Molecular basis of inherited pancreatic disorders:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
Philadelphia [u.a.]
Saunders
2006
|
| Schriftenreihe: | Endocrinology and metabolism clinics of North America
35,2 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XX S., S. 219 - 468 Ill., graph. Darst. |
| ISBN: | 1416038701 |
Internformat
MARC
| LEADER | 00000nam a2200000 cb4500 | ||
|---|---|---|---|
| 001 | BV021593767 | ||
| 003 | DE-604 | ||
| 005 | 20060601 | ||
| 007 | t | ||
| 008 | 060524s2006 ad|| |||| 00||| eng d | ||
| 020 | |a 1416038701 |9 1-4160-3870-1 | ||
| 035 | |a (OCoLC)68967630 | ||
| 035 | |a (DE-599)BVBBV021593767 | ||
| 040 | |a DE-604 |b ger |e rakwb | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-19 |a DE-91 | ||
| 050 | 0 | |a RC648.A1 | |
| 245 | 1 | 0 | |a Molecular basis of inherited pancreatic disorders |c guest ed. Markus M. Lerch ... |
| 264 | 1 | |a Philadelphia [u.a.] |b Saunders |c 2006 | |
| 300 | |a XX S., S. 219 - 468 |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 1 | |a Endocrinology and metabolism clinics of North America |v 35,2 | |
| 650 | 7 | |a Pancreas |2 gtt | |
| 650 | 7 | |a Pathologie |2 gtt | |
| 650 | 4 | |a Diabetes |x Genetic aspects | |
| 650 | 4 | |a Diabetes |x Molecular aspects | |
| 650 | 4 | |a Pancreas |x Cancer |x Treatment | |
| 650 | 4 | |a Pancreas |x Diseases |x Genetic aspects | |
| 650 | 4 | |a Pancreas |x Diseases |x Molecular aspects | |
| 650 | 4 | |a Pancreas |x Diseases |x Treatment | |
| 650 | 4 | |a Pancreas |x hereditary diseases | |
| 650 | 4 | |a Pancreatic Diseases | |
| 650 | 4 | |a Pancreatic Neoplasms | |
| 700 | 1 | |a Lerch, Markus M. |e Sonstige |0 (DE-588)1071337971 |4 oth | |
| 830 | 0 | |a Endocrinology and metabolism clinics of North America |v 35,2 |w (DE-604)BV000625447 |9 35,2 | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014809202&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-014809202 | ||
Datensatz im Suchindex
| _version_ | 1804135371889442816 |
|---|---|
| adam_text | CONTENTS
Foreword xv
Derek LeRoith
Preface xix
Markus M. Lerch, Thomas Griesbacher,
and David C. Whitcomb
Developmental and Metabolic Disorders of the Pancreas 219
Markus M. Lerch, Martin Zenker, Stefan Turi,
and Julia Mayerle
The pancreas is an important exocrine and endocrine organ that
develops from the dorsal and ventral anlagen during embryogen
esis and arises from the endodermal lining of the duodenum within
the first month of human embryonic life. A number of develop¬
mental disorders can either lead to anatomic abnormalities of the
pancreas and its ducts, or can be part of complex disorders that
affect multiorgan systems. Other genetic changes can lead to meta¬
bolic abnormalities that affect the pancreas exclusively or increase
the lifetime risk for developing pancreatitis or pancreatic diabetes.
This article reviews some of the developmental and metabolic dis¬
orders that can affect the endocrine and exocrine pancreas.
Genetic Basis and Pancreatic Biology of Johanson Blizzard
Syndrome 243
Martin Zenker, Julia Mayerle, Andre Reis,
and Markus M. Lerch
The most recent elucidation of an inherited disorder of the pancreas
concerns the Johanson Blizzard syndrome (JBS). Positional cloning
identified loss of function mutations in the UBR1 gene on the long
arm of chromosome 15 to be the cause of JBS in more than a dozen
patients. In patients with JBS the absence of UBR1 results in early
prenatal destruction of the exocrine pancreas that involves
VOLUME 35 • NUMBER 2 • JUNE 2006 vii
impaired apoptosis, induced necrosis, and prominent inflamma ;
tion. Knockout mice with absent UBR1 expression suffer from exo
crine pancreatic insufficiency and increased susceptibility to
experimental pancreatitis. The UBR1 protein substrate, presumably :
impaired degradation of which causes JBS, is not yet known.
