phosphorus-radioisotopes and Neoplasms

Radiolabeled proteins are used in a variety of laboratory applications as well as in radioimmunotherapy. This review focuses on methods that utilize genetic engineering to introduce exogenous phosphorylation sites into proteins. Protein kinase substrate sites can be introduced into target proteins to serve as tags for several purposes. Because many protein kinases, each preferring a unique consensus sequence, are well characterized, the essential structure and function of the target protein can be effectively preserved through judicious selection and design of the phosphate incorporation site. After phosphorylation, these proteins are often indistinguishable from the parent molecules in assays of functional or biological activity. This convenient approach permits incorporation of 32P, 33P, 35S, or nonradioactive 31P, and is rapid, efficient, and safe. Most importantly 32P labeling of monoclonal antibodies or other therapeutic protein candidates has several significant advantages over radioiodination or chemical conjugation of heavy metal isotopes.

Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Cattle; Child; Consensus Sequence; Cytokines; Humans; Immunoconjugates; Isotope Labeling; Membrane Proteins; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Neoplasms; Phosphorus Radioisotopes; Phosphorylation; Protein Interaction Mapping; Protein Kinases; Protein Processing, Post-Translational; Proteins; Radioimmunotherapy; Receptor, Interferon alpha-beta; Receptors, Interferon; Recombinant Fusion Proteins; Substrate Specificity; Sulfur Radioisotopes

Systemic radionuclide therapy is gaining popularity in the radiotherapy community and changing the management of painful osseous metastases. This form of therapy has two major advantages: (i) it addresses all sites of involvement; and (ii) selective absorption limits normal tissue dose. As a result, toxicity is reduced and the therapeutic ratio increased. The biokinetics, dosimetry, and clinical experience with these compounds are reviewed. To date, the best studied and most commonly used radionuclide is strontium-89. Large, prospectively randomized clinical trials have demonstrated its efficacy as a first-line therapy or as an adjuvant to external-beam radiotherapy. It is particularly useful when external-beam therapy options have been exhausted, and normal tissue tolerance has been reached. In metastatic prostate cancer, our recent survey suggests the formation of a new paradigm: local field external-beam radiotherapy to the painful index site in combination with prophylactic administration of systemic radionuclides for clinically occult metastases.

Topics: Bone and Bones; Humans; Neoplasm Metastasis; Neoplasms; Palliative Care; Phosphorus Radioisotopes; Radioisotopes; Rhenium; Samarium; Strontium Radioisotopes; Treatment Outcome

Bone pain is a common symptom in disseminated malignancy and may be difficult to manage effectively. Radiation is of proven benefit for pain palliation and there is growing interest in the therapeutic potential of bone-seeking radiopharmaceuticals. Clinical data relating to the use of phosphorus-32, strontium-89, samarium-153 EDTMP, rhenium-186 HEDP and tin-117m DTPA are reviewed in the context of the pathophysiology of metastatic bone pain. Possible mechanisms of action of palliative radiotherapy and, in particular, the theoretical role of early response genes are discussed. The application of Monte Carlo simulation to targeted radiotherapy for bone metastases may provide the basis for a clearer understanding of the microdosimetry and radiobiology of bone pain palliation and for reliable prediction of clinical response and toxicity.

Topics: Bone Neoplasms; Humans; Neoplasms; Palliative Care; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy Dosage; Rhenium; Samarium; Strontium; Tin Radioisotopes

The covalent binding of xenobiotics to DNA is an important trigger of the multistage process that leads to carcinogenesis. 32P-postlabeling represents a highly sensitive method for biomonitoring exposure to genotoxic agents and for cancer risk assessment; it is capable of detecting less than one DNA adduct per human genome. Recent improvements to the technique have shown that the resistance of adducted DNA to enzyme digestion may lead to an overestimation of the number of different adducts present in a sample.

Topics: Animals; Base Sequence; Cell Division; Cell Transformation, Neoplastic; DNA Adducts; Genome, Human; Humans; Models, Genetic; Molecular Sequence Data; Mutagenesis; Neoplasms; Phosphorus Radioisotopes; Precancerous Conditions; Radioisotope Dilution Technique; Sensitivity and Specificity; Xenobiotics

Estimating the cancer risk posed by heterocyclic amines depends on measuring how chemical dose influences measurable indicators of cancer progression. This data ideally should encompass the range of actual human exposure, at the low dose end, and laboratory animal studies, at the high dose end. Accelerator mass spectrometry (AMS) has been used to measure the absorption, fate, and DNA adduct dosimetry of the heterocyclic amines PhIP and MeIQx at doses equivalent to human consumption following single-dose administration and chronic daily dosing. AMS is a nuclear physics technique which specifically counts nuclei of cosmogenic isotopes, rather than relying on decay. For tracing 14C, sensitivity is increased 10(6)-fold relative to decay counting. We have found that tissue clearance rates for [2-(14)C]-PhIP are rapid (t1/2 = 1 h) at low dose (41 ng/kg), with most of the radiocarbon distributed to the liver and G.I. tract. MeIQx-DNA adduct levels decrease linearly with dose (5 mg/kg-500 ng/kg) in single dose exposures. Likewise, the biologically available dose of [2-(14)C]-MeIQx decreases linearly with decreasing dose (5 mg/kg-1 ng/kg). On chronic daily dosing, it takes 40 days for adducts to reach steady-state in tissues and adduct levels appear to decrease linearly with decreasing dose, except possibly at very low doses. DNA binding of PhIP involves both sulfation or acetylation of the N-hydroxylated PhIP. Quantitatively, sulfation appears to be an important pathway for PhIp activation in rodent tissue cytosols while acetylation appears quantitatively more important in human tissue cytosols. The greatest activity is in liver and intestinal tissues for both pathways. The specific DNA adducts formed in vivo and in vitro from exposure to PhIP and MeIQx are likely guanine adducts. These data suggest that DNA adduct dosimetry responds linearly with dose but may become sub-linear at very low doses for chronic exposure and that factors other than DNA adduction may be critical to explain these heterocyclic amines' tumorigenicity.

Topics: Animals; Carcinogens; DNA Adducts; Humans; Imidazoles; Mass Spectrometry; Mutagens; Neoplasms; Phosphorus Radioisotopes; Quinoxalines; Radioisotope Dilution Technique; Rodentia

Topics: 3-Iodobenzylguanidine; Antibodies, Monoclonal; Bone Neoplasms; Brachytherapy; Humans; Iodine Radioisotopes; Iodobenzenes; Neoplasms; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy Dosage; Rhenium; Samarium; Strontium Radioisotopes; Thyroid Neoplasms

Topics: Adenosine Triphosphate; Carcinogens; DNA; Humans; Neoplasms; Phosphorus Radioisotopes

The diagnostic and therapeutic application of radionuclides in oncology has led to an increased efficiency in the treatment of malignant tumors. Regarding diagnosis, measuring metabolic reactions in tumor tissue, especially by positron emission tomography, opened the potential for assaying tumor response to different treatment modalities and thus eventually for tailoring effective treatment of a given tumor in the individual patient. Regarding treatment, attention is given to the choice of the radionuclide for optimal deposition of the desired radiation in tumor cells avoiding exposure of normal cells; in this context microdosimetric considerations are essential with respect to beta-emitters, alpha-emitters, the Auger-effect and neutron capture therapy. Examples of therapeutic uses of radionuclides in the inorganic form are 131-I for thyroid cancer and 32-P for polycythemia vera; organically bound radionuclides are employed with precursors for tumor cell metabolism or with receptor seeking agents, such as MIBG and monoclonal antibodies which presently enjoy a particular interest and bear great promise. Stable nuclides, if properly accumulated within tumors, may be activated for therapy in situ, for example by thermal neutrons, as in neutron capture therapy using the 10-B (n, alpha)7-Li reaction. Treatment planning and execution with radionuclides have gained momentum over the past decade, yet much more needs to be done.

