- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer CenterNCI CANCERLIT® Search: Prostate Cancer, Hereditary - February 2002
National Cancer Institute®
Last Modified: February 1, 2002
Table of Contents
1
UI - 11734337
AU - Wang Q; Holmes DI; Powell SM; Lu QL; Waxman J
TI -
Analysis of stromal-epithelial interactions in prostate cancer
identifies PTPCAAX2 as a potential oncogene.
SO - Cancer Lett 2002 Jan 10;175(1):63-9
AD - Department of Cancer Cell Biology, Imperial College School of Medicine,
Hammersmith Campus, Du Cane Road, W12 ONN, London, UK.
A PCR-based subtractive hybridisation technique was used to identify
genes involved in stromal-epithelial interactions in prostate cancer.
Eight genes were identified as being differentially expressed in benign
prostatic fibroblast cells after stimulation with tumourigenic LNCaP
conditioned media. One of these genes, protein tyrosine phosphatase
CAAX2 (PTPCAAX2; also described as PTP4A and OV-1), has recently been
shown to be oncogenic in hamster pancreatic epithelial cells. We show
that PTPCAAX2 expression is up-regulated 4-fold in benign prostatic
fibroblast cells 24 h after stimulation with LNCaP conditioned media and
up-regulated 9-fold in prostatic tumour fibroblast cells. PTPCAAX2
overexpression was also detected in both androgen-dependent and
androgen-independent prostate cancer cell lines and prostate tumour
tissue, as determined by RT-PCR analysis and in situ hybridisation.
These observations of PTPCAAX2 overexpression in prostate tumour cells
and tissue suggest that PTPCAAX2 may potentially function as an oncogene
in prostate cancer.
2
UI - 11788727
AU - Collis SJ; Sangar VK; Tighe A; Roberts SA; Clarke NW; Hendry JH;
TI -
Margison GP
Development of a novel rapid assay to assess the fidelity of DNA
double-strand-break repair in human tumour cells.
SO - Nucleic Acids Res 2002 Jan 15;30(2):E1
AD - CRC Experimental Radiation Oncology Group, Paterson Institute for Cancer
Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20
4BX, UK.
Cellular survival following ionising radiation-mediated damage is
primarily a function of the ability to successfully detect and repair
DNA double-strand breaks (DSBs). Previous studies have demonstrated that
radiosensitivity, determined as a reduction in colony forming ability in
vitro, may be related to the incorrect repair (misrepair) of DSBs. The
novel rapid dual fluorescence (RDF) assay is a plasmid-based reporter
system that rapidly assesses the correct rejoining of a
restriction-enzyme produced DSBs within transfected cells. We have
utilised this novel assay to determine the fidelity of DSB repair in the
prostate tumour cell line LNCaP, the bladder tumour cell line MGH-U1 and
a radiosensitive subclone S40b. The two bladder cell lines have been
shown in previous studies to differ in their ability to correctly repair
plasmids containing a single DSB. Using the RDF assay we found that a
substantial portion of LNCaP cells [80.4 +/- 5.3(standard error)%]
failed to reconstitute reporter gene expression; however, there was
little difference in this measure of DSB repair fidelity between the two
bladder cell lines (48.3 +/- 3.5% for MGH-U1; 39.9 +/- 8.2% for S40b).
The RDF assay has potential to be developed to study the relationship
between DSB repair fidelity and radiosensitivity as well as the
mechanisms associated with this type of repair defect.
3
UI - 11525289
AU - Thurman SA; Ramakrishna NR; DeWeese TL
TI -
Radiation therapy for the treatment of locally advanced and metastatic
prostate cancer.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):423-43
AD - Department of Radiation Oncology, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21231, USA.
Radiation therapy for locally advanced PCa continues to evolve. A
current treatment recommendation for nonmetastatic, high-risk disease
includes AS combined with RT. The precise duration and sequencing of AS
has not been established but most frequently includes treatment in the
neoadjuvant, concomitant and, occasionally, adjuvant periods. As
technology allows higher doses without significant increases in
morbidity and as clinical data provide proof of a radiation dose
response, RT doses continue to escalate. The goal of therapy for
metastatic disease continues to focus on the relief of pain and the
improvement in quality of life. Multiple studies document the
significant role RT plays in achieving these goals. Focal RT and
systemic radioisotopes have become the mainstay of management in this
patient group and the development of newer isotopes that cause less
marrow toxicity will improve the therapeutic ratio and provide an
opportunity for their use with systemic chemotherapy. As molecular and
genomic technologies advance, directed targeting of critical cellular
radiation-response pathways hold the promise of improved radiation
response and individualized, tailored therapy.
4
UI - 11525293
AU - Ferrer FA; Rodriguez R
TI -
Prostate cancer gene therapy.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):497-508
AD - The James Buchanan Brady Urological Institute, The Johns Hopkins
Hospital, Baltimore, Maryland 21287-2101, USA.
Cancer-specific gene therapy is still in its infancy. Although the first
gene therapy trials were initiated in the late 1980s, it was only more
recently that the first successful treatment of a genetic disease was
reported.3 The current problems with low efficiency of gene transfer
coupled with the immunologic difficulties with certain vectors indicate
that more effort needs to be directed at the basic science of gene
transfer. Ultimately, successful cancer-specific gene therapy will
require combinations of the lessons learned from the ex vivo and in vivo
paradigms. The next generation of gene therapy trials likely will focus
on combination therapy with conventional chemotherapeutic agents,
differentiating agents, or radiation therapy. The obstacles to the
development of gene-based human therapeutics (i.e., molecular medicine)
are formidable, but the benefits are so great that eventually the
technical issues of gene transfer methodology will be worked out, and
ultimately this will become the standard of care, not only for inborn
errors of metabolism, but also for cancer.