Polygenetic Traits in Pancreatic Disorders 255
David C. Whitcomb
Rapid advances in information and technology provide opportu¬
nities to discover the risks or causes for various disorders within
individual patients. The availability of new data and new technol¬
ogy has outstripped the conceptual framework of simple disorders,
however, and challenges current statistical approaches. The author
addresses the issues surrounding study design and sample size for
complex genetic traits with special attention to meta analysis and
systems biology. The author concludes that meta analysis should
play a limited role in evaluating studies of complex genetic dis¬
eases. Instead, systems biology based approaches should be devel¬
oped to integrate multiple, focused, and mechanistic association
studies, with the goal of assisting in the risk assessment of patients
on a person by person basis.
Trypsinogen Mutations in Pancreatic Disorders 271
Louis J. Vitone, William Greenhalf, Nathan R. Howes,
Michael G.T. Raraty, and John P. Neoptolemos
There are multiple PRSS1 mutations described in hereditary pan¬
creatitis but only a minority of these are clinically relevant. The
two most frequent point mutations are in exon 2 (N29I) and exon
3 (R122H), found in diverse racial populations. Both mutations re¬
sult in early onset pancreatitis but the mechanism underlying this
phenotype is unclear. The frequency of these mutations in such
diverse populations suggests they have spontaneously occurred
many times. The origin of the major mutations may be explained
by gene conversions, accounting for multiple founders. The impli¬
cations are discussed in terms of mechanism of action of the muta¬
tions and clinical presentation.
Germline Mutations and Gene Polymorphism Associated with
Human Pancreatitis 289
F. Ulrich Weiss, Peter Simon, Julia Mayerle, Matthias Kraft,
and Markus M. Lerch
A wide range of mutations and polymorphisms in genes that relate
to pancreatic function seem to be involved in the development of
pancreatitis. Some of these genetic alterations lead to disease phe
notypes with unequivocal mendelian inheritance patterns, whereas
others seem to act as modifier genes in conjunction with environ¬
mental or, as yet unidentified, genetic cofactors. This article reviews
germline changes in the genes for trypsin, pancreatic secretory
™i CONTENTS
trypsin inhibitor, the cystic fibrosis conductance regulator, lipid
metabolism proteins, inflammatory mediators for cytokines, and
cathepsin B.
Biochemical Models of Hereditary Pancreatitis 303
Miklos Sahin Toth
i
The past decade has witnessed remarkable progress in the genetics
of chronic pancreatitis. Despite these accomplishments, the under¬
standing of the molecular mechanisms through which PRSS1 and
SPHSFK1 mutations cause chronic pancreatitis has remained
sketchy. Pancreatitis associated gene mutations are believed to result
in uncontrolled trypsin activity in the pancreas. Experimental iden¬
tification of the disease relevant functional alterations caused by
PRSS1 or SPINK1 mutations proved to be challenging, however,
because results of biochemical analyses lent themselves to different
interpretations. This article focuses on PRSS1 mutations and sum¬
marizes the salient biochemical findings in the context of the mech¬
anistic models that explain the connection between mutations and
hereditary pancreatitis.
Cell Biology of Pancreatic Proteases 313
Manuel Ruthenburger, Julia Mayerle, and Markus M. Lerch,
More than 100 years ago it was proposed that pancreatitis essen¬
tially is a disease in which the pancreas undergoes autodigestion
by its own prematurely activated digestive enzymes. Why and
how digestive zymogens autoactivate within the pancreas early
in the disease process has been a matter of controversy and debate.
Some of the mechanisms that are considered to be involved in
digestive protease activation are inherited and as of recently can
be tested for clinically. Here we review the most recent progress
in elucidating the mechanisms involved in the onset of pancreatitis.
We specifically focus on serine and cysteine proteases in the auto
digestive cascade that precedes acinar cell injury and the biochem¬
ical processes involved in their activation.
