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Precision Medicine In Cancer

Rafael Guerrero-Preston, Fahcina Lawson, Sebastian Rodriguez-Torres, Maartje G Noordhuis, Francesca Pirini, Laura Manuel, Blanca Valle, Tal Hadar, Bianca L Rivera, Oluwasina Folawiyo, Adriana Báez, Luigi Marchionni, Wayne M Koch, William H Westra, Young J Kim, James R Eshleman, David Sidransky
To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer. We examined germ-line and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and Non-Latino White (NLW) head and neck cancer patients. Cox proportional hazards revealed that Black HNSCC patients with PAX5 (p=0.06) and PAX1 (p=0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode and TNM stage (n=118)...
February 18, 2019: Cancer Prevention Research
David M Kingsley, Cassandra L Roberge, Alena Rudkouskaya, Denzel E Faulkner, Margarida Barroso, Xavier Intes, David T Corr
3D multicellular aggregates, and more advanced organotypic systems, have become central tools in recent years to study a wide variety of complex biological processes. Most notably, these model systems have become mainstream within oncology (multicellular tumor spheroids) and regenerative medicine (embryoid bodies) research. However, the biological behavior of these in vitro tissue surrogates is extremely sensitive to their aggregate size and geometry. Indeed, both of these geometrical parameters are key in producing pathophysiological gradients responsible for cellular and structural heterogeneity, replicating in vivo observations...
February 15, 2019: Acta Biomaterialia
Kyungmi Yang, Sang Won Jung, Hyemi Shin, Do Hoon Lim, Jung-Il Lee, Doo-Sik Kong, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam
BACKGROUND AND PURPOSE: To find genetic markers associated with response to radiotherapy (RT) in glioblastoma (GB) patients. MATERIALS AND METHODS: From Jan 2009 to Dec 2016, 161 patients with newly diagnosed IDH-wild type GB were treated with surgery and adjuvant concurrent chemoradiotherapy with the Stupp's regimen, and then genomic research proceeded with their surgical specimens. Among the 161 patients, 49 with clinically measurable disease on postoperative MRI were analyzed...
February 2019: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Daniel Ansari, William Torén, Qimin Zhou, Dingyuan Hu, Roland Andersson
Pancreatic cancer remains the most fatal human tumor type. The aggressive tumor biology coupled with the lack of early detection strategies and effective treatment are major reasons for the poor survival rate. Collaborative research efforts have been devoted to understand pancreatic cancer at the molecular level. Large-scale genomic studies have generated important insights into the genetic drivers of pancreatic cancer. In the post-genomic era, protein sequencing of tumor tissue, cell lines, pancreatic juice, and blood from patients with pancreatic cancer has provided a fundament for the development of new diagnostic and prognostic biomarkers...
February 15, 2019: Cell Biology and Toxicology
Nazish Sayed, Mohamed Ameen, Joseph C Wu
Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure...
February 15, 2019: Cardiovascular Research
Sahand Khakabimamaghani, Yogeshwar D Kelkar, Bruno M Grande, Ryan D Morin, Martin Ester, Daniel Ziemek
MOTIVATION: Patient stratification methods are key to the vision of precision medicine. Here, we consider transcriptional data to segment the patient population into subsets relevant to a given phenotype. Whereas most existing patient stratification methods focus either on predictive performance or interpretable features, we developed a method striking a balance between these two important goals. RESULTS: We introduce a Bayesian method called SUBSTRA that uses regularized biclustering to identify patient subtypes and interpretable subtype-specific transcript clusters...
February 15, 2019: Bioinformatics
Daniela F Duarte Campos, Andrea Bonnin Marquez, Cathal O'Seanain, Horst Fischer, Andreas Blaeser, Michael Vogt, Diana Corallo, Sanja Aveic
In vitro cancer 3D models are valuable tools to provide mechanistic insight into solid tumor growth, invasion, and drug delivery. The 3D spheroid model of solid tumors has been the most popular cancer model in use until now. However, previous studies have shown that these spheroid models lack sufficient morphological parameters, which may affect their response to chemicals. In this work, we proposed the fabrication of miniaturized 3D cancer models using collagen type I-based bioprintable bioinks. In the context of a mimicking model for advanced neuroblastoma studies, we showed that cancer cells contained in bioprintable bioinks formed Homer Wright-like rosettes, maintained their proliferative capacities and produced an equivalent Vimentin-rich matrix unlike that of non-bioprintable bioinks which made for poorer models...
