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51.
Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma 总被引:1,自引:0,他引:1
Heider U von Metzler I Kaiser M Rosche M Sterz J Rötzer S Rademacher J Jakob C Fleissner C Kuckelkorn U Kloetzel PM Sezer O 《European journal of haematology》2008,80(2):133-142
Objectives: Mantle cell lymphoma (MCL) is an incurable B cell lymphoma, and novel treatment strategies are urgently needed. We evaluated the effects of combined treatment with the proteasome inhibitor bortezomib and the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) on MCL. Bortezomib acts by targeting the proteasome, and – among other mechanisms – results in a reduced nuclear factor-kappa B (NF-κB) activity. HDACi promote histone acetylation, and also interfere with NF-κB signaling.
Methods: Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H2 DCFDA. In addition, activated caspases, proteasome- and NF-κB activity were quantified.
Results: Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions: This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL. 相似文献
Methods: Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H
Results: Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions: This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL. 相似文献
52.
Sezer O 《Hematology (Amsterdam, Netherlands)》2005,10(Z1):19-24
Bone destruction is a hallmark of multiple myeloma, and recent studies demonstrated a strong interdependence between tumor progression and bone resorption. Increased bone resorption as a major characteristic of multiple myeloma is caused by osteoclast activation and osteoblast inhibition (uncoupling). Myeloma cells alter the local regulation of bone metabolism by increasing the receptor activator of NF-kappaB ligand (RANKL) and decreasing osteoprotegerin (OPG) expression within the bone marrow microenvironment, thereby stimulating the central pathway for osteoclast formation and activation. In addition, they produce the chemokines MIP-1alpha, MIP-1beta and SDF-1alpha, which also increase osteoclast activity. Furthermore, myeloma cells suppress osteoblast function by the secretion of osteoblast inhibiting factors, e.g. Dickkopf (DKK)-1. The resulting bone destruction releases several cytokines, which in turn promote myeloma cell growth. Therefore, the inhibition of bone resorption could stop this vicious circle and not only decrease myeloma bone disease, but also the tumor progression. Preclinical studies provided strong evidence that the suppression of the osteoclast activity using bisphosphonates, RANKL blockade or inhibition of MIP-1alpha or MIP-1beta is effective both in reducing myeloma bone disease and tumor growth and therefore may offer an important treatment strategy in multiple myeloma. 相似文献
53.
Orhan G Ozay B Tartan Z Kurc E Ketenci B Sargin M Demirtas MM Aykut SA 《Annales de cardiologie et d'angeiologie》2008,57(1):58-61
In some countries, Hydatidosis is a common public health problem but cardiac hydatid cysts are rarely observed. The evaluations of operative results and follow up of cardiac hydatid cases. Twenty-five consecutive unselected patients suffering from cardiac hydatidosis and operated on between 1967 and 2006 in Siyami Ersek Cardiothoracic and Vascular Surgery Center were retrospectively analyzed. In 10 of these patients the hydatid cyst was intracardiac, while in 13 patients cysts were extracavitary but located into the pericardium. In 2 patients the hydatid cyst was both intra and extracavitary. Mean age of the patients was 31+/-9.2. The female/male ratio was 17/8. The 12 patients with intracavitary and 2 patients wit extracavitary hydatid cysts were operated on with the aid of extracorporeal circulation. One patient died postoperatively. In one patient recurrence of the hydatidosis was observed. The majority of cases in previous publications were located in the left side of the heart. In our series, most were located in the right heart. In such cases clamping the pulmonary artery is mandatory to prevent pulmonary migration. Careful resection is important for prevention of recurrence. 相似文献
54.
Yesim Salik Sengul Nergis Kaya Gamze Yalcinkaya Muge Kirmizi Orhan Kalemci 《Explore (New York, N.Y.)》2021,17(4):334-339
ContextPatients who have suffered from persistent symptoms often undergo lumbar spinal surgery (LSS). Motor imagery should be added to postoperative home exercises to reduce patient complaints.ObjectiveThe aim of this study was to compare the effects of home exercise plus motor imagery and only home exercise in patients undergoing LSS.DesignA randomized controlled study.SettingsThis study was designed by researchers at Dokuz Eylul University.ParticipantsThirty-seven patients undergoing LSS were randomized to motor imagery group (n = 19) and control group (n = 18).Main outcome measuresPain was measured by Visual Analogue Scale, disability related to low back pain by Oswestry Disability Index, pain-related fear by Tampa Scale of Kinesiophobia, depression by Beck Depression Inventory, quality of life by World Health Organization Quality of Life Scale-Short Form (WHOQOL-BREF). All assessments were repeated in the preoperative period, three weeks after and six weeks after the surgery.InterventionsMotor imagery group underwent home exercise plus motor imagery program applied by voice recording. Control group underwent only home exercise program. Exercise program compliance was monitored by exercise diary and telephone calls once every week.ResultsThere was a significant improvement in pain at rest and during activity, disability, kinesiophobia, depression, physical health and psychological sub-parameters of WHOQOL-BREF between preoperative period, and the third week and sixth week in both groups (p < 0.05). When comparing groups for gain scores, there was a more significant improvement in pain during activity in motor imagery group (p < 0.05). Motor imagery should be addressed as an effective treatment after LSS. 相似文献
55.