Biochemistry and Biology of SPINK PSTI and Monitor Peptide 333
Rolf Graf and Daniel Bimmler
This article summarizes structural and functional properties of
pancreatic secretory trypsin inhibitor (PSTI), which has been iden¬
tified in many species. Its prominent role is to protect the pancreas
from prematurely activated trypsinogen before entry into the duo¬
denum. In the rat there are two isoforms, one of which is PSTI I,
a 61 amino acid peptide involved in the feedback regulation of
pancreatic enzymes. Independent investigations in neoplastic dis¬
eases led to the discovery of tumor associated trypsin inhibitor,
which is identical to PSTI.
CONTENTS ix
Pathophysiology of SPINK Mutations in Pancreatic
Development and Disease 345
Rodger A. Liddle
The endogenous pancreatic trypsin inhibitor, SPINK, is believed to
limit enzyme activity in the pancreas and reduce the risk of pan¬
creatitis. Recently, mutations in the SPINK1 gene have been asso¬
ciated with development of both acute and chronic pancreatitis.
In most patients with SPINK1 mutations, the genetic variants do
not cause the disease independently, but may act in concert with
other genetic or environmental factors. Recent studies, using mice
in which the trypsin inhibitor gene has been deleted or overex
pressed, provide novel insights into the role of SPINK in pancreatic
development and pancreatitis.
Genes of Type 2 Diabetes in p Cells 357
Mirko Trajkovski, Hassan Mziaut, Peter E. Schwarz,
and Michele Solimena
Type 2 diabetes is a complex polygenic metabolic disorder of epi¬
demic proportions. This review provides a brief overview of the
susceptibility genes in type 2 diabetes that primarily affect pancrea¬
tic P cells, with emphasis on their function and most relevant poly¬
morphisms. We focus on calpain 10, the only susceptibility gene
identified thus far through a positional cloning approach in sub¬
jects with diabetes.
Genetic Basis of Maturity Onset Diabetes of the Young 371
Martine VaxUlaire and Philippe Froguel
Most valuable breakthroughs in the genetics of type 2 diabetes mel
litus have arisen from familial linkage analysis of maturity onset
diabetes of the young, an autosomal dominant form of diabetes
typically occurring before 25 years of age and caused by primary
insulin secretion defects. Despite its low prevalence, MODY is not
a single entity but presents genetic, metabolic, and clinical heteroge¬
neity. MODY can result from mutations in at least six different genes;
one encodes the glycolytic enzyme glucokinase, which is an impor¬
tant glucose sensor, whereas all the others encode transcription fac¬
tors that participate in a regulatory network essential for adult p
cell function. Additional genes, yet unidentified, may explain the
other MODY cases unlinked to a mutation in the known genes.
New Insights in the Molecular Pathogenesis of the Maternally
Inherited Diabetes and Deafness Syndrome 385
Johannes A. Maassen, Roshan S. Jahangir Tafrechi,
George M.C. Janssen, Anton K. Raap, Herman H. Lemkes,
and Leen M. t Hart
The 3243A G mutation in mitochondrial DNA (mtDNA) is a
genetic variant that is associated with a high risk of developing
x CONTENTS
diabetes during life. Enhanced aging of pancreatic p cells, a re¬
duced capacity of these cells to synthesize large amounts of insulin,
and a resetting of the ATP/ADP regulated K channel seem to be
the pathogenic factors involved.
I
{
} Development of the Pancreas and Pancreatic Cancer 399
! Brian C. Lewis
The pancreas is specified during embryonic development from the
gut endoderm. Among the signaling pathways required for the
proper development of the organ are the notch and hedgehog sig¬
naling pathways. Both of these pathways are reactivated in pan¬
creatic cancers, and sustained hedgehog signaling is required for
the viability of most pancreatic cancer cell lines. Further, mouse
models of the disease show activation of these pathways, and
expression of pancreas progenitor markers. These findings indicate
that developmental^ regulated gene expression programs are
important in the pathogenesis of pancreatic cancer.
