Fwd: Pattern of metastatic spread in triple-negative breast cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: Pattern of metastatic spread in triple-negative breast cancer.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res Treat. 2008 Jun 10;
Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA

Purpose The prognosis of women with triple-negative breast cancers (defined as cancers that are estrogen receptor-negative, progesterone receptor-negative and HER2/neu negative) is poor, compared to women with other subtypes of breast cancer. It is proposed that the underlying difference in recurrence rates may be explained in part by different routes of metastatic spread. Experimental design We studied a cohort of 1608 patients diagnosed with breast cancer, diagnosed between January 1987 and December 1997 at Women's College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor-negative, progesterone receptor-negative and HER2/neu-negative. We compared the incidence rates of metastatic spread to bone and to other (non-bone) organs in women with triple-negative and other forms of breast cancer. Results Of the 1,608 patients, 180 (11.2%) had triple-negative breast cancer. The 1608 women were followed for a median of 9.0 years (range 0.1-19 years). Compared to other patients, those with triple-negative breast cancer had an increased likelihood of distant recurrence over the study period (adjusted hazard ratio (HR) 1.9; 95% CI: 1.5-2.5, P

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Fwd: No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: No significance of derivative chromosome 9 deletion on the clearance kinetics of BCR/ABL fusion transcripts, cytogenetic or molecular response, loss of response, or treatment failure to imatinib mesylate therapy for chronic myeloid leukemia.
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[1]Cancer. 2008 Jun 9;
Kim DH, Popradi G, Sriharsha L, Kamel-Reid S, Chang H, Messner HA, Lipton JH

BACKGROUND.: Although deletion of the derivative chromosome 9 (der 9; del-der 9) carries a poor prognosis in patients with chronic myeloid leukemia (CML) who are treated with hydroxyurea or interferon, its significance in patients on imatinib mesylate (IM) therapy is debated. METHODS.: In the current study, the authors used a locus-specific indicator breakpoint cluster region/receptor tyrosine kinase (BCR/ABL) probe to evaluate the significance of del-der 9 in 163 patients with CML who had fluorescence in situ hybridization (FISH) results available. Serial changes in BCR/ABL fusion transcript levels also were monitored by using messenger RNA (mRNA) quantitative polymerase chain reaction (PCR). RESULTS.: Of 163 patients, 22 (13.5%) had del-der 9 before commencing IM therapy. No differences were noted in the time to hematologic response (P = .598), major cytogenetic response (CyR) (P = .281), complete CyR (P = .883), major molecular response (MoR) (P = .125), or complete MoR (P = .834). In addition, the times to loss of response (LOR) (P = .974), treatment failure (P = .455; including primary hematologic or cytogenetic resistance and LOR), transformation-free survival (P = .276), and dose escalation of IM (P = .816) did not differ significantly between patients with and without del-der 9. The results of serial BCR/ABL mRNA quantitative PCR revealed similar patterns of BCR/ABL fusion gene reduction between the 2 groups. CONCLUSIONS.: The presence of del-der 9 in patients with CML did not influence 1) the response to IM therapy in terms of hematologic response, CyR, or MoR; 2) LOR; 3) treatment failure; 4) progression to accelerated phase/blast crisis; or 5) time to dose escalation of IM. Therefore, the authors concluded that the detection of del-der 9 does not have an impact on the current management of patients with CML who are receiving IM therapy. Cancer 2008. (c) 2008 American Cancer Society.



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Fwd: Promoter methylation profile in preneoplastic and neoplastic gallbladder lesions.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: Promoter methylation profile in preneoplastic and neoplastic gallbladder lesions.
To: mesothelioma77@gmail.com


[1]Mol Carcinog. 2008 Jun 9;
García P, Manterola C, Araya JC, Villaseca M, Guzmán P, Sanhueza A, Thomas M, Alvarez H, Roa JC

Gallbladder carcinoma (GBC) is a highly malignant neoplasm and represents the leading cause of cancer death in Chilean women. In order to determine the potential role of promoter methylation in gallbladder carcinogenesis, we investigated the frequency of this epigenetic mechanism by methylation-specific polymerase chain reaction (MSP) in 35 chronic cholecystitis (CC, separated according to the presence or absence of metaplasia), 19 early cancers (mucosa or muscularis propia invasion) and 48 advanced carcinomas with invasion of the gallbladder subserosa (25 cases) and serosa (23 cases). We examined 14 genes and observed an increase of multigenic methylation during tumoral progression which was not significantly associated with the patient's age. Four genes (DAPK1, DLC1, TIMP3, and RARbeta2) displayed a progressive increase in their methylation status from CC without metaplasia to advanced carcinoma invading the serosa layer (P

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Fwd: Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells.
To: mesothelioma77@gmail.com


[1]Oncogene. 2008 Jun 9;
Ueki T, Nishidate T, Park JH, Lin ML, Shimo A, Hirata K, Nakamura Y, Katagiri T

To investigate the detailed molecular mechanism of mammary carcinogenesis and discover novel therapeutic targets, we previously analysed gene expression profiles of breast cancers. We here report characterization of a significant role of DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein) in mammary carcinogenesis. Semiquantitative RT-PCR and northern blot analyses confirmed upregulation of DTL/RAMP in the majority of breast cancer cases and all of breast cancer cell lines examined. Immunocytochemical and western blot analyses using anti-DTL/RAMP polyclonal antibody revealed cell-cycle-dependent localization of endogenous DTL/RAMP protein in breast cancer cells; nuclear localization was observed in cells at interphase and the protein was concentrated at the contractile ring in cytokinesis process. The expression level of DTL/RAMP protein became highest at G(1)/S phases, whereas its phosphorylation level was enhanced during mitotic phase. Treatment of breast cancer cells, T47D and HBC4, with small-interfering RNAs against DTL/RAMP effectively suppressed its expression and caused accumulation of G(2)/M cells, resulting in growth inhibition of cancer cells. We further demonstrate the in vitro phosphorylation of DTL/RAMP through an interaction with the mitotic kinase, Aurora kinase-B (AURKB). Interestingly, depletion of AURKB expression with siRNA in breast cancer cells reduced the phosphorylation of DTL/RAMP and decreased the stability of DTL/RAMP protein. These findings imply important roles of DTL/RAMP in growth of breast cancer cells and suggest that DTL/RAMP might be a promising molecular target for treatment of breast cancer.Oncogene advance online publication, 9 June 2008; doi:10.1038/onc.2008.186.



