Sentences with phrase «of abl»

In order to take full advantage of the ABL, you should be familiar with the NinjaTrader Super DOM.

This rules out the possibility that resistance to inhibitors results from a steric hindrance as proposed for the Thr315 mutations of ABL.13, 33 However, the crystal structures of JAK1 and JAK2 also show that Phe958 or Tyr931, respectively, are in direct contact with the CMP6 inhibitor.21 The replacement of Phe958 by Val / Cys / Ser / Leu abolishes this interaction and should decrease the affinity for this compound (Figure 2C).

Depletion of ABL kinases in breast cancer cells decreased IL - 6 concentrations and was accompanied by increased OPG expression in osteoblasts.

Mechanistically, we found that STAT5 was required for the production of the secreted factors MMP1, IL - 6, and TNC, downstream of ABL kinases.

Depletion of ABL kinases impairs tumor - induced osteoclast activation in part by decreasing IL - 6 secretion.

Depletion of ABL kinases in breast cancer cells also decreased the abundance of MMP1, a protease that cleaves fibrillar collagens and promotes the proteolytic release of bound growth factors (32).

To identify key molecular mediators of the ABL kinases implicated in the regulation of the ABL1 / ABL2 - dependent pathways, we analyzed the expression of individual genes for transcripts altered by loss of the ABL kinases.

To examine the functional role of ABL kinases in these cells, we depleted endogenous ABL kinases with previously characterized short hairpin RNAs (shRNAs) specific against ABL1 and ABL2 (20).

Conversely, overexpression of ABL kinases, predominantly ABL1, in both 1833 and parental MDA - MB - 231 breast cancer cells increased STAT5 phosphorylation (fig.

Further, inactivation of the ABL kinases resulted in decreased expression of the genes in the Hippo, Janus kinase (JAK) / STAT, and cytokine / cytokine receptor pathway signatures (Fig. 6B).

We found that inactivation of the ABL kinases in breast cancer cells also decreased STAT5A mRNA and downstream expression of STAT5 target genes, including TNC (Fig. 6D).

Together, our data suggest that clinical studies may be warranted to evaluate the therapeutic potential of ABL allosteric inhibitors and to determine whether combination therapies that incorporate these compounds are effective in treating metastatic breast cancer.

These results demonstrate that ABL kinase activity is required for osteolytic metastasis in breast cancer and suggest that pharmacological inhibition of the ABL kinases may be an effective treatment for bone metastasis.

Depletion of ABL kinases does not affect YAP1 protein abundance, localization, or tyrosine phosphorylation in breast cancer cells.

However, depletion of ABL kinases decreased the phosphorylation of STAT5 (Fig. 7D and fig.

We found that allosteric inhibition of the ABL kinases effectively impaired breast cancer bone metastasis and blocked tumor - induced osteolysis in mouse models.

Expression of a constitutively active STAT5A mutant (STAT5A *) reversed the reduction in MMP1, IL - 6, and TNC abundance induced by depletion of both ABL kinases in breast cancer cells (Fig. 7, E and F, and fig.

Thus, we evaluated whether addition of IL - 6 could in part rescue defective osteoclastogenesis induced by conditioned medium from breast cancer cells depleted of the ABL kinases.

Our data raise the possibility that inhibition of ABL kinases can increase apoptosis of breast cancer cells and block osteoclast activation, which is required for osteolytic metastasis.

Moreover, we found that treatment with a selective allosteric inhibitor of the ABL kinases or simultaneous depletion of both ABL kinases in breast cancer cells impaired breast cancer bone metastases and decreased osteoclast activation in vitro and osteolysis in vivo.

To further validate that the decreased metastasis induced by double knockdown of ABL1 and ABL2 was not due to off target effects of the lentivirus - encoded shRNAs, we used a second set of ABL shRNAs (shAA # 2) and carried out rescue experiments by expressing mouse Abl1 and Abl2 constructs (mAbl1 / Abl2) that are resistant to shRNAs against human ABL1 and ABL2.

We found that ~ 90 % knockdown of ABL1 alone resulted in enhanced ABL2 expression and did not produce a significant decrease in the phosphorylation of CrkL, a reporter for the activation state of the ABL kinases (Fig. 2K), and did not inhibit metastasis (Fig. 2, L and M).

Inactivation of ABL kinases inhibited the expression of the TAZ target gene AXL, which shows increased expression in several human cancers and correlates with poor prognosis, increased invasiveness and metastasis, and enhanced drug resistance (53, 54).

We showed that inactivation of the ABL kinases in breast cancer cells resulted in decreased expression of genes in the JAK / STAT and cytokine / cytokine receptor pathway signatures, which may be due to decreased STAT5A mRNA expression and reduced STAT5 phosphorylation in ABL1 / ABL2 - depleted breast cancer cells.

