Fwd: Successful Salvage Robotic-Assisted Radical Prostatectomy After External Beam Radiotherapy Failure.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Successful Salvage Robotic-Assisted Radical Prostatectomy After External Beam Radiotherapy Failure.
To: mesothelioma77@gmail.com


[1]Urology. 2008 Jun 3;
Jamal K, Challacombe B, Elhage O, Popert R, Kirby R, Dasgupta P

We describe the first case of salvage robotic-assisted radical prostatectomy for local recurrence after external beam radiotherapy. A 50-year-old man initially underwent combined external beam radiotherapy and hormonal treatment for Stage T2a prostate adenocarcinoma. The prostate-specific antigen level was 10.5 ng/mL, and the Gleason score was 3+3. Two years later, he developed biopsy-proven recurrent disease. He underwent salvage robotic-assisted radical prostatectomy. The patient was discharged on day 1 postoperatively. The histologic analysis revealed an organ-confined tumor. His prostate-specific antigen at 3 months was

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Fwd: Major contribution of MEK1 to the activation of ERK1/ERK2 and to the growth of LS174T colon carcinoma cells.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Major contribution of MEK1 to the activation of ERK1/ERK2 and to the growth of LS174T colon carcinoma cells.
To: mesothelioma77@gmail.com


[1]Biochem Biophys Res Commun. 2008 Jun 1;
Shama J, Garcia-Medina R, Pouysségur J, Vial E

Mammalian cells express two closely related MEK isoforms, MEK1 and MEK2, upstream of the ERK1/ERK2 MAPK module. Although genetic studies have suggested that MEK1 and MEK2 do not have overlapping functions in vivo, little is known about their specific contribution to the activation of ERKs and to tumor cell proliferation. We used Tet-inducible shRNA to investigate the independent role of MEK1 and MEK2 for the oncogenic and the serum-induced activation of ERK1 and ERK2 in LS174T colon carcinoma cells. We show that MEK1 is the main activator of both ERK1 and ERK2. MEK2 removal has no impact by itself but it can cooperate with MEK1 ablation for the inhibition of ERK1/2 activity. In addition, we show that MEK1 is the critical isoform regulating tumor cell proliferation in vitro and in vivo.



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Fwd: Contribution of demographic, psychological and disease-related factors to quality of life in women with high-grade vulval intraepithelial neoplasia.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Contribution of demographic, psychological and disease-related factors to quality of life in women with high-grade vulval intraepithelial neoplasia.
To: mesothelioma77@gmail.com


[1]Gynecol Oncol. 2008 Jun 2;
Shylasree TS, Karanjgaokar V, Tristram A, Wilkes AR, Maclean AB, Fiander AN

AIMS AND OBJECTIVES: To quantify the effect of demographic, psychological and disease-related factors on Quality of life (QoL) outcomes in women with high-grade vulval intraepithelial neoplasia (VIN2-3). To obtain qualitative data on the effect of disease and treatment in these women and their partners. To assess the participants' perception of their risk of developing of vulval cancer and its relation to QoL outcomes. METHODS: A questionnaire was constructed using existing instruments to measure the effect of demographic, psychological and disease-related factors on QoL outcomes. Free text space was provided for qualitative data. The questionnaire was mailed to women attending two specialist VIN clinics. RESULTS: One hundred and fifty women were invited for the study. Eighty-two responded (54.6%) of which forty-four (53.6%) were sexually active. Demographic factors (age and or living situation) had a significant effect on emotional health and body image. Psychological factors (anxiety and depression) had a significant effect on all aspects of QoL. Disease-related factors did not have a measurable effect on QoL outcomes, although the qualitative data revealed that various aspects of VIN had affected the lives of these women and their partners. There was a significant positive association between a perceived risk of developing vulval cancer with worsening general and emotional health. CONCLUSION: Psychological co-morbidity and various demographic factors should be considered while managing women with VIN. Accurate information regarding the development of vulval cancer should be given. The findings of this preliminary study will assist the construction of VIN-specific QoL instruments in the future.



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Fwd: Measuring physiological properties of lymphoedemous tissues by ultrasound: theoretical foundations.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Measuring physiological properties of lymphoedemous tissues by ultrasound: theoretical foundations.
To: mesothelioma77@gmail.com


[1]J Acoust Soc Am. 2008 May; 123(5): 3226
Barbone PE, Leiderman R, Bamber J, Berry G, Oberai AA, Zhang Y

Roughly one in four breast cancer survivors report some degree of arm oedema. Lymphoedema is a build-up of excess lymph fluids in the tissues. Persistent lymphoedema leads to pain, diminished limb function, increased risk of infection, soft tissue fibrosis, and severe cases can be grossly disfiguring. From a mechanics perspective, the lymphoedemous tissue may be thought of as a two phase composite, consisting of both fluid and solid phases. Here we discuss the use of composites mixture theory to model the mechanics of lymphoedemous tissues. By treating the tissue as a fluid-solid composite, rules-of-mixtures may be used to estimate the effective moduli in terms of the properties of the individual components and their respective volume fractions in these two states. The mechanical properties of the tissue may be measured in vivo using a generalization of the methods of ultrasound elasticity imaging. We discuss how the measured ''effective stiffness" depends upon whether the tissue is drained or undrained, and how ultrasound may be used to measure these properties. Thus we explore the possibility of evaluating volume fractions and component properties of the individual tissue phases from ultrasound elasticity imaging.