Topics: Antibodies, Monoclonal; Humans; Immunotherapy; Iodine Radioisotopes; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotopes; Radiotherapy Dosage; Thyroid Neoplasms; Tomography, Emission-Computed

Among several recently developed analytical methods, 32P-postlabeling analysis is a highly sensitive method for the detection and measurement of covalent carcinogen-DNA adducts and other DNA modifications. Since the method does not require radioactive carcinogens, it is suitable for DNA of humans exposed to environmental or occupational genotoxicants. The basic procedure entails the enzymatic incorporation of 32P-label into monomeric or dimeric hydrolysis products of DNA, followed by chromatographic mapping and autoradiography of the 32P-labeled digestion products and quantitation by scintillation spectrometry. Microgram amounts of DNA are analyzed; thus the assay is well suited for limited amounts of cells or tissue. Various versions of the assay afford different sensitivities of adduct detection. Under optimal conditions, one aromatic or bulky/hydrophobic adduct in 10(8)-10(10) nucleotides can be detected and measured (corresponding to 0.3-30 amol adduct/microgram DNA or 0.1-10 nmol adduct/mol DNA-P). The assay has been successfully applied to a variety of mutagenic (genotoxic) as well as non-mutagenic carcinogens. In humans, the 32P-postlabeling assay has been applied to DNA specimens from cigarette smokers, iron foundry workers, and coke oven workers. Estimation of total aromatic adduct levels in exposed individuals gave values of 1 adduct in 10(6)-10(8) DNA nucleotides. These values are similar to the total levels of persistent adducts in tissues of animals after exposure to initiating or carcinogenic doses of authentic aromatic genotoxicants. Among the non-mutagenic carcinogens investigated are estrogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), choline-devoid diet, carbon tetrachloride, and peroxisome proliferators. In addition, age-dependent DNA modifications (I-compounds) are being detected by 32P-postlabeling in animals that have not been knowingly exposed to mutagens/carcinogens. I-compound profiles and levels are dependent on species, tissue, sex, and diet. Reduced levels of I-compounds have been consistently noted in the target organ of carcinogen-exposed animals and in resulting neoplasms, suggesting that I-compound loss may play a role in carcinogenesis.

Topics: Animals; Autoradiography; Chromatography, Thin Layer; Cricetinae; DNA; DNA Damage; DNA Mutational Analysis; Humans; Mass Spectrometry; Mice; Neoplasms; Phosphorus Radioisotopes; Smoking

In 1981, I made the strong statement that "The therapeutic approach of internally administered radiopharmaceuticals offers the potential to outmode the present approaches of conventional radiation therapy and chemotherapy." The present article updates and further supports this statement with new data, especially with the use of [131I]MIBG in several cancers and proposes a plan for application of nonsealed source radionuclide therapy to most solid tumors.

Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Adult; Antibodies, Neoplasm; Brachytherapy; Child; Child, Preschool; Humans; Iodine Radioisotopes; Iodobenzenes; Middle Aged; Neoplasms; Neuroblastoma; Pheochromocytoma; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy Dosage; Risk

Supportive care are a strongly connected constituent of the curative and palliative treatment of cancer. They serve for prevention and early diagnosis, respectively, and treatment of complications during therapy and disturbances which may issue from the tumour disease itself. These are especially the results of the insufficiency of the bone marrow which in the last years increasingly moved into the centre of the therapeutic interest. A survey of the present state of the treatment of these and other general complications in patients with malignant neoplasms is given.

Topics: Anemia; Ascites; Blood Coagulation Disorders; Bone Marrow Transplantation; Cross Infection; Granulocytes; Humans; Hypercalcemia; Intracranial Pressure; Leukopenia; Neoplasms; Patient Isolation; Phosphorus Radioisotopes; Pleural Effusion; Thrombocytopenia; Transfer Factor; Transplantation, Autologous; Transplantation, Homologous

Radioactive colloidal solutions and suspensions are being widely used in the diagnosis and treatment of various diseases. The author considers the behaviour or radioactive disperse preparations in the body and devotes particular attention to the reasons for isotope transition from the colloidal to the ionic state. Questions concerned with producing and investigating radioactive colloidal solutions are discussed. In the light of the physical and chemical properties of the radioisotopes and of the disperse systems themselves, the author considers methods of producing the more important radioactive disperse preparations: colloidal solutions of noble metals; colloidal solutions containing phosphorus-32, yttrium-90 and isotopes of the rare-earth elements; colloidal solutions with with indium-113m, gallium-68, technetium-99m and rhenium-186; suspensions (macroaggregates and microspheres) for the diagnosis of lung diseases; and radioactive colloidal solutions based on quaternary ammonium base compounds.

Topics: Colloids; Drug Stability; Gallium Radioisotopes; Gold Colloid, Radioactive; Humans; Indium; Iodine Radioisotopes; Isotope Labeling; Lung Diseases; Mononuclear Phagocyte System; Neoplasms; Phosphorus Radioisotopes; Quaternary Ammonium Compounds; Radioisotopes; Radionuclide Imaging; Rhenium; Serum Albumin, Radio-Iodinated; Suspensions; Technetium; Yttrium Radioisotopes

The aim of this work was to study the effectiveness of 32P colloids or microspheres, by arterial interventional administration or stromal injection in the treatment of refractory solid tumors.. By arterial intervention, under the guidance of computerized tomography, X-ray, ultrasonogram, or under direct vision of the surgical field, 32P microspheres (259-685 MBq) or radioactive colloid (281-666 MBq) was administered to 60 cases with refractory solid tumors. Tumor inhibition rate, side effects, survival period, and so on were observed.. The tumor growth was obviously inhibited after the intratumoral injection of 32P colloid. The average survival time in the 60 cases was 35 months with a high tumor inhibition rate (93.4%). Thirty-one cases were completely relieved (51.7%), and 25 cases achieved partial remission (PR, 41.7%). One case with right lobe hepatocellular carcinoma has survived 90 months. The drug was ineffective only in four cases, including one patient who died of gastrointestinal hemorrhage and three of hepatic failure. No other obvious side effects were observed. Intratumoral necrosis, intense fibrosis in the tumor mass, and an integrated capsule encompassing the tumor were revealed by histological examination.. Arterial interventional administration or stromal injection with 32P microspheres or colloid revealed a very fair clinical effectiveness in the treatment of refractory solid tumors. The range of safe effective dosage for 32P glass microspheres and 32P chromic phosphate in one treatment course is 555-740 MBq and 185-370 MBq, respectively.

Topics: Adult; Aged; Colloids; Drug Carriers; Female; Humans; Injections, Intra-Arterial; Male; Microspheres; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Radiopharmaceuticals; Treatment Outcome

In this early Phase II study, the authors investigated the efficacy of intratumoral injection of P-32 chromic phosphate in 17 patients with refractory solid tumors or solitary metastases in terms of response rates and overall survival.. Seventeen patients (median age, 60 years) with either cytostatic drug-resistant tumors or tumors known to be primarily chemotherapy-resistant were entered into the study. After sonographic determination of the tumor volume, P-32 chromic phosphate (74-555 MBq) was injected into the central part of the tumor under sonographic guidance. Follow-up investigations included serial scintigraphy, sonographic examinations, and hematologic studies.. Injection of P-32 chromic phosphate into refractory tumors resulted in remarkable regression. The median survival of all patients was 13 months (range, 8-25 months). The response rate was 71% (12 patients). A complete remission was seen in 7 patients (41%), and the rate of partial remissions was 29% (5 patients). However, 5 patients (30%) did not respond to the treatment. In one patient thrombocytopenia was observed, but no other side effects were apparent. Important pathologic and anatomic changes within the tumor tissue were demonstrated in solitary liver metastases of gastrointestinal malignancies excised in second-look operations. In all cases examined, formation of a cyst within the area of central activity, surrounded by a centrifugal necrotic ring and a marginal fibrotic structure, was found.. Lack of persistent systemic or local side effects, as well as noteworthy efficacy, are properties of this optimal regional treatment modality with P-32 chromic phosphate. This modality deserves consideration for further clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Chromium Compounds; Digestive System Neoplasms; Drug Resistance, Neoplasm; Female; Head and Neck Neoplasms; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Neoplasms; Phosphates; Phosphorus Radioisotopes; Survival Rate

Malignant pericardial effusion is usually treated only when signs of cardiac tamponade develop. Several methods of treatment have been reported with an overall response rate of approximately 75%. Since our initial study using intrapericardial 32P-colloid instillation as a treatment modality for pericardial effusion demonstrated a significant higher response rate, this study was conducted to further evaluate the efficacy of intrapericardial 32P-colloid in terms of response rates and duration of remissions. Intrapericardial instillation of 185-370 MBq (5-10 mCi) 32P-colloid in 36 patients with malignant pericardial effusion resulted in a complete remission rate of 94.5% (34 patients) whereas two patients did not respond to treatment due to a foudroyant formation of pericardial fluid. The median duration time was 8 months. No side-effects were observed. These results suggest that intrapericardial instillation of 32P-colloid is a simple, reliable and safe treatment strategy for patients with malignant pericardial effusions. Therefore, since further evidence is provided that 32P-colloid is significantly more effective than external radiation or non-radioactive sclerosing agents, this treatment modality should be considered for the management of malignant pericardial effusion.

