Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of ...mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis. Reciprocally, platelets reinforce tumor growth with proliferation signals, antiapoptotic effect, and angiogenic factors. Platelets also activate tumor invasion and sustain metastasis via inducing an invasive epithelial-mesenchymal transition phenotype of tumor cells, promoting tumor survival in circulation, tumor arrest at the endothelium, and extravasation. Furthermore, platelets assist tumors in evading immune destruction. Hence, cancer cells and platelets maintain a complex, bidirectional communication. Recently, aspirin (acetylsalicylic acid) has been recognized as a promising cancer-preventive agent. It is recommended at daily low dose by the US Preventive Services Task Force for primary prevention of colorectal cancer. The exact mechanisms of action of aspirin in chemoprevention are not very clear, but evidence has emerged that suggests a platelet-mediated effect. In this article, we will introduce how cancer changes platelets to be more cancer-friendly and highlight advances in the modes of action for aspirin in cancer prevention. We also discuss the opportunities, challenges, and opposing viewpoints on applying aspirin and other antiplatelet agents for cancer prevention and treatment.
There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be ...assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.
microRNAs (miRNAs) are small molecules that regulate gene expression posttranscriptionally. In a previous study, we identified miR-96 to be upregulated in prostate cancer specimens in comparison to ...normal adjacent tissue and to be an independent marker of biochemical relapse in a multivariate prediction model. Therefore, we investigated the functional role of miR-96 in prostate carcinogenesis. LNCaP and DU145 prostate cancer cells were transiently transfected with miR-96 precursors and phenotypic changes were analyzed. The miR-96 increased proliferation and impaired apoptosis induced by camptothecine in these cells. In silico target prediction analysis identified FOXO1 as potential pro-apoptotic miR-96 target. miR-96 was able to bind to both bindings sites in the FOXO1 3' UTR in a luciferase reporter gene assay. Overexpression of miR-96 in LNCaP cells resulted in a reduced FOXO1 expression. Overexpression of FOXO1 induced a strong apoptotic phenotype that was partially rescued by coexpression of miR-96. RT-qPCR and immunohistochemistry of 69 prostate cancer specimens revealed a downregulation of FOXO1 and an inverse correlation of miR-96 and FOXO1 protein expression. In conclusion, we show that miR-96 can regulate apoptosis in prostate cancer, by inhibiting the FOXO1 transcription factor.
Objectives: The pathology report serves as a crucial communication tool among a number of stakeholders. It can sometimes be challenging to understand. A communication barrier exists among ...pathologists, other clinicians, and patients when interpreting the pathology report, leaving both clinicians and patients less empowered when making treatment decisions. Miscommunication can lead to delays in treatment or other costly medical interventions. Methods: In this review, we highlight miscommunication in pathology reporting and provide potential solutions to improve communication. Results: Up to one-third of clinicians do not always understand pathology reports. Several causes of report misinterpretation include the use of pathology-specific jargon, different versions of staging or grading systems, and expressions indicative of uncertainty in the pathologist's report. Active communication has proven to be crucial between the clinician and the pathologist to clarify different aspects of the pathology report. Direct communication between pathologists and patients is evolving, with promising success in proof-of-principle studies. Special attention needs to be paid to avoiding inaccuracy while trying to simplify the pathology report. Conclusions: There is a need for active and adequate communication among pathologists, other clinicians, and patients. Clarity and consistency in reporting, quantifying the level of confidence in diagnosis, and avoiding misnomers are key steps toward improving communications.
Abstract
Objectives
The pathology report serves as a crucial communication tool among a number of stakeholders. It can sometimes be challenging to understand. A communication barrier exists among ...pathologists, other clinicians, and patients when interpreting the pathology report, leaving both clinicians and patients less empowered when making treatment decisions. Miscommunication can lead to delays in treatment or other costly medical interventions.
Methods
In this review, we highlight miscommunication in pathology reporting and provide potential solutions to improve communication.
Results
Up to one-third of clinicians do not always understand pathology reports. Several causes of report misinterpretation include the use of pathology-specific jargon, different versions of staging or grading systems, and expressions indicative of uncertainty in the pathologist’s report. Active communication has proven to be crucial between the clinician and the pathologist to clarify different aspects of the pathology report. Direct communication between pathologists and patients is evolving, with promising success in proof-of-principle studies. Special attention needs to be paid to avoiding inaccuracy while trying to simplify the pathology report.
Conclusions
There is a need for active and adequate communication among pathologists, other clinicians, and patients. Clarity and consistency in reporting, quantifying the level of confidence in diagnosis, and avoiding misnomers are key steps toward improving communications.
Disruptive innovation is an invention that disrupts an existing market and creates a new one by providing a different set of values, which ultimately overtakes the existing market. Typically, when ...disruptive innovations are introduced, their performance is initially less than existing standard technologies, but because of their ability to bring the cost down, and with gradual improvement, they end up replacing established service standards.
