PubMed Health⌕ Search

Biomedical subjects

E Ben-Josef

Publications and source records attributed to E Ben-Josef.

29 records · Page 2Linked to original sources
PubMed1995

Solid tumor cells express functional "tethered ligand" thrombin receptor.

Previous work demonstrated that alpha-thrombin promoted tumor cell adhesion to endothelium and extracellular matrix as well as enhanced the metastatic capacity of tumor cells. This study was initiated to investigate whether the thrombin effect on tumor cells is mediated through the "tethered ligand" thrombin receptor. RT-PCR analysis using primers based on the human thrombin receptors detected mRNA in human colon adenocarcinoma cells (clone A), whose authenticity was confirmed by Southern hybridization. The presence of thrombin receptor mRNA in rat (W256 carcinosarcoma) and mouse (melanoma) tumor cells was demonstrated by RT-PCR/Southern blotting using species-specific PCR primers. Sequencing of the PCR fragment of clone A cells revealed complete homology with the reported human cDNA sequence. Subsequently, tumor cells derived from three species, i.e., human, rat, and mouse, were found to express the thrombin receptor protein as revealed by immunoblotting using ligand peptide-derived mAb ATAP138, whose reactivity towards the M(r) approximately 66,000, potential thrombin receptor was blocked by preincubating the antibody with the immunogen peptide SFLLRNPNDKYEPF (TRP 14). Finally, peptides TRP 14 and TRP 7 (SFLLRNP), but not TRP 5 (FLLRN), were found to mimic alpha-thrombin in stimulating tumor cell adhesion to fibronectin, suggesting that the thrombin receptors expressed on solid tumor cells are biologically functional.

Amino Acid Sequence↗
PubMed1995

Whole abdominal radiotherapy and concomitant 5-fluorouracil as adjuvant therapy in advanced colon cancer.

PURPOSE: This analysis was undertaken to assess whole abdomen radiation therapy and concurrent 5-fluorouracil for toxicity and patterns of failure in high-risk colon cancer patients after curative surgical resection. METHODS: Eighteen patients were treated adjuvantly after curative resection. Four patients (22 percent) had Stage B and 14 (78 percent) had Stage C disease. Histology was poorly differentiated in 4 (22 percent) and moderately differentiated in 14 (78 percent) patients. Four patients received whole abdominal radiation only, 30 Gy at 1 Gy/day. Fourteen patients had an additional locoregional boost of 9.6 to 16 Gy at 1.6 Gy/day. The liver received 19.8 Gy at 0.67 Gy/day. 5-Fluorouracil was given as a continuous infusion during therapy. RESULTS: With a median follow-up of three years, 6 of 18 (33 percent) patients have relapsed. Failure occurred locally in 3 of 18 (17 percent) and distantly in 4 of 18 patients (22 percent). Four of six (67 percent) failures occurred in the liver. The five-year actuarial survival and disease-free survival were 78 percent and 66 percent, respectively. Median elapsed time on radiotherapy was 73 days, with 5 of 18 patients (28 percent) requiring two or more weeks of unplanned treatment breaks. Acute Grade 3 to 4 toxicity (diarrhea, leukopenia) occurred in 3 of 18 patients (17 percent), with late complications (bowel obstruction) occurring in 2 of 18 patients (11 percent). CONCLUSIONS: Whole abdominal radiotherapy with concomitant 5-fluorouracil appears to improve local control but not to prevent liver metastases. Significant toxicity resulted in frequent interruption of therapy and protracted its course. Whether this adjuvant regimen impacts on survival or offers an advantage over locoregional irradiation remains to be studied.

Abdomen↗
PubMed1995

A direct measurement of strontium-89 activity in bone metastases.

The total absorbed dose after systemic administration of 89Sr has been determined by measuring directly its activity in bone metastases. Autoradiography was performed on sections of bones obtained from patients treated with 89Sr to study the pattern of deposition. Discs of 5 and 8 mm diameter were cut from metastatic sites and normal bone. The beta-ray activity was determined with a scintillation counter, which was calibrated using similar bovine cancellous bone discs, onto which a known activity of 89Sr was transferred by pipette. From the activity measured, the initial activity (at the time of 89Sr administration) was calculated. The absorbed dose was estimated using the methodology described in NCRP Report No. 58. The estimated initial activity of 89Sr in the bone metastases varied from 2.3 to 240 MBq kg-1, with a mean value of 31 +/- 27 MBq kg-1. The total absorbed dose ranged from 1.3 to 64 Gy, with a mean of 18 +/- 16 Gy. The average total dose to normal bone sites was 1.1 +/- 0.4 Gy. The metastases to normal bone dose ratio in individual samples varied from 8 +/- 4 to 40 +/- 25. These estimates are in agreement with those obtained previously by indirect methods.

