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)

The number of gene assignments to human chromosome 20 has increased slowly until recently. Only seven genes and one fragile site were confirmed assignments to chromosome 20 at the Ninth Human Gene Mapping Workshop in September 1987 (HGM9). One fragile site, 13 additional genes, and 10 DNA sequences that identify restriction fragment length polymorphisms (RFLPs), however, were provisionally added to the map at HGM9. Five mutated genes on chromosome 20 have a relation to disease: a mutation in the adenosine deaminase gene results in a deficiency of the enzyme and severe combined immune deficiency; mutations in the gene for the growth hormone releasing factor result in some forms of dwarfism; mutations in the closely linked genes for the hormones arginine vasopressin and oxytocin and their neurophysins are probably responsible for some diabetes insipidus; and mutations in the gene that regulates both alpha-neuraminidase and beta-galactosidase activities determine galactosialidosis. The gene for the prion protein is on chromosome 20; it is related to the infectious agent of kuru, Creutzfeld-Jacob disease, and Gertsmann-Straussler syndrome, although the nature of the relationship is not completely understood. Two genes that code for tyrosine kinases are on the chromosome, SRC1 the proto-oncogene and a gene (HCK) coding for haemopoietic kinase (an src-like kinase), but no direct relation to cancer has been shown for either of these kinases. The significance of non-random loss of chromosome 20 in the malignant diseases non-lymphocytic leukaemia and polycythaemia vera is not understood. Twenty-four additional loci are assigned to the chromosome: five genes that code for binding proteins, one for a light chain of ferritin, genes for three enzymes (inosine triphosphatase, s-adenosylhomocysteine hydrolase, and sterol delta 24-reductase), one for each of a secretory protein and an opiate neuropeptide, a cell surface antigen, two fragile sites, and 10 DNA sequences (one satellite and nine unique) that detect RFLPs.
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PMID:The map of chromosome 20. 307 44

Subrenal capsule assay(SRC assay) has been reported to be an effective and rapid method for predicting the tumor sensitivity of individual patients to anti-cancer agents. In order to establish a more objective method of determining sensitivity in SRC assay the DNA content was measured by the schmidt-Thannhauser-Schneider method and the protein content was estimated using Bio-Rad protein assay, after removal of a tumor implanted in the subrenal capsular space of ddY mice. Percentage inhibition of DNA/protein had a high correlation with that of relative increase of tumor weight, although three groups treated with mitomycin-C, 5-fluorouracil and cyclophosphamide indicated different values of tumor sensitivity. From these results, the percentage inhibition of DNA/protein seems to be more objective than microscopic measurement for predicting tumor sensitivity.
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PMID:[Sensitivity test of anticancer agents by subrenal capsule assay (SRC assay). II--Determination of tumor sensitivity by percentage inhibition of DNA protein]. 308 Sep 63

We studied fundamentally subrenal capsule assay, using human tumor specimens (gastric, breast and pancreas cancers) serially transplanted in nude mice. Any prominent difference of host reaction was not found between the host of BALB/c-nu/+, BALB/c-+/+ and CDF1 mice. Using immunocompetent BALB/c-nu/+ mice, experimental chemotherapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) was carried out. On day 6, macroscopic and histological findings corresponded relatively well with 5-FU effect but not with MMC. Using BALB/c-nu/nu mice, we tried 15-day SRC assay. When the sensitivity of anti-cancer drugs was compared between early and intermediate phase after inoculation, no obvious difference was found macroscopically and histologically. BALB/c-nu/nu mouse will be useful as a host of SRC assay, and could be applicable to clinical fresh cases.
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PMID:[Subrenal capsule assay as a chemosensitivity test (III)--Comparison of host reaction, experimental chemotherapy and use of nude mice]. 311 83

