S. James Adelstein

S. James Adelstein
Harvard University | Harvard · Medical School

MD, PhD

About

362
Publications
26,867
Reads
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11,244
Citations
Introduction
S. James Adelstein is now an emeritus professor at Harvard Medical School. His current interests are in decision analysis and the history of technology development.
Additional affiliations
July 1968 - present
Harvard University
Position
  • Paul C. Cabot Professor of Medical Biophysics, Emeritus
January 2002 - December 2013
Brigham and Women's Hospital
Position
  • Nuclear Medicine
January 1980 - December 2012
Harvard Medical School
Position
  • Harvard University
Description
  • Radiation Biophysics
Education
July 1954 - June 1957
September 1949 - June 1953
Harvard University
Field of study
  • Medicine

Publications

Publications (362)
Article
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Scitation is the online home of leading journals and conference proceedings from AIP Publishing and AIP Member Societies
Article
Given the central roles that anatomical and functional imaging now play in medical practice, there have been concerns about the increasing levels of radiation exposure and their potential hazards. Despite incomplete quantitative knowledge of the risks, it is prudent to think of radiation, even at low doses, as a potential, albeit weak, carcinogen....
Article
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In recent studies, we showed that several oncogenes and cancer-associated genes and proteins are differentially expressed in phagocytic WBCs of tumor-bearing mice (colon, lung, melanoma, and prostate), compared to non-phagocytic WBCs from the same mice as well as to phagocytic WBCs obtained from non-tumor-bearing mice. Prompted by the translational...
Article
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Purpose: To determine the possible effects of (125)I-to-DNA distance on the magnitude and mechanism of Auger-electron induced-double-strand break (DSB) production. Materials and methods: We have synthesized a series of (125)I-labeled Hoechst (H) derivatives ((125)IE-H, (125)IB-H, (125)I-C(8)-H and (125)I-C(12)-H). While all four molecules share...
Article
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Purpose: To investigate the ability of human lymphocytes labeled with DNA-incorporated (125)I to exert an inhibitory (antiproliferative) bystander effect on co-cultured human colon adenocarcinoma LS174T cells in vitro. Materials and methods: Human peripheral blood lymphocytes were stimulated to synthesize DNA in the presence of phytohemagglutini...
Article
The enlightened formation, by Bert and Kuggie Vallee, of a procedure whereby senior scientists spend short time of about a month at Harvard, Oxford and other institutions, is illustrated by the views and opinions of those selected.
Article
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Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (such as genes, proteins and miRN...
Article
The widely used agarose gel electrophoresis method for assessing radiation-induced single-strand-break (SSB) yield in plasmid DNA involves measurement of the fraction of relaxed-circular (C) form that migrates independently from the intact supercoiled (SC) form. We rationalized that this method may underestimate the SSB yield since the position of...
Article
Human placental alkaline phosphatase has been identified as a hydrolase that is significantly overexpressed on the surface of various solid tumor cells, and is therefore a suitable prodrug design target for non-invasive cancer imaging and therapy. Structure-based prediction of enzymatic activities is essential for rational prodrug design. We have b...
Article
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The value of pediatric nuclear medicine is well established. Pediatric patients are referred to nuclear medicine from nearly all pediatric specialties including urology, oncology, cardiology, gastroenterology, and orthopedics. Radiation exposure is associated with a potential, small, risk of inducing cancer in the patient later in life and is highe...
Article
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Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily ac...
Article
This special report aims to inform the medical community about the many challenges involved in managing radiation exposure in a way that maximizes the benefit-risk ratio. The report discusses the state of current knowledge and key questions in regard to sources of medical imaging radiation exposure, radiation risk estimation, dose reduction strateg...
Article
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The exponential growth of high-throughput Omics data has provided an unprecedented opportunity for new target identification to fuel the dried-up drug discovery pipeline. However, the bioinformatics analysis of large amount and heterogeneous Omics data has posed a great deal of technical challenges for experimentalists who lack statistical skills....
Article
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Prostate cancer is the most common cancer among men worldwide and is the second leading cause of death among those over 50 years of age in the USA. However, many men who develop a prostate tumor never exhibit symptoms in the early stage of the disease or even before it spreads to other parts of the body, such as bones and lymph nodes. Therefore, th...
