Dan Longo

Dan Longo
New England Journal of Medicine

About

1,046
Publications
87,810
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
69,333
Citations

Publications

Publications (1,046)
Article
Large B-cell lymphoma is a spectrum of aggressive B-cell cancers with broad genetic and clinical heterogeneity.¹ First-line chemotherapy cures most patients, but those with relapsed or refractory disease usually die of lymphoma. Salvage chemotherapy followed by autologous stem-cell transplantation (ASCT) is the standard second-line approach to larg...
Article
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in pro-inflammatory cytokines (including TNF and IL-6), which w...
Article
Full-text available
D‐Glucose and 3‐O‐Methyl‐D‐glucose (3OMG) have been shown to provide contrast in magnetic resonance imaging‐chemical exchange saturation transfer (MRI‐CEST) images. However, a systematic comparison between these two molecules has yet to be performed. The current study deals with the assessment of the effect of pH, saturation power level (B1) and ma...
Article
Full-text available
PurposeTriple-negative breast cancer (TNBC) patients have usually poor outcome after chemotherapy and early prediction of therapeutic response would be helpful. [18F]F-FDG-PET/CT acquisitions are often carried out to monitor variation in metabolic activity associated with response to the therapy, despite moderate accuracy and radiation exposure lim...
Article
Imaging technologies are used throughout the life and biomedical sciences to understand mechanisms in biology and diagnosis and therapy in animal and human medicine. We present criteria for globally applicable guidelines for open image data tools and resources for the rapidly developing fields of biological and biomedical imaging.
Article
Purpose The aim of this study was to investigate two clinically approved plasma volume expanders (dextran 70 and voluven) as macromolecular MRI‐chemical exchange saturation transfer (CEST) contrast agents to assess tumor vascular properties. Methods CEST contrast efficiency of both molecules (6% w/v) was measured in vitro at various irradiation sa...
Preprint
Triple-negative breast cancer (TNBC) patients have usually poor outcome after chemotherapy and early prediction of therapeutic response would be helpful. 18F-FDG-PET/CT acquisitions are often carried out to monitor variation in metabolic activity associated to response to the therapy, despite moderate accuracy and radiation exposure limit its appli...
Preprint
Full-text available
Purpose D-Glucose and 3-O-Methyl-D-glucose (3OMG) have been shown to provide contrast in MRI-CEST images. However, a systematic comparison between these two molecules has not yet been performed. This study dealt with the assessment of the effect of pH, saturation power level (B 1 ) and magnetic field strength (B 0 ) on the MRI-CEST contrast with th...
Preprint
Full-text available
Molecular imaging generates large volumes of heterogeneous biomedical imagery with an impelling need of guidelines for handling image data. Although several successful solutions have been implemented for human epidemiologic studies, few and limited approaches have been proposed for animal population studies. Preclinical imaging research deals with...
Article
Purpose Chemical exchange saturation transfer MRI provides new approaches for investigating tumor microenvironment, including tumor acidosis that plays a key role in tumor progression and resistance to therapy. Following iopamidol injection, the detection of the contrast agent inside the tumor tissue allows measurements of tumor extracellular pH. H...
Chapter
Full-text available
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide a noninvasive way for assessing renal functional information following the administration of a small molecular weight gadolinium-based contrast agent. This method may be useful for investigating renal perfusion and glomerular filtration rates of rodents in vivo under various...
Chapter
Full-text available
Magnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange saturation transfer (CEST) has pot...
Chapter
Full-text available
Chemical exchange saturation transfer (CEST) is recognized as one of the premier methods for measuring pH with this environmental variable expected to be an excellent biomarker for kidney diseases. Here we describe step-by-step CEST MRI experimental protocols for producing pH and perfusion maps for monitoring kidney pH homeostasis in rodents after...
Chapter
Full-text available
Renal MRI holds incredible promise for making a quantum leap in improving diagnosis and care of patients with a multitude of diseases, by moving beyond the limitations and restrictions of current routine clinical practice. Clinical and preclinical renal MRI is advancing with ever increasing rapidity, and yet, aside from a few examples of renal MRI...
Chapter
Full-text available
Dynamic contrast-enhanced (DCE) MRI monitors the transit of contrast agents, typically gadolinium chelates, through the intrarenal regions, the renal cortex, the medulla, and the collecting system. In this way, DCE-MRI reveals the renal uptake and excretion of the contrast agent. An optimal DCE-MRI acquisition protocol involves finding a good compr...
Chapter
Full-text available
Here we present an analysis protocol for dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data of the kidneys. It covers comprehensive steps to facilitate signal to contrast agent concentration mapping via T 1 mapping and the calculation of renal perfusion and filtration parametric maps using model-free approaches, model free analysis...
