1/5. Characterization of a renal cell carcinoma cell line derived from a human bone metastasis and establishment of an experimental nude mouse model.PURPOSE: We provide the necessary tools to study the biology of bone metastasis using renal cell carcinoma as a model. A relevant renal cell carcinoma cell line developed from a human bone metastasis is described and an experimental model in the nude mouse was established. MATERIALS AND methods: The novel cell line RBM1 was developed from bone metastasis from a patient with renal cell carcinoma. in vitro methods used to study the cell line included karyotype analysis, reverse-transcriptase polymerase chain reaction, ribonuclease protection assay and Western blot analysis. An intratibial injection model in the nude mouse resulted in bone lesions similar to those in human patients. RESULTS: Chromosomal analysis of this cell line revealed characteristic cytogenetic abnormalities common in renal cell carcinoma. RBM1 cells expressed parathyroid hormone parathyroid hormone related peptide, interleukin-6 and macrophage colony-stimulating factor, which are cytokines involved in osteoclast activation and subsequent bone resorption. Western blot analysis revealed the presence of high levels of epidermal growth factor receptor and c-MET. Reproducible osteolytic lesions developed in the nude mouse after injecting 1 x 106 cells into the tibia. CONCLUSIONS: This cell line and animal model may allow further study of the biology and mechanism of renal cell carcinoma bone metastasis.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
2/5. A neuroendocrine/small cell prostate carcinoma xenograft-LuCaP 49.The late stages of progression of prostate carcinoma are typically characterized by an androgen-insensitive, rapidly proliferative state. Some late-stage tumors are composed predominantly of neuroendocrine cells. Virtually no animal models of a neuroendocrine/small cell variant of prostate carcinoma are available for experimental studies. We report a human neuroendocrine/small cell prostate carcinoma xenograft that was developed from a nodal metastasis of a human prostate carcinoma and that has been propagated as serial subcutaneous implants in severe combined immunodeficient mice for >4 years. Designated LuCaP 49, all tumor passages exhibit a neuroendocrine/small cell carcinoma phenotype-insensitivity to androgen deprivation, expression of neuroendocrine proteins, lack of expression of prostate-specific antigen or androgen receptor, and an unusually rapid growth (a doubling time of 6.5 days) for prostate cancer xenografts. Genetically this tumor exhibits loss of heterozygosity for the short arm of chromosome 8 and has a complex karyotype. This xenograft should prove to be useful in the investigation of mechanisms underlying the androgen-insensitive state of progressive prostate carcinoma.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
3/5. association of pigmentary anomalies with chromosomal and genetic mosaicism and chimerism.We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnormal pigmentation followed Blaschko lines. The literature contains at least 36 similar examples of an association between pigmentary anomalies and chromosomal mosaicism, as well as five examples of an association with chimerism. The pigmentary anomalies are pleomorphic, and the chromosomal anomalies involve autosomes and sex chromosomes. The pigmentation patterns are reminiscent of the archetypal paradigm seen in allophenic mice and demonstrate the clonal origin of melanoblasts from neural crest precursors. patients with anomalous skin pigmentation, particularly when it follows a pattern of Blaschko lines, should be appropriately evaluated for a possible association with chromosomal or genetic mosaicism or chimerism.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
4/5. down syndrome--a gene dosage disease caused by trisomy of genes within a small segment of the long arm of chromosome 21, exemplified by the study of effects from the superoxide-dismutase type 1 (SOD-1) gene.down syndrome (DS), the most common postnatally viable human autosomal chromosomal abnormality is caused by trisomy for chromosome 21. The mechanism whereby the supernumerary chromosome 21 contributes to the pathology of DS remains elusive. There are, however, several evidences that DS is a gene dosage disease. This means that overproduction of certain proteins, encoded by normal genes on the extra chromosome, distorts the delicate balance of some biochemical pathways that are important for proper development and function of the organs affected in DS. It has been shown that only the distal segment of the long arm of chromosome 21 is involved in the pathogenesis of DS. Great efforts to define this "DS specific" segment are made today, with the aim to find the "DS responsible" genes. It is suggested that as few as 10-20 genes might be responsible for the DS phenotype. We will report from a world-wide collaboration study and especially the result from one single patient. It is a woman with a characteristic phenotype of DS, but with microscopically normal karyotype. She had a sister with DS, who is dead. The parents were related, why an autosomal recessive disorder is suspected. Autoradiograms of quantitative Southern blots of DNAs from the patient and her parents were analyzed after hybridization with unique dna sequences regionally mapped on chromosome 21. The patient seems to have three alleles at the VTNR-polymorphism in the Col6A1 gene, one copy from the father and two copies from the mother. The Col6A1 gene is mapped at the very distal segment of the long arm of chromosome 21 (21q22.3). She has only two alleles of all loci analyzed proximal to Col6A1. This might indicate that she has trisomy only for the very distal part of band 21q22.3. It is, however, not enough to find the genes within the "DS specific" segment. The metabolic gene dosage effects from these genes must be evaluated. Although several genes have been mapped on chromosome 21, not one single feature of DS has been proved to be an effect of any single gene. As an example of the difficulties to assign features of DS to chromosome 21 specific genes the gene dosage effects of the superoxide dismutase type I (SOD-1) will be presented.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
5/5. Establishment of a human pancreatic tumor xenograft model: potential application for preclinical evaluation of novel therapeutic agents.adenocarcinoma of the pancreas is currently the fifth leading cause of death in the united states. It remains generally incurable by available treatment modalities. We report here on the characterization of a permanent pancreatic cell line (KCI-MOH1), established as a xenograft in severe combined immune deficient (SCID) mice, from a 74 year-old African American male patient diagnosed with pancreatic cancer. Sections from paraffin-embedded tumors excised from SCID mice revealed typical adenocarcinoma of the pancreas. Karyotypic analysis of cultured cells derived from tumors grown in SCID mice revealed a male karyotype with multiple clonal aberrations: 42, XY, add (3)(p11.2), der(7) t(7;12) (p22;q12), -10, -12, add (14)(p11), -18, add (20)(q13)-22/84, idemx2. Immunostaining of KCI-MOH1 tissues shows strong expression of p53 and p21 proteins. The xenograft model was established by transplanting the KCI-MOH1 cells subcutaneously (s.c.) in SCID mice. When the s.c. tumor was transplanted in vivo to other SCID mice, the success rate was 100%, with a doubling time of 8.5 days. The SCID mouse xenograft model was used to test the efficacy of selected standard chemotherapeutic drugs (taxol, gemcitabine, 5-fluorouracil, and Ara-C) and novel biological agents (Bryostatin 1 and Auristatin-PE). Results show that gemcitabine, Ara-C, and Bryostatin 1 were active against KCI-MOH1. The xenograft described herein can be used as an animal model to facilitate the development of novel therapeutic agents against human pancreatic cancers.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |