Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker

Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group

An exploration of online behaviors and social media use among hookah and electronic-cigarette users

The purpose of this study was to explore the relationship between social norms and attitudes towards ENDS and hookah and use of these products. We conducted surveys with hookah and ENDS users who regularly used the Internet and social media and analyzed the primary social media account (e.g. Facebook) of each participant, coding all references to nicotine or tobacco products. The survey included domains on perceived favorability, perceived vulnerability and subjective norms. We surveyed 21 ENDS users and 20 hookah users. Both groups used the Internet to look up information about their respective tobacco product (95% for hookah vs. 90% for ENDS). Seventy percent of hookah users had references to hookah on their social media profiles while 43% of ENDS users had references to ENDS on their page. The majority of both groups were exposed to content posted by friends in their social media network about their respective products online. Those who posted on social media about hookah and those who read about ENDS online had lower perceived vulnerability to the health risks associated with tobacco products. Hookah and ENDS users actively use the Internet and social media to obtain and share information about nicotine/tobacco products. Study participants who use hookah were more likely to share photos and discuss hookah related activities via social media than those who use ENDS. Social networks also represent valuable and untapped potential resources for communicating with this group about risks and harm reduction related to emerging nicotine/tobacco products

Neurodevelopmental Effects of Cannabis Use in Adolescents and Emerging Adults with ADHD: A Systematic Review.

OBJECTIVE: Systematically review the scientific literature to characterize the effects of cannabis use on brain structure, function, and neurodevelopmental outcomes in adolescents and young adults with ADHD. METHOD: Systematic review following PRISMA guidelines utilizing PubMed, Embase, PsycINFO, and Cochrane CENTRAL trials register from inception until 1 January 2020. Articles that examined the impact of cannabis use on youth with ADHD were included. RESULTS: Eleven studies were identified that compared outcomes for individuals with ADHD who used cannabis or synthetic cannabinoids against those with ADHD who did not. Seven of these studies used neuroimaging techniques, including fMRI, structural MRI, and SPECT. Differential regions of activation were identified, including the right hippocampus and cerebellar vermis, and bilateral temporal lobes. Morphological differences were identified in the right precentral and postcentral gyri, left nucleus accumbens, right superior frontal and postcentral gyri. No study identified any additive or ADHD × cannabis use interaction on neuropsychological tasks of executive function. Two studies found adverse differential impacts of early-onset cannabis use in this population. CONCLUSION: A dearth of evidence is available on the impact of cannabis use on the developing brain and functioning for individuals with ADHD, despite the elevated risk for substance use in this population. The limited, potentially underpowered evidence does not support the hypothesis that cannabis use has a deleterious impact on neuropsychological tasks in transitional age youth with ADHD. Larger and longer-term studies are needed, however, to better inform clinicians and patients as to the impacts of cannabis use in youth with ADHD

Differential proteomics in the search for biomarkers of radiotherapy resistance

The individualization of radiotherapy treatment would be beneficial for cancer patients; however, there are no predictive biomarkers of radiotherapy resistance in routine clinical use. This article describes the body of work in this field where comparative proteomics methods have been used for the discovery of putative biomarkers associated with radiotherapy resistance. A large number of differentially expressed proteins have been reported, mostly from the study of novel radiotherapy-resistant cell lines. Here, we have assessed these putative biomarkers through the discovery, confirmation and validation phases of the biomarker pipeline, and inform the reader on the current status of proteomics-based findings. Suggested avenues for future work are discussed

Repeatedly identified differentially expressed proteins (RIDEPs) from antibody microarray proteomic analysis

Antibody microarrays are powerful new tools in the field of comparative proteomics. The success of the biomarker discovery pipeline relies on the quality of data generated in the discovery phase and careful selection of proteins for the verification phase. Recent meta-analyses found a number of repeatedly identified differentially expressed proteins (RIDEPs) from mass spectrometry-based proteomics research in a range of species. We aimed to assess RIDEPs based on antibody microarray data-sets. A total of 13 independent experiments encompassing a range of oncology-related research on human tissue, cells or cell lines from 5 distinct sample groups were performed utilising a commercial 725 antibody microarray platform (Panorama XPRESS Profiler725; Sigma-Aldrich). Analysis of all microarray slides was carried out by the same individual to reduce inter-observer variability. Fold changes of >= 1.8 were considered significant. A total of 13 RIDEPs were seen, each appearing in at least 4/13 (30%) antibody microarray analyses from at least 2 out of 5 experimental sample groups. The phenomenon of RIDEPs may exist in antibody microarray proteomics and we report a preliminary list of 13 RIDEPs from the XPRESS Profiler725 platform. This information will be useful when interpreting experimental data and considering which DEPs should be prioritised for verification. (C) 2011 Elsevier B.V. All rights reserved