Both isoforms of the hepatitis delta antigen (HDAg) of hepatitis delta virus (HDV) are highly associated with virus proliferation and may act as co-activators of cellular gene expression. Human hepatocellular carcinoma (HCC) cell line Huh7, which stably expresses HDAgs, was differentially screened and the results showed that clusterin gene expression was enhanced. The mechanisms for HDAg-mediated clusterin gene upregulation were investigated. Expression of HDAgs was associated with enhanced histone H3 acetylation within the clusterin promoter in a chromatin immunoprecipitation assay. Transient transfection of HDAg-expressing plasmids into Huh7 cells also enhanced clusterin expression and histone acetylation. Furthermore, HDV replication was associated with histone hyperacetylation and clusterin induction. The effect of increased clusterin expression was determined by a chemosensitivity assay with adriamycin treatment. These data indicated that HDV-induced clusterin protein increases cell survival
Title:Secretory Clusterin: A Promising Target for Chemoresistance of Hepatocellular Carcinoma. VOLUME: 20 ISSUE: 12. Author(s):Jie Zhang, Mengna Wu, Yuqing Xu, Qianqian Song and Wenjie Zheng*. Affiliation:Department of Chemotherapy, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001 Nantong, Jiangsu, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001 Nantong, Jiangsu, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001 Nantong, Jiangsu, Department of Radiology, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, 27157 NC, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001 Nantong, Jiangsu. Keywords:Hepatocellular carcinoma, secretory clusterin, drug resistance, molecular target, cancer, sCLU.. Abstract:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Chemoresistance ...
TY - JOUR. T1 - Interaction of complement and clusterin in renal injury. AU - Correa-Rotter, Ricardo. AU - Hostetter, Thomas H.. AU - Nath, Karl A. AU - Manivel, J. Carlos. AU - Rosenberg, Mark E.. PY - 1992/11. Y1 - 1992/11. N2 - Clusterin is a heterodimeric glycoprotein that has been associated with such diverse biologic functions as reproduction, cell regression, cell aggregation, and regulation of the cytolytic activity of the membrane attack complex of complement. Clusterin is a component of glomerular immune deposits in the kidney, and increased Clusterin expression occurs in a number of renal injury states. To further explore the interaction between Clusterin and complement, the requirement for an intact complement system for renal Clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin ...
Background: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin expression and enhance drug efficacy in xenograft models. The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer. Methods: Subjects (n = 25) with localized prostate cancer with high-risk features who were candidates for prostatectomy were treated with OGX-011 by 2-hour intravenous infusion on days 1, 3, and 5 and then weekly from days 8-29 combined with androgen blockade starting on day 1; prostatectomy was performed on days 30-36. Six different doses were tested, from 40 to 640 mg. OGX-011 plasma and prostate tissue concentrations were measured by an enzyme-linked immunosorbent assay method, and ...
Purpose: The clusterin gene encodes a multi-functional protein that has been identified in different tissues, including a number of different eye tissues, primarily in the mouse and to a much lesser extent in humans. Clusterin has been implicated in a number of cellular processes such as lipid transport, membrane integrity, apoptosis, and neurodegeneration, all of which could be important to the biology of the eye. In the current communication, we provide data that confirms the expression of clusterin in a number of different human eye tissues and establishes the expression profile of this gene in monkey derived eye tissues. The issue that we sought to examine is whether a broad profile of clusterin expression in the eye is consistent in primates (monkey and human). Methods: The majority of our study was done using monkey eye tissues. Where possible, we have used human tissues in order to confirm published findings. Northern and western analysis was performed using tissues derived from monkey eyes. In
Antiestrogens represent the first line of therapy in the treatment of estrogen receptor-positive (ER+) breast cancer patients. Unfortunately, up to 40% of patients develop resistance associated with progression and frequently die for metastatic breast cancer. The molecular events leading to pharmacological resistance are not completely understood. We attempted to verify in an experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective protein found to be up-regulated in antiestrogen-resistant patients, following neoadjuvant treatment with toremifene. The role of cytoplasmic clusterin in modulating response to two antiestrogens (toremifene and tamoxifen) was studied in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+ antiestrogen-resistant cell line (T47D) using siRNA strategy. Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and ...