Article
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In previous studies we demonstrated a high tumor-targeting value of the 123I-labeled thymidine analogue 5-iodo-2'-deoxyuridine (IUdR) infused intra-arterially in patients with liver metastases from colorectal cancer. In the present study we have explored the possibility of enhancing tumor uptake of [123I]IUdR, by biochemical modulation with 5-fluor...
Article
Purpose: The incubation of the DNA minor-groove binder [ 125 I]iodoHoechst 33342 (125 IH) with plasmid DNA leads to the production of one double-strand break (dsb) per decay, both in the presence and absence of dimethylsulfoxide (DMSO). In contrast, when 125 I is incorporated into mammalian cell DNA as an iodinated pyrimidine base, DMSO decreases t...
Article
Full-text available
Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (such as genes, proteins and miRN...
Article
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[This corrects the article on p. e3661 in vol. 3, PMID: 18987750.].
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To determine double-strand-break (DSB) yields produced by decay of minor-groove-bound (123)I-labeled Hoechst 33342 ((123)IEH) in supercoiled (SC) and linear (L) forms of pUC19 DNA, to compare strand-break efficiency of (123)IEH with that of (125)IEH, and to examine the role of DNA topology in DSB induction by these Auger electron emitters. Tritium-...
Article
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To synthesize N-(3-(3-aminopropylamino)propyl)-2-oxo-2H-chromene-3-carboxamide (7), a novel DNA-binding, coumarin-based, fluorescent hydroxylradical ((*)OH) indicator and to assess its quantum efficiency compared with that of coumarin-3-carboxylic acid (1) and N1,N12-bis[2-oxo-2H-chromene-3-carbonyl]- 1,12-diamine-4,9-diazadodecane (9). Using compu...
Article
Full-text available
Neoplastic meningitis is often the final outcome of disseminated cancer and is rapidly lethal. Its limited treatment relies on systemic or intrathecal chemotherapy with methotrexate (MTX) or thiotepa. When 5-iodo-2'-deoxyuridine labeled with (125)I ((125)IUdR) is incorporated into the DNA of mitotic tumor cells, the Auger electrons emitted during i...
Data
Literature-confirmed marker genes (among 35 common markers across prostate, breast and lung cancer) that are prognostic of benign and malignant disease in patients. (0.04 MB DOC)
Data
Unique blood-borne biomarkers for six human tumors (0.16 MB XLS)
Data
Prostate, breast and lung common markers (0.02 MB XLS)
Data
Number of blood-borne cancer markers identified in six common human tumors. (0.04 MB DOC)
Data
Ranked blood-borne biomarkers for six human tumors (0.83 MB XLS)
Article
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Preparations of circular plasmid DNA in either supercoiled or nicked circular form often are contaminated with undesired linear DNA fragments arising from shearing/degradation of chromosomal DNA or linearization of plasmid DNA itself. We report a simple enzymatic method, using a combination of lambda exonuclease and RecJ(f), for the selective remov...
Article
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From a structural perspective, the factors controlling and the mechanisms underlying the toxic effects of ionizing radiation remain elusive. We have studied the consequences of superhelical/torsional stress on the magnitude and mechanism of DSBs induced by low-energy, short-range, high-LET Auger electrons emitted by (125)I, targeted to plasmid DNA...
Article
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With the arrival of the postgenomic era, there is increasing interest in the discovery of biomarkers for the accurate diagnosis, prognosis, and early detection of cancer. Blood-borne cancer markers are favored by clinicians, because blood samples can be obtained and analyzed with relative ease. We have used a combined mining strategy based on an in...
Article
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Most cancer therapeutics (chemo, radiation, antibody-based, anti-angiogenic) are at best partially and/or temporarily effective. In general, the causes for failure can be summarized as: (i) poor diffusion and/or nonuniform distribution of drug/prodrug molecules in solid tumors; (ii) high drug concentration and retention in normal tissues (leading t...
