125I-seeds are extensively used in ocular and interstitial brachytherapy for the treatment of various malignant lesions. Quality assurance and classification performance testing of indigenously produced 125I-seeds were carried out for ensuring their safety in different brachytherapy applications. The sources were found to qualify Class -43211 specifications, in accordance with AERB SS-3 and ISO-2919. (author)
Prostate cancer can be successfully treated using dynamic adaptive external beam radiation techniques along with interstitial brachytherapy to deliver curative therapies with low urinary, rectal and erectile function morbidity. Through the use of sophisticated, state-of-the art radiographic imaging for staging and treatment planning, a precise, individual design for treatment is accomplished. Symptom management and patient education are of paramount importance and are integrated throughout the treatment process.
The dosimetric characteristics for a new brachytherapy seed source (I-Plant"T"M model 3600) were measured using LiF thermoluminescent dosimeters and appropriate phantom materials in conformance with the methodology and guidance provided by the AAPM Task Group 43. The I-Plant"T"M model 3600 is the successor to the I-Plant"T"M model 3500. The major difference between these sources is that the model 3600 contains a leaded-glass core to provide radio-opacity (while the model 3500 contains a silver core), which does not produce spectral contamination upon neutron activation. The dose rate constant #LAMBDA# for the model 3600 was determined to be 1.00 Gy h"-"1 U"-"1 (with a 6% overall relative standard deviation), compared to 1.01 cGy h"-"1 U"-"1 reported for the model 3500 in previous studies. The remaining dosimetric characteristics also are similar for both sources.
The effect of measurement geometry on the determination of the activity of solutions containing "1"2"5I for use in brachytherapy applications has been investigated for 5 mL plastic syringes and 2 mL conical glass dose vials as a function of filling mass. New dial settings for the syringes over a filling mass range of 1 to 3 g have been determined to be 497#+-#8 and 469#+-#8 (expanded, k=2, uncertainties) for the NIST Capintec CRC-12 and Capintec CRC-35R, respectively, with any effect due to the filling mass lying within the uncertainty in the activity calibration. A filling mass effect was observed in the dose vials, causing a 10.5% reduction in the chamber response from a 2 g filling mass to 1 g. Dial settings at 2 g were experimentally found to be 143#+-#2 and 135#+-#2 (expanded uncertainties) for the NIST Capintec CRC-12 and Capintec CRC-35R, respectively. The appropriate dial settings for the same vials with a 1 g filling mass were found to be 120#+-#2 and ...
Derivatives of angiotensin with a sarcosine substitution at the carboxy terminus and an aliphatic amino acid substitution at the amino terminus have been shown to be competitive ligands for the angiotensin receptor. Scatchard plots derived from saturation isotherm data in bovine adrenal particulates consistently demonstrate three to five times the number of binding sites for "1"2"5I-Sarl,Ile8-AII ("1"2"5I-SI-AII) than for "1"2"5I-AII in experiments in which the two ligands are run side-by-side. A significant difference between "1"2"5I-AII and "1"2"5I-SI-AII binding to detergent solubilized angiotensin receptors was observed. Of the "1"2"5I-AII binding sites, about 85-90% were recovered upon solubilization. In contrast, the recovery of "1"2"5I-SI-AII binding sites was only 4-5%. To determine whether binding sites labeled in the soluble state represent biologically significant AII receptors, they examined the ability of selected angiotensin analogs to inhibit "1"2"5I-AII binding and ...
Brachytherapy refers to short distance treatment of cancer with radiation from small, encapsulated radionuclide sources. This type of treatment is given by placing sources directly into or near the volume to be treated. The dose is then delivered continuously, either over a short period of time (temporary implants) or over the lifetime of the source to a complete decay (permanent implants). This technique is extensively used in the treatments of gynecological, breast, prostate, head and neck, and other soft tissue cancers. The clinical outcomes of this treatment depend on accurate dosimetry and dose delivery. The patient is generally considered to be water equivalent. So the treatment planning system software generally is based on measured or calculated dose distributions in homogenous water medium. In real situation, the treatment volume is not homogenous water medium, but it is a heterogeneous medium consisting of bone, soft tissue, lung, air ...
Brachytherapy is used for treating certain types of cancer by inserting radioactive sources into tumours. CDTN/CNEN is developing brachytherapy seeds to be used mainly in prostate cancer treatment. Dose calculations play a very significant role in the characterization of the developed seeds. The current state-of-the-art of computation dosimetry relies on Monte Carlo methods using, for instance, MCNP codes. However, deterministic calculations have some advantages, as, for example, short computer time to find solutions. This paper presents a software developed to calculate doses in a two-dimensional space surrounding the seed, using a deterministic algorithm. The analysed seeds consist of capsules similar to IMC6711 (OncoSeed), that are commercially available. The exposure rates and absorbed doses are computed using the Sievert integral and the Meisberger third order polynomial, respectively. The software also allows the ...
The reference medium for brachytherapy dose measurements is water. Accuracy of dose measurements of brachytherapy sources is critically dependent on precise measurement of the source–detector...Full Text Available
As there are many efforts devoted in order to manage the cancer, here the researcher handle one of these efforts that play a major part in treating the cancer internationally, it is a brachytherapy system. Brachytherapy was carried out mostly with radium sources, but recently some artificial sources are incorporated in this mode of treatment such as Cs-137, Ir-192, Au-198, P-32, Sr-90 and I-125. The research cover history of brachytherapy and radioactive sources used in, techniques of implementation, radiation protection and methods of brachytherapy dose calculation, as well as brachytherapy in radiation and isotopes centre in Khartoum.
The goals of this paper are to describe the fabrication and complete evaluation of a dihydropyridine <- -> pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. Tissue distribution studies of "1"2"5I-labeled 4-iodoaniline and the redox agents were performed in rats. ["1"2"5I]Iodoaniline initially showed moderate brain uptake with subsequent release of the radioactivity from the brain. ["1"2"5I]Iodoaniline, however, when coupled to a dihydropyridine carrier showed significantly higher uptake and retention in the brain. (author).
Hydrophobic labelling is frequently used in the study of membrane-inserted domains of intrinsic proteins. However, the published procedures, fail to incorporate sufficient radioactivity into membrane immunoglobulins of B lymhocytes to permit investigation of their subunit structures and associations with other proteins. In order to increase the specific radioactivity of ["1"2"5I]iodonaphtylazide ["1"2"5I]INA), an improved method for the synthesis of the reagent was developed. In addition, the optimal conditions for labelling B lymhpocytes with ["1"2"5I]INA and commercially available reagent 3-(trifluoromethyl)-3-(trifluoromethyl)-3-(3'-["1"2"5Iliodophenyl)diazirine (["1"2"5I]TID were isolated and analysed in detail by SDS-PAGE. The usefulness of the two reagents for the investigation of lipid-embedded domains of membrane proteins is discussed. (author). 28 refs.; 4 figs.
Objective: To evaluate technical feasibility and acute and subacute radiotolerance of a self-expandable stent loaded with {sup 125}I seeds in the rabbit esophagus. Methods: A self-expandable stent designed for esophageal application was made of 0.16 mm nitinol wire and loaded with {sup 125}I seeds (CIAE-6711). Twenty-seven stents with three different radioactive dosages (n = 9 in each dosage group) were implanted in the esophagus of healthy rabbits, while nine stents alone were used as controls. The stents were perorally deployed into the esophagus under fluoroscopic guidance. Radiological follow-up included plain chest film, CT scan, and barium esophagography which were undertaken in all rabbits of each group at 2, 4, and 8 weeks, respectively, which were correlated to histopathological findings. The stented esophageal segments along with their adjacent tissues were harvested for histopathological ...
(-)-N6-(R-4-Hydroxyphenylisopropyl)adenosine (HPIA) was iodinated with NaI and trace /sup 125/I. Mono- and diiodinated reaction products and the starting material were separated by high pressure liquid chromatography and the structures of the reaction products were verified by NMR. (-)-N6-(R-Phenylisopropyl)adenosine (PIA), IHPIA, and I2HPIA decreased rat atrial contractility with ED50 values of 24, 28, and 33 nM, respectively. The contractile effects of these compounds were competitively blocked by theophylline (KI . 7.9 microM), but were not affected by adenosine deaminase. IHPIA also inhibited (-)isoproterenol-stimulated cyclic AMP accumulation in adipocytes with an ED50 (10 nM) and to an extent (83%) nearly identical to PIA. (/sup 125/I)HPIA prepared using carrier-free /sup 125/I bound to adenosine receptors on membranes from rat cerebral cortex, adipocyte ...
A simple procedure is described for preparing {sup 125}I-labelling hyluronan of high molecular weight. The reducing terminal group of hyaluronic acid was derivatized with tyramine through the formation of a Schiff base which was subsequently reduced with sodium cyanoborohydride. By radioiodination of the aromatic ring, {sup 125}I-labelled hyaluronic acid was obtained in high yield (40%) and high specific activity, 555 GBq/mmol (15 Ci/mmol). (Author).
BACKGROUND AND OBJECTIVE:For treatment of benign prostatic hyperplasia (BPH), Plasma Kinetic loop Resection of the Prostate (PKRP) is an alternative to conventional monopolar...Full Text Available
/sup 125/I-Calmodulin is internalized by isolated rat renal brush border membrane vesicles (BBV) in a time, temperature and calcium dependent manner. Internalization of /sup 125/I-calmodulin into the osmotically sensitive space of BBV was distinguished from binding of the ligand to the outer BBV surface by examining the interaction of ligand and BBV at different medium osmolarities (300-1100 mosm), uptake was inversely proportional to medium osmolarity. Internalized /sup 125/I-calmodulin was intact and Western blots of solubilized BBV with /sup 125/I-calmodulin demonstrated the presence of several calmodulin-binding proteins of 143, 118, 50, 47.5, 46.5 and 35 kilodaltons which could represent potential intravesicular binding sites for the ligand. Heparin and the related glycosaminoglycan heparin sulfate both showed a ...
Two no-carrier-added "1"2"5I-labelled photoaffinity rapamycin analogs were prepared: 7-demethoxy-7-(4-azido-3-"1"2"5I-benzyloxy) rapamycin and its C_2_8-C_2_9 seco analog. The key reactions of the synthesis were substitution of the C_7 methoxyl of rapamycin with 4-azido-3-tributylstannylbenzyloxy group, exchange of tributyltin with "1"2"5I using Na"1"2"5I and Chloramine-T, and a ZnCl_2 mediated retro-Aldol cleavage of the C_2_8-C_2_9 bond of rapamycin. (author).
In order to understand the role of EGF in the development of human mammary epithelial tissue, we analysed the binding of /sup 125/I-EGF to sections of breast cancer biopsies. A mean specific /sup 125/I-EGF binding of 8.9 fmol per mg protein was estimated in thin sections of 17 breast cancer biopsies. Microautoradiographic analysis of /sup 125/I-EGF binding to the tissue sections was applied to demonstrate that EGF was bound predominantly to mammary epithelial cells. The binding was clearly correlated to the number of mitoses of mammary epithelial cells in the same samples. The highest EGF binding and proliferation rates were found in biopsies from breast cancer with axillary lymph-node metastases.
BackgroundThere is no consensus as to the prognostic model for brachytherapy of tongue carcinoma. This study was designed to evaluate the prognostic factors for local control based...Full Text Available
Brachytherapy is a radiotherapeutic modality that makes use of radionuclides to deliver a high radiation dose to a well-defined volume while sparing surrounding healthy structures. At the National Institute for Cancer Research of Genova a High Dose Rate remote afterloading system provides Ir(192) endocavitary brachytherapy treatments. We studied the possibility to use the Geant4 Monte Carlo simulation toolkit in brachytherapy for calculation of complex physical parameters, not directly available by experiment al measurements, used in treatment planning dose deposition models.
It is now known that various growth factors may also act in the central nervous system. Among them, it has recently been shown that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) may possess trophic effects in the mammalian brain. We report here on the respective autoradiographic distribution of ["1"2"5I]EGF and ["1"2"5I]IGF-I receptor binding sites in the rat brain, both during ontogeny and in adulthood. It appears that ["1"2"5I]EGF sites are mostly found in the rat forebrain during brain development. On the other hand, ["1"2"5I]IGF-I sites are more widely distributed both during ontogeny and in adulthood. These results reveal the plasticity of the expression of EGF and IGF-I receptor sites in the mammalian brain. This could be relevant for the respective role of these two growth factors in the development and maintenance of neuronal function.
Subcellular-fractionation techniques were used to characterize the endocytic pathway followed by ricin in rat liver in vivo and tentatively identify the site(s) at which the ricin interchain disulphide...Full Text Available
We have examined the detection by a /sup 125/I-labeled basic protein, cationized cytochrome c, of selected proteoglycans (PGs) and standard preparations of glycosaminoglycans (GAGs) immobilized on Nylon 66 and also on positively charged Nylon 66. Immobilization on Nylon 66 appears to allow a relative freedom of interaction between PGs or GAGs and /sup 125/I-cationized cytochrome c, but a more restricted reaction was observed when PGs and GAGs were immobilized to positively charged Nylon 66. On this support PGs with large numbers of GAG side chains reacted well with /sup 125/I-cationized cytochrome c, but GAGs were minimally reactive. By taking advantage of some of the properties of large-pore agarose-acrylamide gels, rapid partial characterization of some PGs can be accomplished in the 10-ng range, and therefore at a sensitivity equal to PGs with internal ...
The fabrication and complete evaluation are described of a dihydropyridine in equilibrium pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. The pivotal intermediate, N-succinimidyl (1-methylpyridinium iodide)-3-carboxylate was prepared by condensation of nicotinic acid and N-hydroxysuccinimide in the presence of dicyclohexylcarbodimide, followed by quaternization of III with methyl iodide. Tissue distribution studies of "1"2"5I-labeled 4-iodoaniline and the redox agents were performed in rats. ["1"2"5I]Iodoaniline initially showed moderate (0.58% dose/gm) brain uptake with subsequent release of the radioactivity from the brain. ["1"2"5I]Iodoaniline, when coupled to a dihydropyridine carrier showed higher uptake and retention in the brain. The ["1"2"5I]iodophenylethyl analogue showed uptake and retention in the brain to be very similar. Apparently the lipophilic agents cross the blood-brain barrier and are oxidized (quaternized) within the brain. ...