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Fwd: Development and verification of a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Development and verification of a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer.
To: mesothelioma77@gmail.com


[1]J Cancer Res Clin Oncol. 2008 Jun 5;
Yonemori K, Katsumata N, Noda A, Uno H, Yunokawa M, Nakano E, Kouno T, Shimizu C, Ando M, Tamura K, Takeuchi M, Fujiwara Y

PURPOSE: The aim of this study was to develop a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer. METHODS: We retrospectively analyzed a training set of 105 patients with metastatic or recurrent breast cancer. Their chemotherapeutic response had been evaluated according to the World Health Organization (WHO)'s response criteria. Our model for predicting response using carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, and NCC-ST-439 was determined using the area under the receiver operating characteristic curve (ROC-AUC) and the overall misclassification rate (OMR) in a random cross-validation. The prediction model was then verified in a consecutive set of 64 patients. Their response had been evaluated using the response evaluation criteria in solid tumors (RECIST) criteria. RESULTS: The best prediction model consisted of the serum CEA, CA15-3, and NCC-ST-439 levels, but the prediction formula varied according to the baseline CA15-3 level (elevated or normal). The overall ROC-AUC and OMR in the training set were 0.83 and 0.19, respectively. The overall ROC-AUC and OMR in the verification set were 0.72 and 0.28, respectively. When the verification set was stratified according to either the objective response or the predicted response, the time-to-progression, but not the overall survival, was significantly different. CONCLUSION: Our model for predicting the response to first-line chemotherapy of patients with metastatic or recurrent breast cancer may be valid because it predicted the outcome of more than 70% of the patients in an independent verification set.



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Fwd: Breast tumor metastasis: analysis via proteomic profiling.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Breast tumor metastasis: analysis via proteomic profiling.
To: mesothelioma77@gmail.com


[1]Expert Rev Proteomics. 2008 Jun; 5(3): 457-67
Goodison S, Urquidi V

The ability to predict the metastatic behavior of a patient's cancer, as well as to detect and eradicate such recurrences, remain major clinical challenges in oncology. While many potential molecular biomarkers have been identified and tested previously, none have greatly improved the accuracy of specimen evaluation over routine histopathological criteria and, to date, they predict individual outcomes poorly. The ongoing development of high-throughput proteomic profiling technologies is opening new avenues for the investigation of cancer and, through application in tissue-based studies and animal models, will facilitate the identification of molecular signatures that are associated with breast tumor cell phenotype. The appropriate use of these approaches has the potential to provide efficient biomarkers, and to improve our knowledge of tumor biology. This, in turn, will enable the development of targeted therapeutics aimed at ameliorating the lethal dissemination of breast cancer. In this review, we focus on the accumulating proteomic signatures of breast tumor progression, particularly those that correlate with the occurrence of distant metastases, and discuss some of the expected future developments in the field.



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Fwd: Malignant hematopoietic cell lines: In vitro models for the study of Waldenström's macroglobulinemia.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sat, Jun 7, 2008 at 2:25 AM
Subject: Malignant hematopoietic cell lines: In vitro models for the study of Waldenström's macroglobulinemia.
To: mesothelioma77@gmail.com


[1]Leuk Res. 2008 Jun 2;
Drexler HG, Macleod RA

Model cell lines are essential tools for investigating the biology and therapeutics of cancer. Approximately 1500 human hematopoietic neoplastic cell lines have been described, covering most major disease entities. Waldenström's macroglobulinemia (WM) is a rare incurable hematological neoplasm from which only three cell lines have been derived. Mindful that candidate tumor cell lines sometimes arise spuriously by viral immortalization of bystander cells, we review the extent to which WM cell lines portray established disease features in vitro. At closer inspection, it seems that none convincingly displays morphological, immunophenotypic, genotypic or biological features characteristic of WM. Rather it appears that two cell lines (WM1 and BCWM.1) are most probably Epstein-Barr virus-immortalized B-lymphoblastoid cell lines, derived from bystander B-cells. The third cell line (WSU-WM) carries the most common cytogenetic hallmark of Burkitt lymphoma, namely t(8;14)(q24;q32), while none have been shown to carry chromosome 6 deletions recently demonstrated as indicative of disease progression in this entity. In summary, although three WM cell lines are currently used as in vitro models, none convincingly pass muster.



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Fw: Malignant pleural mesothelioma: Computed tomography and correlation with histology.

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From: HubMed - mesothelioma <rssfwd@rssfwd.com>
To: shell8377@yahoo.com
Sent: Wednesday, March 26, 2008 2:22:39 PM
Subject: Malignant pleural mesothelioma: Computed tomography and correlation with histology..

[1]Eur J Radiol. 2008 Mar 20;
Seely JM, Nguyen ET, Churg AM, Müller NL

OBJECTIVE: To review the computed tomography (CT) imaging findings of pleural mesothelioma at presentation and to correlate the CT with the histological subtype. MATERIALS AND METHODS: Pathology reports from 1997 to 2006 were reviewed at two academic institutions to identify patients with proven pleural mesothelioma. Diagnosis was based on histologic findings in specimens obtained by transthoracic needle biopsy, surgical biopsy or resection. All histology slides were reviewed by a lung pathologist. CT scans, available in 92 patients, were reviewed blindly and in random order by two independent radiologists. Kappa analysis was completed to assess inter-observer agreement. Eighty patients in whom there was no significant delay between CT imaging and histological diagnosis were assessed by logistic regression analysis to correlate CT and histologic findings. RESULTS: Seventy-two of the 92 mesotheliomas were epithelial, 15 sarcomatous, and 5 of mixed histology. All patients (77 male, 15 female, mean age 68 years) had pleural thickening on CT; the thickening was nodular in 79 patients (86%) and mediastinal in 87 (95%). Ipsilateral volume loss was seen in 42 patients (46%). Pleural effusions were present in 80 patients (87%), being large (>2/3 hemithorax) in 19 patients (21%). Atypical features at presentation included bilateral disease in three patients (3%), and spontaneous pneumothoraces in nine patients (10%). Internal mammary lymphadenopathy was observed in 48 patients (52%) and cardiophrenic lymphadenopathy in 42 (46%). Inter-observer agreement was excellent (average kappa=0.89). Ipsilateral volume loss was associated with sarcomatous or mixed mesothelioma (p=0.004). Using logistic regression analysis, other CT findings did not correlate with histological subtype. CONCLUSIONS: Ipsilateral volume loss is most frequently associated with sarcomatous or mixed mesothelioma. The remaining imaging findings are not helpful in predicting the histological subtype of malignant mesothelioma.