5
UI - 11525296
AU - Reese DM
TI -
New agents for prostate cancer.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):547-57
AD - Department of Medicine, UCSF Comprehensive Cancer Center, University of
California San Francisco, USA. dreese85@hotmail.com
Given the poor results with currently available therapies, it is
imperative that new treatments be developed for patients with advanced
prostate cancer. The next generation of therapies will include many
novel biologic agents targeted at molecular defects in the cancer cell.
Investigating the efficacy and safety of these compounds and evaluating
their utility in combination with traditional therapies such as
chemotherapy or radiotherapy are major goals of prostate cancer clinical
research for the next decade.
6
UI - 11780394
AU - Yin L; Fu S; Wang X; Nanakorn T; Won J; Deisseroth A
TI -
Sensitization of prostate cancer cell lines to 5-fluorocytosine induced
by adenoviral vector carrying a CD transcription unit.
SO - Chin Med J (Engl) 2001 Sep;114(9):972-5
AD - Department of Pathophysiology, Shanghai Medical University, Shanghai
200032, China. lhyin@shmu.edu.cn
OBJECTIVE: To investigate the efficiency of the cytosine deaminase
adenoviral/5-fluorocytosine system on prostate cancer cell lines.
METHODS: We used cell culture, infectivity and sensitivity tests, to
observe bystander effect by animal tests. RESULTS: Established prostate
cancer cell lines are eventually infectible by adenoviral vector. The
ratio of vector/cell at which infection occurs depends on the specific
cell line. The peak of expression of the transferred cytosine deaminase
gene occurred in cells at different time, but persisted beyond 11 days.
These prostate cell lines are sensitized to 5-fluorocytosine by
infection with adenoviral vector carrying the cytosine deaminase gene.
Only 5% of the LNCap and 10% of the RM-1 cells were infected and
produced 100% cell death. In the animal test, there was significant
inhibition of tumor growth at a ratio of 400 vector particles/cell with
the systematic treatment of 5-fluorocytosine. CONCLUSIONS: Adenoviral
vector carrying a cytosine deaminase transcription unit can sensitize
prostate cancer cell lines to 5-fluorocytosine. The system can
significantly inhibit the growth of prostatic tumors in mice.
7
UI - 11807954
AU - Hursting SD; Shen JC; Sun XY; Wang TT; Phang JM; Perkins SN
TI -
Modulation of cyclophilin gene expression by
N-4-(hydroxyphenyl)retinamide: association with reactive oxygen species
generation and apoptosis.
SO - Mol Carcinog 2002 Jan;33(1):16-24
AD - Laboratory of Biosystems and Cancer, National Cancer Institute at
Frederick, Frederick, Maryland, USA.
To explore the mechanisms underlying the pro-apoptotic effects of the
synthetic retinoid N-4-(hydroxyphenyl)retinamide (4-HPR) on LNCaP human
prostate cancer cells, we used the differential display-polymerase chain
reaction (DD-PCR) technique to identify 4-HPR-responsive genes. RNA
extracted from LNCaP cells that had been treated for 24 h with 4-HPR at
a dose (2.5 microM) optimal for apoptosis induction was used for DD-PCR
analysis using random primers. A differentially expressed 115 bp
fragment was cloned and sequenced and then identified in GenBank as
having a high degree of homology with several members of the cyclophilin
gene family. Northern blot analyses using specific probes for
cyclophilin A, cyclophilin D, and the cloned 115-bp fragment were
performed on RNA extracted from LNCaP cells and MCF-7 human breast
cancer cells treated with 4-HPR, N-acetylcysteine (NAC, an
anti-oxidant), 4-HPR plus NAC, cyclosporin A, R-1881 (a synthetic
androgen), dehydroepiandrosterone, all-trans retinoic acid, or
prednisone. 4-HPR downregulated the transcript detected by the 115-bp
fragment. Expression patterns detected by the 115-bp fragment and
cyclophilin D probes were identical in response to each treatment; none
of these treatments affected cyclophilin A expression. Furthermore,
expression of mRNA transcripts detected by the 115-bp fragment and
cyclophilin D probes correlated with the generation of reactive oxygen
species (ROS), as detected by measurement of 2,7-dichlorofluorescein
oxidation. Therefore, members of the cyclophilin gene family, such as
cyclophilin D (a component of the mitochondrial permeability transition
pore previously linked with oxidative stress and apoptosis), may play a
role in the ROS-mediated apoptotic effects of 4-HPR. Published 2002
Wiley-Liss, Inc.
8
UI - 11501969
AU - Sampson ER; Yeh SY; Chang HC; Tsai MY; Wang X; Ting HJ; Chang C
TI -
Identification and characterization of androgen receptor associated
coregulators in prostate cancer cells.
SO - J Biol Regul Homeost Agents 2001 Apr-Jun;15(2):123-9
AD - Department of Pathology, and The Cancer Center, University of Rochester,
NY, USA.
The androgen receptor (AR) is a member of the nuclear receptor (NR)
superfamily that mediates the effects of androgens on target tissues.