Prostate biopsy is the current gold-standard procedure for prostate cancer diagnosis. Existing prostate biopsy procedures have been mostly focusing on detecting cancer presence. However, they...Full Text Available
A useful method for preparing radioiodinated photoaffinity labels from alkyl anilines which offer significant advantages over present methods is described. The one-pot synthesis gives good radiochemical yields (40-64%) of pure, high specific activity (350-1500 mCi/#mu#mol) "1"2"4I labelled iodaryl azides while minimising manipulation of radioactive materials. Purification of the ["1"2"5I]iodoazido photoaffinity labels is achieved by high performance liquid chromatography. (author).
A useful method for preparing radioiodinated photoaffinity labels from alkyl anilines which offer significant advantages over present methods is described. The one-pot synthesis gives good radiochemical yields (40-64%) of pure, high specific activity (350-1500 mCi/{mu}mol) {sup 124}I labelled iodaryl azides while minimising manipulation of radioactive materials. Purification of the ({sup 125}I)iodoazido photoaffinity labels is achieved by high performance liquid chromatography. (author).
Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for /sup 125/I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of /sup 125/I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of /sup 125/I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after ...
The authors have localized and characterized 2-125I-iodomelatonin binding sites in the chicken brain using in vitro quantitative autoradiography. Binding sites were widely distributed throughout the chicken brain, predominantly in regions associated with the visual system. The specific binding of 2-125I-iodomelatonin to discrete chicken brain areas was found to be saturable, reversible, and of high affinity. The specific binding of 2-125I-iodomelatonin (75 pm) was quantitated for 40 identifiable brain regions. Eight brain regions were chosen for binding characterization and pharmacological analysis: optic tectum, Edinger-Westphal nucleus, oculomotor nucleus, nucleus rotundus, ventral supraoptic decussation, ventrolateral geniculate nucleus, neostriatum, and ectostriatum. These regions showed no rostral-caudal gradient in ...
3-Quinuclidinyl benzilate (QNB) is a potent muscarinic antagonist that binds to muscarinic acetylcholine receptors. Iodination of QNB is difficult because it contains rings that are deactivated, while phenol rings are activated. The purpose of this research is to develop an appropriate method for the iodination of QNB at no-carrier-added concentrations of /sup 125/I/NaI. Phenol was chose as the test compound for direct iodination by adding chloramine T and nonradioactive sodium iodide to the phenol in a phosphate buffer and methanol system. A simple method to radioiodinate QNB at several concentrations was developed in situ in the presence of QNB, thallic trifluoroacetate /sup 125/I/NaI, /sup 127/I/NaI, and aluminium chloride. Using milligram amounts of QNB (7.12 x 10/sup -6/ moles), three reaction steps were involved: QNB was reacted with thallic trifluoroacetate at 60/sup 0/C for 24 hours, then ...
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular ...
Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular ...
A carrier-free radioiodinated phenylazide derivative of forskolin, 3-iodo-4-azidophenethylamido-7-O-succinyl-deacetyl-forskolin (({sup 125}I)IAPS-forskolin), has been shown to be a highly selective photoaffinity probe for the human erythrocyte glucose transported and the glucose transport proteins found in several mammalian tissues and cultured cells where the glucose transport protein is present at a low concentration. The photoincorporation of ({sup 125}I)IAPS-forskolin into these glucose transporters was blocked by D- (but not L-) glucose, cytochalasin B, and forskolin. In addition to labeling the mammalian glucose transport proteins, ({sup 125}I)IAPS-forskolin also labeled the L-arabinose transporter from E. coli. In muscle and adipose tissues, glucose transport is markedly increased in response to insulin. ({sup ...
A carrier-free radioiodinated phenylazide derivative of forskolin, 3-iodo-4-azidophenethylamido-7-O-succinyl-deacetyl-forskolin (["1"2"5I]IAPS-forskolin), has been shown to be a highly selective photoaffinity probe for the human erythrocyte glucose transported and the glucose transport proteins found in several mammalian tissues and cultured cells where the glucose transport protein is present at a low concentration. The photoincorporation of ["1"2"5I]IAPS-forskolin into these glucose transporters was blocked by D- (but not L-) glucose, cytochalasin B, and forskolin. In addition to labeling the mammalian glucose transport proteins, ["1"2"5I]IAPS-forskolin also labeled the L-arabinose transporter from E. coli. In muscle and adipose tissues, glucose transport is markedly increased in response to insulin. ["1"2"5I]IAPS-forskolin was shown to selectivity tag the glucose transporter in membranes derived from these cells. In addition, the covalent derivatization of the transport protein in ...
Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of ["1"2"5I]EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM ["1"2"5I]EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium azide inhibited internalization of label, whereas a series of lysosomal ...
Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of (/sup 125/I)EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM (/sup 125/I)EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, ...
Objective: To analyze the early response of uveal melanomas in patients treated with ruthenium-106 brachytherapy. Materials And Methods: In the period between April 2002 and July 2003, 20 patients diagnosed with uveal melanoma were submitted to ruthenium-106 brachytherapy. The calculated dose delivered at the apex of the tumor ranged between 55 Gy and 100 Gy. Patients with lesions greater than 5 mm were submitted to transpupillary thermotherapy concomitantly with ophthalmic plaque insertion. Results: As regards the lesions site, 75% of the lesions were located in the choroid, 15% in the iris, and the remainder 10% in the ciliary body. In a median 19-month-follow-up, the progression-free survival for brachytherapy was 69%, and 87% for associated brachytherapy and transpupillary thermotherapy. A significant tumor height reduction was observed after treatment. No patient was submitted to enucleation. ...
Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in ...
Purpose HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule ZHER2:342 is a small (7?kDa) affinity protein binding to HER2 with an affinity of 22?pM. The goal of this study was to evaluate the use of ((4-hydroxyphenyl)ethyl)maleimide (HPEM) for radioiodination of ZHER2:342 and to compare the targeting properties of monomeric and dimeric forms of ZHER2:342. Methods The biodistribution of different radioiodinated derivatives of ZHER2:342 was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of 125I-PIB-ZHER2:342 and site-specifically labelled 125I-HPEM-ZHER2:342-C were compared. Biodistributions of monomeric 131I-HPEM-ZHER2:342-C and dimeric 125I-HPEM-(ZHER2:342)2-C were evaluated using a paire...
Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate...Full Text Available
We report a case of symptomatic intraurethral prostatic cyst in a 42-yr-old man without clinical evidence of benign prostatic hyperplasia. The intraurethral cyst makes it unique from the all previously...Full Text Available
Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+...Full Text Available
Prostatic neoplasms are not uniformly distributed within the prostate volume. With recent developments in three-dimensional intensity-modulated and imageguided radiation therapy, it is possible to treat...Full Text Available
Despite numerous investigations, the correlation between alcohol consumption and prostate cancer risk remains uncertain. This report investigated the association between alcohol use and prostate cancer...Full Text Available
1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues...Full Text Available
A series of four 125I-labeled 1-substituted-4-phenylpiperazines were prepared and evaluated in rats as potential brain imaging agents. The compounds were labeled using (125I)iodide/chloramine-T or iodine monochloride and isolated in 48-60% radiochemical yields. The tissue distribution studies indicated that a butyrophenone derivative demonstrated the best overall brain-imaging properties. Compared with the compounds having other 1-substituents this agent had a more prolonged retention of activity in the brain and higher brain-to-blood ratios over the 4-h period studied. The in vivo behavior of this agent is comparable to that of radioiodinated N-isopropyl-p-iodoamphetamine, and, because it can be labeled directly via electrophilic methods, it has substantial potential for use in brain imaging with single photon emission computed tomography.
The human erythrocyte (RBC) Rh blood group system consists of a complex of distinct integral membrane polypeptides with physical properties common to the aminophospholipid transporter responsible for the transbilayer movement of phosphatidylserine (PS) in RBC. To assess the involvement of Rh polypeptides in PS translocation, the aminophospholipid translocase was labeled with a photoactivatable PS analogue, "1"2"5I-azido-PS, and with an inhibitor of PS transport, "1"2"5I-labeled 2-(2-pyridyldithio)ethylamine. The ability of monoclonal Rh antibodies to immunoprecipitate the labeled transporter was determined. Immunoprecipitated Rh polypeptides were found to be labeled with the aminophospholipid translocase markers, suggesting that Rh proteins are involved in the transbilayer movement of PS.
Antibodies to human native and denatured types I, II, III, IV, and V collagens were measured using 125I-radioimmunoassay. Mean levels of binding by sera from 30 rheumatoid arthritis patients were significantly higher than those from 20 normal subjects against all of the collagens tested. The relative antibody concentration was higher in synovial fluid than in simultaneously obtained serum. Many patients with gout or various other rheumatic diseases also had detectable anticollagen antibodies. With a few notable exceptions, the majority of the reactivity detected in all patient groups was directed against covalent structural determinants present on all of the denatured collagens, suggesting a secondary reaction to tissue injury.
PurposeUltrasonically measured intravesical prostatic protrusion may be a promising noninvasive method of assessing bladder outlet obstruction. Previous investigations...Full Text Available
A study of the effects of the action of phenoxybenzamine on bladder neck opening during micturition is reported. Twenty patients with symptoms of prostatism but minimal prostatic enlargement were studied....Full Text Available
PurposeTo determine the dosimetric impact of inter-fraction anatomical movements in prostate cancer patients receiving proton therapy.Full Text Available
Brachytherapy consists of sealed radioactive source implantation. The diversity in the nature of radioelements, in their energy and activity requires strict implantation and utilization rules. These rules include radioactive source physical parameters check, after-loading machine and treatment planning system quality assurance and safe and reproducible dosimetric systems. Patient and medical workers information guarantee radioprotection and prevention of accidental exposures. (authors)
Purpose: To examine the role of brachytherapy in the treatment of cholangiocarcinomas in a relatively large group of patients. Methods and Materials: Using the Surveillance, Epidemiology and End Results database, a total of 193 patients with cholangiocarcinoma treated with brachytherapy were identified for the period 1988-2003. The primary analysis compared patients treated with brachytherapy (with or without external-beam radiation) with those who did not receive radiation. To try to account for confounding variables, propensity score and sensitivity analyses were used. Results: There was a significant difference between patients who received radiation (n = 193) and those who did not (n = 6859) with regard to surgery (p < 0.0001), race (p < 0.0001), stage (p < 0.0001), and year of diagnosis (p <0.0001). Median survival for patients treated with brachytherapy was 11 months (95% confidence ...
1. Several ring-substituted derivatives of diphenyleneiodonium catalyse the exchange of Cl- and OH- ions across the inner membrane of rat liver mitochondria. They also inhibit state 3 and state 3u oxidations...Full Text Available
Nitroaromatic radiosensitizers become metabolically bound preferentially to hypoxic cells and at least 10/sup 9/ adducts/cell can be tolerated as non-toxic. EMT-6 tumor cells have been incubated in hypoxia in the presence of /sup 3/H-Misonidazole and /sup 125/I-Azomycin Riboside for various times and the amount of /sup 3/H or /sup 125/I bound/cell was determined. Cells were stored as monolayers at 25"0C for up to 96 hr to accumulate radioactive decays and transferred at various times to 37"0C for colony-forming assays. No radiation inactivation was measured in cells which had incorporated at least 10/sup 6/ /sup 3/H or 10/sup 5/ /sup 125/I atoms. Previous studies had shown that -- 1% of MISO adducts to EMT-6 cells was associated with cellular DNA. These data indicate that the radiation-induced damage produced by these quantities of bound /sup 3/H or /sup ...
LEW anti-DA kidney and DA anti-LEW kidney sera were assayed using an indirect 125I anti-immunoglobulin-binding assay with kidney homogenate as target. This allowed the full spectrum of antibodies to...Full Text Available
Determination of Mn, Fe, Cu, Zn, Hg, Pb, Br, Se, Rb, Sr and Cd in the medicinal plants by radionuclide X-ray fluorescence analysis (using "2"3"8Pu, "2"4"1Am/Ag and "1"2"5I) is described. (author). 12 refs., 2 tabs.
The influence of carbon monoxide (CO) exposure on regional cerebral blood flow (r-CBF) in rat brain was studied using autoradiography and "1"2"5I-IMP. Fuji computed radiography (FCR) was used to obtain improved autoradiograms in this study. R-CBF was determined in a relative measure by calculating hippocampus/cortex and putamen/cortex ratios of RI accumulation from the autoradiogram using a densitometer. Comparison of autoradiograms with pathological findings in the area of the hippocampus and putamen yield the following results. In the animals that were exposed to 6400 ppm or 10000 ppm of CO for 30 minutes, and then were followed up for 2 weeks without further exposure, r-CBF was decreased but no pathological changes occurred. In the animals that were exposed to 6400 ppm or 10000 ppm of CO, and then were followed up for 4 weeks without further exposure, pathological changes appeared. In animals exposed to 3200 ppm of CO, the r-CBF tended to recover after 4 weeks. Furthermore, ...
The influence of carbon monoxide (CO) exposure on regional cerebral blood flow (r-CBF) in rat brain was studied using autoradiography and {sup 125}I-IMP. Fuji computed radiography (FCR) was used to obtain improved autoradiograms in this study. R-CBF was determined in a relative measure by calculating hippocampus/cortex and putamen/cortex ratios of RI accumulation from the autoradiogram using a densitometer. Comparison of autoradiograms with pathological findings in the area of the hippocampus and putamen yield the following results. In the animals that were exposed to 6400 ppm or 10000 ppm of CO for 30 minutes, and then were followed up for 2 weeks without further exposure, r-CBF was decreased but no pathological changes occurred. In the animals that were exposed to 6400 ppm or 10000 ppm of CO, and then were followed up for 4 weeks without further exposure, pathological changes appeared. In animals exposed to 3200 ppm of CO, the r-CBF tended to ...
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remains an enigmatic medical condition. Creation of the (NIH) Chronic Prostatitis Collaborative Research Network (CPCRN) funded by...Full Text Available
ObjectivesTo assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. MethodsProstate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potenti...
