329 results on '"Slamon DJ"'
Search Results
302. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
- Author
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Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, and McGuire WL
- Subjects
- Axilla, Breast Neoplasms mortality, Breast Neoplasms pathology, DNA genetics, ErbB Receptors genetics, Female, Humans, Lymph Nodes pathology, Nucleic Acid Hybridization, Prognosis, Breast Neoplasms genetics, Gene Amplification, Neoplasm Recurrence, Local genetics, Oncogenes
- Abstract
The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.
- Published
- 1987
- Full Text
- View/download PDF
303. Oncogenes in clinical cancer--a panel discussion.
- Author
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McGuire WL, Johnson BE, Seeger RC, and Slamon DJ
- Subjects
- Breast Neoplasms genetics, Carcinoma, Small Cell genetics, Female, Gene Amplification, Growth Substances genetics, Humans, Lung Neoplasms genetics, Neuroblastoma genetics, Prognosis, Proto-Oncogenes, Neoplasms genetics, Oncogenes
- Published
- 1987
- Full Text
- View/download PDF
304. Identification of new gene products coded from X regions of human T-cell leukemia viruses.
- Author
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Shimotohno K, Miwa M, Slamon DJ, Chen IS, Hoshino H, Takano M, Fujino M, and Sugimura T
- Subjects
- Base Sequence, Cell Line, Electrophoresis, Polyacrylamide Gel, Humans, Immunosorbent Techniques, Leukemia genetics, Molecular Weight, Oligopeptides immunology, T-Lymphocytes, DNA, Viral analysis, Deltaretrovirus genetics, Viral Proteins analysis
- Abstract
Antibodies were raised against oligopeptides deduced from the nucleotide sequence in the conserved region located between env and the 3' long terminal repeat in human T-cell leukemia virus type I (HTLV-I) and type II (HTLV-II) to detect a protein coded from this region in virus-infected cells. Two of these antibodies precipitated a protein of 41 kilo-daltons in HTLV-I-infected cell lines and a protein of 38 kilo-daltons in HTLV-II-infected cells. The protein in HTLV-I-infected cells was precipitated by plasma from patients with adult T-cell leukemia but not by plasma from a normal adult. These results indicate that these proteins were translated from new coding regions (X) present in HTLV-I and HTLV-II.
- Published
- 1985
- Full Text
- View/download PDF
305. Expression of cellular oncogenes in human malignancies.
- Author
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Slamon DJ, deKernion JB, Verma IM, and Cline MJ
- Subjects
- Adenocarcinoma genetics, Breast Neoplasms genetics, Carcinogens pharmacology, Cell Differentiation, Cell Division, Cell Transformation, Neoplastic, Female, Gastrointestinal Neoplasms genetics, Gene Amplification, Genes, Viral, Genital Neoplasms, Female genetics, Humans, Kidney Neoplasms genetics, Leukemia genetics, Lymphoma genetics, Methylation, Mutation, Nucleic Acid Hybridization, RNA, Messenger genetics, RNA, Neoplasm genetics, Sarcoma genetics, Translocation, Genetic, Neoplasms genetics, Oncogenes, Transcription, Genetic
- Abstract
Cellular oncogenes have been implicated in the induction of malignant transformation in some model systems in vitro and may be related to malignancies in vivo in some vertebrate species. This article describes a study of the expression of 15 cellular oncogenes in fresh human tumors from 54 patients, representing 20 different tumor types. More than one cellular oncogene was transcriptionally active in all of the tumors examined. In 14 patients it was possible to study normal and malignant tissue from the same organ. In many of these patients, the transcriptional activity of certain oncogenes was greater in the malignant than the normal tissue. The cellular fes (feline sarcoma) oncogene, not previously known to be transcribed in mammalian tissue, was found to be active in lung and hematopoietic malignancies.