Topics: Breast Neoplasms; Cardiac Tamponade; Chromium Compounds; Female; Gastrointestinal Neoplasms; Humans; Instillation, Drug; Lung Neoplasms; Lymphoma; Neoplasms; Pericardial Effusion; Phosphorus Radioisotopes; Radiopharmaceuticals

Sixty-seven patients with disseminated cancer were randomly allocated to treatment with continuous closed chest drainage removing all fluid for 72 hours (PD) or pleural drainage for 72 hours with the instillation into the pleural space of radioactive colloidal chromic phosphate (PD + 32P). Forty-nine patients had breast carcinoma, and the remaining 18 patients had other cancers. Four of 49 patients with breast cancer and 13 of 18 with other cancer were dead in 8 weeks from the onset of effusion. In the group of patients with breast cancer PD + 32P controlled the effusion in 12 of 22 (54%) and PD alone in 15 of 30 episodes (50%). In the nonbreast group of patients PD + 32P controlled the effusion in five of six evaluable episodes (83%), and PD alone was successful in two of nine (22%). In 33% of breast cancer patients and 25% of the nonbreast-cancer patients, systemic chemotherapy produced objective remissions. Pleural effusion did not recur in any of these patients.

Topics: Adult; Aged; Breast Neoplasms; Drainage; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Phosphorus Radioisotopes; Pleural Effusion; Prospective Studies

Topics: Aged; Breast Neoplasms; Clinical Trials as Topic; Cyclophosphamide; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Neoplasms; Phosphorus Radioisotopes; Remission, Spontaneous; Vincristine

Tumor-associated macrophages (TAMs) are often related with poor prognosis after radiotherapy. Depleting TAMs may thus be a promising method to improve the radio-therapeutic efficacy. Herein, we report a biocompatible and biodegradable nanoplatform based on calcium bisphosphonate (CaBP-PEG) nanoparticles for chelator-free radiolabeling chemistry, effective in vivo depletion of TAMs, and imaging-guided enhanced cancer radioisotope therapy (RIT). It is found that CaBP-PEG nanoparticles prepared via a mineralization method with poly(ethylene glycol) (PEG) coating could be labeled with various radioisotopes upon simple mixing, including gamma-emitting

Topics: Animals; Antineoplastic Agents; Calcium Phosphates; Cell Line; Cell Proliferation; Chelating Agents; Drug Screening Assays, Antitumor; Female; Isotope Labeling; Macrophages; Mice; Mice, Inbred BALB C; Molecular Structure; Nanoparticles; Neoplasms; Particle Size; Phosphorus Radioisotopes; Radiopharmaceuticals; Surface Properties; Tomography, Emission-Computed, Single-Photon; Tumor Microenvironment

Protein kinases have emerged as an important class of therapeutic targets, as they are known to be involved in pathological pathways linked to numerous human disorders. Major efforts to discover kinase inhibitors in both academia and pharmaceutical companies have centered on the development of robust assays and cost-effective approaches to isolate them. Drug discovery procedures often start with hit identification for lead development, by screening a library of chemicals using an appropriate assay in a high-throughput manner. Considering limitations unique to each assay technique and screening capability, intelligent integration of various assay schemes and level of throughput, in addition to the choice of chemical libraries, is the key to success of this initial step. Here, we describe the purification of the protein kinase, eEF-2K, and the utilization of three biochemical assays in the course of identifying small molecules that block its enzymatic reaction.

Topics: Antineoplastic Agents; Elongation Factor 2 Kinase; Fluorometry; Gamma Rays; High-Throughput Screening Assays; Humans; Indicators and Reagents; Luminescent Measurements; Neoplasm Proteins; Neoplasms; Phosphorus Radioisotopes; Protein Kinase Inhibitors; Radiometry; Recombinant Fusion Proteins; Scintillation Counting

To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical.. The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED).. Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and α-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger α-coefficient.. The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy.

Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Radiation; Iodine Radioisotopes; Models, Biological; Neoplasms; Phosphorus Radioisotopes; Radiopharmaceuticals; Survival Analysis; Ytterbium

The aim of this paper was to observe the metabolic mode of 32P at the level of sub-target nuclides.. Twenty-one cancer patients were locally injected with 32P-labelled glass microspheres and then observed to determine the equalization of 32P radionuclide metabolism in the tumor target. We imaged 3 sub-target regions of interest (ROI) 1/3 the size in both the anterior and posterior directions by bremsstrahlung single-photon emission computed tomography (SPECT) X-ray imaging. The radiation dose parameters of the beta rays including the initial dose rate, the effective half-life, and the effective half-life of the cumulative radiation dose were then calculated.. The radionuclide metabolism of the 21 complete tumor targets complied with the mono-compartmental model of index metabolism, but the level of tumor control did not correlate with radiation dose parameters. In contrast, the radionuclide metabolism of the 63 sub-targets did not comply with the mono-compartmental model. Instead, 32 sub-targets were better represented by bi-compartmental or tri-compartmental metabolic models. None of the remaining 31 sub-targets complied with index metabolism.. The complexity of the radiation dose at the sub-target level partially explains poor local tumor control. Future studies will be required to improve the expression of internal exposure to radiation dose parameters.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Child; Female; Humans; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Microspheres; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Radiation Dosage; Rectal Neoplasms; Stomach Neoplasms; Tomography, Emission-Computed, Single-Photon; Young Adult

The search for new therapeutic agents that are effective against cancer has been difficult and expensive. The activity of anticancer candidate agents against human cancer-derived cell lines in immunocompromised mice is an important tool in this search. Because ATP is a naturally occurring small molecule, its radiolabeled form poses many advantages as a potential anticancer therapeutic agent. We previously found that a single, low-dose intravenous injection of [ ( 32) P]ATP inhibited the growth of xenografted tumors in nude mice for up to several weeks. The current study describes the biodistribution and the results and advantages of multi-dose administration of this potential drug. Future studies should investigate the mechanism involved in the possible use of [ ( 32) P]ATP as a cytotoxic agent that homes naturally to the tumor microenvironment.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; HeLa Cells; Humans; Immunocompromised Host; Mice; Mice, Nude; Neoplasms; Phosphorus Radioisotopes; Tissue Distribution; Transplantation, Heterologous

The ability of a potential human anti-cancer therapeutic agent to inhibit the growth of xenografted tumors in nude mice has been an established and accepted testing method for several decades. The current report shows that a single, low-level intravenous dose of [(32)P]ATP significantly inhibits the growth of established xenografted tumors in nude mice. This inhibitory effect becomes appreciable very rapidly, within only five days post-injection and the low dose demonstrates little or no toxicity in the mice. Surprisingly, a narrow dose window of optimum effectiveness is seen, whereby either decreasing or increasing the [(32)P]ATP dose results in far less growth inhibition. Thus, the intravenous systemic injection of [(32)P]ATP may represent a simple, potent method to target and inhibit primary human tumors and malignant lesions.

Topics: Adenosine Triphosphate; Animals; Cell Proliferation; Down-Regulation; HCT116 Cells; HeLa Cells; Humans; Mice; Mice, Nude; Neoplasms; Phosphorus Radioisotopes; Radiotherapy Dosage; Treatment Outcome; Tumor Burden; Xenograft Model Antitumor Assays

Clustering analysis (CA) and principal component analysis (PCA) were applied to dynamic Cerenkov luminescence images (dCLI). In order to investigate the performances of the proposed approaches, two distinct dynamic data sets obtained by injecting mice with (32)P-ATP and (18)F-FDG were acquired using the IVIS 200 optical imager. The k-means clustering algorithm has been applied to dCLI and was implemented using interactive data language 8.1. We show that cluster analysis allows us to obtain good agreement between the clustered and the corresponding emission regions like the bladder, the liver, and the tumor. We also show a good correspondence between the time activity curves of the different regions obtained by using CA and manual region of interest analysis on dCLIT and PCA images. We conclude that CA provides an automatic unsupervised method for the analysis of preclinical dynamic Cerenkov luminescence image data.

Topics: Adenosine Triphosphate; Algorithms; Animals; Beta Particles; Cluster Analysis; Glucose-6-Phosphate; Image Processing, Computer-Assisted; Liver; Luminescent Measurements; Mice; Mice, Nude; Molecular Imaging; Neoplasms; Phosphorus Radioisotopes; Principal Component Analysis; Radioactive Tracers; Radionuclide Imaging; Radiopharmaceuticals; Transplantation, Heterologous; Urinary Bladder

Polychlorinated biphenyls (PCBs) are toxic industrial chemicals, complete carcinogens, and efficacious tumor promoters. However, the mechanism(s) of PCB-mediated carcinogenicity remains largely undefined. One likely pathway by which these agents may play a role in carcinogenesis is the generation of oxidative DNA damage by redox cycling of dihydroxylated PCB metabolites. We have now employed a new (32)P-postlabeling system to examine novel oxidative DNA lesions induced by Cu(2+)-mediated activation of PCB metabolites. (32)P postlabeling of DNA incubated with various PCB metabolites resulted in over a dozen novel polar oxidative DNA adducts that were chromatographically similar for all active agents. The most potent metabolites tested were the hydroquinones (hydroxyl groups arranged para to each other), yielding polar oxidative adduct levels ranging from 55 to 142 adducts/10(6) nucleotides. PCB catechols, or ortho-dihydroxy metabolites, were up to 40% less active than their corresponding hydroquinone congeners, whereas monohydroxylated and quinone metabolites did not produce detectable oxidative damage over that of vehicle. With the exception of 2,4,5-Cl-2',5'-dihydroxybiphenyl, this oxidative DNA damage seemed to be inversely related to chlorine content: no chlorine approximately mono->di->trichlorinated metabolites. Importantly, copper, but not iron, was essential for activation of the PCB metabolites to these polar oxidative DNA adducts, because in its absence or in the presence of the Cu(+)-specific scavenger bathocuproine, no adducts were detected. Intervention studies with known reactive oxygen species (ROS) modifiers suggested that H(2)O(2), singlet oxygen, hydroxyl radical, and superoxide may also be involved in this PCB-mediated oxidative DNA damage. These data indicate a mechanistic role for several ROS, in addition to copper, in PCB-induced DNA damage and provide further support for oxidative DNA damage in PCB-mediated carcinogenesis.