By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as ...
Two methods were used to label pig kidney microvillar membrane proteins from the luminal and cytoplasmic surfaces of closed membrane vesicles. The first method was lactoperoxidase-catalysed radioiodination. Lactoperoxidase and glucose oxidase were positioned inside or outside the vesicles, iodination being initiated by adding glucose and "1"2"5I. After electrophoresis of the proteins, asymmetric labelling patterns on radioautographs were observed. However the major disadvantage of this method was the high degree of intramembrane labelling of the fatty acid chains of membrane lipids. The second method overcame this disadvantage. A new hydophilic photoreagent, 3,5-di("1"2"5I)iodo-4-azidobenzenesulphonate, was transported by a Na"+-dependent system into microvillar vesicles, thus permitting labelling from either side of the membrane when the vesicles were photolysed. The activity of several microvillar peptidases survived the labelling reaction and they could be identified in the ...
The interest in radioiodinated diamines stems from their similarity to /sup 125/I-HIPDM and to the 1-dialkvlamino-acyl-4-phenylpiperazines that the authors have previously examined as potential brain imaging agents. In this study they converted the 1-(dialkylaminoacyl)-4-phenylpiperazines to their corresponding 1-(dialkylaminoacyl) analogs via reduction with diborane in THF. Radioiodination at the no-carrier-added level with Na/sup 125/I and chloramine-T gave the final compounds, after chromatographic separation, in 30-50% yields. The tissue distributions were determined in rats at 0.25, and 4 hrs after an i.v. injection of the radiochemical. The results indicated that all of the agents were readily extracted by the brain (1.5-2.5% ID) with brain to blood ratios >20. The structure-distribution relationships for this series were, however, decidedly different from the aminoacyl compounds in that ...
The interest in radioiodinated diamines stems from their similarity to /sup 125/I-HIPDM and to the 1-dialkvlamino-acyl-4-phenylpiperazines that the authors have previously examined as potential brain imaging agents. In this study they converted the 1-(dialkylaminoacyl)-4-phenylpiperazines to their corresponding 1-(dialkylaminoacyl) analogs via reduction with diborane in THF. Radioiodination at the no-carrier-added level with Na/sup 125/I and chloramine-T gave the final compounds, after chromatographic separation, in 30-50% yields. The tissue distributions were determined in rats at 0.25, and 4 hrs after an i.v. injection of the radiochemical. The results indicated that all of the agents were readily extracted by the brain (1.5-2.5% ID) with brain to blood ratios >20. The structure-distribution relationships for this series were, however, decidedly different from the aminoacyl compounds in that ...
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding ...
1. The stereospecificity of the enantiomers of LY253352, a potent and selective alpha 1-adrenoceptor antagonist, were studied in the human prostate and canine brain using radioligand receptor binding...Full Text Available
BACKGROUND: A number of studies have shown that the early mortality following TURP is higher for patients with prostate cancer than those with benign disease. This study examines the effect of the histological...Full Text Available
BackgroundFinasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have...Full Text Available
Prostate maldevelopment in prune-belly syndrome has only been described at necropsy. No reports are available in the “in vivo” studies. The absence of the verumontanum at voiding cystourethrography...Full Text Available
Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human...Full Text Available
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays...Full Text Available
This paper presents a new deformable model using both population and patient-specific statistics to segment the prostate from CT images. There are two novelties in the proposed method. First,...Full Text Available
BACKGROUNDProtocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess...Full Text Available
Male transgenic mice expressing the polyomavirus middle T (PyV-MT) gene exhibited growth and developmental abnormalities in prostatic and other urogenital epithelium. Expression of PyV-MT was directed...Full Text Available
Benign prostatic hyperplasia (BPH) is the leading cause of lower urinary tract symptoms among the aging male population. Epidemiological, pathophysiological and clinical studies indicate that...Full Text Available
BackgroundRecent data show aberrant and altered expression of regulatory noncoding micro (mi) RNAs in prostate cancer (PCa). A large number of miRNAs are encoded in organized intronic...Full Text Available
BackgroundWith the increasing interest with botulinum toxin – A (BTX-A) application in the lower urinary tract, we investigated the BTX-A effects on the canine prostate and...Full Text Available
PurposePrevious studies suggest that some common medications alter prostate-specific antigen (PSA) levels. It remains unclear whether these reported medication effects are due to...Full Text Available
Every year nearly 200,000 men in the United States are diagnosed with prostate cancer (PCa), and another 29,000 men succumb to the disease. Within certain regions of the world population based...Full Text Available
Benign prostatic hyperplasia (BPH) is a complex and progressive disease common in aging men. While associated with bothersome lower urinary tract symptoms, it may also result in additional serious complications...Full Text Available
The present work was carried out to illuminate the relation between high cholesterol diet and incidence of prostate caner. Also, in this study, the effect of DHEA, selenium or oxygen therapy were tested in order to show to what extent they are valid to ameliorate the deleterious effects of prostate cancer. The obtained results revealed that prostate cancer caused a significant (p<0.01) elevation of TAP, PAP, PSA, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol and prostate COX-2, whereas, testosterone, free testosterone, DHEA-S, FT_4 and FT_3 were decreased significantly as compared with the corresponding levels in control rats in both normal and high cholesterol diet. Supplementation of DHEA, selenium or oxygen therapy ameliorated all variables recorded herein but, their values did not revert to normal. Any how, the results of this investigation showed that the above mentioned ...
In 29 patients with urinary obstruction due to prostatic enlargement, medium-fill water cystometry was performed before prostatectomy and again 3 months after. A high incidence of detrusor hyperreflexia...Full Text Available
PurposeWe previously reported a randomized phase II clinical trial combining a poxvirus-based vaccine encoding PSA with radiotherapy in patients with localized prostate...Full Text Available
In many radiotherapy clinics, geometric uncertainties in the delivery of 3D conformal radiation therapy and intensity modulated radiation therapy of the prostate are reduced by aligning the...Full Text Available
ObjectivesThis feasibility study developed and pilot tested an intervention to: (1) increase knowledge about prostate cancer (CaP) screening; and (2) promote self-efficacy...Full Text Available
The offline adaptive radiotherapy (ART) has been used to effectively correct and compensate the prostate motion and reduce the required margin. The efficacy depends on the characteristics of...Full Text Available
Four /sup 125/I labeled mono- and diamines were prepared and evaluated as potential brain-imaging agents. The diamines are analogues of the previously reported /sup 75/Se labeled diamines, which show high brain uptake and retention. All of the radioiodinated amines display high initial brain uptake in rats after intravenous injection (1.7-2.4% dose/organ). The xylylenediamines show prolonged brain retention (t1/2 approximately 18 h), which is desirable for brain imaging. In contrast, the benzylamine is rapidly cleared from brain tissue (t1/2 approximately 15 min).
The usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. {sup 125}I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a-e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a-c), iodophenoxyethyl ethylenediamine derivatives (9,14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a-e, 6a-c, 8, 13, 17) by this method. (author).
The usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. "1"2"5I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a-e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a-c), iodophenoxyethyl ethylenediamine derivatives (9,14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a-e, 6a-c, 8, 13, 17) by this method. (author).
Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [[sup 125]I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo lability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumor-bearing mice showing limited uptake of radioactivity in tumours and a tumor-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents. (author).
Development of selective serotonin transporter (SERT) tracers for single-photon emission tomography (SPET) is important for studying the underlying pharmacology and interaction of specific serotonin reuptake site inhibitors, commonly used antidepressants, at the SERT sites in the human brain. In search of a new tracer for imaging SERT, IDAM (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol) was developed. In vitro characterization of IDAM was carried out with binding studies in cell lines and rat tissue homogenates. In vivo binding of [[sup 125]I]IDAM was evaluated in rats by comparing the uptakes in different brain regions through tissue dissections and ex vivo autoradiography. In vitro binding study showed that IDAM displayed an excellent affinity to SERT sites (K[sub i]=0.097 nM, using membrane preparations of LLC-PK[sub 1] cells expressing the specific transporter) and showed more than 1000-fold of selectivity for SERT over ...
Abstract Prostate leiomyosarcoma is an extremely rare and highly aggressive neoplasm that accounts for less than 0.1% of primary prostate malignancies. Herein, we present a patient with primary leiomyosarcoma of the prostate with lung metastasis diagnosed primarily on fine-needle aspiration cytology. Characteristic cytological features such as small fascicles of spindle cells with blunt-ended nuclei, positivity for desmin and smooth muscle actin along with the radiological features are helpful in the correct diagnosis. Diagn. Cytopathol. 2010. 2010 Wiley-Liss, Inc.
The murine 3T3-L1 fibroblast under appropriate incubation conditions differentiates into an adipocyte phenotype. This 3T3-L1 adipocyte exhibits many of the morphologic, biochemical, and insulin-responsive features of the normal rodent adipocyte. Using quantitative electron microscopic (EM) autoradiography we find that, when /sup 125/I-insulin is incubated with 3T3-L1 adipocytes, the ligand at early times of incubation localizes to the plasma membrane of the cell preferentially to microvilli and coated pits. When the incubation is continued at 37 degrees C, /sup 125/I-insulin is internalized by the cells and preferential binding to the villous surface is lost. With the internalization of the ligand, two intracellular structures become labeled, as determined by the method of hypothetical grain analysis. These include large clear, presumably endocytotic, vesicles and multivesicular bodies. Over the first ...
The synthesis and brain uptake in mice of the radioidinated derivatives of N,N-dimethyl-N'-(idodimethoxyphenyl)-1,3-propanediamine, as well as the N-substituted derivatives of (iodoalkylphenyl)isopropyl, iodoalkylphenylethylamine and 3,4-(methylenedioxy)phenyl-amphetamine (MDA) are described. These compounds contain structural features of both IMP and HIPDM, the cerebral perfusion agents currently in clinical use. The radiolabeled analogs were obtained via the [{sup 125}I]I exchange method, or by [{sup 125}I]NaI treatment of the iodo-free precursor in the presence of an oxidant. Following intravenous injection in mice, all compounds showed important radioactivity concentrations in the lungs and kidneys. The N-substituted (iodoalkylphenyl)isopropyl and iodoalkylphenyl-ethylamine derivatives displayed a high initial brain uptake (>10%IDg{sup -1}) followed by a rapid clearance phase, ...
The synthesis and brain uptake in mice of the radioidinated derivatives of N,N-dimethyl-N'-(idodimethoxyphenyl)-1,3-propanediamine, as well as the N-substituted derivatives of (iodoalkylphenyl)isopropyl, iodoalkylphenylethylamine and 3,4-(methylenedioxy)phenyl-amphetamine (MDA) are described. These compounds contain structural features of both IMP and HIPDM, the cerebral perfusion agents currently in clinical use. The radiolabeled analogs were obtained via the ["1"2"5I]I exchange method, or by ["1"2"5I]NaI treatment of the iodo-free precursor in the presence of an oxidant. Following intravenous injection in mice, all compounds showed important radioactivity concentrations in the lungs and kidneys. The N-substituted (iodoalkylphenyl)isopropyl and iodoalkylphenyl-ethylamine derivatives displayed a high initial brain uptake (>10%IDg"-"1) followed by a rapid clearance phase, resulting in lower brain-to-blood ratios as those reported for IMP and HIPDM. In contrast, ...
The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [125I]-DNP and used this to localize high-affinity (K(D)=0.2 nmol/L), saturable, specific binding sites in adult human heart (n=6) and coronary artery (n=8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [125I]-DNP was specific to NPR-A. ...
An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose dependent manner (r = 0.98). Based on the IM-9 assay, 1 ml of the PGF had an activity equivalent to 625 ng of the ...
Cytochrome c, labeled with /sup 125/I, has been used by us for staining glycosaminoglycans (GAG) separated by electrophoresis on cellulose acetate strips. As GAG between 1-10 ng could be quantified by autoradiography and densitometry, the reagent is approximately 100-fold more sensitive than currently used non-radiolabeled stains. The authors extend now the use of radiolabeled cytochrome c to the quantification of PG transblotted to solid supports subsequent to separation on polyacrylamine slab gels. Dot blotting used for exploring optimal conditions for detecting PG indicated that because of low background positively charged Nylon 66 was superior to nitrocellulose. Increasing the positive charge of the staining reagent by cationization decreased background radiation even further so that 1 ng PG could be seen readily after 5 hrs of autoradiography. Use of cationized /sup 125/I-cytochrome c has been made ...
Purpose: Antitumor activity of the dichloroplatinum(II)-histamine complexes labeled with I-125 or I-131 was investigated in a transplantable murine adenocarcinoma (MA) model. Methods: The tumor model was obtained in C3H/W female mice after subcutaneous inoculation of the tumor cells derived from the mice bearing a mammary tumor of spontaneous origin. Antitumor activities of the platinum-histamine complexes were investigated in three independent experiments, which differed in applied doses of preparations (PtCl{sub 2}Hist, PtCl{sub 2}[{sup 125}I]Hist, PtCl{sub 2}[{sup 131}I]Hist, PtCl{sub 2}Hist/PtCl{sub 2}[{sup 125}I]Hist and PtCl{sub 2}Hist/PtCl{sub 2}[{sup 131}I]Hist), treatment schedules as well as stages of the disease progress in the animals used. Experiment 1 included long-term, multidose treatment with low single doses (treatment duration 31-32 days; 8-10 doses of ca. 0.25{center_dot}MTD{sub Pt} ...
Full text: Immunoassays for prostate-specific antigen (PSA) are used to detect early-stage prostate cancer, monitor disease progress, and evaluate therapeutic response. At least two forms of PSA, free PSA (F-PSA) and PSA complexed to alpha-1 anti-chymotrypsin (PSA-ACT) are detected by commercial PSA assays. The fraction of F-PSA is shown to be smaller in patients with untreated prostate cancer than in patients with benign prostate hyperplasia (BPH). Thus, combined measurements of both total and free PSA are used for a better discrimination between BPH and prostate cancer. Detection of PSA for screening of prostate cancer has been a subject of debate for many years. The reason of this debate is mainly because screening for prostate cancer is not cost-effective, as was shown by studies undertaken in Europe and United States. In Lebanon, no ...