- Published
- 1984
- Full Text
- View/download PDF
306. Studies of the human c-myb gene and its product in human acute leukemias.
- Author
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Slamon DJ, Boone TC, Murdock DC, Keith DE, Press MF, Larson RA, and Souza LM
- Subjects
- Base Sequence, Cell Line, Cloning, Molecular, DNA analysis, DNA Restriction Enzymes metabolism, Escherichia coli genetics, Hematopoietic Stem Cells microbiology, Humans, Molecular Weight, Proteins analysis, Aspartate Carbamoyltransferase, Avian Leukosis Virus genetics, Avian Myeloblastosis Virus genetics, Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing), Dihydroorotase, Leukemia, Myeloid, Acute genetics, Multienzyme Complexes, Oncogenes
- Abstract
The myb gene is the transforming oncogene of the avian myeloblastosis virus (AMV); its normal cellular homolog, c-myb, is conserved across a broad span of evolution. In humans, c-myb is expressed in malignant hematopoietic cell lines and in primary hematopoietic tumors. Partial complementary DNA clones were generated from blast cells of patients with acute myelogenous leukemia. The sequences of the clones were compared to the c-myb of other species, as well as the v-myb of AMV. In addition, the carboxyl terminal region of human c-myb was placed in an expression vector to obtain protein for the generation of antiserum, which was used to identify the human c-myb gene product. Like v-myb, this protein was found within the nucleus of leukemic cells where it was associated with the nuclear matrix. These studies provide further evidence that c-myb might be involved in human leukemia.
- Published
- 1986
- Full Text
- View/download PDF
307. The x gene is essential for HTLV replication.
- Author
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Chen IS, Slamon DJ, Rosenblatt JD, Shah NP, Quan SG, and Wachsman W
- Subjects
- Base Sequence, Deltaretrovirus growth & development, Genes, Viral, Humans, Mutation, Transcription, Genetic, Deltaretrovirus genetics, RNA, Viral biosynthesis, Virus Replication
- Abstract
The human T-cell leukemia viruses (HTLV) are associated with T-cell malignancies in man and will transform normal human T cells in vitro. The mechanism of malignant transformation by HTLV is unknown but appears to be distinct from that of other classes of retroviruses, which induce malignant transformation through viral or cellular oncogenes. Recently a new gene, termed x, was identified in HTLV. This gene has been hypothesized to be the transforming gene of HTLV because of its conservation within the HTLV class of retroviruses. By in vitro mutagenesis of the HTLV-II x gene, it is now demonstrated that the presence of a functional x gene product is necessary for efficient HTLV transcription. Therefore, these studies provide direct evidence for an important function of the x gene in HTLV replication. The functional analogies between the x gene and transcriptional regulatory genes of some DNA viruses suggest that these viruses share similar mechanisms for cellular transformation.
- Published
- 1985
- Full Text
- View/download PDF
308. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II.
- Author
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Slamon DJ, Shimotohno K, Cline MJ, Golde DW, and Chen IS
- Subjects
- Amino Acid Sequence, B-Lymphocytes microbiology, Cell Line, Deltaretrovirus analysis, Deltaretrovirus physiology, Humans, Immune Sera, Molecular Weight, Trans-Activators, Viral Proteins genetics, Viral Proteins immunology, Cell Transformation, Viral, Deltaretrovirus genetics, Genes, Viral, T-Lymphocytes microbiology, Viral Proteins physiology
- Abstract
The human T-cell leukemia viruses HTLV-I and HTLV-II are unique among the transforming retroviruses of vertebrates in their ability to transform human T cells in vitro and in their close association with human malignancies (T-cell lymphomas and leukemia). Their genomes are relatively simple, containing the genes gag, pol, env, and a 3' region termed "X." This 3' region may be responsible for the transforming potential of the viruses. The existence of proteins encoded by the 3' region has been postulated on the basis of multiple open reading frames. In the present study this region is shown to contain a gene encoding a protein of 40 kilodaltons in HTLV-I and 37 kilodaltons in HTLV-II. It is proposed that these proteins be called, respectively, p40xI and p37xII.
