AXL Inhibition Enhances MEK Inhibitor Sensitivity in Malignant Peripheral Nerve Sheath Tumors.

Dysregulation of the receptor tyrosine kinase AXL is known to promote cancer cell growth and survival in many sarcomas, including the rare subtype, malignant peripheral nerve sheath tumors (MPNST). MPNSTs are largely chemoresistant and carry a poor prognosis. AXL is an attractive potential therapeutic target, as it is aberrantly expressed, and its activation may be an early event in MPNST.

Clinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma.

Importance: Vascular leiomyosarcomas are a rare subtype of leiomyosarcomas that most commonly affect the inferior vena cava and account for 5% of all leiomyosarcomas. These tumors are aggressive malignant tumors for which adjuvant modalities have not shown increased efficacy compared with surgery.

Objectives: To evaluate the outcomes of patients with vascular leiomyosarcoma and the association between vascular leiomyosarcomas and immunohistochemical molecular markers, to determine their potential prognostic and therapeutic utility.

Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic value.

Aims: Well-differentiated leiomyosarcomas show morphologically recognizable smooth muscle differentiation, whereas poorly differentiated tumours may form a spectrum with a subset of undifferentiated pleomorphic sarcomas. The expression of certain muscle markers has been reported to have prognostic impact. We investigated the correlation between the morphological spectrum and the muscle marker expression profile of leiomyosarcoma, and the impact of these factors on patient outcomes.

Localized and metastatic myxoid/round cell liposarcoma: clinical and molecular observations.

Background: Myxoid liposarcoma (MLPS), a disease especially of young adults with potential for local recurrence and metastasis, currently lacks solid prognostic factors and therapeutic targets. The authors of this report evaluated the natural history and outcome of patients with MLPS and commonly deregulated protein biomarkers.

Methods: Medical records were retrospectively reviewed for patients who presented to the authors' institution with localized (n = 207) or metastatic (n = 61) MLPS (1990 to 2010).

Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: a single institution's experience.

Background: Uterine leiomyosarcoma (ULMS) is an aggressive, rapidly progressive tumor lacking clinical and molecular predictors of outcome.

Methods: ULMS patients (n = 349) were classified by disease status at presentation to MDACC as having intra-abdominal (n = 157) or distant metastatic disease (n = 192). Patient, tumor, treatment, and outcome variables were retrospectively retrieved.

Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors.

There is a critical need for efficacious therapeutic strategies to improve the outcome of patients afflicted by malignant peripheral nerve sheath tumors (MPNST). Multiple lines of evidence suggest a role for deregulated phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an attractive target for therapeutic manipulation. On the basis of previous observations obtained from in vitro experimentation, here we aimed to assess the effects of PI3K/mTOR blockade on MPNST growth in vivo.

Dual targeting of mTOR and aurora-A kinase for the treatment of uterine Leiomyosarcoma.

Purpose: The significance of mTOR activation in uterine leiomyosarcoma (ULMS) and its potential as a therapeutic target were investigated. Furthermore, given that effective therapies likely require combination mTOR blockade with inhibition of other targets, coupled with recent observations suggesting that Aurora-A kinase (Aurk-A) deregulations commonly occur in ULMS, the preclinical impact of dually targeting both pathways was evaluated.

Experimental Design: Immunohistochemical staining was used to evaluate expression of activated mTOR components in a large (>200 samples) ULMS tissue microarray.

FAP-related desmoid tumors: a series of 44 patients evaluated in a cancer referral center.

Desmoid tumors (DTs), the commonest extra-intestinal manifestation of familial adenomatosis polyposis (FAP), are monoclonal neoplasms demonstrating fibroblastic - myofibroblastic differentiation; they are locally invasive without metastatic capacity. FAP-associated DT natural history knowledge is limited; we examined patient and tumor characteristics for a FAP-DT cohort and evaluated anti-DT therapy molecular target expression levels (immunohistochemical analyses, FAP-DT tissue microarray; TMA). Forty-four patients were classified as intra-abdominal (IA; n=26), abdominal wall (AW)/extra-abdominal (EA; n=12) or concomitant IA/AW (n=6) based on DT primary diagnosis location.

