Novel flavonoids as anti-cancer agents: mechanisms of action and promise for their potential application in breast cancer.

Flavonoids are a large group of ubiquitous polyphenolic secondary metabolites in plants with a wide range of properties, including a widely reported anti-cancer effect. The present review focuses on the different known mechanisms partaking in said anti-tumour effects, with particular emphasis on breast cancer. Their structure and reactivity allows flavonoids to work as antioxidant agents and phyto-oestrogens, modulating oestrogen signalling and metabolism to induce an overall anti-proliferative response.

Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop.

New therapies are urgently needed for hematologic malignancies, especially in patients with relapsed acute myelogenous leukemia (AML) and multiple myeloma. We and others have previously shown that FDA-approved statins, which are used to control hypercholesterolemia and target the mevalonate pathway (MVA), can trigger tumor-selective apoptosis. Our goal was to identify other FDA-approved drugs that synergize with statins to further enhance the anticancer activity of statins in vivo.

Carbonic anhydrase 9 expression increases with vascular endothelial growth factor-targeted therapy and is predictive of outcome in metastatic clear cell renal cancer.

Background: There is a lack of biomarkers to predict outcome with targeted therapy in metastatic clear cell renal cancer (mccRCC). This may be because dynamic molecular changes occur with therapy.

Objective: To explore if dynamic, targeted-therapy-driven molecular changes correlate with mccRCC outcome.

A descriptive study of juvenile family violence: data from intervention order applications in a Childrens Court.

There is increasing recognition that family violence may be perpetrated by juveniles against their parents and siblings, however empirical research regarding the nature and causes of such violence is relatively limited. This study examines juvenile family violence in the context of an Intervention Order (IO) being sought against a relative aged 18years or less. All cases over a 3-year period involving an IO application in a major metropolitan Children's Court in Australia were analysed (n=438).

Largen: a molecular regulator of mammalian cell size control.

Little is known about how mammalian cells maintain cell size homeostasis. We conducted a novel genetic screen to identify cell-size-controlling genes and isolated Largen, the product of a gene (PRR16) that increased cell size upon overexpression in human cells. In vitro evidence indicated that Largen preferentially stimulates the translation of specific subsets of mRNAs, including those encoding proteins affecting mitochondrial functions.

Treatment decisions for localized prostate cancer: a concept mapping approach.

Objective: Few decision aids emphasize active surveillance (AS) for localized prostate cancer. Concept mapping was used to produce a conceptual framework incorporating AS and treatment.

Methods: Fifty-four statements about what men need to make a decision for localized prostate cancer were derived from focus groups with African American, Latino and white men previously screened for prostate cancer and partners (n = 80).

Physician behaviors to promote informed decisions for prostate cancer screening: a National Research Network study.

Clinical guidelines for prostate cancer screening (PCS) advise physicians to discuss the potential harms and benefits of screening. However, there is a lack of training programs for informed decision-making (IDM), and it is unknown which IDM behaviors physicians have the most difficulty performing. Identifying difficult behaviors can help tailor training programs.

Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells.

Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible to lipophilic statins, such as fluvastatin. To quickly advance statins as effective anticancer agents for breast cancer treatment, it is critical to identify the molecular features defining this sensitive subset.

Custom cerium oxide nanoparticles protect against a free radical mediated autoimmune degenerative disease in the brain.

Cerium oxide nanoparticles are potent antioxidants, based on their ability to either donate or receive electrons as they alternate between the +3 and +4 valence states. The dual oxidation state of ceria has made it an ideal catalyst in industrial applications, and more recently, nanoceria's efficacy in neutralizing biologically generated free radicals has been explored in biological applications. Here, we report the in vivo characteristics of custom-synthesized cerium oxide nanoparticles (CeNPs) in an animal model of immunological and free-radical mediated oxidative injury leading to neurodegenerative disease.

'It's not like you just had a heart attack': decision-making about active surveillance by men with localized prostate cancer.

Background: Growing recognition that active surveillance (AS) is a reasonable management option for many men diagnosed with localized prostate cancer led us to describe patients' conceptualizations of AS and reasons for their treatment decisions.

Methods: Men were patients of a multidisciplinary prostate cancer clinic at a large tertiary cancer center where patients are routinely briefed on treatment options, including AS. We conducted a thematic analysis of interviews with 15 men who had chosen AS and 15 men who received radiation or surgery.

Human tissue in systems medicine.

Histopathology, the examination of an architecturally artefactual, two-dimensional and static image remains a potent tool allowing diagnosis and empirical expectation of prognosis. Considerable optimism exists that the advent of molecular genetic testing and other biomarker strategies will improve or even replace this ancient technology. A number of biomarkers already add considerable value for prediction of whether a treatment will work.

MYC phosphorylation at novel regulatory regions suppresses transforming activity.

Despite its central role in human cancer, MYC deregulation is insufficient by itself to transform cells. Because inherent mechanisms of neoplastic control prevent precancerous lesions from becoming fully malignant, identifying transforming alleles of MYC that bypass such controls may provide fundamental insights into tumorigenesis. To date, the only activated allele of MYC known is T58A, the study of which led to identification of the tumor suppressor FBXW7 and its regulator USP28 as a novel therapeutic target.

Examining the association between oral health and oral HPV infection.

Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey.

Comparison of the accuracy of Hybrid Capture II and polymerase chain reaction in detecting clinically important cervical dysplasia: a systematic review and meta-analysis.