- Published
- 1984
- Full Text
- View/download PDF
309. Expression of a multidrug-resistance gene in human tumors and tissues.
- Author
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Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, and Pastan I
- Subjects
- Animals, Cell Line, Child, Humans, KB Cells, Nucleic Acid Hybridization, RNA analysis, RNA, Neoplasm analysis, Rats, Transcription, Genetic, Vinblastine pharmacology, Drug Resistance, Genes drug effects, Neoplasms genetics
- Abstract
The identification and cloning of a segment of a human multidrug resistance gene (mdr1) was reported recently. To examine the molecular basis of one type of multidrug resistance, we have prepared RNA from human tumors and normal tissues and measured their content of mdr1 RNA. We find that the mdr1 gene is expressed at a very high level in the adrenal gland; at a high level in the kidney; at intermediate levels in the lung, liver, lower jejunum, colon, and rectum; and at low levels in many other tissues. The mdr1 gene is also expressed in several human tumors, including many but not all tumors derived from the adrenal gland and the colon. In addition, increased expression was detected in a few tumors at the time of relapse following initial chemotherapy. Although controlled clinical studies will be required, our results suggest that measurement of mdr1 RNA may prove to be a valuable tool in the design of chemotherapy protocols.
- Published
- 1987
- Full Text
- View/download PDF
310. Organ specific expression of ras oncoproteins during growth and development of the rat.
- Author
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Tanaka T, Ida N, Shimoda H, Waki C, Slamon DJ, and Cline MJ
- Subjects
- Animals, Brain growth & development, Brain Chemistry, Gene Expression Regulation, Immunoelectrophoresis, Oncogenes, Organ Specificity, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins immunology, Proto-Oncogene Proteins p21(ras), Rats metabolism, Rats, Inbred Strains, Sequence Homology, Nucleic Acid, Proto-Oncogene Proteins biosynthesis, Rats growth & development
- Abstract
Expression of proteins encoded by the ras proto-oncogenes was examined in extracts from normal rat organs using anti-ras p21 antibodies generated against synthetic peptides. The highest level of ras p21 was found in brain (cerebrum) and was predominantly of c-Ha-ras origin. Levels of brain ras p21 did not vary from the newborn period of 3 months of age. Moderate levels of ras p21s were detected in lung, spleen and thymus. In contrast to the p21 in brain, these levels varied with the age of the rats and were encoded by other members of ras proto-oncogene family (Ki-ras or N-ras). This organ specific expression of different ras genes might be related to developmental control of gene expressions.
- Published
- 1986
- Full Text
- View/download PDF
311. Proto-oncogenes and human cancers.
- Author
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Slamon DJ
- Subjects
- Gene Amplification, Humans, Mutation, Retroviridae genetics, Neoplasms genetics, Proto-Oncogenes
- Published
- 1987
- Full Text
- View/download PDF
312. Detection of anti-HTLV-I Tax antibodies in HTLV-I enzyme-linked immunosorbent assay-negative individuals.
- Author
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Ehrlich GD, Glaser JB, Abbott MA, Slamon DJ, Keith D, Sliwkowski M, Brandis J, Keitelman E, Teramoto Y, and Papsidero L
- Subjects
- Animals, Blotting, Western, Gene Amplification, HTLV-I Antigens genetics, HTLV-I Antigens immunology, Humans, Male, Precipitin Tests, Rabbits, Recombinant Proteins, Retroviridae Proteins analysis, Retroviridae Proteins genetics, Risk Factors, Virion analysis, Virion genetics, Enzyme-Linked Immunosorbent Assay, HTLV-I Antibodies analysis, HTLV-I Infections diagnosis
- Abstract
The HTLV-I tax gene protein (Tax) is not packaged within the mature viral particle from which the proteins for the commercially available enzyme-linked immunosorbent assay (ELISA) are derived. Screening of 162 individuals within a cohort of white intravenous (IV) drug abusers, previously identified as having an increased incidence of HTLV-I infection, demonstrated that seven of them had antibodies to the HTLV-I Tax protein but tested negative in HTLV-I ELISAs and Western blots prepared from purified virion proteins. Three out of 35 individuals in other behaviorally defined high-risk groups also displayed this limited pattern of reactivity to HTLV-I proteins. The presence of the anti-HTLV-I p40/Tax antibodies was determined by radioimmunoprecipitation assay (RIPA), which also revealed low levels of anti-env reactivity. The specificity of the anti-p40 reactivity was confirmed on specific Tax ELISAs and Western blots prepared from recombinantly produced Tax. In vitro gene amplification by the polymerase chain reaction (PCR) was used to establish the presence of sequences homologous to HTLV-I proviral DNA in four/four of these HTLV-I ELISA negative, Tax ELISA/Tax western blot/RIPA positive individuals. These data suggest that the true incidence of HTLV-I infection within high-risk cohorts is greater than previously reported.
