Table of Contents
1
UI - 11929809
AU - Lott ST; Chandler DS; Curley SA; Foster CJ; El-Naggar A; Frazier M;
TI -
Strong LC; Lovell M; Killary AM
High frequency loss of heterozygosity in von Hippel-Lindau
(VHL)-associated and sporadic pancreatic islet cell tumors: evidence for
a stepwise mechanism for malignant conversion in VHL tumorigenesis.
SO - Cancer Res 2002 Apr 1;62(7):1952-5
AD - Department of Molecular Genetics, The University of Texas M. D. Anderson
Cancer Center, Houston, Texas 77030-4009, USA.
Germ-line mutation of the von Hippel-Lindau (VHL) gene predisposes to
the development of multifocal, benign lesions, including retinal and
central nervous system hemangioblastomas, pheochromocytomas, and renal
and pancreatic cysts. Progression to malignancy in VHL disease is
associated primarily with the development of renal cell carcinoma (RCC)
and pancreatic islet cell tumors (PICT). Although many reports have
documented the multiple functions of the VHL protein, few have
investigated the intriguing question related to the tissue-specificity
of malignant conversion in VHL disease, a problem not easily explained
by strict genotype-phenotype correlations. We investigated a novel VHL
kindred with a preponderance of PICTs to determine whether loss of
additional genetic loci associated with the sporadic forms of RCC and
PICTs might play a role in malignant conversion in this disease. We
report the high frequency loss of heterozygosity (LOH) of genetic loci
distinct from and mapping proximal to VHL within human chromosome 3p in
the VHL kindred under study. Furthermore, chromosome 3p LOH occurs
subsequent to VHL mutation and cyst formation, and correlates with
malignant progression in VHL-associated PICTs. High frequency LOH was
also observed in sporadic PICTs in regions of 3p associated with LOH in
sporadic clear cell RCC as well as homozygous deletion in lung cancer. A
stepwise model for malignant conversion in VHL disease is herein
proposed.
2
UI - 11965607
AU - Anthony LB; Woltering EA; Espenan GD; Cronin MD; Maloney TJ; McCarthy KE
TI -
Indium-111-pentetreotide prolongs survival in gastroenteropancreatic
malignancies.
SO - Semin Nucl Med 2002 Apr;32(2):123-32
AD - Louisiana State University Medical Center, Department of Medicine, the
Louisiana State University Health Sciences Center (LSUHSC), Stanley S.
Scott Cancer Center, New Orleans, LA 70112, USA.
Somatostatin and its analogues bind to somatostatin receptors (sst) 1
through 5 that are overexpressed in neuroendocrine neoplasms such as
gastroenteropancreatic (GEP) malignancies. After ligand-receptor
binding, a fraction of the ligand-receptor complexes internalize. This
internalization process is an effective means of delivering cytotoxic
radiolabeled somatostatin analogues, especially those emitting
short-range decay particles such as Auger electrons, to the neoplastic
cell nucleus. Indium-111-pentetreotide, an sst 2 preferring somatostatin
analogue with gamma and Auger electron decay characteristics, is
commonly used for the scintigraphic evaluation and management of
neuroendocrine cancer patients. This clinical trial was performed to
determine the effectiveness and tolerability of therapeutic doses of
(111)In-pentetreotide in patients with GEP tumors. GEP tumor patients
who had failed all forms of conventional therapy, with worsening of
tumor-related signs and symptoms and/or radiographically documented
progressive disease, an expected survival less than 6 months, and sst
positivity as determined by the uptake on a 6.0 mCi
(111)In-pentetreotide scan (OctreoScan; Mallinckrodt Medical, Inc, St.
