Drug resistance in clinical oncology and hematology:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Philadelphia [u.a.]
Saunders
1995
|
| Schriftenreihe: | Hematology, oncology clinics of North America
9,2 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XII S., S. 239 - 511 Ill., graph. Darst. |
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Datensatz im Suchindex
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DRUG RESISTANCE IN CLINICAL
ONCOLOGY AND HEMATOLOGY CONTENTS
Preface xi
George A. Fisher and Branimir I. Sikic
P glycoprotein in Adult Hematologic Malignancies 239
Jean Pierre Marie
Hematologic malignancies are the most extensively studied tu¬
mors for drug resistance, but wide discrepancies within multi
drug resistance (MDR1) gene expression in the same tumors
underlined the absence of "gold standard" techniques. In acute
myelogeneous leukemia, several studies showed that MDR1 gene
overexpression is correlated with treatment failure. Although not
clearly demonstrated in other hematologic malignancies, tumoral
cells from already treated patients usually expressed P glycopro¬
tein more frequently.
P glycoprotein in Adult Solid Tumors: Expression and
Prognostic Significance 251
John C. Leighton, Jr and Lori J. Goldstein
Several potential mechanisms of chemotherapy resistance have
been identified in adult solid tumors. The multidrug resistance
(MDR) phenotype is one mechanism by which tumors may simul¬
taneously develop resistance to multiple chemotherapeutic agents
and is associated with P glycoprotein expression. In this article,
the authors examine the literature and summarize the various
techniques used to measure MDR1 gene expression, patterns of
expression in adult solid tumors.
HEMATOLOGY/ONCOLOGY CLINICS
OF NORTH AMERICA
VOLUME 9 • NUMBER 2 • APRIL 1995 vii
Multidrug Resistance in Pediatric Malignancies 275
Helen S.L. Chan, Gerrit DeBoer, George Haddad,
Brenda L. Gallie, and Victor Ling
Many sensitive immunohistochemical and molecular biologic
tools have been developed to detect the multidrug resistance P
glycoprotein in tumor samples. In this article, the suitability of
these tools for clinical use is assessed and evidence for the rele¬
vance of P glycoprotein in mediating resistance to chemotherapy
for treatment of childhood malignancies is evaluated. Preliminary
results from some of the current studies suggest that pharmaco
logic modulation of normally effective chemotherapy might over¬
come some therapeutic failures owing to overexpression of P
glycoprotein in certain malignancies with lower levels of multi
drug resistance.
MDR Expression in Normal Tissues: Pharmocologic
Implication for the Clinical Use of P Glycoprotein Inhibitors 319
Bert L. Lum and Michael P. Gosland
In multidrug resistance, the MDR1 gene product, P glycoprotein
(P gp) is thought to function as an efflux transport pump with
broad specificity for a variety of anticancer drugs. The distribu¬
tion of Pgp expression in normal human tissues with secretory
function suggests P gp may have a number of physiologic roles
and that impeding P gp function in these tissues with MDR
modulators could result in increased cytotoxin concentrations and
enhanced toxicity.
Modulators of Multidrug Resistance: Preclinical Studies 337
James M. Ford
Numerous compounds have been identified that sensitize multi
drug resistant cells to chemotherapeutic drugs in experimental
systems. The mechanism of activity of these pharmacologic
agents, termed chemosensitizers, appears to be mediated through
direct inhibition of the drug efflux activity of the MDR1 gene
product, P glycoprotein. This article describes commonly used
experimental models for the discovery and preclinical evaluation
of new chemosensitizers, reviews those agents that possess poten¬
tial for clinical use to circumvent multidrug resistance in humans,
and discusses strategies to identify novel drugs of this type with
improved efficacy and reduced toxicity.
Clinical Studies with Modulators of Multidrug Resistance 363
George A. Fisher and Branimir I. Sikic
A diverse group of noncytotoxic drugs can inhibit the drug efflux
pump, P glycoprotein, and effectively modulate multidrug resis¬
tance (MDR) in vitro. In early clinical studies, MDR modulators
reached dose limiting toxicities at serum levels below that which
Viii CONTENTS
would effectively inhibit multidrug resistance. More potent mod¬
ulators now have been developed and are entering clinical trials.
In this article, the authors review the clinical data and discuss the
challenges that confront us as we design studies to test the effi¬
cacy of P glycoprotein inhibitors.
Modulation of Glutathione and Related Enzymes in
Reversal of Resistance to Anticancer Drugs 383
Peter J. O'Dwyer, Thomas C. Hamilton, Kang shen Yao,
Kenneth D. Tew, and Robert F. Ozols
Eukaryotic cells have evolved several mechanisms to protect cel¬
lular constituents, especially DNA, from highly reactive mole¬
cules entering from without. The greater affinity of electrophiles
for thiol groups than for hydroxyl or amine groups provides a
teleologic rationale that the availability of high concentrations of
thiol could be protective of these other important entities. The
major intracellular nonprotein thiol is the tripeptide glutathione.
