Evaluation of Toxicity Following Electrically Mediated Interleukin-12 Gene Delivery in a B16 Mouse Melanoma Model

PURPOSE: Interleukin-12 (IL-12) has potential as an immunotherapeutic agent for the treatment of cancer but is unfortunately associated with toxicity. Delivery of a plasmid encoding IL-12 with electroporation induces an antitumor effect in the B16 mouse melanoma model without serious side effects. To translate this observation to the clinic, an evaluation of toxicity was done in the mouse model. EXPERIMENTAL DESIGN: Weight change, tumor response, blood chemistry and hematology values, and serum IL-12 levels were evaluated. Multiple tissues were analyzed histopathologically. RESULTS: A pronounced reduction in tumor volume, including a large percentage of complete regressions, was observed after electrically mediated gene therapy. No significant increases in serum IL-12 levels were detected. Tumor-bearing mice showed an increased number of atypical hematology values when compared with normal naive controls. Statistically significant differences in chemistry and hematology values were observed sporadically in most of the standard chemistry and hematology categories in all groups. The only histopathologic abnormality specific to the animals receiving both plasmid and electroporation was inflammation associated with the kidney at the last time point. CONCLUSIONS: In general, mice that received both plasmid and electroporation showed the least abnormal histopathologic findings and were found to be in the best health, reflecting the reduced burden of disease. No significant toxic effects due to the IL-12 gene therapy were observed

The Ursinus Weekly, January 10, 1978

Ursinus news in brief: Craft attempts prior restraint; Lilly Endowment scratched; Band hangs Mandel; Dishes returned; Cornell students march for time off • Library may curtail hours • Task force considers curriculum • Bankruptcy negates loans • C.I.A. investigates U.C. • Directory published • Tobin appointed • Employment curtailed • Opinion: Ursinus safety • Letters to the editor • A Vegetarian\u27s view • Censorship vs. student rights • Movie attack: Close encounters of the third kind • Dr. Parsons working on new book • Matty Simmons: The Man behind National Lampoon • Dylan to tour in the new year • Ursinus b-ball: marked improvement • Wrestling opens season • Men\u27s swimming • Study before you sleephttps://digitalcommons.ursinus.edu/weekly/1080/thumbnail.jp

The Ursinus Weekly, November 23, 1977

Ursinus News in Brief: U.S.G.A. threatens boycott petition; Cafeteria dinner affirmed; Jessup announces computer courses; Williamson nominates two; Four elected to task force; Ursinus appliance team • Vandalism to exceed \u2776 totals: President\u27s dining room vandalized • U.C. unaware of breakout: How safe is Ursinus? • Enrollments decrease • Five call for U.S.G.A. action • Comment • Letters to the editor • Movie attack: MacArthur • A view of Wismer • Burns debuts as deity • Sex and drugs • Medical credentials • Opinion: S.F.A.R.C. • Grizzly Gridiron closes at 2-7 • Women\u27s volleyball: Wrap-up • Soccer finale • 3 & 4 end season 9-1 • Varsity hockey • X-Country dominateshttps://digitalcommons.ursinus.edu/weekly/1077/thumbnail.jp

The Ursinus Weekly, November 23, 1977

Ursinus News in Brief: U.S.G.A. threatens boycott petition; Cafeteria dinner affirmed; Jessup announces computer courses; Williamson nominates two; Four elected to task force; Ursinus appliance team • Vandalism to exceed \u2776 totals: President\u27s dining room vandalized • U.C. unaware of breakout: How safe is Ursinus? • Enrollments decrease • Five call for U.S.G.A. action • Comment • Letters to the editor • Movie attack: MacArthur • A view of Wismer • Burns debuts as deity • Sex and drugs • Medical credentials • Opinion: S.F.A.R.C. • Grizzly Gridiron closes at 2-7 • Women\u27s volleyball: Wrap-up • Soccer finale • 3 & 4 end season 9-1 • Varsity hockey • X-Country dominateshttps://digitalcommons.ursinus.edu/weekly/1077/thumbnail.jp

Proteomic Contributions to Personalized Cancer Care*

Cancer impacts each patient and family differently. Our current understanding of the disease is primarily limited to clinical hallmarks of cancer, but many specific molecular mechanisms remain elusive. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies that improve patient prognosis are not widely available for most cancers. Individualized care plans, also described as personalized medicine, still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics holds great promise in contributing to the prevention and cure of cancer because it provides unique tools for discovery of biomarkers and therapeutic targets. As such, proteomics can help translate basic science discoveries into the clinical practice of personalized medicine. Here we describe how biological mass spectrometry and proteome analysis interact with other major patient care and research initiatives and present vignettes illustrating efforts in discovery of diagnostic biomarkers for ovarian cancer, development of treatment strategies in lung cancer, and monitoring prognosis and relapse in multiple myeloma patients

Patient Blood Management Recommendations From the 2018 Frankfurt Consensus Conference

Importance: Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. Objective: To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. Evidence Review: The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018. Findings: From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization. Conclusions and Relevance: The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.status: publishe