Over the last decade, it has become apparent that NRs require accessory
factors for optimal activation of target gene expression. Numerous NR
coregulators have been identified, with diverse structures and potential
mechanisms of coregulation, creating an increasingly complicated picture
of NR action. Due to the expanding complexity of the coregulator field,
this review will focus on the AR ligand-binding domain (LBD) and
N-terminal interacting proteins identified by our lab. The
LBD-interacting proteins ARA70, ARA55 and ARA54 were first characterized
and ARA70 was found to have a relatively higher specificity for the AR
in human prostate cancer DU145 cells. Characterization of the functional
relationship between the AR and these coregulators indicated that ARA70
and ARA55 could enhance the androgenic effects of 17beta-estradiol (E2)
and hydroxyflutamide (HF), an antiandrogen commonly used in the
treatment of prostate cancer. ARA160, an AR N-terminal interacting
protein also known as TATA element modulatory factor (TMF), was
subsequently shown to cooperate with ARA70 in enhancing AR activity.
Another AR N-terminal interacting protein, ARA24, interacted with the
poly-Q tract, a region within the N-terminus of the AR linked to
Kennedy's disease (X-linked spinal and bulbar muscular atrophy). More
recently, our lab has identified ARA267, a SET domain containing
protein, and supervillin, an F-actin binding protein, as AR
coregulators. Collectively, the data from these studies indicate that
these coregulators are necessary for optimal AR transactivation.
Interruption of the interaction between AR and these proteins may serve
as a new therapeutic target in the treatment of prostate cancer.
9
UI - 11510986
AU - Culp LA; Holleran JL; Miller CJ
TI -
Tracking prostate carcinoma micrometastasis to multiple organs using
histochemical marker genes and novel cell systems.
SO - Histol Histopathol 2001 Jul;16(3):945-53
AD - Department of Molecular Biology and Microbiology, Case Western Reserve
University, School of Medicine, Cleveland, OH 44106, USA.
lac7@po.cwrv.edu
Studies of human prostate carcinoma (PCA) have been hampered by only a
few cell systems from already-metastatic human disease. We have
developed a novel cell system by using tissue cultured CWR22R cells from
a xenograft of a primary tumor from a human patient. These cells were
transfected with the bacterial lacZ gene to maximize their detection
during progression and metastasis in nude mice. LZ-CWR22R cells are
extremely stable for lacZ expression over 25 passages and metastasize to
lung, liver, and bone from the subcutis - major sites of metastasis of
the human disease. A matrigel vehicle facilitated development of primary
tumors and micrometastases in all organs. While some micrometastases
developed into overt metastases, others remained as micrometastases for
long periods of time, possibly providing a model of latency of
metastatic disease. An experimental metastasis model (tail vein
injection) also generated micrometastases in lung, liver, and bone with
differing kinetics of formation and stability. Serial sections of many
individual lung micrometastases within one hour of injection indicated
considerable heterogeneity in cellular composition (from 1 to 19
cells/site) while liver sites at later times were comprised of only 1 or
2 cells (the size of bone sites were comparable to those of liver). By
combining use of these histochemically-tagged PCA cell systems with high
resolution molecular analyses (laser-capture microdissection), it will
now be possible to analyze gene expression patterns characteristic of
micrometastases developing in several different organs.
10
UI - 11519827
AU - Krupski T; Harding MA; Herce ME; Gulding KM; Stoler MH; Theodorescu D
TI -
The role of vascular endothelial growth factor in the tissue specific in
vivo growth of prostate cancer cells.
SO - Growth Factors 2001;18(4):287-302
AD - Department of Molecular Physiology and Biological Physics, University of
Virginia, Health Sciences Center, Charlottesville, USA.
Despite the fact that cancer cells can be found in many vascular beds,
continued growth of the metastatic tumor focus exhibits a significant
degree of 'organ tropism', with only certain organs exhibiting the
ravages of metastatic disease. Since a limiting factor to the growth of
metastases beyond 2 mm in diameter, may be a lack of angiogenesis, we
sought to determine whether tumor overexpression of vascular endothelial
growth factor (VEGF), a potent angiogenic factor related to prostate
cancer metastasis, is causally related to organ specific tumor growth in
a prostate cancer xenograft model. LnCaP-C4-2 is a subline of the human
prostate cancer cell line LnCaP which unlike its parent, has a
predilection for growth in bone, a common site for human prostate cancer
metastasis. LnCaP-C4-2, is tumorigenic when injected intrafemorally in
mice but requires co-injection of stromal components (Matrigel) to be
tumorigenic in the subcutaneous site. Because of this site-specific
tumorigenicity profile and relatively low VEGF mRNA and protein
expression, this line was transfected with a full length cDNA encoding
the 165 isoform of VEGF. Cells either overexpressing or not expressing
the transfected gene were selected for study in vivo and in vitro.
Overexpression of VEGF did not seem to affect in vitro cell growth. Such
overexpression did affect tumorigenicity and in vivo tumor growth rates
when cells were inoculated in the subcutaneus site. Interestingly, the
dependency of subcutaneous tumorigenicity on Matrigel co-inoculation was
still observed in cells overexpressing VEGF. In contrast to the impact
that VEGF overexpression has on subcutaneous tumorigenicity, no such
effect was observed when cells were inoculated in orthotopic/prostate
(primary) or intrafemoral (metastatic) sites. In view of the importance
of tumor-stromal interactions in growth of xenografts, we sought to
determine if the host strain is important to the observed tumorigenicity
effects of VEGF overexpression. No differences in subcutaneous
tumorigenicity as a function of either Matrigel use or VEGF expression
levels were observed when SCID/bg and RAG/pfp mouse strains were
compared. In conclusion, our data indicate that the biological impact of
prostate tumor VEGF overexpression is organ/site specific, leading to
the speculation that it may play a part in the observed organ tropism of
metastatic spread. In addition, these results highlight the importance
of the tumor microenvironment in determining the biological impact of
transfected and overexpressed genes in the study of tumor biology.
11
UI - 11719283
AU - Gregory CW; He B; Wilson EM
TI -
The putative androgen receptor-A form results from in vitro proteolysis.
