Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1835664 (TOC)
 2,763 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tetraamine-[Tyr3]octreotate (Demotate) is a somatostatin (SST) analogue that can be easily labeled with 99mTc at high specific activities and showed promising preclinical properties for SST receptor scintigraphy. This study reports on the first intra-patient comparison of 99mTc-Demotate and another 99mTc-labeled SST analogue, 99mTc-EDDA/HYNIC-TOC (HYNIC-TOC). Five patients with carcinoid tumors (n = 2) and endocrine pancreatic tumors (n = 3) were investigated with both radiopharmaceuticals. 99mTc-Demotate rapidly visualized somatostatin receptor positive tumors as early as 15 minutes post-injection (p.i.) with maximum tumor uptake and tumor/organ ratios already 1 hour p.i. Organs of predominant physiological uptake were the spleen and the kidneys with no intestinal excretion detectable up to 24 hours. 99mTc-Demotate exhibited faster pharmacokinetic properties compared to HYNIC-TOC. Tumor/organ ratios at equivalent time points were higher or comparable for 99mTc-Demotate in three patients with a matching scan result. Equivocal findings were observed in two patients, i.e. comparable uptake behavior in larger lesions with differences in smaller ones. 99mTc-Demotate is a promising agent for somatostatin receptor scintigraphy providing images of excellent quality as early as 1 hour after injection.
Cancer Biother Radiopharm 2004 Feb
PMID:99mTc-N4-[Tyr3]Octreotate Versus 99mTc-EDDA/HYNIC-[Tyr3]Octreotide: an intrapatient comparison of two novel Technetium-99m labeled tracers for somatostatin receptor scintigraphy. 1506 14

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.
Cancer Biother Radiopharm 2004 Apr
PMID:99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma. 1518 2

The clinical usefulness of a new 99mTc-labeled somatostatin analogue has been studied from the standpoint of oncological diagnostics. The group of patients studied included 40 individuals with diagnosed malignant neoplasms (32 primary and 8 metastatic). Among the primary tumors were 7 pituitary adenomas (5 hormonally active and 2 inactive), 1 liposarcoma, 2 carcinoids, 1 breast carcinoma, and 21 cases of lung cancer (2 small cell and 19 non-small cell) were represented. The metastatic tumors consisted of: 3 malignant melanomas, 1 pheochromocytoma, 1 prostatic cancer, 1 leiomyosarcoma, 1 pancreatic carcinoma ectopically secreting ACTH, and 1 carcinoid of the thymus. The radiopharmaceutical, 99mTc-EDDA/HYNIC-octreotide, was i.v. administered at the activity of 740-925 MBq. The imaging was comprized of a whole-body scan and single photon emission computed tomography. Positive scintigrams were obtained in 4 of 5 hormonally active pituitary adenomas, in 1 of 2 cases of carcinoid, in liposarcoma, breast cancer, and all cases of small cell (SCLC) and non-small cell lung cancer (NSCLC). The neoplastic metastases were visualized in 2 of 3 cases of melanoma and in patients with pheochromocytoma, pancreatic carcinoma secreting ACTH, and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, leiomyosarcoma, and in cases of metastasis from the prostatic carcinomas. The results of this pilot study indicated that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for the imaging of a wide range of primary and metastatic tumors. More detailed indications for the clinical usefulness of the new tracer for the imaging of selected tumor types require studies on much larger groups of patients. Special attention should be paid to the successful imaging of all cases of NSCLC.
Cancer Biother Radiopharm 2004 Apr
PMID:Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study. 1518 7

Fifty consecutive patients with solitary pulmonary nodules (SPN) on chest radiographs were studied scintigraphically after the administration of a somatostatin analog 99mTc-EDDA/HYNIC-TOC. The activity amounted to 740-925 MBq and a single photon emission computed tomography (SPECT) technique was applied. Verification of the nodule etiology was based on histology or cytology and bacteriology. As additional criterion for nodule benignity, its stable size in a chest radiograph for at least 3 years was accepted. In 31 patients, malignant etiologies of nodules were found. The diagnoses included: 11 adenocarcinomas, 6 squamous-cell carcinomas, 2 large-cell carcinomas, 6 nonsmall-cell lung cancers (NSCLC) of unspecified, more detailed morphology, 2 small-cell lung cancers (SCLC), 2 typical carcinoids, and 2 metastatic tumors: leiomyosarcoma and malignant melanoma. In 19 patients, the following benign tumors were diagnosed: 6 tuberculomas, 2 other granulomas, 4 hamartomas, 2 nonspecific inflammatory infiltrates, 1 abscess, 1 peripheral carcinoid of morphological characteristics of a benign tumor, 1 ectopic lesion of thyroid tissue, and 2 benign tumors of unspecified etiology, with stable size over 3 and 5 years. Positive scintigraphic results were obtained in 28 of 31 patients (90%) with malignant SPNs; among these there were 26 of 27 (96%) cases of primary pulmonary carcinoma. The remaining 2 false-negative cases included metastatic tumors: liposarcoma and melanoma. Among 19 benign lesions, 15 (79%) did not accumulate the radiopharmaceutical. The remaining 4 tumors visible on scintigrams included: 1 tuberculoma, 1 hamartoma, 1 abscess, and 1 case of nonestablished diagnosis (with stable size over 3 years). In conclusion, scintigraphy with 99mTc-EDDA/HYNIC-TOC appears to be an effective procedure for differentiation between malignant and benign SPNs.
Cancer Biother Radiopharm 2004 Oct
PMID:Efficacy of 99mTc-EDDA/HYNIC-TOC scintigraphy in differential diagnosis of solitary pulmonary nodules. 1565 Apr 54

