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

More than 95% of patients with chronic myelogenous leukemia (CML) contain an abnormal chromosome termed the Philadelphia chromosome (Ph1). Ph1 and the resulting BCR-ABL fused genes are markers for this type of leukemia. The product of the fused BCR-ABL genes is a protein of about 2000 amino acids termed P210 BCR-ABL. Although the BCR-ABL protein can be routinely detected in blood cells from blast crisis CML patients by assaying for its activated tyrosine kinase activity, detection of P210 BCR-ABL in early stage CML patients (chronic phase) has not yet been possible (S. A. Maxwell et al., Cancer Res., 47: 1731, 1987). A procedure involving Western blotting with an anti-ABL monoclonal antibody was developed that allows detection of P210 BCR-ABL and P145 ABL in cells from chronic phase and blast crisis CML patients, but as expected only P145 ABL was found in normal white blood cells. Most chronic phase patients also contained one to two ABL proteins with a molecular weight of about 190,000. Interestingly, the ratio of BCR-ABL to ABL proteins increased in four blast crisis patients compared to 18 chronic phase patients. Also, one chronic phase patient analyzed on three separate occasions lacked P210 BCR-ABL and exhibited only the Mr 190,000 form. This assay should also be useful in other leukemias that express altered forms of the ABL protein.
Cancer Res 1991 Jun 01
PMID:Detection of BCR-ABL proteins in blood cells of benign phase chronic myelogenous leukemia patients. 203 43

The Ph chromosome was the first specific karyotype abnormality associated with a particular neoplastic disease in humans. For many years it was suspected that chromosome abnormalities might cause cancer by alteration of specific genes or their expression. Significant recent developments in our understanding of the molecular consequences of the Ph translocation strengthen that assumption. The Ph translocation generates a hybrid gene consisting of 5' regulatory, promotor, and exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL. Molecular methods can therefore be used as diagnostic tools to detect the Ph chromosome. Presently, the model of oncogenesis provided by our knowledge of how the abl proto-oncogene becomes activated as a result of the Ph translocation is one of the clearest models of oncogene activation. Despite the progress made, many areas remain to be explored. One important question is, how the hybrid protein is involved in leukemia. Research aimed at investigating the normal function of abl and bcr may be important in efforts to understand their abnormal functioning in leukemia and to increase our understanding of the disease.
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PMID:Molecular insights into the Philadelphia translocation. 205 Jun

This study compares the risks of pregnancy, infertility, heart disease, cancer, and death associated with various contraceptive methods with the risks faced by women using no method. Estimated risks are derived from a decision-tree analysis program for a hypothetical cohort of 100,000 women. Method-specific estimates of the probability of various outcomes were obtained from published reports. Low estimates of typical use, first-year failure rates were used in the models. Tabulated data reveal that women who use no contraceptive method throughout their reproductive life (aged 15-44) and never have an abortion would have 18 births as compared to no more than five for women who use any contraceptive method. Data were also tabulated for the method-specific risks of developing upper genital tract infections, ectopic pregnancies, and tubal infertility (caused by the acquisition of a sexually transmitted disease [STD]) were calculated with method differences modeled for women at high and at low risk of acquiring a STD. The third table shows the estimated annual number of deaths per 100,000 ectopic pregnancies, live births, and induced abortions by five-year age groups. The annual pregnancy-related and method-related mortality rates per 100,000 women at risk of unintended pregnancy and at low risk of STDs was also calculated by contraceptive method. The fifth table illustrates the estimated annual incidence of and number of deaths from cardiovascular diseases per 100,000 women by smoking status, age group, and use of nonuse of oral contraceptives. OC use is also compared in a determination of the estimated annual number of ovarian, endometrial, and breast cancers diagnosed per 100,000 women by age at diagnosis. Finally, estimated deaths averted by each age group annually per 100,000 were calculated for current users of barrier and spermicide methods and of OCs and for ever-users before age 45. The conclusions drawn from these comparisons are that each contraceptive method presents different combinations of risks and benefits to women at different stages of their lives. Engaging in multiple sexual relationships, smoking, and irregular or incorrect method use are the three factors which most compromise a woman's ability to reach her reproductive and health goals.
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PMID:Comparing the health risks and benefits of contraceptive choices. 206 Jun 12