February 5, 2019: Cancers
Caitlin Murphy, Andrea Muscat, David Ashley, Violet Mukaro, Linda West, Yang Liao, David Chisanga, Wei Shi, Ian Collins, Sally Baron-Hay, Sujata Patil, Geoffrey Lindeman, Mustafa Khasraw
BACKGROUND: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. PATIENTS AND OUTCOME MEASURES: Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25...
2019: PloS One
Xin Li, Michael Enzerra, Daniel Arnold Smith, Amir Ata Rahnemai-Azar, Elias Kikano, Nikhil H Ramaiya
Until recently, the treatment of small cell lung cancer (SCLC), a malignancy classically described as having a robust response to first-line therapy with near-universal recurrence, has remained relatively unchanged. Advancements in the management of SCLC have lagged behind those seen for non-small cell lung cancers. As the era of precision medicine and targeted immunotherapy evolves, radiologists must be familiar with the modern treatment paradigms of SCLC and associated imaging patterns, including classic and nonclassic appearances of treatment complications...
February 11, 2019: Journal of Computer Assisted Tomography
Ramón M Almela, Agustina Ansón
In dogs, melanomas are relatively common tumors and the most common form of oral malignancy. Biological behavior is highly variable, usually aggressive, and frequently metastatic, with reported survival times of three months for oral or mucosal melanomas in advanced disease stages. Classical clinical management remains challenging; thus, novel and more efficacious treatment strategies are needed. Evidence-based medicine supports the role of the immune system to treat neoplastic diseases. Besides, immunotherapy offers the possibility of a precise medicinal approach to treat cancer...
February 12, 2019: Veterinary Sciences
Shu-Hai Chen, Bing-Yuan Zhang, Bin Zhou, Cheng-Zhan Zhu, Le-Qi Sun, Yu-Jie Feng
Perineural invasion (PNI) can be found in a variety of malignant tumors. It is a sign of tumor metastasis and invasion and portends the poor prognosis of patients. The pathological description and clinical significance of PNI are clearly understood, but exploration of the underlying molecular mechanism is ongoing. It was previously thought that the low-resistance channel in the anatomic region led to the occurrence of PNI. However, with rapid development of precision medicine and molecular biology, we have gradually realized that the occurrence of PNI is not the result of a single factor...
2019: American Journal of Cancer Research
Weerachai Pipatrattanaseree, Arunporn Itharat, Nichamon Mukkasombut, Ubonwan Saesiw
BACKGROUND: The root of Baliospermum montanum has been used as an ingredient of traditional Thai medicines for the treatments of several diseases including itching eczema, muscle and joint inflammation, and cancer. Few studies have been done on phytochemical components of this root. In this study, we isolated major compounds of the crude ethanolic extract of B. montanum root and developed and validated a high performance liquid chromatographic (HPLC) method for the determination of its major components...
February 12, 2019: BMC Complementary and Alternative Medicine
Martina Pagliuca, Carlo Buonerba, Karim Fizazi, Giuseppe Di Lorenzo
Prostate cancer (PC) is a major health issue in developed countries, with, on the one hand, men suffering from sequelae related to unnecessary treatment of non-lethal PC, and, on the other hand, still dying because of advanced PC that progresses to castration-resistant disease. Systemic treatment is the mainstay of therapy of castration-resistant PC (CRPC). To date, a multitude of systemic agents have been tested and many of these have failed to provide a clinically meaningful benefit in CRPC, while others have been approved by the US Food and Drug Administration and/or the European Medicines Agency, including antiandrogen hormonal drugs (abiraterone, enzalutamide, apalutamide), chemotherapy (docetaxel and cabazitaxel), immunotherapy (Sipuleucel-T), and radiopharmaceutical (Radium-223) agents...
