Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate 99mTc-DTPA-HSA as an iliopelvic lymphoscintigraphic agent in 5 normal volunteers and 10 patients with metastases of malignant tumors (cancer, 9; and malignant lymphoma, 1) to the iliopelvic lymph nodes. The subjects underwent intradermal injection of 185 MBq of 99mTc-DTPA-HSA into digital web spaces of the feet. Massage was applied at the injection sites for 30 sec; the subjects then walked around for 2 min. Whole-body scintigrams were obtained 5 min after injection. The whole-body scanning speed was 20 cm/min. The tracer transport was prompt. Within 15 min after injection, the tracer reached the termination of the thoracic duct in all normal volunteers. Normal whole-body images of excellent quality delineated the lymph nodes and channels almost without background radioactivity. The images of 9 patients with metastases of cancer showed clearly the following abnormal patterns: a) obstruction of lymphatic system (5/9, 55.6%); b) absence of visualization of the thoracic duct (44.4%); c) decreased uptake in lymph nodes (88.9%); d) visualization of collateral circulation (44.4%); e) tracer extravasation into more proximal soft tissue (22.2%). The image in the patient with malignant lymphoma showed increased uptake in the enlarged lymph nodes in addition to the all abnormal findings mentioned above. We concluded that 99mTc-DTPA-HSA is an excellent radiopharmaceutical for iliopelvic lymphoscintigraphy.
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PMID:[Lymphoscintigraphy with 99mTc-DTPA-HSA: detection of metastases to iliopelvic lymph nodes]. 192 Sep 55

A 52 year-old woman with recurrent thyroid cancer showed an accumulation of Tl-201 chloride in the left side of the neck. This proved to be reflux and retention of Tl-201 chloride in the left internal jugular vein and was verified with a Tc-99m HSA flow study. This phenomenon could be mistaken for metastases of thyroid cancer.
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PMID:Visualization of jugular vein on a thallium-201 scan for thyroid cancer. 274 96

A dual radionuclide subtraction technique for external detection of tumours has been evaluated to determine the viability of the method for use with radioisotope labelled antibodies. A number of external scintigraphic investigations have been carried out with 131I-labelled antibodies to carcinoembryonic antigen (CEA). The investigations were performed on patients with metastatic disease known to produce CEA. The dual radionuclide subtraction technique was used to account for the blood and tissue background. The 131I-labelled antibodies were found to localise in the metastatic lesions, but the subtraction technique using 99Tcm-labelled HSA and pertechnetate gave ambiguous results, which included the production of artefacts. The ambiguities noted in the clinical results were substantiated by experimental data, which highlight the unreliability of this technique.
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PMID:The limitations of the dual radionuclide subtraction technique for the external detection of tumours by radioiodine-labelled antibodies. 629 51

The effective treatment depth in boron neutron capture therapy with thermal neutrons depends on the beam aperture, heavy water concentration, boron concentrations in the tumor, normal tissue and blood, tolerance dose to normal tissue and the capillary dose modification factor. In this study a 15 cm aperture is used and the tolerance dose to normal tissue is evaluated to be 15 Gy. Human pharmacokinetic data are evaluated for BSH and D, L-BPA, the two compounds currently used in thermal BNCT. Results show that the average measured tumor to blood boron ratios and standard deviations are 1.4 (0.4) for BSH and 4.3 (1.8) for subcutaneous melanoma. Experimental dose-depth phantom results for the Musashi Institute of Technology reactor are used with expected boron concentrations to calculate the maximum therapeutic depth in the brain for a thermal neutron beam. For BPA, the subcutaneous melanoma boron concentrations are assumed for intracranial metastases, and no allowance is made for possible enhanced uptake in the dopamine and noradrenaline tracts. Results for BSH are enhanced by inclusion of the capillary dose reduction factor. Calculations show that for expected boron tumor to blood ratios, the modified advantage depth is about 4 cm and the maximum therapeutic depth is about 1.5 cm for both BSH and BPA. Typical heavy water ratios of 15% increase the treatment depth by 0.5 cm, but this is offset by the use of smaller beam aperture in practice.
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PMID:Maximum therapeutic depth in thermal neutron capture therapy. 843 38

Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes. The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium (99mTc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1.98 microns and 2.02, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2: lipid:HSA) demonstrated a close correlation of size distributions (r = 0.9445; P < 0.001). The entrapment of interleukin 2 in liposomes was 93 +/- 4.3% before nebulization and 90 +/- 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean +/- s.d. central lung-to-peripheral lung deposition was 1.12 +/- 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen. The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers.
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PMID:Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution. 936 3