Louis, MO), were treated with at least 2 monthly 180-mCi intravenous
injections of (111)In-pentetreotide. Baseline clinical assessments,
serum chemistries, and plasma pancreastatin levels were measured and
and 3 pancreatic islet cells) patients were accrued, with 26 patients
evaluable for clinical and radiographic responses, 21 patients evaluable
for biochemical assessments, and 27 patients evaluable for survival
analysis and safety. Toxicity was evaluated by using standard National
Cancer Institute (NCI) Common Toxicity Criteria guidelines. Clinical
benefit occurred in 16 (62%) patients. Pancreastatin levels decreased by
50% or more in 81% of the patients. Objective partial radiographic
responses occurred in 2 (8%) patients, and significant tumor necrosis
(defined by 20 Hounsfield units or greater decrease from baseline)
developed in 7 (27%) patients. The following transient Grades 3/4 NCI
Common Toxicity Criteria side effects were observed, respectively:
leukocyte: 1/1; platelets: 0/2; hemoglobin: 3/0; bilirubin: 1/3;
creatinine: 1/0; neurologic: 1/0. Myeloproliferative disease and/or
myelodysplastic syndrome have not been observed in the 6 patients
followed-up for 48+ months. The median survival was 18 months (range,
3-54+ mo). Two doses (180 mCi) of (111)In-pentetreotide are safe,
well-tolerated, and improve symptoms in 62% of patients, decrease
hormonal markers in 81% of patients, decrease Hounsfield units on
computed tomography (CT) scans in 27% of patients, with 8% partial
radiographic responses and increased expected survival in GEP cancer
patients with somatostatin receptor-expressing tumors. The maximal
tolerated dose of (111)In-pentetreotide and the optimal dosing schedules
remain under investigation. Copyright 2002, Elsevier Science.
3
UI - 10707036
AU - Frittitta L; Sbraccia P; Costanzo BV; Tassi V; D'Adamo M; Spampinato D;
TI -
Ercolino T; Purrello F; Tamburrano G; Vigneri R; Trischitta V
High insulin levels do not influence PC-1 gene expression and protein
content in human muscle tissue and hepatoma cells.
SO - Diabetes Metab Res Rev 2000 Jan-Feb;16(1):26-32
AD - Institute of Internal Medicine, Endocrine and Metabolic Diseases,
University of Catania, Garibaldi Hospital, Catania, Italy.
segmeint@mbox.unict.it
BACKGROUND: To verify whether insulin levels influence PC-1 tissue
content, we studied PC-1 gene expression and protein content in skeletal
muscle of patients with insulinoma, a model of primary hyperinsulinemia.
Data were compared with those obtained in matched insulin sensitive or
resistant healthy subjects. In addition, the effect of high insulin
concentration on PC-1 protein content was studied in HepG2 cells.
METHODS: The following measurements were performed: insulin sensitivity
by euglycemic clamp; PC-1 protein content and insulin receptor
autophosphorylation by specific ELISAs; PC-1 gene expression by
competitive polymerase chain reaction (PCR); phosphatidyl-inositol-3
kinase by immunoprecipitation and thin layer chromatography; glycogen
synthesis by (14)C-glucose incorporation. RESULTS: Muscle PC-1 content
was similar in the insulinoma patients and in insulin sensitive controls
but higher (p<0.01) in insulin resistant controls (21.9+/-4.6 ng/mg
protein, 23.8+/-3.9, 48.0+/-8.7, respectively). PC-1 protein content was
inversely correlated with insulin sensitivity (r=-0.5, p<0.015) but with
neither plasma insulin nor glucose levels. PC-1 protein content was
correlated with PC-1 gene expression (r=0.53, p<0.05, n=14). Exposure to
high insulin (100 nmol/l for 16 h) caused a significant (p<0.05-0.01)
impairment of insulin receptor autophosphorylation,
phosphatidyl-inositol-3 kinase activity and glycogen synthesis, but not
of PC-1 protein content (114+/-3 vs 102+/-14 ng/mg protein) in HepG2
cells. CONCLUSION: These findings suggest that chronic high insulin
levels do not influence PC-1 expression. Copyright 2000 John Wiley &
Sons, Ltd.
4
UI - 11961649
AU - Takamatsu S; Teramoto K; Inoue H; Goseki N; Takahashi S; Baba H; Iwai T;
TI -
Arii S
Laparoscopic enucleation of an insulinoma of the pancreas tail.
SO - Surg Endosc 2002 Jan;16(1):217
AD - Department of Surgery, Tokyo Medical and Dental University, School of
Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
A 29 year-old woman with a tumor of the pancreatic tail was referred to
our institute. The tumor was confirmed to be a solitary benign
insulinoma that protruded from the pancreas and was distant from the
main pancreatic duct. A laparoscopic enucleation was performed with
Laparoscopic Coagulating Shears (LCS). The postoperative course was
uneventful. The laparoscopic enucleation for benign pancreatic tumor was
thought to be a feasible procedure when the appropriate instruments were
used.