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Fw: New Weblog (''Blog''), MyMeso.org, Aims to Raise Awareness of Deadly Form of Lung Cancer

----- Forwarded Message ----
From: Search for mesothelioma diagnosis <rssfwd@rssfwd.com>
To: shell8377@yahoo.com
Sent: Wednesday, March 26, 2008 2:22:36 PM
Subject: New Weblog (''Blog''), MyMeso.org, Aims to Raise Awareness of Deadly Form of Lung Cancer

MONTGOMERY, Ala., BUSINESS WIRE -- Current statistics show 2,000-3,000 people are diagnosed with malignant pleural mesothelioma in the U.S. each year, and 10,000 Americans die from all asbestos-related ...

Wed, 26 Mar 2008 09:20:26 GMT

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Fwd: Insulin receptor substrate 1 modulates the transcriptional activity and the stability of androgen receptor in breast cancer cells.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Insulin receptor substrate 1 modulates the transcriptional activity and the stability of androgen receptor in breast cancer cells.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res Treat. 2008 Jun 4;
Lanzino M, Garofalo C, Morelli C, Le Pera M, Casaburi I, McPhaul MJ, Surmacz E, Andò S, Sisci D

Breast cancer development and progression is regulated by growth factors and steroid hormones. Although the majority of human breast cancers expresses androgen receptor (AR), the role of androgens in breast tumorigenesis remains largely unexplored. Here we demonstrate that an AR ligand, 5-alpha-dihydrotestosterone (DHT), inhibits MCF-7 breast cancer cell growth induced by insulin like growth factor 1 (IGF-I). Our results show that DHT induces association of AR with IRS-1, the major IGF-1 receptor signaling molecule. The AR/IRS-1 complex translocates to the nucleus and is recruited to gene promoters containing androgen responsive elements causing an increase of AR transcriptional activity. Moreover, IRS-1 knockdown suggests that IRS-1/AR interaction decreases the ubiquitin/proteasome dependent degradation of AR, increasing its stability. Taken together, these data indicate that nuclear IRS-1 is a novel AR regulator required to sustain AR activity and demonstrate, for the first time in breast cancer cells, the existence of a functional interplay between the IGF system and AR. This interplay may represent the molecular basis of mechanisms through which androgens exert their inhibitory role on the proliferation of breast cancer cells.



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Fwd: The first functional study of MLH3 mutations found in cancer patients.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: The first functional study of MLH3 mutations found in cancer patients.
To: mesothelioma77@gmail.com


[1]Genes Chromosomes Cancer. 2008 Jun 2;
Korhonen MK, Vuorenmaa E, Nyström M

The MLH3 gene is one of the five mismatch repair (MMR) genes associated with hereditary nonpolyposis colorectal cancer (HNPCC). Eighteen different inherited MLH3 mutations have been reported as pathogenic in an international mutation database. In several cases, a mutation was found in a patient without a family history suggestive of inherited cancer susceptibility. In some cases, a similar mutation was also found in sporadic patients and/or healthy controls. Four patients carried an MLH3 mutation together with another inherited MMR gene variation. No functional analyses have been performed to assess the pathogenicity of these 18 mutations. MLH3 has been assumed to be less important in MMR than the other HNPCC susceptibility genes MSH2, MSH6, MLH1, and PMS2, and accordingly a low-risk gene for colorectal cancer (CRC). To assess the significance of the inherited sequence variations in MLH3, we functionally characterized seven missense mutations (Q24E, R647C, S817G, G933C, W1276R, A1394T, E1451K) scattered throughout the MLH3 polypeptide. The mutations were found in CRC or endometrial cancer patients and reported as pathogenic. Our study showed that the seven mutated MLH3 proteins, in complex with their counterpart MLH1 (MutLgamma), repaired mismatches as the wild type MutLgamma but worse than a heterodimer of MLH1 and PMS2 (MutLalpha). The results confirm that MutLgamma is a less efficient MMR complex than MutLalpha and show that the MLH3 mutations alone do not interfere with MMR. Further studies are needed to evaluate the pathogenicity of MLH3 mutations in compound with other MMR mutations. (c) 2008 Wiley-Liss, Inc.



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Fwd: Acute lymphoblastic leukemia and Down syndrome: presenting features and treatment outcome in the experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP).