SO - J Mol Endocrinol 2001 Dec;27(3):309-19
AD - Laboratories for Reproductive Biology, Department of Pediatrics,
Lineberger Comprehensive Cancer Center, University of North Carolina,
Chapel Hill, NC 27599, USA.
Activation domains in the 114 kDa androgen receptor (AR) NH(2)- and
carboxyl-terminal regions are thought to contribute to different extents
to AR-mediated transactivation. We investigated using anti-peptide
antibodies whether smaller AR forms that migrate like the previously
described 87 kDa AR-A occur in vivo resulting in constitutive or
increased gene activation. Immunoblots of prostate cancer and fibroblast
cell culture extracts revealed 114 and 84 kDa AR forms. Antibody mapping
indicated the 84 kDa AR lacked the ligand-binding domain and comigrated
with the constitutively active AR fragment AR1-660. AR expressed in COS
cells was 114 and 92 kDa. Migration of the 92 kDa AR was slightly slower
than that of a 90 kDa expressed fragment that was designed to initiate
at the second methionine (residue 189) and lacked the NH(2)-terminal
FxxLF interaction sequence. The 92 kDa AR did not result from
alternative initiation since it was observed when the second methionine
was changed to alanine. Optimization of extraction conditions indicated
that both 84 and 92 kDa forms resulted from in vitro proteolytic
cleavage and that cleavage by caspase-3 could account for the 92 kDa
form. The results suggest that AR forms with gel mobility similar to
that of the previously described 87 kDa AR-A result from in vitro
proteolytic cleavage of NH(2)- or carboxyl-terminal regions during cell
extraction and storage and that smaller forms with increased
transcriptional activity do not occur in vivo.
12
UI - 11693894
AU - Stern DF
TI -
HER-2 testing in prostate carcinoma.
SO - Cancer J 2001 Sep-Oct;7(5):372-4
AD - Department of Pathology, Yale University School of Medicine, New Haven,
Connecticut 06510, USA.
13
UI - 11693898
AU - Liu HL; Gandour-Edwards R; Lara PN Jr; de Vere White R; LaSalle JM
TI -
Detection of low level HER-2/neu gene amplification in prostate cancer
by fluorescence in situ hybridization.
SO - Cancer J 2001 Sep-Oct;7(5):395-403
AD - Department of Internal Medicine, University of California, San
Francisco, USA.
PURPOSE: Although expression of the HER-2/neu oncogene has been
correlated with tumor progression in prostate cancer, the biologic
significance of detecting HER-2/neu gene amplification by fluorescence
in situ hybridization (FISH) or evidence for protein overexpression by
immunohistochemistry (IHC) remains unclear. In this study, we directly
compared HER-2/neu FISH and IHC to determine which may be more
predictive of the response to trastuzumab. PATIENTS AND METHODS: Forty
patients with prostate cancer were analyzed for gene amplification by
FISH performed with HER-2/neu and chromosome 17 (CEP 17) DNA probes
(Vysis). Protein expression was examined by immunofluorescence and by
IHC using the DAKO HercepTest antibody protocol and a monoclonal
antibody to Her-2/neu on archival paraffin sections. The patients
included 30 men with primary tumors that were treated with radical
prostatectomy. Of these, 15 demonstrated subsequent disease progression
within 3 years. Five patients with prostatic intraepithelial neoplasia
were tested, as were five with metastatic disease whose samples were
obtained before androgen ablation therapy. RESULTS: None of the 30
primary prostate cancer specimens showed overexpression for HER-2/neu by
immunofluorescence or by IHC with the DAKO protocol. One sample showed
3+ membrane expression with the monoclonal antibody. In contrast, low
copy number gene amplifications (3-8 HER-2/neu signals/nucleus) were
detected in 16 of 30 samples (53%) by FISH. Most amplified cells were
diploid for CEP 17, demonstrating that amplification was not due to
total cell aneuploidy. FISH and IHC determined that prostatic
intraepithelial neoplasia samples were normal. Four of five (80%)
metastatic samples were amplified for HER-2/neu by FISH. Nearly 70% of
metastatic cancer cells among all five specimens demonstrated
aneuploidy. A single lymph node metastasis showed 3+ membrane staining
by IHC (DAKO). CONCLUSIONS: In contrast to breast cancer, FISH detects
HER-2/neu amplification in a substantial proportion of prostate cancers
that do not overexpress HER-2/neuby IHC. Although the biologic
significance of this finding is uncertain, it has implications for the
direction of current and planned clinical trials of trastuzumab in
advanced prostate cancer, including determination of patient
eligibility.
14
UI - 11785977
AU - Zhou Y; Toth M; Hamman MS; Monahan SJ; Lodge PA; Boynton AL; Salgaller
TI -
ML
Serological cloning of PARIS-1: a new TBC domain-containing, immunogenic
tumor antigen from a prostate cancer cell line.
