Differentiation of HL-60 myeloid leukemia cells induced by all-trans retinoic acid is enhanced in combination with caffeic acid

We investigated a possible enhancement of all-trans retinoic acid (ATRA)-induced differentiation of HL-60 human myeloid leukemia cells by caffeic acid (CA), a widely distributed plant phenolic compound. Our results showed that CA, in the concentration of 13 or 52 micro M, had no or minimal influence on cell differentiation, whereas the differentiating activity of ATRA was potentiated by CA treatment. We proved, using flow cytometric detection of the CD66b surface molecule, a synergistic effect of CA: at day 10, 18.3% of CD66b-positive cells were detected after treatment with ATRA only, and 33% when CA and ATRA were combined together. NBT-assay confirmed that this additive effect of CA on ATRA-induced differentiation. Proliferating activity as assessed by MTT-assay was generally not affected by CA at given concentrations. However, cell proliferation was significantly reduced by 52 micro M CA at 96-h intervals. This effect was markedly enhanced when CA, at both concentrations, and ATRA were combined. The possibility to enhance the differentiation potential of ATRA by CA may improve outcomes in the therapy of acute promyelocytic leukemia.     

The effects of paclitaxel on the three phases of restenosis: smooth muscle cell proliferation, migration, and matrix formation: an in vitro study

PURPOSE: We sought to evaluate the growth-modulating potential of paclitaxel on cultured human arterial smooth muscle cells depending on the administered dose. MATERIAL AND METHODS: For all experiments human arterial smooth muscle cells (SMCs) were used. SMCs were either cultured for 5 days or for 20 days with paclitaxel (doses: 10(-7) M, 10(-8) M, 10(-9) M). For a total period of 20 days, proliferation kinetics of the SMC were analyzed. To assess the clonogenic activity of the SMC colony-forming assays were performed. Drug- and dose-dependent cell cycle changes were analyzed by flow cytometry. The effect on cell migration was examined in a 2-chamber migration system. The effects of paclitaxel on the synthesis of tenascin were examined via immunofluorescence. RESULTS: Depending on the dose administered, paclitaxel proved to inhibit SMC proliferation effectively when administered during the total period of 20 days. When incubated for 5 days with doses of paclitaxel ranging between 10(-8) M and 10(-9) M, SMCs showed clear signs of regeneration. When being incubated with 10(-7) M of paclitaxel, however, SMCs reacted with a reduction in cell proliferation, a reduced clonogenic activity, and a drug-induced G2/M phase block. SMC migration was inhibited effectively as well as extracellular matrix formation. CONCLUSION: Paclitaxel is a potent inhibitor of SMC proliferation, SMC migration, and extracellular matrix formation in vitro, with all three phases of the restenosis process inhibited effectively.     

Intramedullary abscess of the spinal cord in children: a case report and review of the literature

A case report of an intramedullary spinal cord abscess in a 13-month-old boy and a review of relevant existing pediatric literature is presented. Thirty-eight cases of pediatric intramedullary spinal cord abscess are analyzed for presenting signs and symptoms, microbiology of isolated organisms, surgical intervention, antibiotic administration and outcome. The most significant variable on outcome is timely surgical intervention, followed by appropriate antibiotic administration.     

Transplacental and other routes of cancer transmission between individuals

Cancer in pregnancy is not rare, and the possibility of transmission of malignancy from mother to child, while infrequent, represents a clinical challenge for the primary pediatric hematologist-oncologist. The authors summarize all reported cases of vertically transmitted cancer and review other reported cases of person-to-person transfer of malignancy. As these cases represent a unique physiologic model of tumor transplantation, the biology of cancer transmission is discussed and provisional guidelines are given for the screening of infants born to women with cancer.     

The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes

Background

Extracellular nucleotides play an important role in the regulation of vascular tone and may be involved in cerebral vasospasm after subarachnoidal haemorrhage. This study was designed to characterise the contractile P2 receptors in endothelium-denuded human cerebral and omental arteries. The isometric tension of isolated vessel segments was recorded in vitro. P2 receptor mRNA expression was examined by RT-PCR.

