Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear magnetic resonance microimaging measurements of the self-diffusion coefficient of water in large (greater than 2 mm) EMT-6 multicellular spheroids were performed in order to elucidate diffusion mechanisms in tumors. Pulsed gradient spin echo-imaging methods were developed for measuring diffusion in an intravoxel multicompartment system. The self-diffusion coefficient (at 22 degrees C) for water in the medium (Dm) consisted of only a single diffusion compartment [Dm = 1.99 +/- 0.03 (SE) x 10(-5) cm2/s]. Similarly, the spheroid necrotic center showed a single water diffusion compartment with a self-diffusion coefficient (Dc) significantly lower than that of the medium (Dc = 1.54 +/- 0.05 x 10(-5) cm2/s). The spheroid viable rim region showed two distinct compartments of approximately equal volume, one with a large diffusion coefficient (1.70 +/- 0.12 x 10(-5) cm2/s) and a second with a significantly smaller diffusion coefficient (0.25 +/- 0.01 x 10(-5) cm2/s). We propose that these two experimentally distinguishable compartments correspond to the extra- and intracellular regions, respectively, of the viable rim of the spheroid. Although the diffusion coefficients were significantly different in the medium, the necrotic center, and the viable rim, the activation energy for diffusion was the same in the three regions (0.20 eV). Studies of perfused spheroids at 37 degrees C show the same dependence of the diffusion coefficients on the diffusion filter as observed for unperfused spheroids at 22 degrees C. These results demonstrate the ability of nuclear magnetic resonance microimaging to investigate diffusion at the cellular level, which will lead to a better understanding of microenvironmental regulation in tumors.
Cancer Res 1991 Aug 01
PMID:Self-diffusion of water in multicellular spheroids measured by magnetic resonance microimaging. 185 22

Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR-derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal.
 ...
PMID:Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. 187 48

Chronic myelogenous leukemia (CML) is the best understood human cancer. The molecular basis of CML involves activation of a cellular proto-oncogene--ABL. The consequence is to increase tyrosine kinase activity. This results in a marked clonal increase in the myeloid mass. Later on, cellular maturation is blocked and the decrease eventuates in acute leukemia. Abnormalities of other proto-oncogenes or antioncogenes, like P53, may be involved in leukemia progression. Treatment of CML involves chemotherapy and, more recently, interferon. Whether this treatment prolongs survival or increases the likelihood of cure is unknown but either result seems unlikely. Bone marrow transplants which cure about 50% of persons with CML are most effective when performed in chronic phase.
 ...
PMID:Chronic myelogenous leukemia: molecule to man. 189 3

The first consistent karyotypic abnormality found to be associated with neoplastic disease was the Philadelphia (Ph) chromosome (Nowell & Hungerford, 1960). Furthermore, the best-studied example of translocation-mediated gene activation occurs in leukaemia patients bearing this abnormality (reviewed by Kurzrock et al, 1988). In these individuals, the Ph translocation (t(9;22)(q34;q11)) results in transposition of the ABL proto-oncogene from chromosome 9q34 to 22q11, where it is fused with part of the BCR gene. It is now known that as a result of the Ph translocation, p160BCR and p145ABL (the normal BCR and ABL gene products) are replaced by p210BCR-ABL. This aberrant protein constitutes the molecular fingerprint of CML. The enhanced tyrosine phosphokinase enzymatic activity (a property possessed by some growth factor receptors and transformation-inducing oncogenes) of p210BCR-ABL implicates a direct role for this molecule in the pathogenesis of CML. Because the Ph translocation is present in the early chronic phase, the union of the BCR and ABL genes is probably involved in the initiation of the leukaemic process. The secondary molecular forces driving progression of CML to blast crisis are however unknown, and may differ from patient to patient. Approximately 10% of CML patients lack a Ph chromosome. One-half of these individuals have bcr rearrangement and express p210BCR-ABL. Ph+ and Ph- bcr+ (p210+) CML are identical and should be treated the same. Molecular follow-up of diploid bcr+ CML patients is essential for detection of persistent malignancy after therapy. The presence of a specific marker--the BCR-ABL message--permits the development of new diagnostic approaches for CML. For instance, detection of a BCR-ABL message with the use of the highly sensitive polymerase chain reaction, a technique capable of detecting up to one leukaemia cell amongst one million normal cells, yields important information about minimal residual disease. Finally, the use of therapy directed against the BCR-ABL product may be a worthwhile strategy which deserves investigation, and may prompt a new era of tumour-specific treatment.
 ...
PMID:The molecular pathology of chronic myelogenous leukaemia. 193 6