Genotype/Phenotype of Familial Pancreatic Cancer 407
Randall E. Brand and Henry T. Lynch
It is estimated that 5% to 10% of pancreatic cancer cases are attribu¬
table to hereditary factors. We believe that the number of cases that
are genetic in etiology are even greater, however, based not on a
classic autosomal dominant pattern of inheritance but rather when
one takes into account low penetrant inherited susceptibility fac¬
tors. There is also a growing recognition that the development of
pancreatic cancer in pancreatic cancer prone families is dependent
not only on genetic variables but on nongenetic factors. The aim of
this article is to review the challenges in identifying pancreatic
cancer prone families and how environmental factors interact with
genetic factors in these families.
Familial Pancreatic Cancer Syndromes 419
Nils Habbe, Peter Langer, Mercedes Sina Frey,
and Detlef K. Bartsch
Hereditary pancreatic cancer (PC) is rare and extremely heteroge¬
neous, and it accounts for approximately 2% of all PC cases. The
major component of hereditary PC is the familial pancreatic cancer
syndrome. Although up to 20% of hereditary PC cases are asso¬
ciated with germline mutations in the BRCA2, CDKN2A, PRSS1,
STK11, or MMR genes, the major underlying gene defect(s) is still
unknown. Although hereditary PC is rare, the data on PC families
that have been collected by various study groups worldwide pro¬
vide a unique opportunity to evaluate the natural history, causative
gene alterations, new diagnosis and chemoprevention strategies as
well as treatment modalities.
CONTENTS xi
Endocrine Tumors of the Pancreas 433
Peter Simon, Elisabeth Spilcke Liss, and Henri Wallaschofski
Neuroendocrine tumors of the pancreas are rare neoplasms of the
heterogeneous group of neuroendocrine gastroenteropancreatic
tumors that originate from totipotential stem cells or pre existing
endocrine cells within the pancreas. Most neuroendocrine tumors
of the pancreas are benign or show an indolent course of disease.
A subset of them shows a very aggressive behavior, becomes
highly malignant, and metastasizes early with hfe Bmiting conse¬
quences. An effective disease management includes the diagnostic
approach with hormonal testing and localization and surgical
treatment with histologic classification in combination with
biotherapy, chemotherapy, or therapy with radionucleotides, de¬
pending on the individual behavior of the tumor. The primary goal
is the improvement of symptoms leading to an acceptable quality
of lif e in the individual patient.
Index 451
* CONTENTS
|
| adam_txt |
CONTENTS
Foreword xv
Derek LeRoith
Preface xix
Markus M. Lerch, Thomas Griesbacher,
and David C. Whitcomb
Developmental and Metabolic Disorders of the Pancreas 219
Markus M. Lerch, Martin Zenker, Stefan Turi,
and Julia Mayerle
The pancreas is an important exocrine and endocrine organ that
develops from the dorsal and ventral anlagen during embryogen
esis and arises from the endodermal lining of the duodenum within
the first month of human embryonic life. A number of develop¬
mental disorders can either lead to anatomic abnormalities of the
pancreas and its ducts, or can be part of complex disorders that
affect multiorgan systems. Other genetic changes can lead to meta¬
bolic abnormalities that affect the pancreas exclusively or increase
the lifetime risk for developing pancreatitis or pancreatic diabetes.
This article reviews some of the developmental and metabolic dis¬
orders that can affect the endocrine and exocrine pancreas.
Genetic Basis and Pancreatic Biology of Johanson Blizzard
Syndrome 243
Martin Zenker, Julia Mayerle, Andre Reis,
and Markus M. Lerch
The most recent elucidation of an inherited disorder of the pancreas
concerns the Johanson Blizzard syndrome (JBS). Positional cloning
identified loss of function mutations in the UBR1 gene on the long
arm of chromosome 15 to be the cause of JBS in more than a dozen
patients. In patients with JBS the absence of UBR1 results in early
prenatal destruction of the exocrine pancreas that involves
VOLUME 35 • NUMBER 2 • JUNE 2006 vii
impaired apoptosis, induced necrosis, and prominent inflamma ;
tion. Knockout mice with absent UBR1 expression suffer from exo
crine pancreatic insufficiency and increased susceptibility to
experimental pancreatitis. The UBR1 protein substrate, presumably :
impaired degradation of which causes JBS, is not yet known.