Disruptive technologies have their fingerprints in health care. Pathology and laboratory medicine are fertile soils for disruptive innovations because they are heavily reliant on technology. Disruptive innovations have resulted in a revolution of our diagnostic ability and will take laboratory medicine to the next level of patient care. There are several examples of disruptive innovations in the clinical laboratory. Digitizing pathology practice is an example of disruptive technology, with many advantages and an extended scope of applications. Next-generation sequencing can be disruptive in two ways. The first is by replacing an array of laboratory tests, which each requires expensive and specialized instruments and expertise, with a single cost-effective technology. The second is by disrupting the current paradigm of the clinical laboratory as a diagnostic service by taking it into a new era of preventive or primary care pathology. Other disruptive innovations include the use of dry chemistry reagents in chemistry analyzers and also point of care testing. The use of artificial intelligence is another promising disruptive innovation that can transform the future of pathology and laboratory medicine. Another emerging disruptive concept is the integration of two fields of medicine to create an interrelated discipline such as "histogenomics and radiohistomics." Another recent disruptive innovation in laboratory medicine is the use of social media in clinical practice, education, and publication.
There are multiple reasons to encourage disruptive innovations in the clinical laboratory, including the escalating cost of health care, the need for better accessibility of diagnostic care, and the increased demand on the laboratory in the era of precision diagnostics. There are, however, a number of challenges that need to be overcome such as the significant resistance to disruptive innovations by current technology providers and governmental regulatory bodies. The hesitance from health care providers and insurance companies must also be addressed.
Adoption of disruptive innovations requires a multifaceted approach that involves orchestrated solutions to key aspects of the process, including creating successful business models, multidisciplinary collaborations, and innovative accreditation and regulatory oversight. It also must be coupled with successful commercialization plans and modernization of health care structure. Fostering a culture of disruptive innovation requires establishing unique collaborative models between academia and industry. It also requires uncovering new sources of unconventional funding that are open to high-risk high-reward projects. It should also be matched with innovative thinking, including new approaches for delivery of care and identifying novel cohorts of patients who can benefit from disruptive technology.
Abstract Background Renal cell carcinoma (RCC) encompasses different histologic subtypes. Distinguishing between the subtypes is usually made by morphologic assessment, which is not always accurate. ...Objective Our aim was to identify microRNA (miRNA) signatures that can distinguish the different RCC subtypes accurately. Design, setting, and participants A total of 94 different subtype cases were analysed. miRNA microarray analysis was performed on fresh frozen tissues of three common RCC subtypes (clear cell, chromophobe, and papillary) and on oncocytoma. Results were validated on the original as well as on an independent set of tumours, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis with miRNA-specific primers. Measurements Microarray data were analysed by standard approaches. Relative expression for qRT-PCR was determined using the ΔΔCT method, and expression values were normalised to small nucleolar RNA, C/D box 44 ( SNORD44 , formerly RNU44 ). Experiments were done in triplicate, and an average was calculated. Fold change was expressed as a log2 value. The top-scoring pairs classifier identified operational decision rules for distinguishing between different RCC subtypes and was robust under cross-validation. Results and limitations We developed a classification system that can distinguish the different RCC subtypes using unique miRNA signatures in a maximum of four steps. The system has a sensitivity of 97% in distinguishing normal from RCC, 100% for clear cell RCC (ccRCC) subtype, 97% for papillary RCC (pRCC) subtype, and 100% accuracy in distinguishing oncocytoma from chromophobe RCC (chRCC) subtype. This system was cross-validated and showed an accuracy of about 90%. The oncogenesis of ccRCC is more closely related to pRCC, whereas chRCC is comparable with oncocytoma. We also developed a binary classification system that can distinguish between two individual subtypes. Conclusions MiRNA expression patterns can distinguish between RCC subtypes.
The von Hippel-Lindau ( VHL ) gene is lost in ∼70% of all renal cell carcinomas (RCCs); however, increasing evidence supports the involvement of alternative mechanisms in the regulation of VHL ...expression, including suppression by microRNAs (miRNAs). miRNAs are small, noncoding RNA molecules that regulate gene expression through binding to target mRNAs. In this study, we found that miRNAs, which are dysregulated in cases of RCC, can target multiple members of RCC-related signaling pathways. Importantly, both VHL and the hypoxia-inducible factor 1-α gene are experimentally validated and are likely direct targets of miR-17-5p and miR-224, as shown by both luciferase assay and Western blot analysis. We found a negative correlation between miR-17-5p and its two predicted targets, VEGF-A and EGLN3 , and between miR-224 and its targets SMAD4 and SMAD5 in RCC specimens, suggesting that downstream signaling pathways are also modulated by clear cell RCC-dysregulated miRs. Results from our bioinformatics analysis show that a single miRNA molecule can target multiple components of the same pathway and that multiple miRNAs can target the same molecule. Our results also indicate that miRNAs represent a mechanism for the inactivation of VHL in cases of RCC and can elucidate a new dimension in cancer pathogenesis. As such, miRNAs exemplify new potential therapeutic targets with a significant effect on both tumor growth and metastatic potential.
Knowledge translation (KT) is the dynamic process of mobilizing best-practice evidence to guide health care decisions.
Using a PubMed search, challenges were identified and milestones defined.
...Substantial challenges exist in integrating discoveries into patient care, including technical limitations related to genomic testing like turnaround time, standardization, reproducibility, and results interpretation. Other challenges include lack of proper training in genetic counseling for health care providers, clarity of scientific evidence, and ethical, legal and social considerations. In addition, most health care systems lack accessibility to genetic testing services. Moving forward, KT should be addressed at three main frontiers. The first is patients centered for proper understanding and decision making; the second is directed toward health care professionals, including clinical decision support and clarity of roles; and the third addresses resources of health care systems.
Implementing KT requires developing strategies to enhance awareness and promote behavioral changes congruent with research evidence, designing a systematic approach by health care providers and stakeholders to achieve patient-centered care.
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