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E Sariban

Publications and source records attributed to E Sariban.

At least 91 records · Page 5Linked to original sources
PubMed1987

Expression of the c-raf protooncogene in human hematopoietic cells and cell lines.

The murine sarcoma virus 3611 contains the transforming v-raf gene that has partial nucleotide homology with the src family of tyrosine kinase-encoding oncogenes. Although this virus induces fibrosarcomas in mice, a recombinant murine retrovirus carrying both the raf and myc oncogenes induces immunoblastic lymphomas and immortalizes mouse macrophages in vitro. The present study has thus monitored the expression of c-raf in human hematopoietic cells. The results demonstrate the presence of a 3.6-kb c-raf transcript in HL-60 promyelocytic leukemic cells. The induction of HL-60 cell differentiation along the monocytic or granulocytic lineages had no detectable effect on the level of c-raf transcripts. Furthermore, in contrast to c-myc and c-fms expression, inhibition of protein synthesis with cycloheximide had no detectable effect on c-raf expression. Similar levels of c-rafRNA were also found in other human cell lines derived from myeloid, B cell, and T cell tumors, as well as in normal granulocytes, monocytes, and macrophages. These findings suggest that the c-raf protooncogene is widely expressed in multiple hematopoietic lineages.

Cell Differentiation↗
PubMed1987

Synthesis of PDGF by cultured human T cells transformed with HTLV-I and II.

Human T cells immortalized by human T lymphotropic virus (HTLV)-I and HTLV-II express the genes encoding both chains of platelet-derived growth factor (PDGF). These cells produce biologically active PDGF-like molecules of 31 and 32 kD, identified in the conditioned media of the virus-infected cells by direct immunoprecipitation, under non-reducing conditions, with antisera to PDGF. Upon reduction, the PDGF-like molecules are converted to mitogenically inactive single chains of 14 and 15 kD. The HTLV-transformed cells produce PDGF-like molecules regardless of their ability to produce viral particles. No PDGF-related mRNAs, PDGF-like proteins, nor PDGF-like mitogenic activity were detected in normal human T cells stimulated by phytohemagglutinin or in a T cell line which is not infected by HTLV. It is possible that one of the pathways of immortalization of T cells by HTLV-I or II might be by activation of PDGF-related genes.

Cell Transformation, Viral↗
PubMed1986

Induction of c-sis gene expression and synthesis of platelet-derived growth factor in human myeloid leukemia cells during monocytic differentiation.

Phorbol esters induce the differentiation of human myeloid leukemia cells HL-60 and U-937 along the monocytic-macrophage lineage. This process has been associated with the induction of several cellular protooncogenes, including the c-fos and c-fms genes. We now report that phorbol ester-induced differentiation of the HL-60 and U-937 cells results in the induction of the expression of the c-sis platelet-derived growth factor 2 (PDGF-2) protooncogene. sis mRNA transcripts were not detectable in the uninduced cells but were detectable within 12 hr of phorbol ester induction. Concomitantly, the induced cells were shown to synthesize and secrete biologically active PDGF-like proteins, identified in the conditioned medium of the phorbol ester-treated cells by direct immunoprecipitation with PDGF antiserum. Addition of cycloheximide to phorbol ester-treated HL-60 cells superinduced sis mRNA transcripts. c-sis gene transcripts were also detected in freshly isolated human monocytes but not in human granulocytes or in HL-60 cells induced to differentiate along the granulocytic lineage. Activation of the c-sis/PDGF-2 gene in human hematopoietic cells during monocytic differentiation may serve in the mediation of physiologic functions of the differentiated cells by means of the secretion of potent PDGF-like mitogen.

Cell Cycle↗
PubMed1986

Effects of 1-beta-D-arabinofuranosylcytosine on proto-oncogene expression in human U-937 cells.

We have previously demonstrated that declines in c-myc expression precede the induction of c-fos and c-fms transcripts during monocytic differentiation of human leukemia (HL-60 and U-937) cell lines. The present study has monitored the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on proto-oncogene expression in U-937 cells. The results demonstrate that ara-C inhibits both U-937 proliferation and c-myc expression in a concentration- and time-dependent manner. At non-toxic concentrations of ara-C, these decreases in c-myc RNA occur in the absence of changes in the level of actin transcripts. The results also demonstrate that ara-C increases c-fos but not c-fms expression. Similar findings have been obtained with retinoic acid. Furthermore, although both agents induce a more mature U-937 phenotype, ara-C is a relatively weak inducer of these cells. These findings would suggest that the changes in proto-oncogene expression induced by ara-C may be related to induction of differentiation or the inhibitory effects of this agent on proliferation.

Actins↗
PubMed1985

Human c-myc and N-ras expression during induction of HL-60 cellular differentiation.