In Vienna, legalized prostitution is tightly controlled by the advisory board of the Viennese Public Health Service. Registered prostitutes are routinely screened for all important STDs, such as syphilis, HIV, gonorrhea, chlamydial- and yeast-infections, and Trichomonas vaginalis. Furthermore, cytological smears are obtained from the cervix and chest X-rays are performed at least once a year. In all pathological findings, an appropriate therapy is implemented. Presenting data of 1989, out of the 713 weekly controlled registered prostitutes, Neisseria gonorrhoeae was detected in 0.3% of all examinations (110/35,368). In non-registered prostitutes, the infection rate of N. gonorrhoeae was 6.9% (27/354), and so far, 20 times higher than in registered ones. The infection rate of Chlamydia trachomatis, which has been routinely diagnosed in registered prostitutes for several years, has decreased from 20.4% in 1980 to 2.2% in 1989 compared with 31.4% and 10.9% in non-registered prostitutes. In registered prostitutes, the prevalence of genital infections, such as C. trachomatis, T. vaginalis, and yeasts was shown to be 4.9%. The corresponding data in non-registered prostitutes were much higher (18.8%). Due to examinations for cervical malignancy the incidence of Papanicolaou stain IV and V has decreased from 3.1% in 1988 to 1.6% in 1989. There was no serologic evidence for syphilis and HIV infection in both special risk groups. The data demonstrate, that due to a good health surveillance of STD-risk groups, a good information service, and free treatment, the prevalence of STDs can be reduced in prostitutes.
 ...
PMID:Medical health care for Viennese prostitutes. 194 14

Chromosome in situ hybridization studies showed that the normal karyotype of leukemic cells from a patient with Ph1-negative, BCR-positive chronic myeloid leukemia (CML) concealed a complex t(9;22;20)(q34;q11;p13). The close association of 5'-BCR and 3'-ABL was demonstrated by field inversion gel electrophoresis, and in situ hybridization showed that BCR-ABL was located on the short arm of chromosome 20. Our findings further indicate that chromosome rearrangement is the cause of BCR-ABL gene fusion in leukemic cells that show a normal karyotype. Results from in situ hybridization studies were consistent with formation of the t(9;22;20) by a two step chromosomal rearrangement, but field inversion gel electrophoresis results indicated a more complex rearrangement.
Genes Chromosomes Cancer 1991 Jul
PMID:A complex chromosome rearrangement forms the BCR-ABL fusion gene in leukemic cells with a normal karyotype. 195 92

The Philadelphia1 (Ph1) chromosome results from a reciprocal translocation between chromosome 9 and chromosome 22, which fuses a portion of the ABL oncogene to the BCR gene, forming the BCR/ABL fusion gene. This produces a fusion protein with a greatly increased protein tyrosine kinase activity in comparison to that of the normal ABL protein. The BCR/ABL gene is transcribed from the promoter of the normal BCR gene, but little is known about the regulation of its expression. In this study, we asked whether there are sequence-specific DNA-binding proteins (DBP) that bind to the breakpoint cluster region (bcr, or Mbcr) within the BCR gene. Sequence-specific DBP located within the Mbcr could have a transcription-regulating effect, and they could participate in the recombination that generates BCR/ABL. Our data show that there are sequence-specific DBP that bind within the Mbcr.
Genes Chromosomes Cancer 1991 Jul
PMID:Sequence-specific DNA-binding proteins within the Mbcr on the Ph1 chromosome. 195 95