Apolipoprotein J Antibody functions as a secreted chaperone that prevents aggregation of nonnative proteins. It prevents stress-induced aggregation of blood plasma proteins and inhibits the formations of amyloid fibrils. Apolipoprotein J does not require ATP or refold proteins by itself. It maintains partially unfolded proteins in a state for subsequent refolding by other chaperones. It is shown to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Binding to cell surface receptors it triggers internalization of chaperone-client complex and subsequent lysosomal or proteasomal degradation. It modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis while mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Anti-Apolipoprotein J Antibody is useful for researchers interested in the immune system, Ubiquitin pathways, and cardiovascular research.
Clusterin is a chaperone protein that is synthesized in response to cellular stress. It often appears in cells undergoing apoptosis - both as part of developmental programmes such as tissue involution and in numerous pathological conditions - but has also been reported to confer resistance to apoptosis in some cases. Whether it is a pro-survival or a pro-death molecule is therefore unclear. Laure Debure and co-workers have examined the effects of clusterin expression in COS-7 cells (see p. 3109). They find that clusterin can accumulate in juxtanuclear aggregates that exhibit features characteristic of aggresomes (inclusion bodies thought to prevent misfolded proteins spreading throughout the cell). They have a vimentin cage, for example, and can be disrupted by treatment with the chaperone Hsp70 or microtubule-depolymerising drugs. The authors also observe, however, that clusterin expression disrupts mitochondria and induces apoptosis through the mitochondrial pathway - this can be prevented by ...
Clusterin was originally described as a major glycoprotein synthesized in the male reproductive systems of the ram and rat.1,2 Since then it has been identified in a wide range of biological fluids and tissues in many species.1,3-9 Identification of rat clusterin messenger ribonucleic acid (mRNA) to TRPM-2 (testosterone repressed prostatic message 2),10-12 a transcript found to be prevalent in vivo in involuting tissues whether induced in experimental models or naturally during development of the embryo, raised the question of a possible involvement of clusterin in programmed cell death.13,14 Reports by several independent groups of researchers on the upregulation of the clusterin gene in brains of hamsters infected with the scrapie agent15 and of humans afflicted with Alzheimers disease (AD),16 epilepsy,17 or gliomas,17 as well as in the degenerating human retina18 gave support to the apoptosis hypothesis and generated strong interest in the role of clusterin in the central nervous system ...
Immature motoneurons are highly susceptible to degeneration following axon injury. The response of perineuronal glia to axon injury may significantly influence neuronal survival and axon regeneration. We have examined the central reactions to neonatal facial nerve transection with emphasis on the expression of complement component C3 (C3) and the multifunctional apolipoprotein J (ApoJ). Axotomy was performed on one-day-old rats. Animals were perfused from eight hours to two weeks after the lesion. The astroglial marker, glial fibrillary acidic protein (GFAP) was increased from one day and the microglial marker OX-42 from two days after injury. ApoJ immunoreactivity was increased in axotomized neuronal perikarya and astroglial cells from one day postaxotomy, but no C3 immunoreactive profiles were found at any postoperative survival time. Cell proliferation as judged by bromodeoxyuridine labeling and immunoreactivity for the cyclin Ki-67 antigen (antibody MIB5) occurred only at two days after ...
Premature senescence of human diploid fibroblasts (HDFs) can be induced by exposures to a variety of oxidative stress and DNA damaging agents. In this study we developed a robust model of UVB-induced premature senescence of skin HDFs. After a series of 10 subcytotoxic (non-proapoptotic) exposures to UVB at 250 mJ/cm2, the so-called biomarkers of senescence were markedly expressed: growth arrest, senescence-associated β-galactosidase activity, senescence-associated gene overexpression, deletion in mitochondrial DNA. A set of 44 stress- and senescence-associated genes were found to be differentially expressed in this model, among which clusterin/apolipoprotein J (apo J) and transforming growth factor-β1 (TGF-β1). Transfection of apo J cDNA provided protection against premature senescence-inducing doses of UVB and other stressful agents. Neutralizing antibodies against TGF-β1 or its receptor II (TβRII) sharply attenuated the senescence-associated features, suggesting a role for TGF-β1 in ...
