66 research outputs found

    A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

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    Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

    The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study.

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    BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug-resistant organisms in healthcare settings worldwide, but little is known about MRSA transmission outside of acute healthcare settings especially in Asia. We describe the methods for a prospective longitudinal study of MRSA prevalence and transmission. METHODS: MRSA-colonized individuals were identified from MRSA admission screening at two tertiary hospitals and recruited together with their household contacts. Participants submitted self-collected nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and monthly thereafter for 6 months. A comparison group of households of MRSA-negative patients provided swab samples at one time point. In a validation sub-study, separate swabs from each site were collected from randomly selected individuals, to compare MRSA detection rates between swab sites, and between samples collected by participants versus those collected by trained research staff. Information on each participant's demographic information, medical status and medical history, past healthcare facilities usage and contacts, and personal interactions with others were collected using a self-administered questionnaire. DISCUSSION/CONCLUSION: Understanding the dynamics of MRSA persistence and transmission in the community is crucial to devising and evaluating successful MRSA control strategies. Close contact with MRSA colonized patients may to be important for MRSA persistence in the community; evidence from this study on the extent of community MRSA could inform the development of household- or community-based interventions to reduce MRSA colonization of close contacts and subsequent re-introduction of MRSA into healthcare settings. Analysis of longitudinal data using whole-genome sequencing will yield further information regarding MRSA transmission within households, with significant implications for MRSA infection control outside acute hospital settings

    Advances in exosome therapies in ophthalmology–From bench to clinical trial

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    During the last decade, the fields of advanced and personalized therapeutics have been constantly evolving, utilizing novel techniques such as gene editing and RNA therapeutic approaches. However, the method of delivery and tissue specificity remain the main hurdles of these approaches. Exosomes are natural carriers of functional small RNAs and proteins, representing an area of increasing interest in the field of drug delivery. It has been demonstrated that the exosome cargo, especially miRNAs, is at least partially responsible for the therapeutic effects of exosomes. Exosomes deliver their luminal content to the recipient cells and can be used as vesicles for the therapeutic delivery of RNAs and proteins. Synthetic therapeutic drugs can also be encapsulated into exosomes as they have a hydrophilic core, which makes them suitable to carry water-soluble drugs. In addition, engineered exosomes can display a variety of surface molecules, such as peptides, to target specific cells in tissues. The exosome properties present an added advantage to the targeted delivery of therapeutics, leading to increased efficacy and minimizing the adverse side effects. Furthermore, exosomes are natural nanoparticles found in all cell types and as a result, they do not elicit an immune response when administered. Exosomes have also demonstrated decreased long-term accumulation in tissues and organs and thus carry a low risk of systemic toxicity. This review aims to discuss all the advances in exosome therapies in ophthalmology and to give insight into the challenges that would need to be overcome before exosome therapies can be translated into clinical practice

    Maternal atrial fibrillation after sequential use of nifedipine and atosiban for treatment of preterm labor: case report

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    Effect on human attention of exposure to the electromagnetic field emitted by mobile phones

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    This study examined the effect of exposure to the electromagnetic field emitted by mobile phones on human attention. Three measures of attention were administered to 72 teenagers, 37 of whom were mobile phone users. The results showed that the mobile phone users performed better on one of the three measures of attention than did the non-mobile phone users. The results suggest that exposure to the electromagnetic field emitted by mobile phones may have a mild facilitating effect on attention functions, which is consistent with previous observations that exposure to the electromagnetic field has a facilitating effect on cognitive processing. The possibility that mobile phone users may be naturally better at multiple tasking tasks was discussed. © 2001 Lippincott Williams & Wilkins.link_to_subscribed_fulltex

    Effect on human attention of exposure to the electromagnetic field emitted by mobile phones

    Get PDF
    This study examined the effect of exposure to the electromagnetic field emitted by mobile phones on human attention. Three measures of attention were administered to 72 teenagers, 37 of whom were mobile phone users. The results showed that the mobile phone users performed better on one of the three measures of attention than did the non-mobile phone users. The results suggest that exposure to the electromagnetic field emitted by mobile phones may have a mild facilitating effect on attention functions, which is consistent with previous observations that exposure to the electromagnetic field has a facilitating effect on cognitive processing. The possibility that mobile phone users may be naturally better at multiple tasking tasks was discussed. © 2001 Lippincott Williams & Wilkins.link_to_subscribed_fulltex
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