Topics: Animals; Carcinogenicity Tests; Carcinogens, Environmental; Copper; DNA; DNA Adducts; Hydroquinones; Hydroxylation; In Vitro Techniques; Mixed Function Oxygenases; Neoplasms; Oxidative Stress; Phenanthrolines; Phosphorus Radioisotopes; Polychlorinated Biphenyls; Reactive Oxygen Species; Salmon

Radioimmunotherapy with biological vector labeled with radioactive nanoparticles is investigated from a dosimetric point of view. Beta (32P, 90Y) and low-energy X-ray radionuclides (103Pd) are considered. Dose distributions inside solid tumors have been calculated using MCNPX 2.5.0. Nanoparticle dimensions and biological vector characteristics are also determined in order to reach the 50 Gy prescribed dose inside the entire tumor volume. The worst case of an avascular tumor is considered. Results show that for beta-emitting nanoparticles, a set of data (covering fraction, biological half-life, and nanoparticle radius) can be found within acceptable ranges (those of classical radioimmunotherapy). These sources (with Emax approximately few MeV) can be used for the treatment of tumors with a maximum diameter of about 1 cm. Low-energy X-rays (E<25 keV) can be used to extend the range of tumor diameter to 4-5 cm but require very tight biological vector characteristics.

Topics: Humans; Metal Nanoparticles; Neoplasms; Palladium; Phosphorus Radioisotopes; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals; Radiotherapy Dosage; Yttrium Radioisotopes

As revealed by previous theoretical studies, targeted radionuclide therapy (TRT) that relies on a single beta-emitting radioisotope is likely to be inappropriate for clinical scenarios such as disseminated malignancy. For a patient with a vast number of tumours and metastases of largely differing sizes a high level of therapeutical efficiency might be achieved only for a restricted range of tumour sizes. This is due to the limited range of beta-electrons in human tissue, essentially causing the therapeutical impact to vary tremendously with tumour size. The dependence of curability on the tumour dimension is expected to be significantly altered if a radionuclide cocktail, consisting of a long-range and a short-range beta-emitter, such as (32)P and (33)P, is involved in the treatment. In this study, a radiation transport simulation was performed, using the MCNP4c2 Monte Carlo code, in order to investigate the relationship between tumour control probability (TCP) and tumour size, associated with concurrent use of (32)P and (33)P. Two different models of intratumoural distribution of cumulated activity were taken into account. One simulated an ideal radionuclide uptake in tumour tissue and the other referred to a limited radiotracer penetration. The results were examined in comparison to tumours targeted with pure (32)P, (33)P and (131)I. For both uptake scenarios a considerable reduction of the overall variation of TCP and thus an increasing chance of achieving tumour cure was observed for tumour sizes ranging from microscopic dimensions up to macroscopic diameters, if the targeted radionuclide treatment relies on a (32)P/(33)P cocktail. It was revealed that particular attention has to be given to the ratio of the (32)P and (33)P specific cumulated activities (SCA) in the tumour, since this is a significant determinant of the resulting behaviour of tumour control probability as the tumour diameter varies. This study suggests that a 32P/33P approach is more applicable to diseases that involve a variety of tumours and metastases differing in size.

Topics: Algorithms; Humans; Models, Statistical; Monte Carlo Method; Neoplasm Metastasis; Neoplasms; Phosphorus Radioisotopes; Probability; Radioisotopes; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Computer-Assisted; Reproducibility of Results

The nuclear p68 RNA helicase is essential for normal cell growth. The protein plays a very important role in early organ development and maturation. In our previous report, we showed that recombinant p68 RNA helicase was phosphorylated at serine/threonine and tyrosine residue(s). In the present study, we examined the phosphorylation status of p68 in six different cancer cell lines and compared the results with those in cells derived from the corresponding normal tissues. We showed here that p68 was phosphorylated at tyrosine residue(s) in all tested cancer cells but not in the corresponding normal cells/tissues. The tyrosyl phosphorylation of p68 also responded to platelet-derived growth factor. It is thus clear that p68 phosphorylation at tyrosine residue(s) is associated with abnormal cell proliferation and cancer development. The tyrosyl phosphorylation(s) was diminished if the cancer cells were treated with apoptosis agents, such as tumor necrosis factor-alpha, tumor necrosis factor-related apoptosis-inducer ligand, and STI-571. The tyrosyl phosphorylation of p68, however, was not affected by other anticancer drugs, such as piceatannol, etoposide, and taxol. The close correlation between p68 phosphorylations and cancer may provide a useful diagnostic marker and potential therapeutic target for cancer treatment.

Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Benzamides; Blotting, Western; Caco-2 Cells; Cell Line, Tumor; Cell Proliferation; Etoposide; HeLa Cells; Humans; Imatinib Mesylate; K562 Cells; Neoplasms; Paclitaxel; Phosphorus Radioisotopes; Phosphorylation; Piperazines; Precipitin Tests; Pyrimidines; RNA Helicases; RNA Interference; Stilbenes; Tumor Necrosis Factor-alpha

In vivo studies have demonstrated that pentavalent technetium-99m dimercaptosuccinic acid [(99m)Tc-(V)-DMSA] may be a useful tumour imaging agent. Several studies have suggested that (99m)Tc-(V)-DMSA uptake may be related to the structural similarity between the (99m)Tc-(V)-DMSA core and the PO(4)(3-) anion. As phosphate ions enter cells via NaPi cotransporters, we investigated whether (99m)Tc-(V)-DMSA uptake is mediated by NaPi cotransporters. (99m)Tc-(V)-DMSA and phosphate uptake kinetics were compared in three cancer cell lines (MCF-7, G152 and MG-63) under several conditions (with and without sodium and NaPi cotransporter inhibitor and at different pH). Determination of molecular NaPi cotransporter mRNA expression was performed by reverse-transcriptase polymerase chain reaction (Rt-PCR) assay. Results obtained in the presence of NaPi inhibitor, in sodium-free medium and at alkaline pH showed that (99m)Tc-(V)-DMSA accumulation is linked to NaPi cotransporter functionality. MCF-7 and G152 exhibited the same tracer uptake, whereas MG-63 showed the highest phosphate accumulation and the lowest (99m)Tc-(V)-DMSA uptake. These results were in accordance with mRNA NaPi expression, i.e. all cell lines expressed NaPi type III but MG-63 also co-expressed NaPi type I. The total level of NaPi cotransporter was highly correlated with phosphate accumulation, while the level of type III was related to (99m)Tc-(V)-DMSA uptake. We have demonstrated that (99m)Tc-(V)-DMSA uptake is specifically mediated by NaPi type III in cancer cells.

Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Hydrogen-Ion Concentration; Kinetics; Metabolic Clearance Rate; Neoplasms; Osteosarcoma; Phosphates; Phosphorus Radioisotopes; Potassium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Sodium; Sodium-Phosphate Cotransporter Proteins; Sodium-Phosphate Cotransporter Proteins, Type I; Symporters; Technetium Tc 99m Dimercaptosuccinic Acid

The risk of development of cancer, and more specifically acute leukaemia, after use of phosphorus-32 in patients with polycythaemia vera has been recognised for approximately 40 years. As a consequence of this risk, the indications for, and contraindications to, 32P are unclear in the physician's mind. This paper aims to clarify the problem. The relation between polycythaemia vera and leukaemia is explored and the question of whether chemotherapy represents an alternative to 32P is discussed. From the results obtained to date, two clear conclusions can be drawn: First, whatever the age of the patient, phlebotomy must be used to avoid the menace of vascular complications before the institution of basic treatment, but it cannot be used as the sole form of treatment. Second, 32P treatment retains an important role at least when chemotherapy fails and in elderly patients (>70 years).

