Expression of a prostate-associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions

The recent demonstration of human glandular kallikrein (hK2) expression in a breast carcinoma cell line has suggested that this putatively prostate-restricted, steroid hormone-regulated protease may also be expressed in breast epithelium in vivo and secreted into the mammary duct system. Given that the only substrate yet identified for hK2 activity is the precursor of prostate-specific antigen (PSA), the expression of which in breast carcinomas may be associated with favourable prognosis, our purpose was to examine the expression pattern of both hK2 and PSA in breast tumour tissues. Cytosolic extracts of 336 primary breast carcinomas prepared for routine oestrogen receptor (ER) and progesterone receptor (PR) analysis, as well as 31 nipple aspirates from six women with non-diseased mammary glands, were assayed for hK2 and PSA using immunofluorometric assays developed by the authors. In the tumour extracts, measurable hK2 and PSA concentrations were detected in 53% and 73% of cases respectively, and were positively correlated to each other (r = 0.59, P = 0.0001). Higher concentrations of PSA and hK2 were found in tumours expressing steroid hormone receptors (P = 0.0001 for PSA and P = 0.0001 for hK2, by Wilcoxon tests for both ER and PR), and both PSA (r = 0.25, P = 0.0001) and hK2 (r = 0.22, P = 0.0001) correlated directly with PR levels. A negative correlation between patient age and PSA (r = –0.12, P = 0.03) was also found. Both proteins were present in nipple aspirate fluid at relatively high concentrations which were positively correlated (r = 0.53, P = 0.002). The molecular weights of the immunoreactive species quantified by the hK2 and PSA assays were established by high-performance liquid chromatography (HPLC) and were consistent with the known molecular weights of hK2 and PSA. Together these data provide the first evidence, to our knowledge, that both malignant breast tissue and normal breast secretion contain measurable quantities of hK2, and that the degree of hK2 expression or secretion is directly proportional to the expression of PSA and steroid hormone receptors. hK2 expression may therefore be a marker of steroid hormone action in breast tissue. © 2000 Cancer Research Campaig

Understanding factors that promote uptake of HIV self-testing among young people in Nigeria: Framing youth narratives using the PEN-3 cultural model

It is important to understand how to frame the formats for promoting HIV self-testing to increase uptake among young people. In this study, we used a culture-centered model to understand the narratives of HIV self-testing preferences among young people in Nigeria. We conducted a crowdsourcing contest to solicit ideas surrounding HIV self-testing promotion among young people (10–24 years) in Nigeria from October to November 2018 as part of the 2018 World AIDS Day event. We received 903 submissions and employed thematic content analysis to evaluate 769 eligible youth narratives. Thematic content analysis of the statements from the youth narratives was guided by the PEN-3 cultural model to examine the positive, existential, and negative perceptions (beliefs and values), enablers (resources), and nurturers (roles of friends and family) of HIV self-testing promotion among young people in Nigeria. Several themes emerged as factors that influence the uptake of HIV self-testing among young people in Nigeria. Specifically, seven themes emerged as perceptions: HIV testing accessibility, stigma reduction, and autonomy (positive); HIV self-testing kit packaging and advertisements (existential); lack of knowledge and increased stigma (negative). Seven themes emerged as enablers: social media, school, and government promotion (positive); gamification and animation (existential); high cost and access to linkage to care services (negative); And seven themes emerged as nurturers: peer, families, and faith-based communities (positive); parents and family-centered approach (existential); and partners and family (negative). Our data suggests that increased awareness around HIV self-testing on current youth-friendly platforms, de-stigmatization of HIV and HIV self-testing, decreased prices for HIV self-testing kits, reliability of testing kits, increased linkage to care services, and promotion of self-testing among family members and the community will be beneficial for HIV self-testing scale-up measures among young people in Nigeria

Protein-Binding Microarray Analysis of Tumor Suppressor AP2α Target Gene Specificity

Cheap and massively parallel methods to assess the DNA-binding specificity of transcription factors are actively sought, given their prominent regulatory role in cellular processes and diseases. Here we evaluated the use of protein-binding microarrays (PBM) to probe the association of the tumor suppressor AP2α with 6000 human genomic DNA regulatory sequences. We show that the PBM provides accurate relative binding affinities when compared to quantitative surface plasmon resonance assays. A PBM-based study of human healthy and breast tumor tissue extracts allowed the identification of previously unknown AP2α target genes and it revealed genes whose direct or indirect interactions with AP2α are affected in the diseased tissues. AP2α binding and regulation was confirmed experimentally in human carcinoma cells for novel target genes involved in tumor progression and resistance to chemotherapeutics, providing a molecular interpretation of AP2α role in cancer chemoresistance. Overall, we conclude that this approach provides quantitative and accurate assays of the specificity and activity of tumor suppressor and oncogenic proteins in clinical samples, interfacing genomic and proteomic assays

Youth engagement in HIV prevention intervention research in sub-Saharan Africa: a scoping review.

INTRODUCTION: Youth engagement in HIV research is generally recognized as essential, but often neglected or minimally implemented in practice. Engagement is a process of working collaboratively with diverse groups of people to address common issues. We conducted a scoping review of youth HIV prevention interventions in sub-Saharan Africa to identify and categorize forms and levels of youth engagement across the lifespan of intervention research. METHODS: We followed Arksey and O'Malley's framework for organizing a scoping review. We searched seven databases for related articles on identified intervention studies through May 28th 2020. Included studies focused on youth (10 to 24 years old) HIV prevention interventions in sub-Saharan Africa. Two reviewers independently examined citations and full manuscripts for inclusion. Data were extracted on study characteristics, location, description of youth engagement and extent of engagement. Youth engagement approaches were categorized based on Hart's ladder as substantial engagement (strong youth decision-making power), moderate engagement (shared decision making with adults), minimal engagement (no youth decision-making power) or no engagement. RESULTS: We identified 3149 citations and included 112 studies reporting on 74 unique HIV interventions. Twenty-two interventions were in low-income countries, 49 in middle-income countries, and three were in both. Overall, only nine interventions (12%) had substantial or moderate youth engagement, two-thirds (48, 65%) had minimal youth engagement and 17 interventions (23%) had no youth engagement. We also identified specific engagement strategies (e.g. youth-led research, crowdsourcing) that were feasible in multiple settings and resulted in substantial engagement. CONCLUSIONS: We found limited youth engagement in youth HIV prevention intervention studies in sub-Saharan Africa. However, several activities resulted in substantial youth engagement and could be relevant in many low-and-middle-income-country (LMIC) settings

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

evolving role of serum biomarkers in the management of ovarian cancer

The availability of an ideal serum tumor marker would be of great clinical benefit for both the diagnosis and management of patients with epithelial ovarian cancer. Serum cancer antigen 125 assay significantly increases the diagnostic reliability of ultrasound in discriminating a malignant from a benign ovarian mass, especially in postmenopausal women, and it is the only well validated tumor marker for monitoring disease course. Several other tumor-associated antigens have been assessed, including glycoprotein antigens other than cancer antigen 125, soluble cytokeratin fragments, kallikreins, cytokines and cytokine receptors, vascular endothelial growth factor, D-dimer, and lisophosphatidic acid. This article assesses the potential diagnostic and prognostic role of these novel biomarkers, both alone and in combination with cancer antigen 125. The future for serum tumor marker research is represented by the emerging technology of proteomics, which may allow scientific advances comparable to those achieved ..