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D Dillon

Publications and source records attributed to D Dillon.

8 recordsLinked to original sources
PubMed2026

Tumor genomic landscape of older patients with metastatic breast cancer☆.

BACKGROUND: Metastatic breast cancer (MBC) in older patients has distinct clinical and histologic characteristics. Elucidating the genomic basis of MBC helps identify potential therapeutic targets to improve outcomes for older patients with MBC. PATIENTS AND METHODS: Using a prospective database and targeted DNA sequencing (OncoPanel), we examined MBC's genomic landscape in older patients (age &#x2265;70 years at MBC diagnosis) and compared findings with those in younger (aged <50 years) and middle-aged (aged 50-69 years) patients. After classifying single nucleotide variants (SNVs) and copy number variations (CNVs) as oncogenic (via OncoKB), the frequencies of SNVs and CNVs, tumor mutational burden (TMB), and oncogenic signaling pathways were compared by age group using Fisher's exact tests. We estimated the association between continuous age at MBC diagnosis and mutations via multivariate logistic regression analysis, adjusting for race, stage at initial diagnosis, subtype, histology, and sample tested (primary versus metastatic). RESULTS: Our study included 2379 patients [853 (35%) younger, 1311 (55%) middle-aged, and 215 (9%) older] who underwent OncoPanel testing between 2013 and 2020. The most frequent tumor alterations in older patients were SNVs in PIK3CA (44%), TP53 (33%), CDH1 (22%) and amplifications in CCND1 (18%). After adjustment, older age was associated with higher frequency of SNVs in CDH1 [odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.21-1.68, q < 0.001], MAP3K1 [OR = 1.30, 95% CI 1.10-1.54, q = 0.008], and PIK3CA [OR = 1.21, 95% CI 1.11-1.31, q < 0.001] and fewer SNVs in TP53 [OR = 0.84, 95% CI 0.77-0.91, q < 0.001]. Patients in the older group were more likely to have tumors with &#x2265;10 mutations/megabase than the youngest patients (26% versus 17%, P = 0.003). CONCLUSIONS: In this large cohort of patients with MBC, the tumor genomic landscape differed between older and younger patients even after accounting for tumor subtype. Older patients were more likely to have high-TMB and PIK3CA-mutated tumors, highlighting the importance of genomic testing for treatment applications in this population.

NGS↗
PubMed1992

Ozone is mutagenic in Salmonella.

Ozone is a highly reactive gas that has been tested for genotoxicity in a number of systems. Induced genetic damage resulting from ozone treatment may not be readily observed because of the high toxicity of the chemical and difficulties in generating and administering controlled concentrations. The mutagenicity of ozone was investigated in Salmonella typhimurium using a plate test protocol designed for reactive vapours and gases. Ozone, at two to three consecutive doses, induced weak, albeit statistically significant, mutagenic responses in tester strain TA102 with and without Aroclor-induced rat liver S9 (lowest effective mean concentration of 0.019 ppm; 35 min total exposure). However, dose-related responses were not always obtained. No mutagenicity was detected in strains TA98, TA100, or TA1535, with or without S9. In strain TA104, ozone induced a weak response only at a single dose with S9; this response was not reproducible. Mutagenicity was dependent on the ozone flow rate and total exposure time, with variations in the optimum dose-time regimen leading to toxicity or complete inactivity. The data show that ozone is a very weak bacterial mutagen and only when tested under narrowly prescribed, subtoxic dosing conditions.

Animals↗
PubMed1992

The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane.

Dichloromethane (DCM) vapour by inhalation is carcinogenic to rodents and is an in vivo rodent cell clastogen and a bacterial mutagen. It has been suggested that the bacterial mutagenicity of DCM is mediated by glutathione (GSH) conjugation. The involvement of endogenous and exogenous GSH in the conversion of DCM to a bacterial mutagen has been studied in a vapour phase protocol using wild-type and GSH-deficient (NG54; gsh) Salmonella typhimurium TA100 strains in the presence and absence of various rat liver fractions. The effect of the duration of exposure was also investigated in these Salmonella strains and in E. coli WP2 uvrA pKM101. Dose- and time-related increases in revertants occurred with all metabolic activation systems used (without exogenous metabolic activation; with Aroclor-induced rat liver S9, microsomes, or cytosol fractions), with minor quantitative differences among the 3 strains. Mutagenicity was marginally highest in the presence of cytosol at the highest DCM concentrations. Strain NG54 gsh, which contains approximately 25% of the TA100 level of GSH/microgram protein, was slightly less responsive to DCM-induced mutagenicity than TA100. Addition of 0.33 mumoles/plate of GSH had little effect on the mutagenic responses of TA100 or NG54 in the presence or absence of S9. In these 2 strains, exogenous S9 produced small increases in mutagenicity at the highest concentrations of DCM (2 and 4% v/v). These results suggest that if an interaction between DCM and GSH is required for the activation of DCM to a bacterial mutagen, it occurs at low levels of endogenous GSH and is not significantly affected by GSH supplementation.