Surface markers have been of proven diagnostic and prognostic use in acute lymphoblastic leukemia (ALL). T cell ALL (T-ALL), where blasts possess receptors for sheep red blood cells (R-SRC+), is associated with an adverse prognosis in children and adults. The presence of common ALL antigen (CALLA)-positive blasts (i.e. common-ALL) in children is indicative of a good response to treatment, in contrast to the poor response shown by pre-B-ALL cases, where the blasts are also CALLA-positive but additionally contain cytoplasmic mu chains. Recently a subgroup of T-ALL, immature T-ALL, was identified, where the blasts lack R-SRC and T cell markers (such as T1, T3, T4, T8, T6) but carry a pan T cell antigen (p40) recognized by the monoclonal antibody LAU-A1(12/103 ALL cases in our series). This new subgroup, immature T-ALL (R-SRC-/p40+), also seems to be associated with a poor prognosis, like T-ALL.
Eur J Cancer Clin Oncol 1985 Mar
PMID:Contribution of immunological markers to the diagnosis and prognosis of human leukemia. 315 79

A monoclonal antibody reactive with the immunoglobulin heavy chain (TEC IgM) has been conjugated to saporin-6 (SAP), which is the major ribosome-inactivating protein from the seeds of the plant Saponaria officinalis. Studies with Burkitt's lymphoma cell line Bjab 113 demonstrate that this immunotoxin is capable of killing 3 logs (99.9%) of clonogenic lymphoma cells after a 2-hour incubation. The presence of human bone marrow inhibits the activity of the conjugate. However, full potency of TEC IgM-SAP immunotoxin is restored by adding 1 mM amantadine to the incubation medium. The reaction is highly specific and is inhibited by the presence of excess anti-mu-antibody or human serum. Clonal growth of other Burkitt's lymphoma cell lines is inhibited to a lesser extent by the immunotoxin. The presence of surface IgM on the different cell lines is directly correlated to target cell killing by TEC IgM-SAP. Isolation of Bjab 113 clones surviving treatment demonstrates that only a minority are truly resistant and that the others randomly escape the treatment. The highly potent and specific activity of this conjugate in the presence of bone marrow buffy coat and its exceptionally rapid onset of action make this conjugate a good candidate for the ex vivo elimination of neoplastic cells from the bone marrow of non-Hodgkin's lymphoma patients.
J Natl Cancer Inst 1988 Jun 01
PMID:Activity of a monoclonal antibody-saporin-6 conjugate against B-lymphoma cells. 325 67

The ABL proto-oncogene on the Philadelphia chromosome is 'activated' by its translocation in a manner similar to its activation by the murine Abelson leukemia virus--with the formation of a fusion protein with a new N-terminus and enhanced tyrosine kinase activity. Study of this BCR-ABL fusion gene has led to the development of molecular probes which are beginning to play an important role in the diagnosis and clinical management of chronic myelogenous leukemia, and may ultimately lead to better understanding of the biology of the disease. The role of ABL on the Philadelphia chromosome in acute lymphoblastic leukemia is only now beginning to be understood, but is likely to be similar, and a new ABL species has already been identified by several groups. It is likely that this protein is the product of a fusion gene, as it is in chronic myelogenous leukemia, but definitive proof awaits molecular cloning of the translocation breakpoint. Aside from its activation by the Ph1 chromosome, ABL has not been found to have a role in any other human cancer.
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PMID:The ABL oncogene in human leukemias. 328 49

We carried out a total of 36 in vivo chemosensitivity tests in 33 cases of human malignant tumor using the subrenal capsule assay, developed by A.E. Bogden et al. Of the 36 assays, 31 were evaluable. The chemosensitivity of each tumor varied individually. UFT, 5-fluorouracil, mitomycin-C and adriamycin were administered to gastrointestinal cancer patients regularly, but our SRC-assay showed a high sensitivity rate for UFT and 5-fluorouracil but a low sensitivity rate for mitomycin-C and adriamycin. Nine patients had clinically evaluable lesions and a correlation between the assay results and clinical response existed in 6 cases. The true positive rate was 50% (3/6), the true negative rate 100% (3/3), and the overall predictive accuracy 66% (6/9). This study suggested that 6-day SRC assay is useful for selecting effective anti-tumor agents for the treatment of cancer patients.
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PMID:[A six-day subrenal capsule assay for predictive testing of primary human tumors]. 333 30