Article
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A high-yield radioiodination method for various types of molecules is described. The approach employs DMSO as precursor solvent, a reaction ratio of 2-5 precursor molecules per iodine atom, 5-10 microg oxidant, and a 10-25 microl reaction volume. The solution is vortexed at room temperature for 1-5 min and progress of the reaction is assessed by HP...
Article
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To develop a molecular probe for detection of hydroxyl radicals in the vicinity of DNA, the coumarin-polyamine complexes, N(1),N(12)-bis[2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (5) and tris[2-(2-oxo-2H-chromene-3-carboxamido)ethyl]amine (7), and their hydroxylated derivatives, N(1),N(12)-bis[7-hydroxy-2-oxo-2H-chromene-3-carbon...
Article
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Our group is developing a novel technology, enzyme-mediated cancer imaging and therapy (EMCIT), that aims to entrap radioiodinated compounds within solid tumors for noninvasive tumor detection and therapy. In this approach, a water-soluble, radioiodinated prodrug is hydrolyzed in vivo to a highly water-insoluble compound by an enzyme overexpressed...
Chapter
The practitioner of pediatric nuclear medicine should have some knowledge of radiation effects and the potential hazards that may result from low-level radiation exposures. There are several reasons such information is essential. First, specialists should ensure that the exposure of patients to radiation from diagnostic or therapeutic procedures is...
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We are developing a noninvasive approach for targeting imaging and therapeutic radionuclides to prostate cancer. Our method, Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), aims to use enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule within the extracellular space of solid tumors. Advanced methods for data mining...
Article
Enzyme-mediated cancer imaging and therapy (EMCIT) is a novel approach in which radioactive water-soluble molecules are precipitated in vivo following their hydrolysis by extracellular enzymes overexpressed by cancer cells. AutoDock 3.0 was used to model the interaction-binding between a series of iodinated quinazolinone derivatives and human place...
Article
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As part of the development of enzyme-mediated cancer imaging and therapy, a novel technology to entrap water-insoluble radioactive molecules within solid tumors, we show that a water-soluble, radioactive quinazolinone prodrug, ammonium 2-(2'-phosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ(2-P)), is hydrolyzed by alkaline phosphatase t...
Article
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To clarify the contribution of apoptosis to cell death in four human solid tumor cell lines, clonogenic cell survival (indicator of radiosensitivity) and induction of caspase-3 (CASP-3)/caspase-3-like proteases (CASP-3LP) and the production of DNA fragmentation (markers for apoptosis) were studied in RKO, LS174T, MCF7 and TE671 cells exposed to DNA...
Article
Full-text available
Previously, the kinetics of strand break production by (125)I-labeled m-iodo-p-ethoxyHoechst 33342 ((125)IEH) in supercoiled (SC) plasmid DNA had demonstrated that approximately 1 DSB is produced per (125)I decay both in the presence and absence of the hydroxyl radical scavenger DMSO. In these experiments, an (125)IEH:DNA molar ratio of 42:1 was us...
Article
Ascertaining the aqueous solubility of compounds is important in the selection of drug candidates. We describe a radiotracer method for estimating water solubility of compounds that are soluble in dimethyl sulfoxide (DMSO). Various volumes of DMSO, saturated with 127I-labeled compound and spiked with the corresponding 125I-labeled derivative, are m...
Data
Data mining hit list for six common cancer types. This file contains detail information about gene products identified in six tumor-tissue types. The genes are listed in six separate Excel spreadsheets by gene name, synonyms, description, UniProt accession codes, and IPA-based cellular location and family.
Article
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The bystander effect, originating from cells irradiated in vitro, describes responses of surrounding cells not targeted by the radiation. Previously we demonstrated that the subcutaneous injection into nude mice of human adenocarcinoma LS174T cells lethally irradiated by Auger electrons from the decay of DNA-incorporated (125)I inhibits growth of c...
Article
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We present an effective, rapid, systematic data mining approach for identifying genes or proteins related to a particular interest. A selected combination of programs exploring PubMed abstracts, universal gene/protein databases (UniProt, InterPro, NCBI Entrez), and state-of-the-art pathway knowledge bases (LSGraph and Ingenuity Pathway Analysis) wa...