The results of the nationwide, population-based cervical cancer screening programme (organized by the Finnish Cancer Society since early 1960s) were analysed to establish the prevalence figures (and their changes) for genital human papillomavirus (HPV) infections in an unselected Finnish female population (aged between 20 and 65 years) screened in Kuopio Province between 1981 and 1989. During the study period 82,393 women were invited on a regular basis for the mass-screening, and also 4131 women in a risk group. Of these, a total of 63,115 and 3249 women attended, resulting in the attendance rates of 76.6% and 78.6%, respectively. As a result of the screening, a total of 509 (0.80%) of the 63,115 smears were diagnosed as having the cytological changes consistent with HPV infection in the mass screening. The corresponding figures in the risk group screening were 58/3249 (1.78%). There was a sharply increasing trend in the prevalence of genital HPV infections from 1981 through 1987, from 0.04% to 1.76% (ie a 44-fold increase in 7 years) which, surprisingly, then declined to 1.43% in 1988 and 1.04% in 1989. Based on a random sample of 2084 routine (non-mass-screening) Pap smears (out of (28,861) collected from the files of our laboratory, the prevalence of HPV infections was stratified by age groups. The highest prevalence (6.1%) was observed in women aged between 20 and 29 years, followed by 2.2% in those aged 30-39 years. Using the figures of the relative risk (RR) of HPV infections by age, an estimation was made to assess the prevalence of clinical HPV infections in the Finnish female population in general.(ABSTRACT TRUNCATED AT 250 WORDS)
Int J STD AIDS 1990 Nov
PMID:Prevalence of genital human papillomavirus infections in a mass-screened Finnish female population aged 20-65 years. 196 68

Expression of the 93-kd tyrosine kinase encoded by the human c-fes proto-oncogene (also known as FES) is restricted to mature hematopoietic cells of the granulocytic and monocytic lineages, suggestive of a function essential to normal myeloid differentiation. However, recent studies have shown that c-fes can transform fibroblasts if sufficient levels of gene expression are achieved. These findings indicate that strict regulation of the c-fes gene is critical to normal myeloid development, whereas elevated c-fes expression may contribute to malignant transformation. In the present study, we compared the c-fes messenger RNA (mRNA) levels in leukemia blasts from patients with myeloid or lymphoid leukemia with those of peripheral monocytes from a normal donor with the use of a quantitative ribonuclease protection assay. The presence of c-fes mRNA was readily detected in both acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, but c-fes mRNA was present in low levels or was absent in lymphoid leukemia cells. The leukemia cells of two of five AML patients and four of four CML patients expressed more c-fes mRNA than monocytes from a normal donor, with more than a threefold elevation in the cells of one CML patient. No evidence of amplification or rearrangement of the c-fes gene was detectable by Southern blot analysis of myeloid leukemia DNA, suggesting that the variation in c-fes mRNA levels are related to differences in transcriptional activity and/or message stability. These results indicate that elevated c-fes expression is a common feature of myeloid leukemia cells that could potentially contribute to the leukemia phenotype.
J Natl Cancer Inst 1991 Jan 02
PMID:Elevated expression of the c-fes proto-oncogene in adult human myeloid leukemia cells in the absence of gene amplification. 198 16

The expression and function of several proto-oncogenes were examined in a human acute T cell leukemia line, JURKAT, during phorbol ester-induced terminal differentiation. Treating JURKAT cells with the phorbol ester tetradecanoyl phorbol acetate (TPA) inhibited their proliferation and induced expression of the gene for the interleukin 2 receptor alpha chain (IL2R-alpha), consistent with previous reports. In unstimulated proliferating JURKAT cells, high levels of C-MYC, N-RAS, and BCL2 mRNAs were found that diminished rapidly following TPA-induced cessation of growth. In contrast, accumulation of mRNAs for the C-FOS, C-JUN, and EGR-1 genes increased markedly in TPA-treated cells and preceded the induction of IL2R-alpha mRNA. Expression of C-MYB, C-RAF-1, C-LCK, C-FYN, and C-FGR proto-oncogenes was relatively unchanged. To explore directly the function of two of these protooncogenes in regulating the growth of JURKAT T cells, we stably transferred C-MYC and BCL2 expression plasmids into these cells. Despite sustained expression of C-MYC, BCL2, or the combination of these protooncogenes, TPA continued to inhibit JURKAT cell growth and to induce IL2R expression. Thus, although C-MYC and BCL2 proto-oncogene expression correlated with proliferation in TPA-treated JURKAT cells, continuous over-expression of even the combination of these oncogenes was insufficient for abrogating the effects of TPA in these leukemic T cells. Because human lymphoid malignancies frequently contain chromosomal translocations that deregulate the expression of C-MYC and BCL2, our findings could have relevance for attempts to induce terminal differentiation of leukemic cells by in vitro exposure of patients' bone marrow cells to phorbol esters.
 ...
PMID:Phorbol ester-mediated inhibition of growth and regulation of proto-oncogene expression in the human T cell leukemia line JURKAT. 201 1


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