PubMed Health⌕ Search

Biomedical subjects

Roger Owen

Publications and source records attributed to Roger Owen.

8 recordsLinked to original sources
PubMed2006

Update on treatment recommendations from the Third International Workshop on Waldenstrom's macroglobulinemia.

Waldenström macroglobulinemia (WM) is a B-cell disorder characterized by the infiltration of lymphoplasmacytic cells into bone marrow and the presence of an IgM monoclonal gammopathy. As part of the Third International Workshop on WM, held October 7 to 10, 2004 in Paris, France, a consensus panel charged with providing treatment recommendations for WM updated its recommendations on both frontline and salvage therapies. The panel considered encouraging results from recent studies that addressed the use of extended-dose rituximab as well as other treatment options: therapy with either nucleoside analogs and alkylator agents, rituximab in combination with nucleoside analogs, nucleoside analogs plus alkylator agents, or combination chemotherapies, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or cyclophosphamide and dexamethasone. The panel determined that these were reasonable treatment options for WM patients and such therapeutic approaches were likely to yield results that are at least as good as if not better than the currently recommended use of single-agent alkylator, nucleoside analog, or standard-dose rituximab therapy. Such approaches were deemed to be reasonable treatment for WM patients in both the upfront and salvage settings, though randomized studies addressing the efficacy and toxicity of such novel approaches over previously established standard of care options are needed.

Alkylating Agents↗
PubMed2006

Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia.

This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial.

BACKGROUND AND PURPOSE: Unlike squamous carcinomas, breast adenocarcinoma may be as sensitive to fraction size as late dose-limiting normal tissues. If so, fewer larger fractions would be as safe and effective as regimens based on 2.0 Gy fractions. The first step is to test the effects of radiotherapy fractions >2.0 Gy on late normal tissue responses in the breast after tumour excision and radiotherapy for early breast cancer. PATIENTS AND METHODS: One thousand four-hundred and ten women with T1-3 N0-1 M0 invasive breast cancer were randomised between 1986-98 into one of three radiotherapy regimens after local tumour excision of early stage breast cancer; 50 Gy in 25 fractions (F) vs two dose levels of a test schedule giving 39 or 42.9 Gy in 13 F over 5 weeks. Fraction sizes were 2.0, 3.0 and 3.3 Gy, respectively. The primary endpoint was late change in breast appearance compared to post-surgical appearance scored from annual photographs blinded to treatment allocation. Secondary endpoints included palpable breast induration (fibrosis) and ipsilateral tumour recurrence. RESULTS: After a minimum 5-year follow up, the risk of scoring any change in breast appearance after 50 Gy/25 F, 39 Gy/13 F and 42.9 Gy/13 F was 39.6, 30.3 and 45.7%, from which an alpha/beta value of 3.6 Gy (95% CI 1.8-5.4) is estimated. The alpha/beta value for palpable breast induration was 3.1 Gy (95% CI 1.8-4.4). CONCLUSIONS: An alpha/beta value of around 3 Gy for late normal tissue changes in the breast is derived from the estimated equivalence of 41.6 Gy in 13 fractions and 50 Gy in 25 fractions over 5 weeks, in line with trial predictions.

Adenocarcinoma↗
PubMed2005

Splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is an indolent B cell malignancy usually involving spleen, bone marrow and blood. The disease presents as an incidental finding or with symptoms of splenic enlargement or anaemia. Diagnosis is based on a combination of lymphocyte morphology, immunophenotype and marrow and /or splenic histology. There is no genetic abnormality specific for SMZL, but deletions of chromosome 7q are the commonest abnormality and are found in 30-50% of cases. SMZL cells may have either mutated or unmutated immunoglobulin variable region genes and probably arise from different subsets of splenic marginal zone B cells. Prognostic factors are poorly defined and only loss or mutation of the p53 gene is consistently associated with a poor outcome. Therapeutic options include splenectomy, splenic irradiation, alkylating agents, purine analogues or anti CD20 antibody. The median survival is 10-13 years and most disease-related deaths are associated with transformation to diffuse large cell lymphoma.

DNA Mutational Analysis↗
PubMed2005

TGFB1 polymorphisms are associated with risk of late normal tissue complications in the breast after radiotherapy for early breast cancer.

Recent studies suggest that normal tissue radiosensitivity is influenced by single nucleotide polymorphisms (SNPs) in certain genes. In order to seek a confirmation of these findings, this study investigated SNPs in genes TGFB1 (position -509, codon 10 and codon 25), SOD2 (codon 16), XRCC1 (codon 399), XRCC3 (codon 241), APEX (codon 148) and ATM (codon 1853) in 26 breast cancer patients with marked changes in breast appearance after radiotherapy and 26 matched controls. Statistically significant associations were found between the TGFB1 codon 10 Pro allele (P=0.005) as well as the TGFB1 position -509 T allele (P=0.018) and increased risk of altered breast appearance. No significant associations were found for the remaining SNPs.

Breast Neoplasms↗
PubMed2002

Variation in the manganese superoxide dismutase gene (SOD2) is not a major cause of radiotherapy complications in breast cancer patients.

BACKGROUND AND PURPOSE: Small proportions of patients receiving radiotherapy develop marked long-term radiation damage. It is thought that this is due, at least in part, to intrinsic differences in cellular radiosensitivity, but the underlying mechanism is unknown. Reactive oxygen species are involved in cellular radiation damage, hence inter-individual differences in free radical detoxification may be related to radiosensitivity. Within mitochondria manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species. MnSOD has been linked to expression of malignant phenotype and apoptosis and polymorphic variation in the gene, SOD2 to risk of breast cancer. MATERIALS AND METHODS: Forty-one breast cancer patients developing marked changes in breast appearance after radiotherapy and 39 patients who showed no clinically detectable reaction after radiotherapy were analyzed for germline sequence variation in SOD2. RESULTS: The Ala-9Val polymorphism was detected, but no other sequence variants were detected in SOD2. Both alleles of the Ala-9Val polymorphism were equally distributed between the two patient groups. CONCLUSIONS: Sequence variation in SOD2 is not the major cause of radiotherapy complications in women with breast cancer.

Breast↗
PubMed2002

Muscarinic receptor antagonist-induced lenticular opacity in rats.

Investigations on compound A, an M2-sparing M3 muscarinic receptor antagonist, showed that focal polar anterior subcapsular lenticular opacities, characterized by focal epithelial proliferation, developed in Sprague-Dawley rats. The incidence and bilateral localization of this change increased generally with dose and time, though plateauing after 8 months of treatment; however the severity progressed very slightly. Over a 1-year period, no anterior cortical lens fiber changes or other histological ocular changes developed. A decreased severity of the change and apoptosis suggested some regression after a 26-week recovery period. Two nonselective muscarinic receptor antagonists, atropine and tolterodine, induced similar lenticular changes in rats. A hypothesis in relation to an indirect effect of the drug, such as increased illumination of the lens due to mydriasis observed with all these compounds, was investigated and disproven. Because these opacities are induced by structurally unrelated muscarinic receptor antagonists (atropine and tolterodine), it is likely that these lenticular changes are the result of muscarinic receptor inhibition. However, hypotheses regarding a direct effect of the drug on muscarinic receptors in the lens epithelium, possibly mediated by drug and/or metabolite(s) in the aqueous humor and/or lens epithelium, remain to be investigated. This lenticular opacity is similar to that observed spontaneously in Sprague-Dawley rats, although the latter occur at a lower incidence. No such lenticular opacities have been reported in other animal species, including man, after treatment with muscarinic receptor antagonists.

Animals↗