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951.
Lapo Alinari Valerie L White Christian T Earl Timothy P Ryan Jeffrey S Johnston James T Dalton Amy K Ferketich Raymond Lai David M Lucas Pierluigi Porcu Kristie A Blum John C Byrd Robert A Baiocchi 《MABS-AUSTIN》2009,1(1):31-40
Mantle cell lymphoma (MCL) is a distinct histologic subtype of B cell non-Hodgkins lymphoma (NHL) associated with an aggressive clinical course. Inhibition of the ubiquitin-proteasome pathway modulates survival and proliferation signals in MCL and has shown clinical benefit in this disease. This has provided rationale for exploring combination regimens with B-cell selective immunotherapies such as rituximab. In this study, we examined the effects of combined treatment with bortezomib and rituximab on patient-derived MCL cell lines (Jeko, Mino, SP53) and tumor samples from patients with MCL where we validate reversible proteasome inhibition concurrent with cell cycle arrest and additive induction of apoptosis. When MCL cells were exposed to single agent bortezomib or combination bortezomib/rituximab, caspase dependent and independent apoptosis was observed. Single agent bortezomib or rituximab treatment of Mino and Jeko cell lines and patient samples resulted in decreased levels of nuclear NFκB complex(es) capable of binding p65 consensus oligonucleotides, and this decrease was enhanced by the combination. Constitutive activation of the Akt pathway was also diminished with bortezomib alone or in combination with rituximab. On the basis of in vitro data demonstrating additive apoptosis and enhanced NFκB and phosphorylated Akt depletion in MCL with combination bortezomib plus rituximab, a phase II trial of bortezomib-rituximab in patients with relapsed/refractory MCL is underway.Key words: mantle cell lymphoma, proteasome inhibition, CD20, survival and death pathways, apoptosis 相似文献
952.
Joleen S. Cheah Kyle A. Jacobs Tzu Wei Lai Reca Caballelo Jacqueline L. Yee Shuji Ueda Volkmar Heinrich Soichiro Yamada 《Molecular biology of the cell》2021,32(13):1221
Sensing physical forces is a critical first step in mechano-transduction of cells. Zyxin, a LIM domain-containing protein, is recruited to force-bearing actin filaments and is thought to repair and strengthen them. Yet, the precise force-induced protein interactions surrounding zyxin remain unclear. Using BioID analysis, we identified proximal proteins surrounding zyxin under normal and force-bearing conditions by label-free mass spectrometry analysis. Under force-bearing conditions, increased biotinylation of α-actinin 1, α-actinin 4, and AFAP1 were detected, and these proteins accumulated along force-bearing actin fibers independently from zyxin, albeit at a lower intensity than zyxin. VASP also accumulated along force-bearing actin fibers in a zyxin-dependent manner, but the biotinylation of VASP remained constant regardless of force, supporting the model of a free zyxin–VASP complex in the cytoplasm being corecruited to tensed actin fibers. In addition, ARHGAP42, a RhoA GAP, was also identified as a proximal protein of zyxin and colocalized with zyxin along contractile actin bundles. The overexpression of ARHGAP42 reduced the rate of small wound closure, a zyxin-dependent process. These results demonstrate that the application of proximal biotinylation can resolve the proximity and composition of protein complexes as a function of force, which had not been possible with traditional biochemical analysis. 相似文献
953.
Chia-Hsiang Hsueh Wen-Pin Chen Jiunn-Lee Lin Chia-Ti Tsai Yen-Bin Liu Jyh-Ming Juang Hsuan-Ming Tsao Ming-Jai Su Ling-Ping Lai 《Journal of biomedical science》2009,16(1):23
The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied
by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead
to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes
Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described.
Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current
accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with
Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch
clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with
steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from
inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential
(7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease
of sodium current. 相似文献
954.
