Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Neurocognitive function in children with compensated hypothyroidism: lack of short term effects on or off thyroxin

BACKGROUND: Although thyroxin therapy clearly is beneficial to children with frank hypothyroidism there is little data on the effects of thyroxin in children with compensated or subclinical hypothyroidism. The objective of this study was to determine the effect of thyroxin therapy on cognitive function in children with compensated hypothyroidism. The hypothesis was that thyroxin therapy would change neuropsychological function. METHODS: Eleven patients with a history of sub clinical hypothyroidism entered the study. At the start of the study, six out of the 11 were on thyroxin therapy, while 5 were off therapy. All patients underwent a battery of neuropsychological testing and thyroid function tests at the start of study. Based on the results of thyroid function tests, two of the 5 patients who were off thyroxin were started back on thyroxin. All of the 6 patients who were on thyroxin were taken off thyroxin. All patients then underwent repeat neuropsychological testing and thyroid functions after an average of 91 days. RESULTS: Thyroxin therapy could not be shown to have an effect on neuropsychological function in this short term study. Our patients had attention problems as compared to the normal population. No significant differences were found between our subjects and normal population standards in verbal processing, visual processing, motor speed/coordination and achievement. CONCLUSION: In this small, short term study, thyroxin therapy could not be shown to affect neuropsychological function in children with compensated hypothyroidism. These children may have attention problems but appear to have normal verbal and visual processing, motor speed/coordination and achievement

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

A Reliable Method for the Selection of Exploitable Melanoma Archival Paraffin Embedded Tissues for Transcript Biomarker Profiling

The source tissue for biomarkers mRNA expression profiling of tumors has traditionally been fresh-frozen tissue. The adaptation of formalin-fixed, paraffin-embedded (FFPE) tissues for routine mRNA profiling would however be invaluable in view of their abundance and the clinical information related to them. However, their use in the clinic remains a challenge due to the poor quality of RNA extracted from such tissues. Here, we developed a method for the selection of melanoma archival paraffin-embedded tissues that can be reliably used for transcript biomarker profiling. For that, we used qRT-PCR to conduct a comparative study in matched pairs of frozen and FFPE melanoma tissues of the expression of 25 genes involved in angiogenesis/tumor invasion and 15 housekeeping genes. A classification method was developed that can select the samples with a good frozen/FFPE correlation and identify those that should be discarded on the basis of paraffin data for four reference genes only. We propose therefore a simple and inexpensive assay which improves reliability of mRNA profiling in FFPE samples by allowing the identification and analysis of “good” samples only. This assay which can be extended to other genes would however need validation at the clinical level and on independent tumor series

Use of complementary/alternative therapies by women with advanced-stage breast cancer

BACKGROUND: This study sought to describe the pattern of complementary/alternative medicine (CAM) use among a group of patients with advanced breast cancer, to examine the main reasons for their CAM use, to identify patient's information sources and their communication pattern with their physicians. METHODS: Face-to-face structured interviews of patients with advanced-stage breast cancer at a comprehensive oncology center. RESULTS: Seventy three percent of patients used CAM; relaxation/meditative techniques and herbal medicine were the most common. The most commonly cited primary reason for CAM use was to boost the immune system, the second, to treat cancer; however these reasons varied depending on specific CAM therapy. Friends or family members and mass media were common primary information source's about CAM. CONCLUSIONS: A high proportion of advanced-stage breast cancer patients used CAM. Discussion with doctors was high for ingested products. Mass media was a prominent source of patient information. Credible sources of CAM information for patients and physicians are needed

Psychiatric rating scales in Urdu: a systematic review

<p>Abstract</p> <p>Background</p> <p>Researchers setting out to conduct research employing questionnaires in non-English speaking populations need instruments that have been validated in the indigenous languages. In this study we have tried to review the literature on the status of cross-cultural and/or criterion validity of all the questionnaires measuring psychiatric symptoms available in Urdu language.</p> <p>Methods</p> <p>A search of Medline, Embase, PsycINFO and <url>http://www.pakmedinet.com</url> was conducted using the search terms; Urdu psychiatric rating scale, and Urdu and Psychiatry. References of retrieved articles were searched. Only studies describing either cross-cultural or criterion validation of a questionnaire in Urdu measuring psychiatric symptoms were included.</p> <p>Results</p> <p>Thirty two studies describing validation of 19 questionnaires were identified. Six of these questionnaires were developed indigenously in Urdu while thirteen had been translated from English. Of the six indigenous questionnaires five had had their criterion validity examined. Of the thirteen translated questionnaires only four had had both their cross-cultural and criterion validity assessed.</p> <p>Conclusion</p> <p>There is a paucity of validated questionnaires assessing psychiatric symptoms in Urdu. The BSI, SRQ and AKUADS are the questionnaires that have been most thoroughly evaluated in Urdu.</p

Incentive or Habit Learning in Amphibians?

Toads (Rhinella arenarum) received training with a novel incentive procedure involving access to solutions of different NaCl concentrations. In Experiment 1, instrumental behavior and weight variation data confirmed that such solutions yield incentive values ranging from appetitive (deionized water, DW, leading to weight gain), to neutral (300 mM slightly hypertonic solution, leading to no net weight gain or loss), and aversive (800 mM highly hypertonic solution leading to weight loss). In Experiment 2, a downshift from DW to a 300 mM solution or an upshift from a 300 mM solution to DW led to a gradual adjustment in instrumental behavior. In Experiment 3, extinction was similar after acquisition with access to only DW or with a random mixture of DW and 300 mM. In Experiment 4, a downshift from DW to 225, 212, or 200 mM solutions led again to gradual adjustments. These findings add to a growing body of comparative evidence suggesting that amphibians adjust to incentive shifts on the basis of habit formation and reorganization

Circumstellar discs: What will be next?

This prospective chapter gives our view on the evolution of the study of circumstellar discs within the next 20 years from both observational and theoretical sides. We first present the expected improvements in our knowledge of protoplanetary discs as for their masses, sizes, chemistry, the presence of planets as well as the evolutionary processes shaping these discs. We then explore the older debris disc stage and explain what will be learnt concerning their birth, the intrinsic links between these discs and planets, the hot dust and the gas detected around main sequence stars as well as discs around white dwarfs.Comment: invited review; comments welcome (32 pages