SO - Biochem Biophys Res Commun 2002 Jan 18;290(2):830-8
AD - Department of Molecular Medicine, Northwest Hospital, Suite 101,
Bothell, Washington 98021, USA. yaling@nwbio.com
Identifying immunogenic tumor antigens plays a critical role in
developing efficient diagnostic and therapeutic strategies for treatment
of cancer. Using a recently developed technology, serological
identification of antigens by recombinant expression cloning (SEREX), we
identified a total of 8 genes whose expression elicited antibody
responses in prostate cancer patients. Of the 8 genes, 5 represented
known genes in the GenBank database, 2 were previously uncharacterized
genes, and 1 showed sequence homology to a mouse gene. The sequence
feature and the expression of one of the novel genes, prostate antigen
recognized and identified by SEREX (PARIS-1), are determined in this
study. The PARIS-1 cDNA is 3257 bp in length and contains a complete
open reading frame of 2751 bp encoding for a primary translation product
of 917 amino acids. Using Northern blot hybridization assay, we detected
a single species of approximately 3.3 kb PARIS-1 mRNA that is
differentially expressed in prostate normal and cancer cells. Western
blot analysis confirmed the expression of the PARIS-1 protein in these
cells. Structure analysis revealed that PARIS-1 protein contains a TBC
domain that is conserved in the family of cell cycle-regulatory and Rab
GTPase-activating proteins (Rab-GAP). Thus, the PARIS-1 protein may play
a role in regulation of cell differentiation and growth or represent a
new member of the Rab-GAP family.
15
UI - 11782371
AU - Fan S; Ma YX; Wang C; Yuan RQ; Meng Q; Wang JA; Erdos M; Goldberg ID;
TI -
Webb P; Kushner PJ; Pestell RG; Rosen EM
p300 Modulates the BRCA1 inhibition of estrogen receptor activity.
SO - Cancer Res 2002 Jan 1;62(1):141-51
AD - Department of Radiation Oncology, Long Island Jewish Medical Center, New
Hyde Park, New York 11040, USA.
We previously reported that expression of the breast cancer
susceptibility gene BRCA1 strongly inhibits the transcriptional activity
of the estrogen receptor (ER-alpha) in human breast and prostate cancer
cell lines but only weakly inhibits ER-alpha activity in cervical cancer
cells (S. Fan et al., Science (Wash. DC), 284: 1354-1356, 1999). We now
report that the ability of BRCA1 to repress ER-alpha activity correlates
with its ability to induce down-regulation of the cellular levels of the
transcriptional coactivator p300 in breast and prostate, but not in
cervical cancer cells. On the other hand, BRCA1 failed to alter the
expression of the CREB binding protein (CBP), the structural and
functional homologue of p300, in any of these cell types. Ectopic
expression of either p300 or CBP "rescued" (i.e., reversed) the BRCA1
inhibition of ER-alpha activity, whereas two other nuclear receptor
coactivators, the p300/CBP-associated factor (PCAF) and the
glucocorticoid receptor-interacting protein-1 (GRIP1), failed to rescue
the ER-alpha activity. The rescue function mapped to the
cysteine-histidine rich domain CH3, a region of p300/CBP that we found
to interact directly with the conserved COOH-terminal activation domain
(AF-2) of ER-alpha. p300 and ER-alpha were also found to interact in
vivo and to colocalize within the nucleus in breast cancer cells. These
findings suggest that the cofactors p300 and CBP modulate the ability of
the BRCA1 protein to inhibit ER-alpha signaling. They further suggest
that the BRCA1 inhibition of ER-alpha activity may be attributable, at
least in part, to the down-regulation of p300.
16
UI - 11782385
AU - Kufer P; Zippelius A; Lutterbuse R; Mecklenburg I; Enzmann T; Montag A;
TI -
Weckermann D; Passlick B; Prang N; Reichardt P; Dugas M; Kollermann MW;
Pantel K; Riethmuller G
Heterogeneous expression of MAGE-A genes in occult disseminated tumor
cells: a novel multimarker reverse transcription-polymerase chain
reaction for diagnosis of micrometastatic disease.
SO - Cancer Res 2002 Jan 1;62(1):251-61
AD - Institute of Immunology, University of Munich, 80336 Munich, Germany.
kufer@ifi.med.uni-muenchen.de
Systemically disseminated tumor cells have become the subject of
intensive research as the presumed seminal precursors of later distant
metastasis. We describe here a novel sensitive multimarker nested
reverse transcription (RT)-PCR capable of detecting the individual
expression of human MAGE-A genes MAGE-1, -2, -3/6, -4, and -12 by rare,
disseminated tumor cells in bone marrow and blood of patients with many
different types of cancer. We analyzed bone marrow aspirates from 106
patients with breast, lung, colorectal, and prostate cancer and with
different sarcomas. Heterogeneous expression of the different MAGE genes
was found frequently in all those kinds of malignancies, in sharp
contrast to 30 bone marrow and 20 blood samples from healthy donors,
which were completely MAGE negative. Expression of at least one MAGE
gene in bone marrow was more frequent than cytokeratin-positive tumor
cells detected by immunocytochemistry, although the results of both
tests overlapped considerably. In 30 patients with clinically localized
prostate cancer, analysis by the multimarker MAGE RT-PCR of bilateral
bone marrow aspirates from the right and left iliac crest revealed a
positivity rate of 60%, which was twice as high as that obtained with
either an established prostate-specific antigen RT-PCR or by
cytokeratin-based immunocytochemistry. Analysis of primary prostate
cancer revealed MAGE expression patterns considerably concordant with
those found in the corresponding bone marrow aspirates. Prostate cancer
patients carrying an exceptionally high risk of metastatic relapse, as
defined by clinical prognostic factors, were significantly more often
MAGE positive than patients with a distinctly lower risk (P = 0.02,
Fisher's exact test). More frequent MAGE expression in the peripheral
blood of patients with metastatic prostate cancer compared with those
with clinically localized disease added further evidence for the
prognostic impact of the multimarker MAGE RT-PCR. Moreover,
MAGE-positive bone marrow samples from a small group of seven sarcoma
patients demonstrated the relevance of our multimarker RT-PCR in
nonepithelial tumors. Because MAGE antigens can induce autologous
cytolytic T lymphocytes in vivo, the determination of individual MAGE
expression patterns in cancer patients may furthermore identify
candidate vaccine targets for adjuvant immunotherapy.
