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)

The Lagergren cage electrode Elema EMT 588 K was implanted in 26 male and 21 female patients for permanent cardiac stimulation. 29 of the 47 cage electrodes were fitted with a platinum and 18 with an Elgiloy head. Acute threshold in the platinum group was 0,52 +/- 0,15 volts (x +/- s), the equivalent electrode resistance being 565 +/- 135 ohms. The threshold mean value for the Elgiloy cage electrodes was shown to be 0,36 +/- 0,11 volts, while the resistance values measured respectively 410 +/- 44 and 418 +/- 23 ohms depending on the method of measurement. In the postoperative period (up to 16 months) the following complications were observed: 3 dislocations (6,38%) and one case of rise in threshold (2,12%). The total correction rate (8,5%) corresponds almost exactly to that recorded by the author in a personal series of 400 electrode implantations of various designs. The cage electrode offers no advantages in comparison to other small surface electrodes, however, the relatively higher current consumption caused by low total electrode resistance must be regarded as disadvantages. Experience with the cage electrode has shown that the transitional resistance depends not only on the surface, but also essentially on the material and shape of the electrode tip.
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PMID:[Clinical experience with the cage electrode EMT 588 K. Threshold--current consumption--postoperative complications (author's transl)]. 62 19

A pulsed-laser microbeam at 532 nm wavelength (optical scissors) and a laser-induced optical trap at 1064 nm wavelength (optical tweezers) have been successively combined to dissect and manipulate chromosomes in live newt lung epithelial cells. These preliminary experimental results demonstrated that chromosome fragments dissected by laser microbeam surgery, regardless of their size, could be easily pulled or rotated by optical forces when positioned at the periphery of the mitotic spindle. In addition, chromosome arms which were not subjected to laser microsurgery also could be moved with the optical tweezers at the spindle periphery. In our previous study on rat kangaroo kidney cells (PTK2), this degree of facilty in manipulating chromosome movement was not possible, most likely due to the close proximity of the intermediate filament "cage" to the spindle. It is concluded herein that optical scissors and tweezers can be used in combination to study the interaction of chromosomes with the mitotic spindle in cells where the peripheral regions of the spindle are unobstructed by intermediate filaments. This can be performed on newt cells, where the diameter of the cage can be substantially larger than the diameter of the spindle.
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PMID:Directed movement of chromosome arms and fragments in mitotic newt lung cells using optical scissors and optical tweezers. 802 Jun 4

The effects of amygdala lesions on passive avoidance of drinking (dPA) and social interactions in a resident-intruder test were examined in two experiments that utilized different lines of Long-Evans hooded rats. The lesions were fairly well restricted to the rostral half of the central nucleus (rACe), or the cholinergically richly innervated basolateral nucleus (ABL) or the medial nucleus (AMe) of the amygdala. In both experiments, dPA deficits indicating disturbances in fear conditioning or fear expression were found with ABL and rACe lesions. The rACe lesions produced a greater deficit. AMe lesions caused no dPA deficit at all, which contrasts with the mild PA deficits reported by others employing larger lesions extending to the cortical nucleus and, perhaps, damaging the central nucleus. Social behavior was not affected by the lesions in any clear manner. In rats from a long-standing home colony, rACe lesions increased a behavior of plowing and kicking the wood-chip cage bedding during social encounters, and AMe lesions increased lateral defense behaviors. Both effects are paradoxical, suggesting increased anxiety in the fear-deficient rACe rats and increased defense with AMe lesions, despite several previous reports of decreased defense. In the second experiment, rats purchased from a supplier showed no lesion effects during social interactions; like the control group, all three lesion groups exhibited increases in offense associated with cohabitation with a female. The ABL lesions, particularly, had no effect comparable to the decreased offense recently reported to occur following neurotoxin lesions.
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PMID:Effects of small amygdala lesions on fear, but not aggression, in the rat. 897 32

Breast cancer antigens RAK-p120, -p42, -p25 were detected in 100% of breast cancer cases tested (71 cases). Only 10% of adjacent tissue cases tested positive for all three cancer antigens, and 17.5% of the cases tested positive for two antigens only. Eighty-five percent of histologically normal breast tissue samples, isolated either from breast cancer patients or patients with advanced fibrocystic disease, tested RAK-negative, with the exception of low expression of p25, observed in some patients. Polymerase chain reaction (PCR) with HIV-1 gp 41-derived primers revealed cancer-associated DNA fragments of similar size (140 bp) as in HIV-1 genome. Fifty-four percent of cancer adjacent tissues, and 50% of malignancy-free breast tissue samples, tested PCR-negative. It is suggested that genetic predisposition to cancer may be associated with the presence of RAK genes, while expression of RAK antigens marks an already ongoing process of malignant changes.
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PMID:New protein and PCR markers RAK for diagnosis, prognosis and surgery guidance for breast cancer. 902 74

