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| Third-line gemcitabine monotherapy for platinum-resistant advanced urothelial cancer.
March 25, 2010 at 8:54 AM
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| | Third-line gemcitabine monotherapy for platinum-resistant advanced urothelial cancer. Int J Clin Oncol. 2010 Mar 24; Authors: Soga N, Kise H, Arima K, Sugimura Y OBJECTIVE: To evaluate the efficacy and toxicity of third-line gemcitabine monotherapy (Gem) in patients with platinum-resistant advanced urothelial cancer (UC). PATIENTS AND METHODS: From July 2005 to March 2009, 13 patients were enrolled. All patients had previously received methotrexate, vinblastine, doxorubicin, and cisplatin as first-line therapy. Second-line therapy consisted of paclitaxel/carboplatin (Pca) therapy: paclitaxel (175 mg/m(2)) followed by carboplatin (area under the curve = 5) was intravenously infused on day 1 of each 21-day cycle. Following Pca failure, Gem was given as third-line treatment: gemcitabine (1,000 mg/m(2)) was intravenously administered on days 1, 8, and 15 of each 28-day cycle. All patients were eligible for toxicity assessment. Survival curves were produced using the Kaplan-Meier method. RESULTS: An average of 3.2 Gem cycles (range, 1-8 cycles) were given. Following Gem treatment, overall response rates were 0% CR, 7.7% PR (n =! 1), 53.8% SD (n = 7), and 38.5% PD (n = 5). Grade 3-4 toxicities included anemia (31%), neutropenia (31%), and thrombocytopenia (31%). One case experienced grade 3-4 hepatic dysfunction during treatment with Gem. Low-grade alopecia was observed in all 13 patients (100%). Median time to progression and overall survival was 2 and 7.3 months, respectively, following Gem. The 1- and 2-year overall survival rate was 30.8% and 15.3%, respectively, for Gem. CONCLUSION: Gem as third-line therapy was performed safely with good tolerability in platinum-resistant advanced UC, even though the efficacy was very limited. PMID: 20333430 [PubMed - as supplied by publisher] | | |
| Prominin-2 is a novel marker of distal tubules and collecting ducts of the human and murine kidney.
March 25, 2010 at 8:54 AM
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| | Prominin-2 is a novel marker of distal tubules and collecting ducts of the human and murine kidney. Histochem Cell Biol. 2010 Mar 24; Authors: Jászai J, Farkas LM, Fargeas CA, Janich P, Haase M, Huttner WB, Corbeil D Prominin-1 (CD133) and its paralogue, prominin-2, are pentaspan membrane glycoproteins that are strongly expressed in the kidney where they have been originally cloned from. Previously, we have described the localization of prominin-1 in proximal tubules of the nephron. The spatial distribution of prominin-2, however, has not yet been documented in the kidney. We therefore examined the expression of this molecule along distinct tubular segments of the human and murine nephron using in situ hybridization and immunohistochemistry. Our findings indicated that human prominin-2 transcripts and protein were confined to distal tubules of the nephron including the thick ascending limb of Henle's loop and the distal convoluted tubule, the connecting duct and to the collecting duct system. Therein, this glycoprotein was enriched at the basolateral plasma membrane of the tubular epithelial cells with exception of the thick ascending limb where it was also found in the apical! domain. This is in contrast with the exclusive apical localization of prominin-1 in epithelial cells of proximal nephron tubules. The distribution of murine prominin-2 transcripts was reminiscent of its human orthologue. In addition, a marked enrichment in the epithelium covering the papilla and in the urothelium of the renal pelvis was noted in mice. Finally, our biochemical analysis revealed that prominin-2 was released into the clinically healthy human urine as a constituent of small membrane vesicles. Collectively our data show the distribution and subcellular localization of prominin-2 within the kidney in situ and its release into the urine. Urinary detection of this protein might offer novel diagnostic approaches for studying renal diseases affecting distal segments of the nephron. PMID: 20333396 [PubMed - as supplied by publisher] | | |
| Tissue engineering and regenerative medicine research perspectives for pediatric surgery.
