Fwd: Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: Delineation of clinical subtypes.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Fri, Jun 13, 2008 at 11:19 PM
Subject: Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: Delineation of clinical subtypes.
To: mesothelioma77@gmail.com


[1]Am J Med Genet A. 2008 Jun 11;
García-Castillo H, Vásquez-Velásquez AI, Rivera H, Barros-Núñez P

Mosaic variegated aneuploidy (MVA) is a rare autosomal recessive syndrome related to BUB1B gene mutations and characterized by multiple mosaic aneuploidies, cancer predisposition, and a distinct phenotype. We report on two mildly affected sibs with MVA syndrome but without BUB1B mutation. Both patients exhibited growth retardation, frontal bossing, triangular face and micrognathia but not microcephaly or cancer. Aneuploidies were assessed both in G-banded metaphases from lymphocyte cultures and in interphase nuclei from buccal cells by FISH. Screening of 23 exons and intron-exon boundaries of BUB1B was also carried out. These patients were then compared with other 19 MVA patients screened for BUB1B mutations. Around one half of the cultured lymphocytes from our patients had aneuploidies ranging from nullisomies to heptasomies; the most frequent abnormalities were trisomies (42%) and monosomies (28%). FISH results demonstrated more chromosomal losses than gains. Screening of BUB1B in our two patients failed to identify any mutation. A review of the 21/35 patients screened for BUB1B demonstrated three clinical pictures. Patients with monoallelic BUB1B mutations were severely affected with Dandy-Walker complex (7/8), cataracts (6/6), and Wilms' tumor (7/8); premature chromatid separation (PCS) was observed in 8/8 propositi and 7/7 carrier parents. Patients without BUB1B mutations were mildly affected with no evidence of cancer, Dandy-Walker malformation or cataract, and rarely (1/7) showed PCS. Finally, patients with biallelic BUB1B mutations showed a moderate phenotype. The distinct MVA clinical groups delineated here point to involvement of at least another mitotic spindle checkpoint gene in addition to the BUB1B gene. (c) 2008 Wiley-Liss, Inc.



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Source: http://www.hubmed.org/display.cgi?uids=18548531
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Fwd: Direct uterine sampling with the Tao brush sampler using a liquid-based preparation method for the detection of endometrial cancer and atypical hyperplasia: a feasibility study.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Fri, Jun 13, 2008 at 11:19 PM
Subject: Direct uterine sampling with the Tao brush sampler using a liquid-based preparation method for the detection of endometrial cancer and atypical hyperplasia: a feasibility study.
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[1]Cancer. 2008 Jun 11;
Kipp BR, Medeiros F, Campion MB, Distad TJ, Peterson LM, Keeney GL, Halling KC, Clayton AC

BACKGROUND.: Endometrial cytology sampling devices for direct uterine sampling have been shown in previous studies to be a reliable and relatively painless method for detecting endometrial lesions. The purpose of the current study was to determine the performance characteristics of endometrial cytology for the detection of malignancy and atypical hyperplasia using liquid-based cytology specimens collected with the Tao brush sampler. METHODS.: Brushings of the endometrial cavity were obtained from 139 hysterectomy specimens before routine histopathologic evaluation. Cytology specimens were fixed in PreservCyt and processed using ThinPrep technology. Cytology diagnoses were classified as nondiagnostic, negative, atypical, or positive for malignancy. Histopathologic findings were used as the gold standard for determining the performance characteristics of cytology. RESULTS.: Histopathologic results from the 139 patients included 81 (58%) endometrial cancers, 7 (5%) complex hyperplasias with atypia, 2 (1%) complex hyperplasias without atypia, and 49 (35%) patients with benign histology. The number of specimens diagnosed cytologically as positive, atypical, negative, or nondiagnostic was 60 (43%), 40 (29%), 37 (27%), and 2 (1%) specimens, respectively. The overall sensitivity and specificity of cytology for detecting endometrial cancer and atypical hyperplasia were 95% and 66% when atypical cytology specimens were considered positive. CONCLUSIONS.: The results of the current study indicate that direct endometrial sampling by liquid-based endometrial cytology collected with the Tao brush sampler produces specimens that contain cellular material that may be identified as endometrial cancer or atypical hyperplasia. Both atypical and positive cytology diagnoses are indicators for triage to more specific methods of diagnosis. Cancer (Cancer Cytopathol) 2008. (c) 2008 American Cancer Society.