- Published
- 1989
313. Seroprevalence and epidemiological correlates of HTLV-I infection in U.S. blood donors.
- Author
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Williams AE, Fang CT, Slamon DJ, Poiesz BJ, Sandler SG, Darr WF 2nd, Shulman G, McGowan EI, Douglas DK, and Bowman RJ
- Subjects
- Adult, Deltaretrovirus isolation & purification, Deltaretrovirus Infections diagnosis, Deltaretrovirus Infections transmission, Female, Humans, Immunoenzyme Techniques, Immunosorbent Techniques, Japan, Male, Middle Aged, Risk Factors, Sexual Partners, Substance-Related Disorders, United States, Antibodies, Viral analysis, Blood Donors, Deltaretrovirus immunology, Deltaretrovirus Infections epidemiology
- Abstract
Screening for human T-lymphotropic virus type I (HTLV-I) antibodies was performed on sera from 39,898 blood donors at eight blood centers in geographically distinct areas of the United States. Ten donors (0.025 percent) showed evidence of HTLV-I seropositivity by enzyme immunoassays; this was confirmed by protein immunoblot and radioimmunoprecipitation. Seroprevalence rates ranged from 0 to 0.10 percent at the locations sampled, with HTLV-I antibodies found predominantly in donors from the southeastern and southwestern United States. Matched case-control interviews and laboratory studies were performed on five seropositive women and two seropositive men who participated in an identity-linked collection of sera from a subset of 33,893 donors at six of the eight blood centers. Four of the women and both men are black; one woman is Caucasian. Four of the seven seropositive individuals admitted to prior intravenous drug abuse or sexual contact with an intravenous drug user. Sexual contact with native inhabitants of an HTLV-I endemic area was the only identified risk factor for one male. The distribution of HTLV-I antibodies in this U.S. blood donor sample corroborates the previously reported epidemiology of this agent and suggests that additional donor screening measures, including the testing of donated blood for HTLV-I markers, may be necessary to prevent the spread of HTLV-I to transfusion recipients.
- Published
- 1988
- Full Text
- View/download PDF
314. Oncogenes: implications for the diagnosis and treatment of cancer.
- Author
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Cline MJ, Slamon DJ, and Lipsick JS
- Subjects
- Animals, Avian Myeloblastosis Virus genetics, Base Sequence, Cell Differentiation, Cell Division, Cell Line, Cell Transformation, Neoplastic, DNA, Viral physiology, DNA-Binding Proteins metabolism, Growth Substances physiology, Humans, Neoplasm Proteins genetics, Neoplasms diagnosis, Neoplasms therapy, Phosphotransferases metabolism, Protein Biosynthesis, Retroviridae genetics, Retroviridae growth & development, Transformation, Genetic, Translocation, Genetic, Viral Proteins genetics, Viral Proteins physiology, Neoplasms genetics, Oncogenes
- Abstract
Cellular oncogenes comprise a small family of genes, highly conserved throughout vertebrate evolution, that code for proteins with diverse functions including DNA binding, protein kinase, and cellular growth factor activities. Cellular oncogenes are important in certain aspects of the proliferation and differentiation of normal cells. Under some circumstances these genes may also induce malignant transformation of normal cells. Various mechanisms may underlie their involvement in carcinogenesis. Incorporation of all, or part of, cellular oncogenes into RNA tumor viruses, mutations in gene structure, or translocation of cellular oncogenes from one chromosome to another may all be associated with the induction of malignant change in cells. In some of these situations altered oncogene products are made. Knowledge about the biology of oncogenes may lead to improved techniques for cancer detection and perhaps new approaches to cancer treatment.