5
UI - 11961650
AU - Tagaya N; Ishikawa K; Kubota K
TI -
Spleen-preserving laparoscopic distal pancreatectomy with conservation
of the splenic artery and vein for a large insulinoma.
SO - Surg Endosc 2002 Jan;16(1):217-8
AD - Second Department of Surgery, Dokkyo University School of Medicine, 880
Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
We report a successful spleen-preserving laparoscopic distal
pancreatectomy for a large insulinoma with conservation of the splenic
artery and vein. The patient was a 48-year-old man with syncope due to
hypoglycemia. Abdominal computed tomography (CT) and ultrasonography
revealed a large 6-cm mass located in the tail of the pancreas. We
adopted the laparoscopic approach to remove the tumor. After careful
dissection and an accurate hemostasis between the pancreas and splenic
vessels, laparoscopic distal pancreatectomy was carried out using a
linear stapler. There were no perioperative complications. The patient
was discharged uneventfully. He had no hypoglycemic episodes or
abdominal symptoms during 8 months of follow-up. When performed by
experienced laparoscopic surgeons in conjunction with intraoperative
ultrasonography, spleen-preserving laparoscopic distal pancreatectomy
with conservation of the splenic artery and vein is a technically
feasible procedure for the treatment of benign lesions of the tail or
body of the pancreas.
6
UI - 11964041
AU - Barth PJ; Ebrahimsade S; Hellinger A; Moll R; Ramaswamy A
TI -
CD34+ fibrocytes in neoplastic and inflammatory pancreatic lesions.
SO - Virchows Arch 2002 Feb;440(2):128-33
AD - Institute of Pathology, Philipps University Marburg, Germany.
barthp@post.med.uni-marburg.de
Besides its function as a matrix-producing cell, the CD34+ fibrocyte has
been reported to be an antigen-presenting cell capable of priming naive
T cells in situ. Therefore, it has been claimed that the CD34+ fibrocyte
may play an important role in host response to tissue damage. The
objective of the present study was to analyze the presence and
distribution of CD34+ fibrocytes and smooth muscle actin (SMA) reactive
myofibroblasts in relation to the underlying pancreatic disease. We
investigated a total of 12 pancreatic adenocarcinomas, 7 endocrine
tumors of the pancreas, and 8 cases of chronic pancreatitis; in 11
cases, normal pancreatic tissue was available. The stroma of normal
pancreatic tissue harbored diffusely scattered CD34+ fibrocytes. Chronic
pancreatitis was characterized by an increased number of stromal CD34+
fibrocytes paralleled by a gain of SMA reactive myofibroblasts which
were not observed in the normal pancreatic stroma. The stroma of
pancreatic ductal adenocarcinomas and endocrine tumors was devoid of
CD34+ fibrocytes or showed at least a focal loss of this cell type,
whereas SMA reactive myofibroblasts were detected in both endocrine
tumors and adenocarcinomas. We conclude that detection of CD34+
fibrocytes may constitute an adjunctive tool in distinguishing chronic
pancreatitis from ductal adenocarcinoma since the absence of this cell
population strongly favors a neoplastic process. Moreover, CD34+
fibrocytes and myofibroblasts appear to be involved in stromal
remodeling associated with chronic pancreatitis and ductal
adenocarcinoma.
7
UI - 11964045
AU - Scarpa A; Orlandini S; Moore PS; Lemoine NR; Beghelli S; Baron A;
TI -
Falconi M; Zamboni G
Dpc4 is expressed in virtually all primary and metastatic pancreatic
endocrine carcinomas.
SO - Virchows Arch 2002 Feb;440(2):155-9
AD - Dipartimento di Patologia, Universita di Verona, Italy.
a.scarpa@univr.it
DPC4/Smad4 is inactivated in about 50% of pancreatic ductal cancers. It
has been recently reported that this gene is also inactivated in
neoplasms arising from pancreatic islet cells, a phenomenon suggested to
be related to similar progressions of malignancy found in common ductal
cancers. To evaluate this possibility, we analysed 20 metastases of
pancreatic endocrine carcinomas and their corresponding primary lesion
for inactivation of DPC4 using immunohistochemical staining. In fact,
immunohistochemical labelling has been shown to correlate with DPC4 gene
status with high sensitivity and specificity. The cancers included 18
nonfunctioning tumours, one gastrinoma and one ViPoma all with liver,
nodal and/or adrenal metastases. Seventeen were well-differentiated and
three poorly differentiated endocrine carcinomas. Dpc4 expression was
absent in only one primary well-differentiated endocrine cancer and its
liver metastasis, while all the remaining 19 primary tumours and their
metastases stained positive for the protein. All positively staining
cases showed diffuse cytoplasmic and nuclear staining in virtually all
neoplastic cells. Our data suggest that DPC4 is only rarely involved in
pancreatic endocrine tumourigenesis and give further weight to the
hypothesis that tumours arising from pancreatic exocrine and endocrine
epithelia are genetically distinct.