Topics: Age Distribution; Aged; Comorbidity; Female; Humans; Incidence; Leukemia; Male; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Sex Distribution; Survival Rate

Topics: Animals; Humans; Mice; Neoplasms; Oligodeoxyribonucleotides, Antisense; Phosphorus Radioisotopes; Radiation Dosage; Radioisotopes; Radiopharmaceuticals; Sulfur Radioisotopes; Thionucleotides

To allow more sensitive, selective, and routine analyses of platinum(Pt)-GG and -AG intrastrand cross-links we have significantly improved our quantitative (32)P-postlabeling assay (M. J. P. Welters et al. Carcinogenesis 18, 1767-1774, 1997). Instead of off-line scintillation counting we introduced an on-line flow radioisotope detector into the HPLC system. Furthermore, the isolation protocol for the adducts was significantly modified and optimized to reduce interfering background peaks that prevented quantification of low levels of the cisplatin-DNA adducts in white blood cells obtained from patients. Reduction of background signals was obtained by boiling the samples, followed by phenol/chloroform/isoamylethanol extraction after the DNA digestion step. The labeling efficiency for the adducts was increased by 40% by using Na-formate instead of NH(4)-formate for elution of the adducts from the strong cation-exchange columns. Finally, a calibration curve and quality controls were implemented. The labeling efficiencies were not different between the dinucleotides. The between- and within-run precision for the Pt-GG and Pt-AG adducts measured at the lower limit of quantification of 87 and 53 amol/microg DNA, respectively, was less than 20% CV. The adducts were stable in DNA stored for a 2-month time period at -80 degrees C. The assay is now routinely used for high-precision analyses of patient and cell line samples containing very low adduct levels.

Topics: Animals; Calibration; Chromatography, High Pressure Liquid; Cisplatin; DNA; DNA Adducts; Formates; Humans; Leukocytes; Mice; Mice, Nude; Neoplasms; Phosphorus Radioisotopes; Quality Control; Reproducibility of Results

Fixed and paraffin-embedded tissues from pathology department archives are available for RNA expression analysis. We describe a general method for quantitation of specific RNA sequence extracted from single 6-8-micron human histological tissue sections cut from paraffin blocks. For each specific mRNA, the range of linear relationship between the log of the initial total RNA concentration and the log of the specific product after reverse transcription (RT)-PCR must be established. We usually perform RT with avian myeloblastosis virus (AMV)-RT, using specific antisense primers and a variable number of cycles of PCR amplification. The number of cycles must be adjusted within the range in which a linear relationship exists between the log of the amount of amplification product and the number of cycles. The quantity of specific product is standardized relative to beta-actin mRNA to normalize for the degree of RNA degradation, which can be quite different among samples. The amplification products were quantified by dot blot and 32P-labeled hybridization probe or by capillary electrophoresis with a laser-induced fluorescence detector. The intratest variation range was for the dot blot mean +/- 10% standard deviation (SD) and for the capillary electrophoresis mean +/- 3% SD.

Topics: Actins; DNA, Antisense; Electrophoresis, Capillary; ErbB Receptors; Fluorescence; Gene Expression; Humans; Neoplasms; Nucleic Acid Hybridization; Oligodeoxyribonucleotides; Paraffin Embedding; Phosphorus Radioisotopes; Polymerase Chain Reaction; Receptor, ErbB-2; RNA, Messenger; Tissue Fixation

The oncogenic protein Bcl-2 functions as a potent inhibitor of programmed cell death. This survival activity has been shown in some settings to be influenced by the Bcl-2 phosphorylation state. It has been demonstrated that treatment with microtubule-targeted agents results in phosphorylation of both Raf-1 kinase and Bcl-2. The Bcl-2-related family member Bcl-xL also exhibits a death suppressive activity, but its potential for phosphorylation following exposure to drugs that interact with microtubules has not been evaluated. Several tumor cell lines with low or undetectable levels of Bcl-2 protein expression were found to express Bcl-xL. A more slowly migrating Bcl-xL band was observed on immunoblots after cells were treated with microtubule-targeted agents. The appearance of this band was responsive to dose and was absent when the cell lysates were treated with lambda protein phosphatase. Using a Bcl-xL-specific monoclonal antibody, the phosphorylated form of Bcl-xL was immunoprecipitated from cells treated with paclitaxel and metabolically labeled with 32P-labeled inorganic orthophosphate. Herein, we report that Bcl-xL is phosphorylated in malignant cells after incubation with agents that target tubulin, including paclitaxel, vincristine, vinblastine, colchicine, and nocodazole. Moreover, paclitaxel-resistant ovarian carcinoma cell lines that have mutations in tubulin failed to exhibit phosphorylation of Bcl-xL after paclitaxel exposure, but they did demonstrate Bcl-xL phosphorylation in the presence of other tubulin-targeting agents. As observed for Bcl-2, phosphorylation of Bcl-xL was accompanied by phosphorylation of Raf-1. Interestingly, phosphorylation of these three proteins failed to occur or was much less pronounced when cells grown at high density were challenged with drug. Also, reduced Raf-1 expression, observed after treatment of cells with geldanamycin prior to and during incubation with the microtubule-active drugs, correlated with diminished Bcl-xL phosphorylation. Taken together, these results suggest that Bcl-xL, like Bcl-2, is phosphorylated by agents that disrupt microtubule architecture. By analogy with Bcl-2, this phosphorylation may play a critical role in modulating Bcl-xL function and may be an important determinant of microtubule-directed chemotherapeutic efficacy in human tumors.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; bcl-X Protein; Benzoquinones; Cell Count; Drug Resistance, Neoplasm; Electrophoresis, Polyacrylamide Gel; Humans; Lactams, Macrocyclic; Microtubules; Neoplasm Proteins; Neoplasms; Paclitaxel; Phosphoprotein Phosphatases; Phosphorus Radioisotopes; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-raf; Quinones; Sodium Dodecyl Sulfate; Tubulin; Tumor Cells, Cultured

Oligodeoxynucleotides (ODNs) labelled with an appropriate radionuclide could provide a means to identify serious diseases early on and thereby help initiate treatment at a very early phase. Regardless of important issues like in-vivo stability and membrane passage, the key issue for the oligonucleotide approach is the ability of the radiolabelled ODN to hybridize to the target mRNA. The secondary structure of mRNA does not permit all complementary ODNs to hybridize and a careful selection of the probe with consecutive testing is therefore necessary. This study was initiated to demonstrate hybridization of a 99Tcm-labelled 20-mer ODN to RNA of CAPL (S100A4), a gene reported to be overexpressed in metastatic cancers like breast carcinoma and osteosarcoma. The phosphodiester ODN GX-1 (antisense) and two control sequences (scrambled and random) were conjugated to the bifunctional chelating agent S-benzoyl-mercaptoacetyltriglycine (S-benzoyl-MAG3) and labelled with 99Tcm. The radiolabelled ODNs were purified on a C18 mini-column and characterized on a reverse-phase HPLC system. The radio-chemical purity was > 90% and the product was stable for > 6 h in aqueous medium. The hydrization properties of unlabelled, 32P-labelled and 99Tcm-labelled ODNs to transcribed RNA were studied using polyacrylamide gel electrophoresis (PAGE). Direct hybridization of GX-1 to transcribed RNA was demonstrated. A 50-fold excess of unlabelled ODN over transcribed RNA caused a near to complete consumption of RNA by RNase H activation. In 1:1 proportions of radiolabelled (32P and 99Tcm) ODNs to RNA, only radiolabelled GX-1 was found to hybridize to RNA in a PAGE system. The radiolabelled control ODNs did not show signs of hybridization. This study demonstrates that 3'-99Tcm-labelling of ODNs does not interfere with the hybridization properties of the ODNs in solution, making 99Tcm-labelling an attractive procedure for the future development of antisense technology in imaging.

Topics: Base Sequence; Calcium-Binding Proteins; Chelating Agents; Female; Glycine; Humans; Neoplasms; Nucleic Acid Hybridization; Oligodeoxyribonucleotides; Phosphorus Radioisotopes; Radionuclide Imaging; RNA, Messenger; S100 Calcium-Binding Protein A4; S100 Proteins; Technetium

Topics: Adenomatous Polyposis Coli; Animals; Biomarkers; Carcinogens; DNA Adducts; DNA Damage; Environmental Monitoring; Enzyme-Linked Immunosorbent Assay; Epidemiologic Methods; Epidemiological Monitoring; Guanine; Humans; Isotope Labeling; Models, Biological; Neoplasms; Phosphorus Radioisotopes; Risk Factors

Topics: Colloids; Humans; Injections, Intralesional; Neoplasms; Phosphorus Radioisotopes

Certain Lilium plants contain (25S)-spirost-5-ene-3 beta,27-diol glycosides embracing 3-hydroxy-3-methylglutaric acid at the C-27 hydroxy position. One of their derivatives, methyl ester of (25R)-27-O-[(S)-3-hydroxy-3-methylglutaryl]-spirost-5-ene-3 beta,27-diol 3-O-(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->4)] - beta-D-glucopyranoside) was found to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32P-incorporation into the phospholipids of human cervical cancer (HeLa) cells and also to inhibit the proliferation of various kinds of human malignant tumor cells, pancreatic cancer (PANC-1), osteosarcoma (OST), human gastric cancer (HGC-27), pheochromocytoma (PC-12) and HeLa cells, in vitro.

