TRAIL and microRNAs in the treatment of prostate cancer: therapeutic potential and role of nanotechnology.

Disruption of spatiotemporal behavior of intracellular signaling cascades including tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling in prostate cancer has gained tremendous attention in the past few years. There is an increasing effort in translating the emerging information about TRAIL-mediated signaling obtained through experimental and preclinical data to clinic. Fascinatingly, novel targeting approaches are being developed to enhance the tissue- or subcellular-specific delivery of drugs with considerable focus on prostate cancer.

TRPC signaling mechanisms and therapeutic opportunities: trapdoors are monitored by gatekeepers.

This Review summarizes our current state of knowledge of the functional role of TRPC channels in health and disease, with particular emphasis on current advancements in the field. Additionally, this Review provides an up-to-date summary of SKF-96365 acting on TRPC channels, and discusses strategies to further investigate the potential of these channels for therapeutic intervention.

Making personalized prostate cancer medicine a reality: challenges and opportunities in the re-establishment of gold standards.

Prostate cancer is a serious multidimensional disorder that arises because of misrepresentation of signaling cascades and acquired resistance against apoptosis. It is progressively becoming more insurmountable because of rheostat like switching of oncogenic signaling in androgen dependent and androgen depleted microenvironment. Additionally, oncogenic fusion proteins have been explored in prostate cancer tissues thus adding another layer of complexity to the targeting of protein network in cancer cell and generate hurdles in the standardization of therapy.

Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes.

HPV encoded proteins can elicit ectopic protein-protein interactions that re-wire signaling pathways, in a mode that promotes malignancy. Moreover, accumulating data related to HPV is now providing compelling substantiation of a central role played by HPV in escaping immunosurveillance and impairment of apoptotic response. What emerges is an intricate network of Wnt, TGF, Notch signaling cascades that forms higher-order ligand-receptor complexes routing downstream signaling in HPV infected cells.

Disease activity score in rheumatoid arthritis with or without secondary fibromyalgia.

Objective: To correlate disease activity score (DAS-28) in the patients with rheumatoid arthritis (RA) with and without secondary fibromyalgia.

Study Design: Comparative cross-sectional study.

Place And Duration Of Study: Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, from November 2011 to April 2012.

Relations among upper-limb movement organization and cognitive function at school age in children born preterm.

Objective: To explore relations between aspects of upper-body spatiotemporal movement organization and intelligence in children born preterm at school age.

Methods: Three-dimensional (3D) kinematic recordings of arm and head movements during a unimanual precision task were related to performance on the Wechsler Intelligence Scale for Children, 4th edition, in a sample of 32 children born preterm (gestational age, mean: 31.5 weeks [range: 22-35 weeks]; birth weight, mean: 1699 g [range: 404-2962 g]) at 6 years to 8 years with no diagnosed cognitive, sensory, or motor impairments compared with 40 age-matched control children born fullterm.

BCR-ABL1 in leukemia: disguise master outplays riding shotgun.

Leukemia is a many-sided molecular disorder that arises because of over expression of oncogenes, suppression of tumor suppressor genes, and chromosomal translocations. These chromosomal rearrangements are nonetheless among the many determinants that underlie transformation of cells from normal to a cancerous phenotype and predispose cells to refractoriness against interventions by reduced drug influx and substantial drug efflux. This review unfolds current understanding of BCR-ABL1 (break point cluster region-c-abl oncogene 1, non-receptor tyrosine kinase) signaling with a focus on apoptotic suppressive mechanisms and alternative approaches to chronic myeloid leukemia therapy.

Breakpoint cluster region-c-abl oncogene 1, non-receptor tyrosine kinase signaling: current patterns of the versatile regulator revisited.

Increasing sophisticated information suggests that cancer cells express constitutively active oncogenic kinases such as breakpoint cluster region- c-abl oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) that promote carcinogenesis independent of extrinsic growth factors. It is a well-established fact that through the aberrant activation of BCR-ABL1 signal transduction cascade, the perception of cellular growth signals becomes disconnected from the processes promoting cell growth, and this underlies the pathophysiology of leukemia. In this particular review we discuss the oncogenes and tumor suppressors comprising the regulatory network upstream and downstream of BCR-ABL1 and dismantle how derailed BCR-ABL1 signaling provides cell a selective growth advantage.

miRNA and TMPRSS2-ERG do not mind their own business in prostate cancer cells.