Article
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The X-ray analysis of the title compound, C19H19IO5, shows that the orientation of the two benzene rings is cis and confirms the E configuration of the mol­ecule. The occurrence of O—H⋯O hydrogen-bonding inter­actions results in the formation of centrosymmetric dimers.
Article
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This study assesses targeting of lung metastases in mice with the radioiodinated thymidine analog 5-[(123)I/(125)I]iodo-2'-deoxyuridine ((123)I-IUdR/(125)I-IUdR), formulated with varying amounts of tributyltin precursor and injected intravenously. Six- to 8-wk-old C57BL/6 mice were injected intravenously with B16F10 melanoma cells. Two weeks later,...
Article
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Although the general radiobiologic principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the radiobiologic effects observed in mammalian cells. External beam and brachytherapy emissions are composed of photons, whereas radiations of interest in radionuclide therapy are particulate. T...
Chapter
IntroductionRadiobiologic EffectsTargeting Principles in Radionuclide TherapyExperimental TherapeuticsSummaryReferences
Article
Molecular modeling and energy minimization calculations were performed to investigate the interaction of iodoHoechst 33342 analogs with DNA. The Lamarckian genetic algorithm (AutoDock 3.0) was used to model the interaction/binding between m-iodo-p-methoxyHoechst (IMH), a ligand available in the Protein Data Bank whose binding to the minor groove of...
Article
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To delineate the mechanisms underlying induction of apoptosis in malignant cells irradiated by DNA-incorporated iodine-125 or gamma-photons. Human tumor cells (RKO, LS174T, TE671, and MCF7) were irradiated by DNA-incorporated 5-[125I]iodo-2'-deoxyuridine (125IdUrd) or by gamma-photons. Clonogenic survival was determined by the colony-forming assay....
Article
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By using computer-assisted molecular modeling software, to assess the effects of structural modification on the interaction of 125I-labeled iodoHoechst ligands and DNA and to design new analogs with specified distances between the Auger-electron-emitting 125I atom and the DNA central axis. The Lamarckian genetic algorithm (AutoDock 3.0) was used to...
Article
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To assess the therapeutic potential of methotrexate (MTX) and 5-[1251]liodo-2'-deoxyuridine (125IdUrd) administered sequentially in rats bearing advanced (ten-day-old) intrathecal (i.t.) TE671 human rhabdomyosarcoma tumours. Nude rats were injected with TE671 cells through an i.t. placed catheter. Ten days later, the animals were injected i.t. over...
Article
Inherent in the application of advances in biomedical science to nuclear medicine is the concept of molecular targeting: the in vivo concentration of labeled tracer by a gene, its transcribed DNA, or its protein product. This mechanism of localization has been and is being exploited for both nuclear imaging and radioisotopic therapy. Agents, such a...
Article
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Auger-electron emitters represent an attractive alternative to beta-particle emitters for cancer therapy if they can be placed intracellularly, especially in close proximity to (or within) nuclear DNA. Based on investigations in animal tumor models, including those for ovarian cancer, bladder cancer, and brain and spinal cord tumors, in which the t...
Article
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Auger-electron cascades with their ability to deposit energy in extremely small volumes, typically in the range of cubic nanometers, have served as valuable probes of radiobiologic phenomena. Results from their experimental use form part of the evidence that nuclear DNA is the most radiosensitive cell element; that chromosomal aberrations and large...
Article
Full-text available
The bystander effect, originating from cells irradiated in vitro, describes the biologic response(s) of surrounding cells not directly targeted by a radiation insult. To overcome the limitations of in vitro tissue culture models and determine whether a bystander effect that is initiated by the in vivo decay of a radionuclide can be demonstrated in...
Article
A number of reasons have led to a reappraisal of dose specification for nuclear medicine. These include an appreciation of non-uniformities in the distribution of radioactivity in the body, at all levels, for even the most common diagnostic and therapeutic agents; an increasing need to deal with the complexities of varying dose rates; the imperativ...
Article
A number of reasons have led to a reappraisal of dose specification for nuclear medicine. These include an appreciation of non-uniformities in the distribution of radioactivity in the body, at all levels, for even the most common diagnostic and therapeutic agents; an increasing need to deal with the complexities of varying dose rates; the imperativ...