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)

This report describes a clinical case of a large cell, immunoblastic plasmacytoid malignant B-cell lymphoma of the rectum in an AIDS patient coinfected with HTLV-I. The malignant cells showed clonal genetic rearrangement of the HC (JH) and LCK genes. Infection by EBV was demonstrated serologically and with slot blots using genomic DNA of the cancer cells. Southern blot analysis with DNA extracted from the lymphoma cells were negative for HTLV-I. The patient received seven cycles of VACO-B which induced complete but transient clinical remission of the tumor. The final outcome of the patient is unknown.
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PMID:Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I. 128 27

Chronically immunosuppressed individuals are susceptible to lymphoreticular tumors. Up to 15% of patients with congenital deficiencies such as ataxia=telangiectasia may develop malignancies, mainly high-grade B cell non=Hodgkin's lymphomas (NHLs). AIDS lymphomas are comprised of NHLs including Burkitt's lymphoma (BL) and primary cerebral lymphomas (PCLs). Almost 3% of all AIDS patients (2824 of 97,258 cases) developed NHL. Epstein-Barr virus (EBV) as a co-factor in AIDS lymphomagenesis has been studied: in 12 cases of 24 AIDS lymphomas EBV by DNA in situ hybridization was found. In an analysis of 6 primary cerebral lymphomas, .5 were positive for EBV DNA by Southern blotting. In Burkitt's lymphoma the characteristic genetic alteration affects the c-myc oncogene. In 1/3 of BL p53 mutations were found but none in the 43 NHLs suggesting that p53 mutations and c-myc activation act synergistically in the pathogenesis of these tumors. Cytotoxic agents dideoxyinosine, dideoxycytosine, and zidovudine may cause secondary neoplasia. 8 of 55 AIDS patients under zidovudine treatment developed high-grade lymphoma 23.8 months subsequently; recently doses were reduced. PCL was found in 21 of 90 patients. A 5.2 months survival was associated with combined treatment with cyclophosphamide, Oncovin (vincristine), methotrexate, etoposide, and cytosine arabinoside compared with 11.3 months with chemotherapy. Colony-stimulating factors (CSFs) alleviate drug-induced myelotoxicity and zidovudine-induced neutropenia, however, l8 of 11 patients receiving granulocyte-macrophage CSF developed hematological toxicity. Interleukine-2 produced by T-helper cells enhancing tumor cells cytotoxicity has been used in AIDS-associated cryptosporidial diarrhea and in 4 patients with AIDS lymphoma with modest response, but its stimulation of the HIV-infected substrate may increase viral proliferation.
Int J STD AIDS
PMID:AIDS lymphomas. 161 63

Oncogene dosage and expression were studied in 16 testicular neoplasms, 14 of germ cell and two of non-germ cell origin. In comparison with normal DNA, tumour DNA of a total of eight patients (seven with germ cell neoplasm and one with testicular lymphoma) showed increased dosages of KRAS2, PDGFA, EGFR, MET and PDGFB. The most frequent (occurring in six tumours) and prominent (up to 3-4-fold) increases were detected in the dosages of KRAS2 (on chromosome 12p) and PDGFA (chromosome 7p), relative to a reference locus from chromosome 2. Importantly, there was a similar increase in 12p dosage in general in these tumours, suggesting the presence of the characteristic isochromosome 12p marker. On the contrary, possible 7p polysomy (assessed by molecular methods) did not explain the PDGFA (or EGFR) changes in all cases. NRAS, MYCN, CSFIR, MYB, MYC, ABL, HRASI, TP53, and ERBB2 did not reveal any consistent alterations in tumour DNA. In RNA dot blot assays the expression of KRAS2, PDGFA, EGFR, or MYC was generally not increased in the tumour samples when compared to that in normal testicular tissue of the same patients although there was interindividual variation in mRNA levels. It thus appears that while oncogene dosage changes occur in a proportion of testis cancers, they are often part of changes in large chromosomal regions or whole arms and are seldom accompanied by altered expression.
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PMID:Oncogenes in human testicular cancer: DNA and RNA studies. 182 52

The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future.
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PMID:[Chemotherapy responsiveness of brain tumors in subrenal capsule assay]. 232 45

The genetic determinant responsible for virulence in Moloney murine leukemia virus (MoMuLV) induced T-cell lymphomagenesis has recently been mapped [J Virol 63:471-480, 1989] by homologous genomic fragment exchange between MoMuLV and MoMuLV-TB to the Clal/Xbal at the 3' end of the genome. This region of MoMuLV and MoMuLV-TB differs in 11 nucleotides. Of these 11 nucleotide differences, 9 are distributed within the two CORE, the two distal NF1, and the two GRE/LVa elements of the enhancer. Since both the CORE binding sites of MoMuLV-TB are mutated with respect to those of MoMuLV, we compared nuclear proteins of a thymus-bone marrow cell line and a T-lymphoma cell line (EMT), which bind to the wild-type and mutant CORE binding sites. Using both the bandshift assay and southwestern analysis with labeled synthetic deoxyoligonucleotides, we showed that a 42-kDa protein from TB and EMT cells bound specifically to the MoMuLV CORE element. The T----C transversion of nucleotide 6 of the CORE consensus, TGTGGT/CTAA, significantly reduced binding of the 42-kDa TB and EMT cell factors. However, the transversion of nucleotide 3 from T----C had little effect on the binding of the 42-kDa protein to the CORE element. In addition, the 42-kDa protein bound weakly to the CCAAT element of MoMuLV. A recombinant virus, NwtTB-6, was generated by introducing the two CORE mutations of MoMuLV-TB into the MoMuLV genome. Although the latency period of NwtTB-6 in the induction of lymphoma was not significantly different from that of MoMuLV, preliminary findings suggest that the lymphoma induced by NwtTB-6 may be more widely distributed.
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PMID:A single mutation in one of the CORE elements of Moloney murine leukemia virus reduced binding of a 42-kDa T lymphoma cell nuclear factor but did not affect lymphomagenesis. 234 87

