Proteomics for studying cancer cells and the development of chemoresistance

Hütter, Gero; Sinha, Pranav

doi:10.1002/1615-9861(200110)1:10<1233::aid-prot1233>3.0.co;2-2

Cited by 42 publications

(8 citation statements)

References 98 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of differential protein expression studies of drug-resistant cancers have also been carried out (for a review, see Ref. 51), but again the roles of most of the proteins identified by these studies in resistance remain unclear. In one study, the protein MGr1-Ag was found to be overexpressed in multidrug-resistant gastric cancer cells.…”

Section: Fig 4 Comparison Of Protein Profiles and Maldi-tof Identifmentioning

confidence: 99%

Proteome Mapping of the Protozoan Parasite Leishmania and Application to the Study of Drug Targets and Resistance Mechanisms

Drummelsmith

Brochu

Girard

et al. 2003

Molecular & Cellular Proteomics

126

114

View full text Add to dashboard Cite

Leishmania is a protozoan parasite responsible for significant morbidity and mortality worldwide. Few parasites have been subjected to proteomic analysis to date, but a genome sequencing project for Leishmania major is currently underway, making these studies possible. Here we present a high resolution proteome for L. major comprising almost 3700 spots, making it the most complete two-dimensional gel representation of a parasite proteome generated to date. We have identified a number of landmark proteins by mass spectrometry and show that several of these are valid for the related species Leishmania donovani infantum. We have also observed several forms and fragments of ␣-and ␤-tubulins and show that the number and amount of these fragments increase with the age of the parasite culture. Trypanothione reductase (TRYR), which replaces glutathione reductase in trypanosomatid parasites, is an essential protein specific to these parasites and as such is under considerable scrutiny as a drug target. Two-dimensional gel analysis of a L. major strain overexpressing TRYR revealed increased amounts of five spots, all at the predicted molecular weight for TRYR and differing by 0.08 pH units in pI. Mass spectrometry identified four of these as TRYR, leading to the novel suggestion that it could be posttranslationally modified. Finally quantitative comparative analysis of a methotrexate-resistant mutant of L. major generated in vitro found that a known primary resistance mediator, the pteridine reductase PTR1, was overexpressed. This constitutes the first proteomic analysis of drug resistance in a parasite and also the clearest identification of a primary drug resistance mechanism using this approach. Together these results provide a framework for further proteomic studies of Leishmania species and demonstrate that these tools are valuable for the essential study of potential drug targets and drug resistance mechanisms.

show abstract

Section: Fig 4 Comparison Of Protein Profiles and Maldi-tof Identifmentioning

confidence: 99%

Proteome Mapping of the Protozoan Parasite Leishmania and Application to the Study of Drug Targets and Resistance Mechanisms

Drummelsmith

Brochu

Girard

et al. 2003

Molecular & Cellular Proteomics

126

114

View full text Add to dashboard Cite

show abstract

“…Modalities that allow realtime, in-vivo analysis of transporter function may prove useful in determining in-situ activity of the resistance mechanism in question (Luker et al 1997). Finally, the advent of proteomics and other genome-scale approaches for the global analysis of cancer biology may accelerate the identification and characterization of previously unrealized mechanisms responsible for tumour drug resistance (Hutter & Sinha 2001).…”

Section: Current Researchmentioning

confidence: 99%

A review of selected anti-tumour therapeutic agents and reasons for multidrug resistance occurrence

Sawicka

Kalinowska

Skierski

et al. 2004

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

It is assumed that proteins from the ABC family (i.e., glycoprotein P (Pgp)) and a multidrug resistance associated protein (MRP) play a main role in the occurrence of multidrug resistance (MDR) in tumour cells. Other factors that influence the rise of MDR are mechanisms connected with change in the effectiveness of the glutathione cycle and with decrease in expression of topoisomerases I and II. The aim of this review is to characterize drugs applied in anti-tumour therapy and to describe the present state of knowledge concerning the mechanisms of MDR occurrence, as well as the pharmacological agents applied in reducing this phenomenon.

show abstract

“…The translational research can provide the new tools for the clinicians to be used in patients and for assessment of their impact. Recent proteomics studies in pancreatic cancer have identified proteins differentially regulated in cancer samples and have led to the discovery of several candidate biomarkers (4)(5)(6)(7)(8). Currently one pilot study has reported of establishing circulating tumor cells as a biomarker for pancreatic cancer (9).…”

mentioning

confidence: 99%

p38β MAP Kinase as a Therapeutic Target for Pancreatic Cancer

et al. 2012

View full text Add to dashboard Cite

† First authors (both have equal contribution).Pancreatic cancer is very difficult to diagnose in its early stage. Molecular marker and imaging have not proven to be accurate modalities for screening of pancreatic cancer. This study aims to develop p38b as a protein marker for pancreatic cancer and to design peptide inhibitor against the same. The serum p38b level of pancreatic cancer (n = 35; 5.06 lg ⁄ mL) was twofold higher compared to that of the chronic pancreatitis (n = 10; 2.92 lg ⁄ mL) and matched normal control (n = 10; 2.86 lg ⁄ ml) (p < 0.0005). Peptide inhibitors were designed to inhibit the activity of p38b and the kinetic assay had shown the dissociation constant, (K D ) to be 3.16 · 10 )8 M and IC 50 , 25 nM by Surface Plasmon Resonance (SPR) and EnzymeLinked Immunosorbent Assay (ELISA), respectively. The peptide inhibitor also significantly reduced viability and induced cytotoxicity in Human Pancreatic carcinoma epithelial-like cell line (PANC-1) cells.

show abstract

Proteomics for studying cancer cells and the development of chemoresistance

Cited by 42 publications

References 98 publications

Proteome Mapping of the Protozoan Parasite Leishmania and Application to the Study of Drug Targets and Resistance Mechanisms

Proteome Mapping of the Protozoan Parasite Leishmania and Application to the Study of Drug Targets and Resistance Mechanisms

A review of selected anti-tumour therapeutic agents and reasons for multidrug resistance occurrence

p38β MAP Kinase as a Therapeutic Target for Pancreatic Cancer

Contact Info

Product

Resources

About