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Annals of Translational Medicine

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https://www.readbyqxmd.com/read/29911116/the-art-of-war-and-oncology-applying-the-principles-of-strategy-and-tactics-to-greater-effect-in-the-era-of-targeted-therapy
#1
EDITORIAL
Emil Lou
No abstract text is available yet for this article.
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911115/transforming-research-engaging-patient-advocates-at-all-stages-of-cancer-research
#2
AnneMarie Ciccarella, Alicia C Staley, Aime T Franco
In recent years there has been a push to include patients and advocates in clinical research, including in clinical trial design and approval processes. Additionally, increased advocate-driven research funding has led to seats for advocates in the funding review process. However, despite advances that include having patients and advocates involved in clinical research projects that may directly, or eventually, affect their care and treatment, we have much further to go to make this a truly inclusionary participation in research...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911114/financial-toxicity-and-implications-for-cancer-care-in-the-era-of-molecular-and-immune-therapies
#3
REVIEW
George Tran, S Yousuf Zafar
Molecular and immune therapies have revolutionized cancer treatment and improved patient outcomes and survival. However, the pricing of these drugs has become an issue as the cost of cancer care continues to rise significantly. Cost sharing policies have increased out-of-pocket expenses for patients, leading to poorer financial well-being, quality of life, psychosocial health, and treatment adherence. In this review, we briefly examine some factors affecting the pricing of these new targeted therapies; the effects of financial toxicity on patients; and highlight potential health policy and patient-provider level interventions to address these issues...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911113/survival-outcomes-for-advanced-kidney-cancer-patients-in-the-era-of-targeted-therapies
#4
Arpit Rao, Charles Wiggins, Richard C Lauer
Background: Advanced renal cell carcinoma (RCC) results in over 14,000 deaths each year in the United States alone. The therapeutic landscape for advanced RCC changed dramatically with the approval of tyrosine kinase inhibitors (TKI) between 2006 and 2012. A large-scale analysis of survival trends has not been performed in the TKI era to determine their impact on outcomes for advanced RCC patients. Methods: The Surveillance, Epidemiology and End-Results (SEER) database was queried for adult patients with advanced RCC diagnosed between 2000 and 2013...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911112/translational-research-and-application-of-basic-biology-to-clinical-trial-development-in-gi-cancers
#5
REVIEW
Elizabeth Smyth, Khurum Khan, Nicola Valeri
Cancers of the gastrointestinal tract have limited available treatments and are often associated with a poor prognosis. Clinical trials and translational work associated with these trials provide the opportunity to increase understanding of the mechanisms of sensitivity and resistance to cytotoxic chemotherapy and targeted therapy in these diseases. In this review we discuss the rationale for intensive translational work within the context of academic clinical trials and the successes and challenges which have been associated with translational work at our institution over the past number of years...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911111/understanding-patterns-of-brain-metastasis-in-breast-cancer-and-designing-rational-therapeutic-strategies
#6
REVIEW
Evelyn M Brosnan, Carey K Anders
One of the most feared sequelae after a diagnosis of advanced breast cancer is development of metastases to the brain as this diagnosis can affect physical function, independence, relationships, quality of life, personality, and ultimately one's sense of self. The propensity to develop breast cancer brain metastases (BCBMs) varies by subtype, occurring in up to one half of those with triple negative breast cancer (TNBC), approximately a third of HER+ breast cancers and 14% in hormone positive disease. Median survival after BCBM diagnosis can be as short as 5 months in TNBC and 10-18 months in the other subtypes...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911110/optimization-of-a-microfluidics-based-next-generation-sequencing-assay-for-clinical-oncology-diagnostics
#7
Christine Henzler, Matthew Schomaker, Rendong Yang, Aaron P Lambert, Rebecca LaRue, Robyn Kincaid, Kenneth Beckman, Teresa Kemmer, Jon Wilson, Sophia Yohe, Bharat Thyagarajan, Andrew C Nelson