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Acute lymphoblastic leukemia and Down syndrome: presenting features and treatment outcome in the experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP).
To: mesothelioma77@gmail.com


[1]Cancer. 2008 Jun 2;
Arico M, Ziino O, Valsecchi MG, Cazzaniga G, Baronci C, Messina C, Pession A, Santoro N, Basso G, Conter V,

BACKGROUND.: The presenting features and treatment outcome of 120 patients with Down syndrome (DS) and childhood acute lymphoblastic leukemia (ALL) were compared with 6237 non-DS patients treated in the same years. METHODS.: We reviewed the database of 6 consecutive Italian Association of Pediatric Hematology and Oncology (AIEOP)-ALL trials conducted between 1982 and 2004. Features of DS patients were compared with those of non-DS patients. RESULTS.: The 120 DS patients (1.9%) were more often girls (P = .027), aged >/=10 years (P = .014), and high risk according to National Cancer Institute (NCI) criteria (P = .045). The distribution of white blood cell count did not differ (P = .32). DS patients belonged less frequently to the current high-risk group (P = .017). In all but 1 case they demonstrated B-cell precursor (BCP) immunophenotype (P

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Fwd: Predicting complications following expander/implant breast reconstruction: an outcomes analysis based on preoperative clinical risk.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Predicting complications following expander/implant breast reconstruction: an outcomes analysis based on preoperative clinical risk.
To: mesothelioma77@gmail.com


[1]Plast Reconstr Surg. 2008 Jun; 121(6): 1886-92
McCarthy CM, Mehrara BJ, Riedel E, Davidge K, Hinson A, Disa JJ, Cordeiro PG, Pusic AL

BACKGROUND: Complications following postmastectomy reconstruction can cause significant morbidity. The compound effect of individual risk factors on the development of complications following expander/implant reconstruction has not, however, been well delineated. This study evaluated the impact of clinical risk factors to predict complications following postmastectomy expander/implant reconstruction. METHODS: From 2003 through 2004, 1170 expander/implant reconstructions were performed at a single center. A prospectively maintained database was reviewed. Variables including age, smoking status, body mass index, history of diabetes, hypertension, chemotherapy and/or radiation, as well as timing and laterality of reconstruction were evaluated. The primary endpoint was the development of a complication; the secondary endpoint was failure of reconstruction. RESULTS: Over the 2 year study period, 1170 expander/implant reconstructions were performed in 884 patients. The odds of developing complications was 2.2 times greater in smokers (p

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Fwd: Chest CT of Incidental Breast Lesions.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Chest CT of Incidental Breast Lesions.
To: mesothelioma77@gmail.com


[1]J Thorac Imaging. 2008 May; 23(2): 148-155
Yi JG, Kim SJ, Marom EM, Park JH, Jung SI, Lee MW

Chest computed tomography (CT) is routinely used for the evaluation of diseases of the chest involving the lung, mediastinum, pleura, chest wall, and diaphragm. Benign and malignant breast lesions are not uncommonly encountered incidentally on chest CT. The chest CT radiologist should be aware of the different breast pathologies and their CT appearances as some can be diagnosed by chest CT, whereas others, such as breast cancer, should not be overlooked. The purpose of this pictorial essay is to show various common and uncommon breast conditions encountered while interpreting chest CT scans in our daily practice.



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Fwd: Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Systemic chemokine levels in breast cancer patients and their relationship with circulating menstrual hormones.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res Treat. 2008 Jun 4;
Potter SM, Dwyer RM, Curran CE, Hennessy E, Harrington KA, Griffin DG, Kerin MJ

Introduction The chemokines Stromal Cell-Derived Factor-1alpha (SDF-1alpha/CXCL12) and Monocyte Chemotactic Protein-1 (MCP-1/CCL2) have been implicated in breast cancer progression. We recently reported elevated systemic MCP-1 in breast cancer patients. This study investigated circulating levels of SDF-1alpha in breast cancer patients, and addressed potential hormonal regulation of these two potent chemokines. Methods SDF-1alpha levels were determined by ELISA in 114 breast cancer patients and 85 controls, and correlated with clinical data. Blood samples were collected from 36 healthy premenopausal volunteers weekly for four weeks to measure Luteinising Hormone (LH), Follicular Stimulating Hormone (FSH), Oestradiol and Progesterone using a Bayer ADVIA((R)) Centaur Immunoassay system, in parallel with SDF-1alpha and MCP-1. CXCL12 expression was determined using RQ-PCR in primary tumour stromal cells (n = 16) harvested at surgery. Results Plasma SDF-1alpha was significantly higher in breast cancer patients than age-matched controls and had a significant correlation with tumour grade and epithelial subtype. Investigation of menstrual variations of these chemokines revealed lower SDF-1alpha levels in the mid-luteal phase of the menstrual cycle and a significant positive correlation with circulating Oestradiol. MCP-1 levels showed no correlation with menstrual hormones. There was a trend towards increased CXCL12 expression in tumour compared to normal stromal cells. Conclusions The elevated level of SDF-1alpha detected in breast cancer patients, and it's correlation with prognostic indicators, highlights the importance of this chemokine in disease progression. Elucidation of factors influencing chemokine secretion supports clarification of their role in tumourigenesis.



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Fwd: Survival and degree of spread for female breast cancers in New South Wales from 1980 to 2003: implications for cancer control.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Survival and degree of spread for female breast cancers in New South Wales from 1980 to 2003: implications for cancer control.
To: mesothelioma77@gmail.com


[1]Cancer Causes Control. 2008 Jun 3;
Tracey E, Roder D, Zorbas H, Villanueva E, Jelfs P, Bishop J

This study investigated associations of degree of spread at diagnosis of breast cancer and socio-demographic factors with the risk of death among NSW females diagnosed in 1980-2003. Trends by diagnostic period, socio-demographic differences, and the implications for cancer control were considered. NSW Central Cancer Registry data were analyzed using regression and rank-order tests to show predictors of death from breast cancer and trends in degree of spread. Compared with localized disease, case fatality was thrice and 14 times higher for cancers with regional spread and distant metastases, respectively. After adjusting for degree of spread and socio-demographic differences, the relative risk of death from breast cancer has declined in recent diagnostic periods compared with the 1980-1983 baseline, reaching a low of 0.38 (0.35, 0.40) for 1999-2003. Age-specific analyses indicated that relative risks were lower in 1999-2003 for 50-69 year olds (RR = 0.31) than younger (RR = 0.40), or older (RR = 0.46) females. Regional or distant disease at diagnosis was lowest in the older age groups, the highest socio-economic stratum and in more recent periods. Females born in nonEnglish speaking countries presented with more advanced disease, as did metropolitan women with the highest access to health services. Degree of spread of cancer at diagnosis is a powerful predictor of case fatality. Case fatalities from breast cancer have declined by diagnostic period, after adjusting for degree of spread, which may reflect treatment and screening advances. Attention should be directed at reducing disparities by socio-economic status and encouraging migrant women to present earlier.