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TY - JOUR. T1 - Sulfated Glycoproteins, Glycolipids, and Glycosaminoglycans from Synaptic Plasma and Myelin Membranes. T2 - Isolation and Characterization of Sulfated Glycopeptides. AU - Simpson, David L.. AU - Thorne, Donald R.. AU - Loh, Horace H. PY - 1976/12/1. Y1 - 1976/12/1. N2 - In this report we provide biochemical evidence that a highly purified synaptic plasma membrane fraction derived from rat brain, after intraventricular injection of 35S-labeled sodium sulfate, is enriched in a number of large sulfated glycoproteins compared with a purified myelin fraction studied concurrently. A fraction of the detergent-solubilized sulfated glycoprotein bound specifically to concanavalin A-Sepharose. In addition, we have identified the 35S-labeled lipid-soluble material in these membrane fractions as cerebroside sulfate. The sulfated protein in the lipid-extracted membranes was shown to consist predominantly of a class of glycoproteins containing sulfate in ester linkage to oligosaccharide chains, ...
Anti-human Clusterin mAb, is derived from hybridization of mouse SP2/O myeloma cells with spleen cells from BALB/c immunized mice.
Clusterin also named Apoliprotein J (APO-J) is a 75-80 kD disulfide-linked heterodimeric protein containing about 30% of N-linked carbohydrate rich in sialic acid but truncated forms targeted to the nucleus have also been identified.
Figure 3. Ocular clusterin localization by immunohistochemistry and in situ analysis. Shown are sections of cornea (panels A-C, serial sections), skin/eyelid (panels D, E, serial sections), ciliary body (unfilled arrow and * in panel F), and lens (panels G, H, serial sections). Immunodetection with G7 are shown in panels B, E, F, and H; panels A, D, and G are the negative controls in which the G7 antibody was omitted. In situ hybridization of an anti-sense clusterin mRNA probe on cornea is shown in panel C. Panel I: graph illustrating the distribution of silver grain over different regions of the cornea shown in panel C, for each general region 10 independent counts within a fixed area were taken. Solid arrows indicate the interface between epithelial and stromal cells (cs) in the cornea, arrow heads indicate the area of epithelial cells in the lens.. ...
Loss of cardiomyocytes occurs with aging and contributes to cardiovascular complications. In the present study, we highlighted the role of clusterin, a protein that has recently been associated with the protection of cardiomyocytes from apoptosis. Clusterin protects cardiac cells against damage from myocardial infarction, transplant, or myocarditis. Clusterin can act directly or indirectly on apoptosis by regulating several intracellular pathways. These pathways include (1) the oxidant and inflammatory program, (2) insulin growth factor 1 (IGF-1) pathway, (3) KU70 / BCL-2-associated X protein (BAX) pathway, (4) tumor necrosis factor alpha (TNF-α) pathway, (5) BCL-2 antagonist of cell death (BAD) pathway, and (6) mitogen-activated protein kinase (MAPK) pathway ...
Joel 3:1-21. The Lord Will Be A Refuge Joel 3:1-21 Lesson 3 Key Verse: 3:16b JoelBibleSchool NIU UBF 5/29/08 Delivered by Jennifer Jesmer "…But the LORD will be a refuge for his people, a stronghold for the people of Israel." From the last passage I learned that repentance is the most important thing to […]. Read More... ...
This work has been made available to the staff and students of the University of Sydney for the purposes of research and study only. It constitutes material that is held by the University for the purposes of reporting for HERDC and the ERA. This work may not be downloaded, copied and distributed to any third party ...
As we can see the amount of discrete information held in working memory at any one time is quite limited. However, by writing things out as we process our information rather than simply listing the desired outcomes we can formulate a greater number of possibilities.. Lets look through our planners and pick a to-do. Let us suppose we wish to communicate good tidings to Macbeth and hail him Thane of Cawdor. The most obvious choice is to climb to the top of the highest tower and contact him via semaphore. However this would be time consuming not to mention hazardous. What are the options? By exploring the alternatives on paper we have provided ourselves with three choices each one conveys the main message- Macbeth you are now Thane of Cawdor plus a deeper more subjective one. For example:. * Carrier pigeons - Speedy yet impersonal.. * Messenger - slower but makes the receiver feel important.. * Three Fates wearing false beards appear out of thin air - dramatic; the sender is prone to ...
While I have always been extremely health conscious and am presently in excellent health, I did become temporarily out-of-commission (i.e. I was really sick) in 2005 with a number of at the time unexplainable symptoms. I was quite puzzled at the time because I had been eating mainly organically grown food, drinking spring water, doing Yoga every morning, and going to the gym several times a week. In other words, I was doing everything one is supposed to do to stay healthy. I was not supposed to get sick. It took me six months before discovering or even imagining the main source of the problem - which was in fact "overexposure to electromagnetic" - especially microwave - radiation. I was living within 200 meters of two cell phone towers at the time and within 500 meters of a 3rd one with numerous WiFi signals bleeding into my apartment from adjacent neighbors. I developed a host of symptoms, which are found in what has been misleadingly described as Chronic Fatigue Syndrome (CFS) -- but much more ...