Polygenetic Traits in Pancreatic Disorders 255
David C. Whitcomb
Rapid advances in information and technology provide opportu¬
nities to discover the risks or causes for various disorders within
individual patients. The availability of new data and new technol¬
ogy has outstripped the conceptual framework of simple disorders,
however, and challenges current statistical approaches. The author
addresses the issues surrounding study design and sample size for
complex genetic traits with special attention to meta analysis and
systems biology. The author concludes that meta analysis should
play a limited role in evaluating studies of complex genetic dis¬
eases. Instead, systems biology based approaches should be devel¬
oped to integrate multiple, focused, and mechanistic association
studies, with the goal of assisting in the risk assessment of patients
on a person by person basis.
Trypsinogen Mutations in Pancreatic Disorders 271
Louis J. Vitone, William Greenhalf, Nathan R. Howes,
Michael G.T. Raraty, and John P. Neoptolemos
There are multiple PRSS1 mutations described in hereditary pan¬
creatitis but only a minority of these are clinically relevant. The
two most frequent point mutations are in exon 2 (N29I) and exon
3 (R122H), found in diverse racial populations. Both mutations re¬
sult in early onset pancreatitis but the mechanism underlying this
phenotype is unclear. The frequency of these mutations in such
diverse populations suggests they have spontaneously occurred
many times. The origin of the major mutations may be explained
by gene conversions, accounting for multiple founders. The impli¬
cations are discussed in terms of mechanism of action of the muta¬
tions and clinical presentation.
Germline Mutations and Gene Polymorphism Associated with
Human Pancreatitis 289
F. Ulrich Weiss, Peter Simon, Julia Mayerle, Matthias Kraft,
and Markus M. Lerch
A wide range of mutations and polymorphisms in genes that relate
to pancreatic function seem to be involved in the development of
pancreatitis. Some of these genetic alterations lead to disease phe
notypes with unequivocal mendelian inheritance patterns, whereas
others seem to act as modifier genes in conjunction with environ¬
mental or, as yet unidentified, genetic cofactors. This article reviews
germline changes in the genes for trypsin, pancreatic secretory
™i CONTENTS
trypsin inhibitor, the cystic fibrosis conductance regulator, lipid
metabolism proteins, inflammatory mediators for cytokines, and
cathepsin B.
Biochemical Models of Hereditary Pancreatitis 303
Miklos Sahin Toth
i
' The past decade has witnessed remarkable progress in the genetics
of chronic pancreatitis. Despite these accomplishments, the under¬
standing of the molecular mechanisms through which PRSS1 and
SPHSFK1 mutations cause chronic pancreatitis has remained
sketchy. Pancreatitis associated gene mutations are believed to result
in uncontrolled trypsin activity in the pancreas. Experimental iden¬
tification of the disease relevant functional alterations caused by
PRSS1 or SPINK1 mutations proved to be challenging, however,
because results of biochemical analyses lent themselves to different
interpretations. This article focuses on PRSS1 mutations and sum¬
marizes the salient biochemical findings in the context of the mech¬
anistic models that explain the connection between mutations and
hereditary pancreatitis.
Cell Biology of Pancreatic Proteases 313
Manuel Ruthenburger, Julia Mayerle, and Markus M. Lerch,
More than 100 years ago it was proposed that pancreatitis essen¬
tially is a disease in which the pancreas undergoes autodigestion
by its own prematurely activated digestive enzymes. Why and
how digestive zymogens autoactivate within the pancreas early
in the disease process has been a matter of controversy and debate.
Some of the mechanisms that are considered to be involved in
digestive protease activation are inherited and as of recently can
be tested for clinically. Here we review the most recent progress
in elucidating the mechanisms involved in the onset of pancreatitis.
We specifically focus on serine and cysteine proteases in the auto
digestive cascade that precedes acinar cell injury and the biochem¬
ical processes involved in their activation.
