Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retinoblastoma (RB) tumour suppressor gene has been associated not only with retinoblastoma but also with several other tumours like osteosarcoma, small cell lung carcinoma and prostate and breast cancer. We have studied the incidence of RB gene alterations in 96 primary breast tumours using Southern blotting techniques. The outcome has been related with patient and tumour characteristics, oncogene amplifications, p53 mutations and prognosis. RB gene alterations were found to occur more frequently in estrogen receptor (ER)-positive than in ER-negative tumours and less frequently in tumours with oncogene amplification than in tumours without oncogene amplification of HER2/neu, c-myc or 11q13. RB gene alteration was observed in tumours both with and without a p53 gene mutation. Data on 87 patients (mean age, 59.6 years; median follow-up, 108 months) and RB gene alterations revealed a significant association between the frequency of RB gene alterations and node-negative patients (p < 0.01) or smaller (< 2 cm) tumours (p < 0.01), but no relation with age, differentiation grade or (relapse-free) survival. Patients with and without RB gene alterations showed the same relapse-free and overall survival.
...
PMID:Association between RB-1 gene alterations and factors of favourable prognosis in human breast cancer, without effect on survival. 761 56

Human hepatocarcinoma cells (SK-HEP-1) were induced to die through apoptosis by treatment with delta 12-prostaglandin (PG)J2, as characterized by the appearance of a typical DNA ladder. The induction of apoptosis by delta 12-PGJ2 was specifically blocked by cycloheximide (CHX). Western analysis using anti-p53 or anti-WAF1 monoclonal antibodies demonstrated that these two protein levels were increased 3 h after delta 12-PGJ2 treatment, and accumulated for up to 12 h. The induction of p53 protein seemed to be dependent on the increase of p53 mRNA level, which was inhibited by CHX treatment. However, delayed addition of CHX after delta 12-PGJ2 treatment failed to affect both p53 mRNA levels and DNA fragmentation following delta 12-PGJ2 treatment, indicating that the inhibition of p53 synthesis may contribute to the protective effect of CHX against delta 12-PGJ2-mediated cytotoxicity. Therefore, our results suggest that the initial events caused by delta 12-PGJ2, leading ultimately to SK-HEP-1 cell death, involve a certain process required for p53 induction. However, the finding that delta 12-PGJ2 is also active against Hep 3B cells which are devoid of a functional p53 indicates that p53 may not be the critical requirement for inducing apoptosis by delta 12-PGJ2.
...
PMID:Induction of p53 and apoptosis by delta 12-PGJ2 in human hepatocarcinoma SK-HEP-1 cells. 762 35

Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from Schistosoma-hematobium-infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single-strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively. Only one of the tumors, the only one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-->Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and 249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H-ras gene.
...
PMID:Molecular events underlying schistosomiasis-related bladder cancer. 762 66

Bax is a homologue of Bcl-2 that promotes apoptosis. Bax protein levels were assessed by immunohistochemical methods in primary tumors derived from 119 women with metastatic breast cancer. These patients had received combination chemotherapy either with a once a month dosage schedule or in 4 weekly divided doses. The BAX immunostaining results were retrospectively compared with overall survival, time to tumor progression (TTP), and response, as well as several laboratory markers. Normal breast epithelium and in situ carcinomas immunostained positively for Bax. Marked reductions in Bax immunostaining were observed in 40 (34%) of 119 evaluable tumors. Reduced Bax correlated with shorter overall survival (median, 8.1 versus 15.7 months; P = 0.04), faster TTP (median, 2.0 versus 6.3 months; P = 0.009), and failure to respond (complete response, partial responses; 6% versus 42%, P = 0.01) in the subgroup of patients who received divided dose therapy. Reduced Bax immunostaining was not significant in the monthly dose group. When the two groups were combined, however, reduced Bax was significantly correlated in univariate analysis with failure to respond (21 versus 43% achieving complete response or partial response; P = 0.02), faster TTP (median, 3.7 versus 9.0 months; P = 0.02), and shorter survival (median, 10.7 versus 17.1 months; P = 0.04). Bax immunostaining was not significantly correlated with tumor histology, S-phase fraction, aneuploidy, p53 HER2, or cathepsin D, but was positively associated with Bcl-2 (P = 0.005). In multivariate analysis (Bax, tumor grade, and treatment group), reduced Bax was strongly associated with faster TTP (P approximately equal to 0.009) and shorter survival (P approximately equal to 0.001). Although highly preliminary, the finding suggest that loss of Bax immunostaining represents a novel prognostic indicator of poor response to chemotherapy and shorter survival in women with metastatic breast cancer, and raise the possibility that the subgroup of women with Bax-negative tumors may benefit from more aggressive therapy.
...
PMID:Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. 767 Dec 62

