Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.

SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Surface modification of inorganic nanoparticles for development of organic–inorganic nanocomposites—A review

Biocompatibility, Pharmaceutical and Biomedical Applications L. Harivardhan Reddy,†,‡ Jose ́ L. Arias, Julien Nicolas,† and Patrick Couvreur*,† †Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Universite ́ Paris-Sud XI, UMR CNRS 8612, Faculte ́ de Pharmacie, IFR 141, 5 rue Jean-Baptiste Cleḿent, F-92296 Chat̂enay-Malabry, France Departamento de Farmacia y Tecnología Farmaceútica, Facultad de Farmacia, Campus Universitario de Cartuja s/n, Universidad de Granada, 18071 Granada, Spain ‡Pharmaceutical Sciences Department, Sanofi, 13 Quai Jules Guesdes, F-94403 Vitry-sur-Seine, France

Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications.

Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging

Inorganic colloidal nanoparticles are very small, nanoscale objects with inorganic cores that are dispersed in a solvent. Depending on the material they consist of, nanoparticles can possess a number of different properties such as high electron density and strong optical absorption (e.g. metal particles, in particular Au), photoluminescence in the form of fluorescence (semiconductor quantum dots, e.g. CdSe or CdTe) or phosphorescence (doped oxide materials, e.g. Y(2)O(3)), or magnetic moment (e.g. iron oxide or cobalt nanoparticles). Prerequisite for every possible application is the proper surface functionalization of such nanoparticles, which determines their interaction with the environment. These interactions ultimately affect the colloidal stability of the particles, and may yield to a controlled assembly or to the delivery of nanoparticles to a target, e.g. by appropriate functional molecules on the particle surface. This work aims to review different strategies of surface modification and functionalization of inorganic colloidal nanoparticles with a special focus on the material systems gold and semiconductor nanoparticles, such as CdSe/ZnS. However, the discussed strategies are often of general nature and apply in the same way to nanoparticles of other materials.

https://faculty.washington.edu/mzhang/mse599/Surface-modification.full.pdf

Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles

The complexity of delivering oncology patient care is reflected in the intricate aggregation of realworld data (RWD), data collected from clinical practice settings outside of interventional studies (e.g., administrative claims, electronic health records, reports, imaging), utilized to generate realworld evidence (RWE). Embracing collaborative interdisciplinary teams and enhancing clinical data scientist training opportunities are ways to begin harnessing the volume, variety, veracity, and velocity of health data for evidence-based patient care.

Harnessing the Power of Collaboration and Training Within Clinical Data Science to Generate Real-World Evidence in the Era of Precision Oncology

PURPOSEPerformance status (PS) is a key factor in oncologic decision making, but conventional scales used to measure PS vary among observers Consumer-grade biometric sensors have previously been i

Quantified Kinematics to Evaluate Patient Chemotherapy Risks in Clinic.

Intracellular particle tracking microrheology

Physical oncology. Preface.

Funders of biomedical research are often challenged to understand how a new funding initiative fits within the agency’s portfolio and the larger research community. While traditional assessment relies on retrospective review by subject matter experts, it is now feasible to design portfolio assessment and gap analysis tools leveraging administrative and grant application data that can be used for early and continued analysis. We piloted such methods on the National Cancer Institute’s Provocative Questions (PQ) initiative to address key questions regarding diversity of applicants; whether applicants were proposing new avenues of research; and whether grant applications were filling portfolio gaps. For the latter two questions, we defined measurements called focus shift and relevance, respectively, based on text similarity scoring. We demonstrate that two types of applicants were attracted by the PQs at rates greater than or on par with the general National Cancer Institute applicant pool: those with clinical degrees and new investigators. Focus shift scores tended to be relatively low, with applicants not straying far from previous research, but the majority of applications were found to be relevant to the PQ the application was addressing. Sensitivity to comparison text and inability to distinguish subtle scientific nuances are the primary limitations of our automated approaches based on text similarity, potentially biasing relevance and focus shift measurements. We also discuss potential uses of the relevance and focus shift measures including the design of outcome evaluations, though further experimentation and refinement are needed for a fuller understanding of these measures before broad application.

/pdf/piloting-an-approach-to-rapid-and-automated-assessment-of-a-1bkp06p169.pdf

Piloting an approach to rapid and automated assessment of a new research initiative: Application to the National Cancer Institute's Provocative Questions initiative.

Jerry S.H. Lee

Papers

Harnessing the Power of Collaboration and Training Within Clinical Data Science to Generate Real-World Evidence in the Era of Precision Oncology

Quantified Kinematics to Evaluate Patient Chemotherapy Risks in Clinic.

Intracellular particle tracking microrheology

Physical oncology. Preface.

Piloting an approach to rapid and automated assessment of a new research initiative: Application to the National Cancer Institute's Provocative Questions initiative.