- Published
- 1984
- Full Text
- View/download PDF
315. Expression of cellular oncogenes during embryonic and fetal development of the mouse.
- Author
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Slamon DJ and Cline MJ
- Subjects
- Age Factors, Animals, Gene Expression Regulation, Mice embryology, Mice growth & development, RNA, Messenger genetics, Mice genetics, Oncogenes
- Abstract
Cellular oncogenes are conserved with great fidelity across a broad span of evolution. This avid conservation suggests possible roles in critical physiologic functions. Little, however, is known about their activity in normal cellular processes. In this study, we examined the expression pattern of eight cellular oncogenes during embryonic and fetal development of the mouse. Five of these genes (c-myc, c-erb, c-Ha-ras, c-src, and c-sis) were expressed at appreciable levels, and four were modulated in a consistent manner during the course of prenatal development.
- Published
- 1984
- Full Text
- View/download PDF
316. N-myc protein expression in small round cell tumors.
- Author
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Triche TJ, Cavazzana AO, Navarro S, Reynolds CP, Slamon DJ, and Seeger RE
- Subjects
- Child, Child, Preschool, DNA analysis, Gene Amplification, Humans, Immunohistochemistry, Neuroblastoma genetics, Neuroectodermal Tumors, Primitive, Peripheral genetics, RNA, Messenger analysis, Sarcoma, Ewing genetics, Neuroblastoma metabolism, Neuroectodermal Tumors, Primitive, Peripheral metabolism, Oncogenes, Sarcoma, Ewing metabolism
- Published
- 1988
317. HTLV-II transactivation is regulated by the overlapping tax/rex nonstructural genes.
- Author
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Rosenblatt JD, Cann AJ, Slamon DJ, Smalberg IS, Shah NP, Fujii J, Wachsman W, and Chen IS
- Subjects
- Base Sequence, DNA, Recombinant, DNA, Viral genetics, Mutation, Promoter Regions, Genetic, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Viral genetics, RNA, Viral metabolism, Simian virus 40 genetics, Transfection, Deltaretrovirus genetics, Genes, Regulator, Genes, Viral, Transcription, Genetic
- Abstract
The human T-cell leukemia virus (HTLV) types I and II have two nonstructural genes that are encoded in overlapping reading frames. One of these genes, known as tax, has been shown to encode a protein responsible for enhanced transcription (transactivation) from the viral long terminal repeats (LTRs). Genetic evidence indicates that the second nonstructural gene of HTLV-II, here designated rex, acts in trans to modulate tax gene-mediated transactivation in a concentration-dependent fashion. The rex gene may regulate the process of transactivation during the viral life cycle.
- Published
- 1988
- Full Text
- View/download PDF
318. HTLV x gene mutants exhibit novel transcriptional regulatory phenotypes.
- Author
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Wachsman W, Cann AJ, Williams JL, Slamon DJ, Souza L, Shah NP, and Chen IS
- Subjects
- Gene Expression Regulation, Mutation, Transcription, Genetic, Deltaretrovirus genetics, Genes, Viral, Transcription Factors genetics
- Abstract
The human T-cell leukemia viruses, HTLV-I and HTLV-II, contain a gene, termed x, with transcriptional regulatory function. The properties of the x proteins were analyzed by constructing mutant genes containing site-directed deletions and point mutations. The results demonstrate that the amino terminal 17 amino acids of the x protein constitute part of a functional domain that is critical for the transcriptional activating properties of the protein. Within this region, substitution of a leucine residue for a proline residue results in major changes in the trans-activation phenotype of the protein. The mutant HTLV-II x protein, though incapable of activating the HTLV-II long terminal repeat, will block trans-activation of the HTLV-II long terminal repeat by the wild-type protein. The altered phenotype of this mutant suggests a potential negative regulatory function of the x protein.