Immunohistochemical stainings for EGFR, c-erbB-2, p53 and PCNA were performed on 36 and 30 cases of intramucosal and advanced carcinomas of large intestine. Positive rate was 58.3%, 41.6%, 58.3% and 60.6% for EGFR, c-erbB-2, p53 and PCNA in the intramucosal cases, and 66.7%, 50%, 66.7% and 72.6% in the advanced ones, respectively. Relationship between EGFR and c-drbB-2 was more significant in the advanced carcinomas than that in the intramucosal ones. It seemed likely that relationship between p53 and c-erbB-2 was more significant than that between p53 and EGFR. Positive rate of PCNA was of intimate relationship among that of EGFR, c-erbB-2 and p53, and the positive rate increased in the advanced carcinomas.
...
PMID:[Immunohistochemical study of PCNA, EGFR, c-erbB-2 and p53 in carcinomas of large intestine]. 767 43

Recent results using very low doses of radiation have suggested that there is a hypersensitive region where cultures show an enhanced level of cell killing leading to a non-monotonic survival curve. This effect has been observed at doses below 2 Gy in mammalian systems and at much higher doses in insect cells. In this paper we report observation of the effect in primary human uroepithelial cell cultures. The effect was measured using a postirradiation proliferation assay where irradiated explants of standard size were allowed to proliferate for 14 days after exposure to 60Co gamma irradiation. By 14 days the majority of cultures derived from explants irradiated with 2-5 Gy showed little evidence of growth inhibition and cell numbers approached or even exceeded those obtained in the controls. There was, however, a significant reduction in cell number and growth rate in all cultures exposed to doses lower than 1 Gy. Oncoprotein (p53, c-myc, bcl-2, p21 ras) and EGFR expression were also measured in these cultures and were significantly increased. Morphological evidence of apoptosis was present in all irradiated cultures at 4 h after exposure, but this persisted for longer periods in cultures exposed to low doses.
...
PMID:Primary explants of human uroepithelium show an unusual response to low-dose irradiation with cobalt-60 gamma rays. 772 33

The development of cancer is a multistep process involving accumulation of genetic changes which progressively transform normal cells to neoplastic cells. During the last few years, our understanding and knowledge of the genetic changes involved in ovarian carcinogenesis have increased dramatically. In this review I will focus on karyotypic abnormalities in ovarian cancer and will also refer to molecular studies involving alterations in oncogenes and tumour suppressor genes in ovarian tumorigenesis. Cytogenetic analyses have identified two distinct subgroups. Simple karyotypic changes, trisomy 12 being the most common aberration in this group, are recurrently found in well differentiated ovarian carcinomas. Complex karyotypic abnormalities, including predominantly chromosome losses, deletions and unbalanced translocations, are found in moderately and poorly differentiated carcinomas. The bands and regions most commonly involved in structural rearrangements have been, in decreasing order of frequency, 19p13, 1p36, 1q21, 1q23-25, 3p11-13, 6q21, 19q13, 11p13-15, 11q13, 11q23, 12q24, 12p11-13, and 7p13-22. The finding of identical karyotypic and other genetic changes in tumour samples taken from different sites, such as tumours from both ovaries and omental metastases, indicate that ovarian cancer is of unicentric origin with subsequent metastatic spread giving rise to multiple implants. Molecular genetic changes important in ovarian cancer involve both classes of tumor-associated genes: RAS activation is generally not observed in ovarian cancer. Alterations of MYC1, ERBB2, AKT2, TP53 has been described in some ovarian carcinomas. The temporal relationship of these mutations, i.e. early or late events in ovarian carcinogenesis, remains to be determined.
...
PMID:Genetic changes in ovarian cancer. 774 4