Results

In human cerebral arteries, the selective P2Y₆ receptor agonist, UDPβS was the most potent of all the agonists tested (pEC₅₀ = 6.8 ± 0.7). The agonist potency; UDPβS > αβ-MeATP > UTPγS > ATPγS > ADPβS = 0, indicated the presence of contractile P2X₁ P2Y₂, P2Y₄ and P2Y₆, but not P2Y₁ receptors, in human cerebral arteries. In human omental arteries, UDPβS was inactive. The agonist potency; αβ-MeATP > ATPγS = UTPγS > ADPβS = UDPβS = 0, indicated the presence of contractile P2X₁, and P2Y₂ receptors, but not P2Y₁ or P2Y₆ receptors, in human omental arteries. RT-PCR analysis of endothelium-denuded human cerebral and omental arteries demonstrated P2X₁, P2Y₁, P2Y₂ and P2Y₆ receptor mRNA expression. There were no bands for the P2Y₄ receptor mRNA in the omental arteries, while barely detectable in the cerebral arteries.

Conclusions

P2Y₆ receptors play a prominent role in mediating contraction of human cerebral arteries. Conversely, no such effect can be observed in human omental arteries and previous results confirm the absence of P2Y₆ receptors in human coronary arteries. The P2Y₆ receptor might be a suitable target for the treatment of cerebral vasospasm.     

Prominent Tc-99m MIBI skeletal uptake in renal osteodystrophy: a possible role for whole-body scanning

Renal osteodystrophy is a process whereby renal failure causes profound bone disease. Effects on bone include osteosclerosis, osteomalacia, osteoporosis, pathologic fractures, aseptic necrosis of the hips, and bone pain. The authors present a case of renal osteodystrophy with intense Tc-99m 2-methoxy isobutyl isonitrile (MIBI) radiotracer uptake in the mandible and propose that Tc-99m MIBI may have a potential role in diagnosing renal osteodystrophy.     

Potential antitumor effects of statins (Review)

Statins, which have been introduced to the clinic for the treatment of hypercholesterolemia, are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA to mevalonic acid (MA). MA is the precursor in the biosynthesis of isoprenoid compounds including cholesterol, dolichol and ubiquinone. Furthermore, mevalonate-derived prenyl groups enable precise cellular localization and function of many proteins such as Ras and Rho proteins. Therefore, besides lowering cholesterol level, statins exert pleiotropic effects on many essential cellular functions including cell proliferation, differentiation, and survival but also participate in the regulation of cell shape and motility. Statins have been shown to inhibit proliferation and to induce apoptosis in a variety of tumor cells. They have also been found to display antitumor effects against melanoma, mammary carcinoma, pancreatic adenocarcinoma, fibrosarcoma, glioma, neuroblastoma, and lymphoma in animal tumor models resulting in retardation of tumor growth, and/or inhibition of the metastatic process. In preclinical studies statins have also been demonstrated to potentiate the antitumor effects of some cytokines and chemotherapeutics. The molecular mechanisms underlying antitumor activity of statins have not been fully elucidated but interference with the function of Ras and Rho family GTPases, inhibition of the activity of certain cyclin-dependent kinases (CDK), and activation of CDK inhibitors, all seem to participate in this activity. The results of several clinical studies of statins in cancer patients including phase I, phase I/II, and phase II trials have been published. Although evaluation of the therapeutic efficacy is not the purpose of early clinical trials and all conclusions might be premature at this stage, some preliminary conclusions have already been drawn. The results of these studies do not show any significant therapeutic effects of statins in cancer patients. However, the results of one of these studies suggest that statins could effectively strengthen the therapeutic activity of some chemotherapeutics. This observation seems to agree with the results of preclinical studies. However, as toxic side effects of statins have been particularly evident in their combination with some other drugs great caution should be advised while planning clinical trials based on combination therapy including statins in cancer patients.     

Pentoxifylline inhibits leukocyte infiltration and splenocyte cytotoxicity against murine colon adenocarcinoma

Pentoxifylline (PTX), a methylxanthine derivative, is commonly used in patients suffering from peripheral vascular diseases. Besides its well-known hemorheological properties PTX has been found to decrease the secretion of some inflammatory cytokines such as TNF, IL-12 and IFN-gamma. PTX also suppresses lymphocyte cytotoxicity, affecting mainly the perforin-dependent pathway. We investigated the influence of PTX on the splenocyte cytotoxicity and leukocyte infiltration in a murine colon adenocarcinoma model. We observed that PTX decreased the cytotoxic activity of isolated splenocytes against C-26 cells and reduced the inflammatory cell infiltration in the peritumoral tissue. Thus, our results strongly suggest the necessity of further studies concerning the safety of PTX use, especially in elderly patients or patients with already diagnosed cancer.