An ytterbium-169 high dose rate brachytherapy source, distinguished by an intensity-weighted average photon energy of 92.7 keV and a 32.015#+-#0.009 day half-life, is characterized in terms of the updated AAPM Task Group Report No. 43 specifications using the MCNP5 Monte Carlo computer code. In accordance with these specifications, the investigation included Monte Carlo simulations both in water and air with the in-air photon spectrum filtered to remove low-energy photons below 10 keV. TG-43 dosimetric data including S_K, D(r,#theta#), #LAMBDA#, g_L(r), F(r,#theta#), #phi#_a_n(r), and #phi#_a_n were calculated and statistical uncertainties in these parameters were derived and calculated in the appendix.
Monte Carlo calculations using the codes PENELOPE and GEANT4 have been performed to characterize the dosimetric properties of monoenergetic photon point sources in water. The dose rate in water has been calculated for energies of interest in brachytherapy, ranging between 10 keV and 2 MeV. A comparison of the results obtained using the two codes with the available data calculated with other Monte Carlo codes is carried out. A chi2-like statistical test is proposed for these comparisons. PENELOPE and GEANT4 show a reasonable agreement for all energies analyzed and distances to the source larger than 1 cm. Significant differences are found at distances from the source up to 1 cm. A similar situation occurs between PENELOPE and EGS4.
Purpose To evaluate the methods of applicator reconstruction in 3D MR-based planning for brachytherapy of cervical cancer, and to investigate applicator shifts and changes in DVH parameters during PDR treatment. Methods For each application MR scans with applicator in situ were made: three T2-weighted (4.5mm slices) Turbo Spin Echo (TSE) scans and a balanced Steady State Free Precession scan (1.5mm). Three observers tested two applicator reconstruction methods: (A) directly on the bSSFP scan and (B) on a resampled combination of the three T2-weighted scans. For 10 patients MR imaging was repeated on the second day of each PDR fraction to determine applicator shifts and changes in DVH parameters. Results For both applicator reconstruction methods the interobserver variation for the DVH para...
Four "1"2"5I labeled mono- and diamines were prepared and evaluated as potential brain-imaging agents. The diamines are analogues of the previously reported "7"5Se labeled diamines, which show high brain uptake and retention. All of the radioiodinated amines display high initial brain uptake in rats after intravenous injection (1.7-2.4% dose/organ). The xylylenediamines show prolonged brain retention (t1/2 approximately 18 h), which is desirable for brain imaging. In contrast, the benzylamine is rapidly cleared from brain tissue (t1/2 approximately 15 min).
The human articular cartilagineous proteoglycans (PG) R.I.A. is highly specific. The PG used as the standard and the /sup 125/I labelled molecule appear to be pure. Under these conditions, all the potential interfering substances which have been tested show no cross reaction. For instance, the Ag-Ab equilibrium is not affected by adding human IgG, human albumin, hyaluronic acid, chondroitin sulfate, rat type II collagen or total human serum proteins. This R.I.A. also exhibits a species spcificity since there is no cross reaction with rat PG and negligible cross section with dog PG. The results obtained after addition of enzymes to the antigen demonstrate that the antigenic sites are localized on the protein region and not on the glycosaminoglycan region of the molecule.
One of the research challenges in oncology is to develop new biochemical methods for noninvasive tumor therapy evaluation to determine whether the chemotherapeutics is effective. Vascular endothelial growth factor (VEGF) was labeled with radioiodine and evaluated in vitro as well as in vivo, using A2058, a melanoma cell line overexpressing VEGFR-1 and -2. Saturation binding analysis with [{sup 125}I]-VEGF resulted in a K {sub d} of 0.1 nM. Internalization assays indicate the preserved ligand induced internalization and metabolization of the tracer. Biodistribution studies with [{sup 123}I]-VEGF in wild type and A2058 tumor-bearing athymic mice showed low background activity and a tumor to reference tissue ratio of maximum 6.12. These results suggest that [{sup 123}I]-VEGF is a potentially suitable tracer for tumor therapy evaluation.
In the present study the authors have shown that glycoproteins are present in the plasma membrane of Acanthamoeba castellanii by utilizing different radioactive labeling techniques. Plasma membrane proteins in the amoeba were iodinated by "1"2"5I-lactoperoxidase labeling and the solubilized radiolabeled glycoproteins were separated by lectin-Sepharose affinity chromatography followed by polyacrylamide gel electrophoresis. The periodate/NaB"3H_4 and galactose oxidase/NaB"3H_4 labeling techniques were used for labeling of surface carbohydrates in the amoeba. Several surface-labeled glycoproteins were observed in addition to a diffusely labeled region with M_r of 55,000-75,000 seen on electrophoresis, which could represent glycolipids. The presence of glycoproteins in the plasma membrane of Acanthamoeba castellanii was confirmed by metabolic labeling with ["3"5S]methionine followed by lectin-Sepharose affinity chromatography and polyacrylamide gel electrophoresis.
A radioassay for the rapid determination of Gsub(M1) ganglioside concentration in small volumes of CSF from individual patients is described. The assay utilizes the high-affinity interaction between cholera enterotoxin ("1"2"5I-labelled) and Gsub(M1) ganglioside. The lower detection limit of Gsub(M1) ganglioside by this radioassay under the described incubation conditions is 2.5 ng/ml. The radioassay-determined lumbar CSF Gsub(M1) ganglioside concentrations in a small group of patients with diverse neurologic disorders are presented. The radioassay Gsub(M1) ganglioside concentration is in good agreement with the G(M1) ganglioside concentration determined, in one patient, by the tlc-densitometry technique. (author).
Several randomized studies have been completed in prostate cancer that show a benefit to immediate postoperative treatment in patients undergoing prostatectomy. In one of the studies, there was even...Full Text Available
Abstract Background: G proteins are ubiquitously expressed signal transduction proteins playing a key role in multiple signal transduction pathways. The Gas subunit has been considered as an apoptosis factor. In this study the role of GNAS T393C genotypes of the GNAS gene encoding Gas was analyzed for its influence on the development and progression of prostate cancer. Methods: Genotyping of the GNAS T393C polymorphism in 196 prostate cancer patients and 200 healthy controls was performed by DNA extraction followed by PCR and restriction analysis. Results: We observed no evidence of effects related to GNAS T393C genotype as demonstrated by a comparison of the genotype distribution in prostate cancer patients and healthy controls, the genotype distribution dependent on grade of the primary ...
OBJECTIVE --To evaluate the consequences on male sexual function of intraprostatic injection of botulinum toxin type A (BoNT/A) as a treatment for benign prostatic hyperplasia (BPH). Although BoNT/A is effective in decreasing symptoms of BPH, neuronal impairment caused by the neurotoxin might affect emission/ejaculation. These aspects have not been evaluated before. PATIENTS AND METHODS --In all, 16 sexually active men aged >60 years with BPH/benign prostatic enlargement (BPE), International Prostate Symptom Score (IPSS) -8 and a maximum urinary flow rate (Qmax) <15mL/s refractory to standard medical therapy volunteered for the study. --Patients were injected transrectally, under ultrasonographic control, with 200U of BoNT/A in the prostate. Evaluation was carried out at baseline and 1, 3 ...
The cause of the female urethral syndrome has previously been obscure, as it has been associated by definition with a lack of objective findings but a plethora of subjective complaints of retropubic...Full Text Available
Malignancies Breast Malignancies Bladder, Prostate, and Testicular Malignancies Uses of Cancer Registry Data Brain Tumor Reporting Training Materials Overview Presentation and...
Malignancies Breast Malignancies Bladder, Prostate, and Testicular Malignancies Uses of Cancer Registry Data Brain Tumor Reporting Training Materials Overview Presentation and...
Malignancies Breast Malignancies Bladder, Prostate, and Testicular Malignancies Uses of Cancer Registry Data Brain Tumor Reporting Training Materials Overview Presentation and...
The results of interstitial brachytherapy in 13 patients with malignant brain tumors (malignant glioma 9 cases, metastatic brain tumor 4 cases) were reported. In all patients, Ir-192 thin wires were implanted temporarily in afterloading catheters, which were implanted appropriately by means of MRI or CT guided stereotactic technique. Clinical results on CT scan were as follows: CR (complete response) 1 case, PR (partial response) 6 cases and NC (no change) 6 cases. Even in the NC group, tumor growth was inhibited temporarily. Tumor free intervals were ranged 2-17 months. In early series, the intervals were about 2 months due to incomplete arrangement of radioactive implants. In recent series, prolongation of tumor free interval more than 12 months was achieved due to precise arrangements of implants. MRI guided stereotactic interstitial brachytherapy may provide safe and precise intracranial arrangements of implants, which yield high radiation ...
The results of interstitial brachytherapy in 13 patients with malignant brain tumors (malignant glioma 9 cases, metastatic brain tumor 4 cases) were reported. In all patients, Ir-192 thin wires were implanted temporarily in afterloading catheters, which were implanted appropriately by means of MRI or CT guided stereotactic technique. Clinical results on CT scan were as follows: CR (complete response) 1 case, PR (partial response) 6 cases and NC (no change) 6 cases. Even in the NC group, tumor growth was inhibited temporarily. Tumor free intervals were ranged 2-17 months. In early series, the intervals were about 2 months due to incomplete arrangement of radioactive implants. In recent series, prolongation of tumor free interval more than 12 months was achieved due to precise arrangements of implants. MRI guided stereotactic interstitial brachytherapy may provide safe and precise intracranial arrangements of implants, which yield high radiation ...
The absorbed dose delivered to the patient in brachytherapy is directly proportional to the source strength in terms of the reference air-kerma rate (RAKR). Verification of this quantity by the hospitals is widely recognized as an important part of a quality assurance program. An external audit was performed on behalf of the Secondary Standard Dosimetry Laboratory at the Swedish Radiation Protection Authority (SSI). The aim was to investigate how accurately the source-strength in 192Ir brachytherapy is determined at Swedish hospitals. The SSI reference well-type ion chamber and calibrated equipment were used to measure the RAKR of an 192Ir source in each of the 14 Swedish afterloading units. Comparisons with values determined by vendors and hospitals were made. Agreement in values of RAKR as determined by SSI, hospitals and vendors were in all cases within the +-3% uncertainty (at a coverage factor of k=2), typically guaranteed by the vendors. ...
High dose rate (HDR) brachytherapy for treating a cervix carcinoma has become popular, because it eliminates many of the problems associated with conventional brachytherapy. In order to improve the clinical effectiveness with HDR brachytherapy, a dose calculation algorithm, optimization procedures, and image registrations need to be verified by comparing the dose distributions from a planning computer and those from a humanoid phantom. In this study, the humanoid phantom was fabricated in order to verify the absolute doses and the relative dose distributions. The measured doses from the humanoid phantom were then compared with the treatment planning system for the dose verification. The humanoid phantom needs to be designed such that the dose distributions can be quantitatively evaluated thermoluminescent dosimeter (TLD) chips with a dimension of 1/8 and film dosimetry with a spatial resolution of <1 mm used to ...
PurposeRTOG protocol 95-17 was a phase I/II trial to evaluate multi-catheter brachytherapy as the sole method of adjuvant breast radiotherapy for stage I/II breast...Full Text Available
Aim: Treatment of carcinoma of the uterine cervix by remote afterloading brachytherapy has been accompanied with new isotopes having dose rates different from the classical low-dose rate (LDR) radium source. The dose rate conversion factor from LDR to high-dose rate (HDR) found to be around 0.54 in most studies. As regards medium-dose rate (MDR) brachytherapie, the published data are very few and the experience is still short. In this study the experience of Osaka University Hospital with micro-HDR-Selectron and Selectron-MDR, as a preliminary report of the clinical trial, is presented. Results: The 3-year survival and loco-regional control rates for both modalities were nearly equivalent (62% and 67% for HDR and 68% and 74% for MDR)(totally 45 patients). The cumulative rectal and bladder complication rates were the same in both groups (29% at 3 years), with only 1 patient (MDR-group) developed grade 3 rectal and bladder complication. In this ...
To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular ...
The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate (U-/sup 14/C)glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10/sup 5/ cells/ml) were incubated with either (/sup 125/I)insulin or (/sup 125/I)hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated ...
The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U-"1"4C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10"5 cells/ml) were incubated with either ["1"2"5I]insulin or ["1"2"5I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and "1"4C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, ...
We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with ["1"2"5I]NGF suggested that high affinity ...
Photoaffinity labeling analogs of the adenylate cyclase activator forskolin (PF) have been synthesized, purified and tested for their effect on preparations of membrane-bound, Lubrol solubilized and forskolin affinity-purified adenylate cyclase (AC). All analogs of forskolin significantly activated AC. However, in the presence of 0.1 to 0.3 microM forskolin, the less active forskolin photoaffinity probes at 100 microM caused inhibition. This inhibition was dose-dependent for PF, suggesting that PF may complete with F for the same binding site(s). After cross-linking (125I)PF-M to either membrane or Lubrol-solubilized AC preparations by photolysis, a radiolabeled 100-110 kDa protein band was observed after autoradiography following SDS-PAGE. F at 100 microM blocked the photoradiolabeling of this protein. Radioiodination of forskolin-affinity purified AC showed several protein bands on autoradiogram, however, only one band (Mr = 100-110 kDa) was ...
Aminophenpyramine, a derivative of mepyramine (pyrilamine), a typical antagonists of histamine at its H_1 receptor was synthesized and converted into ["1"2"5I]iodoazidophenpyramine, a potential photoaffinity probe for the H_1 receptor. In the dark, reversible binding of this probe to cerebellar membranes occurred with a K/sub d/ of 1.2 x 10"-"1"1 M and a B/sub max/ of 240 fmol/mg of protein and was inhibited by various H_1-receptor antagonists with the expected potencies. These features establish the compound as one of the most potent H_1-receptor antagonists known so far. Upon IV irradiation, 5% of the bound radioactivity was covalently incorporated into cerebellar membrane polypeptides as shown by standard NaDodSO_4/PAGE. Two bands of 47 and 56 kDa were consistently labeled, labeling being prevented by various H_1-receptor antagonists with the expected potencies and stereoselectivity. In the presence of protease inhibitors, labeling of the 56-kDa peptide increased at the expense of ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected ...