Clusterin, ubiquitously distributed in mammalians, was cloned and identified as the most potently induced gene during rat prostate involution following androgen deprivation. Also found to be involved in many other patho-physiological processes, its biological significance is still controversial, particularly with regard to apoptosis. We previously showed that transient over-expression of clusterin blocked cell cycle progression of simian-virus-40-immortalized human prostate epithelial cell lines PNT1A and PNT2. We show in the present study that the accumulation of an intracellular 45 kDa clusterin isoform was an early event closely associated with death of PNT1A cells caused by cell detachment followed by apoptosis induction (anoikis). Cell morphological changes, decreased proliferation rate and cell cycle arrest at G0/G1-S-phase checkpoint were all strictly associated with the production and early translocation to the nucleus of a 45 kDa clusterin isoform. Later, nuclear clusterin was found ...
The CLU gene is located on p21-p12 of human chromosome 8, with CLU as its encoded product, which has various physiological functions, including participating in lipid metabolism (28), oxidative stress reaction (29), and cell cycle regulation (30). CLU is highly expressed in cerebrospinal fluid and amyloid plaques in brain tissues, and is involved in the pathogenesis of AD (4,5,31). Yerbury et al (32) demonstrated that the deposition of CLU in senile plaques and neurofibrillary tangles of AD. Howlett et al (33) further reported a correlation between CLU and senile plaque Aβ40 in the brain cortex of patients with AD. Martin-Rehrmann et al (34) demonstrated the presence of dysfunctional neurons with phosphorylated tau protein surrounding the senile plaques in 71% of CLU-positive patients with AD. Furthermore, they also showed that the tau and phosphorylated tau protein were significantly increased in the rat hippocampus, following the injection of a CLU-rich solution (34). It was suggested that ...
Objective: To investigate the differences between chondrocytes of the superficial and underlying zones of articular cartilage at the level of gene expression. Methods: Messenger RNA (mRNA) was isolated from chondrocytes harvested from the superficial and deep zones of immature bovine articular cartilage. This mRNA was reverse transcribed, radiolabeled, and then each complementary DNA (cDNA) sample was used to screen duplicate filters of a bovine chondrocyte cDNA library. By comparing autoradiographic signals on matching filter sets, clones exclusively expressed in the superficial zone of articular cartilage were isolated and characterized further. Results: Of the superficial-specific gene clones isolated, 25% were found to be a single gene product, clusterin. Northern hybridization was used to show that clusterin is expressed specifically in the superficial zone of articular cartilage and that its expression is up-regulated in mature cartilage. In situ hybridization was used to precisely ...
This is a randomized, double-blind, placebo-controlled, multicenter, international trial enrolling patients with metastatic CRPC who had a response to first-line docetaxel therapy and have prostate cancer-related pain with progression of disease. The intended intervention is second-line treatment with docetaxel retreatment or cabazitaxel plus study agent, where custirsen is to be administered in the investigational arm and placebo is to be administered in the control arm.. Selection of the chemotherapy (docetaxel re-treatment or cabazitaxel) is to be determined by the treating physician, based on the patients first-line response.. The study will primarily assess pain and analgesic use for evaluation of durable pain palliation in response to study treatment. Pain and analgesic use will be obtained via a 3rd party contact center (direct contact with patient).. Study treatment starts with a Loading Dose Period during which three infusions of study agent (custirsen vs. placebo) will be ...
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Expression of CLU (APOJ, CLI, CLU1, CLU2, KUB1, SGP-2, SP-40, TRPM-2) in oral mucosa tissue. Antibody staining with HPA000572 and CAB016253 in immunohistochemistry.
α2-Macroglobulin (α2M) is an extracellular chaperone that inhibits amorphous and fibrillar protein aggregation. The reaction of α2M with proteases results in an activated conformation, where the proteases become covalently-linked within the interior of a cage-like structure formed by α2M. This study investigates, the effect of activation on the ability of α2M to inhibit amyloid formation by Aβ1-42 and I59T human lysozyme and shows that protease-activated α2M can act via two distinct mechanisms: (i) by trapping proteases that remain able to degrade polypeptide chains and (ii) by a chaperone action that prevents misfolded clients from continuing along the amyloid forming pathway.