Background: Massively parallel, or next-generation, sequencing is a powerful technique for the assessment of somatic genomic alterations in cancer samples. Numerous gene targets can be interrogated simultaneously with a high degree of sensitivity. The clinical standard of care for many advanced solid and hematologic malignancies currently requires mutation analysis of several genes in the front-line setting, making focused next generation sequencing (NGS) assays an effective tool for clinical molecular diagnostic laboratories...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911109/prostate-cancer-in-the-era-of-omic-medicine-recognizing-the-importance-of-dna-damage-repair-pathways
#8
REVIEW
Zachary Kornberg, Jonathan Chou, Felix Y Feng, Charles J Ryan
Data from recent high-throughput studies analyzing local and advanced prostate cancer have revealed an incredible amount of biological diversity, which has led to the classification of distinct molecular tumor subtypes. While integrating prostate cancer genomics with clinical medicine is still at its infancy, new approaches to treat prostate cancer are well underway and being studied. With the recognition that DNA damage repair (DDR) mutations play an important role in the pathogenesis of this disease, clinicians can begin to utilize genomic information in complex treatment decisions for prostate cancer patients...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911108/emerging-application-of-genomics-guided-therapeutics-in-personalized-lung-cancer-treatment
#9
REVIEW
Aubhishek Zaman, Trever G Bivona
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911107/colorectal-cancer-genomics-and-designing-rational-trials
#10
REVIEW
Sebastian Mondaca, Rona Yaeger
The widespread use of next generation sequencing (NGS) has led to a refined understanding of the genomics of colorectal cancer (CRC). However, progress in the use of molecular biomarkers in standard practice has been slow, and there is no approved targeted therapy for CRC based on a positive predictive marker yet. In this review, we will first summarize biomarkers with clinical utility in standard practice or targeted therapy trials and then consider how to rationally design clinical trials to more effectively target CRC...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29911106/translational-approaches-to-investigation-of-solid-tumor-malignancies-shifting-landscapes-smarter-strategies-and-tactics-for-therapeutic-design-improving-patient-outcomes
#11
https://www.readbyqxmd.com/read/29862246/the-search-for-gene-gene-interactions-in-genome-wide-association-studies-challenges-in-abundance-of-methods-practical-considerations-and-biological-interpretation
#12
Marylyn D Ritchie, Kristel Van Steen
One of the primary goals in this era of precision medicine is to understand the biology of human diseases and their treatment, such that each individual patient receives the best possible treatment for their disease based on their genetic and environmental exposures. One way to work towards achieving this goal is to identify the environmental exposures and genetic variants that are relevant to each disease in question, as well as the complex interplay between genes and environment. Genome-wide association studies (GWAS) have allowed for a greater understanding of the genetic component of many complex traits...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862245/abnormal-chest-x-ray-leading-to-diagnosis-of-partial-anomalous-pulmonary-venous-connection
#13
Zahava Farkas, Abbas Haidry, Srikanth Yandrapalli, Marc Lim, Diwakar Jain, Wilbert S Aronow
With the growing use of imaging to aid in both diagnosis and treatment of patients presenting with a myriad of clinical presentations, incidental findings on imaging have become commonplace. Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital cardiovascular condition that often goes undiagnosed due to lack of symptoms early in life. In adulthood, it can manifest clinically as right-sided heart failure or pulmonary hypertension. We present a case of PAPVC, which, like most cases, was discovered incidentally on chest X-ray...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862244/immune-checkpoint-inhibitors-and-radiotherapy-concept-and-review-of-current-literature
#14
REVIEW
Loka Thangamathesvaran, Roshni Shah, Rebeka Verma, Omar Mahmoud
Traditional chemotherapeutic agents non-selectively eliminate cancer cells at the expense of normal tissue; in an attempt to minimize such effects, a new class of targeted agents, immunotherapy, was introduced in the late 1950s with the discovery of interferons and the development of the first cancer vaccine. Ever since, immunotherapy evolved, exploiting different cellular mechanisms including dendritic cell therapy, monoclonal antibodies, and cytokines. Immune checkpoint inhibitors (ICPI) are the most recent subclass of this family and we herein review the basis of exploiting this new subclass of immunotherapy with radiotherapy in the context of studies evaluating their effects on human subjects and focusing on the synergism between the molecular pathways operating in the background...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862243/aminoquinoline-antimalarial-therapy-in-dermatomyositis-are-we-missing-opportunities-with-respect-to-comorbidities-and-modulation-of-extracutaneous-disease-activity