17
UI - 11782357
AU - Filippova GN; Qi CF; Ulmer JE; Moore JM; Ward MD; Hu YJ; Loukinov DI;
TI -
Pugacheva EM; Klenova EM; Grundy PE; Feinberg AP; Cleton-Jansen AM;
Moerland EW; Cornelisse CJ; Suzuki H; Komiya A; Lindblom A;
Dorion-Bonnet F; Neiman PE; Morse HC 3rd; Collins SJ; Lobanenkov VV
Tumor-associated zinc finger mutations in the CTCF transcription factor
selectively alter tts DNA-binding specificity.
SO - Cancer Res 2002 Jan 1;62(1):48-52
AD - Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle,
Washington 98109, USA.
CTCF is a widely expressed 11-zinc finger (ZF) transcription factor that
is involved in different aspects of gene regulation including promoter
activation or repression, hormone-responsive gene silencing,
methylation-dependent chromatin insulation, and genomic imprinting.
Because CTCF targets include oncogenes and tumor suppressor genes, we
screened over 100 human tumor samples for mutations that might disrupt
CTCF activity. We did not observe any CTCF mutations leading to
truncations/premature stops. Rather, in breast, prostate, and Wilms'
tumors, we observed four different CTCF somatic missense mutations
involving amino acids within the ZF domain. Each ZF mutation abrogated
CTCF binding to a subset of target sites within the promoters/insulators
of certain genes involved in regulating cell proliferation but did not
alter binding to the regulatory sequences of other genes. These
observations suggest that CTCF may represent a novel tumor suppressor
gene that displays tumor-specific "change of function" rather than
complete "loss of function."
18
UI - 11802201
AU - Patel S; Turner PR; Stubberfield C; Barry E; Rohlff CR; Stamps A; Tyson
TI -
K; Terrett J; Box G; Eccles S; Page MJ
Hyaluronidase gene profiling and role of hyal-1 overexpression in an
orthotopic model of prostate cancer.
SO - Int J Cancer 2002 Feb 1;97(4):416-24
AD - Oxford GlycoSciences, Abingdon Science Park, Abingdon, Oxfordshire,
United Kingdom.
The mRNA levels of hyal-1, hyal-2, LUCA3 and PH20, the 4 hyaluronidases
with demonstrated endoglucosaminidase activity, were extensively
profiled in normal and tumor tissues and cell lines, using dot blot
analysis and quantitative PCR. In normal tissues, hyal-1, hyal-2 and
LUCA3 all showed unique patterns of mRNA expression, but were generally
of widespread distribution, whereas PH20 mRNA was restricted to testes.
In a small set of breast tumor samples, no elevations in hyal-1, hyal-2
or LUCA3 mRNA were seen. Hyaluronidase activity measured by a novel
assay or zymography was also not elevated in sera from a number of
breast cancer patients, compared to sera from normal volunteers. In ex
vivo xenograft tumor cell lines, however, hyal-1 or hyal-2 mRNA levels
were frequently elevated, whereas LUCA3 was only infrequently elevated
and PH20 not at all. Two cell lines were engineered to overexpress
hyal-1: a breast cancer line (CAL51) and a prostate cancer line (PC3M).
Although the in vitro properties of the hyal-1 overexpressing cell lines
were indistinguishable from the parental cells, the orthotopic growth of
hyal-1 expressing PC3M cells in nu/nu mice resulted in significantly
increased numbers of metastases, supportive of a role for hyal-1 in
extravasation and metastatic tumor formation in this model of prostate
cancer. Copyright 2001 Wiley-Liss, Inc.
19
UI - 11796315
AU - Platz EA; Krithivas K; Kantoff PW; Stampfer MJ; Giovannucci E
TI -
ATAAA repeat upstream of glutathione S-transferase P1 and prostate
cancer risk.
SO - Urology 2002 Jan;59(1):159-64
AD - Department of Epidemiology, Johns Hopkins University Bloomberg School of
Public Health, Baltimore, Maryland 21205, USA.
OBJECTIVES: Expression of glutathione S-transferase pi (GSTP1), a
detoxification enzyme that also binds steroid hormones, is diminished or
absent in human prostate tumors possibly because of promoter
hypermethylation. Upstream of its promoter is a polymorphic ATAAA repeat
of unknown functional significance. We evaluated whether this
polymorphism is associated with prostate cancer. METHODS: Incident
prostate cancer cases (n = 186) and controls (n = 398) were identified
among participants in the Physicians' Health Study. DNA was extracted
from peripheral whole blood, and the region encompassing the repeat was
amplified using fluorescent-labeled primers. The fragments were run on
polyacrylamide gels and sized by Genescan software. Alleles were
designated by polymerase chain reaction fragment size. We estimated the
relative risk of prostate cancer for the GSTP1 gene ATAAA alleles and
genotype from logistic regression models controlling for age and
cigarette smoking status. RESULTS: Fifteen GSTP1 ATAAA alleles were
observed; C (19 repeats), G (21 repeats), and I (22 repeats) accounted
for 80% among the controls. Compared with C, the relative risks for
prostate cancer were 1.1 (95% confidence interval 0.7 to 1.7) for G and
0.8 (95% confidence interval 0.6 to 1.2) for I. The relative risks were
also not statistically significantly elevated for the less common
alleles. Compared with CC, the most common genotype, none of the other
genotypes appeared to be associated with an increased risk of prostate
cancer. CONCLUSIONS: The results of this study do not support an
important role of the ATAAA repeat polymorphism upstream from the GSTP1
promoter in prostate cancer incidence.