Interferon-alpha B2 (IFN-a8) (mPEG-ALD), 1 mg. Clusterin also names Apoliprotein J is a 75-80 kD disulfide-linked heterodimeric protein containing about 30% of N-linked carbohydrate rich in sialic acid but truncated forms targeted to the nucleus have
Mouse monoclonal antibody raised against partial recombinant CLU. Recombinant protein corresponding to a portion of the alpha subunit of human CLU. (MAB9601) - Products - Abnova
With age, forgetfulness and other signs of memory loss sometimes appear, prompting elderly individuals to seek a medical evaluation amid fears that they may be experiencing early symptoms of Alzheimers disease (AD), the ...
April 28,2009- OncoGenex Receives Confirmation from FDA on the Design of a Second Phase 3 Trial Evaluating OGX-011 for the Treatment of Advanced Prostate Cancer
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... Signed-off-by: Jens Axboe ,[EMAIL PROTECTED], --- drivers/scsi/aha1542.c , 32 +++++++++++++++----------------- 1 files changed, 15 insertions(+), 17 deletions(-) diff --git a/drivers/scsi/aha1542.c b/drivers/scsi/aha1542.c index cbbfbc9..961a188 100644 --- a/drivers/scsi/aha1542.c +++ b/drivers/scsi/aha1542.c @@ -61,15 +61,15 @@ static void BAD_DMA(void *address, unsigned int length) } static void BAD_SG_DMA(Scsi_Cmnd * SCpnt, - struct scatterlist *sgpnt, + struct scatterlist *sgp, int nseg, int badseg) { printk(KERN_CRIT sgpnt[%d:%d] page %p/0x%llx length %u\n, badseg, nseg, - page_address(sgpnt[badseg].page) + sgpnt[badseg].offset, - (unsigned long long)SCSI_SG_PA(&sgpnt[badseg]), - sgpnt[badseg].length); + page_address(sgp-,page) + sgp-,offset, + (unsigned long long)SCSI_SG_PA(sgp), + sgp-,length); /* * Not safe to continue. @@ -691,7 +691,7 @@ static int aha1542_queuecommand(Scsi_Cmnd * SCpnt, void (*done) (Scsi_Cmnd *)) ...
You are at: Home » Products » Health Projects » Environmental Rose Scented Envelope Sachet for clu In total 213268 number ofProductsinfo,Released today. 0 number of ...
Results Between ALS patients and healthy controls, there was significant difference in the expression of 30 proteins, including complement proteins and inflammatory markers. Of these, plasma Gelsolin concentration was 1.5 fold higher in healthy control in comparison with ALS patients (p=0.001). There were significant differences in 22 proteins between healthy controls and ALS patients with CI. Clusterin level was 1.2 fold upregulated in heathy people compared with patients with CI (p=0.03). Between ALS with and without CI, there was significant difference in expression of 25 proteins. CD5L concentration was significantly raised in patients without CI (p=0.013). The IPA shows that the complement pathway and coagulation pathway plays an important role in the ALS pathogenesis. ...
The goal of the present study was to determine whether treatment with cigarette smoke extract (CSE) induces cell loss, cellular senescence, and extracellular matrix (ECM) synthesis in primary human retinal pigment epithelial (RPE) cells. Primary cultured human RPE cells were exposed to 2, 4, 8, and 12% of CSE concentration for 24 hours. Cell loss was detected by cell viability assay. Lipid peroxidation was assessed by loss of cis-parinaric acid (PNA) fluorescence. Senescence-associated ß-galactosidase (SA-ß-Gal) activity was detected by histochemical staining. Expression of apolipoprotein J (Apo J), connective tissue growth factor (CTGF), fibronectin, and laminin were examined by real-time PCR, western blot, or ELISA experiments. The results showed that exposure of cells to 12% of CSE concentration induced cell death, while treatment of cells with 2, 4, and 8% CSE increased lipid peroxidation. Exposure to 8% of CSE markedly increased the number of SA-ß-Gal positive cells to up to 82%, and the mRNA
Expression of CLU (APOJ, CLI, CLU1, CLU2, KUB1, SGP-2, SP-40, TRPM-2) in vagina tissue. Antibody staining with HPA000572 and CAB016253 in immunohistochemistry.