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Fwd: Anthropometric factors and breast cancer risk among urban and rural women in South India: a multicentric case-control study.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: Anthropometric factors and breast cancer risk among urban and rural women in South India: a multicentric case-control study.
To: mesothelioma77@gmail.com


[1]Br J Cancer. 2008 Jun 10;
Mathew A, Gajalakshmi V, Rajan B, Kanimozhi V, Brennan P, Mathew BS, Boffetta P

Breast cancer (BC) incidence in India is approximately twice as high in urban women than in rural women, among whom we investigated the role of anthropometric factors and body size. The study was conducted at the Regional Cancer Centre, Trivandrum, and in three cancer hospitals in Chennai during 2002-2005. Histologically confirmed cases (n=1866) and age-matched controls (n=1873) were selected. Anthropometric factors were measured in standard ways. Information on body size at different periods of life was obtained using pictograms. Odds ratios (OR) of BC were estimated through logistic regression modelling. Proportion of women with body mass index (BMI)>25.0 kg/m(2), waist size >85 cm and hip size >100 cm was significantly higher among urban than rural women. Risk was increased for waist size >85 cm (pre-menopausal: OR=1.24, 95% CI: 0.96-1.62; post-menopausal: 1.61, 95% CI: 1.22-2.12) and hip size >100 cm (pre-menopausal: OR=1.47, 95% CI: 1.05-2.06; post-menopausal 2.42, 95% CI: 1.72-3.41). Large body size at age 10 (OR=1.75, 95% CI: 1.01-3.03) and increased BMI (OR=1.33, 95% CI: 1.05-1.69 for 25.0-29.9 kg/m(2) and OR=1.56, 95% CI: 1.03-2.35 for 30+ kg/m(2)) were associated with pre-menopausal BC risk. Our data support the hypotheses that increased anthropometric factors are risk factors of BC in India.British Journal of Cancer advance online publication, 10 June 2008; doi:10.1038/sj.bjc.6604423 www.bjcancer.com.



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Fwd: Somatically Acquired Hypomethylation of IGF2 in Breast and Colorectal Cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: Somatically Acquired Hypomethylation of IGF2 in Breast and Colorectal Cancer.
To: mesothelioma77@gmail.com


[1]Hum Mol Genet. 2008 Jun 9;
Ito Y, Koessler T, Ibrahim AE, Rai S, Vowler SL, Abu-Amero S, Silva AL, Maia AT, Huddleston JE, Uribe-Lewis S, Woodfine K, Jagodic M, Nativio R, Dunning A, Moore G, Klenova E, Bingham S, Pharoah PD, Brenton JD, Beck S, Sandhu MS, Murrell A

The imprinted Insulin-like growth factor 2 gene (IGF2) is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from Colorectal cancer patients (SEARCH (n= case 192, controls 96)), breast cancer patients (ABC (n= case 364, controls 96)) and the European Prospective Investigation of Cancer (EPIC-Norfolk (n=breast 228, colorectal 225, controls 895)), were analysed. The EPIC samples were collected two to five years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI.



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Fwd: Design and validation of specific inhibitors of 17{beta}-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jun 11, 2008 at 11:46 PM
Subject: Design and validation of specific inhibitors of 17{beta}-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis.
To: mesothelioma77@gmail.com


[1]Endocr Relat Cancer. 2008 Jun 9;
Day J, Tutill H, Purohit A, Reed M

17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are enzymes which are responsible for reduction or oxidation of hormones, fatty acids and bile acids in vivo, regulating the amount of the active form which is available to bind to its cognate receptor. All require NAD(P)(H) for activity. Fifteen 17beta-HSDs have been identified to date, and with one exception, 17beta-HSD Type 5 (17beta-HSD5), an aldo-keto reductase (AKR), they are all short chain dehydrogenases / reductases (SDRs), although overall homology between the enzymes is low. Although named as 17beta-HSDs, reflecting the major redox activity at the 17beta-position of the steroid backbone, the activities of these fourteen enzymes vary, with several of the 17beta-HSDs able to reduce and/or oxidise multiple substrates at various positions. These activities are involved in the progression of a number of diseases, including those related to steroid metabolism. Despite the success of inhibitors of steroidogenic enzymes in the clinic, such as those of aromatase and steroid sulphatase, the development of inhibitors of 17beta-HSDs is at a relatively early stage, as at present none have yet reached clinical trials. However, many groups are now working on inhibitors specific for several of these enzymes for the treatment of steroid-dependent diseases, including breast and prostate cancer, and endometriosis, with demonstrable efficacy in in vivo disease models. In this review the recent advances in the validation of these enzymes as targets for the treatment of these diseases, with emphasis on 17beta-HSD1, 3, and 5, the development of specific inhibitors, the models used for their evaluation, and their progress towards the clinic will be discussed.



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