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Full-Text Articles in Medicine and Health Sciences

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock Aug 2019

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …


The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall Jul 2019

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …


Evaluating The Effectiveness And Implementation Of Evidence-Based Treatment: A Multisite Hybrid Design., Jamile A Ashmore, Kirk W Ditterich, Claire C Conley, Melissa R Wright, Peggy S Howland, Kelly L Huggins, Jena Cooreman, Priscilla S Andrews, Donald R Nicholas, Lind Roberts, Larissa Hewitt, Joan N Scales, Jenny K Delap, Christine A Gray, Lynelle A Tyler, Charlotte Collins, Catherine M Whiting, Brittany M Brothers, Marlena M Ryba, Barbara L Andersen May 2019

Evaluating The Effectiveness And Implementation Of Evidence-Based Treatment: A Multisite Hybrid Design., Jamile A Ashmore, Kirk W Ditterich, Claire C Conley, Melissa R Wright, Peggy S Howland, Kelly L Huggins, Jena Cooreman, Priscilla S Andrews, Donald R Nicholas, Lind Roberts, Larissa Hewitt, Joan N Scales, Jenny K Delap, Christine A Gray, Lynelle A Tyler, Charlotte Collins, Catherine M Whiting, Brittany M Brothers, Marlena M Ryba, Barbara L Andersen

Articles, Abstracts, and Reports

The gap between treatment development and efficacy testing to scaled up implementations of evidence-based treatment (EBT) is an estimated 20 years, and hybrid research designs aim to reduce the gap. One was used for a multisite study in cancer control, testing coprimary aims: (a) determine the feasibility and utility of a flexible EBT implementation strategy and (b) determine the clinical effectiveness of an EBT as implemented by newly trained providers. Therapists from 15 diverse sites implemented the biobehavioral intervention (BBI) for cancer patients (N = 158) as part of standard care. For implementation, therapists determined treatment format, number of …


Commonly Integrated Epigenetic Modifications Of Differentially Expressed Genes Lead To Adaptive Resistance In Cancer., Abdullah Al Emran, Diego M Marzese, Dinoop R Menon, Heinz Hammerlindl, Farzana Ahmed, Erika Richtig, Pascal Duijf, Dave Hoon, Helmut Schaider May 2019

Commonly Integrated Epigenetic Modifications Of Differentially Expressed Genes Lead To Adaptive Resistance In Cancer., Abdullah Al Emran, Diego M Marzese, Dinoop R Menon, Heinz Hammerlindl, Farzana Ahmed, Erika Richtig, Pascal Duijf, Dave Hoon, Helmut Schaider

Articles, Abstracts, and Reports

Aim: To investigate the integrated epigenetic regulation of acquired drug resistance in cancer. Materials & methods: Our gene expression data of five induced drug-tolerant cell models, one resistant cell line and one publicly available drug-resistant dataset were integrated to identify common differentially expressed genes and pathways. ChIP-seq and DNA methylation by HM450K beadchip were used to study the epigenetic profile of differential expressed genes. Results & conclusion: Integrated transcriptomic analysis identified a common 'viral mimicry' related gene signature in induced drug-tolerant cells and the resistant state. Analysis of the epigenetic regulation revealed a common set of down-regulated genes, which are …


The Need For A Network To Establish And Validate Predictive Biomarkers In Cancer Immunotherapy., Giuseppe V Masucci, Alessandra Cesano, Alexander Eggermont, Bernard A Fox, Ena Wang, Francesco M Marincola, Gennaro Ciliberto, Kevin Dobbin, Igor Puzanov, Janis Taube, Jennifer Wargo, Lisa H Butterfield, Lisa Villabona, Magdalena Thurin, Michael A Postow, Paul M Sondel, Sandra Demaria, Sanjiv Agarwala, Paolo A Ascierto Nov 2017

The Need For A Network To Establish And Validate Predictive Biomarkers In Cancer Immunotherapy., Giuseppe V Masucci, Alessandra Cesano, Alexander Eggermont, Bernard A Fox, Ena Wang, Francesco M Marincola, Gennaro Ciliberto, Kevin Dobbin, Igor Puzanov, Janis Taube, Jennifer Wargo, Lisa H Butterfield, Lisa Villabona, Magdalena Thurin, Michael A Postow, Paul M Sondel, Sandra Demaria, Sanjiv Agarwala, Paolo A Ascierto

Articles, Abstracts, and Reports

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and …


The Isb Cancer Genomics Cloud: A Flexible Cloud-Based Platform For Cancer Genomics Research., Sheila M Reynolds, Michael Miller, Phyliss Lee, Kalle Leinonen, Suzanne M Paquette, Zack Rodebaugh, Abigail Hahn, David L Gibbs, Joseph Slagel, William J Longabaugh, Varsha Dhankani, Madelyn Reyes, Todd Pihl, Mark Backus, Matthew Bookman, Nicole Deflaux, Jonathan Bingham, David Pot, Ilya Shmulevich Nov 2017

The Isb Cancer Genomics Cloud: A Flexible Cloud-Based Platform For Cancer Genomics Research., Sheila M Reynolds, Michael Miller, Phyliss Lee, Kalle Leinonen, Suzanne M Paquette, Zack Rodebaugh, Abigail Hahn, David L Gibbs, Joseph Slagel, William J Longabaugh, Varsha Dhankani, Madelyn Reyes, Todd Pihl, Mark Backus, Matthew Bookman, Nicole Deflaux, Jonathan Bingham, David Pot, Ilya Shmulevich