Topics: Carbohydrate Sequence; Cell Division; Drug Interactions; HeLa Cells; Humans; Molecular Sequence Data; Neoplasms; Phospholipids; Phosphorus; Phosphorus Radioisotopes; Saponins; Stimulation, Chemical; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.

Topics: Adenosine Triphosphate; Binding, Competitive; Blood Platelets; Cell Membrane; Cross Reactions; Cyclic AMP; Drug Interactions; Humans; Ligands; Mast Cells; Neoplasms; Neoplasms, Experimental; Neutrophils; Phosphorus Radioisotopes; Receptors, Somatostatin; Receptors, Vasoactive Intestinal Peptide; Somatostatin; Thymidine; Tritium; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

The very-long-term follow-up of patients initially included in the PVSG protocols provides useful information. The excess risk of cancer after chlorambucil appears to persist for 5 years after stopping this treatment. The risk of leukaemia induced by marrow suppression (32P or chemotherapy) was marked before the 10th year, but low thereafter. Phlebotomy is unacceptable as permanent treatment because of the poor clinical tolerance and the frequency of vascular complications. This treatment is also associated with a risk of early progression towards myelofibrosis with myeloid splenomegaly. In the very long term, 15 years or more after the diagnosis, this complication is the major clinical risk, affecting almost 50% of our patients surviving at this time. The prevention of this type of complication could constitute one of the objectives of future protocols dealing with this disease.

Topics: Aged; Bloodletting; Chlorambucil; Follow-Up Studies; Humans; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radiotherapy; Treatment Outcome; Vascular Diseases

Bremsstrahlung SPECT imaging and activity quantitation have been performed using 32P-chromic phosphate.. Attenuation correction was applied to the reconstructed transverse SPECT slices using a commercially available first-order postprocessing algorithm. The patient's body contour was defined through the use of four externally placed sources and attenuation correction was then performed with an experimentally determined effective linear attenuation coefficient for 32P. Phantom studies were performed to determine the activity needed in the four external sources and also to validate absolute activity analysis on the reconstructed SPECT slices. A computer algorithm was written to facilitate ROI activity determination based on a fixed threshold method. Four cancer patients enrolled in clinical Phase I protocols were injected with 2.5 million particles of macro-aggregated albumin followed by colloidal 32P-chromic phosphate by direct interstitial injection into the tumor-bearing region under CT guidance. The in vivo 32P activity distribution was restricted to a small volume with minimal background activity. SPECT images were obtained in these patients and the activity of 32P present in the tumors was calculated from their attenuation-corrected reconstructed SPECT slices.. The effective linear attenuation coefficient for 32P was determined to be 0.13 cm-1. A fixed 39% threshold was best for activity calculation since it provided the best correlation between known and measured activity levels in the phantom. The calculated activities were within 16.9% of the actual activities in the patients studied.. Accurate quantitative bremsstrahlung SPECT imaging with a commercially available postprocessing attenuation correction algorithm can be performed in a clinical setting.

Topics: Chromium Compounds; Humans; Models, Structural; Neoplasms; Phosphates; Phosphorus Radioisotopes; Tomography, Emission-Computed, Single-Photon

The application of a 32P-postlabeling assay for 7-methylguanines in DNA was studied either by labeling the imidazole ring-opened dinucleotide derivatives or by using strong-anion-exchange column chromatography for the adduct enrichment from normal nucleotides. Data showed that 7-methylguanines can be efficiently labeled as dinucleotides when in vitro methylated DNA was first imidazole ring-opened and then digested to the dinucleotide level with deoxyribonuclease I, snake venom phosphodiesterase, and prostatic acid phosphatase. When using ion exchange chromatography for the adduct enrichment, DNA was digested with micrococcal nuclease and spleen phosphodiesterase. Anion exchange chromatography was applied for 7-methylguanine measurements in white blood cell DNA of healthy nonsmokers (n = 17) and patients (n = 4) treated with the methylating drugs procarbazine and decarbazine. We found that the mean level of 7-methylguanine residues in nonsmokers was 2.5 per 10(7) nucleotides. The corresponding level in the patient samples immediately after the drug treatment was 57 per 10(7) nucleotides.

Topics: Adult; Aged; Chromatography, Ion Exchange; Dacarbazine; DNA; Dose-Response Relationship, Drug; Guanine; Humans; Leukocytes; Middle Aged; Neoplasms; Oligodeoxyribonucleotides; Phosphorus Radioisotopes; Procarbazine

In this report we describe the identification and characterization of a novel tumor-associated receptor-type tyrosine kinase (hek). We produced a monoclonal antibody (III.A4) that detected a novel glycoprotein on the immunizing pre-B cell acute lymphoblastic leukemia cell line (LK63). This antigen was shown to be expressed sporadically on hemopoietic tumor cell lines and on ex vivo tumors. However, using antibody staining, the molecule was undetectable on normal tissues. Further biochemical characterization showed this molecule (hek) to be a phosphoroprotein. This observation taken together with the tumor-associated nature of hek expression suggested that hek might be a receptor-type protein tyrosine kinase. This was demonstrated by affinity purification of hek. In in vitro kinase experiments the purified hek protein was autophosphorylated on tyrosine and also mediated tyrosine phosphorylation of casein. Purified hek was subjected to N-terminal amino acid sequence analysis which showed that hek had a unique N terminus. Amino acid sequence determination of peptides from a V8 protease digest of hek yielded one 21-amino acid stretch of sequence which showed close homology with the eph subfamily of protein tyrosine kinases. These studies show hek to be a novel human tumor-associated protein tyrosine kinase, which by analogy with previously characterized protein tyrosine kinase proto-oncogenes, may have a role in tumorigenesis.

Topics: Amino Acid Sequence; Amino Acids; Animals; B-Lymphocytes; Biopsy; Cell Line; Female; Glycosylation; Humans; Immunoenzyme Techniques; Kinetics; Methionine; Molecular Sequence Data; Neoplasms; Peptide Mapping; Phosphorus Radioisotopes; Protein-Tyrosine Kinases; Reference Values; Sequence Homology, Nucleic Acid

A 32P-postlabelling method was developed to measure 7-methylguanine in human DNA. DNA was digested to nucleotides and 7-methyl-2'-deoxyguanosine-3'-monophosphate (7-me-dGMP) was isolated from normal nucleotides using strong anion-exchange column chromatography. Overall the method gave 35-45% yield as measured with DNA methylated with tritiated dimethyl sulfate. Total white blood cell DNA from healthy non-smokers (n = 17) contained from 2.5 7-methylguanine residues/10(7) nucleotides, corrected for the losses in preparation. Among four patients sampled immediately after a total dose of 1050-2800 mg of dacarbazine or procarbazine, the mean adduct level was 57 7-methylguanine residues/10(7) nucleotides. As further method development, we also investigated the phosphorylation reaction by T4 polynucleotide kinase using dinucleotides containing 7-methylguanine and corresponding imidazole ring-opened products as substrates. We found that imidazole ring-opened dTpdG-Me is resistant to digestion with deoxyribonuclease I, snake venom phosphodiesterase and prostatic acid phosphatase. It is quantitatively phosphorylated at femtomolar levels. This method is shown to be suitable for the detection of 7-methylguanine in DNA, and is suggested to be the approach most suited to postlabelling large and labile 7-alkylguanines in DNA.

Topics: Chromatography, Thin Layer; Dacarbazine; Deoxyguanine Nucleotides; DNA; DNA, Neoplasm; Guanine; Humans; Leukocytes; Neoplasms; Phosphorus Radioisotopes; Phosphorylation; Procarbazine

Natural killer (NK) cell number and activity were measured in 26 patients with myeloproliferative disorders and the results were compared with 16 age-matched control patients. The percent of Leu-11b-positive cells was 11% +/- 3% in the patients, compared with 12% +/- 4% in the control patients. Ten of 26 patients, however, had NK activity lower than all of the control values at three different effector to target cell ratios (E:T) (P less than 0.005). The values of those patients with low unstimulated NK activity remained low despite stimulation with interleukin-2 (IL-2) or alpha-interferon (alpha-IFN), whereas the values of those patients with normal unstimulated activity responded to IL-2 and alpha-IFN like the control patients. Three of the ten patients with low NK activity had a history of malignant neoplasms. None of the 16 patients with normal NK activity had a history of malignant neoplasms (P less than 0.05). We conclude that patients with myeloproliferative disorders frequently have low endogenous NK cell activity in vitro. The dysfunction of the NK system appears to be intrinsic because the relative number of NK cells was similar to control values and the response to stimulation with IL-2 and alpha-IFN was suboptimal. There may be a relationship between low NK activity and the development of malignant disease in such patients.