Oncogenic fusion proteins belong to an important class that disrupts gene expression networks in a cell. Astonishingly, fusion-positive prostate cancer cells enable the multi-gene regulatory capability of miRNAs to remodel the signal transduction landscape, enhancing or antagonizing the transmission of information to downstream effectors. Accumulating evidence substantiates the fact that miRNAs translate into dose-dependent responsiveness of cells to signaling regulators in transmembrane protease serine 2:ETS-related gene (TMPRSS2-ERG)-positive cells.

Behaviours related to executive functions and learning skills at 11 years of age after extremely preterm birth: a Swedish national prospective follow-up study.

Aim: We investigated a national cohort of children born extremely immature (<26 weeks gestation, EI) regarding the nature, frequency and severity of the behavioural problems related to the executive functions (EF) and concerning learning skills, from the perspectives of parents and teachers.

Methods: At 11 years of age 86 of 89 survivors of this cohort were studied and compared with an equal number of controls. Behaviours related to EF, and learning skills were assessed by a validated instrument, namely the Five to Fifteen questionnaire sent by mail to parents and teachers.

While at Rome miRNA and TRAIL do whatever BCR-ABL commands to do.

It is a well-acclaimed fact that proteins expressed as a consequence of oncogenic fusions, mutations or amplifications can facilitate ectopic protein-protein interactions that re-wire signal dissemination pathways, in a manner that escalates malignancy. BCR-ABL-mediated signal transduction cascades in leukemic cells are assembled and modulated by a finely controlled network of protein-protein interactions, mediated by characteristic signaling domains and their respective binding motifs. BCR-ABL functions in a cell context-specific and cell type-specific manner to integrate signals that affect uncontrolled cellular proliferation.

Algae extracts and methyl jasmonate anti-cancer activities in prostate cancer: choreographers of 'the dance macabre'.

There is an overwhelmingly increasing trend of analysis of naturally occurring ingredients in treatment of prostate cancer. Substantial fraction of information has been added that highlights activity at various levels and steps of deregulated cellular proliferation, metastasis and apoptosis. Among such ingredients, algae extracts and jasmonates are documented to have anti-cancer activity in vitro and in vivo and induce growth inhibition in cancer cells, while leaving the non-transformed cells intact.

Lung cancer associated with cystic airspaces.

Objective: The objectives of this study were to determine the frequency of lung cancers associated with a discrete cystic airspace and to characterize the morphologic and pathologic features of the cancer and the cystic airspace.

Materials And Methods: We reviewed all diagnosed cases of lung cancer resulting from baseline screening (n=595) and annual screening (n=111) in the International Early Lung Cancer Action Program to identify those abutting or in the wall of a cystic airspace. We also reviewed the pathologic specimens.

Breast cancer proteome takes more than two to tango on TRAIL: beat them at their own game.

Breast carcinogenesis is a multidimensional disease that has resisted drug-related solutions to date because of heterogeneity, disorganized spatiotemporal behavior of signal transduction cascades, cell cycle checkpoints, cell transition, plasticity, and impaired pro-apoptotic response. These synchronized oncogenic events, including protein-protein interaction, transcriptional-regulatory, and signaling networks, trigger genomic and transcriptional disturbances in TRAIL-mediated signaling network neighborhoods. Therefore, tumor cells often acquire the ability to escape death by suppressing cell death pathways that normally function to eliminate damaged and harmful cells.

Prostate cancer is known by the companionship with ATM and miRNA it keeps: craftsmen of translation have dual behaviour with tailors of life thread.

Research on prostate cancer progression has focused extensively on the concept of miRNA, which can operate either as promoters or as suppressors of carcinogenesis. Moreover, recent genetic studies and emerging functional work show that strikingly similar and overlapping pathways are involved in prostate carcinogenesis. Unswervingly, these elements constitute a recently explored 'network of networks' that dynamically reorganizes during DNA damage and is responsible for positively or negatively regulating genome organization and integrity.