The effectiveness of screening programs for cervical cancer has benefited from the inclusion of Human papillomavirus (HPV) DNA assays; which assay to choose, however, is not clear based on previous reviews. Our review addressed test accuracy of Hybrid Capture II (HCII) and polymerase chain reaction (PCR) assays based on studies with stronger designs and with more clinically relevant outcomes. We searched OvidMedline, PubMed, and the Cochrane Library for English language studies comparing both tests, published 1985-2012, with cervical dysplasia defined by the Bethesda classification.

Experimental characterization of next-generation expanded-bed adsorbents for capture of a recombinant protein expressed in high-cell-density yeast fermentation.

Expanded-bed adsorption (EBA) can be particularly useful in protein recovery from high-cell-density fermentation broth where conventional methods for harvest and clarification, such as continuous centrifugation and depth filtration, demand long processing times and are associated with high costs. In this work, the use of next-generation high-particle-density EBA adsorbents, including two mixed-mode resins, for the direct capture of a recombinant protein expressed in yeast at high cell densities is evaluated. Using classical experimental approaches and under different conditions (pH, salt, etc.

A case-linkage study of crime victimisation in schizophrenia-spectrum disorders over a period of deinstitutionalisation.

Background: Despite high rates of self-reported crime victimisation, no study to date has compared official victimisation records of people with severe mental illness with a random community sample. Accordingly, this study sought to determine whether persons with schizophrenia-spectrum disorders have higher rates of recorded victimisation than the general population, and to explore whether there have been changes in rates of recorded victimisation over a period of deinstitutionalisation.

Methods: The schizophrenia-spectrum cases were drawn from a state-wide public mental health register, comprising all persons first diagnosed with a schizophrenic illness in five year cohorts between 1975 - 2005.

Children's skin cancer prevention: a systematic review of parents' psychosocial measures.

Context: Parents' knowledge, attitudes, and beliefs may be influenced through intervention to increase children's sun protection. Little is known about measures of these psychosocial characteristics, including psychometric properties. This paper systematically reviews parents' psychosocial measures in children's skin cancer prevention studies.

The use of reverse phase protein arrays (RPPA) to explore protein expression variation within individual renal cell cancers.

Currently there is no curative treatment for metastatic clear cell renal cell cancer, the commonest variant of the disease. A key factor in this treatment resistance is thought to be the molecular complexity of the disease. Targeted therapy such as the tyrosine kinase inhibitor (TKI)-sunitinib have been utilized, but only 40% of patients will respond, with the overwhelming majority of these patients relapsing within 1 year.

Comparing violence in schizophrenia patients with and without comorbid substance-use disorders to community controls.

Objective: This study examined crime and violence in patients with schizophrenia with and without comorbid substance-use disorders.

Method: A case-linkage design was used to compare patterns of violence and offending between 4168 schizophrenia patients drawn from a state-wide public mental health register, both with and without comorbid substance-use disorders, and a randomly selected community control group who had never been diagnosed with schizophrenia.

Results: Schizophrenia patients were significantly more likely than controls to be guilty of violent and non-violent offences, and to have been involved in family violence.

Primary care physicians' use of an informed decision-making process for prostate cancer screening.

Purpose: Leading professional organizations acknowledge the importance of an informed decision-making process for prostate cancer screening. We describe primary care physicians' reports of their prescreening discussions about the potential harms and benefits of prostate cancer screening.

Methods: Members of the American Academy of Family Physicians National Research Network responded to a survey that included (1) an indicator of practice styles related to discussing harms and benefits of prostate-specific antigen testing and providing a screening recommendation or letting patients decide, and (2) indicators reflecting physicians' beliefs about prostate cancer screening.

A systematic development process for patient decision aids.

Background: The original version of the International Patient Decision Aid Standards (IPDAS) recommended that patient decision aids (PtDAs) should be carefully developed, user-tested and open to scrutiny, with a well-documented and systematically applied development process. We carried out a review to check the relevance and scope of this quality dimension and, if necessary, to update it.

Methods: Our review drew on three sources: a) published papers describing PtDAs evaluated in randomised controlled trials and included in the most recent Cochrane Collaboration review; b) linked papers cited in the trial reports that described how the PtDAs had been developed; and c) papers and web reports outlining the development process used by organisations experienced in developing multiple PtDAs.

Commentary: exploring hormonal influences on problem sexual behavior.

The conceptualization of sexual offending remains problematic and prey to fashion and enthusiasm. Progress can come only on the basis of sound research on the biological, social, and psychological associations to such offending. This study, though in some ways modest in its contribution, offers a model of the systematic approaches which offer the best chances of eventually understanding and managing sexual offending.

Pathways linking socioeconomic status and postpartum smoking relapse.

Background: Low socioeconomic status (SES) exacerbates the high rate of smoking relapse in women following childbirth.

Purpose: This study examined multiple models of potential mechanisms linking SES and postpartum smoking relapse among women who quit smoking due to pregnancy.

Methods: Participants were 251 women enrolled in a randomized clinical trial of a new postpartum smoking relapse prevention intervention.

New strategies for targeting the hypoxic tumour microenvironment in breast cancer.

Radiation and drug resistance remain major challenges and causes of mortality in the treatment of locally advanced, recurrent and metastatic breast cancer. Metabolic reprogramming is a recently recognised hallmark of cancer with the hypoxic acidic extracellular environment as a major driver of invasion and metastases. Nearly 40% of all breast cancers and 50% of locally advanced breast cancers are hypoxic and their altered metabolism is strongly linked to resistance to radiotherapy and systemic therapy.