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Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs.

Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While antimicrotubule drugs are well-established, antiactin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other antitropomyosin analogues for anticancer and on-target activity using a series of cell-based and biochemical assays. ATM-3507 was selected as the new lead based on its ability to disable Tpm3.1-containing filaments, its cytotoxicity potency, and more favorable drug-like characteristics. We tested ATM-3507 and TR100 alone and in combination with antimicrotubule agents against neuroblastoma models and Both ATM-3507 and TR100 showed a high degree of synergy with vinca alkaloid and taxane antimicrotubule agents. , combination-treated animals bearing human neuroblastoma xenografts treated with antitropomyosin combined with vincristine showed minimal weight loss, a significant and profound regression of tumor growth and improved survival compared with control and either drug alone. Antitropomyosin combined with vincristine resulted in G-M phase arrest, disruption of mitotic spindle formation, and cellular apoptosis. Our data suggest that small molecules targeting the actin cytoskeleton via tropomyosin sensitize cancer cells to antimicrotubule agents and are tolerated together This combination warrants further study. .

1482 related Products with: Identification of Cancer-Targeted Tropomyosin Inhibitors and Their Synergy with Microtubule Drugs.

Cat bladder cancer associ Recombinant Human Androge GI cancer (esophageal, ga Stomach cancer tissue arr Multiple Kidney cancer ti Breast cancer test tissue Ovary cancer tissue array Lung cancer and normal ti Thyroid cancer and adenom Breast cancer tissue micr Multiple cancer tissue ar Androsta-1,4,6-triene-3,1

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Anti-actin IgA antibodies identify celiac disease patients with a Marsh 3 intestinal damage among subjects with moderate anti-TG2 levels.

A new diagnostic tool (algorithm-1) for coeliac disease (CD) permitting the diagnosis without performing the duodenal biopsy has been recently proposed by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). It combines symptoms associated with CD, high anti-transglutaminase type 2 antibody (anti-TG2) levels, anti-endomysium-IgA antibodies (EMA), and at-risk HLA. Our aims were (i) to evaluate retrospectively in 227 individuals (149 CD patients and 78 controls) the algorithm-1, (ii) to reduce the number of duodenal biopsies among CD patients for whom algorithm-1 is not applicable through the addition of antiactin IgA antibodies (AAA-IgA), and (iii) to evaluate prospectively algorithm-1 and AAA-IgA in 50 patients with suspected CD. Algorithm-1 identified 70 out of 149 CD patients with Marsh 3 lesions. Adding AAA-IgA to the remaining patients with anti-TG2 levels comprised between 4 and 10 times upper limit of normal (ULN) allowed the detection of further 20 patients with a Marsh 3 damage. In our prospective study, algorithm-1 identified 23 out of 50 patients, whilst further 7 were recognized adding AAA-IgA. We confirm that algorithm-1 may avoid the duodenal biopsy in many CD patients and underscores the usefulness of AAA-IgA in reducing the number of duodenal biopsies in patients with moderate anti-TG2 levels.

1616 related Products with: Anti-actin IgA antibodies identify celiac disease patients with a Marsh 3 intestinal damage among subjects with moderate anti-TG2 levels.

Mouse Anti-M. tuberculosi Mouse Anti-Marek Disease Rabbit Anti-B. burgdorfer Mouse Anti-Human IgA1 [+H Rabbit Anti-Human Actin ( FDA normal and tumor orga Mouse Anti-Human IgA1 Ant Mouse Anti-Human Actin (S Mouse Anti-Human IgA2 [+H Mouse Anti-HHV-6 37kDa EA Goat Anti-Rat Actin-like Mouse Anti-RSV 33kDa & 19

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Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001).

1362 related Products with: Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

Rabbit Anti-Rat Androgen Goat Anti-Human Androgen Rabbit Anti-Human Androge 3β-O-Acetyl-androsta-5,1 Androgen Receptor (Ab 650 5α-Androstan-3β-ol � Rabbit Anti-Actin (Muscle Anti Androgen Receptor pr Androstane 3a, 17b diol 5 19 Hydroxy 4 androstene 3 Hepatitis C Virus antibod Androgen Receptor (Phosph

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Exacerbation of AIH in a patient with an AIH/systemic sclerosis overlap syndrome and pulmonary arterial hypertension treated with the endothelin-1 receptor antagonist sitaxentan.

Increase of liver enzymes during therapy with endothelin receptor antagonist (ERA) because of pulmonary arterial hypertension (PAH) has been observed quite frequently the cause of which is unknown. Here we describe a female patient who suffered from autoimmune hepatitis (AIH) type I [positive for antinuclear (ANA) and antiactin antibodies] who developed systemic sclerosis (SSc) with PAH. AIH was treated with corticosteroids and azathioprine, and PAH with the ERA sitaxentan. Reactivation of AIH was observed in the course of therapy with sitaxentan as shown by an increase of liver enzymes, immunoglobulin G globulins, the reappearance of antinuclear and antiactin antibodies and the induction of a further AIH marker antibody reacting with the soluble liver/liver pancreas antigen. Therapy with ERA for pulmonary hypertension may increase the risk for development or exacerbation of AIH.