Biochemistry and Biology of SPINK PSTI and Monitor Peptide 333
Rolf Graf and Daniel Bimmler
This article summarizes structural and functional properties of
pancreatic secretory trypsin inhibitor (PSTI), which has been iden¬
tified in many species. Its prominent role is to protect the pancreas
from prematurely activated trypsinogen before entry into the duo¬
denum. In the rat there are two isoforms, one of which is PSTI I,
a 61 amino acid peptide involved in the feedback regulation of
pancreatic enzymes. Independent investigations in neoplastic dis¬
eases led to the discovery of tumor associated trypsin inhibitor,
which is identical to PSTI.
CONTENTS ix
Pathophysiology of SPINK Mutations in Pancreatic
Development and Disease 345
Rodger A. Liddle
The endogenous pancreatic trypsin inhibitor, SPINK, is believed to
limit enzyme activity in the pancreas and reduce the risk of pan¬
creatitis. Recently, mutations in the SPINK1 gene have been asso¬
ciated with development of both acute and chronic pancreatitis.
In most patients with SPINK1 mutations, the genetic variants do
not cause the disease independently, but may act in concert with
other genetic or environmental factors. Recent studies, using mice
in which the trypsin inhibitor gene has been deleted or overex
pressed, provide novel insights into the role of SPINK in pancreatic
development and pancreatitis.
Genes of Type 2 Diabetes in p Cells 357
Mirko Trajkovski, Hassan Mziaut, Peter E. Schwarz,
and Michele Solimena
Type 2 diabetes is a complex polygenic metabolic disorder of epi¬
demic proportions. This review provides a brief overview of the
susceptibility genes in type 2 diabetes that primarily affect pancrea¬
tic P cells, with emphasis on their function and most relevant poly¬
morphisms. We focus on calpain 10, the only susceptibility gene
identified thus far through a positional cloning approach in sub¬
jects with diabetes.
Genetic Basis of Maturity Onset Diabetes of the Young 371
Martine VaxUlaire and Philippe Froguel
Most valuable breakthroughs in the genetics of type 2 diabetes mel
litus have arisen from familial linkage analysis of maturity onset
diabetes of the young, an autosomal dominant form of diabetes
typically occurring before 25 years of age and caused by primary
insulin secretion defects. Despite its low prevalence, MODY is not
a single entity but presents genetic, metabolic, and clinical heteroge¬
neity. MODY can result from mutations in at least six different genes;
one encodes the glycolytic enzyme glucokinase, which is an impor¬
tant glucose sensor, whereas all the others encode transcription fac¬
tors that participate in a regulatory network essential for adult p
cell function. Additional genes, yet unidentified, may explain the
other MODY cases unlinked to a mutation in the known genes.
New Insights in the Molecular Pathogenesis of the Maternally
Inherited Diabetes and Deafness Syndrome 385
Johannes A. Maassen, Roshan S. Jahangir Tafrechi,
George M.C. Janssen, Anton K. Raap, Herman H. Lemkes,
and Leen M. 't Hart
The 3243A G mutation in mitochondrial DNA (mtDNA) is a
genetic variant that is associated with a high risk of developing
x CONTENTS
diabetes during life. Enhanced aging of pancreatic p cells, a re¬
duced capacity of these cells to synthesize large amounts of insulin,
and a resetting of the ATP/ADP regulated K channel seem to be
the pathogenic factors involved.
I
{
} Development of the Pancreas and Pancreatic Cancer 399
! Brian C. Lewis
The pancreas is specified during embryonic development from the
gut endoderm. Among the signaling pathways required for the
proper development of the organ are the notch and hedgehog sig¬
naling pathways. Both of these pathways are reactivated in pan¬
creatic cancers, and sustained hedgehog signaling is required for
the viability of most pancreatic cancer cell lines. Further, mouse
models of the disease show activation of these pathways, and
expression of pancreas progenitor markers. These findings indicate
that developmental^ regulated gene expression programs are
important in the pathogenesis of pancreatic cancer.