Takashi Yamamoto Padma Nair Shou-wu Ma Peg Davis Henry I. Yamamura Todd W. Vanderah Frank Porreca Josephine Lai Victor J. Hruby 《Bioorganic & medicinal chemistry》2009,17(20):7337-7343
In order to improve metabolic stability, a ring structure with a cystine moiety was introduced into TY027 (Tyr-d-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3′,5′-(CF3)2Bzl]), which is a lead compound of our developing bifunctional peptide possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr-cyclo[d-Cys-Gly-Phe-Met-Pro-d-Cys]-Trp-NH-[3′,5′-(CF3)2Bzl]) was found as a highly selective δ opioid agonist over μ receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24 h half life in rat plasma. 相似文献
955.
Chung-Hin Chui Raymond Siu-Ming Wong Roberto Gambari Gregory Yin-Ming Cheng Marcus Chun-Wah Yuen Kit-Wah Chan See-Wai Tong Fung-Yi Lau Paul Bo-San Lai Kim-Hung Lam Cheuk-Lam Ho Chi-Wai Kan Kelvin Sze-Yin Leung Wai-Yeung Wong 《Bioorganic & medicinal chemistry》2009,17(23):7872-7877
A list of diethynylfluorenes and their gold(I) derivatives have been studied for their antitumor activity as a function of their structure–activity relationships. End-capping the fluoren-9-one unit with gold(I) moieties could significantly strengthen the cytotoxic activity in vitro on three human cancer cell lines with induction of reactive oxygen species generation on Hep3B hepatocellular carcinoma cells and exhibit attractive antitumor activity from in vivo nude mice Hep3B xenograft model with limited adverse effects on vital organs including liver and kidney. 相似文献
956.
The majority of Hevea (Hevea brasiliensis Muell. Arg.) genetic resource in Vietnam derived from the IRRDB’81 germplasm collected in the Amazonian habitats of the genus.
Random amplified polymorphic DNA (RAPD) analysis was used to examine the genetic diversity and structure of the IRRDB’81 germplasm.
A total of 59 accessions from 13 different districts of the Brazilian states namely Acre, Rondonia, and Mato Grosso were brought
into the study using six arbitrarily preselected primers. Sixty-five RAPD band patterns ranging in size from 0.2 to 3.0 kbp
were scored for analysis. Differences in the level of DNA polymorphism among the districts and states were revealed. The percentage
of the polymorphic DNA fragments calculated for 13 individual districts varied from 15.38 to 70.77%. The mean values of heterozygosity
within the district varied from 0.064 to 0.264. Pairwise district Nei’s genetic distance values ranged from 0.046 for Catriquacu
and Itanba of Mato Grosso to 0.304 for Tarauaca of Acre and Aracatuba of Mato Grosso. The estimated values of Shannon’s diversity
index ranged from 0.093 for the Assis-Brasil district of Acre to 0.389 for the Jiparana district of Rondonia. The analysis
of molecular variance (AMOVA) indicated that most of the genetic variations were found among accessions within the districts,
while interdistrict variance component accounted for 14.1% only. The low interdistrict differentiation probably implied an
extensive gene flow among them. Both the principal coordinate analysis and UPGMA cluster analysis based on genetic distance
values revealed a varying degree of separation among the districts and that conformed to geographical origins of Hevea IRRDB’81 collection. 相似文献
957.
