Overexpression of p53 protein and point mutation of K-ras genes in primary carcinoma of the small intestine

2002 ◽  
Author(s):  
Ken-ichi Nishiyama ◽  
Takashi Yao ◽  
Hirotoshi Yonemasu ◽  
Koji Yamaguchi ◽  
Masao Tanaka ◽  
...  
Keyword(s):  
Small Intestine ◽  
Point Mutation ◽  
P53 Protein ◽  
Primary Carcinoma ◽  
Ras Genes

scholarly journals Point mutation in codon 61 of N-RAS genes in human myeloma cell lines

1989 ◽  
Vol 17 (21) ◽  
pp. 8867-8867 ◽  
Author(s):  
Makoto Sawada ◽  
Shiro Shimizu ◽  
Toshihide Arai ◽  
Susuma Konda ◽  
Nobuyuki Enomoto ◽  
...  
Keyword(s):  
Point Mutation ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Ras Genes ◽  
Human Myeloma Cell ◽  
Codon 61

scholarly journals Co-localization of Endogenous and Exogenous p53 Proteins in Nasopharyngeal Carcinoma Cells

1997 ◽  
Vol 45 (7) ◽  
pp. 991-1003 ◽  
Author(s):  
Jenn-Kuo Hwang ◽  
Chin-Tarng Lin
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Point Mutation ◽  
Transcriptional Activation ◽  
Polyclonal Antibodies ◽  
P53 Protein ◽  
Activation Function ◽  
P53 Mutation ◽  
Polymorphism Analysis ◽  
Mutant P53

Recently, we have established nine nasopharyngeal carcinoma (NPC) cell lines in which only one cell line showed the p53 mutation. For investigation of the p53 mutation in this line, immunostaining using anti-p53 antibody was applied and showed the presence of p53 protein in the cytoplasm but not in the nucleus. Single strand conformation polymorphism analysis of the p53 gene showed one normal and one additional DNA band. Cloning and sequencing of PCR-amplified DNA showed an AGA (arginine) to ACA (threonine) heterozygous point mutation at codon 280. Transfection of the p53 DNA binding sequence and chloramphenicol acetyltransferase assay revealed loss of transcriptional activation function of endogenous p53 protein. Co-localization of the endogenous and the transfected exogenous p53 protein by polyclonal antibodies to anti-p53 protein revealed strong exogenous p53 staining in the transfected nuclei and weak staining of endogenous p53 protein in the cytoplasm. We concluded that (a) a heterozygous point mutation at codon 280 was identified in the NPC-TW 06 cell line; (b) the point mutation may cause the stagnation of mutant p53 protein in the cytoplasm, and loss of its transcriptional activation function; (c) endogenous and exogenous p53 protein can be co-localized at the same time in the transfected cells; and (d) 280 mutant p53 protein in NPC cells does not cause a decrease or increase in sensitivity to chemotherapy.

Expression of p53 protein in cancers of small intestine and its relationship to clinical course and prognosis

1997 ◽  
Vol 9 (1) ◽  
pp. 49-52
Author(s):  
Chunlin Ge ◽  
Sanguang He ◽  
Yulin Tian ◽  
Hengchun Qu ◽  
Anguang He
Keyword(s):  
Small Intestine ◽  
Clinical Course ◽  
P53 Protein

scholarly journals PRIMARY CARCINOMA OF THE SMALL INTESTINE

BMJ ◽  
1935 ◽  
Vol 1 (3878) ◽  
pp. 923-962 ◽  
Author(s):  
D. J. Harries ◽  
C. V. Harrison
Keyword(s):  
Small Intestine ◽  
Primary Carcinoma

scholarly journals A CASE OF ADULT INTUSSUSCEPTION DUE TO PRIMARY CARCINOMA OF THE SMALL INTESTINE DIAGNOSED PREOPERATIVELY

2003 ◽  
Vol 64 (7) ◽  
pp. 1668-1672
Author(s):  
Yuji FUJITA ◽  
Masatoshi SHIGETA ◽  
Yoshitaka IKEDA ◽  
Yasuhiro KOUCHI ◽  
Hiroshi MIYASHITA
Keyword(s):  
Small Intestine ◽  
Primary Carcinoma ◽  
Adult Intussusception

scholarly journals A CASE OF PRIMARY ADENOCARCINOMA OF THE PROXIMAL JEJUNUM, WITH REVIEW ON PRIMARY CARCINOMA OF THE SMALL INTESTINE IN JAPAN

1985 ◽  
Vol 18 (11) ◽  
pp. 2419-2422
Author(s):  
Takashi HIGASHIGUCHI ◽  
Tsutomu SEKOGUCHI ◽  
Yoshifumi KAWARADA ◽  
Ryuji MIZUMOTO
Keyword(s):  
Small Intestine ◽  
Primary Carcinoma ◽  
Primary Adenocarcinoma ◽  
Proximal Jejunum