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Source: http://www.hubmed.org/display.cgi?uids=18548528
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Fwd: Anastrozole : a review of its use in postmenopausal women with early-stage breast cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Jun 13, 2008 at 11:19 PM
Subject: Anastrozole : a review of its use in postmenopausal women with early-stage breast cancer.
To: mesothelioma77@gmail.com


[1]Drugs. 2008; 68(9): 1319-40
Sanford M, Plosker GL

Anastrozole (Arimidex((R))) is an aromatase inhibitor approved in the EU, the US and in other countries worldwide for use as an adjuvant treatment in postmenopausal women with early-stage, hormone receptor-positive breast cancer. It is also approved in the EU and other countries worldwide for continuing adjuvant treatment in women who have already had 2-3 years of adjuvant tamoxifen treatment for breast cancer.Anastrozole is an effective primary adjuvant treatment for postmenopausal women with early-stage breast cancer. In patients with hormone receptor-positive tumours, 5 years of anastrozole treatment was more efficacious in reducing breast cancer recurrence than 5 years of tamoxifen, both in a head-to-head comparison and in switching trials when given after 2-3 years of tamoxifen treatment. The treatment benefits have now been shown to extend to 100 months following breast surgery. To date, overall survival was better in anastrozole than tamoxifen recipients in one switching trial and in a meta-analysis of three switching trials. There was no increased benefit in health-related quality of life with anastrozole over tamoxifen. In women who had received 5 years of tamoxifen treatment, continuation of treatment with anastrozole further reduced the risk of breast cancer recurrence. Ongoing head-to-head trials against other third-generation aromatase inhibitors will provide data as to its relative efficacy against these agents. Anastrozole is a generally well tolerated treatment for early-stage breast cancer. Like other aromatase inhibitors, its most important adverse effect was an increased risk of bone fractures, which for anastrozole was restricted to the treatment period. It is still unclear whether primary adjuvant treatment extended beyond 5 years is of benefit and whether primary adjuvant treatment with anastrozole for 5 years is preferable to switching to anastrozole after 2-3 years of tamoxifen treatment. However, the evidence to date establishes anastrozole as a valuable adjuvant and extended adjuvant treatment for postmenopausal women with hormone receptor-positive, early-stage breast cancer.



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Source: http://www.hubmed.org/display.cgi?uids=18547136
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Fwd: Overweight, obesity and breast cancer prognosis: optimal body size indicator cut-points.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, Jun 13, 2008 at 11:19 PM
Subject: Overweight, obesity and breast cancer prognosis: optimal body size indicator cut-points.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res Treat. 2008 Jun 12;
Majed B, Moreau T, Asselain B,

Background Evidence from the data provided in numerous published articles indicates that obesity and overweight can have a negative prognosis role in breast cancer. However, different Body Size Indicators (BSI) and cut-points have been employed and may partly explain discrepancies between the findings of various studies. Material and methods 14,709 women were recruited, treated and followed for a first unilateral breast cancer. After randomly splitting the patients' data into two groups, a maximum statistical outcome approach was used to select optimal BSI cut-points from a "training sample", when prognosis events were investigated. External validation was then carried out using a "validation sample", and agreement between the selected optimal BSI cut-points was assessed. Body Mass Index (BMI), weight (W), Ideal Weight Ratio (IWR) and Body Surface Area (BSA) were used, and were assessed at the time of diagnosis. Results The selected optimal BSI cut-points were reliable when overall survival, metastasis recurrence and disease free interval events were investigated. The chosen BMI cut-point values matched the overweight cut-point value given by the World Health Organization. Agreement between defined binary BSI was acceptable; however, it varied from "fair" to "very good". Analysis of second primary cancer occurrence and contralateral recurrence events was not conclusive. When local and node recurrence events were taken into account, the results were inconsistent and were linked to an unconfirmed relationship between stoutness and these prognosis events. Conclusions Efficient, optimal BSI cut-points indicate a poorer prognosis, illustrated by a shortened overall survival and an increase of metastasis recurrences, from a BMI value of 25 kg/m(2), a W value of 60 kg, an IWR value of 20% and a BSA value of 1.7 m(2). Further BSI cut-point investigations are needed, taking into account contralateral recurrence and second primary cancer events.



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Source: http://www.hubmed.org/display.cgi?uids=18546073
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