Chapter
Full-text available
The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally in...
Article
Full-text available
Background Tumour acidosis is considered to play a central role in promoting cancer invasion and migration, but few studies have investigated in vivo how tumour pH correlates with cancer invasion. This study aims to determine in vivo whether tumour acidity is associated with cancer metastatic potential. Methods Breast cancer cell lines with differ...
Article
The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO)....
Article
The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO)....
Article
PD-1 expression is a hallmark of both early antigen-specific T-cell activation and later chronic stimulation suggesting key roles in both naive T-cell priming and memory T-cell responses. Although important similarities exist between T cells and NK cells, there are critical differences reflecting their biology and functions. The putative role of PD...
Article
The introduction of “personalized medicine” has spurred major changes in oncology, but success has been spread unevenly across the spectrum of solid tumors. Although prognoses for adenocarcinoma of the lung and melanoma have been profoundly altered, other diseases, such as colon cancer and ovarian cancer, have lagged behind owing to differences in...
Article
Screening asymptomatic patients for cancer is based on a simple premise: cancers that are detected early before they produce symptoms should be easier to cure than those that progress to become clinically detectable. In practice, tools have been developed to realize the detection of clinically undetectable cancers, but the effect of their applicati...
Article
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a viable treatment option for many cancers but its clinical utility is limited due to the occurrence of graft-versus-host disease (GVHD). Understanding the impact of obesity on immune function has become increasingly important in the setting of the current obesity pandemic. We r...
Article
Improving communication with patients about treatment risks and benefits has long been recognized as a critical priority. But perhaps a necessary first step is for investigators to communicate with clinicians openly and specifically about the toxic effects of treatment.
Article
Full-text available
The cover image is based on the RESEARCH ARTICLE Quantification of hydroxyl exchange of D‐Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla by Moritz Zaiss et al., https://doi.org/10.1002/nbm.4113.
Article
Full-text available
Aims: To determine individual glucose hydroxyl exchange rates at physiological conditions and use this information for numerical optimization of glucoCEST/CESL preparation. To give guidelines for in vivo glucoCEST/CESL measurement parameters at clinical and ultra-high field strengths. Methods: Five glucose solution samples at different pH values...
Article
Objective: The early embryo implantation is characterized by enhanced uterine vascular permeability at the site of blastocyst attachment, followed by extracellular-matrix remodeling and angiogenesis. Two TG (transglutaminase) isoenzymes, TG2 (tissue TG) and FXIII (factor XIII), catalyze covalent cross-linking of the extracellular-matrix. However,...
Article
In July 2018, the Journal published the results of TAILORx (Trial Assigning Individualized Options for Treatment).¹ This randomized trial conducted by Sparano et al. showed the noninferiority of endocrine therapy to chemoendocrine therapy with respect to invasive disease–free survival among women with hormone-receptor–positive, human epidermal grow...
Article
Full-text available
Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic produ...
Article
Of all the physiological parameters affecting human health, few have generated such an overwhelming consensus of adverse effects as obesity (typically defined as having a body mass index [BMI] ≥30). The incidence of obesity has been steadily rising in developed countries, reaching pandemic proportions, with a prevalence of more than 39% in the Unit...
Article
Full-text available
The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors impacting outcome. Obesity is reaching pandemic proportions and is a major risk factor for certain malignancies, but the impact of obesity on immune resp...
Article
The article by Moore et al.¹ in this issue of the Journal is the culmination of a long march for olaparib in the treatment of BRCA-mutated high-grade serous ovarian cancer — one that began with its discovery by means of synthetic lethality screening, followed by years of clinical trials to define its activity and refine its uses, and finally led to...
Article
More than 1 million apheresis platelet collections are performed annually in the United States. After 2 healthy plateletpheresis donors were incidentally found to have low CD4+ T-lymphocyte counts, we investigated whether plateletpheresis causes lymphopenia. We conducted a cross-sectional single-center study of platelet donors undergoing plateletph...
Article
Macrophages are an essential component of the tumor microenvironment and have been ascribed a role in cancer-promoting inflammation.1,2 Phagocytic cells (a component of innate immunity) mediate first-line resistance against pathogens and, when appropriately activated, can mediate extracellular killing and phagocytosis of tumor cells.¹⁻³ However, tu...
Article
Full-text available
