Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.

MLL/KMT2A amplifications and translocations are prevalent in infant, adult, and therapy-induced leukemia. However, the molecular contributor(s) to these alterations are unclear. Here, we demonstrate that histone H3 lysine 9 mono- and di-methylation (H3K9me1/2) balance at the MLL/KMT2A locus regulates these amplifications and rearrangements.

Statins repress hedgehog signaling in medulloblastoma with no bone toxicities.

The Hedgehog (Hh) pathway plays an indispensable role in bone development and genetic activation of the pathway results in medulloblastoma (MB), the most common malignant brain tumor in children. Inhibitors of Hh pathway (such as vismodegib and sonedigib), which are used to treat MB, cause irreversible defects in bone growth in young children. Cholesterol is required for the activation of the Hh pathway, and statins, inhibitors of cholesterol biosynthesis, suppress MB growth by repressing Hh signaling in tumor cells.

Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro.

Influence of the length and positioning of the antiestrogenic side chain of endoxifen and 4-hydroxytamoxifen on gene activation and growth of estrogen receptor positive cancer cells.

Tamoxifen has biologically active metabolites: 4-hydroxytamoxifen (4OHT) and endoxifen. The E-isomers are not stable in solution as Z-isomerization occurs. We have synthesized fixed ring (FR) analogues of 4OHT and endoxifen as well as FR E and Z isomers with methoxy and ethoxy side chains.

Cerebral cavernous malformations arise independent of the heart of glass receptor.

Background And Purpose: The Heart of Glass (HEG) receptor binds KRIT1 and functions with KRIT1, CCM2, and PDCD10 in a common signaling pathway required for heart and vascular development. Mutations in KRIT1, CCM2, and PDCD10 also underlie human cerebral cavernous malformation (CCM) and postnatal loss of these genes in the mouse endothelium results in rapid CCM formation. Here, we test the role of HEG in CCM formation in mice and in humans.

The effect of 5-aminolevulinic acid and its derivatives on protoporphyrin IX accumulation and apoptotic cell death in castrate-resistant prostate cancer cells.

Objective: To examine whether pharmacologically relevant zinc-binding agents are capable of depleting X-linked inhibitor of apoptosis protein in tumor cells. Our prior work reveals that treatment with zinc-chelating agents induces selective downregulation of the X-linked inhibitor of apoptosis protein in cancer cells of various origins. A precursor of the heme synthetic pathway, 5-aminolevulinic acid, is metabolized to protoporphyrin IX, which is highly reactive with zinc.

Chemical genetic screening for compounds that preferentially inhibit growth of methylthioadenosine phosphorylase (MTAP)-deficient Saccharomyces cerevisiae.

Methylthioadenosine phosphorylase (MTAP), a key enzyme in the methionine salvage pathway, is inactivated in a variety of human cancers. Since all human tissues express MTAP, it would be of potential interest to identify compounds that selectively inhibit the growth of MTAP-deficient cells. To determine if MTAP inactivation could be targeted, the authors have performed a differential chemical genetic screen in isogenic MTAP(+) and MTAP(-) Saccharomyces cerevisiae.

Mechanisms of systemic adaptation to univentricular Fontan conversion.

Objective: After univentricular Fontan conversion, systemic venous pressure serves as the sole driving force for transpulmonary blood flow. Consequently, systemic venous return is markedly altered and ventricular filling is subnormal. The mechanisms and time course of systemic adaptation to Fontan conversion are incompletely understood.

Structure-function relationships of estrogenic triphenylethylenes related to endoxifen and 4-hydroxytamoxifen.

Estrogens can potentially be classified into planar (class I) or nonplanar (class II) categories, which might have biological consequences. 1,1,2-Triphenylethylene (TPE) derivatives were synthesized and evaluated against 17beta-estradiol (E2) for their estrogenic activity in MCF-7 human breast cancer cells. All TPEs were estrogenic and, unlike 4-hydroxytamoxifen (4OHTAM) and Endoxifen, induced cell growth to a level comparable to that of E2.

Parent-Child Pain Relationships from a Psychosocial Perspective: A Review of the Literature.

Chronic or recurrent pain is a widespread health issue that affects a large proportion of the population, including adults and children. Family factors in the development of pain have received increasing attention of late as research has shown that pain tends to run in families, A burgeoning literature has also demonstrated the influence of parental factors in children's responses to chronic and laboratory pain. This review attempts to integrate: first,) the literature documenting an association between parent and child pain both within the clinical chronic pain and laboratory pain literatures; and second,) research accounting for likely mechanisms explaining the parent-child pain association.

Anxiety sensitivity and catastrophizing: associations with pain and somatization in non-clinical children.

This study examined the relationships among anxiety sensitivity (AS), catastrophizing, somatization and pain in 240 non-clinical children (121 girls; mean age = 12.7 years). Children with pain problems (n = 81; 33.

Sex differences in the relationship between maternal negative life events and children's laboratory pain responsivity.

Objectives: Previous research has demonstrated links between psychosocial factors, including negative life events (NLE) and pain in children. This study examined sex differences in the relationship among mother-reported NLE, child NLE, mother somatization, and children's laboratory pain responses for heat, cold, and pressure pain tasks. We predicted that maternal NLE would be moderately associated with girls' pain responses but would not be associated with boys' pain responses.

