Using quantitative anatomical techniques, we show that after intraorbital optic nerve transection in adult rats, virtually all retinal ganglion cells (RGCs) survive for 5 d and then die abruptly in large numbers, reducing the RGC population to approximately 50% of normal by day 7 and to less than 10% on day 14. During this period of rapid cell loss, some RGCs show cytochemical alterations indicative of apoptosis ("programmed cell death"), a change not previously categorized after axotomy in adult mammals. With intracranial lesions 8-9 mm from the eye, the onset of cell death is delayed until day 8 and is greater with cut than crush. The demonstration that axotomy results in apoptosis, the long interval between axonal injury and RGC death, and the different time of onset of the massive RGC loss with optic nerve lesions near or far from the eye suggest that axonal interruption triggers a cascade of molecular events whose outcome may be critically dependent on the availability of neuronal trophic support from endogenous or exogenous sources. The role of such molecules in RGC survival and the reversible nature of these injury-induced changes is underscored by the temporary rescue of most RGCs by a single intravitreal injection of brain-derived neurotrophic factor during the first 5 d after intraorbital optic nerve injury (Mansour-Robaey et al., 1994). The delayed pattern of RGC loss observed in the present experiments likely explains such a critical period for effective neurotrophin administration.
Aberrant regulation of the Wnt/β-catenin pathway plays important roles in colorectal carcinogenesis, with over 90% of cases of sporadic colon cancer featuring β-catenin accumulation. While ubiquitination-mediated degradation is widely accepted as a major route for β-catenin protein turnover, little is known about the regulation of β-catenin in transcriptional level. Here we show that Elf3, a member of the E-twenty-six family of transcription factors, drives β-catenin transactivation and associates with poor survival of colorectal cancer (CRC) patients. We first found recurrent amplification and upregulation of Elf3 in CRC tissues, and further Gene Set Enrichment Analysis identified significant association between Elf3 expression and activity of WNT/β-catenin pathway. Chromatin immunoprecipitation and electrophoretic mobility shift assay consistently revealed that Elf3 binds to and transactivates β-catenin promoter. Ectopic expression of Elf3 induces accumulation of β-catenin in both nucleus and cytoplasm, causing subsequent upregulation of several effector genes including c-Myc, VEGF, CCND1, MMP-7 and c-Jun. Suppressing Elf3 in CRC cells attenuates β-catenin signaling and decreases cell proliferation, migration and survival. Targeting Elf3 in xenograft tumors suppressed tumor progression in vivo. Taken together, our data identify Elf3 as a pivotal driver for β-catenin signaling in CRC, and highlight potential prognostic and therapeutic significance of Elf3 in CRC.
Robotic thyroidectomy appears to be a feasible and safe surgical procedure for patients with differentiated thyroid cancer. However, more high-quality randomised clinical trials should be undertaken to confirm these findings.
Arsenic trioxide (ATO) and proteasome inhibitor bortezomib have been successfully applied to treat acute promyelocytic leukemia (APL) and multiple myeloma (MM), respectively. Their synergistic effects with other anticancer drugs have been widely studied. Here, we investigated the potential synergy of bortezomib and ATO on Bcr-Abl þ leukemic K562 cells. The results showed that cotreatment of bortezomib at 32 nM, a half concentration for growth arrest, and ATO at 1 lM, a dose with no significant cytotoxic effect, synergistically induced apoptosis in the cell line, followed by enhanced mitochondrial dysfunction, release of cytochrome c and apoptosis-inducing factor, caspase-3 cleavage and degradation of poly-adenosine diphosphate-ribose polymerase together with the decreased Bcr-Abl protein. These two drugs synergistically induced proteolytic activation of protein kinase Cd (PKCd) with enhanced activation of two mitogen-activated protein kinases phospho-c-Jun NH 2 -terminal kinase and p38. The specific PKCd inhibitor rottlerin markedly decreased bortezomib plus ATO-induced apoptosis, suggesting that PKCd plays an important role in bortezomib plus ATO-induced apoptosis. Moreover, apoptosis synergy of bortezomib and ATO could also be seen in some kinds of acute leukemic cell lines and primary cells. Totally, our results indicate that combined regimen of bortezomib and ATO might be a potential therapeutic remedy for the treatment of leukemia.
Hairy root cultures of Artemisia annua L. were cultivated in three different mist bioreactors, each fitted with three stainless steel meshes. The growth rates in the three 2.3-L mist bioreactors differed. After 25 d, the growth index (final dry weight/initial dry weight) of the roots was 42 in a nutrient mist bioreactor, 61 in an inner-loop nutrient mist bioreactor, and 68 in a modified inner-loop nutrient mist bioreactor. Under a misting cycle of 3/30 (ON 3 min/OFF 30 min) for 25 d, dry weight reached 13.6 g/L of medium in the modified inner-loop nutrient mist bioreactor in which nutrient could be supplied without dilution of mist by air flow.
Summary:The efficacy of ciprofloxacin as antibacterial prophylaxis for allogeneic bone marrow transplantation has been well documented, and it virtually eliminated bacteremias caused by gram-negative pathogens in early reports. Ciprofloxacin was therefore incorporated into the prophylactic antibiotic regimen during allogeneic bone marrow or peripheral blood stem cell transplantation at Veterans General Hospital, Kaohsiung from February 1997. In 12 consecutive patients receiving allogeneic bone marrow or peripheral blood stem cell transplantation, ciprofloxacin-resistant Escherichia coli bacteremia developed in three (25%). In addition to our data, increasing evidence suggests that the widespread use of a fluoroquinolone is associated with the emergence of resistant isolates as well as documented infections caused by these resistant strains. The incidence of Escherichia coli bacteremia in our transplant patients was 25%, which was similar to that in patients not receiving preventive therapy or in those receiving trimethoprim-sulfamethoxazole prophylaxis. The prophylactic efficacy of ciprofloxacin in allogeneic bone marrow transplant or peripheral blood stem cell transplant recipients should therefore be reassessed.
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