8
UI - 11959716
AU - Oshikawa O; Tanaka S; Ioka T; Nakaizumi A; Hamada Y; Mitani T
TI -
Dynamic sonography of pancreatic tumors: comparison with dynamic CT.
SO - AJR Am J Roentgenol 2002 May;178(5):1133-7
AD - Division of Digestive Organs, Department of Cancer Survey, Osaka Medical
Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi,
Higashinari, Osaka, 537-8511, Japan.
OBJECTIVE: The aim of this study was to examine the usefulness of
dynamic sonography in the characterization of pancreatic tumors.
MATERIALS AND METHODS: IV contrast-enhanced pancreatic sonography
(dynamic sonography) with Levovist was performed in 43 patients with
pancreatic mass lesions (32 with pancreatic adenocarcinomas, four with
inflammatory pancreatic masses, three with islet cell tumors, two with
serous cystadenomas, one with a solid and cystic tumor, and one with
metastatic pancreatic cancer). We calculated a contrast index using a
time-intensity curve: contrast index equals elevation of intensity in
the tumor divided by elevation of intensity in the pancreatic
parenchyma. We classified the tumors into three groups according to the
contrast index: a slightly enhanced group (contrast index < 0.5), a
moderately enhanced group (contrast index = 0.5-1.5), and a
well-enhanced group (contrast index > 1.5), and we compared these
results with those from dynamic CT. RESULTS: The contrast indexes of 32
adenocarcinomas, four inflammatory pancreatic masses, three islet cell
tumors, two serous cystadenomas, one solid and cystic tumor, and one
metastatic tumor were, respectively, 0.12 +/- 0.095 (mean +/- SD), 0.54
+/- 0.420, 1.74 +/- 0.555, 1.09 +/- 1.380, 1.67, and 2.07. Thirty-five
tumors, including all 32 adenocarcinomas, were classified in the
slightly enhanced group, three were classified in the moderately
enhanced group, and five were classified in the well-enhanced group. In
93% (40/43) of tumors, the grade of enhancement on dynamic sonography
was closely correlated with the grade of enhancement on dynamic CT.
CONCLUSION: Dynamic sonography can assist in the characterization of
pancreatic tumors.
9
UI - 11753234
AU - Camera L; Bresciani M; Soscia E; Percopo V; Mainenti PP; Salvatore M
TI -
[Morphological imaging of gastroenteropancreatic neuroendocrine tumours]
SO - Minerva Endocrinol 2001 Sep;26(3):123-8
AD - Consiglio Nazionale delle Ricerche, Dipartimento di Scienze
Bio-morfologiche, Universita degli Studi Federico II, Naples, Italy.
Biologically active neuroendocrine tumours produce early symptoms and
are often difficult to diagnose owing to their small dimensions (<1 cm),
whereas biologically inactive forms are often coarse and sometimes found
by chance. As well as identifying the lesion, locoregional staging is
also particularly important for therapeutic planning. Morphological
imaging plays an important role in the identification of
gastroenteropancreatic neuroendocrine tumours, providing an anatomic
substrate for receptorial imaging which usually precede it in the
diagnostic work-up, whereas it plays a primary role in the locoregional
staging of these neoplasms for which surgery is the first and essential
therapeutic approach. In the case of endocrine tumours of the pancreas
alone, the most accurate method of diagnosis is currently echo-endoscopy
using high-frequency probes. Two-phase spiral CT and dynamic MR have
proved equally effective means of identifying endocrine tumours of the
pancreas with slightly higher sensitivity for MR, both playing a role in
the locoregional staging of biologically active and inactive tumours.
Traditional radiology also plays a role in the identification of
intestinal carcinoids.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
About OncoLink Contact OncoLink Privacy statement Disclaimer Link to OncoLink Home