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Fwd: Antiproliferative Activity of Derivatives of Ouabain, Digoxin and Proscillaridin A in Human MCF-7 and MDA-MB-231 Breast Cancer Cells.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Antiproliferative Activity of Derivatives of Ouabain, Digoxin and Proscillaridin A in Human MCF-7 and MDA-MB-231 Breast Cancer Cells.
To: mesothelioma77@gmail.com


[1]Biol Pharm Bull. 2008 Jun; 31(6): 1131-40
Winnicka K, Bielawski K, Bielawska A, Surazyński A

Three derivatives of ouabain, digoxin and proscillaridin A containing the carboxylic group instead of the lactone moiety were synthesized and examined for cytotoxicity in human breast cancer cells. Evaluation of the cytotoxicity of these compounds employing an MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MCF-7 and MDA-MB-231 breast cancer cells demonstrated that compound 3, the most active of the series, proved to be only slightly less potent than proscillaridin A. We evaluated the effects of these compounds 1-3 on change in intracellular Ca(2+), appearance of apoptosis, inhibition of DNA topoisomerase I and II, and the activity of caspase-3 in breast cancer cells. These studies indicate that the increase in potency for 3 may be related, in part, to an activation of caspase-3, increasing free calcium concentration and topoisomerase II inhibition. All these data emphasize the potential usefulness of these derivatives of cardiac glycosides as anticancer agents.



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Fwd: Effects of Phosphorylation of Immunomodulatory Agent FTY720 (Fingolimod) on Antiproliferative Activity against Breast and Colon Cancer Cells.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Thu, Jun 5, 2008 at 1:34 AM
Subject: Effects of Phosphorylation of Immunomodulatory Agent FTY720 (Fingolimod) on Antiproliferative Activity against Breast and Colon Cancer Cells.
To: mesothelioma77@gmail.com


[1]Biol Pharm Bull. 2008 Jun; 31(6): 1177-81
Nagaoka Y, Otsuki K, Fujita T, Uesato S

FTY720 (fingolimod), a novel immunosuppressant, was found to become biologically activated by phosphorylation into FTY720-1-phosphate (FTY720-P), which is a high-affinity agonist for sphingosine-1-phosphate (sphingosine-1-P)-receptors. FTY720 has also been reported to have a strong antitumor activity. The association between the phosphorylation of FTY720 and the growth inhibition of FTY720 against cancer cells are still not completely understood. In this study, we investigated the effects of FTY720, sphingosine, and their related compounds on the proliferation of human breast cancer cell lines (MCF-7, MDA-MB-231 and Sk-Br-3) and human colon cancer cell lines (HCT-116 and SW620). Non-phosphorylated FTY720, sphingosine and an FTY720 derivative, ISP-I-55, showed significant growth inhibition against these cells, with IC(50) values of 5-20 muM at 48 h post-drug treatment. We confirmed that FTY720 induces the activation of a major mitogen-activated protein kinase, JNK, without the activation of p38 and down-regulation of phospho-ERK in MCF-7 breast cancer cells. In contrast, the phosphorylated derivatives, FTY720-P and sphingosine-1-P, as well as a phosphinane FTY720 derivative, cFTY720-P, did not inhibit the growth of the cells in the concentration range of 5-50 muM, whereas FTY720-P and sphingosine-1-P slightly induced the growth of MCF-7 cells. Combining FTY720 with dimethylsphingosine, a sphingosine kinase inhibitor, augmented the inhibitory effect of FTY720. These results indicate that the antiproliferative activity of FTY720 does not result from its phosphorylation, either endogenous or exogenous.



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Fwd: Erbitus prolongs life expectancy for lung cancer patients: study (AFP via Yahoo! News)

---------- Forwarded message ----------
From: Yahoo! News Search Results for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 3, 2008 at 1:20 AM
Subject: Erbitus prolongs life expectancy for lung cancer patients: study (AFP via Yahoo! News)
To: mesothelioma77@gmail.com


The cancer drug Erbitux (cetuximab) prolonged the lives of patients with advanced lung cancer by five weeks, according to a clinical study described Sunday as an important gain for such individuals.

Mon, 02 Jun 2008 06:48:18 GMT

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Fwd: Stocks down after tepid economic data, bank woes

---------- Forwarded message ----------
From: Search for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 3, 2008 at 1:20 AM
Subject: Stocks down after tepid economic data, bank woes
To: mesothelioma77@gmail.com

Wall Street retreated Monday on more signs of economic weakness and executive shake-ups at two major banks _ reminders of the ongoing fallout from the credit crisis.

Tue, 03 Jun 2008 04:56:04 GMT

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Fwd: Study: Drug Extendes Lives Of Lung Cancer Patients (WCSH 6 Portland)

---------- Forwarded message ----------
From: Yahoo! News Search Results for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 3, 2008 at 1:20 AM
Subject: Study: Drug Extendes Lives Of Lung Cancer Patients (WCSH 6 Portland)
To: mesothelioma77@gmail.com


CHICAGO, IL (AP) -- Adding the novel cancer drug Erbitux to standard chemotherapy helped advanced lung cancer patients live just a month longer than chemo alone, a study found.