Chronic myelogenous leukemia (CML) is characterized cytogenetically by the presence of the Philadelphia chromosome, which is the result of a reciprocal translocation between chromosomes 9 and 22. Analysis of the rearranged chromosome 22 have demonstrated that the DNA breakpoints fall within a 5.8-kilobase (kb) region termed M-bcr. In Ph1-acute lymphocytic leukemia, approximately half of the patients have a breakpoint within M-bcr, whereas the remaining half have the break within the first intron of the BCR gene (m-bcr). We have investigated five cases with CML in the blastic phase to search the molecular mechanism of blastic crisis in CML. Using a method of reverse transcriptase-polymerase chain reaction (RT-PCR), we have identified both types of breakpoints in samples of the three cases, suggesting the existence of M-bcr/ABL and m-bcr/ABL chimeric mRNAs in the RNA samples derived from blasts of the three cases. We have further analysed for alterations in the p53 gene in those cases. The p53 gene is now considered to be a tumor suppressor gene and its mutations play a role in the development of many human malignancies. We have attempted to determine whether the p53 gene is involved in the mechanism of blastic crisis in CML. Using the methods of RT-PCR and single stand-conformational polymorphism (SSCP), we have detected expression of only a mutated p53 allele in a case with CML blastic crisis, indicating that inactivation of the p53 gene in both alleles may contribute to the blastic crisis in this case. Accumulation of molecular analysis in more cases will clarify the mechanism of blastic crisis in CML.
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PMID:[Analysis of Ph1-positive leukemia by PCR]. 206 73

We have previously described a patient in whom the breakpoint occurred within the first intron of the BCR gene and have cloned the 9q+ and 22q- junctions. We have now determined the nucleotide sequence around the breakpoints on both translocation products from this patient as well as the corresponding regions from the normal chromosomes 9 and 22. We have compared the sequence with that of the breakpoint regions in the Ph1-positive leukemic patients in order to check for the presence of conserved motifs. A + T-rich sequences and ALU repeat elements are the only sequence characteristics which appear to be very common around translocation regions. The chromosome 9 ABL sequences at or adjacent to the breakpoints present in the 22q- product show homology to the consensus ALU sequence while the chromosome 22 sequences do not, suggesting a non-homologous recombination mechanism. While no sequences are deleted, there is a two-base-pair "homology" at the junction. Therefore, staggered breaks followed by ligation and repair could be part of the mechanism involved in the process of translocation in some cases of Ph1-positive ALL.
Genes Chromosomes Cancer 1990 Jan
PMID:Characterization of the translocation breakpoint sequences in Philadelphia-positive acute lymphoblastic leukemia. 208 18

Several studies have examined the synergism of hyperthermia or chemotherapy agents in combination with photodynamic therapy (PDT) to enhance tumor eradication. In our unique approach to treatment, multiple photosensitizers and wavelengths were used: two photosensitizers, Photofrin II and meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4), irradiated at the appropriate therapeutic wavelength for each photosensitizer. EMT-6 mammary tumors were induced in the flanks of BALB/c mice. The mice were assigned to a control group (50 mice) or treatment group (150 mice). All treatment animals and some control animals received photosensitizing drug (5 mg/kg of TPPS4, 5 mg/kg of Photofrin II, or 2.5 mg/kg of both TPPS4 and Photofrin II). All treatment animals and some control animals also received light treatment (630 nm for TPPS4 and/or 658 nm for Photofrin II). The results show that the approach using both drugs and the corresponding therapeutic wavelengths enhanced the effectiveness of PDT. This approach achieved a cure rate of up to 100%, which was, depending on the light intensity used, as much as 40% greater than the rate achieved by the approach using one drug and one wavelength. The results also show that lesser amounts of drug and/or light may be required if both drugs and wavelengths are used, thus lowering the chances of side effects common to PDT. Furthermore, the results indicate that the increased tumor kill is due to a synergistic effect of the two photosensitizers that was tested on the tumor microvasculature in the first few hours after PDT.
J Natl Cancer Inst 1990 May 16
PMID:Use of multiple photosensitizers and wavelengths during photodynamic therapy: a new approach to enhance tumor eradication. 213 4