#15
REVIEW
Richard D Sontheimer
It is now widely accepted that long-term aminoquinoline antimalarial therapy with hydroxychloroquine (HCQ) can mitigate one of the most important comorbidities of systemic lupus erythematosus (LE)-atherosclerotic cardiovascular disease (ASCVD). Increasing evidence suggests that idiopathic inflammatory myopathy (IIM) patients have a risk for ASCVD comorbidity that is similar to that of systemic LE. I would like to explore the primary hypothesis that long-term HCQ therapy could provide those with IIM, especially dermatomyositis (DM) patients, an ASCVD comorbidity benefit similar to that of systemic LE...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862242/traditional-chinese-medicine-qiliqiangxin-attenuates-phenylephrine-induced-cardiac-hypertrophy-via-upregulating-ppar%C3%AE-and-pgc-1%C3%AE
#16
Rong-Rong Gao, Xiao-Dong Wu, Hui-Min Jiang, Yu-Jiao Zhu, Yan-Li Zhou, Hai-Feng Zhang, Wen-Ming Yao, Yong-Qin Li, Xin-Li Li
Background: Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862241/rosiglitazone-inhibits-pm2-5-induced-cytotoxicity-in-human-lung-epithelial-a549-cells
#17
Xian-Juan Pu, Jin Li, Qiu-Lian Zhou, Wen Pan, Yong-Qin Li, Yuhui Zhang, Jinhua Wang, Zheng Jiao
Background: Exposure to fine particulate matter <2.5 µm in diameter (PM2.5) leads to global adverse health effects, including increases in morbidity and mortality of respiratory diseases. PM2.5 increases production of reactive oxygen species (ROS) in the lung, which further lead to oxidative stress, cell apoptosis and cell death. According to results of previous studies, oxidative stress and subsequent cell apoptosis can be reduced by peroxisome proliferator-activated receptor gamma (PPARγ) in various cell types, however, its role in oxidative stress-related cell apoptosis caused by PM2...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862240/the-practical-benefit-of-phadiatop-test-as-the-first-line-in-vitro-allergen-specific-immunoglobulin-e-sige-screening-of-aeroallergens-among-chinese-asthmatics-a-validation-study
#18
Guangqiao Zeng, Haisheng Hu, Peiyan Zheng, Ge Wu, Nili Wei, Xueqing Liang, Baoqing Sun, Xiaowen Zhang
Background: Phadiatop test is a variant of ImmunoCAP assay that covers a mixture of common aeroallergens. Its diagnostic efficiency in Chinese population remains so far inadequate. We validated Phadiatop testing with ImmunoCAP assays in a Chinese cohort. Methods: Phadiatop test was performed for serum samples from 290 asthmatics and 92 healthy controls previously tested with "classic" ImmunoCAP for house dust mix (hx2), molds and yeasts mix (mx2), tree pollen mix (tx4) and weed mix (wx5)...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862239/a-technique-of-hand-digit-reconstruction-using-scarred-and-deformed-donor-segments
#19
Nikolay M Alexandrov, Michail G Volovik, Denis V Kiselev, Sergey V Petrov
Background: Hand digit reconstruction with transposition of hand segments in cases of hand injury is not used frequently by surgeons, at least in part because of potential ischemic complications after cicatricial changes in tissues. The aim of this study was to investigate the opportunities for expanding the set of indications for hand digit reconstruction using scarred and deformed donor segments. Methods: We developed a technique of ischemic preconditioning and preforming the segment before transfer to improve macro-circulation and micro-circulation in scarred donor segments with a view to preventing ischemic complications in reconstructed digits...
April 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29862238/targets-without-tolerances-improper-evaluation-of-medical-personnel
#20
Robert S Butler, Douglas Johnston, Michael W Kattan
Background: Mandated assessment of medical personnel by comparing individual performance averages to external targets is standard practice in many health care systems. This method of assessment uses only raw or adjusted averages without considering the associated variation. Failure to correctly incorporate variation in the assessment of medical personnel results in evaluations which are neither accurate nor fair with respect to assessing personnel performance. Methods: Accepted statistical methods for process evaluation and quality control, including regression, control charts, and adjusted means comparisons will be used to analyze hospital length of stay (LOS) patient data for the period between January and October 2010 for 12 physicians in the Cardiothoracic Surgery service line at the Cleveland Clinic...
April 2018: Annals of Translational Medicine
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