- Published
- 1987
- Full Text
- View/download PDF
319. Studies of the putative transforming protein of the type I human T-cell leukemia virus.
- Author
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Slamon DJ, Press MF, Souza LM, Murdock DC, Cline MJ, Golde DW, Gasson JC, and Chen IS
- Subjects
- Antigens, Polyomavirus Transforming, Antigens, Viral, Tumor immunology, Cell Fractionation, Cell Line, Cell Nucleus metabolism, Cell Transformation, Viral, Half-Life, Humans, Immune Sera, Precipitin Tests, Viral Proteins immunology, Antigens, Viral, Tumor metabolism, Deltaretrovirus metabolism, Viral Proteins metabolism
- Abstract
The putative transforming protein of the type I human T-cell leukemia virus (HTLV-1) is a 40-kilodalton protein encoded by the X region and is termed p40XI. On the basis of both subcellular fractionation techniques and immunocytochemical analysis, it is now shown that p40XI is a nuclear protein with a relatively short half-life (120 minutes). It is synthesized de novo in considerable quantities in a human T-cell line infected with and transformed by the virus in vitro, and it is not packaged in detectable amounts in the extracellular virus.
- Published
- 1985
- Full Text
- View/download PDF
320. Detection of antibodies to human T-lymphotropic virus type 1 (HTLV-1).
- Author
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Fang CT, Williams AE, Sandler SG, Slamon DJ, and Poiesz BJ
- Subjects
- Antigen-Antibody Reactions, Collodion, Deltaretrovirus genetics, Electrophoresis, Polyacrylamide Gel, Gene Products, gag, Humans, Immunoenzyme Techniques, Paper, Precipitin Tests, Retroviridae Proteins immunology, Antibodies, Viral isolation & purification, Deltaretrovirus immunology
- Abstract
Sera from 39,898 blood donors were tested for HTLV-1 antibodies using two enzyme immunoassays (EIA). Sera testing initially reactive (IR) were retested in duplicate by both EIAs. Sera testing repeatedly reactive (RR) were further tested by two Western blots (WB) and by two radioimmunoprecipitation assays (RIPA). There were 176 (0.44%) EIA IR and 68 (0.17%) RR results. On WBs, 10 of the 68 EIA RR sera demonstrated reactivity to HTLV-1 gag gene-encoded core protein p24, with or without reactivity to other core proteins (p19, p28, p53/55). These ten sera were the only ones demonstrating reactivity on RIPAs to other HTLV-1 gene products - env gene-encoded glycoproteins gp46, gp61/68, or tat gene-encoded HTLV-1 transcriptional activator p40x. These ten sera were interpreted as positive for HTLV-1 antibodies. Of the remaining 58 EIA RR sera, 21 were negative by WBs and RIPAs, 37 sera demonstrated reactivity to various combinations of p19, p28, and p53/55, but not to p24 on WBs. These 37 sera were interpreted as "indeterminate", because they were negative by RIPAs. We conclude that: 1) EIA testing and WB/RIPA verification identified 10 (0.025%) HTLV-1 infected individuals among 39,898 low-risk blood donors; 2) anti-p24 may be a more sensitive and specific indicator of HTLV-1 infection than antibodies to p19, p28, or p53/55; and 3) presently, both WB and RIPA are needed to verify HTLV-1 EIA reactivity.
- Published
- 1988
- Full Text
- View/download PDF
321. Characterization of human neuroblastoma cell lines that lack N-myc gene amplification.
- Author
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Wada RK, Seeger RC, Brodeur GM, Slamon DJ, Rayner SA, Tomayko M, and Reynolds CP
- Subjects
- Cell Division, Cell Line, Child, Preschool, Flow Cytometry, Humans, Infant, Male, Chromosomes, Human, Pair 1, Gene Amplification, Neuroblastoma genetics, Oncogenes, Tumor Cells, Cultured analysis