Survivin is a viable target for the treatment of malignant peripheral nerve sheath tumors.

Purpose: To examine the role of survivin as a therapeutic target in preclinical models of human malignant peripheral nerve sheath tumors (MPNST) EXPERIMENTAL DESIGN: Survivin protein expression levels and subcellular localization were examined immunohistochemically in an MPNST tissue microarray. Human MPNST cells were studied in vitro and in vivo; real-time PCR, Western blotting, and immunocytochemical analyses were used to evaluate survivin expression and localization activation. Cell culture assays were used to evaluate the impact of anti-survivin-specific siRNA inhibition on cell growth and cell-cycle progression and survival.

Increased midkine expression correlates with desmoid tumour recurrence: a potential biomarker and therapeutic target.

Desmoid tumours (DTs) are soft tissue monoclonal neoplasms exhibiting a unique phenotype, consisting of aggressive local invasiveness without metastatic capacity. While DTs can infrequently occur as part of familial adenomatosis polyposis, most cases arise sporadically. Sporadic DTs harbour a high prevalence of CTNNB1 mutations and hence increased β-catenin signalling.

Expression of 'drugable' tyrosine kinase receptors in malignant peripheral nerve sheath tumour: potential molecular therapeutic targets for a chemoresistant cancer.

Aims: Novel therapeutic approaches for the treatment of malignant peripheral nerve sheath tumors (MPNSTs) are critically needed. Tyrosine kinase receptors are commonly deregulated in cancer and constitute attractive targets. We assessed the protein expression level of a panel of ‘drugable’ TKRs in a relatively large cohort of human plexiform and MPNST surgical specimens.

Incidence and risk factors of venous thromboembolism in colorectal surgery: does laparoscopy impart an advantage?

Objectives: Laparoscopy is increasingly used in colon and rectal procedures. However, little is known regarding the incidence of venous thromboembolism (VTE) in laparoscopic colorectal (LC) compared with that in open colorectal (OC) procedures. We aimed to compare the incidences and to highlight the risk factors of developing VTE after LC and OC surgery.

Comparison of bloat potential between a variety of soft-red versus a variety of hard-red winter wheat forage.

Some aspects of wheat pasture bloat have been researched extensively, but few studies have evaluated the effect of wheat type or variety on bloat. Eight Gelbvieh x Angus ruminally cannulated heifers (515 +/- 49 kg of BW) and 48 Angus heifers (238 +/- 12 kg of BW) grazed 1-ha pastures of hard-red or soft-red winter wheat (Triticum aestivum L.) to evaluate the effect of wheat variety on bloat potential.

Animal performance and economic comparison of novel and toxic endophyte tall fescues to cool-season annuals.

Increased costs of annual establishment of small grain pasture associated with fuel, machinery, and labor are eroding the profitability of stocker cattle enterprises. Interest has therefore increased in development of cool-season perennial grasses that are persistent and high quality. This study occurred on 24 ha (divided into thirty 0.

Nutrition programs for lightweight calves.

As long as beef farms have orphaned calves and late-calving cows and as long as many small beef herds continue year-round calving,large numbers of lightweight calves are likely to be presented to the marketplace. In addition, dairies produce male calves that must be grown for beef production as well as heifers that need to be developed for milking replacements. All require specialized growing programs.

Incidence of puberty in beef heifers fed high- or low-starch diets for different periods before breeding.

Spring-born Hereford x Angus heifers (n = 206) were used to determine effects of energy supplementation programs and amount of starch in the diet on incidence of puberty. In Exp. 1, heifers (205 +/- 5 kg; n = 68) grazing dormant native pasture were fed 0.