For effective targeting of somatostatin receptor (sst) expressing tumors by radiolabeled octreotide analogues, high ligand uptake into sst-positive cells is mandatory. To optimize it, two modifications have been introduced into [(125)I]Tyr(3)-octreotide ([(125)I]TOC): C-terminal Thr-for-Thr(ol) exchange (leading to Tyr(3)-octreotate (TOCA)) and N-terminal derivatization with different carbohydrates. Both have significant impact on radioligand uptake into sst(2)-expressing cells in vitro and in vivo. Glucose conjugation via Amadori reaction by itself led to improved tumor uptake of [(123)I]Gluc-TOC in vivo, which is based on an enhancement of peptide internalization despite a reduction in receptor affinity. In the case of the doubly modified analogues [(123)I]Gluc-TOCA, [(123)I]Gluc-S-TOCA, and [(123)I]Gal-S-TOCA, a cumulative effect of both structural modifications was observed, leading up to a 5-fold increased uptake of these compounds in sst-expressing tumors compared to [(125)I]TOC. Thus, glycosylation with small carbohydrates was found to be a suitable tool to enhance receptor-mediated uptake of radiolabeled octreotide analogues into sst-positive malignancies, leading to tracers with excellent characteristics for in vivo sst-imaging applications.
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PMID:N-terminal sugar conjugation and C-terminal Thr-for-Thr(ol) exchange in radioiodinated Tyr3-octreotide: effect on cellular ligand trafficking in vitro and tumor accumulation in vivo. 1582 16

Swimming pool water must be treated to prevent infections caused by microbial pathogens. In Korea, the most commonly used disinfection methods include the application of chlorine, ozone/chlorine, and a technique that uses electrochemically generated mixed oxidants (EGMOs). The purpose of this study was to estimate the concentrations of total trihalomethanes (TTHMs) in indoor swimming pools adopting these disinfection methods, and to examine the correlations between the concentrations of THMs and TTHMs and other factors affecting the production of THMs. We also estimated the lifetime cancer risks associated with various exposure pathways by THMs in swimming pools. Water samples were collected from 183 indoor swimming pools in Seoul, Korea, and were analyzed for concentrations of each THM, TOC, and the amount of KMnO(4) consumption. The free chlorine residual and the pH of the pool water samples were also measured. The geometric mean concentrations of TTHMs in the swimming pool waters were 32.9+/-2.4 microg/L for chlorine, 23.3+/-2.2 microg/L for ozone/chlorine, and 58.2+/-1.7 microg/L for EGMO. The concentrations of THMs differed significantly among the three treatment methods, and the correlation between THMs and TTHMs and the other factors influencing THMs varied. The lifetime cancer risk estimation showed that, while risks from oral ingestion and dermal exposure to THMs are mostly less than 10(-6), which is the negligible risk level defined by the US EPA, however swimmers can be at the greater risk from inhalation exposure (7.77x10(-4)-1.36x10(-3)).
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PMID:Characteristics of trihalomethane (THM) production and associated health risk assessment in swimming pool waters treated with different disinfection methods. 1910 Oct 17

The cyclic ether 1,4-dioxane is a synthetic industrial chemical that is used as a solvent in producing paints and lacquers. The EPA and the International Agency for Research on Cancer(IARC) classified 1,4-dioxane as a GROUP B2(probable human) carcinogen. 1,4-dioxane is also produced as a by-product during the manufacture of polyester. In this research, a polyester manufacturing company (i.e. K Co.) in Gumi, Korea was investigated regarding the release of high concentrations of 1,4-dioxane (about 600 mg/L) and whether treatment prior to release should occur to meet with the level of the regulation standard (e.g., 5 mg/L in 2010). A 10 ton/day pilot-scale treatment system using photo-Fenton oxidation was able to remove approximately 90% of 1,4-dioxane under the conditions that concentrations of 2800 ppm H(2)O(2) and 1,400 ppm FeSO(4) were maintained along with 10 UV-C lamps (240 microW/cm(2)) installed and operated continuously during aeration. However, the effluent concentration of 1,4-dioxane was still high at about 60 mg/L where TOC concentration in the effluent had been moreover increased due to decomposed products such as aldehydes and organic acids. Thus, further investigation is needed to see whether the bench scale (reactor volume, 8.9 L) of activated sludge could facilitate the decomposition of 1,4-dioxane and their by-products (i.e., TOC). As a result, 1,4-dioxane in the effluent has been decreased as low as 0.5 mg/L. The optimal conditions for the activated sludge process that were obtained are as follows: DO, 3-3.5 mg/L; HRT, 24 h; SRT 15 d; MLSS, 3,000 mg/L. Consequently, photo-Fenton oxidation coupled with activated sludge can make it possible to efficiently decompose 1,4-dioxane to keep up with that of the regulation standard.
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PMID:Decomposition of 1,4-dioxane by photo-Fenton oxidation coupled with activated sludge in a polyester manufacturing process. 1927