This study was designed to evaluate the interaction of photodynamic therapy (PDT) and chemotherapy in an animal model. PDT is based on the interaction of hematoporphyrin derivative and red light of the appropriate wavelength (630 nm) and intensity. Two tumor models were utilized: C3H/Km mice bearing the RIF-1 tumor and BALB/c mice bearing the EMT-6 tumor. Tumor-bearing mice were treated with either cisplatin (DDP), doxorubicin (ADM), PDT, or a combination of drug and PDT. It was demonstrated that the RIF-1 tumor was sensitive to DDP and insensitive to both PDT and ADM. There was no additional antitumor effect when either drug was combined with PDT. The EMT-6 tumor was moderately sensitive to PDT and mildly sensitive to both DDP and ADM. Although the addition of DDP did not potentiate tumor destruction, the addition of ADM significantly enhanced the effect of PDT (P = .01). The enhanced activity of the combination of PDT and ADM appeared to be the result of increased activity of ADM alone, when illuminated with red (630 nm) light. This potentiation may be due to a photochemical process or may be secondary to the mild hyperthermia generated by illumination with the laser. This study demonstrates that PDT combined with cytotoxic chemotherapy is well tolerated in these animals and that certain combinations of PDT and chemotherapy may result in an enhanced tumoricidal effect.
J Natl Cancer Inst 1988 Jul 20
PMID:Combination cytotoxic chemotherapy with cisplatin or doxorubicin and photodynamic therapy in murine tumors. 338 81

The Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML) contains sequences from chromosome 9, including the ABL protooncogene, that have been translocated to the breakpoint cluster region (bcr) of chromosome 22, giving rise to a bcr-ABL fusion gene, whose product has been implicated in the genesis of CML. Although chromosome 22 translocation breakpoints in CML virtually always occur within the 5.8-kilobase (kb) bcr, chromosome 9 breakpoints have been identified within the known limits of ABL in only a few instances. For a better understanding of the variability of the breakpoints on chromosome 9, we studied the CML cell line BV173. Using pulsed-field gel electrophoresis (PFGE), large-scale maps of the t(9;22) junctions were constructed. The chromosome 9 breakpoint was shown to have occurred within an ABL intron, 160 kb upstream of the v-abl homologous sequences, but still 35 kb downstream of the 5'-most ABL exon. bcr-ABL and ABL-bcr fusion genes were demonstrated on the Ph1 and the 9q+ chromosomes, respectively; both of these genes are expressed. These results suggest that the 9;22 translocation breakpoints in CML consistently occur within the limits of the large ABL gene. RNA splicing, sometimes of very large regions, appears to compensate for the variability in breakpoint location. These studies show that PFGE is a powerful new tool for the analysis of chromosomal translocations in human malignancies.
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PMID:Long-range mapping of the Philadelphia chromosome by pulsed-field gel electrophoresis. 342 29

4'-(9-acridinylamino) methanesulfon-m-anisidide (amsacrine or AMSA), an antitumor drug which has been tested in clinical trials, is known to bind to DNA by the intercalation of its 9-amino acridine moiety between DNA base pairs. Like AMSA, a peptidic derivative of 4-(9-acridinylamino) aniline, 4-(9-acridinylamino)-N-(lysylglycyl) aniline (ALGA) binds to DNA by intercalation and its affinity for the target was found to be higher than the parent drug. The antitumor effect of AMSA and ALGA has been monitored by drug exposure assays on EMT 6 cells. AMSA showed a slightly higher cytotoxic activity. The cell cycle effects of both drugs were studied using flow cytofluorimetry; an accumulation of cells in the S phase followed by a cycle arrest in the G2 phase, characteristic of intercalating drugs, was observed.
Cancer Biochem Biophys 1987 Sep
PMID:Cytotoxic action and cell cycle effects of ALGA, a peptidic derivative of the antileukemic drug amsacrine. 343 97


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