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191.
H F Mark D Feldman M Samy C Sun S Das S Mark J Lathrop 《Experimental and molecular pathology》1999,66(2):157-162
Cervical carcinoma is a malignancy which typically occurs at the transformation zone between squamous and glandular epithelium. The vast majority falls into two histologic types, squamous cell and adenocarcinoma. In an effort to identify a subset of cervical cancer characterized by chromosome 8 trisomy, a biomarker extensively explored by this laboratory, we conducted a study of formalin-fixed, paraffin-embedded materials of cervical cancer. A total of 24 cases of cervical cancer were identified from the archives of the Rhode Island Hospital. Fluorescent in situ hybridization (FISH) using a chromosome 8 centromere enumeration probe was conducted to assess the chromosome 8 copy number in these specimens. Hybridization signals were scored among tumor cells in a blinded fashion. Tumors with >/=15% of cells with three signals were scored as trisomic. Of 24 cases studied, 23 were informative. Of the 23 informative cases, 12 (52.2%) were found to be trisomic. Eleven cases (47.8%) were disomic. The frequency of trisomy in a control chromosome 17 probe was 13.0% (3/23). Selected clinicopathologic characteristics of the tumors were also reviewed. The frequency of trisomy 8 among cases of invasive squamous cell carcinoma was 44.4% (8 of 18 tumors) and that of invasive adenocarcinoma was 80% (4 of 5 tumors). The sole tumor which was both trisomic 8 and amplified for the HER-2/neu oncogene was found to be an invasive adenocarcinoma. While the sample size in this pilot study is not large, the data obtained thus far clearly demonstrate that FISH is an appropriate technique for detecting chromosomal trisomies and that a subset of cervical cancer exists that is characterized by chromosome 8 trisomy. Further exploration of this biomarker is warranted. 相似文献
192.
193.
Hend Kothayer Samy M. Ibrahim Moustafa K. Soltan Samar Rezq Shireen S. Mahmoud 《Drug development research》2019,80(3):343-352
In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED50) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED50 values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABAA binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.
相似文献
Hit, Lead & Candidate Discovery |
194.
An animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines 总被引:1,自引:0,他引:1
IPT-AFM is a proprietary animal component free medium that was developed for rabies virus (strain LP 2061) production in Vero cells. In the present work, we demonstrated the versatility of this medium and its ability to sustain the growth of other cell lines and different virus strains. Here, three models were presented: Vero cells/rabies virus (strain LP 2061), MRC-5 cells/measles virus (strain AIK-C) and BHK-21 cells/rabies virus (strain PV-BHK21). The cell lines were first adapted to grow in IPT-AFM, by progressive reduction of the amount of serum in the culture medium. After their adaptation, BHK-21 cells grew in suspension by forming clumps, whereas MRC-5 cells remained adherent. Then, kinetics of cell growth were studied in agitated cultures for both cell lines. In addition, kinetics of virus replication were investigated. 相似文献
195.
Tarek K. Motawi Samy A. Abdelazim Hebatallah A. Darwish Samia A. Shouman 《Nutrition and cancer》2016,68(3):435-445
Despite tamoxifen (TAM) is beneficial in treating a significant proportion of patients with breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis, with a plethora of important biological actions including anticancer activity. This study aimed to explore the cytotoxicity, the type of drugs interaction as well as the apoptotic and autophagic pathways of the combined treatment of TAM and CAPE in MCF-7 cells. Their antitumor activity and effect on survival of mice bearing Ehrlich tumor were also analyzed. The results showed synergistic cytotoxic effects, manifested by significant activation of apoptotic machinery, along with downregulation of protein levels of Bcl-2 and beclin-1, upon using the combination regimen. However, the ratio between microtubule-associated protein light chain 3-II and -I was not altered. Moreover, a decrease in vascular endothelial growth factor level was detected. Similarly, TAM + CAPE increased the life span of tumor-bearing animals and caused a marked regression in their tumor size and weight compared with those treated with either TAM or CAPE alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials. 相似文献
196.
Bradley G. Stiles Kisha Pradhan Jodie M. Fleming Ramar Perumal Samy Holger Barth Michel R. Popoff 《Toxins》2014,6(9):2626-2656
Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin. 相似文献
197.
Elhammady MS Benglis DM Bhatia S Sandberg DI Ragheb J 《Journal of neurosurgery. Pediatrics》2008,2(1):68-70
Ventriculoatrial (VA) shunts remain the most used alternative to ventriculoperitoneal shunts in infants with hydrocephalus. The authors report a case of an acute VA shunt malfunction as a result of distal catheter displacement in an 18-month-old girl with partial anomalous pulmonary venous return. The child presented with respiratory compromise, and a chest radiograph revealed a lung infiltrate and normal position of the distal shunt catheter tip. Computed tomography demonstrated stable ventricle size in comparison with previous studies. As the patient's respiratory distress progressed, she required intubation, mechanical ventilation with high airway pressures and inspired oxygen concentrations, muscle relaxants, and sedation. A routine morning chest radiograph several days after admission revealed displacement of the distal catheter into the left innominate vein. Later that day the child's pupils were noted to be large and unreactive and a distal shunt malfunction was diagnosed. Complications of VA shunts and the presumed mechanism by which the catheter became displaced are discussed. 相似文献
198.
Enas Reda Abdelaleem Mamdouh Nabil Samy Samar Yehia Desoukey Miaomiao Liu Ronald J. Quinn Usama Ramadan Abdelmohsen 《RSC advances》2020,10(57):34959
Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities. Sponges which belong to the order Dictyoceratida are distinctly classified into 5 families: Dysideidae, Irciniidae, Spongiidae, Thorectidae, and Verticilliitidae. In this review, compounds isolated from Dictyoceratida sponges were discussed with their biological potential within the period 2013 to December 2019. Moreover, analysis of the physicochemical properties of these marine natural products was investigated and the results showed that 78% of the compounds have oral bioavailability potential. This review highlights sponges of the order Dictyoceratida as exciting source for discovery of new drug leads.Marine organisms have been considered an interesting target for the discovery of different classes of secondary natural products with wide-ranging biological activities. 相似文献
199.
Hanchen Xu Kevin Van der Jeught Zhuolong Zhou Lu Zhang Tao Yu Yifan Sun Yujing Li Changlin Wan Ka Man So Degang Liu Michael Frieden Yuanzhang Fang Amber L. Mosley Xiaoming He Xinna Zhang George E. Sandusky Yunlong Liu Samy O. Meroueh Chi Zhang Aruna B. Wijeratne Cheng Huang Guang Ji Xiongbin Lu 《The Journal of clinical investigation》2021,131(10)
One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy. 相似文献
200.
Selim S Sunkara M Salous AK Leung SW Berdyshev EV Bailey A Campbell CL Charnigo R Morris AJ Smyth SS 《Clinical science (London, England : 1979)》2011,121(12):565-572
Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma S1P (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma S1P levels. Plasma S1P from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R2 = 0.51, P < 0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2 ± 0.34% (value is the mean ± S.D.) increased Hct to 28.3 ± 0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S1P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P. After 30 days of storage, RBC S1P decreased to 19% of that observed in fresh (3-7-day-old) RBC segments. RBC membranes contain low levels of both S1P phosphatase and S1P lyase activities that may account for the decline in S1P levels with storage. Our results support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P. 相似文献