Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a new nonrandom rearrangement, dic(4;17)(p11;p11), which was identified in three patients with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). All three cases had in common atypical morphological features with a significant component of prolymphocytes, an unusual clinical outcome, and were refractory to chemotherapy. To further define the cytogenetic breakpoints, we investigated the cases by whole chromosome painting and fluorescence in situ hybridization (FISH) with centromeric probes. FISH analysis detected the same cytogenetic rearrangement in all patients, suggesting that the dic(4;17)(p11;p11) is a recurrent translocation in SLL/CLL. Moreover, FISH analysis showed a monoallelic deletion of the TP53 gene in all cases, suggesting a correlation with the aggressive course of the disease and the clinical outcome observed in these patients.
 ...
PMID:dic(4;17)(p11;p11): a new recurrent chromosomal abnormality in chronic B-lymphoid disorders. 894 98

Myxoid and round cell liposarcoma represents a morphological spectrum in which tumor progression from low-grade myxoid to high-grade round cell areas is frequently observed. A distinctive t(12;16)(q13;p11) reciprocal translocation rearranges the CHOP gene localized to 12q13 in most cases. Data concerning the occurrence of cell cycle aberrations in this subset of mesenchymal malignancies are very limited. Therefore, we analyzed a histologically homogeneous series of 21 cases of myxoid and round cell liposarcoma. The p53 pathway was studied by investigating the TP53 gene and protein, mdm2 protein, and p21Waf1 protein. The Rb-cyclin D pathway was analyzed by studying the pRb protein, the p16MTS1 gene, cyclin D1, cyclin D3, p27Kip1, cdk4, and cdk6 proteins. In contrast with the rare involvement of the TP53 gene in well differentiated liposarcoma, aberrations of the TP53 gene were observed in approximately 30% of cases of myxoid and round cell liposarcoma. Notably, mdm2 overexpression was seen in 56% of cases and correlated with histological grade, therefore indicating a possible role in tumor progression. Abnormalities involving the Rb-cyclin D pathway were observed in more than 90% of cases. pRb loss was present in one-third of cases and, at variance with that observed in other subsets of sarcoma, overexpression of cyclin Ds represented a rare event. Interestingly, upregulation of either cdk4 or cdk6 was demonstrated in 85% of cases.
 ...
PMID:Molecular aberrations of the G1-S checkpoint in myxoid and round cell liposarcoma. 940 3

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.
 ...
PMID:Establishment of a human pancreatic tumor xenograft model: potential application for preclinical evaluation of novel therapeutic agents. 943 58

An 8 year old girl with partial duplication of the short arm of chromosome 17 had a mosaic 46,XX,der(17)?del(17)(p12)dup(17) (p11.2p12).ish dup(17)(p11.2p13.3)(D17S 379x2, p53x2, D17S122x2, D17S29+) karyotype. The extent of mosaicism was 20% in lymphoblasts and 100% in fibroblasts. Fluorescence in situ hybridisation (FISH) proved invaluable in defining the abnormality precisely. The cytogenetic morphology by FISH assay ruled out a microdeletion of the Miller-Dieker syndrome (MDS) region. However, there was no MDS deletion but a duplication of this region. The duplication was extensive and included proximal p53 and D17S122, Charcot-Marie-Tooth type 1A (CMT1A), but not D17S29, the Smith-Magenis syndrome (SMS) region. This patient has the clinical features and generalised decreased peripheral nerve conduction velocity characteristic of CMT1A. The clinical management of paediatric cases of mosaic trisomy 17p cases would ential testing for CMT1A duplication. If duplicated, a decrease in nerve conduction velocity (NCV) of the peripheral motor neurones would be necessary to ensure the manifestation of CMT1A neuropathy. The parents of probands with delayed NCV should be counselled about the risk of CMT1A in later life.
 ...
PMID:A molecular, cytogenetic, and clinical evaluation of mosaic tandem duplication 17p and Charcot-Marie-Tooth type 1A neuropathy. 950 2