- Published
- 1988
322. Cell type-specific expressions of c-ras gene products in the normal rat.
- Author
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Tanaka T, Ida N, Waki C, Shimoda H, Slamon DJ, and Cline MJ
- Subjects
- Animals, Gene Expression Regulation, Histocytochemistry, Immunoenzyme Techniques, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), Rats, Rats, Inbred Strains, Tissue Distribution, Proto-Oncogene Proteins metabolism
- Abstract
Expression of proteins encoded by the ras proto-oncogenes was examined immunohistochemically in formalin-fixed, paraffin-embedded tissues of the normal rat using anti-ras p21 antibodies generated against synthetic peptides. Cell type specific expressions of ras gene products were detected in distal tubules of kidney, megakaryocytes in spleen, neural cells in cerebrum, Purkinje cells in cerebellum, cells lining the pulmonary alveoli and cells in the epithelium of intestinal villi. Region specific expressions of the ras proteins were observed in spleen and thymus, where the ras proteins were detected in splenic nodules including germinal centers and thymic medulla, respectively. These findings suggest that the c-ras gene products in normal rat organs are expressed in specific cell-types within a tissue and may be associated with degree of cellular differentiation.
- Published
- 1987
- Full Text
- View/download PDF
323. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse.
- Author
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Müller R, Slamon DJ, Tremblay JM, Cline MJ, and Verma IM
- Subjects
- Age Factors, Animals, Gene Expression Regulation, Mice genetics, Sarcoma Viruses, Murine genetics, Tissue Distribution, Mice embryology, Oncogenes
- Published
- 1982
- Full Text
- View/download PDF
324. Expression of p21 ras oncoproteins in human cancers.
- Author
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Tanaka T, Slamon DJ, Battifora H, and Cline MJ
- Subjects
- Antigens, Neoplasm analysis, Gene Expression Regulation, Humans, Immunosorbent Techniques, Neoplasm Proteins immunology, Neoplasms immunology, Proto-Oncogene Proteins immunology, Neoplasm Proteins metabolism, Neoplasms metabolism, Oncogenes, Proto-Oncogene Proteins metabolism
- Abstract
The expression of proteins encoded by ras oncogenes was examined in 52 fresh human tumors of 19 different types using antibodies generated to different peptide domains of ras proteins of molecular weight 21,000 (p21). Proteins related to ras genes were detected in 90% of tested tumors. In 21% of tumors there were high levels of ras p21 of greater than 40% of the level in a Harvey murine sarcoma virus transformed cell line. Predominance of either cellular Ha-ras or other ras p21s was found in 20 and 14% of tumors, respectively, and predominance of p21 other than Ha-ras was frequent in breast cancers. Abnormal electrophoretic mobility of p21 was observed in two cancers, and a novel rapidly migrating ras p21 was found in a rare malignant fibrohistiocytoma.
- Published
- 1986
325. Amplification of c-erbB-2 and aggressive human breast tumors?
- Author
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Slamon DJ and Clark GM
- Subjects
- Chromosomes, Human, Pair 17, DNA, Neoplasm genetics, Humans, Neoplasm Proteins genetics, Phosphoproteins genetics, Tumor Suppressor Protein p53, Breast Neoplasms genetics, Gene Amplification, Proto-Oncogene Proteins genetics
- Published
- 1988
- Full Text
- View/download PDF
326. Insertion of drug resistance genes in animals.
- Author
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Bar-Eli M, Mercola KE, Slamon DJ, Mauritzson N, Stang HD, and Cline MJ
- Subjects
- Animals, Cell Fractionation, Chromosomes physiology, Cloning, Molecular, Drug Resistance, Microbial, Genes, Genetic Vectors, Mice, Microinjections, Genetic Engineering, Hematopoietic Stem Cells, Methotrexate pharmacology, Tetrahydrofolate Dehydrogenase genetics, Transformation, Genetic
