1,720,965 research outputs found
The effect of rhGM-CSF on the proliferation of osteogenic sarcoma cells
No full textRecombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) promotes the growth of a variety of hematopoietic and nonhematopoietic cells, both benign and malignant. There is now evidence that osteoblast-like cells produce GM-CSF and their growth is stimulated by this cytokine in vitro. We have studied the effect of rhGM-CSF on DNA synthesis and cell proliferation in the human osteogenic sarcoma cell lines U-20S, G-292, MG-63, and HOS. RhGM-CSF stimulated a dose-dependent increase in radioactive thymidine incorporation in each of the four cell lines in the presence of serum-free media, and in two cell lines (HOS and U-20S) in the presence of fetal bovine serum (FBS). In addition, rhGM-CSF produced significant increases in cell proliferation in two cell lines (MG-63 and U-20S) in the presence of 2% FBS. These results suggest that GM-CSF may have an important role in the biology of human osteogenic sarcoma cells. The clinical implications of these findings merit further investigation
Suramin, a novel antitumor compound
No full textSuramin, a polyanionic compound originally synthesized for use as an antiparasitic agent, has recently entered clinical trials for the treatment of a variety of human cancers refractory to conventional modalities of therapy. This is based on suramin's ability to bind and to inactivate growth factor and enzyme systems critical to cellular homeostasis and proliferation. In addition, this compound possesses adrenocorticolytic properties in vivo and exerts significant cytostatic and cytocidal effects against a variety of human tumor cell lines in vitro. Pilot studies using suramin have thus far been conducted in adrenocortical carcinoma, prostate cancer refractory to conventional hormonal manipulation and nodular lymphomas
Pattern of growth factor, proto-oncogene and carcinoembryonic antigen gene expression in human colorectal carcinoma cell line
No full textThe aim of the present study was to examine whether the expression of growth factor genes, proto-oncogenes and carcinoembryonic antigen (CEA) gene in human colorectal cancer cell lines was related to their clinicobiological behavior. A significant variability among cell lines was detected for both insulin-like growth factor II and transforming growth factor beta gene message. Detectable levels of c-myc, Her-2, c-myb, K-ras and EGF receptor mRNA were found in most cell lines, whereas only 1/11 and 2/11 cell lines were positive for N-myc and c-sis message, respectively. N-myc expression was limited to a cell line originated from a tumor with neuroendocrine features, while high levels of K-ras message were found only in a cell line derived from a radioresistant tumor. CEA mRNA levels correlated well with the concentration of antigen in each cell line. On the basis of these results, our findings demonstrated that human colorectal cancer cell lines show heterogeneous expression of growth factor and CEA genes and proto-oncogenes; however, with the exception of K-ras, N-myc and CEA, other correlations between gene expression and the clinicobiological characteristics of these cell lines could not be demonstrated
Effect of suramin on human prostate cancer cells in vitro
No full textSuramin, a polyanionic compound with known antiparasitic activity, has been shown to be adrenocorticolytic in primates and to have clinical efficacy in the treatment of patients with metastatic prostate cancer refractory to conventional hormonal manipulation. To better characterize the activity of suramin on prostate cancer biology, we studied the effect of the drug on plasma adrenal androgens of patients and on the human prostate adenocarcinoma cell lines PC-3, DU 145 and LNCaP-FGC. Five cancer patients treated with suramin had an approximate 40% decline in circulating androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. The drug inhibited the colony formation in two of the three cell lines at concentrations clinically achievable in humans without excessive drug-related toxicity. The presence of suramin 300 micrograms./ml. partially inhibited the growth stimulatory effect of testosterone and basic fibroblast growth factor, but not that of epidermal growth factor. The cellular concentration of suramin following exposure to a single dose increases linearly over time in each of the cell lines with LNCaP-FGC accumulating the highest levels of the drug; cellular levels of suramin, not androgen or growth factor sensitivity, correlated with the sensitivity to the drug. The concentrations of prostatic acid phosphatase and prostatic specific antigen released by LNCaP-FGC cells in cell culture medium declined in the presence of increasing levels of suramin in a manner which exceeded the decrease in cell number. We conclude that suramin, aside from decreasing circulating androgens through its adrenocorticolytic effect, is also capable exerting a direct inhibitory effect on cell proliferation of prostate cancer cells, and interfere at a cellular level with the growth stimulatory effects of exogenous testosterone and basic fibroblast growth factor
Suramin in adrenal cancer: modulation of steroid hormone production, cytotoxicity in vitro, and clinical antitumor effect
No full textSuramin, a drug known to have antiparasitic effects, has been previously shown to have adrenocorticolytic activity in primates. We now confirm preferential accumulation of this compound in the normal adrenal gland, evaluate its in vitro effect against two human adrenocortical carcinoma cell lines (SW-13 and NCI-H295), and report the clinical activity of suramin in 17 patients with metastatic adrenocortical carcinoma. Inhibition of colony formation occurred in both adrenal cell lines in vitro at concentrations that are clinically achievable in humans. In addition, suramin concentrations as low as 100 μg/mL were able to inhibit glucocorticoid, mineralocorticoid, and androgen production by the NCI-H295 cell line. Of 16 patients with adrenocortical carcinoma now evaluable for tumor response, 2 achieved a partial response, 2 had a minor response, and 5 remained with stable disease for periods ranging from 3-10 months; the remainder progressed. One of 7 patients with excessive steroid hormone production achieved a partial normalization of her steroid levels for the duration of suramin therapy in the setting of radiographic disease stabilization. An additional patient treated off-study for lack of radiographically measurable disease, achieved complete normalization of plasma aldosterone levels. We conclude that suramin preferentially accumulates in adrenal cells, induces cytotoxicity and significant down-regulation of steroid hormone production in vitro, and has some therapeutic efficacy as a single agent in patients with metastatic adrenocortical carcinoma
A pilot study of suramin in the treatment of metastatic renal cell carcinoma
No full textSuramin sodium is an aromatic polysulfonated compound that was originally introduced as an antiparasitic agent in the 1920s. Recently, in view of its ability to bind and disrupt the function of multiple growth factors and cellular enzyme systems, the authors have been evaluating the role of suramin as an antitumor agent. In this study, 12 patients with metastatic renal cell carcinoma received parenteral suramin by continuous infusion to a peak plasma suramin level greater than 200 micrograms/ml. No objective radiographic responses were observed, although greater than 90% necrosis of multiple tumor sites was documented at autopsy in one patient and normalization of tumor-related hypercalcemia occurred in another patient. Two patients had stable disease of 10 and 28 weeks' duration, respectively. Significant toxicities included hypotension related to sepsis and resulting in renal insufficiency (one patient), development of liver function abnormalities (one patient) marked thrombocytopenia (one patient), prothrombin time prolongation (all patients), vortex keratopathy (two patients), and Grade 1 sensory neuropathy (two patients). On the basis of the current results, suramin does not appear to be an active single agent against metastatic renal cell carcinoma when administered by this dosing schedule
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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