Cellular or proto-oncogenes are normal cellular genes important in normal cell growth and development. In some instances abnormal expression of these genes is associated with altered cell growth or with malignant transformation. Abnormalities of cellular oncogenes are common in human leukemias. These arise by multiple mechanisms such as mutation, translocation, amplification, and others. Sometimes more than one abnormality is present within a single oncogene. In other instances, a leukemia cell may contain abnormalities of several different oncogenes. Some oncogene abnormalities are relatively specific for certain leukemias and occur in almost all cases; examples include ABL in chronic myelogenous leukemia or MYC in Burkitt leukemia/lymphoma. Other abnormalities are also relatively specific but occur in only some cases such as NRAS in acute myelogenous leukemia or BCL2 in B-cell acute lymphoblastic leukemia. In other leukemias, such as most cases of acute lymphoblastic leukemia and chronic lymphocytic leukemia, oncogene abnormalities are uncommon. The precise role of oncogenes in the pathogenesis of human leukemia is unknown. Retrovirus transduced versions of some of the oncogenes modified in human leukemias cause leukemia in animals. Other oncogenes, modified or unmodified, transform animal and human hematopoietic cells in vitro. Some oncogene products are hematopoietic growth factors or growth factor receptors while others regulate cell proliferation or differentiation by diverse mechanisms. Disruption of the balance between these processes seems the most likely mechanism of oncogene related leukemogenesis. If the role of oncogenes in human leukemias can be defined, innovative diagnostic and therapeutic strategies may be forthcoming.
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PMID:Oncogenes and leukemia. 240 17

A translocation between chromosomes 7 and 9, t(7;9), has been described in cell lines derived from the malignant cells of children with acute T-cell lymphoblastic leukemia or lymphoma. Our cytogenetic analysis of one such cell line, SUP-T3, demonstrates that the breakpoints on chromosomes 7 and 9 lie within bands q36 and q34, respectively, corresponding to the location of the gene encoding the beta chain of the T-cell receptor, TCRB, and the gene homologous to the transforming gene of the Abelson murine leukemia virus, ABL. We investigated the role of these genes in the t(7;9). In situ chromosomal hybridization of TCRB and ABL probes to metaphase cells from SUP-T3 demonstrated that ABL is translocated from chromosome 9 to 7 and that all or part of TCRB is translocated from chromosome 7 to 9. Southern blot analysis revealed that both TCRB alleles were rearranged; however, it could not be determined whether the translocation breakpoint lies within this gene. Pulsed-field gel electrophoresis and Southern blot analysis were used to examine more than 500 kilobases of the ABL locus; we concluded that there are no rearrangements within 250 kb in either direction of the sequences homologous to v-abl. Additionally, no abnormal ABL protein was detected in an in vitro phosphorylation assay. These results indicate that, in SUP-T3, the breakpoint on chromosome 9 lies proximal to ABL and that the break results in no apparent alteration of the ABL protein. We therefore hypothesize that another gene on chromosome 9, at band q34, plays a role in this translocation. This study also demonstrates that pulsed-field gel electrophoresis is a powerful new tool for the analysis of human chromosomal translocations.
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PMID:Molecular analysis of TCRB and ABL in a t(7;9)-containing cell line (SUP-T3) from a human T-cell leukemia. 302 59

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.
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PMID:Activity of a monoclonal antibody-saporin-6 conjugate against B-lymphoma cells. 325 67

This study was carried out on five types of experimental tumors maintained by serial subcutaneous transplants in isogeneic mouse hosts. These tumors involved three mammary carcinomas (dbrB, DBAH, MT2), a spindle-cell sarcoma (TEC) and a lymphoblastic type of lymphoma (DBA/3). Growth curves of these tumors are presented. Computed percent labeled mitoses curves for the five types of tumors, the derived cell cycle parameters (TG1, TG2, TS, Tc), and the volume-doubling time (VDT) in days are also presented. The histologic and morphologic appearance of each type of tumor is seen by light microscopy, and the ultrastructural morphology of each type of tumor is seen in electron micrographs. The variation in the kinetic parameters and the autoradiographic exposure time needed to obtain comparable labeling intensity for the five types of tumors is interpreted on the basis of the ultrastructural integrity of the cytoplasmic components of the individual tumor type. The response of these five tumor types to radiotherapy was investigated. The therapy consisted of administering combined treatments of three agents: X-rays, the radiosensitizing drug, misonidazole, and microwave hyperthermia. This treatment resulted in an enhancement factor of 3.9, compared with that of X-rays alone. Total tumor regressions were obtained with microwave hyperthermia alone. The required time of exposure to hyperthermic treatments differed, depending on the response of each type of tumor.
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PMID:Cell kinetics, cell structure, and radiotherapy. 696 41

Apoptin, a small protein encoded by chicken anemia virus (CAV) was expressed in various human hematologic malignant cell lines derived from leukemias and lymphoma. Three of these cell lines contain bcl-2 or BCR-ABL proteins, known to block apoptosis induced by chemotherapeutic compounds. By immunofluorescence and propidium-iodide staining apoptin was shown to induce apoptosis in all analysed cell lines. Early after expression, apoptin exhibited a fine-granular distribution in the still intact nucleus. Later, apoptin became aggregated and the nucleus segmented. The data with truncated apoptin indicate that for optimal induction of apoptosis apoptin has to be located in the nucleus.
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PMID:Apoptin, a protein encoded by chicken anemia virus, induces cell death in various human hematologic malignant cells in vitro. 747 2


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