SKA1 promotes oncogenic properties in oral dysplasia and oral squamous cell carcinoma, and augments resistance to radiotherapy.

Oral squamous cell carcinoma (OSCC) is a malignancy associated with high morbidity and mortality, yet treatment options are limited. In addition to genetic alterations, aberrant gene expression contributes to the pathology of malignant diseases. In the present study, we identified 629 genes consistently dysregulated between OSCC and normal oral mucosa across nine public gene expression datasets.

Pharmacological Inhibition of Lipid Import and Transport Proteins in Ovarian Cancer.

Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5-year survival rate of 49%. This is caused by late diagnosis when cells have already metastasized into the peritoneal cavity and to the omentum. OC progression is dependent on the availability of high-energy lipids/fatty acids (FA) provided by endogenous de novo biosynthesis and/or through import from the microenvironment.

The Pharmacological or Genetic Blockade of Endogenous Fatty Acid Synthesis Does Not Increase the Uptake of Exogenous Lipids in Ovarian Cancer Cells.

Ovarian cancer(OC) is a serious threat to women worldwide. Peritoneal dissemination, ascites and omental metastasis are typical features for disease progression, which occurs in a micro-environment that is rich in high-energy lipids. OC cells require high amounts of lipids for survival and growth.

Membrane disruption, but not metabolic rewiring, is the key mechanism of anticancer-action of FASN-inhibitors: a multi-omics analysis in ovarian cancer.

Fatty-acid(FA)-synthase(FASN) is a druggable lipogenic oncoprotein whose blockade causes metabolic disruption. Whether drug-induced metabolic perturbation is essential for anticancer drug-action, or is just a secondary-maybe even a defence response-is still unclear. To address this, SKOV3 and OVCAR3 ovarian cancer(OC) cell lines with clear cell and serous histology, two main OC subtypes, were exposed to FASN-inhibitor G28UCM.

Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells.

Receptor-PI3K-mTORC1 signaling and fatty acid synthase (FASN)-regulated lipid biosynthesis harbor numerous drug targets and are molecularly connected. We hypothesize that unraveling the mechanisms of pathway cross-talk will be useful for designing novel co-targeting strategies for ovarian cancer (OC). The impact of receptor-PI3K-mTORC1 onto FASN is already well-characterized.

HER Specific TKIs Exert Their Antineoplastic Effects on Breast Cancer Cell Lines through the Involvement of STAT5 and JNK.

Background: HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood.

Methods: Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines.

Prominin-1 (CD133, AC133) and dipeptidyl-peptidase IV (CD26) are indicators of infinitive growth in colon cancer cells.

Advanced colorectal cancer is characterized by uncontrolled growth and resistance against anti-cancer agents, including ErbB inhibitors. Recent data suggest that cancer stem cells (CSC) are particularly resistant. These cells may reside within a CD133+ fraction of the malignant cells.

Fatty acid synthase is a metabolic marker of cell proliferation rather than malignancy in ovarian cancer and its precursor cells.

Ovarian cancer (OC) is caused by genetic aberrations in networks that control growth and survival. Importantly, aberrant cancer metabolism interacts with oncogenic signaling providing additional drug targets. Tumors overexpress the lipogenic enzyme fatty acid synthase (FASN) and are inhibited by FASN blockers, whereas normal cells are FASN-negative and FASN-inhibitor-resistant.

Blockade of fatty acid synthase induces ubiquitination and degradation of phosphoinositide-3-kinase signaling proteins in ovarian cancer.

Aberrations within the phosphoinositide-3-kinase (PI3K) pathway occur in greater than 45% of ovarian carcinomas. The PI3K cascade transmits signals from ErbB receptors downstream to S6 and 4EBP1, which are involved in protein biosynthesis. Many ovarian carcinomas reveal hyperactivation of ErbB1 (epidermal growth factor receptor) or ErbB2 (HER2/neu).

Brief report--associations of personality disorder with early separation anxiety in patients with adult separation anxiety disorder.

A recent study has suggested a link between early separation anxiety and personality disorder. It is possible that this relationship is mediated or confounded by the presence of adult separation anxiety disorder (ASAD). In a clinic study of 397 anxiety patients, we found that ASAD patients with heightened early separation anxiety had higher rates of any Cluster C personality disorder compared to ASAD patients without elevated early separation anxiety, and higher rates of any Cluster B or C personality disorder compared to anxiety patients with low early separation anxiety and no ASAD.

The PI3 kinase/mTOR blocker NVP-BEZ235 overrides resistance against irreversible ErbB inhibitors in breast cancer cells.

Resistance against first and second generation (irreversible) ErbB inhibitors is an unsolved problem in clinical oncology. The purpose of this study was to examine the effects of the irreversible ErbB inhibitors pelitinib and canertinib on growth of breast and ovarian cancer cells. Although in vitro growth-inhibitory effects of both drugs exceeded by far the effects of all reversible ErbB blockers tested (lapatinib, erlotinib, and gefitinib), complete growth inhibition was usually not reached.

The prevalence and correlates of adult separation anxiety disorder in an anxiety clinic.

Background: Adult separation anxiety disorder (ASAD) has been identified recently, but there is a paucity of data about its prevalence and associated characteristics amongst anxiety patients. This study assessed the prevalence and risk factor profile associated with ASAD in an anxiety clinic.

