Analysis of p53 and
vascular endothelial growth factor expression in human gallbladder
carcinoma for the determination of tumor vascularity.
Tian Y, Ding RY, Zhi YH, Guo RX, Wu SD.
Department of General Surgery, Second Affiliated
Hospital, China Medical University, Shenyang 110004, China. surgeon_ty@yahoo.com.cn.
AIM:To examine the expression of p53 and vascular endothelial growth factor
(VEGF) as well as microvessel count (MVC) and to
investigate the role of VEGF as an angiogenic
marker and the possible role of p53 in the regulation of angiogenesis in
human gallbladder carcinoma.METHODS:Surgically resected specimens of 49 gallbladder carcinomas were
studied by immunohistochemical staining for p53
protein, VEGF, and factor VIII-related antigen. VEGF expression and mutant
p53 expression were then correlated with Nevin
stage, differentiation grade, MVC, and lymph node metastasis.RESULTS:Positive p53 protein and VEGF expressions were
found in 61.2% and 63.3% of tumors, respectively. p53
and VEGF staining status was identical in 55.1% of tumors. The Nevin staging of p53- or VEGF-positive tumors was
significantly later than that of negative tumors. The MVC in p53- or
VEGF-positive tumors was significantly higher than that in negative tumors,
and MVC in both p53- and VEGF-negative tumors was significantly lower than
that in the other subgroups.CONCLUSION:Our
findings suggest that p53-VEGF pathway can regulate tumor angiogenesis in
human gallbladder carcinoma. Combined analysis of p53 and VEGF expression
might be useful for predicting the tumor vascularity
of gallbladder cancer.
PMID: 16489641 [PubMed - in process]
Biological activity of paediatric cerebral cavernomas:
an immunohistochemical study of 28 patients.
Tirakotai W,
Fremann S,
Soerensen N,
Roggendorf W,
Siegel AM,
Mennel HD,
Zhu Y, Bertalanffy H,
Sure U.
Department of Neurosurgery, Philipps University, Baldingerstrasse, 35033, Marburg, Germany, sure@med.uni-marburg.de.
OBJECTIVE: According to the hypothesis that paediatric
cerebral cavernomas may have different biological
activity compared to adult cavernomas, immunohistochemical analysis was used to elucidate the
biological nature of paediatric cavernomas. PATIENTS AND METHODS: We examined the
histological features and the proliferative and angiogenic capacity of the tissue specimens acquired
from 28 paediatric patients. Normal paediatric brain tissues obtained from paediatric autopsy cases were used as a control group.
The proliferative activity of the endothelium and
the neoangiogenetic capacity were investigated by
immunohistochemistry for proliferating cell
nuclear antigen (PCNA), Ki-67 epitope (MIB-1),
Flk-1 receptor, vascular endothelial growth factor (VEGF),
hypoxia-inducible factor (HIF)-1 alpha, and endoglin
antibody, respectively. Afterwards, the results of the paediatric
lesions were analysed and compared with the
correspondent values of previously reported immunohistochemical
analysis in adult cavernomas. RESULTS: Positive immunostaining of VEGF was detected significantly less
in paediatric cavernomas
compared to adult cases (p<0.05). In contrast, endoglin,
a protein that is upregulated during an increased
vascular shear stress, was expressed more often in paediatric
cavernomas (p<0.05). Neither the expression of
the PCNA nor the expression of the HIF-1alpha was found significantly
different between paediatric and adult cavernomas. However, the positive immunoreaction
for MIB-1 occurred more often in the paediatric
cases (p<0.05). CONCLUSIONS: The immunohistochemical
study indicates that paediatric cavernomas are dynamic lesions. The VEGF/Flk-1
associated neoangiogenesis may play a minor role
for the biology of paediatric cavernomas,
while endoglin seems to act more prominently than
previously thought, particularly for the biology of paediatric
cavernomas.
PMID: 16489474 [PubMed - as supplied by
publisher]
The role of interleukin
1 in growth and metastasis of human cancer xenografts.
Elaraj
DM, Weinreich
DM, Varghese S,
Puhlmann
M, Hewitt SM,
Carroll NM,
Feldman ED,
Turner EM,
Alexander HR.
Authors' Affiliations: Surgical Metabolism Section, Surgery Branch, and
Laboratory of Pathology, Center for Cancer Research, National Cancer
Institute, Bethesda, Maryland.
Background: Interleukin 1 (IL-1) is a pluripotent
cytokine that promotes angiogenesis, tumor growth, and metastasis in
experimental models; its presence in some human cancers is associated with
aggressive tumor biology. The purpose of these studies was to characterize
the role of IL-1 in human cancers and determine if inhibition of IL-1 via
its receptor antagonist, IL-1Ra, alters tumor growth and metastatic potential.Methods:
IL-1 mRNA or protein levels were determined in clinical tumor samples,
cancer cell lines, and xenografts using
quantitative reverse transcription-PCR or ELISA. Biological activity of
tumor-derived IL-1 protein was shown via induction of permeability across
endothelial cell monolayers. The effects of
recombinant IL-1Ra on tumor lines in culture (cell proliferation and IL-8
secretion) and in xenograft models (tumor growth,
metastatic potential, and intratumoral
levels of IL-8 and VEGF) were characterized. The effects of IL-1Ra-mediated
regression of xenograft growth on angiogenic proteins (IL-8 and VEGF) were evaluated in
an IL-1-producing melanoma (SMEL) xenograft model.RESULTS: IL-1 mRNA was highly expressed in more
than half of all tested metastatic human tumor
specimens including non-small-cell lung carcinoma, colorectal adenocarcinoma, and melanoma tumor samples.
Constitutive IL-1 mRNA expression was identified in several cancer cell
lines; tumor supernatant from these cell lines produced a significant
increase in endothelial cell monolayer permeability, a hallmark event in
early angiogenesis, in an IL-1-dependent manner. Moreover, systemic
recombinant IL-1Ra resulted in significant inhibition of xenograft growth and neovessel
density of IL-1-producing, but not non-IL-1-producing, tumor cell lines.
Subsequent analysis of SMEL, a melanoma cell line with constitutive IL-1
production, showed that neither exogenous IL-1 nor IL-1Ra altered tumor
cell proliferation rates in vitro. Gene expression analyses of IL-1Ra-treated
SMEL xenografts showed a >3-fold
down-regulation of 100 genes compared with control including a marked
down-regulation of IL-8 and VEGF.CONCLUSIONS: These data show that the IL-1
gene is frequently expressed in metastases from patients with several types
of human cancers. IL-1Ra inhibits xenograft
growth in IL-1-producing tumors but has no direct antiproliferative
effects in vitro; decreased tumor levels of IL-8 and VEGF may be an early
surrogate of IL-1Ra-mediated antitumor activity.
IL-1Ra may have a role alone or with other agents in the treatment of human
cancers.
PMID: 16489061 [PubMed - in process]
Cervical Cancer
P