For patients with local recurrence of prostate cancer after definitive irradiation therapy there is no treatment widely considered safe and effective. After extensive preclinical testing of prodrug gene therapy in vitro and in vivo, we conducted a phase I dose escalation clinical trial of intraprostatic injection of a replication-deficient adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene (HSV-tk) injected directly into the prostate, followed by intravenous administration of the prodrug ganciclovir (GCV). Our goal was to determine safe dose levels of the vector for future trials of efficacy. Patients with a rising serum prostate-specific antigen (PSA) level and biopsy confirmation of local recurrence of prostate cancer without evidence of metastases one or more years after definitive irradiation therapy were eligible for the trial. After giving informed consent, patients received injections of increasing concentrations of ADV/HSA-tk in 1 ml into the prostate under ultrasound guidance. Ganciclovir was then given intravenously for 14 days (5 mg/kg every 12 hr). Patients were monitored closely for evidence of toxicity and for response to therapy. Eighteen patients were treated at 4 escalating doses: group 1 (n = 4) received 1 x 10(8) infectious units (IU); group 2 (n = 5) received 1 x 10(9) IU; group 3 (n = 4) received 1 x 10(10) IU; group 4 (n = 5) received 1 x 10(11) IU. Vector was detected by PCR of urine samples after treatment, increasing in frequency and duration (up to 32 days) as the dose increased. All cultures of blood and urine specimens were negative for growth of adenovirus. Minimal toxicity (grade 1-2) was encountered in four patients. One patient at the highest dose level developed spontaneously reversible grade 4 thrombocytopenia and grade 3 hepatotoxicity. Three patients achieved an objective response, one each at the three highest dose levels, documented by a fall in serum PSA levels by 50% or more, sustained for 6 weeks to 1 year. This study is the first to demonstrate the safety of ADV/HSV-tk plus GCV gene therapy in human prostate cancer and the first to demonstrate anticancer activity of gene therapy in patients with prostate cancer. Further trials are underway to identify the optimal distribution of vector within the prostate and to explore the safety of repeat courses of gene therapy.
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PMID:In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. 1034 May 55

Nuclear medicine plays an important role in the diagnosis and treatment of thyroid and parathyroid disorders. Basic nuclear medicine in the diagnosis of thyroid and parathyroid disorders and our clinical study on 131I treatment for differentiated thyroid cancer are described. Characteristics of thyroid, parathyroid, tumor scans and typical bone scintigrams in hyperparathyroidism are presented. Combined 99mTc-MIBI/99mTc-HSA-D SPECT imaging clearly demonstrated localization of ectopic parathyroid adenoma. Very interesting uncommon three cases of thyroid cancer are presented. 99mTcO4- thyroid scan in the first patient demonstrated intense tracer uptake in the lymph node metastasis from papillary microcancer. Post-therapy 131I scan following total thyroidectomy visualized multiple pulmonary metastases. The second patient with metastatic follicular cancer developed thyrotoxicosis with high TSH receptor antibodies. Post-therapy 131I total body scan in the third patient with papillary cancer demonstrated large skull metastasis. Cardiac blood pool and large blood vessel visualization was also clearly seen at this time.
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PMID:[Nuclear medicine of the thyroid and parathyroid glands]. 1180 77

Disseminated metastases of colorectal cancer in liver are incurable. The trial EORTC 11001 investigates whether autotransplantation after extracorporeal irradiation of the liver by boron neutron capture therapy (BNCT) might become a curative treatment option because of selective uptake of the compounds sodium mercaptoundecahydro-closo-dodecaborate (BSH) or L-para-boronophenylalanine (BPA). BSH (50 mg/kg bw) or BPA (100 mg/kg bw) were infused into patients who subsequently underwent resection of hepatic metastases. Blood and tissue samples were analyzed forthe (10)B-concentration with prompt gamma ray spectroscopy (PGRS). Three patients received BSH and 3 received BPA. Adverse effects from the boron carriers did not occur. For BSH, the highest (10)B-concentration was observed in liver (31.5 +/- 2.7 microg/g) followed by blood (24.8 +/- 4.7 microg/g) and tumor (23.2 +/- 2.1 microg/g) with a mean (10)B-concentration ratio metastasis/liver of 0.72 +/- 0.07. For BPA, the highest (10)B-concentration was measured in metastases (12.1 +/- 2.2 microg/g) followed by liver (8.5 +/- 0.5 microg/g) and blood (5.8 +/- 0.8 microg/g). As BPA is transported actively into cells, viable, metabolically active cells accumulate exclusively this compound. Consequently, a model is proposed to adjust the values measured by PGRS for the proportion of viable cells to express the relevant (10)B-concentration in the tumor cells, revealing a (10)B-concentration ratio metastasis/liver of 6.8 +/- 1.7. In conclusion, BSH is not suitable as (10)B-carrier in liver metastases as the (10)B-concentration in liver was higher compared to metastasis. BPA accumulates in hepatic metastases to an extent that allows for extracorporeal irradiation of the liver with BNCT.
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PMID:Uptake of two 10B-compounds in liver metastases of colorectal adenocarcinoma for extracorporeal irradiation with boron neutron capture therapy (EORTC Trial 11001). 1798 41