March 25, 2010 at 8:54 AM
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| | Tissue engineering and regenerative medicine research perspectives for pediatric surgery. Pediatr Surg Int. 2010 Mar 24; Authors: Saxena AK Tissue engineering and regenerative medicine research is being aggressively pursued in attempts to develop biological substitutes to replace lost tissue or organs. Remarkable degrees of success have been achieved in the generation of a variety of tissues and organs as a result of concerted contributions by multidisciplinary groups in the field of biotechnology. Engineering of an organ is a complex process which is initiated by appropriate sourcing of cells and their controlled proliferation to achieve critical numbers for seeding on biodegradable scaffolds in order to create cell-scaffold constructs, which are thereafter maintained in bioreactors to generate tissues identical to those required for replacement. Extensive efforts in understanding the characteristics of cells and their interaction with specifically tailored scaffolds holds the key to their attachment, controlled proliferation and differentiation, intercommunication, and organization to form tissues. ! The demand for tissue-engineered organs is enormous and this technology holds the promise to supply customized organs to overcome the severe shortages that are currently faced by the pediatric patient, especially due to organ-size mismatch. The contemporary state of tissue-engineering technology presented in this review summarizes the advances in the various areas of regenerative medicine and addresses issues that are associated with its future implementation in the pediatric surgical patient. PMID: 20333389 [PubMed - as supplied by publisher] | | |
| Characterization of Human Chondrocytes Exposed to Simulated Microgravity.
March 25, 2010 at 8:54 AM
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| | Characterization of Human Chondrocytes Exposed to Simulated Microgravity. Cell Physiol Biochem. 2010;25(4-5):551-560 Authors: Ulbrich C, Westphal K, Pietsch J, Winkler HD, Leder A, Bauer J, Kossmehl P, Grosse J, Schoenberger J, Infanger M, Egli M, Grimm D Background: Tissue engineering is a strategy of cartilage regeneration, but scaffolds, required for 3D growth of chondrocytes, are still a problem. Methods: Searching for possibilities to improve scaffold-free engineering of cartilage, we characterized human chondrocytes incubated on a random positioning machine (RPM) to simulate microgravity (mug). Results: When cultured in simulated mug, human chondrocytes start forming 3D cell assemblies within 5 days. After 24h, we could not detect caspase-3, Fas, p53 or Bcl-2 proteins in these cells, Annexin V flow cytometry, however, revealed 18% of apoptotic chondrocytes in 1g cultures but only 10% on the RPM. Both rates of apoptosis were not changed, when vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) was added. 24 h, simulated microgravity also had significantly decreased collagen type I and X, but did not change collagen type IV and laminin, while collagen type II, chondroitin sulfate ! and aggrecan were elevated as compared with 1g controls. The production of collagen type II/X, chondroitin sulfate and aggrecan was modified, when external bFGF or VEGF had been applied. Conclusion: Chondrocytes exposed to simulated mug seem to change their extracellular matrix production behavior, while they rearrange their cytoskeletal proteins prior to forming 3D aggregates. PMID: 20332636 [PubMed - as supplied by publisher] | | |
| Deer Antlers - A Model of Mammalian Appendage Regeneration: An Extensive Review.
March 25, 2010 at 8:54 AM
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| | Deer Antlers - A Model of Mammalian Appendage Regeneration: An Extensive Review. Gerontology. 2010 Mar 23; Authors: Kierdorf U, Kierdorf H Background: Compared with other vertebrate taxa, mammals possess a very limited capacity for appendage regeneration. The antlers of deer are an exception in that they are periodically lost and fully regenerated throughout the life of an individual. Objective: In this paper we compare certain aspects of antler regeneration with regenerative processes in other vertebrates. Methods: Review of the literature. Results: Recent studies suggest that antler regeneration is a stem cell-based process and that these stem cells are located in the pedicle periosteum. There is evidence that signaling pathways known to operate during appendage regeneration in other vertebrates are also activated during antler regeneration. There are, however, also differences between antlers and other systems of epimorphic regeneration. Thus, contrary to amphibian limb regeneration, signaling from the wound epidermis appears not to be of crucial importance for antler regeneration. Healing of the ! casting wound typically involves no or only minor scarring, making antlers interesting subjects for researchers attempting to reduce scar formation during wound healing in humans. The fact that despite their enormous growth rate the antlers of intact and castrated deer appear to be resistant to malignant transformation furthermore offers research opportunities for cancer biology. Conclusions: Studying antler renewal as an example of mammalian appendage regeneration may provide crucial information for regenerative medicine to achieve its ultimate goal of stimulating limb regeneration in humans. A deeper understanding of the developmental mechanisms involved in antler renewal can also be useful for controlling induced regeneration processes in mammals. PMID: 20332600 [PubMed - as supplied by publisher] | | |
| Expression and role of phosphodiesterase 5 in human malignant melanoma cell line.