Performance of a 3-bladed propeller pump to provide cavopulmonary assist in the failing Fontan circulation.

Purpose: We hypothesized that a propeller pump design would function optimally to provide cavopulmonary assist in a univentricular Fontan circulation.

Description: The hydraulic and hemolysis performance of a rigid three-bladed propeller prototype (similar to a folding propeller design) was characterized. Pressure and flow measurements were taken for flow rates of 0.

The value of massage therapy in cancer care.

Massage therapy is increasingly available as a supportive therapy to patients in medical centers providing cancer treatment. This article provides an overview of the evidence base relevant to the use of massage with the intended goal of alleviating symptoms and side effects experienced by cancer patients. Collectively, the available data support the view that massage, modified appropriately, offers potential beneficial effects for cancer patients in terms of reducing anxiety and pain and other symptoms.

Familial and perceived risk of breast cancer in relation to use of complementary medicine.

Aim: To examine the use of complementary and alternative medicine (CAM) by women with varying levels of familial and perceived risk of breast cancer with the goal of preventing breast cancer.

Methods: Cross-sectional data on CAM use were collected on 2,198 women (mean age, 63 years) personally unaffected by breast cancer in the Minnesota Breast Cancer Family Study. CAM use was compared across women at high, moderate, or average risk based on family history, as well as across categories of perceived risk of breast cancer.

An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase.

Autoregulatory domains found within kinases may provide more unique targets for chemical inhibitors than the conserved ATP-binding pocket targeted by most inhibitors. The kinase Pak1 contains an autoinhibitory domain that suppresses the catalytic activity of its kinase domain. Pak1 activators relieve this autoinhibition and initiate conformational rearrangements and autophosphorylation events leading to kinase activation.

Massage modalities and symptoms reported by cancer patients: narrative review.

The results of several studies on the use of massage therapies for cancer patients have been published in the peer-reviewed literature over the past 20 years. The current article provides a summary and critique of published studies in which patient-reported symptom ratings were assessed in relation to massage. Twenty-two studies are discussed.

Mechanical cavopulmonary assist for the univentricular Fontan circulation using a novel folding propeller blood pump.

A blood pump specifically designed to operate in the unique anatomic and physiologic conditions of a cavopulmonary connection has never been developed. Mechanical augmentation of cavopulmonary blood flow in a univentricular circulation would reduce systemic venous pressure, increase preload to the single ventricle, and temporarily reproduce a scenario analogous to the normal two-ventricle circulation. We hypothesize that a folding propeller blood pump would function optimally in this cavopulmonary circulation.

Research on therapeutic massage for cancer patients: potential biologic mechanisms.

There is preliminary evidence that therapeutic massage is a useful modality for the relief of a variety of symptoms and symptom-related distress affecting cancer patients. Mechanistic studies are necessary to delineate underlying biologic and psychological effects of massage and their relationship to outcomes. The current article discusses a model for using nuclear magnetic resonance techniques to capture dynamic in vivo responses to biomechanical changes induced in the soft tissues by massage.

Self-care behaviors associated with myofascial temporomandibular disorder pain.

Aims: To document the frequency of self-care in a clinical sample of patients with myofascial temporomandibular disorder (TMD) pain; report the perceived relief and control of pain for each of the self-care behaviors; and to test for associations between the frequency and efficacy of each self-care behavior and pain, depression and sleep quality, as assessed during a clinical visit, and to determine whether the frequency was associated with changes in pain intensity, depression, and sleep quality 30 days later.

Methods: The sample consisted of 99 female and 27 male myofascial TMD pain patients who were participants in a multidisciplinary facial pain evaluation program. The subjects participated in a structured interview during a clinical visit and a follow-up telephone interview 30 days later.

Coping predictors of children's laboratory-induced pain tolerance, intensity, and unpleasantness.

Unlabelled: This study examined coping predictors of laboratory-induced pain tolerance, intensity, and unpleasantness among 244 healthy children and adolescents (50.8% female; mean age, 12.73 +/- 2.

Complementary and alternative therapy use in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

Background: Little information is available on the use of complementary and alternative medicine (CAM) in long-term survivors of childhood and adolescent cancer.

Procedure: The Childhood Cancer Survivor Study (CCSS) is a resource evaluating the long-term effects of cancer and associated therapies in 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986 before the age of 21 years. A survey of CAM use during the previous year was distributed in 2000-2001 and completed by 9,984 survivors and 2,474 sibling controls.

Conservative management of mechanical neck disorders: a systematic review.

Objective: To determine if conservative treatments (manual therapies, physical medicine methods, medication, and patient education) relieved pain or improved function/disability, patient satisfaction, and global perceived effect in adults with acute, subacute, and chronic mechanical neck disorders (MND) by updating 11 systematic reviews of randomized controlled trials (RCT).

Methods: Two independent authors selected studies, abstracted data, and assessed methodological quality from computerized databases. We calculated relative risks and standardized mean differences (SMD) when possible.

Massage for mechanical neck disorders: a systematic review.

Study Design: Systematic review.

Objective: To assess the effects of massage on pain, function, patient satisfaction, cost of care, and adverse events in adults with neck pain.

Summary Of Background Data: Neck pain is common, disabling, and costly.