New ELISA assays were developed to measure immunoreactivity for XMRV. Antibody titers were measured in a cohort of prostate cancer cases and cancer free controls from the central United States. No statistically significant differences were observed in immunoreactivity between cases and controls for either the XMRV-env or the XMRV-gag antigen.
Background. Through PSA screening the rate of prostate cancers detected at an early stage has increased significantly; thus a decrease in mortality can be expected in the near future. Despite all scientific efforts, however, the molecular mechanisms underlying the development and progression of prostate cancer remain poorly understood. Prostate cancer is a disease of aging men and epidemiological evidence supports a major contribution to its development through diet, lifestyle and environmental factors. Genetic instability is the basic phenomenon of tissue cell cancerisation. This instability can be hereditary or due to mutations and other chromosomal aberrations acquired during life. In recent years a large number of interesting data have been collected which show the relationships between focal atrophy and genetic instability of the prostate epithelia. Atrophy can be the result of ...
Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding...Full Text Available
Megavoltage photon intensity-modulated radiation therapy (IMRT) is typically used in the treatment of prostate cancer at our institution. Approximately 1% to 2% of patients with prostate cancer have hip prostheses. The presence of the prosthesis usually complicates the planning process because of dose perturbation around the prosthesis, radiation attenuation through the prosthesis, and the introduction of computed tomography artifacts in the planning volume. In addition, hip prostheses are typically made of materials of high atomic number, which add uncertainty to the dosimetry of the prostate and critical organs in the planning volume. When the prosthesis is bilateral, treatment planning is further complicated because only a limited number of beam angles can be used to avoid the prostheses. In this case study, we will report the observed advantages of using noncoplanar beams in the delivery of IMRT to a ...
Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin #alpha#2#beta#1"h"i and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 #mu#g/ml insulin (DMEM + 10% FBS + Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including ...
Purpose: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). Material and methods: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). Results: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. conclusion: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.
Purpose: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). Material and methods: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). Results: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. conclusion: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material
A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the...
BACKGROUND Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARb) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells. METHODS In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARb and PDLIM4 promoters. Forced Myc overexpression inhibited the RARb and PDLIM4 expression. RESULTS Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2prime-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARb and PDLIM4. CONCLUSION The epigenetic r...
Based on the replies to a questionnaire distributed throughout Japan in 1983, genetically significant dose (GSD), per Caput mean bone marrow dose (CMD), leukemogenically significant dose (LSD), malignantly significant dose (MSD), and per Caput effective dose equivalent (EDE) from using small sealed radiation sources for radiotherapy were estimated. Annual frequencies of brachytherapy were estimated to be 2.6 x 10"3 for men and 36.3 x 10"3 for women, with a total of 38.9 x 10"3. The annual frequencies of using afterloading technique were 0.3 x 10"3 for men and 18.8 x 10"3 for women, with a total of 19.1 x 10"3. The annual population doses per person were 7.9 nGy for GSD, 118 #mu#Gy for CMD, 19.3 #mu#Gy for LSD, 172 #mu#Gy for MSD, and 428 #mu#Gy for EDE. The annual collective effective dose equivalent was estimated to be 5.13 x 10"4 man Sv. (Namekawa, K.).
Rectum reference dose points have a direct impact on the morbidity seen in gynecological intracavitaty radiotherapy. The aim of this study is to obtain less morbidity by marking rectum with radio opaque solution. Fourteen patients with gynecological cancer who underwent external radiotherapy received 15 Gray (Gy) intracavitary radiotherapy. During the internal radiotherapy planning, radio opaque solution has been administered into the rectum to observe it on lateral radiogram. Thus rectum reference dose point and five points were marked at sites nearest to the sources. Nucletron Planning system was used for obtaining three-dimensional planning. After therapy patients were followed at every three months. Median follow-up was 18 months. Most frequently observed morbidities were grade 1-2 rectitis and cystitis in six patients. As a result, more accurate rectum dose values and less factors causing dose changing can provide better results for gynecological intracavitary ...
Purpose: The purpose of this course is to review the physical principles underlying design, clinical application and execution of interstitial and intracavitary implants in the classical low dose-rate (LDR) range. This year, the course will focus on quality assurance of sources, applicators and treatment planning software. In addition, development of procedures and QA checks designed optimize treatment delivery accuracy and patient safety during each individual procedure will be reviewed. The level of presentation will be designed to accommodate both physicists and physicians. Implementation of recently published AAPM Task Group reports (no. 40, 'Comprehensive Quality Assurance' and No. 43, 'Dosimetry of Interstitial Brachytherapy Sources') will be reviewed. Outline: (A) General Principles (1) QA endpoints: temporal accuracy, positional accuracy, dose delivery accuracy, and safety of the patient, personnel, and the institution (2) QA procedure development: forms, ...
Objective: To retrospectively evaluate the results of conservative therapy using escorpal iodine-125 (model 6711, Amershan) plaque for brachytherapy of choroidal melanoma. Materials And Methods: We evaluated 49 patients with choroidal melanoma treated at 'Hospital do Cancer', Sao Paulo, Brazil, from March 2001 to January 2003. The following clinical parameters were analyzed and correlated with local control and survival rate: gender, age, lesion dimension, treatment duration, as well as doses in apex and base of the tumors. Results: The maximum diameter and height of the base of the tumors treated were 17 mm and 12 mm, respectively. Doses at those points ranged from 213 to 463 Gy (median: 347 Gy) and 51 to 250 Gy (median: 91 Gy), respectively. The actuarial rates of ocular preservation, disease free survival and ocular preservation in 2-years were 96%, 93.5% and 96.3%, respectively. A tumor height < 6 mm was the only predictive factor for ...
The Thomsen-Friedenreich (T) antigen, #betta#-D-Gal-(1->3)-#alpha#-D-GalNAc, is exposed in reactive form on many human adenocarcinomata, but not on corresponding benign tissues. Peanut lectin (PNA) has a strong binding affinity for the T antigen and reportedly binds preferentially to certain malignant tissues. We investigated the potential of radio-labelled PNA as a tumour localising agent in an animal model system using a mouse lymphoma (RI) shown to bind fluorescein-labelled PNA in vitro. The radio-iodinated lectin showed good tumour localisation and rapid blood clearance. Clear images of tumours were obtained, in serial scintigraphic imaging, by 24 and 48 h. No blood background subtraction was necessary. Biodistribution studies revealed tumour to blood ratios in mice were 6:1 (at 24 h) and 17:1 (at 48 h), and tumour to muscle ratios were 34:1 (at 24 h) and 40:1 (at 48 h). Rapid in vivo breakdown of _1_2_5I-PNA led to some localisation of free iodide in the kidneys, stomach, ...
The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with "2"0"3Pb, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-"1"2"5I-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the "2"0"3Pb-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as immunoscintigraphy studies. ...
The present investigation compares the suitability of two radiolabeling techniques for hemoglobin. "1"2"5I labeling of hemoglobin with Iodogen as iodinating agent caused major changes in the chromatographic behaviour and an accelerated plasma clearance of the labeled hemoglobin in rats. A recently developed two-step procedure for "9"9"mTc labeling gave better results. The label had only minimal influence on the chromatographic behaviour of hemoglobin. In vivo, no free label occurred in the circulation and no transfer of the label to other plasma proteins took place. The plasma clearance of "9"9"mTc-labeled hemoglobin in rats was slowed. However, this could be explained entirely by diminishing glomerular filtration, probably by inhibition of the dissociation of the hemoglobin molecule into dimers. The plasma clearance of hemoglobin modified by intramolecular cross-linking, which prevents dissociation of the molecule into dimers and thus excretion by the kidney, was not influenced by the ...
Blood flow changes in the periodontal ligament (PDL) were measured indirectly by monitoring the local clearance of /sup 125/I/sup -/ during electric sympathetic nerve stimulation or close intra-arterial infusions of either noradrenaline (NA) or adrenaline (ADR) before and after administration of phentolamine (PA), phenoxybenzamine (PBZ) or Idazoxan (RX). At the doses used in the present study, PA was the only antagonist that significantly reduced the blood flow decrease seen on activation of sympathetic fibers, although PBZ also reduced this response. Idazoxan, however, did not induce the consistent effect on blood flow decreases seen on sympathetic activation. All three ..cap alpha..-adrenoceptor antagonists almost abolished the effects of exogenously administered NA and ADR. The results suggest the presence of functional post-junctional adrenoceptors of both the ..cap alpha.. 1 and ..cap alpha.. 2 subtypes in the sympathetic regulation of the ...
The specific receptor sites and the endocytosis of transferrin (Tf) are evidenced in a cell line (HT-29) derived from a human colic adenocarcinoma by means of "1"2"5I radiolabeled Tf. The receptor density is studied in undifferentiated (UD) or differentiated (D) cells with respective doubling times of about 24 hours and 46 hours. The number of binding sites for Tf is 162,000 (K_d = 7.8 nmol/l in ND cells and 68,000 (K_d = 7.40 nmol/l) in D cells. The distribution between the Tf bound to the cell surface and the internalized Tf is investigated by elimination of Tf bound to the surface by an acid wash method. The intracellular cycle of Tf seems to be characterized by a slower kinetics in UD cells. The high density of Tf receptor sites in HT-29 UD cells should allow the detection or the treatment of highly evolutive colic adenocarcinoma by means of Tf.
PurposeWe conducted a comparative study of Clinical Target Volume (CTV) definition of pelvic lymph nodes by multiple GU radiation oncologists looking at the levels...Full Text Available
PurposeDutasteride and finasteride are 5α-reductase inhibitors that dramatically decrease serum levels of dihydrotestosterone. Because androgens...Full Text Available
BackgroundZibotentan (ZD4054) is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of prostate cancer. As zibotentan is eliminated...Full Text Available
... The basal markers CK5, alpha 6 integrin (CD49f), CD44, and p63 were strongly expressed by the majority of sphere-forming cells. ... p63 p63 PSCA ...
Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their...Full Text Available
Finasteride, a specific and competitive inhibitor of 5α-reductase enzyme Type 2, inhibits the conversion of testosterone to dihydrotestosterone (DHT). In adults, DHT acts as primary androgen...Full Text Available
The Electronic REference To access In vivo Concentrations (ERETIC) method was applied to 1H HR-MAS spectroscopy. The accuracy, precision, and stability of ERETIC as a quantitative...Full Text Available
Objective: To evaluate effects of epigallocatechin-3-gallate (EGCG) on the viability, membrane properties, and zinc distribution, with and without the presence of Zn2+, in human prostate...Full Text Available
Mutational inactivation of the RB1 tumor suppressor gene initiates retinoblastoma and other human cancers. RB1 protein (pRb) restrains cell proliferation by binding...Full Text Available
XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs....Full Text Available
Introduction:Although radical prostatectomy (RP) is an effective treatment for prostate cancer, it has potentially deleterious effects on health-related quality of life (HRQoL)....Full Text Available
OBJECTIVE: To test the hypothesis that perioperative transfusion of allogeneic and autologous red blood cells (RBCs) stored for a prolonged period speeds biochemical recurrence of prostate cancer...Full Text Available
A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated...Full Text Available
4-methylumbelliferone (4-MU) is a hyaluronic acid (HA) synthesis inhibitor with anticancer properties; the mechanism of its anticancer effects is unknown. We evaluated the effects of 4-MU on...Full Text Available
BackgroundCentrosome aberrations can cause genomic instability and correlate with malignant progression in common human malignancies such as breast and prostate cancer. Deregulation...Full Text Available
PurposeWe investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial. Materials and MethodsPatients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose (160 or 80 mg in 125 each), or were re-randomized from leuprolide 7.5 mg to degarelix 240/80 mg (69) or 240/160 mg (65). Data are shown on the approved degarelix 240/80 mg dose. The primary end point was safety/tolerability and the secondary end points were testosterone, prostate specific antigen, luteinizing hormone and follicle-stimulating hormone responses, and prostate specific antigen failure and progression-free survival....
Background and purpose: We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas. Methods: Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20 mg/m"2). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60 mg/m"2), every 3 weeks. Patients had to receive LHRH agonist during 3 years. Results: The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3-4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced ...
Despite the widely recognized usefulness of the AAPM TG-43 brachytherapy dose calculation formalism, a straightforward application of this approach to describe the dose distribution about intravascular line sources as proposed by TG-60 may be difficult or even impossible, especially when these line sources emit low-energy photons or beta particles. The causes of these limitations are investigated and illustrated by means of some numerical examples. In order to solve the observed limitations an adapted formalism is proposed, intended specifically for the description of the dose rate distribution about line sources but conceptually similar to the TG-43/TG-60 formalism. Several examples are presented to illustrate the usefulness of the proposed line source dose calculation formalism.
Quantitative bone scintigraphy was performed in 24 patients with prostatic carcinoma before orchiectomy and up to one to four years after operation. The gamma camera count rate was recorded over the lower thoracic and all lumbar vertebrae 4 h after injection of [sup 99m]Tc-MDP. Twelve patients has normal bone scintigrams throughout the study. They showed from two years after operation a slight increase in count rate values compared with the preoperative values, probability due to hormonal changes after orchiectomy and to age-related alterations in skeletal metabolism. Twelve patients had abnormal bone scintigrams. They showed as a response to treatment the flare phenomenon with an increase in count rate over the abnormal vertebrae when measured two weeks after operation followed by a decrease after two months. The lowest count rate values were obtained between six months and one year after operation. Thereafter the count rate seemed to remain on the same level. An ...
Quantitative bone scintigraphy was performed in 24 patients with prostatic carcinoma before orchiectomy and up to one to four years after operation. The gamma camera count rate was recorded over the lower thoracic and all lumbar vertebrae 4 h after injection of "9"9"mTc-MDP. Twelve patients has normal bone scintigrams throughout the study. They showed from two years after operation a slight increase in count rate values compared with the preoperative values, probability due to hormonal changes after orchiectomy and to age-related alterations in skeletal metabolism. Twelve patients had abnormal bone scintigrams. They showed as a response to treatment the flare phenomenon with an increase in count rate over the abnormal vertebrae when measured two weeks after operation followed by a decrease after two months. The lowest count rate values were obtained between six months and one year after operation. Thereafter the count rate seemed to remain on the same level. An ...
Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their re-expression. Whether this re-expression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA methylation of several classes of retroelements in human prostate cancer tissues and cell lines by quantitative reverse transcription-polymerase chain reaction and pyrosequencing, respectively. The most striking finding was strong and generalized increased expression of the HERV-K_22q11.23 provirus in cancers, including de novo expression of a spliced accessory Np9 transcript in some tumors. In parallel, DNA methylation in the long terminal repeat (LTR) decreased. Conversely, HER...
The potential association between xenotropic murine leukaemia virus-related gammaretrovirus (XMRV) and prostate cancer (PCa) has been documented since 2006. It is important for furthering our understanding of the biological mechanisms of PCa to ascertain whether this association is causal. To summarize the available information on the epidemiological and laboratory findings of the association, we conducted a literature search of the PubMed electronic database (from March 2006 to February 2011) to identify relevant published studies that examined the association between XMRV and PCa. Although several studies showed the positive association between XMRV and PCa, more recent studies did not support this conclusion. The positive findings might be due to contamination of human samples. Further ...
Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.
Positron emission tomography (PET) imaging of {beta}-amyloid (A{beta}) plaques in the brain is a potentially valuable tool for studying the pathophysiology of Alzheimer's disease (AD). It may also be applicable for measuring the effectiveness of therapeutic drugs aimed at lowering A{beta} plaques in the brain. We have successfully reported a series of {sup 18}F-labeled fluoropegylated stilbenes for PET imaging studies. Encouraging results clearly demonstrated the usefulness of {sup 18}F-labeled stilbenes as potential A{beta} plaque-imaging agents. In the present study, we applied a similar approach to a styrylpyridine backbone structure. Among all derivatives examined (E)-2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-5-(4-dimethylaminostyryl) -pyridine (2) displayed high binding affinity in postmortem AD brain homogenates (K {sub i}=2.5{+-}0.4 nM, with [{sup 125}I]IMPY as radioligand). No-carrier-added [{sup 18}F]2 was successfully prepared ...
A {lambda}gt11 cDNA library was constructed from poly(U)-Spharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S-transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion of the fusion protein. A 29-kDa protein was ...
A #lambda#gt11 cDNA library was constructed from poly(U)-Spharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S-transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion of the fusion protein. A 29-kDa protein was ...
Three regio-isomers of N-(N-benzylpiperidin-4-yl)-4-iodobenzamide, IBP, were prepared and evaluated for their sigma affinities. All three isomers (2, 3, and 4-substituted) showed high affinities for sigma-1 receptors in guinea pig brain membranes (Ki - 1.64 nM, 3.02 nM, 1.70 nM respectively) against ["3H]-(+)-pentazocine, a sigma-1 selective ligand. 2-IBP and 4-IBP showed modest affinities for sigma-2 sites in rat liver (Ki = 29.6 nM. 25.2 nM respectively) against ["3H]DTG in the presence of dextrallorphan to mask sigma-1 sites. The homologous competition binding studies of 4-["1"2"5I]BP in MCF-7 human breast tumor cells showed high affinity dose-dependent binding. Competition binding studies with haloperidol and DTG also showed a high affinity binding (Ki = 4.6 nM, 60 nM respectively), demonstrating the sigma specificity. The saturation binding (Scatchard analysis) of ["3H]DTG with MCF-7 cell membrane preparations gave Kd of 24.54 nM and a Bmax of 2071 fmol/mg protein. These results ...
The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) #alpha#subunit forms a binding site for #alpha#-bungarotoxin (#alpha#-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR #alpha#1 subunits were tested for their ability to bind "1"2"5I-#alpha#-BTX, and differences in #alpha#-BTX affinity were determined by using solution (IC_5_0s) and solid-phase (K_ds) assays. Panels of overlapping peptides corresponding to the complete #alpha#1 subunit of mouse and human were also tested for #alpha#-BTX binding, but other sequence segments forming the #alpha#-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased #alpha#-BTX binding, whereas oxidation of the peptides had little ...
For the purpose of searching some effective absorbents of gaseous radioactive iodine, 16 substances considered as having an affinity for iodine were investigated with regular iodine and /sup 125/I. In a preliminary survey, only tetrathiafulvalene (TTF) was found to have satisfactory absorbing properties comparable to activated charcoal. A further detailed comparison of the properties between TTF and activated charcoal led us to the conclusion that the former has more preferable properties as absorbent of radioactive iodine than the latter in all points studied. The results are summarized as follows: (1) The absorption of iodine on TTF in atmosphere was about twice as much as that on activated charcoal. Desorption of iodine from saturatedly absorbed iodine on TTF was practically negligible except trace amount of initial desorption, while that on activated charcoal was considerable (3%/50h) even in the air at room temperature. (2) Absorbed amount ...
The authors have shown previously that the domain recognizing receptors on activated human platelets is located on the human fibrinogen {gamma} chain between residues 400 and 411. To study the correlation between the structure of this segment of the {gamma} chain and its reactivity toward receptors on ADP-activated human platelets, they designed a series of analogues containing replacements at 9 out of 12 positions. A double substitution of the normal His{sup 400}-His{sup 401} sequence by Ala-Ala reduced the inhibitory potency of the dodecapeptide 3-fold. When Lys{sup 406} was replaced by Arg, the inhibitory potency of the dodecapeptide decreased 15 times. On the other hand, substitution of Ala{sup 408} with Arg increased the inhibitory potency of the dodecapeptide 6-fold. A drastic decrease in the reactivity of the dodecapeptide toward platelet receptors was observed when Val{sup 411} was replaced by leucine or cysteine or tyrosine. A 3-fold decrease in reactivity was noted when ...
Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10/sup -5/M ADP in the presence of /sup 125/I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- ...
The radioiodination and in vivo evaluation of p-iodocaramiphen a muscarinic antagonist which binds with high affinity to the M[sub 1] receptor subtype in vitro are described. Biodistribution studies in female Fischer rats demonstrated that [[sup 125]I]-piodocaraminphen had significant cerebral localization, but the uptake did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors, and radioactivity washed out rapidly from the brain. In addition there was no significant blockage of activity when the rats were preinjected with quinuclidinyl benzilate. These results suggest that p-iodocaramiphen is not a good candidate for the in vivo study of M[sub 1] muscarinic receptor populations by SPECT. Because of the widespread interest and expected importance of the availability of large amounts of tungsten-188 required for the tungsten-188/rhenium-188 generator systems, we have investigated the large-scale production of ...
Insulin receptors on the surface of isolated rat adipocytes were photoaffinity labeled at 12 degrees C with the iodinated photoreactive insulin analogue, 125I-B2 (2-nitro-4-azidophenylacetyl)-des-PheB1-insulin, and the pathways in the intracellular processing of the labeled receptors were studied at 37 degrees C. During 37 degrees C incubations, the labeled 440-kDa insulin receptors were continuously internalized (as assessed by trypsin inaccessibility) and degraded such that up to 50% of the initially labeled receptors were lost by 120 min. Metabolic poisons (0.125-0.75 mM 2,4-dinitrophenol (DNP) and 1-10 mM NaF), which led to dose-dependent depletion of adipocyte ATP pools, inhibited receptor loss, and caused up to 3-fold increase in intracellular receptor accumulation. This effect was due to inhibition of intracellular receptor degradation, and there was no apparent effect of the metabolic poisons on initial internalization of the receptors. ...
Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified binding protein yielded a lower limit molecular weight of 79,000 +/- 7,000. ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; down-regulation was dependent on TSH ...
The hypothesis that intracellular Ca/sup 2 +/ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca/sup 2 +/ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl/sub 2/ and the Ca/sup 2 +/ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl/sub 2/ from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 ..mu..M quin-2 or quin-2 AM had ...
The hypothesis that intracellular Ca"2"+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca"2"+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl_2 and the Ca"2"+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl_2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 #mu#M quin-2 or quin-2 AM had no effect on intracellular ...
Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the ...
A factor produced by the plerocercoid stage of S. mansonoides mimics some, but not all, of the actions reported for hGH. The biological actions of plerocercoid growth factor (PGF) suggest structural similarity to human GH (hGH). Plerocercoid membranes were solubilized, and PGF was purified more than 1000-fold by hGH receptor affinity chromatography. The ability of purified PGF to displace [125I]hGH from monoclonal antibodies specific for four distinct nonoverlapping antigenic determinants of hGH and from an anti-hGH polyclonal antibody was tested in liquid phase RIA. All of the hGH antibodies cross-reacted with PGF, with potencies ranging from more than 60% to less than 1% that of the hGH standard. Of the four major epitopes of hGH defined by the monoclonal antibodies used in this study, only one is not represented to a significant extent in PGF. The epitope of hGH that is only marginally present in PGF is highly conformationally dependent, and ...
The xenotropic murine leukaemia virus-related virus (XMRV), a gammaretrovirus, was discovered in prostate cancer tumours by Virochip technology in 2006. It was subsequently detected in chronic fatigue patients in 2009. The association between XMRV and chronic fatigue has proved to be controversial. No study has confirmed these findings and many have refuted them. Here, we present the evidence for our contention that XMRV is not a human pathogen. PMID:21978843
The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the α1a and α1d adrenergic...Full Text Available
The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.
Between October 1990 and March 1991, 8 patients with cystic lesions in the region of the posterior bladder wall, the seminal vesicles and the prostate were examined by MRI. In all cases there was accurate characterisation of the lesion and of its anatomy. In 3 patients with abnormalities in the retrovesical space there was very good agreement with the operative findings. 4 patients were treated conservatively. In these patients there was good agreement with the findings on cystoscopy, CT and sonography. (orig.).
BackgroundTo compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated...Full Text Available
Purpose: To report outcomes of a single institution study of stereotactic body radiotherapy (SBRT) for unresectable cholangiocarcinoma. The dose-volume dependency of the observed gastrointestinal toxicity is explored. Methods and materials: Twenty-seven patients with unresectable cholangiocarcinoma (n = 26 Klatskin tumours and one intrahepatic cholangiocarcinoma (IHCC)) were treated by linac-based SBRT. The dose schedule was 45 Gy in three fractions prescribed to the isocenter. Results: The median progression-free survival and overall survival were 6.7 and 10.6 months, respectively. With a median follow-up of 5.4 years, 6 patients had severe duodenal/pyloric ulceration and 3 patients developed duodenal stenosis. Duodenal radiation exposure was higher in patients developing moderate to high-grade gastrointestinal toxicity with the difference in mean maximum dose to 1 cm"3 of duodenum reaching statistical significance. A statistically significant association between grade #>=# 2 ...
Monte Carlo calculations using the codes PENELOPE and GEANT4 have been performed to characterize the dosimetric parameters of the new 20 mm long catheter based $^{32}$P beta source manufactured by Guidant Corporation. The dose distribution along the transverse axis and the two dimensional dose rate table have been calculated. Also, the dose rate at the reference point, the radial dose function and the anisotropy function were evaluated according to the adapted TG-60 formalism for cylindrical sources. PENELOPE and GEANT4 codes were first verified against previous results corresponding to the old 27 mm Guidant $^{32}$P beta source. The dose rate at the reference point for the unsheathed 27 mm source in water was calculated to be $0.215 \\pm 0.001$ cGy s$^{-1}$ mCi$^{-1}$, for PENELOPE, and $0.2312 \\pm 0.0008$ cGy s$^{-1}$ mCi$^{-1}$, for GEANT4. For the unsheathed 20 mm source these values were $0.2908 \\pm 0.0009$ cGy s$^{-1}$ mCi$^{-1}$ and $0.311 \\pm 0.001$ cGy s$^{-1}$ mCi$^{-1}$, ...
We present a development of the use of the AAPM TG-43 dose formalism applied to "1"3"7Cs gynecological implant sources. The geometry factor, radial dose function, and anisotropy function of a "1"3"7Cs source modeled after the Nuclear Associates 67-809 series stainless steel jacketed tube source were derived following the AAPM TG-43 formalism. The dose rate distribution through the center of the source using the AAPM TG-43 dose formalism is calculated and compared with the calculations obtained using the Sievert summation and Monte Carlo simulation. The three methods resulted in an agreement within less than 5%, or an isodose rate line agreement within 2 mm. We demonstrate that the AAPM TG-43 formalism can be applied to "1"3"7Cs linear sources and is capable of serving as a "1"3"7Cs dose calculation algorithm that can be used for treatment planning purpose.
Bone scintigraphy was performed in 16 men with newly diagnosed prostatic carcinoma before orchiectomy as well as 2 weeks and 2 months after operation. The uptake in the lower thoracic and lumbar vertebrae was registered up to 240 min after injection of /sup 99m/Tc-MDP and was then calculated for each patient and vertebra. The relative standard deviation in measured uptake due to measuring technique was estimated to be +-7%. In eight patients, who had normal bone scintigraphies before orchiectomy, there were no changes in the uptake values after operation. The remaining eight patients had widespread metastatic involvement prior to treatment, six of these patients showed a so-called 'flare phenomenon' in the abnormal vertebrae which means an initial increase in uptake after operation followed by a decreased uptake in response to therapy. One patient had a continuously increased uptake in all the abnormal vertebrae which correlated well with the ...
Bone scintigraphy was performed in 16 men with newly diagnosed prostatic carcinoma before orchiectomy as well as 2 weeks and 2 months after operation. The uptake in the lower thoracic and lumbar vertebrae was registered up to 240 min after injection of "9"9"mTc-MDP and was then calculated for each patient and vertebra. The relative standard deviation in measured uptake due to measuring technique was estimated to be #+-#7%. In eight patients, who had normal bone scintigraphies before orchiectomy, there were no changes in the uptake values after operation. The remaining eight patients had widespread metastatic involvement prior to treatment, six of these patients showed a so-called 'flare phenomenon' in the abnormal vertebrae which means an initial increase in uptake after operation followed by a decreased uptake in response to therapy. One patient had a continuously increased uptake in all the abnormal vertebrae which correlated well with the clinical progression of ...