20
UI - 11781655
AU - van der Poel HG; McCadden J; Verhaegh GW; Kruszewski M; Ferrer F;
TI -
Schalken JA; Carducci M; Rodriguez R
A novel method for the determination of basal gene expression of
tissue-specific promoters: an analysis of prostate-specific promoters.
SO - Cancer Gene Ther 2001 Dec;8(12):927-35
AD - Brady Urologic Institute, Johns Hopkins Medical School, Baltimore,
Maryland 21287, USA.
Because the toxicity of suicide gene therapeutics is directly related to
basal promoter activity, we developed an assay to test for promoter
"leakiness" using a diphtheria toxin mutant. Sequences of 15
prostate-specific gene promoter constructs were cloned in an expression
plasmid (pBK; Stratagene, La Jolla, CA) backbone driving expression of
an attenuated mutant of diphtheria toxin A (tox176). Low expression
levels of the DT-tox176 result in significant protein synthesis
inhibition reflected by a decreased expression of the luciferase
activity of a simultaneously transfected CMV luciferase construct. ID50
(dose of plasmid with 50% luciferase inhibition) was calculated for each
promoter construct in different cell lines. Highest transactivational
activity (ID50 <75 ng) was found for the CMV promoter in all cell lines,
which is in agreement with the dual luciferase assay findings. Unlike
the dual luciferase findings, however, the DT-tox176 assay showed
protein inhibition of CN65 (PSA promoter/enhancer) and PSE-hK2 (PSA
enhancer and basal human kallikrein 2 promoter) in HEK293 and DLD cells
indicating "leakiness" of these promoter constructs. Low basal promoter
activity in nonprostate cell lines was found for the minimal PSA
promoter, hK2, DD3, and OC promoters. The DT-tox176 assay can better
predict basal promoter activity compared to less sensitive dual
luciferase assay.
21
UI - 11795433
AU - Nelson WG; De Marzo AM; Deweese TL; Lin X; Brooks JD; Putzi MJ; Nelson
TI -
CP; Groopman JD; Kensler TW
Preneoplastic prostate lesions: an opportunity for prostate cancer
prevention.
SO - Ann N Y Acad Sci 2001 Dec;952():135-44
AD - The Johns Hopkins Comprehensive Cancer Center, Baltimore, Maryland
21231-1000, USA. bnelson@jhmi.edu
Environmental factors, especially the diet, play a prominent role in the
epidemic of prostate cancer (PCA), in the United States. Many candidate
dietary components have been proposed to influence human prostatic
carcinogenesis, including fat, calories, fruits and vegetables,
anti-oxidants, and various micronutrients, but the specific roles
dietary agents play in promoting or preventing PCA remain controversial.
We have collected evidence to suggest that GSTP1, the gene encoding the
pi-class glutathione S-transferase (GST), may serve a "caretaker"
function for prostatic cells. Although GSTP1 can be detected in normal
prostatic epithelium, in almost all PCA cases, PCA cells fail to express
GSTP1 polypeptides, and lack of GSTP1 expression most often appears to
be the result of somatic "CpG island" DNA methylation changes. Loss of
GSTP1 function also appears to be characteristic of prostatic epithelial
neoplasia (PIN) lesions, thought to represent PCA precursors. We have
recently learned that a new candidate early PCA precursor lesion,
proliferative inflammatory atrophy (PIA), characterized by proliferating
prostatic cells juxtaposed to inflammatory cells, contains epithelial
cells that express high levels of GSTP1. These findings have formed the
basis for a new model of prostatic carcinogenesis, in which prostatic
cells in PIA lesions, subjected to a barrage of inflammatory oxidants,
induce GSTP1 expression as a defense against oxidative genome damage.
When cells with defective GSTP1 genes appear amongst the PIA cells, such
cells become vulnerable to oxidants and electrophiles that inflict
genome damage that tends to promote neoplastic transformation to PIN and
PCA cells. Subsequently, PIN and PCA cells with defective GSTPI genes
remain vulnerable to similar stresses tending to promote malignant
progression. This new model for prostatic carcinogenesis has
implications for the design of new prostate cancer prevention
strategies. Rational prevention approaches might include: (i)
restoration of GSTPI expression via treatment with inhibitors of CpG
methylation, (ii) compensation for inadequate GSTPI activity via
treatment with inducers of general GST activity, and (iii) abrogation of
genome-damaging stresses via avoidance of exogenous carcinogens and/or
reduction of endogenous carcinogenic (particularly oxidant) stresses.
22
UI - 11795434
AU - Brawley OW; Barnes S; Parnes H
TI -
The future of prostate cancer prevention.
SO - Ann N Y Acad Sci 2001 Dec;952():145-52
AD - Office of the Director, National Cancer Institute, Bethesda, Maryland
20852, USA.
The dramatic international variation in prostate cancer mortality rates
suggest an environmental influence. This combined with a building
understanding of the genetic mechanisms of carcinogenesis encourages a
search for ways to prevent it. Androgenic stimulation over a period of
time has been suggested a cause of prostate cancer. The corollary to
this hypothesis is that lowering androgenic stimulation over time will
prevent prostate cancer. Decreasing androgenic stimulation of the
prostate with 5-alpha-reductase inhibitors such as finasteride has been
shown to decrease prostate size and may prevent prostate cancer. A
large, long-term clinical trial is underway using finasteride to
determine if it can prevent prostate cancer. Results are expected in
2004. Epidemiologic and laboratory studies also suggest that high
selenium and vitamin E intake lowers risk of prostate cancer. Recent
serendipitous findings of two randomized clinical trials support the
hypothesis that selenium and vitamin administration will decrease
prostate cancer risk. A study to assess these compounds is beginning.
