Table of Contents
1
UI - 11399379
AU - Moppett J; Oakhill A; Duncan AW
TI -
Second malignancies in children: the usual suspects?
SO - Eur J Radiol 2001 Jun;38(3):235-48
AD - Department of Paediatric Oncology, Bristol Royal Hospital for Sick
Children, St. Michael's Hill, BS2 8BJ, Bristol, UK.
The aim of this article is to provide an up to date review of second
malignant neoplasms (SMN's) following treatment for childhood cancer,
referring to their incidence, the role of genetic factors, and how the
primary malignancy and treatment received influence the type, site and
prognosis of SMN's. The role of genetic factors will be discussed as far
as they impact upon a predisposition to later development of SMN's. The
primary malignancies that have important associations with SMN's will
then be discussed, in particular Hodgkin's disease, retinoblastoma and
acute lymphoblastic leukaemia. The important second malignancies will be
highlighted, including tumours of the CNS and thyroid, osteosarcoma,
secondary acute myeloid leukaemia and melanoma. Emphasis will be put
upon identifying which patients are most likely to suffer from these
tumours. An important part of the article are case histories. These are
provided in combination with illustrations as a useful adjunct to the
text, with a particular emphasis on radiological features, diagnosis and
screening. Finally, the important but different roles of causal agents,
in particular chemotherapy and radiotherapy are highlighted.
2
UI - 11549509
AU - Haitel A; Wiener HG; Neudert B; Marberger M; Susani M
TI -
Expression of the cell cycle proteins p21, p27, and pRb in clear cell
renal cell carcinoma and their prognostic significance.
SO - Urology 2001 Sep;58(3):477-81
AD - Department of Pathology, University of Vienna, Vienna, Austria.
OBJECTIVES: To determine whether p21, p27, and pRb can predict disease
progression in clear cell renal cell carcinoma. METHODS: The expression
of three negative regulators of the cell cycle, the retinoblastoma gene
product (pRb), the WAF1/Cip1 gene product (p21), and the Kip1 gene
product (p27), was investigated by immunohistochemistry on paraffin
sections from 104 formalin-fixed clear cell carcinoma specimens and
related to p53 overexpression, the clinicopathologic parameters, and
survival. RESULTS: pRb expression was not associated with tumor stage,
but the correlation with p27 and p21 positivity was statistically
significant (r = 0.26, P = 0.008 and r = 0.3, P = 0.002, respectively).
Tumors representing p53 overexpression showed a higher pRb labeling
index compared with p53-negative tumors (P = 0.0004). p21 protein
expression correlated significantly with p27 positivity (r = 0.2, P =
0.04) and was associated with p53 overexpression (P = 0.0005), but did
not correlate with tumor stage or grade. No association could be found
between p27 positivity and tumor grade, tumor stage, or p53
overexpression. In univariate survival analysis, an increased pRb
positivity (P = 0.002) and a low p27 expression (P = 0.0001) predicted a
poor outcome, especially if combined with p53 overexpression (P = 0.004
and P = 0.0002, respectively). p21 did not give any prognostic
information. Moreover, in multivariate analysis, pRb and p27 were
revealed to be statistically significant. CONCLUSIONS: The results of
our study indicate that in clear cell renal cell carcinoma, the cell
cycle proteins p27 and pRb are powerful and independent prognostic
factors and that p21 has no predictive value.
3
UI - 11953594
AU - Fuchs B; Pritchard DJ
TI -
Etiology of osteosarcoma.
SO - Clin Orthop 2002 Apr;(397):40-52
AD - Mayo Clinic, Department of Orthopedics, Rochester, MN 55905, USA.
Although the prognosis and quality of life of patients with osteosarcoma
were improved significantly during the past decades, the pathogenesis
and etiology of this disease remain obscure. Significant interest and
effort in this cancer led to the identification of numerous etiologic
agents. Several chemical agents such as beryllium, viruses such as FBJ,
subsequently found to contain the src-oncogene, and radiation were shown
to be potent inducers of osteosarcoma. Paget's disease, electrical burn,
or trauma all are thought to be other factors that may contribute to the
pathogenesis. More recently, patients with hereditary diseases such as
Rothmund-Thomson syndrome, Bloom syndrome, and Li-Fraumeni syndrome were
found to have an increased risk of having osteosarcoma develop. During
the past few years, the molecular analysis brought a wealth of new
information with numerous genes that were associated with osteosarcoma
and its clinical disease progression. They can be categorized into
self-sufficiency in growth signals, insensitivity to growth inhibitory
signals, evasion of apoptosis, limitless replicative potential,
sustained angiogenesis, and tissue evasion and metastasis. Although the
understanding of these processes in osteosarcoma still is incomplete, it
may have the potential to significantly affect the patient care in the
future.