February 11, 2019: Drugs
Aaron C Elkins, Myrna A Deseo, Simone Rochfort, Vilnis Ezernieks, German Spangenberg
The social push for the therapeutic use of cannabis extracts has increased significantly over recent years. Cannabis is being used for treatment for conditions such as epilepsy, cancer and pain management. There are a range of medicinal cannabis products available, but the use of cannabis resin obtained by super critical fluid extraction, often diluted in oil, is becoming increasingly more prominent. Much of the research on cannabis has focused on plant biomass or the final therapeutic product with a concerning lack of information on the intermediate resin...
January 30, 2019: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Guilherme D Kolinger, David Vállez García, Gerbrand M Kramer, Virginie Frings, Egbert F Smit, Adrianus J de Langen, Rudi A J O Dierckx, Otto S Hoekstra, Ronald Boellaard
BACKGROUND: Total metabolic active tumour volume (TMATV) and total tumour burden (TTB) are increasingly studied as prognostic and predictive factors in non-small cell lung cancer (NSCLC) patients. In this study, we investigated the repeatability of TMATV and TTB as function of uptake interval, positron emission tomography/computed tomography (PET/CT) image reconstruction settings, and lesion delineation method. We used six lesion delineation methods, four direct PET image-derived delineations and two based on a majority vote approach, i...
February 7, 2019: EJNMMI Research
Anja van de Stolpe, Laurent Holtzer, Henk van Ooijen, Marcia Alves de Inda, Wim Verhaegh
Signal transduction pathways are important in physiology and pathophysiology. Targeted drugs aim at modifying pathogenic pathway activity, e.g., in cancer. Optimal treatment choice requires assays to measure pathway activity in individual patient tissue or cell samples. We developed a method enabling quantitative measurement of functional pathway activity based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the pathway-associated transcription factor...
February 7, 2019: Scientific Reports
Xin Qi, Yuxin Lin, Jiajia Chen, Bairong Shen
Crosstalk between competing endogenous RNAs (ceRNAs) is mediated by shared microRNAs (miRNAs) and plays important roles both in normal physiology and tumorigenesis; thus, it is attractive for systems-level decoding of gene regulation. As ceRNA networks link the function of miRNAs with that of transcripts sharing the same miRNA response elements (MREs), e.g. pseudogenes, competing mRNAs, long non-coding RNAs, and circular RNAs, the perturbation of crucial interactions in ceRNA networks may contribute to carcinogenesis by affecting the balance of cellular regulatory system...
January 30, 2019: Briefings in Bioinformatics
Paulina Krzyszczyk, Alison Acevedo, Erika J Davidoff, Lauren M Timmins, Ileana Marrero-Berrios, Misaal Patel, Corina White, Christopher Lowe, Joseph J Sherba, Clara Hartmanshenn, Kate M O'Neill, Max L Balter, Zachary R Fritz, Ioannis P Androulakis, Rene S Schloss, Martin L Yarmush
Cancer is a devastating disease that takes the lives of hundreds of thousands of people every year. Due to disease heterogeneity, standard treatments, such as chemotherapy or radiation, are effective in only a subset of the patient population. Tumors can have different underlying genetic causes and may express different proteins in one patient versus another. This inherent variability of cancer lends itself to the growing field of precision and personalized medicine (PPM). There are many ongoing efforts to acquire PPM data in order to characterize molecular differences between tumors...
September 2018: Technology
Chunmei Cen, Fengfeng Cai, Manuel Antonio Falar Luis, Ewelina Biskup
In recent years, the clinical application of circulating tumor cell (CTCs) detection has become one of the research hotspots in the field of precision medicine. CTCs detection is non-invasive, easy to obtain, can be repeatedly collected, highly repeatable and other advantages. It not only can be a real-time comprehensive monitoring of cancer treatment, but also have a large number of applications, including early diagnosis of tumor, timely evaluation of efficacy, condition monitoring, resistance factor analysis, prognosis judgment, individualized treatment of tumors, drug guidance, etc...
February 2, 2019: Rejuvenation Research
Steven B Ouellette
Personalized diagnostic testing (PDx) is a key component of the precision medicine toolkit and has shown the most development in cancer applications. Recent changes in the regulatory and legal landscapes regarding PDx development and commercialization have brought uncertainties to both intellectual property strategies and business model development. While the regulatory and legal uncertainties have been well-documented, there has been little reported analysis of the recent patent landscape and movement of IP into the PDx market...
February 2, 2019: Expert Opinion on Therapeutic Patents
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