Thirty-four patients with prostatic carcinoma were studied with quantitative bone scintigraphy and whole-body counting (WBC) 1 and 24 h after injection of [sup 99m]Tc-MDP before as well as two weeks and two months after orchiectomy. Thirteen of the patients had normal bone scintigrams and WBR at the three different investigations; 21 had skeletal metastases. The latter showed throughout the study higher local gamma camera count rates as well as WBR values than the patiens with normal scintigrams. In these patients a ''flare phenomenon'', with an increase in count rate two weeks after orchiectomy followed by a decrease two months post-operatively, was seen with quantitative bone scintigraphy but not with WBC. However, WBC may be a valuable method indicating the total extent of skeletal metastases in the body, while quantitative bone scintigraphy is more accurate in the interpretation of individual skeletal metastases. (orig.).
Thirty-four patients with prostatic carcinoma were studied with quantitative bone scintigraphy and whole-body counting (WBC) 1 and 24 h after injection of "9"9"mTc-MDP before as well as two weeks and two months after orchiectomy. Thirteen of the patients had normal bone scintigrams and WBR at the three different investigations; 21 had skeletal metastases. The latter showed throughout the study higher local gamma camera count rates as well as WBR values than the patiens with normal scintigrams. In these patients a ''flare phenomenon'', with an increase in count rate two weeks after orchiectomy followed by a decrease two months post-operatively, was seen with quantitative bone scintigraphy but not with WBC. However, WBC may be a valuable method indicating the total extent of skeletal metastases in the body, while quantitative bone scintigraphy is more accurate in the interpretation of individual skeletal metastases. (orig.).
Dynamic quantitative bone scintigraphy was performed on 31 men with prostatic carcinoma before orchiectomy as well as 2 weeks, 2 and 6 months postoperatively. After injection of technetium methylene diphosphonate Tc 99m ("9"9"mTc-MDP) the count rate was recorded as serial images over the lower thoracic and all the lumbar vertebrae from 1 to 240 min post-injection. Thirteen men had normal bone scintigrams with no changes in "9"9"mTc-MDP content at the four different investigation times. Eighteen men had skeletal metastases. Throughout the study half of the abnormal vertebrae in these patients showed an abnormal count rate after only 6 min post-injection. After 1 h it was possible in almost all abnormal vertebrae to predict abnormal bone uptake. In response to therapy a 'flare phenomenon' with an increase in count rate was seen 2 weeks after orchiectomy followed by a decrease 2 months postoperatively in most of the abnormal vertebrae. The count rate decreased even ...
Quantitative bone scintigraphy was performed at 4 and 24 h after injection of {sup 99m}Tc-MDP. The lower thoracic and all the lumbar vertebrae were recorded in 37 patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months postoperatively. Fourteen patients had normal bone scintigrams. By means of the measured variation in the count rate between normal vertebrae, the criterion for a vertebra to be considered as abnormal was determined using the 4 h-uptake values. For patients with normal scintigrams the count rate at 24 h was below the 4 h level and the mean 24 h/4 h ratio was determined to be 0.85 {+-} 0.09 (1 SD). Normal vertebrae in patients with skeletal metastases had only slightly lower count rate values at 24 h than at 4 h. Abnormal vertebrae showed a higher count rate at 24 h, especially two weeks postoperatively, while a tendency towards lower values than at 4 h was seen after 6 months. If the 24 h/4 h ratio is used as an ...
Quantitative bone scintigraphy was performed at 4 and 24 h after injection of "9"9"mTc-MDP. The lower thoracic and all the lumbar vertebrae were recorded in 37 patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months postoperatively. Fourteen patients had normal bone scintigrams. By means of the measured variation in the count rate between normal vertebrae, the criterion for a vertebra to be considered as abnormal was determined using the 4 h-uptake values. For patients with normal scintigrams the count rate at 24 h was below the 4 h level and the mean 24 h/4 h ratio was determined to be 0.85 #+-# 0.09 (1 SD). Normal vertebrae in patients with skeletal metastases had only slightly lower count rate values at 24 h than at 4 h. Abnormal vertebrae showed a higher count rate at 24 h, especially two weeks postoperatively, while a tendency towards lower values than at 4 h was seen after 6 months. If the 24 h/4 h ratio is used as an ...
In the treatment of prostatic cancer using a newly proposed intermittent multiportal therapy (DIMT), acute reactions, change in tumor marker levels, and complications more than 6 months after treatment were evaluated. From June 1989 to September 1990, 26 patients with prostatic cancer (stage A2, 3 patients; B, 9; C, 2; D, 10; recurrence, 2) were treated. Fifteen patients were followed up for more than one year, with a mean period of 11.6 months. The treatment schedule is 52.5 Gy in 16 fractions in 4 weeks for radical treatment, and 30.0 Gy in 8 fractions in 2 weeks for palliative treatment. The 360 degree rotation about the patient was divided into 16 fractions, and 2 opposing fractions were used in one day as parallel opposed portals to treat the target volume. The fractions were serially treated one per day, so that 8 treatment days produced a total dose of distribution similar to that for conventional conformational therapy. The size of the ...
Purpose: The results of therapy in 288 men with pathologic Stage C prostate cancer who underwent radical retropubic prostatectomy (RRP) were analyzed to determine the effects of adjuvant therapy. Methods and Materials: Twenty-seven of the 288 patients received preoperative neoadjuvant hormonal therapy (leuprolide acetate). Postoperatively, 60 patients received adjuvant radiotherapy (RT) to the prostate bed. Follow-up ranged from 3 to 83 months (median = 32 months). Freedom from failure (FFF) was defined as maintaining a serum PSA level of #<=# 0.3 ng/ml. Results: The FFF was 61% at 3 years and 45% at 5 years for the entire group. The FFF following RRP plus RT was 75% at 3 years and 57% at 5 years as compared to 56% at 3 years and 40% at 5 years for RRP without RT (p = 0.049). The FFF following RRP plus neoadjuvant hormonal therapy was 58% at 3 years and 40% at 5 years as compared to 60% at 3 years and 45% at 5 years following RRP without ...
The p75 neurotrophin receptor (p75"N"T"R) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75"N"T"R retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (#DELTA#DD) dominant-negative antagonist of p75"N"T"R showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75"N"T"R-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75"N"T"R expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and ...
Full text: An adaptive response is a decreased biological effect induced by a priming radiation dose given prior to a challenge dose. Adaptive responses contradict the linear-nothreshold model of risk estimation. The pKZ1 mouse chromosomal inversion assay is an extremely sensitive assay for studying the mutagenic effect of low dose radiation. A non-linear dose response for chromosomal inversion has been observed in pKZ1 spleen and prostate after a single whole body irradiation with doses between 1?Gy and 10mGy. Doses between 5-10?Gy resulted in an induction in inversions and doses between 1-10mGy resulted in a reduction below endogenous inversion frequency. These results suggest that doses in the 1-10 mGy range cause host responses which overcompensate by not only preventing inversions that would normally occur as a result of the low doses of radiation but also by preventing some of the endogenous inversions that would have occurred in the absence of radiation. It ...
Immunoassays are versatile analytical techniques that had a leading role in various clinical applications, during the last four decades. The studies carried out by Rosalyn Yalow, Solomon Berson and Roger Ekins in the 1960s gave a breakthrough in the development of this novel analytical method. Sensitivity up to femtomolar concentrations, high specificity and universal application to different classes of molecular species made immunoassay a very useful tool in analytical investigation. The expertise acquired by immunochemists in producing antibodies against any antigen and the ability of radiochemists in labeling the antigens with "1"2"5I without affecting the active site are the two main factors responsible for the above development. There are concerns about the safety and health of humans due to the high-level contamination of environment by pesticides, industrial compounds and metals, anabolic steroids in milk and meat products, and presence of mycotoxins in food and feed ...
Abstract Septins are highly conserved cytoskeletal GTP-binding proteins implicated in numerous cellular processes from apoptosis to vesicle trafficking. Septins have been associated with leukemia and solid tumor malignancies, including breast, ovarian, and prostate. We previously reported that high SEPT9_i1 expression in human mammary epithelial cell lines (HMECs) led to malignant cellular phenotypes such as increased cell proliferation, invasiveness, motility, and genomic instability. Our goal here was to better understand how SEPT9_i1 expression might contribute to genomic instability and malignant progression. First, we confirmed that even transient expression of SEPT9_i1 was sufficient to increase aneuploidy in HMECs. We then analyzed SEPT9_i1 by immunoprecipitation and immunofluoresce...
Robotic surgery will give surgeons the ability to perform essentially tremorless microsurgery in tiny spaces with delicate precision and may enable procedures never before possible on children, neonates, and fetuses. Collaboration with radiologists, engineers, and other scientists will permit refinement of image-guided technologies and allow the realization of truly remarkable concepts in minimally invasive surgery. While robotic surgery is now in clinical use in several surgical specialties (heart bypass, prostate removal, and various gastrointestinal procedures), the greatest promise of robotics lies in pediatric surgery. We will briefly review the history and background of robotic technology in surgery, discuss its present benefits and uses and those being explored, and speculate on the future, with attention to the current and potential involvement of imaging modalities and the role of image guidance. (orig.)
The effects of oral administration of aqueous extract of Bulbine natalensis Baker stem at daily doses of 25, 50, and 100mg/kg body weight on the reproductive function of Wistar rats were evaluated. The indices of mating and fertility success as well as quantal frequency increased after 7 days of treatment in all the dose groups except the 100mg/kg body weight group. The number of litters was not statistically different (P>0.05) from the control. Whereas the absolute weights of the epididymis, seminal vesicle, and prostate were not affected, that of the testes was significantly increased. The epididymal sperm count, motility, morphology, and viscosity were not different from the control after 7 days of treatment. The male rat serum testosterone, progesterone, luteinizing hormone, and follic...
In this work an analysis of the influence of the choice of the algorithm or planning system, on the calculus of the same treatment plan is introduced. For this purpose specific software has been developed for comparing plans of a series of IMRT cases of prostate and head and neck cancer calculated using the convolution, superposition and fast superposition algorithms implemented in the XiO 4.40 planning system (CMS). It has also been used for the comparison of the same treatment plan for lung pathology calculated in XiO with the mentioned algorithms, and calculated in the Plan 4.1 planning system (Brainlab) using its pencil beam algorithm. Differences in dose among the treatment plans have been quantified using a set of metrics. The recommendation for the dosimetrist of a careful choice of the algorithm has been numerically confirmed. (Author).
The optimal management of men with very favorable clinicopathological factors who develop biochemical recurrence (BCR) after radical prostatectomy (RP) has not been previously reported. Both local and systemic recurrences are unlikely in this cohort. This study examines their management and outcomes. Between October 2000 to March 2010, 1627 men underwent open RP by a single surgeon. In all, 448 (27.5%) met the following criteria for extremely low risk disease: preoperative PSA level <10?ng?ml?1, clinical stage T1c/T2a, Gleason score ?6, estimated cancer volume in the surgical specimen ?5% and no evidence for positive surgical margin. Undetectable PSA was defined as ?0.04?ng?ml?1. BCR was defined as PSA ?0.2?ng?ml...
There is a need for earlier and more accurate cancer diagnostics as well as new targets for cancer immunotherapy. To this end, it is important to identify sets of tumour antigens specific for different cancer forms. Several methods that identify potential tumour antigens in an arrayed and high-throughput format have been developed during the last years of SEREX (serological identification of antigens by recombinant expression cloning) related research. Such techniques may hold the potential to describe the complete immunogenic part of the cancer proteome, also called the cancer immunoproteome.We have developed a powerful platform for automated serological high-throughput filter screening of tumour cDNA libraries. The screening format of this method is 18,000 single cDNAs clones, which is s...
XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV in the blood of 86.5% of patients with CFS [1]. These findings are important because since the initial discovery of XMRV in CFS, several studies have failed to find XMRV in specimens collected from CFS patients. While the current study also did not find XMRV in CFS, Lo et al. did detect sequences that belong to polytropic mouse endogenous retroviruses (PMV), which share considerable similarity with XMRV. Criteria for future studies that will help bring greater clarity to the issue of retroviral sequences in CFS are proposed below. PMID:21994623
TP63, a member of the TP53 gene family, is a nuclear marker of myoepithelial cells. Antibody against p63 is frequently used to aid in the diagnosis of prostate carcinoma, as well as in the identification of myoepithelial cells in other tissues including the breast. p63 is also a marker for squamous cell carcinoma. Recently, it was found that all p53 family members are involved in regulating the process of muscle differentiation through the retinoblastoma (RB) protein. Ablation of these p53 family functions blocks the differentiation program and promotes malignant transformation by enabling cooperating oncogenes to transform myoblasts. We therefore studied p63 expression in a number of neoplasms with myogenic differentiation. Immunohistochemical staining for p63 was performed on paraffin se...
Background Despite potentially relevant chemical differences between filtered and boiled coffee, this study is the first to investigate consumption in relation to the risk of incident cancer. Methods Subjects were from the V?sterbotten Intervention Project (64,603 participants, including 3,034 cases), with up to 15?years of follow-up. Hazard ratios (HR) were calculated by multivariate Cox regression. Results No associations were found for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, boiled coffee ?4 versus <1 occasions/day was associated with a reduced risk (HR?=?0.52, CI?=?0.30?0.88, p trend?=?0.247). An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total (HRpremenopausal?=?1.69, CI?=?0.96?2.98...
From 1977 through 1984, 293 previously untreated patients with biopsy proven carcinoma of the uterine cervix were treated by whole pelvis irradiation and high intensity 60Co remote afterloading (RAL) intrauterine tandem techniques in Haiti. The treatment results were analyzed retrospectively to evaluate the therapeutic results and prognostic factors of a strict protocol involving 40 Gy to the whole pelvis (2 Gy/day, 5 days/week). In addition, on the 5th day of the 3rd week, the first outpatient 60Co remote afterloading intracavitary insertion, delivering 7.5 Gy to point A with each insertion, repeated 3 times by a week separation for a total of 4 times. The total TDF for external beam plus RAL was 158 and 175 for early and late effects respectively. One hundred-four patients were evaluable after 1 year or more follow-up, with a median of 26.5 months. No evidence of disease (NED) by Stage at 1 year was: Stage I of 100% (3/3), Stage II of 82% (9/11), Stage III of 80% (47/59), and Stage ...