Ovarian carcinoma has the highest mortality rate among gynaecological malignancies. In this project, we investigated the hypothesis that molecular markers are able to predict outcome of ovarian cancer independently of classical clinical predictors, and that these molecular markers can be validated using independent data sets. We applied a semi-supervised method for prediction of patient survival. Microarrays from a cohort of 80 ovarian carcinomas (TOC cohort) were used for the development of a predictive model, which was then evaluated in an entirely independent cohort of 118 carcinomas (Duke cohort). A 300-gene ovarian prognostic index (OPI) was generated and validated in a leave-one-out approach in the TOC cohort (Kaplan-Meier analysis, p = 0.0087). In a second validation step, the prognostic power of the OPI was confirmed in an independent data set (Duke cohort, p = 0.0063). In multivariate analysis, the OPI was independent of the post-operative residual tumour, the main clinico-pathological prognostic parameter with an adjusted hazard ratio of 6.4 (TOC cohort, CI 1.8-23.5, p = 0.0049) and 1.9 (Duke cohort, CI 1.2-3.0, p = 0.0068). We constructed a combined score of molecular data (OPI) and clinical parameters (residual tumour), which was able to define patient groups with highly significant differences in survival. The integrated analysis of gene expression data as well as residual tumour can be used for optimized assessment of the prognosis of platinum-taxol-treated ovarian cancer. As traditional treatment options are limited, this analysis may be able to optimize clinical management and to identify those patients who would be candidates for new therapeutic strategies.
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PMID:A prognostic gene expression index in ovarian cancer - validation across different independent data sets. 1929 37

Drinking ground water containing high arsenic (As) concentrations has been associated with blackfoot disease and the occurrence of cancer along the southwestern coast of Taiwan. As a result, 28 ground water observation wells were installed to monitor the ground water quality in this area. Dynamic factor analysis (DFA) is used to identify common trends that represent unexplained variability in ground water As concentrations of decommissioned wells and to investigate whether explanatory variables (total organic carbon [TOC], As, alkalinity, ground water elevation, and rainfall) affect the temporal variation in ground water As concentration. The results of the DFA show that rainfall dilutes As concentration in areas under aquacultural and agricultural use. Different combinations of geochemical variables (As, alkalinity, and TOC) of nearby monitoring wells affected the As concentrations of the most decommissioned wells. Model performance was acceptable for 11 wells (coefficient of efficiency >0.50), which represents 52% (11/21) of the decommissioned wells. Based on DFA results, we infer that surface water recharge may be effective for diluting the As concentration, especially in the areas that are relatively far from the coastline. We demonstrate that DFA can effectively identify the important factors and common effects representing unexplained variability common to decommissioned wells on As variation in ground water and extrapolate information from existing monitoring wells to the nearby decommissioned wells.
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PMID:Dynamic factor analysis for estimating ground water arsenic trends. 2004 5

Current observations in the literature suggest that vitamin E may be a suitable candidate for cancer chemotherapy. To investigate this further, we examined the ability of the vitamin E natural homologs [alpha-, beta-, gamma-, delta-tocopherols (alpha-TOC, beta-TOC, gamma-TOC, delta-TOC) and alpha-, beta-, gamma-, delta-tocotrienols (alpha-TT, beta-TT, gamma-TT, delta-TT)] and their corresponding succinate synthetic derivatives [alpha-, beta-, gamma-, delta-tocopheryl succinates and alpha-, beta-, gamma-, delta-tocotrienyl succinates (alpha-TS, beta-TS, gamma-TS, delta-TS)] to induce cell death in AR- (DU145 and PC3) and AR+ (LNCaP) prostate cancer cell lines. The most effective of all the natural homologs of vitamin E was determined to be delta-TT, whereas delta-TS was the most potent of all the natural and synthetic compounds of vitamin E examined. Both gamma-TT and delta-TT induced caspase activity selectively in AR+ LNCaP cells, suggesting a possible role for AR for the activation of caspase-dependent programmed cell death (CD-PCD). More important, however, gamma-TT, delta-TT, gamma-TS, and delta-TS activated dominant caspase-independent programmed cell death (CI-PCD) in all prostate cancer cell lines examined. Thus, vitamin E homologs and synthetic derivatives may find applications in the treatment of prostate tumors that are resistant to caspase-activating therapeutic agents.
Nutr Cancer 2009
PMID:Induction of caspase-independent programmed cell death by vitamin E natural homologs and synthetic derivatives. 2015 28


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