In Vitro Colony Growth, RAS Genes Sequencing, and Expression of Bcl-2 and Bax Proteins in Chronic Myelomonocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2379-2379
Author(s):  
Francesco Onida ◽  
Clara Ricci ◽  
Federica Servida ◽  
Elisa Fermo ◽  
Mauro Molteni ◽  
...  
Keyword(s):  
Point Mutation ◽  
Colony Growth ◽  
Chronic Myelomonocytic Leukemia ◽  
Control Group ◽  
Spontaneous Growth ◽  
Gm Csf ◽  
Ras Genes ◽  
Myelomonocytic Leukemia ◽  
Normal Controls

Abstract Chronic myelomonocytic leukemia (CMML) is a heterogeneous hematological malignancy, which shows features of both myelodysplastic and myeloproliferative disorders. It has poor prognosis due to the lack of effective treatment and very little is known about its pathogenesis. A point mutation in the RAS genes is detected in 20 to 35% of patients with CMML, with higher percentage among patients with proliferative variant of the disease (MP-CMML, WBC > 13 x 109/L). The expression of Bcl-2 family proteins, which are key regulators of the mitochondrial-mediated pathway of apoptosis, have been reported as being altered in MDS and other hematological disorders. However, the role of these proteins has not been systematically investigated in CMML. In this study, we evaluated by Western Blotting the expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins in peripheral blood mononuclear cells (PBMNC) from 21 CMML patients and 8 age-matched healthy controls. We also investigated the presence of point mutations within codons 12, 13, and 61 of N- and K-RAS by sequencing analysis, and assessed in vitro colony growth of PBMNC with and without growth factors (GFs) [SCF, GM-CSF, IL-3, Epo]. Our series included 10 males and 11 females, with a median age of 74 years. Median WBC value was 9.2 x 109/L (range 3.2 to 17.2), while differential showed median monocyte values of 27.5% and 2.0 x 109/L. Six out of the 21 patients had MP-CMML. All patients but one had normal karyotype. A point mutation within N-RAS (G12D) was detected in two patients, both with MP-CMML. Spontaneous growth was observed both in normal controls and in CMML (median 19 and 14 CFU-GM/105 MNCs, respectively), with a higher number of CFU-GM in the MP-CMML than in the dysplastic subgroup (MD-CMML) (46 vs 12). After addition of GFs, we observed an increase of colony number in all groups. Interestingly, in vitro colony growth was remarkably higher in the two patients with mutant N-RAS than in patients with wild type RAS, especially after the addition of GFs (200 vs 57, p <0.05). The expression of Bax was higher in CMML than in the control group (3.81 vs 1.39, p = 0.07), whereas Bcl-2 was lower (0.88 vs 1.41, p = .16), even though these differences were not statistically significant. No differences were observed between subgroups of patients with MD- and MP-CMML. When the Bcl-2/Bax ratio was calculated, we observed lower values in CMML than in normal controls (0.27 vs 1.08, p <0.01). In the two patients with mutated RAS, Bcl-2 expression was significantly higher than in patients with wt-RAS (2.07 vs 0.75, p <0.05). Noteworthy, Bcl-2 expression in patients with mutant RAS was also higher than in the control group. In conclusion, our data suggest a deregulation of mechanisms controlling apoptosis in CMML, with no significant differences between MD and MP variants. The finding of higher Bcl-2 expression in patients with mutant RAS suggests a possible cooperation of this anti-apoptotic protein with RAS-activated intracellular pathways, warranting further confirmation in larger CMML series. In agreement with previous reports, we observed higher in vitro spontaneous growth in MP-CMML than in MD-CMML. Hypersensitivity to GFs (possibly GM-CSF) in cells from patients with mutant RAS is suggested and merits further investigation.

scholarly journals Assessment of TP53 lesions for p53 system functionality and drug resistance in multiple myeloma using an isogenic cell line model

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Umair Munawar ◽  
Markus Roth ◽  
Santiago Barrio ◽  
Harald Wajant ◽  
Daniela Siegmund ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Cell Line ◽  
Point Mutation ◽  
P53 Protein ◽  
Line Model ◽  
Therapeutic Implications ◽  
Isogenic Cell Line ◽  
Cell Line Model ◽  
Double Hit

AbstractRecent advances in molecular diagnostics have shown that lesions affecting both copies of the gene for tumor suppressor protein 53 (TP53) count among the most powerful predictors for high-risk disease in multiple myeloma (MM). However, the functional relevance and potential therapeutic implications of single hits to TP53 remain less well understood. Here, we have for the first time approximated the different constellations of mono- and bi-allelic TP53 lesions observed in MM patients within the frame of a single MM cell line model and assessed their potential to disrupt p53 system functionality and to impart drug resistance. Both types of common first hit: point mutation with expression of mutant p53 protein or complete loss of contribution from one of two wildtype alleles strongly impaired p53 system functionality and increased resistance to melphalan. Second hits abolished remaining p53 activity and increased resistance to genotoxic drugs even further. These results fit well with the clinical drive to TP53 single- and double-hit disease in MM patients, provide a rationale for the most commonly observed double-hit constellation (del17p+ TP53 point mutation), and underscore the potential increases in MM cell malignancy associated with any type of initial TP53 lesion.

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