Mon, 02 Jun 2008 22:11:57 GMT

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Fwd: Mix of Good, Bad News for ImClone's Erbitux at ASCO

---------- Forwarded message ----------
From: Search for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 3, 2008 at 1:20 AM
Subject: Mix of Good, Bad News for ImClone's Erbitux at ASCO
To: mesothelioma77@gmail.com

While data from the much-anticipated FLEX Phase III study showed that ImClone Systems Inc.'s Erbitux prolonged life by about five weeks for patients with non-small-cell lung cancer , findings from another study ...

Tue, 03 Jun 2008 02:57:31 GMT

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Fwd: Colleagues become triumphant survivors

---------- Forwarded message ----------
From: Search for lung cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 3, 2008 at 1:20 AM
Subject: Colleagues become triumphant survivors
To: mesothelioma77@gmail.com

A year ago, Bob Gilliam didn't feel like a survivor. He'd been diagnosed with lung cancer in January of 2007.

Tue, 03 Jun 2008 02:01:53 GMT

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Fwd: Unite Backs High Court Test Case on Behalf of Thousands of Asbestos Victims (PR Newswire via Yahoo! Finance)

---------- Forwarded message ----------
From: Yahoo! News Search Results for asbestos cancer <rssfwd@rssfwd.com>
Date: Tue, Jun 3, 2008 at 1:20 AM
Subject: Unite Backs High Court Test Case on Behalf of Thousands of Asbestos Victims (PR Newswire via Yahoo! Finance)
To: mesothelioma77@gmail.com


Unite the Union is backing a High Court test case next week to protect the legal rights of thousands of vulnerable asbestos victims throughout the UK.

Sun, 01 Jun 2008 09:00:00 GMT

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Fwd: Cancer stem cells as targets for cancer therapy: selected cancers as examples.

---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Jun 1, 2008 at 5:03 PM
Subject: Cancer stem cells as targets for cancer therapy: selected cancers as examples.
To: mesothelioma77@gmail.com


[1]Arch Immunol Ther Exp (Warsz). 2008 May 30;
Hombach-Klonisch S, Paranjothy T, Wiechec E, Pocar P, Mustafa T, Seifert A, Zahl C, Gerlach KL, Biermann K, Steger K, Hoang-Vu C, Schulze-Osthoff K, Los M

It is becoming increasingly evident that cancer constitutes a group of diseases involving altered stem-cell maturation/differentiation and the disturbance of regenerative processes. The observed malignant transformation is merely a symptom of normal differentiation processes gone astray rather than the primary event. This review focuses on the role of cancer stem cells (CSCs) in three common but also relatively under-investigated cancers: head and neck, ovarian, and testicular cancer. For didactic purpose, the physiology of stem cells is first introduced using hematopoietic and mesenchymal stem cells as examples. This is followed by a discussion of the (possible) role of CSCs in head and neck, ovarian, and testicular cancer. Aside from basic information about the pathophysiology of these cancers, current research results focused on the discovery of molecular markers specific to these cancers are also discussed. The last part of the review is largely dedicated to signaling pathways active within various normal and CSC types (e.g. Nanog, Nestin, Notch1, Notch2, Oct3 and 4, Wnt). Different elements of these pathways are also discussed in the context of therapeutic opportunities for the development of targeted therapies aimed at CSCs. Finally, alternative targeted anticancer therapies arising from recently identified molecules with cancer-(semi-)selective capabilities (e.g. apoptin, Brevinin-2R) are considered.



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Fwd: Clinical identification of colorectal cancer patients benefiting from adjuvant uracil-tegafur (UFT): a randomized controlled trial.

---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Jun 1, 2008 at 5:03 PM
Subject: Clinical identification of colorectal cancer patients benefiting from adjuvant uracil-tegafur (UFT): a randomized controlled trial.
To: mesothelioma77@gmail.com


[1]J Cancer Res Clin Oncol. 2008 May 30;
Fujii M, Takayama T, Kochi M

PURPOSE: A randomized controlled trial was conducted to determine whether pathologic necrosis in response to preoperative treatment with uracil-tegafur(UFT) could be used to identify patients with colorectal cancer most likely to benefit from postoperative adjuvant therapy with the drug. PATIENTS AND METHODS: The 152 patients with colorectal cancer who received preoperative UFT at a dose of 600 mg/day for at least 10 days were classified into two groups according to the pathologic necrosis in resected tumor specimens: 90% or more necrosis (sensitive) versus less than 90% necrosis (insensitive). After excluding 13 ineligible patients, the remaining 139 were then randomly assigned to receive postoperative adjuvant UFT (400 mg/day) for 12 months or no treatment. RESULTS: Preoperative and postoperative UFT produced no serious toxicity in any of the patients. Among the 22 patients with sensitive tumors, overall survival was significantly better in the UFT group (n = 12) than in the control (n = 10) (100 vs. 70.0%; P = 0.023). Among the 117 patients with insensitive tumors, there was no significant difference between the two groups (n = 60, 68.1% vs. n = 57, 76.6%; P = 0.373). CONCLUSION: Our method involving neoadjuvant UFT can identify patients most likely to benefit from postoperative UFT, as well as those unlikely to benefit from such treatment.



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Fwd: Comparison of short-and long-term outcomes following either insertion of self-expanding metallic stents or emergency surgery in malignant large bowel obstruction.