Articles, Abstracts, and Reports

The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute to explore new approaches to computing on large cancer datasets in a cloud environment. With a focus on Data as a Service, the ISB-CGC offers multiple avenues for accessing and analyzing The Cancer Genome Atlas, TARGET, and other important references such as GENCODE and COSMIC using the Google Cloud Platform. The open approach allows researchers to choose approaches best suited to the task at hand: from analyzing terabytes of data using complex workflows to developing new analysis methods in common languages such …


Induction And Characterization Of Anti-Tumor Endothelium Immunity Elicited By Vallovax Therapeutic Cancer Vaccine., Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari Apr 2017

Induction And Characterization Of Anti-Tumor Endothelium Immunity Elicited By Vallovax Therapeutic Cancer Vaccine., Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari

Articles, Abstracts, and Reports

ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium. Using defined antigens associated with tumor endothelial cells, specific molecular entities were identified as being targeted by ValloVax induced antibodies. Binding of predominantly IgG …


Immunotherapy Biomarkers 2016: Overcoming The Barriers., James L Gulley, Jay A Berzofsky, Marcus O Butler, Alessandra Cesano, Bernard A Fox, Sacha Gnjatic, Sylvia Janetzki, Shyam Kalavar, Vaios Karanikas, Samir N Khleif, Ilan Kirsch, Peter P Lee, Cristina Maccalli, Holden Maecker, Jeffrey Schlom, Barbara Seliger, Janet Siebert, David F Stroncek, Magdalena Thurin, Jianda Yuan, Lisa H Butterfield Mar 2017

Immunotherapy Biomarkers 2016: Overcoming The Barriers., James L Gulley, Jay A Berzofsky, Marcus O Butler, Alessandra Cesano, Bernard A Fox, Sacha Gnjatic, Sylvia Janetzki, Shyam Kalavar, Vaios Karanikas, Samir N Khleif, Ilan Kirsch, Peter P Lee, Cristina Maccalli, Holden Maecker, Jeffrey Schlom, Barbara Seliger, Janet Siebert, David F Stroncek, Magdalena Thurin, Jianda Yuan, Lisa H Butterfield

Articles, Abstracts, and Reports

This report summarizes the symposium, 'Immunotherapy Biomarkers 2016: Overcoming the Barriers', which was held on April 1, 2016 at the National Institutes of Health in Bethesda, Maryland. The symposium, cosponsored by the Society for Immunotherapy of Cancer (SITC) and the National Cancer Institute (NCI), focused on emerging immunotherapy biomarkers, new technologies, current hurdles to further progress, and recommendations for advancing the field of biomarker development.


Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough Jan 2017

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …


New Cancer Immunotherapy Agents In Development: A Report From An Associated Program Of The 31, Prasad S Adusumilli, Edward Cha, Mark Cornfeld, Thomas Davis, Adi Diab, Thomas W Dubensky, Elizabeth Evans, Jane L Grogan, Bryan A Irving, Rom Leidner, Shane A Olwill, Patrick Soon-Shiong, Frederic Triebel, David Tuck, Adrian Bot, Roger D Dansey, Charles G Drake, Gordon J Freeman, Ramy Ibrahim, Salil Patel, Daniel S Chen Jan 2017

New Cancer Immunotherapy Agents In Development: A Report From An Associated Program Of The 31, Prasad S Adusumilli, Edward Cha, Mark Cornfeld, Thomas Davis, Adi Diab, Thomas W Dubensky, Elizabeth Evans, Jane L Grogan, Bryan A Irving, Rom Leidner, Shane A Olwill, Patrick Soon-Shiong, Frederic Triebel, David Tuck, Adrian Bot, Roger D Dansey, Charles G Drake, Gordon J Freeman, Ramy Ibrahim, Salil Patel, Daniel S Chen

Articles, Abstracts, and Reports

This report is a summary of 'New Cancer Immunotherapy Agents in Development' program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy.


Logic Models To Predict Continuous Outputs Based On Binary Inputs With An Application To Personalized Cancer Therapy., Theo A Knijnenburg, Gunnar W Klau, Francesco Iorio, Mathew J Garnett, Ultan Mcdermott, Ilya Shmulevich, Lodewyk F A Wessels Nov 2016

Logic Models To Predict Continuous Outputs Based On Binary Inputs With An Application To Personalized Cancer Therapy., Theo A Knijnenburg, Gunnar W Klau, Francesco Iorio, Mathew J Garnett, Ultan Mcdermott, Ilya Shmulevich, Lodewyk F A Wessels

Articles, Abstracts, and Reports

Mining large datasets using machine learning approaches often leads to models that are hard to interpret and not amenable to the generation of hypotheses that can be experimentally tested. We present 'Logic Optimization for Binary Input to Continuous Output' (LOBICO), a computational approach that infers small and easily interpretable logic models of binary input features that explain a continuous output variable. Applying LOBICO to a large cancer cell line panel, we find that logic combinations of multiple mutations are more predictive of drug response than single gene predictors. Importantly, we show that the use of the continuous information leads to …