Biomedical subjects

A Tobler

Publications and source records attributed to A Tobler.

132 records · Page 8Linked to original sources

PubMed1987

Recombinant human tumor necrosis factor alpha regulates c-myc expression in HL-60 cells at the level of transcription.

Recombinant human tumor necrosis factor alpha (TNF alpha) effectively inhibits clonal growth of leukemic cells from patients and several cell lines, including the promyelocytic HL-60 cells. Decreased expression of the c-myc oncogene is linked to growth arrest and terminal cellular differentiation. The present study characterizes the effect of TNF alpha on the regulation of the c-myc gene in HL-60 cells. TNF alpha (100 U/mL) rapidly inhibited messenger RNA (mRNA) accumulation of c-myc with a 50% reduction in less than one hour. Dose-response studies showed that a 50% reduction of c-myc mRNA occurred in the range of 15 U/mL. In vitro nuclear run-on experiments showed that this decrease of c-myc-mRNA accumulation was the result of a reduced rate of transcription of c-myc by TNF alpha. Further studies demonstrated that TNF alpha did not post-transcriptionally alter levels of c-myc mRNA, and the inhibitory action of TNF alpha on c-myc expression in HL-60 cells did not depend on new protein synthesis. In the conditions of all the experiments, TNF alpha did not affect cell viability. By contrast, TNF alpha (500 U/mL) did not decrease mRNA levels of c-myc in an HL-60 variant cell line whose growth was not inhibited by TNF alpha; also TNF alpha (500 U/mL) increased c-myc-mRNA levels in normal fibroblasts whose growth is known to be stimulated by TNF alpha. These findings, in concert with prior studies, show a close association between growth inhibition of HL-60 cells and decreased levels of mRNA coding for c-myc.

Cell Line↗

PubMed1986

Retinoids. Structure-function relationship in normal and leukemic hematopoiesis in vitro.

Retinoids were studied both to identify what skeletal components are important in the modulation of normal and leukemic human myeloid clonal proliferation and differentiation in vitro and to elucidate the mechanism by which retinoids modulate proliferation of hematopoietic cells. Retinoids with a derivatized terminal carboxyl group were significantly less active than all-trans-retinoic acid, and those with the addition of two methyl groups to the cyclohexenyl ring of retinoic acid or substitution of its beta-cyclogeranylidene group with a 1,1,3,3-5-indanyl ring system were markedly more active than all-trans-retinoic acid. Five of the retinoids strongly inhibited clonal growth of the HL-60 and KG-1 human leukemic cell lines (50% inhibition in the range of 3 X 10(-10)-1 X 10(-8) M) and markedly stimulated normal human myeloid colony formation (granulocyte-macrophage colony-forming cells [GM-CFC] 150% stimulation in the range of 3 X 10(-9)-3 X 10(-8) M). Further studies suggested that: Common structural requirements of the retinoids were important in the modulation of both normal and leukemic hematopoiesis. The retinoids were able to inhibit leukemic proliferation without induction of differentiation of the neoplastic cells. Studies on normal human GM-CFC suggested that the retinoids did not act by themselves as a colony-stimulating factor (CSF), or by stimulating accessory cells to produce CSF, but either required earlier progenitor cells to become GM-CFC or enhanced the sensitivity of GM-CFC to the action of CSF.

Bone Marrow Cells↗

PubMed1984

Undifferentiated thyroid tumors of diffuse small cell type. Histological and immunohistochemical evidence for their lymphomatous nature.

A histological review of 72 undifferentiated thyroid tumors was performed in order to discover small cell anaplastic carcinomas and Non-Hodgkin lymphomas. Cases suspected to be lymphoma were examined for the presence of Ig and keratin and lectins with a PAP-procedure. Among the 72 cases, 68 (94,5%) were anaplastic carcinomas of various types. Four cases (5,5%) were diffuse small cell tumors, which had previously been regarded as anaplastic carcinomas. All four could be identified as Non-Hodgkin lymphomas by histology, immunohistochemistry, repeat biopsy or autopsy. The findings suggest that the majority of small cell anaplastic thyroid tumors are lymphomas and that true anaplastic small cell carcinoma of the thyroid must be extremely rare. Its diagnosis requires electronmicroscopy and/or immunohistochemistry to demonstrate the epithelial nature of tumor cells.

Adenocarcinoma↗

PubMed1981

[Stenosing ganglioneuromatosis of the small intestine with ileus and ileal rupture].

Report on a 64-year-old man who presented with ileus and rupture of the ileum due to diffuse ganglioneuromatosis of the small bowel. The patient had a 16-year history of recurrent ileus. In addition, there were clinical and radiographic signs of an inflammatory bowel affection which were interpreted as Crohn's disease, a diagnosis which could not be proven by pathologic examination of the resection specimen. The features of intestinal ganglioneuromatosis and its possible relation to the accompanying inflammation are discussed in the light of the pertinent literature.

Crohn Disease↗

PubMedDate not supplied

Single institution experience with mobilization, harvesting, and reinfusion of peripheral blood stem cells in children with a solid tumor or leukemia.

The aim of our single center pilot study was to evaluate the feasibility of peripheral blood stem cell autotransplantation (PBSCT) in a pediatric population. Only children with solid and hematological malignancies and poor prognosis who were without a HLA-identical bone marrow donor were included in this study. Mobilization of PBSC was done by treatment with myelosuppressive chemotherapy followed by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Circulating progenitor cells were harvested by a total of 24 leukaphereses on an AS 104 cell separator in eight patients. Seven patients had undergone conditioning with high-dose chemotherapy with or without irradiation prior to PBSCT. All patients showed a rapid hematological recovery, although reconstitution of thrombopoiesis was incomplete in three children. We conclude that PBSCT is feasible in childhood and that it results in a rapid hematologic recovery.

Adolescent↗

PubMedDate not supplied

Different p16INK4a and p14ARF expression patterns in acute myeloid leukaemia and normal blood leukocytes.

The p16INK4a gene is often disrupted or transcriptionally silenced by CpG island methylation in human cancers. However, in acute myeloid leukaemia (AML) alterations of the INK4a-ARF tumour suppressor locus are rarely found despite the noted variable p16INK4a mRNA and protein levels. The p14ARF, an alternative reading frame protein encoded from the same INK4a-ARF locus, is a potent tumour suppressor functionally linked to p53. There is little known regarding the role of p14ARF in primary human tumours. Therefore, we analysed the expression patterns of these two tumour suppressors in 37 cases of AML. The relative expression of p16INK4a and p14ARF mRNA in AML blasts, measured by a specific p16INK4a/p14ARF multiplex RT-PCR, was significantly shifted towards p14ARF whereas relatively lower levels of p16INK4a were detected. Quantitative RT-PCR revealed significantly higher expression of both transcripts in AML blasts when compared to normal differentiated myeloid cells or CD34+ progenitor cells. Furthermore, a good correlation between p16INK4a protein and mRNA was observed, whereas no correlation was found with p14ARF. Our results suggest: a) increased levels of both p16INK4a and p14ARF may participate in the pathogenesis of AML, b) that high p14ARF mRNA expression might influence p16INK4a transcription and c) that post-transcriptional regulatory mechanisms are important for p14ARF expression.

Acute Disease↗