The genome of the human HL-60 promyelocytic leukemia cell contains amplified c-myc sequences and the transforming N-ras oncogene. The present study has monitored c-myc and N-ras expression in HL-60 cells during induction of myeloid and monocytic differentiation with dimethyl sulfoxide, hexamethylene bisacetamide, 12-O-tetradecanoylphorbol-13-acetate and 1,25 dihydroxy-vitamin D3. The results demonstrate that induction of HL-60 differentiation is associated with decreases in c-myc RNA, while there is little if any effect on expression of the N-ras gene. Although the diminution in c-myc expression occurred as an early event in the induction of HL-60 differentiation, the rate of decrease in c-myc transcripts varied with respect to cessation of proliferation. Thus, the appearance of the mature phenotype and loss of proliferative capacity are associated with declines in c-myc RNA, while these events appear to occur in the absence of significant alterations in N-ras expression.

Acetamides↗
PubMed1985

Interrelationships of protein and DNA syntheses during replication of mammalian cells.

During the replication of chromatin, the syntheses of the histone protein and DNA components are closely coordinated but not totally linked. The interrelationships of total protein synthesis, histone protein synthesis, DNA synthesis, and mRNA levels have been investigated in Chinese hamster ovary cells subjected to several different types of inhibitors in several different temporal combinations. The results from these studies and results reported elsewhere can be brought together into a consistent framework which combines the idea of autoregulation of histone biosynthesis as originally proposed by W. B. Butler and G. C. Mueller (Biochim. Biophys. Acta 294:481-496, 1973] with the presence of basal histone synthesis and the effects of protein synthesis on DNA synthesis. The proposed framework obviates the difficulties of Butler and Mueller's model and may have wider application in understanding the control of cell growth.

Animals↗
PubMed1985

Effects of 1-beta-D-arabinofuranosylcytosine and phorbol ester on differentiation of human K562 erythroleukemia cells.

We have previously demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces hemoglobin synthesis in human K562 erythroleukemia cells. The present study extends these findings by demonstrating that ara-C treatment of K562 cells results in both increased heme synthesis and accumulation of alpha-, gamma-, epsilon-, and zeta-globin RNA. The results also demonstrate that ara-C enhances K562 cell surface expression of glycophorin. Furthermore, we demonstrate that phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) inhibits the effects of ara-C on heme production, accumulation of globin RNA, and glycophorin expression. The inhibitory effect occurs maximally when K562 cells are treated with TPA before undergoing ara-C-induced commitment to erythroid differentiation. These findings suggest that TPA inhibits an early step in the process required for ara-C to enhance expression of genes involved in the erythroid program.

Cell Differentiation↗
PubMed1984

Acute megakaryoblastic leukemia in childhood.

Routine morphologic and cytochemical study of the leukemic cells of a 13-month-old child did not permit definitive determination of either a lymphoid or a myeloid cell origin. However, ultrastructural cytochemical analysis revealed platelet peroxidase (PPO) reactivity. The malignant cells expressed PPO in both unfixed and fixed preparations. PPO was observed in the perinuclear space and reticulum but not in the Golgi saccules. In a 1% glutaraldehyde, 1% formaldehyde solution known to inhibit PPO but not myeloperoxidase, no reaction product was observed. The demonstration of PPO activity in these undifferentiated cells established their megakaryoblastic lineage. Further studies including DNA flow cytometry confirmed that these cells were megakaryoblasts. This study demonstrates that megakaryoblastic malignancy may occur as an acute leukemia of childhood and emphasizes the value of ultrastructural cytochemistry in cases of acute leukemia which defy routine classification. Abnormalities of chromosome 21 were present in our patient as in four previous cases of megakaryoblastic leukemia in childhood. The nonrandomness of chromosome 21 involvement in this disease should therefore be considered.

Acute Disease↗
PubMed1984

Jaw involvement in American Burkitt's Lymphoma.

A total of 100 patients with American Burkitt's lymphoma (AMBL) (mean age, 15 years; M:F ratio 3:1; 3% black) have been treated at the National Cancer Institute since 1964. Eighteen of these had jaw involvement, 16 at presentation and 2 at relapse (mean age, 16 years; M:F ratio 1.6:1). None of these 18 patients was black. Of the 16 patients presenting initially with jaw tumors, 14 were first evaluated by their dentist; 8 were 16 years of age or older (adults) and 6 were younger than 16 years of age (children). Toothache and perioral numbness were the most frequent findings in adults, whereas toothache, loose teeth, intra-oral and extra-oral swelling were the most common complaints in children. Ten patients were treated with antibiotic therapy and/or dental extractions for presumed tooth infection. The distribution of jaw lesions was: unilateral mandibular (7), unilateral maxillary (4), bilateral mandibular (5), and four quadrants (2). Radiologic evaluation was abnormal in all 17 cases evaluated. Only three patients (all children) had disease limited to the jaw. Four of eight children and 3 of 10 adults are long-term survivors with a median follow-up of seven years (range, 2-15 years). American Burkitt's lymphoma with jaw involvement differs from African Burkitt's lymphoma (AFBL) with jaw involvement in a number of ways: (1) the incidence of jaw tumors in adults is similar to that in children; (2) the incidence of jaw tumors is not greater in males; (3) tumor is considerably more limited in extent with a single quadrant mandibular lesion being the most common presentation; and (4) clinical presentation also differs, with toothache and perioral numbness, uncommon in AFBL, being the most frequent complaints. These marked differences in the frequency and clinical characteristics of jaw tumor of AMBL and AFBL are consistent with other findings indicating that these diseases may differ phenotypically.

