Association of ESR1 Germline Variants with TP53 Somatic Variants in Breast Tumors in a Genome-wide Study.

Unlabelled: In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors.

Blending Behavioural Theory and Narrative Analysis to Explore the Lived Experience of Obesity and Assess Potential Engagement in a UK Weight Management Service: Theory and Narrative Approaches in Weight Management.

Background: Current treatments for people with obesity emphasise the need for person-centred approaches that consider complex biopsychosocial factors and value the lived experience of people when attempting to lose weight.

Methods: Narrative interviews ( = 20) were conducted with people living with obesity to explore the causes of their weight gain and their expectations and engagement with treatment at a Weight Management Clinic. A mixed inductive and deductive qualitative analysis identified utterances that represented psychological constructs used to understand self-appraisal and health behaviour.

Association of germline variants with somatic variants in breast tumors in a genome-wide study.

Background: In breast tumors, somatic mutation frequencies in and vary by tumor subtype and ancestry. HER2 positive and triple negative breast cancers (TNBC) have a higher frequency of somatic mutations than other subtypes. mutations are more frequently observed in hormone receptor positive tumors.

Characterization of mismatch-repair/microsatellite instability-discordant endometrial cancers.

Background: Mismatch-repair (MMR)/microsatellite instability (MSI) status has therapeutic implications in endometrial cancer (EC). The authors evaluated the concordance of testing and factors contributing to MMR expression heterogeneity.

Methods: Six hundred sixty-six ECs were characterized using immunohistochemistry (IHC), MSI testing, and mut-L homolog 1 (MLH1) methylation.

Rare Missense Alleles Confer Risk for Ovarian and Breast Cancer.

Germline loss-of-function mutations in BRCA1 interacting protein C-terminal helicase 1 (BRIP1) are associated with ovarian carcinoma and may also contribute to breast cancer risk, particularly among patients who develop disease at an early age. Normal BRIP1 activity is required for DNA interstrand cross-link (ICL) repair and is thus central to the maintenance of genome stability. Although pathogenic mutations have been identified in , genetic testing more often reveals missense variants, for which the impact on molecular function and subsequent roles in cancer risk are uncertain.

MAX Mutations in Endometrial Cancer: Clinicopathologic Associations and Recurrent MAX p.His28Arg Functional Characterization.

Background: Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered.

Differential mutation frequencies in metastatic cutaneous squamous cell carcinomas versus primary tumors.

Background: Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but typically is associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die each year of this disease.

TGF-β and CTGF are Mitogenic Output Mediators of Wnt/β-Catenin Signaling in Desmoid Fibromatosis.

Desmoid fibromatosis is a locally aggressive clonal fibroblastic proliferation with high recurrence rates and no metastatic potential. Implicated molecular aberrations occur within the Wnt/β-catenin pathway (APC and β-catenin gene mutations). Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are profibrotic growth factors, downstream from nuclear translocation of β-catenin, that lead to increased fibrogenesis.

Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks.

Genes associated with hereditary breast and ovarian cancer (HBOC) are often sequenced in search of mutations that are predictive of susceptibility to these cancer types, but the sequence results are frequently ambiguous because of the detection of missense substitutions for which the clinical impact is unknown. The BARD1 protein is the heterodimeric partner of BRCA1 and is included on clinical gene panels for testing for susceptibility to HBOC. Like BRCA1, it is required for homology-directed DNA repair (HDR).

Inhibition of LPS-induced TLR4 signaling products in murine macrophages by phenylmethimazole: an assay methodology for screening potential phenylmethimazole analogs.

Preclinical Research Phenylmethimazole (C10) is an inhibitor of Toll-like receptor (TLR3 and TLR4) expression and signaling. In this study, we carried out a detailed investigation of the effect of C10 on TLR4 and its molecular signaling products in RAW 264.7 macrophages using quantitative real-time polymerase chain reaction (PCR), ELISA and cell toxicity assays, a set of in vitro assays that may be used to screen future C10 analogs.

The efficacy of exercise therapy in reducing shoulder pain related to breast cancer: a systematic review.

Purpose: Recent research indicates that physiotherapy interventions, such as exercise and manual therapy, may be effective in decreasing the frequency of side effects linked with breast cancer treatment, including fatigue, pain, nausea, and decreased quality of life. This systematic review aims to determine the efficacy of exercise therapy in reducing shoulder pain related to breast cancer treatment and to identify outcome measures that can be used to assess shoulder pain in this population.

Methods: A systematic review of the current literature was conducted using portals such as the Physiotherapy Evidence Database (PEDro), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Ovid MEDLINE (1996 to April 2011), and Allied and Complementary Medicine (AMED) (1985 to April 2011).

Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice.

Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA) expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR.

Botox therapy for ischemic digits.

Background: Treating patients with Raynaud's phenomenon who have chronic pain and ulcerations is extremely challenging. Unrelenting pain can lead to dysfunction and disuse, rendering the patient debilitated and/or chronically depressed. Pharmacologic vasodilators and surgical sympathectomies offer variable benefits.