Genotype/Phenotype of Familial Pancreatic Cancer 407
Randall E. Brand and Henry T. Lynch
It is estimated that 5% to 10% of pancreatic cancer cases are attribu¬
table to hereditary factors. We believe that the number of cases that
are genetic in etiology are even greater, however, based not on a
classic autosomal dominant pattern of inheritance but rather when
one takes into account low penetrant inherited susceptibility fac¬
tors. There is also a growing recognition that the development of
pancreatic cancer in pancreatic cancer prone families is dependent
not only on genetic variables but on nongenetic factors. The aim of
this article is to review the challenges in identifying pancreatic
cancer prone families and how environmental factors interact with
genetic factors in these families.
Familial Pancreatic Cancer Syndromes 419
Nils Habbe, Peter Langer, Mercedes Sina Frey,
and Detlef K. Bartsch
Hereditary pancreatic cancer (PC) is rare and extremely heteroge¬
neous, and it accounts for approximately 2% of all PC cases. The
major component of hereditary PC is the familial pancreatic cancer
syndrome. Although up to 20% of hereditary PC cases are asso¬
ciated with germline mutations in the BRCA2, CDKN2A, PRSS1,
STK11, or MMR genes, the major underlying gene defect(s) is still
unknown. Although hereditary PC is rare, the data on PC families
that have been collected by various study groups worldwide pro¬
vide a unique opportunity to evaluate the natural history, causative
gene alterations, new diagnosis and chemoprevention strategies as
well as treatment modalities.
CONTENTS xi
Endocrine Tumors of the Pancreas 433
Peter Simon, Elisabeth Spilcke Liss, and Henri Wallaschofski
Neuroendocrine tumors of the pancreas are rare neoplasms of the
heterogeneous group of neuroendocrine gastroenteropancreatic
tumors that originate from totipotential stem cells or pre existing
endocrine cells within the pancreas. Most neuroendocrine tumors
of the pancreas are benign or show an indolent course of disease.
A subset of them shows a very aggressive behavior, becomes
highly malignant, and metastasizes early with hfe Bmiting conse¬
quences. An effective disease management includes the diagnostic
approach with hormonal testing and localization and surgical
treatment with histologic classification in combination with
biotherapy, chemotherapy, or therapy with radionucleotides, de¬
pending on the individual behavior of the tumor. The primary goal
is the improvement of symptoms leading to an acceptable quality
of lif e in the individual patient.
Index 451
*" CONTENTS |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author_GND | (DE-588)1071337971 |
| building | Verbundindex |
| bvnumber | BV021593767 |
| callnumber-first | R - Medicine |
| callnumber-label | RC648 |
| callnumber-raw | RC648.A1 |
| callnumber-search | RC648.A1 |
| callnumber-sort | RC 3648 A1 |
| callnumber-subject | RC - Internal Medicine |
| ctrlnum | (OCoLC)68967630 (DE-599)BVBBV021593767 |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01692nam a2200433 cb4500</leader><controlfield tag="001">BV021593767</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20060601 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">060524s2006 ad|| |||| 00||| eng d</controlfield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">1416038701</subfield><subfield code="9">1-4160-3870-1</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)68967630</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV021593767</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-19</subfield><subfield code="a">DE-91</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC648.A1</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Molecular basis of inherited pancreatic disorders</subfield><subfield code="c">guest ed. Markus M. Lerch ...</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">Philadelphia [u.a.]</subfield><subfield code="b">Saunders</subfield><subfield code="c">2006</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XX S., S. 219 - 468</subfield><subfield code="b">Ill., graph. Darst.