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Tom Williams

Publications and source records attributed to Tom Williams.

4 recordsLinked to original sources
PubMed2004

Trisomy 14pter --> q21: a case with associated ovarian germ cell tumor and review of the literature.

We report a patient with trisomy X and a supernumerary marker chromosome. The marker chromosome was characterized by comparative genomic hybridization and shown to be derived from chromosome 14, resulting in trisomy for 14pter --> q21. The karyotype was thus redefined as 48,XXX,+mar.rev ish enh(14pterq21). The patient presented with facial dysmorphism and a high-pitched cry, exhibited severe developmental delay, and developed an aggressive ovarian immature teratoma. In this paper, we also review reports of 11 other patients with constitutional trisomy of the same chromosomal region. Previous studies have identified somatic gains of chromosome 14 in ovarian germ cell tumors. We propose that the constitutional gain of chromosomal 14 material may have predisposed to the development of this tumor.

Abnormalities, Multiple↗
PubMed2003

Pharmacokinetics and safety of ILX23-7553, a non-calcemic-vitamin D3 analogue, in a phase I study of patients with advanced malignancies.

PURPOSE: Differentiation therapy is an alternative to chemotherapy with potentially less toxicity, improved quality of life, and survival. We conducted a phase I trial of ILX23-7553, a formulation of 1,25-dihydroxy-16-ene-23-yne-vitamin D(3), a 1,25-dihydroxyvitamin D(3) analog with preclinically demonstrated antitumor and differentiating effects and diminished hypercalcemic effects. PATIENTS AND METHODS: The protocol consisted of five daily oral treatments during 14-day cycles at 15 dose levels from 1.3 to 45.0 mug/m(2)/day. We treated 42 heavily pretreated patients who had a variety of malignancies with 162 treatment cycles, and obtained pharmacokinetics from three patients at the two highest dose levels. RESULTS: There were no grade 3 or 4 toxicities. Grade 1-2 toxicities included diarrhea, nausea, fatigue, constipation, and one grade 1 hypercalcemia. Average day 6 calcium was 9.26 +/- 0.55 mg/dl in cycle 1 and 9.30 +/- 0.67 mg/dl in cycle 2. Pharmacokinetics at dose levels 14 (40 mug/m(2)/day) (1 patient) and 15 (45 mug/m(2)/day) (2 patients) demonstrated an average C(max) of 30.4 +/- 7.8 pg/ml (0.07 nM) and 104 +/- 38.2 pg/ml (0.25 nM), and AUCs of 222.5 +/- 225.2 pg.h/ml and 855 +/- 536 pg h/ml, respectively. Eight patients (19%) had stable disease. While in vitro effects have been reported at these concentrations, they were at least 10-fold lower than ED(50)s, and the study was terminated before an MTD was reached. CONCLUSION: The drug is safe and has potential benefits at serum concentrations where effects begin to be noted in vitro. Further study is needed with a reformulated higher unit dose compound to determine the safety and efficacy of higher serum concentrations.

Adult↗
PubMed2002

Integrating cancer genomics and proteomics in the post-genome era.

The dawn of the post-genome era is leading to extraordinary opportunities in biomedicine. Our group has embarked on a major effort to integrate genomics, transcriptomics and proteomics for the profiling of tumor tissues, an approach we refer to as operomics. Our major goals are the molecular classification of tumors and the identification of markers for the early detection of cancer. Molecular analyses of tumors rely on microdissected tissues, which are simultaneously investigated for genomic, transcriptomic and proteomic changes. Genomic alterations in tumor cells being investigated include deletions, amplifications and methylation changes across the entire genome as well as point mutations in specific genes. Expression analysis at the RNA level is being undertaken using oligonucleotide and cDNA based microarrays. An important aspect of our approach is the large-scale identification and quantitative analysis of tumor proteins in whole cell lysates as well as in protein compartments. Protein separation strategies include two-dimensional polyacrylamide gel electrophoresis and liquid chromatography. Specific protein subsets, of interest include membrane proteins, secreted proteins and antigenic proteins as sources of biomarkers for early detection of cancer. Our current approach is illustrated with findings stemming from our studies of human gliomas.

Brain Neoplasms↗