Publications by authors named "Christopher S Hamilton"

Purpose: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using (11)C-choline positron emission tomography PET scans in patients with localized prostate cancer.

Methods And Materials: This was an RT planning study of 8 patients with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)).

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Background And Purpose: To evaluate the accuracy of (11)C-choline PET scans in defining dominant intraprostatic lesions (DILs) for radiotherapy target volume definition.

Material And Methods: Eight men with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy were studied. Several methods were used to contour the DIL on the PET scans: visual, PET Edge, Region Grow, absolute standardised uptake value (SUV) thresholds and percentage of maximum SUV thresholds.

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Telomerase activity is primarily determined by transcriptional regulation of the catalytic subunit, human telomerase reverse transcriptase (hTERT). Several mRNA splice variants for hTERT have been identified, but it is not clear if telomerase activity is determined by the absolute or relative levels of full-length (functional) and variant hTERT transcripts. We have developed an SYBR green-based reverse transcription-quantitative polymerase chain reaction assay for the enumeration of the four common hTERT mRNA variants and correlated these with telomerase activity and telomere length in 24 human melanoma cell lines.

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To identify factors that can influence breast edema in women undergoing breast-conserving therapy. Breast edema was assessed clinically and via high frequency ultrasound (HFUS) prior to, during and following radiotherapy. Fifty-four women were assessed.

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RluA is a dual-specificity enzyme responsible for pseudouridylating 23S rRNA and several tRNAs. The 2.05 A resolution structure of RluA bound to a substrate RNA comprising the anticodon stem loop of tRNA(Phe) reveals that enzyme binding induces a dramatic reorganization of the RNA.

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The pseuoduridine synthases (psi synthases) isomerize uridine (U) to pseudouridine (psi) in RNA, and they fall into five families that share very limited sequence similarity but have the same overall fold and active-site architecture, including an essential Asp. The mechanism by which the psi synthases operate remains unknown, and mechanistic work has largely made use of RNA containing 5-fluorouridine (f5U) in place of U. The psi synthase TruA forms a covalent adduct with such RNA, and heat disruption of the adduct generates a hydrated product of f5U, which was reasonably concluded to result from the hydrolysis of an ester linkage between the essential Asp and f5U.

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The pseudouridine synthase TruB is responsible for the universally conserved post-transcriptional modification of residue 55 of elongator tRNAs. In addition to the active site, the "thumb", a peripheral domain unique to the TruB family of enzymes, makes extensive interactions with the substrate. To coordinate RNA binding and release with catalysis, the thumb may be able to sense progress of the reaction in the active site.

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All known pseudouridine synthases have a conserved aspartic acid residue that is essential for catalysis, Asp-48 in Escherichia coli TruB. To probe the role of this residue, inactive D48C TruB was oxidized to generate the sulfinic acid cognate of aspartic acid. The oxidation restored significant but reduced catalytic activity, consistent with the proposed roles of Asp-48 as a nucleophile and general base.

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Article Synopsis
  • The paper evaluates how decision models can help reduce systematic errors in portal imaging during conformal therapy for prostate cancer patients.
  • Daily and weekly portal images from 16 patients were analyzed, revealing small random variations but frequent systematic errors larger than 2 mm.
  • The Hotelling's evaluation process (HEP) effectively identified small systematic errors (2-4 mm) and, when combined with one-dimensional models, can significantly eliminate these errors in the critical early treatment phase.
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Introduction: Fatigue is commonly reported in patients receiving radiotherapy for breast conservation, but the underlying mechanisms remain unclear.

Methods: Patients with early breast cancer participating in a prospective study of the impact of inflammatory processes on early and delayed breast morbidity were assessed for fatigue levels using the Functional Assessment of Cancer Therapy (FACT) fatigue subscale before and at intervals during and after radiotherapy. Blood for analysis of a variety of circulating cytokines, coagulation factors, peripheral blood indices and biochemical factors was collected at the same time points.

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Purpose: To describe the natural history of mucosal changes, in particular the development of telangiectases in the rectum, after radiotherapy (RT) for prostate cancer.

Methods And Materials: Twenty patients undergoing local-field, nonconformal RT for prostate cancer underwent flexible sigmoidoscopy every 6 months for up to 3 years after RT completion. Telangiectasis was scored as absent, single, multiple, or multiple confluent.

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Purpose: To quantify the oral mucosal cell density and proliferation rate during conventional radiotherapy of head-and-neck tumors and to compare these parameters with clinical scoring of oral mucositis.

Materials And Methods: Between 1996 and 1999, 22 patients were included in this study. Mucosal biopsies were taken before or during the radiotherapy course (5 x 2 Gy/wk).

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