- Published
- 1982
- Full Text
- View/download PDF
327. Studies of the retinoblastoma gene in human sarcomas.
- Author
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Reissmann PT, Simon MA, Lee WH, and Slamon DJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Chromosome Deletion, DNA, Neoplasm analysis, Humans, Middle Aged, RNA, Neoplasm analysis, Eye Neoplasms genetics, Retinoblastoma genetics, Sarcoma genetics, Suppression, Genetic
- Abstract
The retinoblastoma susceptibility gene, (RB), is a tumor suppressor gene which, when deleted is associated with the development of retinoblastoma. The observation that children with heritable retinoblastoma frequently develop second malignancies, principally sarcomas, led to the detection of similar RB gene deletions in some osteosarcomas. We studied 44 unselected sarcomas from patients with no antecedent retinoblastoma to determine the prevalence and nature of RB gene alterations. DNA and RNA were extracted from fresh tumors and analysed by Southern and Northern blotting. Three of nine osteosarcomas and 4 of 29 soft-tissue sarcomas had deletions of the RB gene. Four of these were full-length, and three were partial deletions of the gene. RNA from 5 of the 7 deleted tumors was studied, and 4 cases completely lacked the RB transcript. Transcripts were found in 19 of 20 tumors with an apparently intact RB gene, and in all the normal tissues studied. An additional tumor lacked the RB transcript, but the gene appeared intact at the DNA level. In total, 8 of 38 sarcomas were found to have alterations of the RB gene. These data indicate that the RB gene is inactivated in a significant number of sarcomas unrelated to retinoblastoma, and that the potential role for the gene in the pathogenesis of human malignancy may not be limited to retinoblastoma.
- Published
- 1989
328. Regulation of expression of human granulocyte/macrophage colony-stimulating factor.
- Author
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Chan JY, Slamon DJ, Nimer SD, Golde DW, and Gasson JC
- Subjects
- Acetyltransferases genetics, Animals, Base Sequence, Chloramphenicol O-Acetyltransferase, Humans, Interleukin-3 analysis, Interleukin-3 biosynthesis, Lymphocyte Activation, Rabbits, T-Lymphocytes metabolism, Tetradecanoylphorbol Acetate pharmacology, Transcription, Genetic, Gene Expression Regulation, Interleukin-3 genetics
- Abstract
Colony-stimulating factors (CSFs) are glycoproteins that stimulate the growth of hematopoietic progenitors and enhance the functional activity of mature effector cells. Human granulocyte/macrophage colony-stimulating factor (GM-CSF) is a 22-kDa glycoprotein that stimulates the growth of myeloid and erythroid progenitors in vitro and increases the responsiveness of neutrophils, monocytes, and eosinophils to physiologic stimuli. Elucidation of the cell and tissue sources of CSFs, as well as study of their regulation of expression, is required to understand their role in physiologic and pathophysiologic states. An extensive survey of normal and neoplastic human tissues did not reveal constitutive production of detectable levels of GM-CSF mRNA in any of the 64 samples studied. Antigen- or lectin-activated T lymphocytes have been shown to produce GM-CSF; therefore, to elucidate the genetic sequences required, we constructed recombinant plasmids containing 5' flanking DNA of the GM-CSF gene linked to the marker chloramphenicol acetyltransferase gene. The recombinant constructs were transfected into a human T-cell leukemia virus type I (HTLV)-infected T-lymphoblast cell line that can be stimulated to produce high levels of GM-CSF. We show here that the 5' flanking sequences of the GM-CSF gene can direct increased expression of the chloramphenicol acetyltransferase gene in activated T-lymphoblast cells.
- Published
- 1986
- Full Text
- View/download PDF
329. Protective effect of the double-stranded polyribonucleotide, polyinosinic polycytidylic acid, against rat erythroblastosis induced by murine erythroblastosis virus.
- Author
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Slamon DJ
- Subjects
- Animals, Blood Cell Count, Blood Platelets, Female, Hematologic Diseases etiology, Hematologic Diseases pathology, Lymphoma etiology, Male, Neoplasms, Experimental etiology, Rats, Rats, Inbred WF, Spleen pathology, Hematologic Diseases prevention & control, Leukemia Virus, Murine drug effects, Poly I-C therapeutic use, Tumor Virus Infections pathology
- Published
- 1973
- Full Text
- View/download PDF
Catalog
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