Sialyl Lewis(a) (sLe(a)), also termed CA19-9 antigen, is recognized by murine mAb19-9 and is expressed on the cancer cell surface as a glycolipid and as an O-linked glycoprotein. It is highly expressed in a variety of gastrointestinal epithelial malignancies including colon cancer and pancreatic cancer, and in breast cancer and small cell lung cancer, but has a limited expression on normal tissues. sLe(a) is known to be the ligand for endothelial cell selectins suggesting a role for sLe(a) in cancer metastases and adhesion. For these reasons, sLe(a) may be a good target for antibody mediated immunotherapy including monoclonal antibodies and tumor vaccines. However, sLe(a) is structurally similar to sLe(x) and other blood group related carbohydrates which are widely expressed on polymorphonucleocytes and other circulating cells, raising concern that immunization against sLe(a) will induce antibodies reactive with these more widely expressed autoantigens. We have shown previously both in mice and in patients that conjugation of a variety of carbohydrate cancer antigen to keyhole limpet hemocyanin (KLH) and administration of this conjugate mixed with saponin adjuvants QS-21 or GPI-0100 are the most effective methods for induction of antibodies against these cancer antigens. We describe here for the first time the total synthesis of pentenyl glycoside of sLe(a) hexasaccharide and its conjugation to KLH to construct a sLe(a)-KLH conjugate. Groups of five mice were vaccinated subcutaneously four times over 6 weeks. Sera were tested against sLe(a)-HSA by ELISA and against sLe(a) positive human cell lines adenocarcinoma SW626 and small cell lung cancer (SCLC) DMS79 by FACS. As expected, mice immunized with unconjugated sLe(a) plus GPI-0100 or unconjugated sLe(a) mixed with KLH plus GPI-0100 failed to produce antibodies against sLe(a). However, mice immunized with sLe(a)-KLH conjugate without GPI-0100 produced low levels of antibodies and mice immunized with sLe(a)-KLH plus GPI-0100 produced significantly higher titer IgG and IgM antibodies against sLe(a) by ELISA. These antibodies were highly reactive by FACS and mediated potent complement mediated cytotoxicity against sLe(a) positive SW626 and DMS79 cells. They showed no detectable cross reactivity against a series of other blood group-related antigens, including Le(y), Le(x), and sLe(x) by dot blot immune staining. This vaccine is ready for testing as an active immunotherapy for treating sLe(a) positive cancer in clinical settings.
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PMID:Synthesis of sialyl Lewis(a) (sLe (a), CA19-9) and construction of an immunogenic sLe(a) vaccine. 1919 Sep 7

The CCL2-CCR2 chemokine axis has an important role in cancer progression where it contributes to metastatic dissemination of several cancer types (e.g., colon, breast, prostate). Tumor cell-derived CCL2 was shown to promote the recruitment of CCR2(+)/Ly6C(hi) monocytes and to induce vascular permeability of CCR2(+) endothelial cells in the lungs. Here we describe a novel decoy protein consisting of a CCL2 mutant protein fused to human serum albumin (dnCCL2-HSA chimera) with enhanced binding affinity to glycosaminoglycans that was tested in vivo. The monocyte-mediated tumor cell transendothelial migration was strongly reduced upon unfused dnCCL2 mutant treatment in vitro. dnCCL2-HSA chimera had an extended serum half-life and thus a prolonged exposure in vivo compared with the dnCCL2 mutant. dnCCL2-HSA chimera bound to the lung vasculature but caused minimal alterations in the leukocyte recruitment to the lungs. However, dnCCL2-HSA chimera treatment strongly reduced both lung vascular permeability and tumor cell seeding. Metastasis of MC-38GFP, 3LL, and LLC1 cells was significantly attenuated upon dnCCL2-HSA chimera treatment. Tumor cell seeding to the lungs resulted in enhanced expression of a proteoglycan syndecan-4 by endothelial cells that correlated with accumulation of the dnCCL2-HSA chimera in the vicinity of tumor cells. These findings demonstrate that the CCL2-based decoy protein effectively binds to the activated endothelium in lungs and blocks tumor cell extravasation through inhibition of vascular permeability.
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PMID:Targeting of CCL2-CCR2-Glycosaminoglycan Axis Using a CCL2 Decoy Protein Attenuates Metastasis through Inhibition of Tumor Cell Seeding. 2680 51


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