Quantitative bone scintigraphy was performed in patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months after operation. The count rate was recorded as serial gamma camera images over the lower thoracic and all lumbar vertebrae from 1 to 240 min and at 24 h after injection of "9"9"Tc"m-MDP. In almost all abnormal vertebrae an increased count rate was observed within one hour after injection. Most of the vertebrae which were considered normal at 4 h after injection, but had an increased 24h/4h ratio developed into abnormal vertebrae later in the study. The patients with normal bone scintigrams showed no change in "9"9Tc"m-MDP uptake during the study. The reproducibility of quantitative bone scintigraphy was found to be #+-# 7% (1 SD). In response to therapy, most of the patients with abnormal bone scintigrams showed an increase in count rate two weeks after operation followed by a decrease to the pre-operative level after two ...
Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not significantly impair T cell ...
The high incidence and mortality rates of prostate cancer have stimulated research for prevention, early diagnosis and appropriate treatment. DNA ploidy status of tumour cells is an important parameter with diagnostic and prognostic significance. In the current study, DNA ploidy analysis was performed using image cytometry technique and digital image processing and analysis. Tissue samples from prostate patients were stained using the Feulgen method. Images were acquired using a digital imaging microscopy system consisting of an Olympus BX-50 microscope equipped with a color CCD camera. Segmentation of such images is not a trivial problem because of the uneven background, intensity variations within the nuclei and cell clustering. In this study specific algorithms were developed in Matlab based on the most prominent image segmentation approaches that emanate from the field of Mathematical Morphology, focusing on region-based watershed ...
Purpose: To develop an accurate, fast, and robust algorithm for registering portal and computed tomographic (CT) images for radiotherapy using a combination of sparse and dense field data that complement each other. Methods and Materials: Gradient Feature Weighted Minimax (GFW Minimax) method was developed to register multiple portal images to three-dimensional CT images. Its performance was compared with that of three others: Minimax, Mutual Information, and Gilhuijs' method. Phantom and prostate cancer patient images were used. Effects of registration errors on tumor control probability (TCP) and normal tissue complication probability (NTCP) were investigated as a relative measure. Results: Registration of four portals to CTs resulted in 30% lower error when compared with registration with two portals. Computation time increased by nearly 50%. GFW Minimax performed the best, followed by Gilhuijs' method, the Minimax method, and Mutual Information. Conclusions: ...
Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10"1"0 vp) of the replication-competent ...
In this paper, we put forward a systematic method to analyze, control and evaluate the safety issues of medical robotics. We created a safety model that consists of three axes to analyze safety factors. Software and hardware are the two material axes. The third axis is the policy that controls all phases of design, production, testing and application of the robot system. The policy was defined as hazard identification and safety insurance control (HISIC) that includes seven principles: definitions and requirements, hazard identification, safety insurance control, safety critical limits, monitoring and control, verification and validation, system log and documentation. HISIC was implemented in the development of a robot for urological applications that was known as URObot. The URObot is a universal robot with different modules adaptable for 3D ultrasound image-guided interstitial laser coagulation, radiation seed implantation, laser resection, and electrical resection of the ...
Between 1970 and 1981, 348 patients underwent definitive irradiation. Of these patients 6 (1.7 per cent) sustained severe rectal injury as manifest by major rectal bleeding, rectal stricture, rectal mucosal slough and rectal ulceration. Severe rectal injury was observed in 0 of 13 patients (0 per cent) treated with 125iodine, 3 of 329 (1 per cent) treated with 6,400 to 6,800 rad external irradiation, 2 of 39 (5 per cent) treated with 7,000 to 7,300 rad external irradiation, and 1 of 7 (14 per cent) treated with 198gold and external irradiation. The impact of radiation dose, radiation therapy technique and surgical trauma was assessed. Rectal injury was managed by supportive measures in 2 patients and by diverting colostomy in 3 with benefit. One patient underwent abdominoperineal resection. A small bowel fistula and an intra-abdominal abscess developed, and the patient died.
The Eph tyrosine kinase receptors and their ephrin ligands play a central role in several human cancers and their deregulated expression or function promotes tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE) have been recently found to inhibit Eph-kinase phosphorylation. In order to evaluate the potential contribution of edible and medicinal plants on EphA2-ephrinA1 modulation, 133 commercially available plant extracts used as food supplements, essential and fixed oils were screened with an ELISA-based binding assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in a dose-dependent manner (IC"5"0 0.83-24@mg/ml). Functional studies on PC3 prostate adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc-induced EphA2-pho...
The anatomical patterns of anorectal malformations have so far been studied according to the principles which inspire Pena's technique for the surgical treatment of anorectal anomalies. Thus, the diagnostic study of anorectal malformation has by the authors been considered a work of classification, but of identification. Among the diagnostic procedures in use in author's Institute, preoperative CT of pelvis is performed to assess the presence and to define the development of muscular sphincteric structure towards prognostic evaluation of continence, the major long-term goal. Seven patients, aged 1-30 months, with anorectal anomalies were studied with preoperative CT of the pelvis. CT scans showed well-developed sphinteric muscles in 3 patients (2 with recto-ureteral and 1 with recto-vestibular fistulas), poorly-developed muscular structure in 3 patients (with recto-vaginal, cloacal and prostatic fistulas), absence of muscular structure in 1 case (with recto-vesical ...
Xenotropic murine leukemia virus-related virus (XMRV) was discovered in human prostate tumors and later in some chronic fatigue syndrome (CFS) patients. However, subsequent studies have identified various sources of potential contamination with XMRV and other murine leukemia virus (MLV)-related sequences in test samples. Biological and nucleotide sequence analysis indicates that XMRV is distinct from known xenotropic MLVs and has a broad host range and cell tropism including human cells. Therefore, it is prudent to minimize the risk of human exposure to infection by evaluating XMRV contamination in cell lines handled in laboratory research and particularly those used in the manufacture of biological products. Nested DNA PCR assays were optimized for investigating XMRV gag and env sequences in various cell lines, which included MRC-5, Vero, HEK-293, MDCK, HeLa, and A549, that may be used in the development of some vaccines and other cell lines broadly used in ...
BACKGROUND: Since the identification of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer patients in 2006 and in chronic fatigue syndrome patients in 2009, conflicting findings have been reported regarding its etiologic role in human diseases and prevalence in general populations. In this study, we screened both plasma and peripheral blood mononuclear cells (PBMNCs) collected in Africa from blood donors and human immunodeficiency virus Type 1 (HIV-1)-infected individuals to gain evidence of XMRV infection in this geographic region. STUDY DESIGN AND METHODS: A total of 199 plasma samples, 19 PBMNC samples, and 50 culture supernatants from PBMNCs of blood donors from Cameroon found to be infected with HIV-1 and HIV-1 patients from Uganda were screened for XMRV infecti...
The performance of a convolution/superposition based treatment planning system depends on the ability of the dose calculation algorithm to accurately account for physical interactions taking place in the tissue, key components of the linac head and on the accuracy of the photon beam model. Generally the user has little or no control over the performance of the dose calculation algorithm but is responsible for the accuracy of the beam model within the constraints imposed by the system. This study explores the dosimetric impact of limitations in photon beam modeling accuracy on complex 3D clinical treatment plans. A total of 70 photon beam models was created in the Pinnacle(TM) treatment planning system. Two of the models served as references for 6 MV and 15 MV beams, while the rest were created by perturbing the reference models in order to produce specific deviations in specific regions of the calculated dose profiles (central axis and transverse). The beam models were then used to ...
Prostate and cervical cancer patients are often treated with external X-ray beams of bi-lateral incidence. Such treatment may incur some dose effect that cannot be predicted precisely in commercial treatment planning systems (TPS) for patients having undergone total hip replacement. This study performs a Monte Carlo (MC) simulation and an analytical calculation (convolution superposition algorithm which is implemented in ADAC TPS) of a 6 MV, 5x5 cm"2 X-ray beam incident into water with the existence of hip prosthesis, e.g. Ti6Al4V and CoCrMo alloy. The results indicate that ADAC TPS cannot precisely account for the scatter and backscatter radiation that a metal hip prosthesis causes. For percent depth dose (PDD) curves, the maximum underdosage of ADAC TPS up to 5 mm above the interface between dense material and water is 5%, 20% and 27% for PDD_B_o_n_e, PDD_T_i and PDD_C_o, respectively. The dose re-buildup, which occurs behind the hip region, becomes more and more ...
Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and ...
To evaluate repeated hepatic intraarterial chemotherapy (HIC) as a palliative treatment option for unresectable cholangiocarcinoma and liver metastases of various origins that were progressive under systemic chemotherapy. Between 2002 and 2006, 55 patients were treated in 4-week intervals (mean five sessions). Combined gemcitabine/mitomycin was administered intraarterially within 1 h. Tumor response was evaluated after the third session according to RECIST. Treated tumor entities were colorectal carcinoma (CRC) (n = 12), breast cancer (BC) (n = 12), cholangiocarcinoma (CCC) (n = 10), pancreatic (n = 4), ovarian (n = 3), gastric, cervical, papillary (each n = 2), prostate, esophageal carcinoma, leiomyosarcoma (each n = 1), cancer of unknown primacy (CUP) (n = 5). All patients tolerated the treatment well without any major side effects or complications. In total, there were 1 complete response (CR), 19 partial responses (PR), 19 stable (SD) and 16 progressive ...
BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer ...
A new leaf-sequencing approach has been developed that is designed to reduce the number of required beam segments for step-and-shoot intensity modulated radiation therapy (IMRT). This approach to leaf sequencing is called continuous-intensity-map-optimization (CIMO). Using a simulated annealing algorithm, CIMO seeks to minimize differences between the optimized and sequenced intensity maps. Two distinguishing features of the CIMO algorithm are (1) CIMO does not require that each optimized intensity map be clustered into discrete levels and (2) CIMO is not rule-based but rather simultaneously optimizes both the aperture shapes and weights. To test the CIMO algorithm, ten IMRT patient cases were selected (four head-and-neck, two pancreas, two prostate, one brain, and one pelvis). For each case, the optimized intensity maps were extracted from the Pinnacle"3 treatment planning system. The CIMO algorithm was applied, and the optimized aperture shapes and weights were ...
Purpose: An inverse treatment planning algorithm for tomotherapy is described. Methods and Materials: The algorithm iteratively computes a set of nonnegative beam intensity profiles that minimizes the least-squares residual dose defined in the target and selected normal tissue regions of interest. At each iteration the residual dose distribution is transformed into a set of residual beam profiles using an inversion method derived from filtered backprojection image reconstruction theory. These 'residual' profiles are used to correct the current beam profile estimates resulting in new profile estimates. Adaptive filtering is incorporated into the inversion model so that the gross structure of the dose distribution is optimized during initial iterations of the algorithm, and the fine structure corresponding to edges is obtained at later iterations. A three dimensional, kernel based, convolution/superposition dose model is used to compute dose during each iteration. Results: Two clinically ...
Purpose: Patients with ataxia-telangiectasia (A-T) show greatly increased radiation sensitivity and cancer predisposition. Family studies imply that the otherwise clinically silent heterozygotes of this autosomal recessive disease run a 3.5 to 3.8 higher risk of developing cancer. In vitro studies suggest moderately increased cellular radiation sensitivity of A-T carriers. They may also show elevated clinical radiosensitivity. We retrospectively examined patients who presented with severe adverse reactions during or after standard radiation treatment for mutations in the gene responsible for A-T, ATM, considering a potential means of future identification of radiosensitive individuals prospectively to adjust dosage schedules. Material and Methods: We selected 20 cancer patients (breast, 11; rectum, 2; ENT, 2; bladder, 1; prostate, 1; anus, 1; astrocytoma, 1; Hodgkins lymphoma, 1) with Grade 3 to 4 (RTOG) acute and/or late tissue radiation side effects by reaction ...
Minimally invasive thermotherapies for focal tissue destruction on the basis of laser-, microwave-, focused ultrasound-, or cryogeninduced changes of tissue temperature represent an alternative to surgical tissue ablation, particularly in the treatment of tumors. The thermotherapy modalities listed necessitate indirect guidance and monitoring, since they often do not lend themselves to immediate visual control. In the brain, in head and neck tumors, in the liver, and in the prostate, MRI reliably and accurately delineates both the positions of interstitial thermotherapy applicators and - in contrast-enhanced, T1-weighted images - the perfusion defects in tissue necrosis induced by thermotherapy. The transfer of results of in-vitro and in-vivo model studies to assess interstitial temperature and lesion development during thermotherapy to the actual treatment of patients, however, is still in an initial phase. Further development of both rapid MRI sequences and MRI ...
For the step-and-shoot intensity-modulated radiation therapy (IMRT) technique, the combination of high dose rate, multiple beam segments and low dose per segment can lead to significant differences between the planned dose and the dose delivered to the patient. In this technique, a dose delivery inaccuracy known as the 'overshoot' effect is caused by the dose servo control system. This typically occurs in the first and last beam segments and causes an over- and underdose, respectively. Some dose positional error in the segment sequence is also possible there. Commercial ionization chambers (RK-type) and radiographic Kodak films were used for the measurements. The reported results were obtained using the Pinnacle{sup 3}-V6.2 treatment planning system and a Varian Clinac 21 EX linear accelerator equipped with a 120-leaf Millennium MLC. The dose inaccuracy measurements were based on the comparison of the dose and profiles for reference fields and fields irradiated with ...
Automatic segmentation of anatomical structures in medical images is a valuable tool for efficient computer-aided radiotherapy and surgery planning and an enabling technology for dynamic adaptive radiotherapy. This paper presents the design, algorithms and validation of new software for the automatic segmentation of CT images used for radiotherapy treatment planning. A coarse to fine approach is followed that consists of presegmentation, anatomic orientation and structure segmentation. No user input or a priori information about the image content is required. In presegmentation, the body outline, the bones and lung equivalent tissue are detected. Anatomic orientation recognizes the patient's position, orientation and gender and creates an elastic mapping of the slice positions to a reference scale. Structure segmentation is divided into localization, outlining and refinement, performed by procedures with implicit anatomic knowledge using standard image processing operations. ...
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