Autoradiography↗
PubMed1995

Selective accumulation of strontium-89 in metastatic deposits in bone: radio-histological correlation.

The systemic administration of 89Sr has proven effective in the palliation of painful osseous metastases. Biodistribution studies with the gamma-emitter 85Sr suggest that both its uptake and retention are increased in bone metastases, where increased mineral turnover takes place. To study the pattern and nature of this process further, bones containing metastatic deposits were obtained from three patients who had previously been treated with 148 MBq of 89Sr. The bones were cut into 0.5-1.0 cm sections. The cut surfaces which faced together were marked with India ink, and adjacent sections were submitted for histology and autoradiography. Strontium deposition and retention were observed in regions which exhibited significant osteoblastic activity, mostly in areas adjacent to metastatic deposits, but also in subchondral and endosteal locations, as well as in an area corresponding to a pathological fracture with callus formation. With these exceptions, strontium deposition was not observed in histologically normal bone or within the marrow. Our findings demonstrate directly the selective nature of accumulation and retention of 89Sr and confirm previous clinical impressions.

Adenocarcinoma↗
PubMed1995

Topical application of WR-2721 achieves high concentrations in the rectal wall.

Rectal wall injury is an important treatment-related morbidity in patients treated with radiation for prostate cancer. We have undertaken this study to investigate the merits of topical intrarectal application of the radioprotective compound WR-2721. Male Copenhagen rats were injected intrarectally with 2% WR-2721 gel. At 10, 20, 30 and 40 min after application, a laparotomy was performed, and the rectum and prostate were removed. Concentrations of total WR-1065 (the active metabolite of WR-2721) were determined in these samples by an HPLC assay. While the concentration in the rectal wall tended to increase with time, it did not change substantially in the prostate. The concentration in the rectal wall was found to be significantly higher at all times. We conclude that preferential accumulation of WR-2721 in the rectal wall can be achieved by topical application. This is a promising approach to modifying rectal wall tolerance that deserves more study.

Administration, Topical↗
PubMed1995

Radiotherapy of T1c prostate cancer.

With a 10-year local control rate of 85% to 100% and a low complication rate, radiotherapy is an effective treatment option for T1c prostate cancer. Controversial topics, such as treatment volumes and dose-response, are critically reviewed. New investigational approaches will be discussed.

Humans↗
PubMed1994

Systemic administration of new therapeutic radioisotopes, including phosphorus, strontium, samarium, and rhenium.

New advances in systemic radionuclide therapy have increased the number of treatment options available for patients with painful osseous metastases. This form of therapy has three major appeals: 1) it addresses all sites of involvement; 2) selective absorption into bone limits irradiation of normal tissues; and 3) as a result, toxicity may be reduced and the therapeutic ratio improved. The clinical experience with radioactive phosphorus, strontium, samarium, and rhenium are reviewed. To date, the best studied and the only Food and Drug Administration approved agent is strontium-89. About 60% to 90% of patients treated with strontium-89 respond with complete or partial relief of pain for a median duration of 6 months. Large, prospectively randomized clinical trials have established the efficacy of strontium-89 as a first-line therapy and as an adjuvant to external-beam radiotherapy. Particularly advantageous is its usefulness in situations in which external-beam radiotherapy options have been exhausted and normal tissue tolerance has been reached. Newer radiopharmaceuticals are still under investigation.

Bone Neoplasms↗
PubMedDate not supplied

Systemic bone-seeking radionuclides for palliation of painful osseous metastases: current concepts.

Bone metastases require multidisciplinary treatment, the primary goal of which is to relieve pain and improve quality of life. Among the options available, bone-seeking radioisotopes are attractive because they can treat several symptomatic metastases simultaneously. This therapy may have antitumor efficacy in addition to analgesic properties. Although the ultimate place of systemic radionuclides in the treatment of bone metastases has not been firmly established, some patients clearly benefit from these modalities.

Analgesics↗
PubMedDate not supplied

Clinical strategies for improving the radiotherapeutic management of prostate cancer.

The goal of treatment of localized and locally advanced prostate cancer is to cure without causing unacceptable complications. The recognition that cure rates for localized and locally advanced prostate cancer treated with traditional means are far lower than previously estimated (1-4) has provided the impetus to seek improved local therapies. In particular, 3D conformal radiation therapy (3D-CRT) and the combination of radiation and hormone therapy are promising. Advances in these and other areas are discussed below.

Adenocarcinoma↗