---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Sun, Jun 1, 2008 at 5:03 PM
Subject: Comparison of short-and long-term outcomes following either insertion of self-expanding metallic stents or emergency surgery in malignant large bowel obstruction.
To: mesothelioma77@gmail.com


[1]Tech Coloproctol. 2008 Mar; 12(1): 51-5
Dastur JK, Forshaw MJ, Modarai B, Solkar MM, Raymond T, Parker MC

BACKGROUND: Self-expanding metallic stents (SEMS) are now regarded as a safe and effective treatment for an acute obstructing colorectal cancer. SEMS insertion is an invasive procedure that could potentially worsen prognosis. This study assessed the short-and long-term outcomes in patients stented for acute large bowel obstruction and in patients who underwent primary emergency surgery. METHODS: We retrospectively identified 19 patients who underwent SEMS insertion and 23 patients who had primary emergency surgery for left-sided large bowel obstruction as the first presentation of colorectal cancer. RESULTS: There were no significant differences between the 19 patients in the SEMS group and the 23 patients in the primary emergency surgery group in terms of demographics and tumour location and stage. Stent insertion was successful in 16 patients (84%). One patient died from a stent-related perforation and another had a stoma fashioned for stent migration. Stents were a definitive procedure in 2 patients with advanced disease and acted as a "bridge to surgery" in the remaining 12 patients. Compared to the primary surgery group, there was a trend towards a higher primary anastomosis rate in the SEMS group (p=0.08); there were no significant differences in length of hospital stay, 30-day mortality or complication rates between the groups. Long-term prognosis (estimated 3-year survival) did not differ significantly between the groups (p=0.54); this persisted when only curative resections were considered (p=0.80). CONCLUSIONS: Preoperative stent insertion is a safe and effective treatment for large bowel obstruction, and may result in a higher primary anastomosis rate. Stent insertion does not seem to have a deleterious effect on prognosis.



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Fwd: Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Jun 1, 2008 at 5:03 PM
Subject: Prevalence and treatment patterns of physical impairments in patients with metastatic breast cancer.
To: mesothelioma77@gmail.com


[1]J Clin Oncol. 2008 Jun 1; 26(16): 2621-9
Cheville AL, Troxel AB, Basford JR, Kornblith AB

PURPOSE: Physical impairments cause profound functional declines in patients with cancer. Although common rehabilitation measures can address many impairments, the extent of their delivery is unknown. We studied these issues by quantifying physical impairments in patients with metastatic breast cancer and by assessing how they are addressed. PATIENTS AND METHODS: A consecutive sample of 163 community-dwelling patients with metastatic breast cancer was stratified by Karnofsky performance score and administered the Medical Outcomes Study Physical Function Subscale and the Older Americans Resource Study Activities of Daily Living subscales. Cancer-related physical impairments were identified through a physical examination, the 6-Minute Walk Test, and the Functional Independence Measure Mobility Subscale. Patients were questioned regarding the nature, type, and setting of treatments for impairments. Physical rehabilitation needs were determined through a consensus process involving physiatrists and physical/occupational therapists specializing in cancer. RESULTS: Ninety-two percent of patients (150 of 163) had at least one physical impairment. Among 530 identified impairments, 484 (92%) required a physical rehabilitation intervention and 469 (88%) required physical therapy (PT) and/or occupational therapy (OT). Only 30% of impairments requiring rehabilitation services and 21% of those requiring PT/OT received treatment. Impairments detected during hospitalization were overwhelmingly more likely to receive a rehabilitation intervention (odds ratio [OR] = 87.9; 95% CI, 28.5 to 271.4), and PT/OT (OR = 558.8; 95% CI, 187.0 to 1,669.6). Low socioeconomic and minority status were significantly associated with nontreatment. CONCLUSION: Remediable physical impairments were prevalent and poorly addressed among patients with metastatic breast cancer, drastically so in the outpatient setting. Undertreatment was particularly prominent among minority and socioeconomically disadvantaged groups.



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Fwd: Estrogen receptor expression and efficacy of docetaxel-containing adjuvant chemotherapy in patients with node-positive breast cancer: results from a pooled analysis.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Sun, Jun 1, 2008 at 5:03 PM
Subject: Estrogen receptor expression and efficacy of docetaxel-containing adjuvant chemotherapy in patients with node-positive breast cancer: results from a pooled analysis.
To: mesothelioma77@gmail.com


[1]J Clin Oncol. 2008 Jun 1; 26(16): 2636-43
Andre F, Broglio K, Roche H, Martin M, Mackey JR, Penault-Llorca F, Hortobagyi GN, Pusztai L

PURPOSE: Several adjuvant chemotherapy trials suggested that cytotoxic treatment is less effective in patients with estrogen receptor (ER)-positive breast cancers. The aim of the present study was to assess the efficacy of adjuvant docetaxel and anthracycline therapy according to ER expression in two randomized clinical trials. PATIENTS AND METHODS: Pooled data from two randomized trials, BCIRG001 and PACS01, were examined. Hazard ratios for recurrence and survival were estimated by Cox proportional hazards models and were adjusted for clinical variables. Interaction between docetaxel and ER expression was tested. RESULTS: ER status was available for 3,329 patients (95% of all randomly assigned patients), of whom 75% (n = 2,493) were ER positive. Docetaxel therapy was associated with a 30% reduction in the risk of death (hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.91) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.52 to 0.94) in ER-negative patients. Docetaxel therapy was associated with a 21% reduction in the risk of recurrence (HR = 0.79; 95% CI, 0.66 to 0.93) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.54 to 0.97) in ER-negative patients. The interaction between docetaxel therapy and ER status was not statistically significant for either overall survival (P = .87) or disease-free survival (P = .30). ER expression was also not predictive for docetaxel efficacy when it was analyzed as a semi-continuous variable based on percent of positive cells by immunohistochemistry (test for heterogeneity, P = .56 and .86 for overall survival and disease-free survival, respectively). CONCLUSION: In the pooled analysis of these two trials, docetaxel did not have a statistically significantly different effect on the risk of recurrence or death in ER-positive and ER-negative patients.



