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National Cancer Institute®
Ultima Vez Modificado: 1 de mayo del 2002
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.
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.
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.
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
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.
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. firstname.lastname@example.org
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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