We have found that the E6 oncoprotein of Bovine Papillomavirus Type 1 (BE6) as well as the E6 protein of the cancer associated HPV-16 (16E6) interact with the focal adhesion protein paxillin. Mutational analysis of paxillin revealed that BE6 binds paxillin through small protein interaction motifs called LD motifs that have been previously identified as important in regulating association of paxillin with vinculin and focal adhesion kinase (FAK), and that BE6 can interact with at least two separate binding sites on paxillin. The LD motifs of paxillin that bind BE6 share homology with the E6 binding site of E6-AP, a ubiquitin ligase that together with 16E6 targets the degradation of the p53 tumor suppressor. Paxillin binding to BE6 excludes simultaneous binding to E6-AP. Mutational analysis of BE6 can distinguish the interaction of BE6 with E6-AP compared to paxillin and revealed that the interaction of BE6 with paxillin may be necessary for the induction of anchorage independent growth of cells by BE6.
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PMID:Association of Bovine Papillomavirus Type 1 E6 oncoprotein with the focal adhesion protein paxillin through a conserved protein interaction motif. 946 41

Breast and gynecological cancer-associated antigens RAK p120, p42 and p25 exhibit molecular, immunological and genetic homology to HIV-1 proteins. Normal tissues, including the majority of tissues adjacent to cancer, do not express these unique cancer markers. Antigens RAK are now detected in 100% of prostate cancer and in the majority of prostate benign hyperplasia (BPH) cases. Polymerase chain reaction (PCR) with HIV-1 gp41-derived primers revealed prostate cancer-associated DNA fragments of similar size (140 bp) as in HIV-1 genome. Ninety-five percent of BPH samples obtained from prostate cancer patients tested PCR-positive. For comparison, only 61.9% of BPH samples obtained from cancer-free patients tested PCR-positive. The DNA fragments amplified in prostate cancer and in BPH showed more than 90% homology to the HIV-1 gene for gp41. The obtained results strongly suggest that a retrovirus related to HIV-1 may be associated with cancers of the reproductive system.
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PMID:Prostate, breast and gynecological cancer markers RAK with homology to HIV-1. 950 Feb 13

Ovarian cancer cells were isolated from ascites fluid of 30 different patients diagnosed with cystadenocarcinoma of ovaries. Large colonies of malignant ASC cells were observed during the first week of cell growth in vitro. Colony formation was followed by fusion of cells and formation of large multinucleated and highly vacuolated syncytia. In contrast, cells isolated from the ascites fluid produced by patients with benign mucinous cystadenoma of ovaries did not form syncytia. Nonmalignant Brenner tumor cells, isolated from the ascites fluid, also did not form syncytia. Syncytia, but not the nonmalignant tumor cells, were immunofluorescence stained with an anti-human immunodeficiency virus type 1 (HIV-1) gp120 monoclonal antibody (MAb) and MAb RAK-BrI. Both MAbs recognized cancer-associated antigens RAK (for Rakowicz markers) p120, p42, and p25. Exposure of ASC cells to either the anti-HIV-1 gp120 MAb or MAb RAK-BrI inhibited syncytium formation. PCR with HIV-1 Env-derived primers revealed DNA sequences with over 90% homology to HIV-1 gp41 in syncytia and in ovarian cancer cells but not in normal ovary cells. Electron microscopic analysis revealed viral particles, hexagonal in shape (90 nm in diameter), with a dense central core surrounded by an inner translucent capsid and dense outer shell with projections. Negative staining detected membrane-covered particles (100 to 110 nm in diameter) in the cell culture medium. Incubation of normal breast cells with viral particles resulted in drastic morphological changes and syncytium formation by the transformed breast cells. The cytopathic effects of the identified virus resembled those of spumaviruses, which, in addition to their epitopic and genetic homology to HIV-1, might suggest a common phylogeny.
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PMID:Giant syncytia and virus-like particles in ovarian carcinoma cells isolated from ascites fluid. 987 74