4
UI - 12011162
AU - Lefevre SH; Chauveinc L; Stoppa-Lyonnet D; Michon J; Lumbroso L; Berthet
TI -
P; Frappaz D; Dutrillaux B; Chevillard S; Malfoy B
A T to C mutation in the polypyrimidine tract of the exon 9 splicing
site of the RB1 gene responsible for low penetrance hereditary
retinoblastoma.
SO - J Med Genet 2002 May;39(5):E21
5
UI - 11980640
AU - Zheng L; Flesken-Nikitin A; Chen PL; Lee WH
TI -
Deficiency of Retinoblastoma gene in mouse embryonic stem cells leads to
genetic instability.
SO - Cancer Res 2002 May 1;62(9):2498-502
AD - Department of Molecular Medicine and Institute of Biotechnology,
University of Texas Health Science Center at San Antonio, San Antonio,
Texas 78245, USA.
Genetic instability has been recognized as a hallmark of human cancers.
Retinoblastoma (Rb) tumor suppressor protein has an essential role in
modulating cell cycle progression. However, there is no direct evidence
supporting its role in maintaining genetic stability. Here, we developed
a sensitive method to examine the level of chromosome instability by
using retrovirus carrying both positive and negative selectable markers
that integrated randomly into individual chromosomes, and the frequency
of loss of this selectable chromosomal marker (LOM) in normal mammalian
cells was measured. Our results showed that normal mouse embryonic stem
(ES) cells had a very low frequency of LOMs, which was less than
10(-8)/cell/generation. In Rb-/- mouse ES cells, the frequency was
increased to approximately 10(-5)/cell/generation, whereas in Rb+/- ES
cells, the frequency was approximately 10(-7)/cell/generation. LOMs was
mediated mainly through chromosomal mechanisms and not through point
mutations. These results, therefore, revealed that Rb, with a
haploinsufficiency, plays a critical role in the maintenance of
chromosome stability. The mystery of why Rb heterozygous carriers have
early-onset tumor formation with high penetrance can be, at least,
partially explained by this novel activity.
6
UI - 11919466
AU - Acikbas I; Keser I; Kilic S; Bagci H; Karpuzoglu G; Luleci G
TI -
Detection of LOH of the RB1 gene in bladder cancers by PCR-RFLP.
SO - Urol Int 2002;68(3):189-92
AD - Department of Medical Biology, Faculty of Medicine, Pamukkale
University, Denizli, Turkey. iacikbas@pamukkale.edu.tr
OBJECTIVES: Retinoblastoma (RB1) gene involves in retinoblastoma,
osteosarcoma, bladder, prostate, lung, breast carcinomas, and soft
tissue sarcomas. Loss of heterozygosity (LOH) is the most common
mutation of the gene. METHODS: Xba I polymorphism in intron 17 of the
gene was used to detect LOH in 20 bladder cancer patients. A cystitis
and an osteosarcoma were used as control. LOH was investigated in three
different kinds of samples (blood, paraffin-embedded tissue and fresh
tissue) belonging to the same patients, and 20 blood samples, 20
paraffin-embedded tissue samples and 16 fresh tissue samples were
obtained from 20 cancer patients. RESULTS: None of the 20 blood samples
showed LOH. Eleven out of 20 paraffin-embedded bladder tissues were
amplified, 3 of them homozygous and all 8 informative paraffin-embedded
tissues showed LOH. Five out of 16 fresh tumor tissues obtained were
amplified, in 1 the fresh tissue was normal, 1 fresh tissue showed LOH
and 3 were not digested by Xba I. CONCLUSION: The results of the study
have suggested that detection of LOH of the RB1 gene by PCR-RFLP can be
a good adjunctive test for evaluation of the bladder cancer. Copyright
2002 S. Karger AG, Basel
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