Transcripts coding for transcription factors (RB, P53, FOS, MYC, MYB, ERBA, REL), growth factors (FGF1, FGF2, INT2, TGFA, TGFB, PDGF, IGF1, IGF2), interleukins, (IL1, IL2, IL3, IL4, IL6, TNF), growth-factor receptors or cytosolic protein kinases (RAF, PIM, FES, MET, SRC, ROS, TRK, KIT, CSFR, IGFR, PDGFR, EGFR, NEU) were quantified in cultured human mammary fibroblasts from normal tissues, benign tumours, carcinomas and post-radiation fibrosis lesions by slot-blot autoradiography and image analysis. The effects of a differentiating agent (cholera toxin) and of a tumour promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. The drugs modulated the levels of the anti-oncogene transcripts (RB, P53) and of ERBA, REL, RAF, MET, ROS, TRK, CSFR, EGFR, NEU, FGF1, INT2, IGF1, IL1, IL2, IL4 and IL6. Apart from this variation, there were multiple differences in gene expression among normal and pathological cells (concerning all but P53, TGFB and interleukin transcripts) and between sub-types defined by the presence of alpha-sm-actin (myofibroblasts) or EDB-fibronectin (RAF, ROS, FES, KIT, IGFR, NEU, INT2, TGFB, PDGF, IGFs, ILs). It appears, therefore, that mammary stroma progress irreversibly along with the epithelium during tumoral development, and that breast cancer is not only a multi-gene but also a multi-tissue phenotype.
...
PMID:Quantitative variation of proto-oncogene and cytokine gene expression in isolated breast fibroblasts. 776 44

Quantitative imbalance in chromosomal material relative to the normal diploid situation is the most conspicuous genetic change in breast tumors, affecting virtually all chromosomes in varying frequencies. This imbalance is reflected by deviant DNA stemlines observed in DNA flow cytometry analysis, by numerical chromosome abnormalities in karyotype analysis and by loss of heterozygosity in DNA polymorphism studies. Gene amplification might be caused by the same genetic mechanisms that cause these chromosomal abnormalities [134]. The number of known genes for which there is now good evidence for their role in the development of breast cancer is still limited, and basically restricted to TP53 and ERBB2. Clearly, the estrogen receptor, not discussed here, can be conjectured to be of importance in breast cancer development, yet the significance of the reported sequence variants [157] for hormone-independent growth is presently undetermined [158]. For many others, such as MYC, CCND1, EMS1, EGF, RB1, NME, DCC and prohibitin, the evidence is still largely circumstantial, or obtained only by in vitro studies on breast cancer cell lines. In many cases of chromosomal imbalance and certainly those affecting whole chromosomes or chromosome arms, it is unclear what their effect on tumor growth will be, because multiple potential candidate genes are located in the affected region. In addition, it is obvious that multiple chromosomes are affected simultaneously in a single tumor, but that the total set of chromosome changes varies in different tumors. This intra- and intertumor heterogeneity of chromosome involvement suggests that an unknown number of the observed abnormalities are not important for tumor development, but merely result from genetic instability. On the other hand, there is accumulating evidence, particularly from flow cytometry and allelotype studies reviewed here, to suggest that the genetic evolution associated with tumor development and progression does reach a stage of equilibrium despite the presence of extensive tumor heterogeneity. The number of genetic events found per tumor raises the question whether each event of heterozygosity loss represents the second step in the inactivation of a tumor suppressor gene. Also, LOH observed with polymorphic markers can sometimes be interpreted as allelic copy number gain instead of loss. Possibly, some of these allelic imbalances contribute to the tumorigenic process simply because they create a dosage effect in certain gene products [2]. This supposes that the sole presence of allelic imbalance at certain chromosomes is sufficient to provide selective growth advantage in certain cases.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Somatic genetic changes in human breast cancer. 781 70

The recent results obtained from investigations based on molecular biological techniques have led to a better understanding of recurrent genetic causes important for the pathogenesis of tumors. Several genes have been identified as being involved in the development of cancer. In many cases, the activation of oncogenes or the inactivation of tumor-suppressor genes is the predominant reason for cancerogenic cell transformation. Functional dysregulation is frequently the consequence of mutations, resulting in an alteration of the primary structure of the DNA. As our understanding of the nature, function, and interaction of these genes evolves, new opportunities for early diagnosis, classification, prevention, and treatment of malignant tumors will arise. The present report summarizes the current molecular biological aspects of several oncogenes (erbB, ras, myc, raf, fos, jun, bcl, mdm2, myb, kit CSF1R, met) and tumor suppressor genes (p53, rb, mts) involved in lung-cancer development with respect to the pathology of lung tumors, including the importance of these genes as far as the clinical course of the disease is concerned.
...
PMID:[Oncogenes and tumor suppressor genes in the pathogenesis of lung tumors]. 785


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---