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Fwd: Presence of Lobular Carcinoma In Situ Does Not Increase Local Recurrence in Patients Treated with Breast-Conserving Therapy.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, May 30, 2008 at 1:52 AM
Subject: Presence of Lobular Carcinoma In Situ Does Not Increase Local Recurrence in Patients Treated with Breast-Conserving Therapy.
To: mesothelioma77@gmail.com


[1]Ann Surg Oncol. 2008 May 28;
Ciocca RM, Li T, Freedman GM, Morrow M

BACKGROUND: Lobular carcinoma in situ (LCIS) is known to be a risk factor for the development of invasive breast cancer. Debate continues as to whether LCIS is also a precursor lesion. We hypothesized that, if LCIS were a precursor, its presence in the lumpectomy specimen, particularly at the margin, could increase local recurrence (LR) after breast-conserving therapy (BCT). METHODS: 2894 patients treated with BCT for ductal carcinoma in situ (DCIS), stage I or II breast cancer between 1/80 and 5/07 were identified. Patients with DCIS or invasive cancer at the margins or those receiving neoadjuvant therapy were excluded. Group A had 290 patients with LCIS in the lumpectomy; 84 had LCIS at the final margin. Group B included 2604 patients with no evidence of LCIS. RESULTS: Median patient age in group A and B was 57 and 58 years, respectively (P = 0.05); 12% and 13%, respectively, of patients in group A and B had margins

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Fwd: Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, May 30, 2008 at 1:52 AM
Subject: Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases.
To: mesothelioma77@gmail.com


[1]Br J Cancer. 2008 Jun 3; 98(11): 1753-8
Generali D, Dovio A, Tampellini M, Tucci M, Tedoldi S, Torta M, Bonardi S, Allevi G, Aguggini S, Milani M, Harris AL, Bottini A, Dogliotti L, Angeli A, Berruti A

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (P

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Fwd: Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, May 30, 2008 at 1:52 AM
Subject: Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy.
To: mesothelioma77@gmail.com


[1]Int J Cancer. 2008 May 27;
Flesch-Janys D, Slanger T, Mutschelknauss E, Kropp S, Obi N, Vettorazzi E, Braendle W, Bastert G, Hentschel S, Berger J, Chang-Claude J

In a large population-based case-control study in Germany, including 3,464 breast cancer cases aged 50-74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face-to-face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%-confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55-1.94) and heterogeneous by histological type (p

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Fwd: Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Fri, May 30, 2008 at 1:52 AM
Subject: Incidence of interstitial pneumonitis among breast cancer patients: a 10-year Danish population-based cohort study.
To: mesothelioma77@gmail.com


[1]Br J Cancer. 2008 Jun 3; 98(11): 1870-5
Christensen S, Pedersen L, Grijota M, Kornum JB, Beiderbeck A, Sørensen HT

Chemotherapy and radiation therapy may increase risk for interstitial pneumonitis (IP) in breast cancer patients, but there are little current population-based data on IP incidence in these patients. We assessed population-based incidence rates (IRs) of IP among Danish breast cancer patients and compared these with IRs for the Danish general population. Through the Danish Cancer Registry, we identified all Danish breast cancer patients (n=35 823) diagnosed between 1994 and 2004. Treatment data were obtained from the Danish Breast Cancer Cooperation Group database, and data on IP, from the Danish National Registry of Patients. We computed IRs of IP among breast cancer patients and age-standardised incidence rate ratios (SIRs) comparing breast cancer patients with the general population. During follow-up, 28 breast cancer patients were registered with an IP diagnosis (IR=17.3 per 100,000 person-years (p-y) (95% confidence intervals (95% CI): 11.7-24.6)). When follow-up was restricted to 1 year after the first breast cancer diagnosis, eight patients with IP were identified (IR=23.4 per 100,000 p-y (95% CI: 11.0-44.1)). The SIR comparing breast cancer patients with the general population was 8.4 (95% CI: 5.7-11.9). Thus, although IP is a rare adverse event among breast cancer patients, its risk is substantially higher than that in the general population.



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Fwd: Quantifiable mRNA transcripts for tamoxifen-metabolising enzymes in human endometrium.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, May 28, 2008 at 10:29 AM
Subject: Quantifiable mRNA transcripts for tamoxifen-metabolising enzymes in human endometrium.
To: mesothelioma77@gmail.com


[1]Toxicology. 2008 Apr 22;
Singh MN, Stringfellow HF, Walsh MJ, Ashton KM, Paraskevaidis E, Abdo KR, Martin-Hirsch PL, Phillips DH, Martin FL

Tamoxifen has been used in the management of receptor-positive breast cancer for >20 years. Usage confers an elevated risk of developing endometrial carcinoma. Its mechanism of carcinogenicity remains unresolved with controversy as to whether or not this is mediated through a genotoxic mechanism. Usage is not only associated with an elevated occurrence of endometrioid endometrial carcinoma, but also type 2 and mixed epithelial-stromal tumours (MESTs) that have a poorer prognosis. Following hysterectomy, endometrial tissues (n=18) classified as benign (n=6), non-tamoxifen-associated carcinoma (n=6) and tamoxifen-associated carcinoma (n=6) were obtained; quantitative gene expression was performed. Employing real-time RT-PCR, the relative gene expressions of phase I/II metabolic enzymes CYP1A2, CYP1B1 and CYP3A4, cathechol-O-methyltransferase (COMT) and SULT2A1 were ascertained. Measurable mRNA transcripts, especially for those genes associated with tamoxifen bioactivation, were quantifiable in all the tissues examined. Whether this is evidence that generation of genotoxic tamoxifen metabolites may occur in human endometrial tissue remains to be ascertained.



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