Topics: Bloodletting; Humans; Hydroxyurea; Interferon Type I; Interleukin-2; Killer Cells, Natural; Myeloproliferative Disorders; Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Thrombocytosis

Topics: Endocrine System Diseases; Humans; Intraoperative Period; Neoplasms; Phosphorus Radioisotopes; Radiometry; Radionuclide Imaging

The bioenergetic state of 15 human tumours was examined with phosphorus-31 magnetic resonance spectroscopy. A striking diversity in metabolic patterns was observed, and significant differences from normal tissue were seen in all cases. A common feature was an elevation of intracellular pH, which may be related to an increase in Na+/H+ exchange during cell activation. It is unlikely that the patterns observed directly correlate with malignancy, but characterisation of the energetic state of a given tumour in a given physiological environment may help in the design and evaluation of interventions for that specific case.

Topics: Adult; Aged; Brain Neoplasms; Breast Neoplasms; Female; Humans; Hydrogen-Ion Concentration; Kinetics; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neoplasms; Phosphorus Radioisotopes; Spectrum Analysis

When liver, kidney, lung and heart DNA preparations of untreated Sprague-Dawley rats of different ages (3 days-10 months) were analyzed for the possible presence of covalent modifications by a 32P-postlabeling assay, characteristic tissue-specific patterns of 32P-labeled spots (termed I-spots) were observed on thin-layer chromatograms. Amounts of these DNA derivatives (termed I-compounds), which were not detected in newborn rat DNA, markedly increased with age. This novel type of DNA modification could be due to environmental (e.g. dietary) factors or to endogenous DNA-reactive metabolites and may conceivably play a role in the initiation of spontaneous cancers or other adverse health effects related to aging.

Topics: Aging; Animals; Carcinogens; DNA; Kidney; Liver; Male; Neoplasms; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains

Topics: Humans; Magnetic Resonance Spectroscopy; Neoplasms; Phosphorus Radioisotopes

Topics: Electrons; Humans; Neoplasms; Phosphorus Radioisotopes; Radionuclide Imaging; Semiconductors

Basis, indications and results of the endolymphatic therapy with radionuclides, of the selective therapy with radiophosphorus and radiostrontium and of the intraarticular and endocavitary therapy with radiocolloids are described. Future scientific engagement and intensive basic research in radionuclide therapy is required. However, because of the expected therapeutic profit the efforts seem to be justified.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Child; Child, Preschool; Female; Gold Colloid, Radioactive; Humans; Infant; Iodine Radioisotopes; Male; Middle Aged; Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioisotopes; Radiotherapy; Radiotherapy Dosage

Two-hundred-eighty-nine patients received treatment with chronic phosphate (32P) colloidal suspension (CPCS) 346 times since 1963. One-hundred-seventy-eight patients received 200 intraperitoneal treatments. One-hundred-fifteen patients received 144 intrapleural treatments. Six patients received both intraperitoneal and intrapleural treatments. Two patients received two intrapericardial treatments. Results of therapy were evaluated three months later and then at yearly intervals. In those patients who survived three months, the referring physician observed improvement in 85% of intraperitoneal treatment and in 75% of intrapleural treatments.

Topics: Brachytherapy; Chromium; Chromium Compounds; Follow-Up Studies; Humans; Male; Neoplasms; Peritoneal Diseases; Peritoneum; Phosphates; Phosphorus Radioisotopes; Pleura; Pleural Effusion

Pleural and peritoneal effusion secondary to primary malignancy is a significant problem in the management of the cancer patient. Respiratory embarrassment and discomfort associated with the formation and collection of fluid in the chest and abdomen are among the most distressing symptoms encountered as a result of malignant disease. The guidelines for treatment should be based on respiratory symptoms, and with the understanding that the procedure is palliative. Both surgical and medical forms of treatment have been used. These include thoracostomy-tube drainage alone or with the instillation of antimicrobial agents. Pleurectomy is effective but should be reserved for situations in which conservative approaches have failed. Antitumor agents, such as nitrogen mustard, are effective but toxic. The mode of action of antineoplastic agents is related to their ability to cause pleural sclerosis and obliterate the pleural space. Systemic chemotherapy and external beam radiation are rarely effective. The intracavitary application of radioactive colloids has been used since 1945. Colloidal radioactive gold Au 198 has been replaced by the pure beta emitter, colloidal chromic phosphate P 32. Instillation of a colloidal suspension of radioactive phosphorus represents a significant and effective palliative therapeutic modality for malignant effusion.

Topics: Adult; Ascites; Bleomycin; Colloids; Drainage; Female; Humans; Neoplasms; Palliative Care; Pericardial Effusion; Phosphorus Radioisotopes; Pleural Effusion; Pregnancy

Topics: History, 20th Century; Humans; Iodine Radioisotopes; Kidney Function Tests; Neoplasms; Phosphorus Radioisotopes; Radiometry; Scintillation Counting; United States

A pleural effusion is a frequent complication of malignant disease. Essential to the care of oncology patients is a fundamental knowledge of the pathophysiology and treatment of such effusions. This article discusses the current thoughts concerning the occurrence of malignant effusions, outlines the current available methods and agents employed for control, and presents a modification of the thoracostomy procedure that appears to be more effective than the standard procedure.

Topics: Bleomycin; Fluorouracil; Gold Radioisotopes; Humans; Mechlorethamine; Methods; Neoplasms; Phosphorus Radioisotopes; Pleura; Pleural Effusion; Quinacrine; Talc; Tetracycline; Thiotepa; Thoracic Surgery; Thorax

A survey is given on the modern possibilities of the therapy of malignant tumours with radiopharmaca. In detail the following methods of treatment introduced into the nuclearmedical therapy are described: 1. Radioiodine therapy in folliculary and papillary carcinomas of the thyroid gland, 2. Radiophosphorus therapy in polycythaemia vera and myeloproliferative syndrome, 3. Radiogold therapy in peritoneal and pleural carcinoses, 4. Intrathecal radionuclide application in meningeosis leucaemica, 5. Intralymphatic radionuclide application to the therapy of malignant lymphomas, 6. Radionuclide therapy of multiple bone metastases. With the help of literature and own experiences the author enters the indication and the performance of the therapy as well as the possible successes of treatment, when using the therapy forms mentioned.

Topics: Aged; Gold Radioisotopes; Humans; Injections, Spinal; Iodine Radioisotopes; Male; Neoplasms; Phosphorus Radioisotopes; Pleural Neoplasms; Polycythemia Vera; Radioisotopes; Thyroid Neoplasms

Topics: Humans; Iodine Radioisotopes; Neoplasms; Phosphorus Radioisotopes; Radioisotope Teletherapy; Radioisotopes; Radiotherapy; Thyroid Diseases; Thyroid Neoplasms

Treatment of 28 patients with malignant pericardial effusion was accomplished primarily by intrapericardial instillation of radioactive chromic phosphate. At time of diagnosis of pericardial disease, 14 patients had major manifestations of tamponade; the rest had little or no clinical evidence of effusion. Only eight of the 28 patients had further problems with effusion after the initial pericardiocentesis and 32P instillation. Additional aspirations were done on those patients 2 weeks to 5 months later. The average survival was 9 months; seven patients lived more than 1 year.