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="490" ind1="1" ind2=" "><subfield code="a">Endocrinology and metabolism clinics of North America</subfield><subfield code="v">35,2</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Pancreas</subfield><subfield code="2">gtt</subfield></datafield><datafield tag="650" ind1=" " ind2="7"><subfield code="a">Pathologie</subfield><subfield code="2">gtt</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Diabetes</subfield><subfield code="x">Genetic aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Diabetes</subfield><subfield code="x">Molecular aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreas</subfield><subfield code="x">Cancer</subfield><subfield code="x">Treatment</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreas</subfield><subfield code="x">Diseases</subfield><subfield code="x">Genetic aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreas</subfield><subfield code="x">Diseases</subfield><subfield code="x">Molecular aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreas</subfield><subfield code="x">Diseases</subfield><subfield code="x">Treatment</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreas</subfield><subfield code="x">hereditary diseases</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreatic Diseases</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pancreatic Neoplasms</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lerch, Markus M.</subfield><subfield code="e">Sonstige</subfield><subfield code="0">(DE-588)1071337971</subfield><subfield code="4">oth</subfield></datafield><datafield tag="830" ind1=" " ind2="0"><subfield code="a">Endocrinology and metabolism clinics of North America</subfield><subfield code="v">35,2</subfield><subfield code="w">(DE-604)BV000625447</subfield><subfield code="9">35,2</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014809202&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-014809202</subfield></datafield></record></collection> |
| id | DE-604.BV021593767 |
| illustrated | Illustrated |
| index_date | 2024-07-02T14:45:19Z |
| indexdate | 2024-07-09T20:39:27Z |
| institution | BVB |
| isbn | 1416038701 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-014809202 |
| oclc_num | 68967630 |
| open_access_boolean | |
| owner | DE-19 DE-BY-UBM DE-91 DE-BY-TUM |
| owner_facet | DE-19 DE-BY-UBM DE-91 DE-BY-TUM |
| physical | XX S., S. 219 - 468 Ill., graph. Darst. |
| publishDate | 2006 |
| publishDateSearch | 2006 |
| publishDateSort | 2006 |
| publisher | Saunders |
| record_format | marc |
| series | Endocrinology and metabolism clinics of North America |
| series2 | Endocrinology and metabolism clinics of North America |
| spelling | Molecular basis of inherited pancreatic disorders guest ed. Markus M. Lerch ... Philadelphia [u.a.] Saunders 2006 XX S., S. 219 - 468 Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Endocrinology and metabolism clinics of North America 35,2 Pancreas gtt Pathologie gtt Diabetes Genetic aspects Diabetes Molecular aspects Pancreas Cancer Treatment Pancreas Diseases Genetic aspects Pancreas Diseases Molecular aspects Pancreas Diseases Treatment Pancreas hereditary diseases Pancreatic Diseases Pancreatic Neoplasms Lerch, Markus M. Sonstige (DE-588)1071337971 oth Endocrinology and metabolism clinics of North America 35,2 (DE-604)BV000625447 35,2 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014809202&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Molecular basis of inherited pancreatic disorders Endocrinology and metabolism clinics of North America Pancreas gtt Pathologie gtt Diabetes Genetic aspects Diabetes Molecular aspects Pancreas Cancer Treatment Pancreas Diseases Genetic aspects Pancreas Diseases Molecular aspects Pancreas Diseases Treatment Pancreas hereditary diseases Pancreatic Diseases Pancreatic Neoplasms |
| title | Molecular basis of inherited pancreatic disorders |
| title_auth | Molecular basis of inherited pancreatic disorders |
| title_exact_search | Molecular basis of inherited pancreatic disorders |
| title_exact_search_txtP | Molecular basis of inherited pancreatic disorders |
| title_full | Molecular basis of inherited pancreatic disorders guest ed. Markus M. Lerch ... |
| title_fullStr | Molecular basis of inherited pancreatic disorders guest ed. Markus M. Lerch ... |
| title_full_unstemmed | Molecular basis of inherited pancreatic disorders guest ed. Markus M. Lerch ... |
| title_short | Molecular basis of inherited pancreatic disorders |
| title_sort | molecular basis of inherited pancreatic disorders |
| topic | Pancreas gtt Pathologie gtt Diabetes Genetic aspects Diabetes Molecular aspects Pancreas Cancer Treatment Pancreas Diseases Genetic aspects Pancreas Diseases Molecular aspects Pancreas Diseases Treatment Pancreas hereditary diseases Pancreatic Diseases Pancreatic Neoplasms |
| topic_facet | Pancreas Pathologie Diabetes Genetic aspects Diabetes Molecular aspects Pancreas Cancer Treatment Pancreas Diseases Genetic aspects Pancreas Diseases Molecular aspects Pancreas Diseases Treatment Pancreas hereditary diseases Pancreatic Diseases Pancreatic Neoplasms |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014809202&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV000625447 |
| work_keys_str_mv | AT lerchmarkusm molecularbasisofinheritedpancreaticdisorders |