, Steven N Wolff, Henricus J Broxterman, Rik J ScheperAbstract:The monoclonal antibody LRP56 recognizes a 110-kD major vault protein (Lung-Resistance protein [LRP]) overexpressed in several P-glycoprotein- negative (Pgp-), multidrug resistant tumor cell lines. To determine the frequency of LRP overexpression, its prognostic significance, and its relation to Pgp, we analyzed bone marrow specimens from 87 consecutive patients with acute leukemia. Diagnoses included de novo acute myeloid leukemia (AML; 21 patients), leukemia arising from an antecedent hematologic disorder or prior cytotoxic therapy (secondary AML; 27 patients), AML in relapse (29 patients), and blast phase of chronic myeloid leukemia (CML-BP; 10 patients). A granular cytoplasmic staining pattern was detected by immunocytochemistry in 32 (37%) cases, including 7 (33%) de novo AML, 13 (48%) secondary AML, 11 (38%) relapsed AML, and 1 of 10 CML-BP. Among 66 evaluable patients with AML, LRP overexpression was associated with an inferior response to induction chemotherapy (P = .0017). Remissions were achieved in 35% of LRP+ patients as compared with 68% of LRP- patients. Although Pgp adversely affected response in univariate analysis (P = .0414), only LRP had independent prognostic significance when compared in a logistic regression model (P = .0046). Differences in remission duration (P = .075) and overall survival (P = .058) approached significance only for LRP. Sequential specimens from remitting patients receiving treatment with the Pgp modulator cyclosporin-A showed emergence of the LRP phenotype despite a decrease or loss of Pgp at the time of treatment failure (P =.0304). Significant associations were observed between LRP and age greater than 55 years (P = .017), Pgp (P = .040), and prior treatment with mitoxantrone (P = .020) but not with CD34. These findings indicate that overexpression of the novel transporter protein LRP is an important predictor of treatment outcome in AML.
Anouk B Schroeijers - One of the best experts on this subject based on the ideXlab platform.
-
Detection of the Mr 110,000 Lung Resistance-related protein LRP/MVP with monoclonal antibodies
Journal of Histochemistry and Cytochemistry, 2001Co-Authors: Anouk B Schroeijers, Adriana C. L. M. Pijnenborg, Ciro Abbondanza, Erik A.c. Wiemer, George L. Scheffer, Anneke W. Reurs, Rik J ScheperAbstract:The Mr 110,000 Lung Resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug Resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.
-
Lung Resistance-related protein/major vault protein and vaults in multidrug-resistant cancer.
Current opinion in oncology, 2000Co-Authors: George L. Scheffer, Anouk B Schroeijers, Erik A.c. Wiemer, Miguel A. Izquierdo, Rik J ScheperAbstract:Tumor cells that are insensitive to anticancer drugs frequently have a multidrug-resistant (MDR) phenotype. Proteins that can be involved in this phenomenon are transport-associated proteins such as P-glycoprotein, multidrug-Resistance protein 1, breast cancer Resistance protein, and Lung Resistance-related protein (LRP). LRP was identified as the major vault protein (MVP), the main component of multimeric vault particles. With the recent identification of the two minor vault proteins as telomerase-associated protein (TEP1) and vault-poly (ADP-ribose) polymerase (VPARP), and with high-resolution three-dimensional imaging, the composition of vaults is almost unraveled. Although the first direct evidence for a causal relationship between LRP/MVP expression and drug Resistance has been obtained, many functional aspects of vaults in normal physiology and in MDR still need to be clarified. The current clinical data on LRP/MVP detection indicate that LRP/MVP expression can be of high clinical value to predict the response to chemotherapy of several tumor types.
Erik A.c. Wiemer - One of the best experts on this subject based on the ideXlab platform.
-
Detection of the Mr 110,000 Lung Resistance-related protein LRP/MVP with monoclonal antibodies
Journal of Histochemistry and Cytochemistry, 2001Co-Authors: Anouk B Schroeijers, Adriana C. L. M. Pijnenborg, Ciro Abbondanza, Erik A.c. Wiemer, George L. Scheffer, Anneke W. Reurs, Rik J ScheperAbstract:The Mr 110,000 Lung Resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug Resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.
-
Lung Resistance-related protein/major vault protein and vaults in multidrug-resistant cancer.
Current opinion in oncology, 2000Co-Authors: George L. Scheffer, Anouk B Schroeijers, Erik A.c. Wiemer, Miguel A. Izquierdo, Rik J ScheperAbstract:Tumor cells that are insensitive to anticancer drugs frequently have a multidrug-resistant (MDR) phenotype. Proteins that can be involved in this phenomenon are transport-associated proteins such as P-glycoprotein, multidrug-Resistance protein 1, breast cancer Resistance protein, and Lung Resistance-related protein (LRP). LRP was identified as the major vault protein (MVP), the main component of multimeric vault particles. With the recent identification of the two minor vault proteins as telomerase-associated protein (TEP1) and vault-poly (ADP-ribose) polymerase (VPARP), and with high-resolution three-dimensional imaging, the composition of vaults is almost unraveled. Although the first direct evidence for a causal relationship between LRP/MVP expression and drug Resistance has been obtained, many functional aspects of vaults in normal physiology and in MDR still need to be clarified. The current clinical data on LRP/MVP detection indicate that LRP/MVP expression can be of high clinical value to predict the response to chemotherapy of several tumor types.