March 25, 2010 at 8:54 AM
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| | Expression and role of phosphodiesterase 5 in human malignant melanoma cell line. Anticancer Res. 2010 Feb;30(2):355-8 Authors: Murata T, Shimizu K, Watanabe Y, Morita H, Sekida M, Tagawa T BACKGROUND: Eleven phosphodiesterase (PDE) gene families (PDE1-11) have been identified, and some PDE isoforms are selectively expressed in various cell types. Previously, we reported PDE1, PDE3 and PDE4 expressions in human malignant melanoma cells. However, the expression and role of PDE5 in malignant melanoma cells is not clear. Therefore, we characterized PDE5 in human malignant melanoma MAA cells. MATERIALS AND METHODS: PDE5 activity and PDE5A mRNA expression were investigated in MAA cells. The full open reading frames for human PDE5A1 were sequenced. Effects of PDE5 inhibitors on cell growth were determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays. RESULTS: PDE5 activity and PDE5A1 mRNA expression were detected in MAA cells. The nucleotide sequence of PDE5A1 was identical to that of human PDE5A1, previously published. Two PDE5 inhibitors inhibited the growth of cells. CONCLUSION: PDE! 5A1 mRNA is expressed and may play an important role in the growth of human malignant melanoma MAA cells. PMID: 20332439 [PubMed - in process] | | |
| Ultrasound standing wave fields induce endothelial cell sprouting within three-dimensional engineered tissue.
March 25, 2010 at 8:54 AM
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| | Ultrasound standing wave fields induce endothelial cell sprouting within three-dimensional engineered tissue. J Acoust Soc Am. 2010 Mar;127(3):1940 Authors: Garvin KA, Hocking DC, Dalecki D The field of tissue engineering is working to develop fully functional replacement tissues and organs. To achieve this goal, methodologies aimed at controlling the growth of new vascular systems in three-dimensional (3-D) engineered tissues are needed. We hypothesized that organizing endothelial cells into multicellular, planar bands of cells within 3-D collagen gels using the radiation forces developed in an ultrasound standing wave field (USWF) would promote an angiogenic endothelial cell phenotype. Human umbilical vein endothelial cells were suspended in an unpolymerized type-I collagen solution and were exposed to continuous wave USWFs. The collagen solution was allowed to polymerize during the 15 min USWF treatment to maintain the USWF-induced banded pattern of cells within a 3-D collagen gel. Following a 24 h incubation period, endothelial cell sprouts were observed emerging from USWF-induced endothelial cell bands. The average length of these sprouts was ap! proximately 100 mum. Sprouting was absent in sham samples where a rounded cell morphology was observed. The influence of acoustic exposure parameters on endothelial cell sprouting was investigated. These studies indicate that USWF technologies promote formation of capillary precursors in 3-D engineered tissue and thus, this technology has the potential to advance the field of tissue engineering. PMID: 20330811 [PubMed - in process] | | |
| The future of CACs in wound healing.
March 25, 2010 at 8:54 AM
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| | The future of CACs in wound healing. Arch Surg. 2010 Mar;145(3):266 Authors: Maggi J, Brem H PMID: 20329349 [PubMed - in process] | | |
| Seventh Annual International Umbilical Cord Blood Transplantation Symposium, Los Angeles, California, June 5-6, 2009.
March 25, 2010 at 8:54 AM
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| | Seventh Annual International Umbilical Cord Blood Transplantation Symposium, Los Angeles, California, June 5-6, 2009. Biol Blood Marrow Transplant. 2010 Jan;16(1):12-27 Authors: Wagner JE, Laughlin M, Petz L PMID: 19748592 [PubMed - indexed for MEDLINE] | | | | 
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