Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Molecular pathways to therapeutics: Paradigms and challenges in oncology meeting report: Carcinogenesis 2015

The search for the most effective therapy with minimum side effects has always been the goal of oncologists and efforts to develop such therapies through understanding disease mechanisms has been the focus of many basic scientists in cancer research, leading to a common interest of convergence. The 5 th International Conference organized by the Carcinogenesis Foundation, USA and Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, India, was held between February 11 th and 13 th 2015, at ACTREC. During these proceedings, the scientific community engaged in oncology research discussed novel ideas emerging from the laboratory and their translation into improved clinical outcomes. However, the lack of major success in the genesis of novel cancer therapeutics that is safe and provides long-term relief to patients is a challenge that needs to be overcome. The focus of this meeting was to highlight these challenges and to encourage collaborations between scientists and clinicians and clearly a message through exemplary scientific contribution was conveyed to all the dedicated scientists and clinician that even if two decades of tireless work on a single idea does not generate a reliable and safe therapy, the combat to rein cancer must not cease. In this report we have communicated some of the outstanding work done in the areas of cancer therapeutics, biomarkers and prevention and described the salient observations associated with cancer stem cells in disease progression and some of the pathways implicated in tumor progression

Gene HI1472 of <i>Haemophilus influenzae </i>Rd is a novel gene involved in DNA repair

530-535A chimeric plasmid, pJPuvr4, consists of a 16.7 kbp Haemophilus influenzae Rd chromosomal DNA insert at the EcoRI site of vector pJ 1-8. This plasmid complements the UV and gamma ray sensitivity of the mutant strain MBH4.This plasmid carries the wild type allele of gene uvr4 which was localised to a 3.8 kbp DraI fragment, with an internal Eco RI site. Partial sequencing of the gene and its alignment with the published genome sequence of H. influenzae Rd revealed uvr4 to be HI1472. HI1472 is a putatively identified open reading frame (ORF), which has been assigned no function so far. The partial sequence did show nt database match with 3D exon of N cadherin gene of homosepians and moaA gene of H. Inf luenzae. Cadherins are involved in cell adhesion, cell to cell contact and morphogenesis in homosepians and moaA gene codes for molybdenum biosynthesis subunit A. This report implicates HI 1472 of Haemophilus influenzae Rd in DNA repair. Nucleotide sequence obtained for the gene uvr4 was compared with the published sequence of gene HI1472. A wild type strain variation was observed at the 592nd nucleotide position corresponding to a change from aspartic acid to threonine

Aspirin Inhibition of Group VI Phospholipase A2 Induces Synthetic Lethality in AAM Pathway Down-Regulated Gingivobuccal Squamous Carcinoma

Background: To elucidate the role of iPLA2/PLA2G6 in gingivobuccal squamous cell carcinoma (GB-SCC) and to ascertain the synthetic lethality-based chemoprevention role of aspirin in arachidonic acid metabolism (AAM) pathway down-regulated GB-SCC. Methods: The in vitro efficacy of aspirin on GB-SCC cells (ITOC-03 and ITOC-04) was assessed by cell proliferation, colony formation, apoptosis, cell migration, cell cycle assay and RNA-seq, while inhibition of PLA2G6 and AAM pathway components was affirmed by qPCR, Western blot and immunofluorescence staining. The in vivo effect of aspirin was evaluated using NOD-SCID mice xenografts and immunohistochemical analysis. Results: We found that aspirin, which has been reported to act through the COX pathway, is inhibiting PLA2G6, and thereby the COX and LOX components of the AAM pathway. The findings were validated using PLA2G6 siRNA and immunohistochemical marker panel. Moreover, a pronounced effect in ITOC-04 cells and xenografts implied aspirin-induced synthetic lethality in the AAM pathway down-regulated GB-SCC. Conclusions: This study reveals that aspirin induces the anti-tumor effect by a previously unrecognized mechanism of PLA2G6 inhibition. In addition, the effect of aspirin is influenced by the baseline AAM pathway status and could guide precision prevention clinical trials of AAM pathway inhibitors

Case-control study of breast cancer in India: Role of PERIOD3 clock gene length polymorphism and chronotype

Background: This study examined a PERIOD3 (PER3) gene variable number tandem repeat polymorphism and chronotype as potential BrCA risk factors among Indian women. Methods: This case-control study included sporadic, histologically confirmed BrCA cases (n = 255) and controls (n = 249) from India with data collection from 2010-2012. Results: Women with the 4/5 or 5/5 PER3 genotype had a nonstatistically significant 33% increased odds of BrCA. Cases were more likely to have a morning (OR = 2.43, 95% CI = 1.23-4.81) or evening (OR = 2.55, 95% CI = 1.19-5.47) chronotype. Conclusions: Findings are consistent with the possibility that extremes in chronotype may elicit circadian desynchronization, resulting in increased BrCA susceptibility. © 2014 Informa Healthcare USA, Inc

Supplementary Table S6 from Natural History of Germline <i>BRCA1</i> Mutated and <i>BRCA</i> Wild-type Triple-negative Breast Cancer

This table shows the annotation information from Annovar for clonal architecture of Patient P4</p

Supplementary Table S5 from Natural History of Germline <i>BRCA1</i> Mutated and <i>BRCA</i> Wild-type Triple-negative Breast Cancer

This table shows the annotation information from Annovar for clonal architecture of Patient P2</p

Supplementary Table S9 from Natural History of Germline <i>BRCA1</i> Mutated and <i>BRCA</i> Wild-type Triple-negative Breast Cancer

This table lists the cellular prevalence values for clones across each patient on this study.</p

Supplementary Table S3 from Natural History of Germline <i>BRCA1</i> Mutated and <i>BRCA</i> Wild-type Triple-negative Breast Cancer

This table shows the primer information for all point mutations in the targetted ultra-deep sequencing assay.</p

Supplementary Table S7 from Natural History of Germline <i>BRCA1</i> Mutated and <i>BRCA</i> Wild-type Triple-negative Breast Cancer

This table shows the annotation information from Annovar for clonal architecture of Patient P7</p