Purpose Prostate cancer (PCa) is the most widespread tumor affecting males in Western countries. We propose a novel MRI molecular tetrameric probe based on the heptadentate gadolinium (Gd)‐AAZTA (6‐amino‐6‐methylperhydro‐1,4‐diazepinetetraacetic acid) that is able to in vivo detect PCa through the recognition of the fibrin–fibronectin (FB–FN) compl...
Chapter
Full-text available
In humans, the adaptive and innate immune system works in concert to combat a variety of insults stemming from foreign invasion by pathogens to abnormal cancer cell growth. An increase in cancer as well as increased incidence and severity of infectious diseases occur with age. Changes in the function of the immune system with age, often termed immu...
Article
Two thulium-based ParaCEST responsive contrast agents, Tm-DOTAm-py and Tm-DOTAm-βAla-py, have been synthesized and evaluated for imaging copper and zinc. Unusual for responsive MRI contrast agents, both agents display a complete on/off response in the presence of the transition metals. Both complexes function as paraCEST agents in the absence of co...
Article
Purpose of review: We intend to highlight progress made in 2017 to lung cancer molecular nosology and application of new knowledge to treatment. Recent findings: Studies have shown that agents targeting specific molecular defects in lung cancers such as epidermal growth factor receptor(egfr) mutations, alk or ros1 gene rearrangements, are more e...
Chapter
Lymphomas can occur in conjunction with other diseases, most commonly those with associated immune dysregulation. In most cases, immune dysfunction is the result of an inherited or acquired immunodeficiency. Acquired deficiencies result from various infections, typically viruses, or from iatrogenic immune suppression. Alternatively, immune dysregul...
Article
Full-text available
Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza...
Article
This article has no abstract; the first 100 words appear below. The initial successes of combination chemotherapy were stunning. Childhood acute leukemia, several forms of lymphoma, and testicular cancer all became largely curable malignant conditions. Adjuvant chemotherapy led to dramatically longer survival among persons with breast cancer. The f...
Article
Full-text available
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide...
Article
Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in t...
Article
This article has no abstract; the first 100 words appear below. A paradox of DNA biology is that sequence integrity must be maintained in order for the organism to maintain life and normal functions, yet evolution requires some variability in gene expression so that changes that are more adaptive are positively selected. Indeed, more highly evolved...
Article
Full-text available
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signa...
Article
There has been substantial progress in clinical outcomes for patients with multiple myeloma. This encouraging trend derives in large part from the increasing number of effective therapeutic options and the ability as a result of this to achieve higher quality responses to treatment. The approval of both daratumumab and of elotuzumab in combination...
Article
A dynamic contrast enhanced (DCE) approach for tumor photoacoustic (PA) imaging is described. Novel water soluble melanin-based derivatives are synthesized that exhibit good PA properties, stability, safety and accumulation in tumor bearing mice. This melanin derivative is capable to characterize tumor vasculature and to monitor vessel permeability...
Article
Full-text available
The vast majority of cancers exhibit increased glucose uptake and glycolysis regardless of oxygen availability. This metabolic shift leads to an enhanced production of lactic acid that decreases extracellular pH (pHe), a hallmark of the tumor microenvironment. In this way, dysregulated tumor pHe and upregulated glucose metabolism are linked tightly...
Article
Full-text available
Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved h...
Article
Follicular lymphoma (FL) represents more than 20% of all non-Hodgkin lymphomas worldwide (1) and approximately 30% of the non-Hodgkin lymphomas diagnosed in the United States.(2) Although occasionally localized at the time of diagnosis, most patients have disseminated disease.(3) However, patients are frequently asymptomatic and this, in combinatio...
Article
Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here w...
Article
The aerial view of the concept of data sharing is beautiful. What could be better than having high-quality information carefully reexamined for the possibility that new nuggets of useful data are lying there, previously unseen? The potential for leveraging existing results for even more benefit pays appropriate increased tribute to the patients who...
Article
Full-text available
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide...
Article
Long-term survival after a diagnosis of Hodgkin’s lymphoma depends on two interrelated factors — successful elimination of disease and the avoidance of treatment-related second cancers and cardiovascular disease. Ever since the importance of this balance between treatment efficacy and toxicity was recognized, attempts have been made to maintain or...
Article
For hospitalized patients whose death is imminent, palliative care can alleviate distressing symptoms that are common during the last few days or weeks of life. The essentials of such care that are presented in this review are intended to provide both generalists and specialists in fields other than palliative care with a practical, evidence-based...