Hongmin Lai Changbin Sun Huaying Tang Xianwei Fan Yili Ma Youzhi Li 《Journal of microbiology (Seoul, Korea)》2009,47(6):736-745
Copper (Cu)-transporting P-type ATPase (CTPA) genes have been documented to play an important role in resistance to heavy
metals. However, our understanding of roles of CTPA genes of the filamentous fungi was based only on sequence similarity prediction
before. In a previous study, we isolated a Penicillum janthinellum strain GXCR of higher tolerance to Cu (200 mM). In this study, we cloned the partial cDNA of CTPA gene, named PcpA, from the strain GXCR. Sequence alignment indicated that the cloned cDNA sequence has the highest identity (94.4%) with a
predictive CTPA gene of Aspergillus clavatus. The PcpA-encoded protein, termed PcpA, has classical functional domains of CTPAs, and shows differences from reported CTPAs in some
specific sequence motifs and transmembrane regions. Expression of the PcpA was induced by extracellular Cu, cadmium (Cd), and silver (Ag). PcpA RNA interference (RNAi) mutants with a reduced level of PcpA mRNA were more sensitive to Cu, iron, Cd, and Ag than the wild-type (WT) strain GXCR. When grown in the presence of Cu, iron,
and Cd, intracellular Cu and iron contents in the PcpA RNAi mutant were significantly (P<0.05) lower than those in the WT; However, intracellular Cd content in the mutant was significantly (P<0.05) higher than that in the WT. Taken together, it can be concluded that the PcpA functions in Cu uptake and homeostasis, iron uptake, and Cd export from the cytosol to the extracytosol. 相似文献
958.
Sanna D Lai T Francalacci P Curini-Galletti M Casu M 《Genetics and molecular biology》2009,32(4):864-867
Monocelis lineata consists of a complex of sibling species, widespread in the Mediterranean and Atlantic Ocean. Previous genetic analysis placed in evidence at least four sibling species. Nevertheless, this research was not conclusive enough to fully resolve the complex or to infer the phylogeny/phylogeography of the group. We designed specific primers aiming at obtaining partial sequences of the mtDNA gene Cytochrome c Oxidase subunit I (COI) of M. lineata, and have identified 25 different haplotypes in 32 analyzed individuals. The dendrogram generated by Neighbor-Joining analysis confirmed the differentiation between Atlantic and Mediterranean siblings, as well as the occurrence of at least two Mediterranean sibling species. Thus validated, the method here presented appears as a valuable tool in population genetics and biodiversity surveys on the Monocelis lineata complex. 相似文献
959.
Li Li Daxin Pang Tiedong Wang Limei Chen Mingjun Zhang Daibang Nie Liangxue Lai 《Biochemical and biophysical research communications》2009,382(2):232-201
The pig is thought to be the most suitable non-human source of organs for xenotransplantation and is widely used as a model of human disease. Using pigs as disease models requires the design of conditional Cre recombinase-loxP gene modifications, which, in turn, requires a Cre-expressing pig with defined patterns of expression controlled by the use of a tissue-specific promoter. In order to monitor Cre recombinant expression in vivo, it is important to create a reporter strain. We have generated reporter a pig that is based on a single vector that drives the ubiquitous expression of the enhanced green fluorescent protein (EGFP). The EGFP gene is expressed only after Cre-mediated excision of loxP-flanked stop sequences. These reporter transgenic pigs will be of great value for monitoring Cre recombinase activity in vivo. 相似文献
960.
Mice Lacking the ISG15 E1 Enzyme UbE1L Demonstrate Increased Susceptibility to both Mouse-Adapted and Non-Mouse-Adapted Influenza B Virus Infection
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Caroline Lai Jessica J. Struckhoff Jana Schneider Luis Martinez-Sobrido Thorsten Wolff Adolfo García-Sastre Dong-Er Zhang Deborah J. Lenschow 《Journal of virology》2009,83(2):1147-1151
ISG15 functions as a critical antiviral molecule against influenza virus, with infection inducing both the conjugation of ISG15 to target proteins and production of free ISG15. Here, we report that mice lacking the ISG15 E1 enzyme UbE1L fail to form ISG15 conjugates. Both UbE1L−/− and ISG15−/− mice display increased susceptibility to influenza B virus infection, including non-mouse-adapted strains. Finally, we demonstrate that ISG15 controls influenza B virus infection through its action within radioresistant stromal cells and not bone marrow-derived cells. Thus, the conjugation of ISG15 to target proteins within stromal cells is critical to its activity against influenza virus. 相似文献