Oral Radiology - Dental professionals have always been meticulous about infection control due to high risk of cross-contamination during dental procedures. Nevertheless, there is an urgent need to... 相似文献
56.
Objectives:
This study assessed the influence of different voxel resolutions of two different CBCT units on the in vitro detection of periodontal defects.Methods:
The study used 12 dry skulls with a maxilla and a mandible. Artificial defects (dehiscence, tunnel, fenestration) were separately created on the anterior, premolar and molar teeth using burrs. A total of 14 dehiscences, 13 fenestrations, 8 tunnels and 16 non-defect controls were used in the study. Images were obtained from two different CBCT units in six voxel sizes (voxel size: 0.080, 0.100, 0.125, 0.150, 0.160 and 0.200 mm3). Kappa coefficients were calculated to assess both intra- and interobserver agreements for each image set.Results:
Overall intraobserver kappa coefficients ranged between 0.978 and 0.973 for the 0.080-mm3 images and between 0.751 and 0.737 for the 0.160-mm3 images, suggesting notably high intraobserver agreement for detecting periodontal defects. CBCT performed significantly better at detecting fenestrations (p < 0.05) than tunnel and dehiscence defects. No statistically significant difference was found between the detection of dehiscence and tunnel defects (p > 0.05).Conclusions:
A voxel size of 0.150 mm3 was identified as the cut-off point for overall detection of periodontal defects. CBCT should be considered the most reliable imaging modality for the diagnosis of periodontal defects. 相似文献57.
H. Nursun ?zcan Berna O?uz Mithat Halilo?lu Diclehan Orhan Mu?turay Kar?aalt?ncaba 《Diagnostic and interventional radiology (Ankara, Turkey)》2015,21(4):355-360
Fatty liver can present as focal, diffuse, heterogeneous, and multinodular forms. Being familiar with various patterns of steatosis can enable correct diagnosis. In patients with equivocal findings on ultrasonography, magnetic resonance imaging can be used as a problem solving tool. New techniques are promising for diagnosis and follow-up. We review imaging patterns of steatosis and new quantitative methods such as proton density fat fraction and magnetic resonance elastography for diagnosis of nonalcoholic fatty liver disease in children.Nonalcoholic fatty liver disease (NAFLD) is as widely encountered in children as in adults, with an estimated prevalence of 9.6% (1). It occurs due to accumulation of triglyceride in hepatocytes without alcohol ingestion. Nonalcoholic steatohepatitis (NASH) was first defined in children in 1983 (2). NAFLD includes a broad range of clinicopathologic features ranging from simple steatosis (fat with inflammation and/or fibrosis), steatohepatitis/NASH to cirrhosis. Some other diseases of liver can also cause hepatic steatosis including hepatitis B and C, Wilson’s disease, α-1-antitrypsin deficiency, autoimmune hepatitis, drug-induced liver injury (valproate, methotrexate, tetracycline, amiodarone, and prednisone), and total parenteral nutrition (3). Furthermore, fatty liver is a risk factor for cirrhosis, diabetes, and cardiovascular disease.In clinical practice, the diagnosis of NAFLD is made by increased serum ALT and/or presence of enlarged echogenic liver in ultrasonography. Being overweight or obese, and/or insulin resistance are highly indicative but not absolutely necessary for diagnosing NAFLD (4). The gold standard for diagnosis is liver biopsy, which additionally provides semi-quantitative analysis of NASH damage in children (5). It is an expensive, invasive procedure with a risk of morbidity (0.06%–0.35%) and mortality (0.01%–0.1%) (6).The evaluation of liver fat in children via noninvasive imaging modalities is needed to avoid complications of biopsy and for follow-up. Main imaging modalities for the assessment of pediatric NAFLD are ultrasonography (US) and magnetic resonance imaging (MRI). Computed tomography is the other imaging method for liver fat assessment, but ionizing radiation is a major drawback in children (7). Assessment of fat accumulation may cause diagnostic dilemmas and confusion due to manifestations with unusual structural patterns and imaging appearance of the liver. This article reviews the histopathology of pediatric NAFLD, radiologic evaluation and different structural patterns of childhood NAFLD/NASH on US and MRI. We also discuss diagnostic pitfalls and briefly review new imaging techniques. 相似文献
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