Adolescent↗
PubMed1984

Effects of carbamoylation on cell survival and DNA repair in normal human embryo cells (IMR-90) treated with various 1-(2-chloroethyl)-1-nitrosoureas.

The possibility was examined that the carbamoylating activity of some chloroethylnitrosoureas could interfere with the activity of normal human cells to survive treatment with these drugs; 1-(2-chloroethyl)-3-(trans-4-hydroxycyclohexyl)-1-nitrosourea, which has strong carbamoylating activity, inhibited the rejoining of drug or X-ray-induced DNA strand breaks in IMR-90 cells, whereas the noncarbamoylating cis-2-hydroxy isomer had little or no effect; 1-(2-chloroethyl)-3-(trans-4-hydroxycyclohexyl)-1-nitrosourea was twice as potent as the cis-2-hydroxy isomer in reducing colony survival. The moderate or high carbamoylating drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(cyclohexyl)-1-nitrosourea had effects resembling those of 1-(2-chloroethyl)-3-(trans-4-hydroxycyclohexyl)-1-nitrosourea. The low carbamoylating drug 1-(2-chloroethyl)-3-(2,6-dioxo-1-piperidyl)-1-nitrosourea had effects resembling those of the cis-2-hydroxy isomer. 1-(2-chloroethyl)-1-nitrosourea, although a strong carbamoylator in chemical systems, behaved biologically as if it were a low carbamoylator. This can be rationalized on the basis of limited cellular uptake of cyanate ion. The results suggest that carbamoylation may inhibit the nucleotide excision repair of chloroethylnitrosourea-induced DNA damage that may be crucial to the ability of normal human cells to recover from the action of these drugs. Previous work has indicated that susceptible human tumor cells are sensitive to chloroethylnitrosoureas because of a lack of a DNA repair protein (guanine O6-alkyltransferase) that is not involved in nucleotide excision repair. On the basis of these findings and other evidence, further clinical trials of appropriate noncarbamoylating chloroethylnitrosoureas would be justified.

Carmustine↗
PubMed1984

Surgical resection and limited chemotherapy for abdominal undifferentiated lymphomas.

Fourteen patients (less than or equal to 35 years of age) with intra-abdominal undifferentiated lymphomas, without evidence of disease elsewhere, were treated by surgical resection and six cycles of combination chemotherapy which included cyclophosphamide, vincristine, doxorubicin, prednisone, and 42-hour methotrexate infusion with leucovorin rescue. One patient with very extensive retroperitoneal disease prior to surgery had rapid tumor regrowth and subsequently died. One patient has relapsed twice, but is currently alive and has been disease-free for 2 years. All other patients have remained in complete remission for 25-63 months from presentation. The major toxic effects encountered in this protocol were mucositis (which necessitated a reduction in methotrexate duration in two patients) and fever and neutropenia (which complicated chemotherapy in 15 of the total of 79 cycles delivered). There were three documented infections; all were diagnosed before chemotherapy was started, and all resolved with appropriate antibiotic treatment. The 92% actuarial survival rate in this protocol is comparable to results with more prolonged chemotherapy or a combination of prolonged chemotherapy and irradiation. Since prolonged maintenance therapy and irradiation were not utilized in our protocol, they appear to be unnecessary for patients with intra-abdominal undifferentiated lymphoma whose disease can be at least 90% resected.

Abdominal Neoplasms↗
PubMed1983

Central nervous system involvement in American Burkitt's lymphoma.

Sixty-four patients with American Burkitt's lymphoma (AMBL) treated at the National Cancer Institute were reviewed to determine the frequency and characteristics of central nervous system (CNS) involvement. Patients with minimal or completely resected tumor never had CNS disease. Of the 45 patients with more extensive disease, 15 had CNS disease: nine presented with CNS disease, six of whom subsequently had recurrent CNS disease, and six developed CNS disease only at relapse. There was a significant association between CNS and bone-marrow disease at presentation. Therapy of CNS disease consisted of short courses of intrathecal chemotherapy with cytosine arabinoside and methotrexate. Cranial irradiation was given only to patients with CNS relapse. There are six long-term survivors (LTS) who have been disease free for four to six years post chemotherapy. Of these six LTS, three presented with CNS disease, two experienced isolated CNS relapse, and one had CNS disease both at presentation and at relapse. Three of the six LTS never received cranial irradiation. It is concluded that CNS involvement in AMBL can be effectively treated, and that long-term remission, which is probably cure, can be achieved.

Adolescent↗