2119 related Products with: Exacerbation of AIH in a patient with an AIH/systemic sclerosis overlap syndrome and pulmonary arterial hypertension treated with the endothelin-1 receptor antagonist sitaxentan.

Anti-Androgen Receptor pr Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Androgen Receptor Polyclonal Antibody Recep Rabbit Anti-Insulin Recep Rabbit Anti-Insulin Recep Androgen Receptor (Ab-650 Rabbit Anti-Insulin Recep

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MyTH4, independent of its companion FERM domain, affects the organization of an intramacronuclear microtubule array and is involved in elongation of the macronucleus in Tetrahymena thermophila.

Myo1 is a class XIV Tetrahymena myosin involved in amitotic elongation and constriction of the macronucleus into two subnuclei at cell division. Elongation of the macronucleus is accompanied by elongation of an intramacronuclear microtubule array, which is oriented parallel to the axis of nuclear elongation. Elongation of the macronucleus often fails to occur or is only partially completed in a MYO1 knockout, and division of the macronucleus is frequently uncoupled from cytokinesis. Myo1 contains a myosin tail homology 4 (MyTH4) and a band 4.1, ezrin, radixin, moesin homology (FERM) domain. Recently, we used green fluorescent protein (GFP) fusions to demonstrate that the entire FERM domain, independent of MyTH4, is essential for localization of FERM to the cytoskeleton and does not appear to directly affect nuclear division. Antiactin coprecipitates GFP-FERM, tubulin, actin, and Myo1. The immunoprecipitated GFP-FERM cosediments with either exogenous F-actin or exogenous microtubules. Here, we show that overexpressed GFP-MyTH4 colocalized with antitubulin to intramacronuclear microtubules. Ninety percent of overexpressing cells assembled intramacronuclear microtubules that did not become organized into a parallel array. Amitosis did not advance in the absence of the parallel array of intramacronuclear microtubules. Five percent of overexpressing cells organized the parallel array, but the microtubules and the macronucleus did not achieve full elongation. Partially elongated macronuclei constricted without cytokinesis. Antiactin coprecipitated GFP-MyTH4, tubulin, and actin. AntiGFP pulled down GFP-MyTH4, tubulin, and actin. GFP-MyTH4 cosedimented with either exogenous microtubules or exogenous F-actin. A novel finding from this study is that MyTH4 and FERM have overlapping and distinct roles in the function of a myosin.

2515 related Products with: MyTH4, independent of its companion FERM domain, affects the organization of an intramacronuclear microtubule array and is involved in elongation of the macronucleus in Tetrahymena thermophila.

FDA Standard Frozen Tissu FDA Standard Frozen Tissu Multiple organ tumor tiss FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Rabbit Anti-Integrin β2 Cervix carcinoma for anti Mouse Anti-Insulin(1G11) Endocrine cancer tissue a CREB Phospho-Specific Arr

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Identification of C-kit-positive interstitial cells in the dog lower urinary tract and relationship with smooth muscle and nerves. Hypotheses for a likely pacemaker role.

The aim of this work was to give an evidence of the likely presence of interstitial cells in the canine lower urinary tract and to study their possible interactions with the musculature and the intramural innervation. Cryosections of normal canine bladder and urethra were immunofluorescently labelled with c-kit, a transmembrane, tyrosine kinase growth factor receptor, known to be expressed on the interstitial cells of Cajal (ICCs) of the gut. The relationship with antiactin positive smooth muscle cells and PGP9.5-positive intramural innervation was also investigated by confocal microscopy. Anti-c-kit labelling demonstrated a network of elongated and branched c-kit positive cells, which were located in interstitial spaces, oriented in parallel to the smooth muscle bundles that form the bladder muscular layer, irrespective of dog sex. Cells with a similar localization were also PAS- and NADPH-diaphorase-positive. A contact between c-kit immunofluorescent cells and intramural innervation was demonstrated, too. The roles of interstitial cells might include regulation of smooth muscle activity of the bladder detrusor, integrating neuronal signals during urine storage and voiding.

1140 related Products with: Identification of C-kit-positive interstitial cells in the dog lower urinary tract and relationship with smooth muscle and nerves. Hypotheses for a likely pacemaker role.

Interstitialoma of gastro Anti bodywall muscle cell GLP 1 ELISA Kit, Rat Gluc Goat Anti-Human Androgen Actin, Smooth Muscle Ab 1 (5α,16β)-N-Acetyl-16-ac Androgen Receptor Androst-4-ene-3,17-dion-1 FDA Standard Frozen Tissu Androstadienone C19H26O C Epidermal Growth Factor ( Androstane-3a, 17b-diol 5

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Dynamics of celiac disease-specific serology after initiation of a gluten-free diet and use in the assessment of compliance with treatment.