Clinical Resistance to Antimetabolites 397
Colin Paul Spears
This article discusses clinically approved and available antimetab¬
olites along with the clinical example of fluorouracil. The thymi
dylate synthase mechanism of cytotoxicity and results of clinical
tumor pharmacodynamics are examined. Some investigational
antimetabolites and modulators of fluoropyrimidines, including
biological response modifiers, are discussed, as are pharmacoki
netic and pharmacogenetic considerations.
Preclinical and Clinical Experience with Cisplatin Resistance 415
John Lindsay Marshall and Paul A. Andrews
Despite the general lack of clinical evidence supporting the pre¬
clinical data, there have been many attempts to overcome cis¬
platin resistance in clinical situations. These efforts have focused
on both the proposed mechanisms of resistance as well as novel
approaches to renew efficacy. In this article, the authors summa¬
rize the available clinical studies that have intentionally or seren
dipitously uncovered modulators of cisplatin sensitivity.
O6 Alkylguanine DNA Alkytransferase: A Target for the
Modulation of Drug Resistance 431
Stanton L. Gerson and James K.V. Willson
The DNA repair protein, O" alkylguanine DNA alkyltransferase,
is a major contributor to the resistance to the nitrosourea, triazine,
and tetrazine class of alkylating agents. Many tumor cells and
primary tumor samples contain high levels of this protein, al¬
though a great deal of heterogeneity exists between and within
CONTENTS ix
tumors. Inhibition of the alkyltransferase by O6 benzylguanine I"
results in significant potentiation of the cytotoxic effects of these
chemotherapeutic agents, generating responses in human tumor L
xenografts that are completely resistant to nitrosoureas alone.
These studies may rekindle the interest in the nitrosourea class
of alkylating agents and stimulate the search for inhibitors of
other mechanisms of chemotherapy resistance.
BCL 2: Prevention of Apoptosis as a Mechanism of
Drug Resistance 451
John C. Reed
Programmed cell death (also known as apoptosis) plays an essen¬
tial role in tissue homeostasis, where it ensures that new cell
production in the body is offset by a commensurate rate of cell
loss. Defects in the genetic pathway that regulate the cell death
process can figure prominently in the origins of cancer and also
in problems with cancer treatment. Eventually, it may be possible
to develop novel treatments for cancer that specifically seek to
modulate the physiologic cell death pathway as opposed to
nearly all currently available drugs, which are intended to inter¬
fere with some aspect of the cell division cycle.
Physiologic Mechanisms of Therapeutic Resistance:
Blood Flow and Hypoxia 475
Beverly A. Teicher
The tools now are available to characterize oxygenation/hypoxia
in the clinic. The clinical investigations conducted thus far have
shown that significant regions of hypoxia exist in solid tumors in
patients. Of the various strategies developed in the laboratory for
reducing (or eliminating) hypoxia in tumors, the intravenous
administration of nontoxic oxygen carrying materials is probably
the most generally applicable in a clinical setting.
Index 507
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| spelling | Drug resistance in clinical oncology and hematology George A. Fisher ... guest ed. Philadelphia [u.a.] Saunders 1995 XII S., S. 239 - 511 Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Hematology, oncology clinics of North America 9,2 Cytostatikum (DE-588)4068347-3 gnd rswk-swf Hämatologie (DE-588)4022796-0 gnd rswk-swf Krebs Medizin (DE-588)4073781-0 gnd rswk-swf Arzneimittelresistenz (DE-588)4143180-7 gnd rswk-swf (DE-588)4143413-4 Aufsatzsammlung gnd-content Arzneimittelresistenz (DE-588)4143180-7 s Hämatologie (DE-588)4022796-0 s DE-604 Krebs Medizin (DE-588)4073781-0 s Cytostatikum (DE-588)4068347-3 s Fisher, George A. Sonstige oth Hematology, oncology clinics of North America 9,2 (DE-604)BV000625446 9,2 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=006786548&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Drug resistance in clinical oncology and hematology Hematology, oncology clinics of North America Cytostatikum (DE-588)4068347-3 gnd Hämatologie (DE-588)4022796-0 gnd Krebs Medizin (DE-588)4073781-0 gnd Arzneimittelresistenz (DE-588)4143180-7 gnd |
| subject_GND | (DE-588)4068347-3 (DE-588)4022796-0 (DE-588)4073781-0 (DE-588)4143180-7 (DE-588)4143413-4 |
| title | Drug resistance in clinical oncology and hematology |
| title_auth | Drug resistance in clinical oncology and hematology |
| title_exact_search | Drug resistance in clinical oncology and hematology |
| title_full | Drug resistance in clinical oncology and hematology George A. Fisher ... guest ed. |
| title_fullStr | Drug resistance in clinical oncology and hematology George A. Fisher ... guest ed. |
| title_full_unstemmed | Drug resistance in clinical oncology and hematology George A. Fisher ... guest ed. |
| title_short | Drug resistance in clinical oncology and hematology |
| title_sort | drug resistance in clinical oncology and hematology |
| topic | Cytostatikum (DE-588)4068347-3 gnd Hämatologie (DE-588)4022796-0 gnd Krebs Medizin (DE-588)4073781-0 gnd Arzneimittelresistenz (DE-588)4143180-7 gnd |
| topic_facet | Cytostatikum Hämatologie Krebs Medizin Arzneimittelresistenz Aufsatzsammlung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=006786548&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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