I have an appointment with my favorite vet tomorrow to see what can be done for Tweezer. If he can still be made comfortable by anything I can do, then I will do everything I can for him. If there is nothing that can be done then it will be time to let him go with dignity. I can trust Dr. Tom to advise me correctly. Meanwhile I am a basket case. If Tweezer must crosst the bridge then a bright ray of sunshine will be leaving this world. -Original Message- From: [email protected] [mailto:[email protected]] On Behalf Of Natalie Sent: Thursday, February 03, 2011 3:50 PM To: [email protected] Subject: Re: [Felvtalk] HELP! Tweezer is sick I was giving her sub-q fluids for a while, which I assume helped her because she never had any seizures again. FIV is so much more manageable than FeLV! BTW - I sent the info to the dumb vet at the clinic so she would know for the next time someone brings in a cat that was FIV+, not to immediately make the diagnosis of ...
Demattos RB, ODell MA, Parsadanian M, Taylor JW, Harmony JA, Bales KR, Paul SM, Aronow BJ, Holtzman DM. Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimers disease ...
Demattos RB, Cirrito JR, Parsadanian M, May PC, ODell MA, Taylor JW, Harmony JA, Aronow BJ, Bales KR, Paul SM, Holtzman DM. ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo ...
A phase III ITT controlled trial of Cbz/P/C in pts with previously-treated metastatic, castration-resistant PC shown no significant survival gain
Progression Free Survival: time from date of randomization to first objective documented progression per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Tumor lesions measured in at least one dimension with minimum size of 10 mm by CT scan, 10 mm caliper by clinical exam. Malignant lymph nodes must be ,15 mm in short axis when assessed by CT scan. All measurable lesions up to a maximum of 2 lesions per organ and 5 in total representative of all involved organs should be identified as target lesions and measured and recorded ...
A study carried out with a new human stem cell-derived model reveals that the most prevalent genetic risk factor of Alzheimers disease (AD), apolipoprotein E4 (APOE4), impairs the function of human brain immune cells, microglia.
Background: Bridging integrator 1 (BIN1 ) has been identified as one of the most associated loci for Alzheimers disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro . However, the effects of BIN1 on the AD related
Protein expressions of Prx II and CLU in plasma by Western blot analysis. A: Single samples of normal and liver fibrosis. Immunoblotting with Prx II or CLU poly
Use Bio-Rads PrimePCR assays, controls, templates for your target gene. Every primer pair is optimized, experimentally validated, and performance guaranteed.
There is a strong genetic risk for late-onset Alzheimers disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ∼88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter ...
Presenter - M Wagoner, L Cheatham, D Eisinger, F Sace, K M Lynch, J McDuffie, M Sonee, K Marshall, M Damour, L Stephen, Y P Dragan, J Fikes, L B Kinter. Conference - Society of Toxicologists 2013 Annual Meeting. ...
Late-onset Alzheimers disease (AD) accounts for the majority of AD cases. A characteristic feature of AD is the accumulation of β-amyloid (Aβ) plaques in the brain. Several mutations are associated with risk for late-onset AD, particularly mutations in the genes encoding apolipoproteins APOE4 and clusterin (also known as APOJ), which alter the metabolism and impair the clearance of Aβ. Mutations in the gene encoding TREM2 (triggering receptor expressed on myeloid cells 2), a protein with a single transmembrane domain that is present in microglia in the brain, are also associated with increased risk of AD. Yeh et al. found that the three risk factors are mechanistically linked. A protein microarray screen using a library of secreted ligands immobilized on glass slides and a fusion antibody construct containing the extracellular domain of TREM2 or TREM1 identified various lipoproteins as potential selective ligands of TREM2. These included low-density lipoprotein, lipidated APOE and lapidated ...
This was a randomized study in patients with mCRPC designed to evaluate 2 second-line, custirsen-based combination regimens, DCP and MCP. On the basis of preclinical data (25), the protocol was enriched for patients who progressed while receiving or shortly after completing initial docetaxel treatment. Half of all patients progressed during initial docetaxel therapy, and the median time from the end of first-line therapy to disease progression for patients who progressed after discontinuation of first-line therapy was 3.0 months. A PSA decline of 30% or more with first-line docetaxel was not achieved in 14% of patients. At the time of study initiation, it was unknown whether such patients with docetaxel-recurrent/refractory disease could tolerate many additional cycles of chemotherapy.. The results of this study indicate that treatment with either combination was feasible and safe in the second-line setting, with a median of 8 cycles of DCP and 6 of MPC delivered. Except for fatigue and ...