The usefulness of celiac disease-related serology in monitoring patients on a gluten-free diet has been debated.

1314 related Products with: Dynamics of celiac disease-specific serology after initiation of a gluten-free diet and use in the assessment of compliance with treatment.

Multiple organ tumor tiss Cervical intraepithelial Jak Stat II Phospho-Speci Rat Visceral adipose spec Brain-Specific Angiogenes T-Cell Receptor Signaling Beta Amyloid (1 40) ELISA Cytokine (Human) Antibody Cytokine (Mouse) Antibody Th1 Th2 Th17 (Human) Anti Cytokine (Human) Antibody Apoptosis antibody array

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Protein profile of capacitated versus ejaculated human sperm.

Freshly ejaculated sperm acquire the fertilizing potential by a continuing process that occurs during sperm transport through the female genital tract, and it is physiologically not complete until the spermatozoon reaches the oocyte. The process termed capacitation can be mimicked in vitro by using appropriate capacitation media. Despite its importance, the molecular mechanisms underlying capacitation are poorly understood. This work deals with a proteomic approach to the analysis of protein profile variations in human normospermic samples as a consequence of three hours in vitro capacitation. 2DE gels were produced per freshly ejaculated sperm and per capacitated sperm and several quantitative and qualitative significant variations were found. Among the MS obtained identifications, proteins with a significant decrease after capacitation were found to be involved in protein fate, metabolism, and flagellar organization; on the contrary, increasing proteins were found to be related to cellular stress. Interestingly, the detected flagellar organization proteins decreased during capacitation whereas their corresponding fragments increased. A swim-up selected and three-hour capacitated sperm subpopulation has also been resolved by 2DE, and its synthetic gel has been analyzed for the variations observed in the entire sperm population. An immunofluorescence analysis of this sperm typology was carried out with antiactin and antitubulin antibodies.

1047 related Products with: Protein profile of capacitated versus ejaculated human sperm.

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Positive association of anticytoskeletal endothelial cell antibodies and cardiac allograft rejection.

Using an indirect immunofluorescence method on human umbilical vein endothelial cells (HUVEC), we investigated the presence of antiendothelial cell antibodies (AECA) in 136 pre- and posttransplant serum samples sequentially collected from 31 patients during the first year after cardiac transplantation. A healthy control group was also included (n = 87). Colocalization studies demonstrated a positive staining pattern of different cytoskeletal components (cytoskeletal-antiendothelial cell antibodies, CSK-AECA) including antivimentin, antiactin, antitubulin, and anticytokeratin among heart transplanted patients. Frequency of CSK-AECA in the control group and at day 0 in the transplant group was 18.3 and 22.5%, respectively (p = NS). A progressive increase in the frequency of CSK-AECA was observed after cardiac transplantation: 13.3% at day 15; 22.2% at day 30; 53.8% at day 90, and 58% at day 360. Interestingly, rejection episodes within the first year after transplantation occurred in 83.3% of CSK-AECA-positive and in 30.7% of CSK-AECA-negative patients (p = 0.0045). The presence of antibodies was detected prior to the rejection event and was associated with a poor clinical outcome: rejection episodes occurred at a mean of 36.14 +/- 17 days after transplantation in patients with preexisting AECA and 174.25 +/- 51.9 days after de novo antibody appearance in patients with no antibodies at day 0 (p = 0.029). In conclusion, a progressive increase in the frequency of CSK-AECA was observed following cardiac transplantation; the presence of these antibodies is strongly associated and precedes the rejection episodes. Thus, CSK-AECA could be a good marker for acute graft rejection.

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Mouse Anti-Human Endothel Rat anti mouse Pan Endoth Human Cardiac Microvascul Mouse Anti-Human Endothel Mouse Anti-Pig Endothelia Rat Anti-Human Endothelia Human Saphenous Vein Endo Monoclonal Mouse Anti Hum Cultrex In Vitro Angiogen Mouse Anti-Human CD94 (Na Rat monoclonal anti mouse Mouse Anti-Human CD40 (CD

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Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background.

Concurrent autoimmune disorders (CAIDs) have been shown to occur in 22% to 34% of the patients with autoimmune hepatitis (AIH). Their presence has been linked to female gender, older age, and to certain HLA antigens, namely HLA-A11, DRB1*04, and DRB4*01.

2337 related Products with: Frequency of concurrent autoimmune disorders in patients with autoimmune hepatitis: effect of age, gender, and genetic background.

Anti-SSA (Ro-52) ELISA Ki Syringe pump can be contr Human Positive Control Se Ofloxacin CAS Number [824 Cytokine (Human) Antibody GSK3B & FOXO1 Protein Pro Prostate cancer tissue ar Recombinant Human Interfe Indole 5 carboxaldehyde ( Interleukins Recombinant Liver cancer and normal t Goat Anti-Human MEPI SERP

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