Efficacy of intramuscular treatment of beef cows with oxytetracycline to reduce mastitis and to increase calf growth.

Spring-calving multiparous Angus x Hereford cows were used to determine the efficacy of intramuscular treatment with oxytetracycline to reduce the incidence of mastitis-causing bacteria, decrease milk somatic cell counts (SCC), and increase calf growth. During 2 yr, milk samples were collected from each quarter from a total of 319 cows at 8 to 14 d after calving and at weaning, to determine the presence of bacteria and SCC. A California mastitis test (CMT) was performed on milk from each quarter of each cow at the initial sample collection.

Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection.

The cytokine interferon (IFN)-gamma regulates immune clearance of parasitic, bacterial, and viral infections; however, the underlying mechanisms are poorly understood. Recently, a family of IFN-gamma-induced genes has been identified that encode 48-kD GTP-binding proteins that localize to the endoplasmic reticulum of cells. The prototype of this family, IGTP, has been shown to be required for host defense against acute infections with the protozoan parasite Toxoplasma gondii, but not for normal clearance of the bacterium Listeria monocytogenes and murine cytomegalovirus (MCMV).

Effects of growth rate on carcass composition and lipid partitioning at puberty and growth hormone, insulin-like growth factor I, insulin, and metabolites before puberty in beef heifers.

The effect of three rates of gain on carcass composition, lipid partitioning, age and BW at puberty, and concentrations of growth hormone (GH), IGF-I, insulin, glucose, and NEFA in plasma were evaluated in 38 Angus x Hereford heifers. Heifers were allotted by BW and age to three treatments with a replication in each of 2 yr: full-fed (n = 13; FF) to gain 1.36 kg/d; limit-fed (n = 12; LF) to gain .

Effects of feeding energy or protein supplements before or after calving on performance of spring-calving cows grazing native range.

In three consecutive years, spring-calving Hereford and Hereford x Angus cows (n = 348) were used to determine effects of level of supplemental energy or protein before and after calving on cowherd performance. Beginning on November 1, cows were individually fed 1.22 kg/d of a 40% CP (PROTEIN) or 2.

Effects of energy or protein supplements and stage of production on intake and digestibility of hay by beef cows.

In two consecutive years, primi- and multiparous, spring-calving Hereford and Hereford x Angus cows (n = 32, yr 1; n = 42, yr 2) were used to determine the effects of supplements and lactational status on forage intake, digestibility, and energy intake. Cows were randomly alloted to treatments after being blocked by age, breed, and weight. Supplements fed during gestation provided .

Effects of postweaning diet on age and weight at puberty and mild production of heifers.

One hundred 7-mo-old spring-born beef heifers (215 kg) were used to evaluate effects of level of supplementation and short-term concentrate feeding on age and weight at puberty and milk production. In each of two winters, heifers were individually fed .9 kg/d of a 40% CP supplement (SBM) or 1.

GnRH in the infundibular stalk-median eminence is related to percentage body fat in carcasses of beef cows.

Mature Hereford cows (n = 28) were used to determine the effect of percentage body fat on secretion of LH and content of GnRH in the infundibular stalk-median eminence (ISME). Cows were fed to maintain, lose, or gain weight to achieve body condition scores (BCS; 1 = emaciated; 9 = obese) of 3 to 7. Then cows were fed to maintain weight and body condition.

Effects of lactational status on forage intake, digestibility, and particulate passage rate of beef cows supplemented with soybean meal, wheat middlings, and corn and soybean meal.

Sixteen mature, lactating (453 kg) and 16 nonlactating (487 kg) Hereford and Angus x Hereford cows were used to determine effects of different dietary supplements and lactational status on forage intake, digestibility, and particulate passage rate. Supplement treatments and amounts fed (kg/d) were as follows: control, 0; and equal daily amounts of CP from soybean meal (SBM), 1.36; wheat middlings (WM), 3.