Animals↗
PubMed1992

Immunohistochemical expression of endometrial proteins and pregnancy outcome in frozen embryo replacement cycles.

The expression of two endometrial proteins, pregnancy-associated endometrial alpha-2 globulin (alpha-2 PEG) and 24K protein, was examined immunohistochemically in an attempt to identify a marker or a pattern which would predict subsequent implantation. Patients who had undergone in-vitro fertilization cycles and had at least three frozen embryos were recruited into the study. They received two cycles of hormone replacement therapy. The first was a monitored cycle in which dated endometrial biopsies were taken for immunohistochemical assessment using monoclonal antibodies to alpha-2 PEG and 24K protein and also for standard histological dating. In the second cycle, the frozen-thawed embryos were replaced. The results of the monitored cycle were then correlated with the pregnancy outcome in the transfer cycle. Ten patients conceived, of whom eight had a pattern of low immunohistochemical staining of alpha-2 PEG and high immunohistochemical staining of 24K. In the 15 patients who did not conceive, four had the same endometrial protein pattern (P less than 0.05). In the 13 specimens classified as histologically in phase, 10 (71%) showed incompatible protein expression. We conclude that the pattern of expression of the endometrial proteins alpha-2 PEG and 24 K may be potentially useful to indicate a receptive endometrium. Immunohistochemistry may yield information on endometrial development which is not apparent from routine histological assessment.

Antibodies, Monoclonal↗
PubMed1991

Spontaneous mutation at the mtr locus of Neurospora: the spectrum of mutant types.

We have isolated 135 strains of Neurospora which have mutations at the mtr locus resulting from independent spontaneous events. mtr is the structural gene for the neutral amino acid permease. The mutants have been characterized by their reversion behavior (both spontaneous and induced) and by hybridization studies of restriction digests of their DNA. About half of the mutants (54%) appear to result from single base-pair substitutions. Thirty-four percent have deletions, including some which extend into neighboring genes. Most of the remaining mutants have insertions. Several of the insertions are tandem duplications of 400-1000 bp and these mutants are unstable, reverting to mtr+ with a high frequency. When tandem-duplication mutants go through a cross, they are modified: the mutant progeny are fully stable. This modification is probably due to RIP (repeat-induced point mutation). This process has an important bearing on the comparison of germinal to somatic mutation.

Aminoacridines↗
PubMed1991

Myocardial aging: antioxidant enzyme systems and related biochemical properties.

The effects of aging on myocardial antioxidant enzyme activity, lipid peroxidation, and other related biochemical properties were investigated in male Wistar-Furth rats at 4, 26, and 31 mo of age at rest and after an acute exercise bout. The results showed that resting heart cytosolic superoxide dismutase (CuZn SOD) activity was significantly decreased in the heart with aging (66 +/- 6.5 U/mg protein at 4 mo vs. 49 +/- 3.8 U/mg protein at 31 mo) and was elevated in all age groups after exercise. Mitochondrial Mn SOD activity was almost doubled in both 26- and 31-mo-old rats compared with that at 4 mo. Myocardial catalase and cytosolic glutathione peroxidase (GPX) activities were significantly decreased with age, whereas mitochondrial GPX was 29% higher (P less than 0.05) in 31- than 4-mo-old rats. Glutathione S-transferase activity in the heart also declined with age (P less than 0.05 at 31 mo). Malondialdehyde contents in both heart homogenate and mitochondria were significantly increased at old age. Activity of several enzymes related to myocardial energy production, e.g., citrate synthase, malate dehydrogenase, and lactate dehydrogenase, as well as myocardial protein content showed an age-related decline. These data indicate that myocardial antioxidant capacity is weakened during aging and that the compensatory increases of mitochondrial SOD and GPX may be an important mechanism in coping with free radical damage in senescent heart. Findings in the present investigation seem to support the free radical theory of aging.

Aging↗
PubMed1990

Sodium D-lactate infusion of panic disorder patients.

Nineteen patients with panic disorder received sodium D,L-lactate (racemic) and pure sodium D-lactate infusions in a pilot study. Sodium D-lactate, which is less metabolically active than L-lactate, produced panic attacks in half the patients. D-Lactate also produced hypocapnia and alkalosis, indicating hyperventilation. These findings suggest that metabolism of lactate is not necessary for the induction of panic in susceptible patients. D-Lactate appears similar to other agents that cause panic in its capacity to stimulate respiration in the preliminary study.

Adult↗