TRAIL and vitamins: opting for keys to castle of cancer proteome instead of open sesame.

Cancer is a multifaceted molecular disorder that is modulated by a combination of genetic, metabolic and signal transduction aberrations, which severely impair the normal homeostasis of cell growth and death. Accumulating findings highlight the fact that different genetic alterations, such as mutations in tumor suppressor genes, might be related to distinct and differential sensitivity to targeted therapies. It is becoming increasingly apparent that a multipronged approach that addresses genetic milieu (alterations in upstream and/or parallel pathways) eventually determines the response of individual tumors to therapy.

Prostate cancer and immunoproteome: awakening and reprogramming the guardian angels.

Prostate cancer is a life-threatening molecular disorder that is undruggable to date because of stumbling blocks in the standardization of therapy. An emerging framework of research is addressing how pathways that are derailed during tumorigenesis are linked to immunological responses, which are instrumental in immunosurveillance of cancer. However, interestingly, cancer cells circumvent such immunosurveillance through development of poorly immunogenic tumor cell variants (immunoselection) and through subversion of the immunological nanomachinery (immunosubversion).

Prevalence of dyslipidemias in autoimmune rheumatic diseases.

Objective: To determine the frequency of dyslipidemias in various autoimmune rheumatic diseases and the difference in lipid profile according to the activity of these diseases.

Study Design: Cross-sectional study.

Place And Duration Of Study: The Rheumatology Department of Pakistan Institute of Medical Sciences (PIMS), Islamabad, from May 2010 to April 2011.

Lung cancers diagnosed at annual CT screening: volume doubling times.

Purpose: To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types.

Materials And Methods: All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included.

Upon the tightrope in prostate cancer: two acrobats on the same tightrope to cross the finishline.

Prostate cancer is a multifactorial, multistep progressive disorder that is undruggable to date because of stumbling blocks in the standardization of therapy. It is triggered by a broad range of proteins, signaling networks and DNA damage response modulators. It is becoming increasingly apparent that DNA repair mediators have split personalities, as they are instrumental in suppressing and promoting carcinogenesis.

Feasibility of a structured group education session to improve self-management of blood pressure in people with chronic kidney disease: an open randomised pilot trial.

Objectives We aimed to test, at pilot level, a structured group educational intervention to improve self-management of blood pressure in people with chronic kidney disease (CKD). The current paper explores patient acceptability of the intervention. Design This was an open randomised pilot trial.

The utility of cytodiagnostic urinalysis as a tool to diagnose kidney allograft dysfunction in the era lymphocyte-depleting induction therapy.

Cytodiagnostic urinalysis (CDU) has been used to evaluate causes of kidney allograft dysfunction, such as an acute rejection episode (ARE), calcineurin inhibitor (CNI) toxicity, or polyoma virus infection. We examined the concordance between CDU and allograft biopsy in patients with allograft dysfunction. Between 2002 and 2006, 201 patients had CDU performed within 7 days of a biopsy.

NutriTRAILomics in prostate cancer: time to have two strings to one's bow.

The astonishing development of broad genomics and proteomics tools have catalyzed a new era in both therapeutic interventions and nutrition in prostate cancer. The terms pharmacogenomics and nutrigenomics have been derived out of their genetic forbears as large-scale genomics technologies have been established in the last decade. It is unquestionable that rationale of both disciplines is to individualize or personalize medicine and food and nutrition, and eventually health, by tailoring the drug or the food to the individual genotype.

Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation.

Objective: Prostate cancer is a polyfactorial molecular anomaly that is offering refractoriness against a broad range of therapeutic drugs. Growth factor receptors are actively implicated in oncogenesis. PDGFR/EGFR mediated exacerbated signaling has a central participation and is contributory in fueling the signal transductions that gear up prostate cancer progression.

Emphysema scores predict death from COPD and lung cancer.

Objective: Our objective was to assess the usefulness of emphysema scores in predicting death from COPD and lung cancer.

Methods: Emphysema was assessed with low-dose CT scans performed on 9,047 men and women for whom age and smoking history were documented. Each scan was scored according to the presence of emphysema as follows: none, mild, moderate, or marked.