In 1986 and 1987 11 children with TEC (transient erythroblastopenia of childhood) were referred to our hospital. Bone marrow aspirations were performed to exclude haematological malignancy. There was a marked reduction of erythropoiesis in 9 cases (1%-8%), two children had already recovered (33% and 44% erythropoiesis). Eight patients exhibited high percentages of stimulated lymphoid cells. The subsequent immunotyping revealed the expression of CALLA (common acute lymphoblastic leukaemia antigen) on these cells but there was no other sign for malignancy. The patients recovered without any specific treatment except transfusions of packed red cells. Eight patients were followed up 11-18 months after initial presentation and were all found to be in good health. A prominent increase of CALLA-positive stimulated lymphoid cells has also been found in other haematological diseases such as neutropenia and immune thrombocytopenia. The expression of CALLA in bone marrow lymphocytes is a general reactive change to various alterations.
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PMID:Increase of CALLA-positive stimulated lymphoid cells in transient erythroblastopenia of childhood. 214 Jul 75

In the great majority of patients with chronic myelogenous leukemia (CML) the reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), resulting in the Philadelphia (Ph) chromosome produces fusion DNA sequences consisting of the 5' part of the major breakpoint cluster region-1 (M-BCR-1) and the ABL protooncogene which encodes for the P210BCR-ABL phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML. Molecular analysis was performed on 25 patients with Ph-positive CML using 2 breakpoint cluster region (bcr) probes within the M-BCR-1 DNA sequences, and two of them did not contain either detectable rearranged DNA homologous to the 5' side bcr probe or ABL-related fusion mRNA. The chromosomal in situ hybridization technique revealed that these two Ph-positive CML cases did not carry DNAs homologous to the 5' bcr or ABL probes on the Ph chromosome. Furthermore, one of the two Ph-positive CML cases did not show either rearranged DNA or regions homologous to the 3' bcr probe on a 9q+ chromosome, while the other CML case showed a rearrangement detected by the 3' bcr probe and transposition of the 3' bcr homologous to the 9q+ chromosome. Thus, the possibility is raised that the BCR/ABL fusion DNA has been deleted in rare CML cases, and that the deletion possibly occurred in a stepwise manner following the formation of the Ph chromosome at any stage of the disease.
Jpn J Cancer Res 1990 Jan
PMID:Philadelphia chromosome-positive chronic myelogenous leukemia with deleted fusion of BCR and ABL genes. 215 92

Cytogenetic studies on fresh human breast cancers revealed that homogeneously staining regions (HSRs), which are assumed to represent DNA amplification, are observed in almost half of the cases. To search for a possible relationship between HSRs and proto-oncogene amplification, 16 proto-oncogenes, including ERBB2, were studied by Southern blot analysis in four tumors with two or three HSRs, and in three tumors without HSRs. Only four proto-oncogenes were found to be amplified in at least one tumor each: HST and INT2 (x3), MYC (x2-3), and FES (x greater than 10). The large sizes of the HSRs, which each corresponded to several percent of the haploid genome, were hardly compatible with the low rate of amplification, except for FES and then only if a large adjacent segment was co-amplified. This incomplete correlation was demonstrated by in situ hybridization, using biotinylated probes, which showed fluorescent spots on only one HSR for FES in one tumor and for INT2 in another one. Our results indicate that most of the large amplifications corresponding to HSRs do not involve the proto-oncogenes usually studied in breast cancer. The large amplification of FES, detected in one tumor, may be coincidental.
Genes Chromosomes Cancer 1990 May
PMID:Proto-oncogene amplification and homogeneously staining regions in human breast carcinomas. 217 39

Polymerase chain reaction (PCR) is a novel tool for the in vitro amplification of DNA segments up to several kb. Repeated cycles of DNA synthesis by heat-stable Taq DNA polymerase enables to obtain more than 10(5) copies of the target sequence. Recently its enormous attitude of amplification has been applied for the detection of tumor-specific gene alterations. Examples include the detection of point mutation of RAS oncogenes at codons 12, 13, and 61 and the detection of minimal residual neoplastic cells in patients in complete clinical remission. Among many kinds of tumor specific gene translocations, BCR-ABL gene in t(9;22)(q34;q11) and BCL-2-IgH gene in t(14:18)(q32;q21) have been successfully PCR-amplified around their fused regions. In lymphoid malignancies gene rearrangements of T cell receptor chain or immunoglobulin heavy chain can be used as clonal markers for leukemic cells. PCR technique permits the detection of leukemia DNA at dilution of 10(-4) to 10(-6). Although further investigation of patients' follow-up in large scale is needed, this technique seems to hold promise for the monitoring of residual neoplastic cells.
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PMID:[Polymerase chain reaction (PCR)--a novel tool for the molecular diagnosis of neoplasms]. 220 61


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