Topics: Adult; Aged; Catheterization; Chromium; Female; Humans; Injections; Male; Middle Aged; Neoplasms; Pericardial Effusion; Phosphorus Radioisotopes

Topics: Dysgerminoma; Humans; Lymphatic System; Melanoma; Neoplasms; Phosphorus Radioisotopes

Topics: Ascitic Fluid; Chromates; Female; Follow-Up Studies; Gold Colloid, Radioactive; Humans; Neoplasms; Palliative Care; Peritoneal Cavity; Peritoneal Diseases; Phosphorus Radioisotopes; Pleural Effusion; Punctures; Radioisotopes; Radiotherapy; Radiotherapy Dosage; Silicic Acid; Time Factors; Yttrium Isotopes

Topics: Acyltransferases; Age Factors; Blood Sedimentation; Cholesterol; Clinical Enzyme Tests; Female; Hot Temperature; Humans; Liver Diseases; Lysophosphatidylcholines; Male; Neoplasms; Phosphatidylcholines; Phosphorus Radioisotopes; Serum Albumin; Sex Factors; Tritium

Topics: Female; Humans; Male; Neoplasms; Phosphorus Radioisotopes; Radionuclide Imaging

Topics: Animals; Leukemia, Experimental; Liver; Mice; Neoplasms; Neoplasms, Experimental; Phospholipids; Phosphorus Radioisotopes; Rats; Sarcoma, Experimental

Topics: Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radiometry; Uterine Cervical Neoplasms

Topics: Early Diagnosis; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Skin; Skin Neoplasms

Topics: Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Animals; Hominidae; Liver; Lymph Nodes; Mice; Neoplasms; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Spleen

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Carcinoma; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Breast Neoplasms; Diagnosis, Differential; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Mediastinal Neoplasms; Mediastinum; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Bone and Bones; Bone Neoplasms; Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Edible Grain; Humans; Hypophysectomy; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Stomach Neoplasms

Topics: Bone and Bones; Bone Neoplasms; Breast; Breast Neoplasms; Humans; Nandrolone; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Testosterone

Topics: DNA; Neoplasms; Nucleosides; Nucleotides; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Neoplasms; Phosphorus; Phosphorus Radioisotopes; Thyroid Gland; Thyroid Neoplasms

Topics: Chromium; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Bone and Bones; Bone Neoplasms; Humans; Joints; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Sarcoma

Topics: Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Uterine Cervical Neoplasms

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Skin; Skin Neoplasms

Topics: Bone and Bones; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Laryngeal Neoplasms; Larynx; Neoplasms; Pharyngeal Neoplasms; Pharynx; Phosphorus; Phosphorus Radioisotopes

Topics: Ear Neoplasms; Humans; Neoplasms; Nose Neoplasms; Otolaryngology; Pharyngeal Neoplasms; Pharynx; Phosphorus; Phosphorus Radioisotopes

Topics: Endometrial Neoplasms; Endometrium; Female; Gold Radioisotopes; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioisotopes; Uterine Neoplasms

Topics: Humans; Melanoma; Melanoma, Cutaneous Malignant; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Skin Neoplasms

Topics: Autoradiography; Bone Marrow; Gold Radioisotopes; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Ascites; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Bone and Bones; Bone Neoplasms; Breast; Breast Neoplasms; Humans; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes

Topics: Bone and Bones; Bone Neoplasms; Hodgkin Disease; Humans; Leukemia; Multiple Myeloma; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Plasma Cells; Polycythemia Vera; Radioactivity

Topics: Child; Exophthalmos; Humans; Infant; Neoplasms; Orbit; Orbital Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Bone and Bones; Bone Neoplasms; Dose Fractionation, Radiation; Humans; Incidence; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Humans; Neoplasms; Peritoneal Neoplasms; Peritoneum; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Chromium; Chromium Compounds; Chromium Radioisotopes; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Pleural Effusion, Malignant

Topics: Gold Radioisotopes; Leg; Mechlorethamine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes; Radioisotopes

Topics: Brain Neoplasms; Diagnosis, Differential; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Bone and Bones; Bone Neoplasms; Carcinoma; Humans; Male; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Prostatic Neoplasms

Topics: Disease; Humans; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Pleura; Pleural Diseases

Topics: Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Breast Neoplasms; Exudates and Transudates; Gold Radioisotopes; Humans; Lung Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioisotopes

Topics: Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Uterine Cervical Neoplasms

Topics: Brain; Brain Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Stereotaxic Techniques

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Bone and Bones; Bone Neoplasms; Breast; Breast Neoplasms; Humans; Male; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Prostatic Neoplasms; Testosterone

Topics: Genitalia; Genitalia, Female; Gold Radioisotopes; Gynecology; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioisotopes

Topics: Chromium Compounds; Humans; Male; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Pituitary Gland; Prostatic Neoplasms

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Pleura; Pleural Effusion; Radioactivity; Thorax

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Pituitary Gland

Topics: Gold Radioisotopes; Humans; Neoplasms; North Carolina; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Adenocarcinoma; Animals; Breast Neoplasms; Cortisone; Humans; Mice; Neoplasm Transplantation; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Cardia; Digestive System Neoplasms; Esophagus; Gastrointestinal Tract; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioisotopes

Topics: Chromium Compounds; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Pleural Effusion, Malignant

Topics: Bronchi; Bronchial Neoplasms; Carcinoma, Bronchogenic; Chromium; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Digestive System Neoplasms; Early Detection of Cancer; Gastrointestinal Tract; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Biochemical Phenomena; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Guanine; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Animals; Neoplasms; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Rats

Topics: Animals; Antineoplastic Agents; Mice; Neoplasms; Nucleic Acids; Phosphorus; Phosphorus Radioisotopes

Topics: Gold Radioisotopes; Neoplasm Transplantation; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Radioisotopes; Sarcoma; Transplantation, Heterologous

Topics: Breast Neoplasms; Cervix Uteri; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Cobalt; Cobalt Radioisotopes; Female; Humans; Iodine; Iodine Radioisotopes; Neoplasms; Nucleic Acids; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Uterine Neoplasms

Topics: Cervix Uteri; Cobalt; Cobalt Radioisotopes; Female; Humans; Iodine; Iodine Radioisotopes; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radioisotopes; Uterine Cervical Neoplasms; Vaginal Smears

Topics: Cervix Uteri; Cobalt; Cobalt Radioisotopes; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radioisotopes; Uterine Cervical Neoplasms

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radiotherapy

Topics: Chromium; Chromium Compounds; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Urinary Bladder Neoplasms

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Animals; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Rats; Sarcoma; Sarcoma, Experimental

Topics: Gold Radioisotopes; Humans; Iodine; Iodine Radioisotopes; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radioisotopes

Topics: Animals; DNA; Kinetics; Liver; Neoplasms; Nucleic Acids; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Rats

Topics: Animals; Gold Radioisotopes; Neoplasm Transplantation; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Radioisotopes; Sarcoma, Experimental; Transplantation, Heterologous

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Animals; Humans; Neoplasms; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radiotherapy

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Acridines; Antineoplastic Agents; Colchicine; Coloring Agents; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Animals; Bone Neoplasms; Mice; Neoplasms; Neoplasms, Experimental; Osteosarcoma; Phosphorus; Phosphorus Radioisotopes; Sarcoma

Topics: Leukemia; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Breast Neoplasms; Humans; Neoplasms; Neoplasms, Second Primary; Orbit; Orbital Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Humans; Neoplasms; Neoplasms, Second Primary; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Cytoplasm; Glycine; Neoplasms; Nucleic Acids; Nucleotides; Phosphorus; Phosphorus Radioisotopes; Proteins; Radioactivity

Topics: Chromium Compounds; Humans; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Tongue; Tongue Neoplasms

Topics: Animals; Humans; Liver; Male; Neoplasms; Nucleic Acids; Nucleoproteins; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Rats; Testis

Topics: Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Eye Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Eye Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Bone Neoplasms; Neoplasms; Osteosarcoma; Phosphorus; Phosphorus Radioisotopes; Propiophenones; Radioisotopes

Topics: Combined Modality Therapy; Lung Neoplasms; Mechlorethamine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes

Topics: Lung Neoplasms; Mechlorethamine; Neoplasms; Nitrogen Mustard Compounds; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Liver; Neoplasms; Nucleic Acids; Phosphorus; Phosphorus Radioisotopes

Topics: Chromium Compounds; Neoplasms; Phosphates; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary

Topics: Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; X-Rays

Topics: Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Carcinoma; Cervix Uteri; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Fluorides; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Quinacrine; Radioactivity

Topics: Brain; Brain Mapping; Brain Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Carcinoma; Cervix Uteri; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Uterine Cervical Neoplasms

Topics: Animals; Azo Compounds; Carcinogens; Coloring Agents; Cytoplasm; Liver Neoplasms; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Rats

Topics: Breast; Breast Neoplasms; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; X-Rays

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Hospitals; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Bone Neoplasms; Breast; Carcinoma; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Animals; Breast Neoplasms; Chickens; Humans; Mammary Neoplasms, Animal; Mice; Mice, Inbred C3H; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Cervix Uteri; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Uterine Cervical Neoplasms

Topics: Animals; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Rats

Topics: Humans; Iodine; Iodine Radioisotopes; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Polycythemia; Radioactivity; Radiotherapy

Topics: Humans; Multiple Myeloma; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioisotopes; Strontium; Strontium Radioisotopes

Topics: Humans; Iodine; Iodine Radioisotopes; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Radioisotopes

Topics: Elements, Radioactive; Humans; Iodides; Iodine; Iodine Radioisotopes; Neoplasms; Phosphorus; Phosphorus Radioisotopes

Topics: Multiple Myeloma; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Urethane

Topics: Animals; Lymphoma; Mice; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity

Topics: Hematologic Diseases; Humans; Lymphoma; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity

Topics: Animals; Lymphoma; Mice; Neoplasms; Neutrons; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Radiotherapy

Topics: Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity