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Biomedical subjects

R S Marks

Publications and source records attributed to R S Marks.

25 records · Page 2Linked to original sources

Phase II study of combined levamisole with recombinant interleukin-2 in patients with advanced malignant melanoma.

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) is an antineoplastic modality in which immune-activated cells are administered to a host with advanced cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested to have therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients with advanced malignant melanoma. Nineteen patients were entered in the trial. They received IL-2 at 3 x 10(6) U/m2 subcutaneously daily x 5 plus LEV 50 mg/ m2 orally three times daily (p.o. t.i.d.) x 5. Patients were reevaluated at four-week intervals. None of the patients achieved a partial or complete regression (PR, CR). The median time to treatment failure (refusal, progression, or off study due to toxicity) was 56 days. Grade IV toxicities included vomiting (3 patients), lethargy (1 patient), and musculoskellar pain (1 patient). This regimen is not recommended for further testing in patients with advanced malignant melanoma.

Adjuvants, Immunologic↗

Evaluation of continuous infusion suramin in metastatic breast cancer: impact on plasma levels of insulin-like growth factors (IGFs) and IGF-binding proteins.

Suramin represents a new class of antitumor drugs that targets growth factor networks. In this Phase II trial, suramin was administered by continuous infusion to 10 patients with advanced breast cancer. The target level of 280 microgram/ml suramin was achieved in a median of 10 days; toxicities in this patient group were low. We monitored the insulin-like growth factor (IGF) network in these patients because of the previously defined growth-promoting role of the IGFs in breast cancer. Plasma levels of total IGF-I and total IGF-II showed variable responses to suramin with median decreases of 24 and 23%, respectively, for the 10 patients; for total IGF-I levels, this did not reach statistical significance. On the other hand, free IGF-I plasma levels were consistently and dramatically increased (over 250%) after suramin infusion. IGF-binding proteins (IGFBPs), modulators of IGF bioavailability, were also measured. Levels of IGFBP-3, the major carrier of IGFs in the circulation, were decreased 21% after suramin treatment when measured by immunoradiometric assay. However, the majority of the plasma IGFBP-3 remaining after suramin was not the intact high-affinity IGF-binding form but rather a 30-kDa fragment with markedly reduced affinity for IGF-I. IGFBP-3 protease activity was evident in the plasma of 3 of 10 patients after suramin. Measurements of plasma IGFBP-1, IGFBP-2, and IGFBP-4 revealed no significant changes in response to suramin. The dramatic increase in active free IGF-I seen after suramin raises concern and underscores the importance of measuring relevant biomarkers in clinical trials.

Adult↗

A phase II study of paclitaxel and granulocyte colony-stimulating factor in previously untreated patients with extensive-stage small cell lung cancer: a study of the North Central Cancer Treatment Group.

In 1994, approximately 34,000 to 43,000 Americans will be diagnosed with small cell lung cancer, and 60% to 70% of these individuals will have extensive-stage disease. The median survival time of patients with extensive-stage small cell lung cancer is 8 to 10 months and 10% or less will survive 2 years. There have been no major advances in the treatment of this stage of disease in the past decade. Phase II trials with promising new single-agent chemotherapeutic drugs are justifiable. We report the design and toxicity of a phase II trial with single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in previously untreated patients with extensive-stage small cell lung cancer.

Carcinoma, Small Cell↗

Water toxicity detection by a panel of stress-responsive luminescent bacteria.

A panel of Escherichia coli strains harbouring different stress-responsive promoters fused to a lux reporter system was used to assess the potential toxicity of 17 unknown model water samples. Using liquid cultures, nine out of 14 toxic samples were properly identified as toxic, whereas five were false negatives. All three non-toxic controls were identified correctly (no false positives). Two strains containing promoter-lux fusions were also tested when immobilized onto fibre-optic tips. One genotoxic sample and six toxic samples were correctly identified in this manner. The potential advantages and limitations in the use of genetically engineered bacteria as biosensors for water toxicity are discussed in view of these results.

Biosensing Techniques↗

Monitoring genotoxicity during the photocatalytic degradation of p-nitrophenol.

p-Nitrophenol is a common structural unit of many pesticides and was chosen as a model compound to monitor genotoxicity during photocatalytic degradation. The genotoxicity of p-nitrophenol (PNP) and its breakdown products was measured using a bioluminescent bacterial bioassay, Vitotox. The genotoxic potential decreased with the concomitant photocatalytic degradation of the parent PNP concentration. The rate of genotoxicity reduction was slower than the rate of removal of the parent PNP, due to the formation of genotoxic by-products. After 6 h of photocatalytic treatment the total genotoxicity was removed. These results indicate that bioassays can be used as a simple and highly sensitive method for monitoring the general toxicity of chemical pollutants before, during and after photocatalytic treatment or other destructive processes.

Aliivibrio fischeri↗

Development of a chemiluminescent optical fiber immunosensor to detect Streptococcus pneumoniae antipolysaccharide antibodies.

A chemiluminescent-based optical fiber immunosensor was developed for the detection of antipneumococcal antibodies. This was accomplished by developing a different chemical procedure utilizing 3-aminopropyl trimethoxysilane and cyanuric chloride to conjugate pneumococcal cell wall polysaccharides to the optical fiber tips, and by improving the sensitivity of the photodetection system. The lowest titer of antipneumococcal antibodies detected by the optical fiber was at a 1:819,200 dilution. The lowest corresponding value by standard enzyme-linked immunosorbent assay was at a 1:98,415 dilution. It was concluded that the optical immunosensor system is an accurate and sensitive method to detect antipneumococcal antibodies and may be an adequate tool to monitor antibodies in specimens such as saliva and urine.

Antibodies↗