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Sunday, April 20, 2008

Fwd: Acute Radiation Dermatitis and Pneumonitis in Japanese Breast Cancer Patients with Whole Breast Hypofractionated Radiotherapy Compared to Conventional Radiotherapy.



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Apr 19, 2008 at 5:00 AM
Subject: Acute Radiation Dermatitis and Pneumonitis in Japanese Breast Cancer Patients with Whole Breast Hypofractionated Radiotherapy Compared to Conventional Radiotherapy.
To: mesothelioma77@gmail.com


[1]Jpn J Clin Oncol. 2008 Apr 16;
Osako T, Oguchi M, Kumada M, Nemoto K, Iwase T, Yamashita T

OBJECTIVE: To evaluate acute morbidity, radiation dermatitis and pneumonitis, of Japanese patients treated with whole breast hypofractionated radiotherapy (RT) after breast-conserving surgery (BCS), compared to conventional RT. METHODS: Japanese patients who received whole breast RT after BCS between October 2003 and September 2006 were retrospectively reviewed. Patients who had selected the conventional or hypofractionated schedule received whole breast irradiation of 50 Gy in 25 fractions plus boost or 40 Gy in 16 fractions plus boost. Radiation dermatitis and symptomatic pneumonitis were graded according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Of 443 consecutive patients, 377 (85%) received the conventional schedule and 66 (15%) received the hypofractionated schedule. Of patients treated with the conventional schedule, Grade 0, 1, 2 and 3 radiation dermatitis were observed in 16 (4%), 278 (74%), 77 (20%) and 6 (2%), respectively. Of patients treated with the hypofractionated schedule, Grade 0, 1, 2 and 3 dermatitis were observed in 11 (17%), 49 (74%), 5 (8%) and 1 (1%), respectively. Grade 2-3 dermatitis by the hypofractionated schedule (9%) was observed less frequently than that by the conventional schedule (22%) (chi-square test; P = 0.016). Moreover, of patients treated with the conventional schedule, 4 (1%) had Grade 2 radiation pneumonitis. No patient treated with the hypofractionated schedule had symptomatic pneumonitis. CONCLUSIONS: Radiation dermatitis and pneumonitis in Japanese patients treated with the hypofractionated schedule is acceptable. Especially, radiation dermatitis by the hypofractionated schedule is milder than that by the conventional schedule.



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Source: http://www.hubmed.org/display.cgi?uids=18417501
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Fwd: Convergence on chromatin of non-genomic and genomic pathways of hormone signaling.



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Apr 19, 2008 at 5:00 AM
Subject: Convergence on chromatin of non-genomic and genomic pathways of hormone signaling.
To: mesothelioma77@gmail.com


[1]J Steroid Biochem Mol Biol. 2008 Mar 13;
Vicent GP, Ballaré C, Nacht AS, Clausell J, Subtil-Rodríguez A, Quiles I, Jordan A, Beato M

Gene regulation by steroid hormones involves genomic and non-genomic signaling pathways and the relationship between these two pathways is unknown. Genomic actions are often mediated by binding of the ligand-activated hormone receptors to hormone responsive elements (HREs) followed by recruitment of co-regulators, remodeling of chromatin and formation of the transcription initiation complex. The non-genomic effects of steroid hormones involve the rapid and transient activation of several kinase cascades often mediated by a subpopulation of "nuclear" receptors located in the cytoplasmic side of the cell membrane. The progesterone effect on breast cancer cell proliferation involves activation of the Src/Ras/Erk cascade mediated by a specific interaction between two domains of the N-terminal half of PR and the ligand-binding domain of ERalpha. Unexpectedly, selective inhibition of Erk, or its target kinase Msk1, interferes with chromatin remodeling and blocks MMTV transcriptional activation. A complex of activated PR, Erk and Msk1 is recruited to promoter already 5min after hormone treatment and phosphorylates histone H3 at serine 10, leading to displacement of HP1gamma, as a requisite for recruitment of Src1, chromatin remodeling complexes (hSnf2h and Brg1) and RNA polymerase II. Thus, activation of signaling cascades in the cytoplasm is essential for chromatin remodeling and transcriptional activation of a subset of steroid hormone target genes.



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Fwd: Population-Calibrated Gene Characterization: Estimating Age at Onset Distributions Associated With Cancer Genes.



---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Apr 19, 2008 at 5:00 AM
Subject: Population-Calibrated Gene Characterization: Estimating Age at Onset Distributions Associated With Cancer Genes.
To: mesothelioma77@gmail.com


[1]J Am Stat Assoc. 2005; 100: 399-409
Iversen ES, Chen S

Phenotypic characterization of rare disease genes poses a significant statistical challenge, but the need to do so is clear. Clinical management of patients carrying a disease gene depends crucially on an accurate characterization of the genetically predisposed disease, including its likelihood of occurrence among mutation carriers, natural history, and response to treatment. We propose a formal yet practical method for controlling for bias due to ignoring ascertainment, defined as the sampling mechanism, when quantifying the association between genotype and disease using data on high-risk families. The approach is more statistically efficient than conditioning on the variables used in sampling. In it, the likelihood is adjusted by a factor that is a function of sampling weights in strata defined by those variables. It requires that these variables and the sampling probabilities in the strata they define either are known or can be estimated. The latter requires a second, population-based dataset. As an example, we derive ascertainment-corrected estimates of penetrance for the breast cancer susceptibility genes BRCA1 and BRCA2. The Bayesian analysis that we use incorporates a modified segregation model and prior data on penetrance derived from the literature. Markov chain Monte Carlo methods are used for inference.



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Source: http://www.hubmed.org/display.cgi?uids=18418465
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