To determine the ability to induce tumor-specific immunity with individual mutant K-ras-or p53-derived peptides and to monitor clinical outcome.Patients in varying stages of disease underwent genetic analysis for mutations in K-ras and p53. Thirty-nine patients were enrolled. Seventeen-mer peptides were custom synthesized to the corresponding mutation. Baseline immunity was assessed for cytotoxic T-lymphocyte (CTL) response and interferon gamma (IFN-gamma) release from mutant peptide-primed lymphocytes. Patients' peripheral-blood mononuclear cells were pulsed with the corresponding peptide, irradiated, and applied intravenously. Patients were observed for CTL, IFN-gamma, interleukin (IL) -2, IL-5, and granulocyte-macrophage colony-stimulating factor responses, for treatment-related toxicity, and for tumor response.No toxicity was observed. Ten (26%) of 38 patients had detectable CTL against mutant p53 or K-ras, and two patients were positive for CTL at baseline. Positive IFN-gamma responses occurred in 16 patients (42%) after vaccination, whereas four patients had positive IFN-gamma reaction before vaccination. Of 29 patients with evident disease, five experienced a period of stable disease. Favorable prognostic markers were detectable CTL activity and a positive IFN-gamma reaction but not IL-5 release. Median survival times of 393 v 98 days for a positive versus negative CTL response (P = .04), respectively, and of 470 v 88 days for a positive versus negative IFN-gamma response (P = .02), respectively, were detected.Custom-made peptide vaccination is feasible without any toxicity. CTL and cytokine responses specific to a given mutation can be induced or enhanced with peptide vaccines. Cellular immunity to mutant p53 and K-ras oncopeptides is associated with longer survival.
Abstract Data on the carcinogenicity and Ames Salmonella test muta‐genicity were compiled for 671 organic chemicals reported to be potential air pollutants. Development of the data base entailed an evaluation of published reports of carcinogenicity and mutagenicity test results available in the open literature. Criteria were established for classifying the chemicals as recognized carcinogens, suspected carcinogens, tumor promoters or cocarcinogens, and mutagens or suspected mutagens. Confirmation of chemicals as ambient air pollutants was attempted only for the chemicals classified into a category of potential carcinogenicity other than unknown. Primary and secondary literature sources were searched for the reported detection of the chemicals as ambient air pollutants. This work resulted in the classification of 77 air pollutants as potential human carcinogens, as demonstrated by the categorization of 25 air pollutants as recognized carcinogens, 20 air pollutants as suspected carcinogens, 15 air pollutants as tumor promoters/cocarcinogens, and 50 air pollutants as mutagens or suspected mutagens. For 17 of the 50 air pollutants classified as mutagens or suspected mutagens, no adequate positive carcino‐genicity data were found. No evidence of mutagenicity determined by the Ames test was found for seven of the 25 recognized carcinogens or for nine of the 20 suspected carcinogens. Notes This study was supported by the National Cancer Institute, Contract No. NO1‐CP‐95607 Reprints may be obtained from C. T. Helmes and also from Dr. H. F. Kraybill, Scientific Coordinator for the Office of Environmental Cancer, Division of Cancer Cause and Prevention, National Cancer Institute, Landow Building, Room C337, 7910 Woodmont Avenue, Bethesda, Maryland 20205
Mycotrophein, a growth factor required by some biotrophic contact mycoparasites, was isolated from Arthrobotrys musiformis. Mycotrophein was partially purified using a combination of silicic acid and high performance liquid chromatographies. The partially purified compound promoted axenic growth of Stephanoma phaeospora, Gonatobotrys simplex, Calcarisporium parasiticum and Gonatorrhodiella highlei, contact mycoparasites which require this factor for axenic growth. There was essentially no growth-promoting activity with any of the many authentic biochemicals tested. Electron impact mass spectral measurements on the purified mycotrophein indicated only the presence of a mixture of tetra-and pentaethylene-glycol mono-(nonylphenyl) ethers that could possibly act as carriers of the biologically active factor.
Abstract Lithocholic acid‐3α‐sulfate is metabolized by human intestinal microflora to nonpolar metabolites which have been partially purified by Sephadex LH‐20 chromatography. These metabolites were characterized by thin layer and gas liquid chromatography as well as combined gas liquid chromatography‐mass spectrometry. The chromatographic properties of one of the metabolites are consistent with those described for a Δ 2 ‐or Δ 3 . The formation of cholenates by the microflora may represent a retoxification of the sulfate ester of lithocholic acid.
Abstract Background and aims Inflammatory bowel disease (IBD) is associated with a higher risk of developing colorectal cancer, according to the inflammation-dysplasia-cancer (IDC) sequence from inflammation to colitis-associated colorectal cancer (CAC). The objective of this study was to identify and generate a transcriptomic signature and score, related to the IDC sequence, that could ultimately classify dysplasia and cancer in IBD. Methods Demographics, clinical parameters, histological characteristics and RNA-sequencing data were evaluated on 134 formalin-fixed paraffin-embedded lesions from 2 independent cohorts of IBD patients with low- or high-grade dysplasia (LGD, HGD) and/or CAC. An ordinal logistic regression screened for significant IDC sequence-associated genes that were computed in a transcriptomic signature score. Results Principal component analysis and unsupervised clustering on 1% of the most variable genes showed a good clustering between the 4 lesion groups (Normal Mucosa, Inflamed Mucosa, LGD/HGD, and CAC). A gene signature was identified on 27 genes that correlated with the lesion groups in the exploratory cohort. The most weighted gene in this transcriptomic signature was the long non-coding regulatory RNA KCNQ1OT1, a gate keeper against genomic instability and transposon activation. Based on these 27- genes expression, we built and validated a transcriptomic signature score to classify dysplasia and CAC. The overall accuracy of the transcriptomic signature score was 85.71% in the exploratory cohort and 90.91% in the validation cohort. Conclusion We identified a tissue-based transcriptomic score to classify IDC lesions in IBD patients and uncovered some of the pivotal genes in the carcinogenesis related to inflammation in IBD.
In “Clinical Evaluation of Safety and Immunogenicity of PADRE-Cytomegalovirus (CMV) and Tetanus-CMV Fusion Peptide Vaccines With or Without PF03512676 Adjuvant” (J Infect Dis2012; 205:1294–304), Sanjeet Dadwal was mistakenly omitted from the coauthor list.
The authors regret the error. A corrected author list is below.