Other promising, but less developed, interventions in chemoprevention of
prostate cancer include vitamin D supplementation and diet modification.
All will need to be rigorously evaluated before they can be advocated
for prostate cancer prevention.
23
UI - 11772238
AU - Mitsiades CS; Koutsilieris M
TI -
Molecular biology and cellular physiology of refractoriness to androgen
ablation therapy in advanced prostate cancer.
SO - Expert Opin Investig Drugs 2001 Jun;10(6):1099-115
AD - Department of Experimental Physiology, Medical School, University of
Athens, 75 Micras Asias, Goudi 11527, Athens, Greece.
We review the extensive body of data on the molecular aetiology of
hormone refractory disease in metastatic prostate cancer patients.
Particular emphasis is placed on the crucial role of the bone
micro-environment, especially the intercellular interactions of
metastatic prostate cancer cells and osteoblasts in promoting the
establishment of hormone refractory disease. Resistance of tumour cells
to anticancer therapies is generally viewed as a phenomenon almost
exclusively determined by chromosomal defects and/or gene mutations.
However, it is now well-documented that the local milieu of the bone
metastases can also protect tumour cells from anticancer therapy-
induced apoptosis, either independently or synergistically with
resistance-related genetic alterations. A key determinant of this
protection is the urokinase/plasmin cascade which modulates the local
concentration of survival factors, such as insulin-like growth factor
(IGF-1). The molecular pathways whereby this major growth and survival
factor for prostate cancer cells exerts its anti-apoptotic effect on
prostate cancer cells are discussed.
24
UI - 11572417
AU - Barnholtz-Sloan JS; de Andrade M; Chakraborty R
TI -
The impact of population admixture on traditional linkage analysis.
SO - Ethn Dis 2001 Autumn;11(3):519-31
AD - Karmanos Cancer Institute and Wayne State University, Integrated
Biostatistics Unit, Detroit, Michigan 48201, USA. barnholz@karmanos.org
INTRODUCTION: Families of admixed ancestry are routinely excluded from
traditional (Log of the Odds [LOD] score) linkage analysis or are
analyzed as being derived from a homogeneous population using the
proband's ethnicity. Using traditional linkage analysis with these
families can cause complications due to the mixing of different disease
rates and allele frequencies that occurs. The presence of admixture
violates the key assumptions of Hardy-Weinberg Equilibrium (HWE) and
Linkage Equilibrium (LE) invoked in the current methods of linkage
analysis. If one or more of these assumptions are violated, incorrect
inference for linkage could result. DESIGN AND METHODS: Through
simulation, we investigated the effect of admixture of two populations
on the LOD score under various conditions, using prostate cancer as our
underlying disease model. Four-generation homogeneous and admixed
families were simulated with 27 markers and two linked, bi-allelic
disease loci. Two different types of admixture were tested: admixture
within a family unit and a mixture of homogeneous families within a data
set. All mixing was done at the founder level in three different
proportions: 30/70, 50/50 and 70/30. RESULTS AND CONCLUSIONS: We
observed that the LOD scores under both models of admixture were closest
to the homogeneous family scores of the population having the highest
mixing proportion. Random sampling of families or ascertainment of
families with disease affection status did not affect this observation,
nor did the mode of inheritance (dominant/recessive) or sample size.
Thus, the presence of families of mixed population ancestry impacts
linkage analysis in terms of the LOD score and the estimate of the
recombination fraction.
25
UI - 11773976
AU - Kawakami K; Husain SR; Bright RK; Puri RK
TI -
Gene transfer of interleukin 13 receptor alpha2 chain dramatically
enhances the antitumor effect of IL-13 receptor-targeted cytotoxin in
human prostate cancer xenografts.
SO - Cancer Gene Ther 2001 Nov;8(11):861-8
AD - Laboratory of Molecular Tumor Biology, Division of Cellular and Gene
Therapies, Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, Maryland 20892, USA.
IL-13Ralpha2 chain, the primary interleukin-13 (IL-13) binding protein,
plays an important role in IL-13 binding and internalization. Based on
these findings, in our previous study we transiently transfected four
cancer cell lines that do not express IL-13Ralpha2 chain and
demonstrated that these cells acquired increased sensitivity to IL-13
receptor-targeted recombinant cytotoxin, IL13-PE38QQR, which is composed
of IL-13 and a mutated form of a Pseudomonas exotoxin. Although some
prostate cancer cell lines express functional IL-13R, they are not
highly sensitive to IL-13 cytotoxin. Here we investigated whether human
prostate cancer and normal prostate epithelial cell lines express
IL-13Ralpha2 chain and whether they can be sensitized to the cytotoxic
effect of IL-13 cytotoxin after transient or stable gene transfer of
IL-13Ralpha2 chain. Gene transfer of IL-13Ralpha2 chain improved binding
activity of IL-13 and sensitivity to IL-13 cytotoxin in vitro. In vivo
experiments demonstrated that gene transfer of IL-13Ralpha2 chain
dramatically enhanced the antitumor activity of IL-13 cytotoxin in human
prostate cancer xenograft models. These results suggest that
IL-13R-targeted cytotoxin therapy of prostate cancer may be dramatically
enhanced by gene transfer of IL-13Ralpha2 chain and this strategy, the
combination of gene therapy and cytotoxin therapy, may be utilized in
the treatment of localized prostate cancer.
26
UI - 11790283
AU - Vis AN; Oomen M; Schroder FH; van der Kwast TH
TI -
Feasibility of assessment of promoter methylation of the CD44 gene in
serum
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