A new cancer cell line (KKP) was established from an ascitic effusion of an advanced gastric adenocarcinoma, intestinal type. The line has been maintained in continuous monolayer culture with a doubling time of 48 hours for more than 2 years. KKP cells, whose ultrastructural features are presented, showed an aneuploid DNA content, a modal number of 53 chromosomes, and the presence of one double minute chromosome. The karyotype showed trisomies of chromosomes 7, 12, 13, and 14, tetrasomy of chromosome 18, a reciprocal translocation [t(1;20)(q21;p11.2)], and a [t(4;?)] rearrangement. No amplification or rearrangements were evident in the c-MYC, c-ERB B2, H-RAS, INT-2, HST-1, c-MOS, and K-RAS genes, whereas somatic rearrangements were present in the sequences corresponding to c-MET and cyclin E genes by Southern blotting analysis. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of P53 and RB genes did not reveal alterations or point mutations in the SSCP pattern of conformers. The chemosensitivity pattern assay of the KKP cell line indicated that it was sensitive to cisplatin, etoposide, and doxorubicin and resistant to 4'-hydroperoxycyclophosphamide. The clinical history of the patient from whom the cell line was derived is reported and compared with the results observed in the cell line in vitro. High levels of the tumor-associated antigens CEA (carcinoembryonic antigen) and CA19-9 were evident in the KKP cytosol, whereas the KKP spent culture medium maintained the same low levels of CEA and CA 19-9 found in the patient's serum. This new cell line may represent a useful tool for studying the biology of gastric cancer and for planning new therapeutic approaches.
 ...
PMID:Molecular genetics and in vitro sensitivity of a new human cell line, KKP, from a gastric adenocarcinoma. 968 29

An isochromosome of the long arm of chromosome 17, i(17q), is the most frequent genetic abnormality observed during the disease progression of Philadelphia chromosome-positive chronic myeloid leukemia (CML), and has been described as the sole anomaly in various other hematologic malignancies. The i(17q) hence plays a presumably important pathogenetic role both in leukemia development and progression. This notwithstanding, the molecular consequences of this abnormality have not been investigated in detail. We have analyzed 21 hematologic malignancies (8 CML in blast crisis, 8 myelodysplastic syndromes [MDS], 2 acute myeloid leukemias, 2 chronic lymphocytic leukemias, and 1 acute lymphoblastic leukemia) with i(17q) by fluorescence in situ hybridization (FISH). Using a yeast artificial chromosome (YAC) contig, derived from the short arm of chromosome 17, all cases were shown to have a breakpoint in 17p. In 12 cases, the breaks occurred within the Smith-Magenis Syndrome (SMS) common deletion region in 17p11, a gene-rich region which is genetically unstable. In 10 of these 12 cases, we were able to further map the breakpoints to specific markers localized within a single YAC clone. Six other cases showed breakpoints located proximally to the SMS common deletion region, but still within 17p11, and yet another case had a breakpoint distal to this region. Furthermore, using chromosome 17 centromere-specific probes, it could be shown that the majority of the i(17q) chromosomes (11 of 15 investigated cases) were dicentric, ie, they contained two centromeres, strongly suggesting that i(17q) is formed through an intrachromosomal recombination event, and also implicating that the i(17q), in a formal sense, should be designated idic(17)(p11). Because i(17q) formation results in loss of 17p material, potentially uncovering the effect of a tumor suppressor on the remaining 17p, the occurrence of TP53 mutations was studied in 17 cases by sequencing the entire coding region. In 16 cases, no TP53 mutations were found, whereas one MDS displayed a homozygous deletion of TP53. Thus, our data suggest that there is no association between i(17q) and coding TP53 mutations, and that another tumor suppressor gene(s), located in proximity of the SMS common deletion region, or in a more distal location, is of pathogenetic importance in i(17q)-associated leukemia.
 ...
PMID:Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations. 1038 17

p53 exerts important physiological functions in cell-cycle control, gene regulation, cell differentiation, apoptosis and tumor suppression by interacting with many cellular proteins. Using the yeast two-hybrid system, we screened a HeLa cDNA library and identified a novel gene encoding a p53-binding protein (p53BP3). The full-length cDNA of p53BP3 was isolated from a HeLalambdagt10 cDNA library. This predicted protein was composed of 815 amino acids. Sequence analysis indicated that p53BP3 contained two bipartite nuclear localization signals and was confirmed to be a nuclear protein. FISH mapping results showed that this novel gene was located at human chromosome 12, region p11.2-p12.1. Northern blot analysis suggested that p53BP3 was broadly expressed in human tissues. A further study showed that p53BP3 had a homologue in mouse.
 ...
PMID:Identification of a novel gene encoding a p53-associated protein. 1041 37

Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar genotypic properties. By using an automated DNA sequencer, a K-ras mutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-ras mutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 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, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a combination of bryostatin 1 and gemcitabine and a combination of spongistatin and gemcitabine produced remissions in only one of seven mice. From these results, we conclude that (a) this is the first study illustrating that clonal characteristics of primary pancreatic tumors remained unchanged when implanted in mice and as a permanent cell line grown in vitro; and (b) there is a synergistic effect between gemcitabine and selected marine products tested in this study, which is more apparent in the gemcitabine and auristatin-PE combination. The results of this preliminary study suggest that these agents should be explored clinically in the treatment of pancreatic cancer.
 ...
PMID:Clonal preservation of human pancreatic cell line derived from primary pancreatic adenocarcinoma. 1054 95

The t(X;18)(p11.2;q11.2) translocation commonly found in synovial sarcoma (SS) results in the fusion of the SYT gene on chromosome 18 to either of two closely related genes, SSX1 and SSX2, on chromosome X. It has been suggested that patients who have SS bearing SYT-SSX1 fusion have worse prognosis than those bearing SYT-SSX2 fusion. However, little is known about the biologic basis or the relationship with the histopathologic risk factors in regard to the different fusion types. We analyzed 19 cases of SS with no metastasis at diagnosis. These tumors were classified by reverse transcription-polymerase chain reaction to SYT-SSX1 and SYT-SSX2 types. The expression of Ki-67, p27, p53, and bcl-2 and various clinicopathologic parameters including mitotic rate were compared between the two fusion types. The SYT-SSX1 type fusion was associated with high Ki-67 expression (P = .011) and high mitotic rate (P = .070). No significant differences were found between the two types as to the expression of p27, p53, and bcl-2 and other clinicopathologic parameters. The survival analysis showed that SYT-SSX1-type fusion, high Ki-67 expression, and high mitotic rate correlated with shorter metastasis-free survival. These data suggested that SYT-SSX fusion type is associated with tumor cell proliferative activity and prognosis of patients who have SS.
 ...
PMID:Association of SYT-SSX fusion types with proliferative activity and prognosis in synovial sarcoma. 1082 18

Cancer of the prostate remains poorly characterized cytogenetically. This is due in part to methodological problems and in part to the paucity of radical prostatectomies, until now the main source of material for cytogenetic analyses. We have improved existing techniques for the culturing of prostatic neoplasms removed by radical prostatectomy or sampled by ultrasound-guided needle biopsy. Successful short-term cultures were obtained from all 10 prostatectomy samples and from all 10 ultrasound-guided needle biopsies, always with a pure epithelial morphology. Of the 19 cases yielding a sufficient number of high-quality metaphases for chromosome banding analysis, the single atypical epithelial hyperplasia had a normal karyotype, whereas both prostatic intraepithelial neoplasias and 12 of 16 (75%) invasive carcinomas were shown to have clonal abnormalities. Ten of the 12 (83%) karyotypically abnormal invasive carcinomas presented structural chromosomal rearrangements. A recurrent deletion, del(10)(p13), was seen in three tumors; in one of them the terminal nature of the deletion was confirmed by two-color FISH. A del(17)(p11) was seen in one PIN lesion, but since the analysis of exons 4-8 of the TP53 tumor suppressor gene revealed no mutations, there probably was no inactivation of the second TP53 allele. Our study thus leads to the following main conclusions. First, better culturing methods allow the detection of abnormal karyotypes in a much higher percentage of prostatic neoplasms than has hitherto been possible. Second, ultrasound-guided needle biopsies of prostatic neoplasms are a sufficient source of material for cytogenetic analysis. Third, a terminal deletion of the short arm of chromosome 10, del(10)(p13), seems to identify a subgroup of prostatic cancer.
 ...
PMID:High frequency of clonal chromosome abnormalities in prostatic neoplasms sampled by prostatectomy or ultrasound-guided needle biopsy. 1082 6


<< Previous 1 2 3 4 5 6 Next >>