One major obstacle to the effective treatment of cancer is to distinguish between tumor cells and normal cells. The chimeric molecules created by cancer-associated chromosomal abnormalities are ideal therapeutic targets because they are unique to the disease. We describe the use of a novel approach based on the catalytic RNA subunit of RNase P to destroy specifically the tumor-specific fusion genes created as a result of chromosome abnormalities. Using as a target model the abnormal BCR-ABL p190 and p210 products, we constructed M1-RNA with guide sequences that recognized the oncogenic messengers at the fusion point (M1-p190-GS and M1-p210-GS). To test the effectiveness and the specificity of M1-p190-GS and M1-p210-GS, we studied in vitro and in vivo effects of these RNA enzymes against BCR-ABL(p190) and BCR-ABL(p210), bearing in mind that both fusion genes share the ABL sequence but differ in the sequence coming from the BCR gene. We showed that M1-p190-GS and M1-p210-GS can act as sequence-specific endonucleases and can exclusively cleave target RNA that forms a base pair with the guide sequence (GS). We also demonstrated that when M1-p190-GS and M1-p210-GS were expressed in proper mammalian cell models, they abolished the effect of BCR-ABL by specifically decreasing the amount of the target BCR-ABL mRNA and preventing the function of the BCR-ABL oncogenes. These data clearly demonstrate the usefulness of the catalytic activity of M1-GS RNA to cleave specifically the chimeric molecules created by chromosomal abnormalities in human cancer and to represent a novel approach to cancer treatment.
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PMID:In vivo inhibition by a site-specific catalytic RNA subunit of RNase P designed against the BCR-ABL oncogenic products: a novel approach for cancer treatment. 1064 80

A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during breast tumorigenesis. SYK, a candidate tumor suppressor, has been found not expressed in a subset of breast cancer cell lines, but the mechanism by which SYK is silenced is unclear. In this study, we examined the 5' CpG island methylation status of the SYK gene in breast cancer cell lines and primary breast cancer tissues. We found SYK 5' CpG hypermethylation in 30% (6/20) of breast cancer cell lines, and the aberrant methylation status was strongly associated with loss of SYK gene expression. Treatment of cells with a methylation inhibitor, 5-aza-2'-deoxycytidine, led to a reactivation of SYK expression in SYK-negative cells, as detected by reverse transcription-PCR. Using methylation-specific PCR, we demonstrated that SYK is hypermethylated in 32% (12/37) of unselected breast tumors, whereas all of the matched neighboring normal breast tissues exhibited unmethylated DNA status. We concluded that SYK is frequently inactivated through an epigenetic pathway in breast cancer. Because SYK has been shown to function as a tumor suppressor, and its loss of expression in breast cancer has been correlated with tumor invasiveness, the aberrant SYK methylation is responsible for the loss of expression and may consequently play a permissive role for tumor aggressiveness.
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PMID:Hypermethylation leads to silencing of the SYK gene in human breast cancer. 1145 7

Formation of the hybrid BCR-ABL gene is responsible for >95% of chronic myeloid leukemia (CML). The alternative, downstream ABL promoter (Pa), which is usually retained in this chimeric oncogene, was reported to be methylated in many CML patients, but there has been controversy as to whether this methylation is a frequent change in bone marrow (BM) in early chronic phase (CP) or only past this stage. Also, the relevance of Pa promoter methylation to BCR-ABL expression in CML is unclear. We examined methylation of the ABL Pa promoter in uncultured BM samples and in colonies derived from their hematopoietic precursor cells by bisulfite and PCR-based assays (combined bisulfite restriction analysis and methylation-specific PCR). BM from seven CP CML patients at diagnosis had about 20-60% of the copies of the ABL Pa promoter methylated. No Pa methylation was detected in normal BMs or colonies derived from them. In contrast, most colonies from CP CML patients had Pa methylation. Surprisingly, 18-49% of the CML-derived colonies with this methylation reproducibly had no detectable BCR-ABL RNA on nested reverse transcription-PCR. Furthermore, the percentage of BCR-ABL RNA-positive colonies was almost same among the colonies not displaying Pa methylation as among the colonies in which this methylation was found. We conclude that ABL Pa methylation is often an early marker of CML in hematopoietic precursors and in total mononuclear BM cells but that it is not associated with an increased frequency of BCR-ABL RNA-positive cells. This methylation might be emblematic of cancer-associated hypermethylation elsewhere in the genome with the consequent silencing of tumor suppressor genes seen in many malignancies.
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PMID:ABL1 promoter methylation can exist independently of BCR-ABL transcription in chronic myeloid leukemia hematopoietic progenitors. 1155 72


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