TRAIL - enhanced apoptosis as measured by cleavage of caspase - 3 (Fig. 4I), and knockdown of ABL kinases increased the sensitivity of 1833 breast cancer cells to the proapoptotic effects of TRAIL (Fig. 4, G to I).

However, these reciprocal decreases were much lower than those induced by knockdown of the ABL kinases (Fig. 7).

Depletion of ABL kinases does not inhibit metastasis of 4175 breast cancer cells, which show tropism to the lung.

To evaluate whether loss of ABL kinases affected TAZ activity, we performed chromatin immunoprecipitation (ChIP) analysis using primers for TAZ targets identified by ChIP sequencing analysis (42).

We found that depletion of the ABL kinases decreased TAZ binding to some of its target genes (fig.

To evaluate whether altered expression of the ABL genes is associated with breast cancer progression and metastasis, we examined the expression of ABL1 and ABL2 in normal and invasive breast tumor specimens using published TCGA (The Cancer Genome Atlas) data sets (14 — 16).

To evaluate whether the TAZ and STAT5 pathways promote breast cancer bone metastasis downstream of the ABL kinases, we expressed the constitutively active mutants TAZ S89A and STAT5 * in ABL1 / ABL2 knockdown cells.

In addition to inhibiting STAT5 signaling, we found that depletion of ABL kinases decreased the expression of the Hippo pathway mediator TAZ and downstream target genes in triple - negative and HER2 + breast cancer cells.

We found that depletion of ABL kinases in breast cancer cells decreased STAT5A mRNA expression (Fig. 6D) without decreasing total STAT5 protein abundance as measured by Western blotting with antibodies that detect both STAT5A and STAT5B (Fig. 7D and fig.

Previous reports have shown that in a genetic abnormality called Philadelphia chromosome, fusion of ABL and BCR genes cause leukemia.

Once deprived of Abl, the tumor cells stop reproducing and die.

According to the Chief Executive Officer of ABL, Ugo Udezue, «this is the first of its kind in the history of private sports in Africa, our goal is to provide a safe and socially conducive entertaining environment with basketball as the epicenter».

A year after she leaves Tennessee and a few months before she joins the Philadelphia Rage of the ABL, Michelle meets a 15 - year - old girl named Amanda Spengler, who plays basketball at a high school a few miles from Allentown, where Michelle grew up.

In an ABF Journal interview, three active participants share their outlook on the current state of ABL capital markets.

Regular ABF Journal contributor Lisa A. Miller spoke with five ABL leaders to get the pulse of the ABL outlook for 2015.

A new generation of appraisers has emerged to meet the growing need of ABLs to value collateral and execute on transactions, with growing access to actionable data, along with associated offerings that mitigate risk and unleash value in a constricted marketplace.

Not exact matches

Note 3: We recorded additional interest expense related to the amortization of debt issuance costs affiliated with our Term Loan Credit Agreement and ABL Facility.

ABL is one of the most flexible, option - rich financing alternatives available, letting you secure financing that includes — but goes far beyond — the value of your accounts receivable.

A skilled mortgage broker can accommodate a range of client needs by cross-selling products like factoring or ABL, unsecured lines of credit, purchase - order financing, mezzanine loans, merchant - cash advances, or short - term working - capital loans.

Businesses that are acquiring commercial real estate may have additional financing needs such as working capital, equipment needs or some form of asset - based lending (ABL).

To support acquisition by Fred's of 865 Rite Aid stores, Bank of America, Merrill Lynch and Regions Capital have provided $ 1.05 billion of committed ABL financing.

Remington will then have a new Asset Based Loan (ABL) facility of $ 193 million, the proceeds of which will refinance the existing ABL facility in full.

«The Staples acquisition of Office Depot is a good example on M&A driving ABL demand.

In addition, every issue of the ABF Journal includes timely cover stories and articles authored by industry specialists, plus our regular features encompassing briefs of the top industry related news stories, exclusive interviews with industry leaders, notable ABL transaction summaries and commentary from our team of contributing writers on turnaround management, legal topics and case studies and other relevant insights from ABL industry practitioners.

«Banks are mindful of the amount and magnitude of transactions consummated in the ABL market that are characterized as special mention credits and / or leveraged loans,» stresses Feinberg.

HERE»S WHAT YOU CAN LOOK FORWARD TO... Every issue of the ABF Journal is themed around a core ABL industry topic including: risk management, bankruptcy trends and views from the bench, insights from specialty - lending shops, annual survey and ABL roundtable, cutting - edge solutions from ABL industry service providers, a borrowers» issue focused on the challenges facing middle - market CFOs, restructuring insights from turnaround managers, plus ABF Journal's year - end conference and capital markets issue.