Methods: Clinical psychologists assigned 520 consecutive patients to DSM-IV adult anxiety subcategories using the SCID.

Interaction between fatty acid synthase- and ErbB-systems in ovarian cancer cells.

Fatty acid synthase (FASN) represents a metabolic oncogene. It produces phospholipids for membrane microdomains that accommodate receptor tyrosine kinases including Epidermal Growth Factor-Receptor (EGFR, ErbB1) and ErbB2 (HER2/neu). FASN and ErbBs are overexpressed in ovarian cancer.

Adult attachment styles in panic disorder with and without comorbid adult separation anxiety disorder.

Objective: Attachment theory suggests that anxious attachment styles are associated with risk to psychiatric disorder, especially anxiety disorders. Separation anxiety would appear to be a core form of anxiety that is associated with anxious attachment. Nevertheless, as yet no research has examined the relationship of attachment styles to adult separation anxiety disorder, a condition that has only recently been fully recognized.

Process evaluation in an intervention designed to promote physical activity among adults with anxiety disorders: evidence of acceptability and adherence.

Issue Addressed: To assess the adherence and acceptability of a physical activity program delivered as an adjunct to the usual cognitive behavioural group therapy (CBGT) for adults with anxiety disorders.

Methods: Seventy-three participants with either a generalised anxiety disorder, social phobia or panic disorder were randomised to either exercise-enhanced CBGT (CBGT+EX) or the usual CBGT plus nutrition education (CBGT+ED) group. Physical activity, stress, anxiety, depression were assessed at baseline; session attendance, compliance and satisfaction were assessed during the eight-week intervention.

Promoting walking as an adjunct intervention to group cognitive behavioral therapy for anxiety disorders--a pilot group randomized trial.

A group randomized trial of adding a home-based walking program to a standard group cognitive behavioral therapy (GCBT+EX) was compared with groups receiving GCBT and educational sessions (GCBT+ED). The study was implemented in an outpatient clinic providing GCBT for clients diagnosed with panic disorder, generalized anxiety disorder or social phobia. Pre- and post-treatment measures included the self-report depression, anxiety, and stress scale (DASS-21) and measures of physical activity.

Separation anxiety in adulthood: dimensional or categorical?

Recent evidence suggests that a clinical form of separation anxiety can be observed in adults. An important question of relevance to defining the construct of adult separation anxiety is whether there is discontinuity between that constellation and other forms of anxiety. In the present study, 2 taxometric procedures - Mean Above Minus Below a Cut and Maximum Eigenvalue - were used to assess whether adult separation anxiety conformed primarily to a categorical or a dimensional pattern.

The DNA-binding epidermal growth factor-receptor inhibitor PD153035 and other DNA-intercalating cytotoxic drugs reactivate the expression of the retinoic acid receptor-beta tumor-suppressor gene in breast cancer cells.

We have previously shown that the epidermal growth factor-receptor (EGFR) tyrosine kinase inhibitor PD153035 induces retinoic acid receptor-beta (RAR-beta) expression in malignant cells by mechanisms that are independent of its blocking activity on EGFR (ErbB1) or on any other ErbB receptor (ErbB2, ErbB3, ErbB4). RAR-beta2, one of three human RAR-beta isoforms (RAR-beta1, RAR-beta2, RAR-beta4), is silenced in many tumors and acts as a tumor suppressor. Forced expression of RAR-beta2 reverts the malignant phenotype of RAR-beta2-negative breast cancer cells and reconstitutes retinoid sensitivity in these cells.

Upregulation of retinoic acid receptor-beta by the epidermal growth factor-receptor inhibitor PD153035 is not mediated by blockade of ErbB pathways.

Inhibiting epidermal growth factor-receptor (ErbB-1) represents a powerful anticancer strategy. Activation of retinoid pathways is also in development for cancer treatment. Retinoic acid receptor-beta-the tumor suppressor and main retinoid mediator--is silenced in many tumors.

Characteristics of Vietnamese patients attending an anxiety clinic in Australia and perceptions of the wider Vietnamese community about anxiety.

This article examined the causes underlying low utilization of mental health services by Vietnamese immigrants in Australia. Study 1 examined cases of Vietnamese patients who had attended an anxiety disorders clinic, while Study 2 surveyed Vietnamese people in the community on their knowledge and attitudes towards common mental problems. Results from Study 1 showed that Vietnamese patients had significantly higher attrition rates, and presented with a larger number of nonanxiety disorders than their Australian-born counterparts.

Delays in referral of patients with social phobia, panic disorder and generalized anxiety disorder attending a specialist anxiety clinic.

Individuals with anxiety disorders experience substantial delays in obtaining treatment, but little is known about whether people with specific anxiety subcategories are differentially affected. The present study used a modified Encounter Form to examine the cause and length of delays in reaching primary care and specialist services amongst patients with panic disorder (PD/PD-Ag), social phobia (SP), and generalized anxiety disorder (GAD). Participants were 142 consecutive patients attending a specialist anxiety clinic in South Western Sydney.

Elevated plasma osteoprotegerin levels are associated with venous thrombosis and bleeding in patients with polycythemia vera.

Patients with polycythemia vera (PV) have an increased risk for the development of thrombohemorrhagic complications. The pathogenesis of these complications is still unclear. An important role in vascular disease has recently been attributed to osteoprotegerin (OPG).