Fwd: Nanotechnology for breast cancer therapy.

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From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: Nanotechnology for breast cancer therapy.
To: mesothelioma77@gmail.com


[1]Biomed Microdevices. 2008 Jul 29;
Tanaka T, Decuzzi P, Cristofanilli M, Sakamoto JH, Tasciotti E, Robertson FM, Ferrari M

Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of 'resistance' to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists-in the clinic, the pharmaceutical and the basic biological laboratory-and nanotechnologists-engineers, physicists, chemists and mathematicians-optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other 'environmental' divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may result. The paper initiates with an introductory overview of breast cancer, its current treatment modalities, and the current role of nanotechnology in the clinic. Our perspectives are then presented on what the greatest opportunities for nanotechnology are; this follows from an analysis of the role of biological barriers that adversely determine the biological distribution of intravascularly injected therapeutic agents. Different generations of nanotechnology tools for drug delivery are reviewed, and our current strategy for addressing the sequential bio-barriers is also presented, and is accompanied by an encouragement to the community to develop even more effective ones.



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Fwd: Does the eradication of Helicobacter pylori delay the diagnosis of gastric cancer?

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: Does the eradication of Helicobacter pylori delay the diagnosis of gastric cancer?
To: mesothelioma77@gmail.com


[1]Scand J Gastroenterol. 2008 Jul 29; 1-5
Kokkola A, Sipponen P, Arkkila P, Danielson H, Puolakkainen P

Objective. To assess the frequency of gastric cancer patients having received eradication treatment of Helicobacter pylori, and whether this treatment has any influence on the delay in the diagnosis or the stage of the tumours at the time of the operation. Material and methods. A total of 119 consecutive patients with gastric cancer were interviewed preoperatively between 2001 and 2003 at the Department of Surgery, Helsinki University Central Hospital. Abdominal symptoms, previous endoscopies, previous H. pylori testing and eradication therapies were recorded. Results. Of these patients, 112 (94%) had abdominal symptoms before the cancer diagnosis, and in 110 patients (92%) these symptoms were alarming or had changed before the cancer diagnosis. Thirty-five patients (29%) had received H. pylori eradication therapy prior to the diagnosis of gastric cancer (15 after onset or change in symptoms, 10 more than 5 years prior to the cancer diagnosis). The median duration of alarm, new or changed symptoms was longer among patients with H. pylori eradication therapy after the onset or change in their symptoms as compared to other patients (12.0 versus 4.5 months, p=0.001). However, there was no difference in the tumour stages at time of the operation between the eradication and no eradication groups. A previous gastroscopy within 2 years prior to the cancer diagnosis was performed in 17 (14%) patients. Diffuse-type cancers were missed significantly more often in endoscopies than cancers of intestinal type. Conclusion. Previous H. pylori eradication may delay the detection of gastric cancer if it is given during symptoms caused by tumour.



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Source: http://www.hubmed.org/display.cgi?uids=18663664
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Fwd: The Performance of Risk Prediction Models.

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From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: The Performance of Risk Prediction Models.
To: mesothelioma77@gmail.com


[1]Biom J. 2008 Jul 29; 50(4): 457-479
Gerds TA, Cai T, Schumacher M

For medical decision making and patient information, predictions of future status variables play an important role. Risk prediction models can be derived with many different statistical approaches. To compare them, measures of predictive performance are derived from ROC methodology and from probability forecasting theory. These tools can be applied to assess single markers, multivariable regression models and complex model selection algorithms. This article provides a systematic review of the modern way of assessing risk prediction models. Particular attention is put on proper benchmarks and resampling techniques that are important for the interpretation of measured performance. All methods are illustrated with data from a clinical study in head and neck cancer patients. ((c) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).



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Fwd: Complexation Study of the Anticancer Agent EO-9 with 2-hydroxypropyl-beta-Cyclodextrin.

---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: Complexation Study of the Anticancer Agent EO-9 with 2-hydroxypropyl-beta-Cyclodextrin.
To: mesothelioma77@gmail.com


[1]Drug Dev Ind Pharm. 2008 Jul 29; 1-10
Beijnen JH, van der Schoot SC, Nuijen B, Flesch FM, Gore A, Mirejovsky D, Lenaz L

For the development of a bladder instillation of the indoloquinone agent EO-9, use of the complexing agent 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) was considered. Therefore, a complexation study of EO-9 with HPbetaCD was performed. Complexation was studied in aqueous solution and in solid freeze-dried products. A phase solubility study, UV-visible spectroscopy (UV/VIS), and analysis of the effect of HPbetaD on the stability of EO-9 were performed. With the phase solubility study, a complexation constant (K1:1) of 32.9, a complexation efficiency (CE) of 0.0457, and a utility number (UCD) of 38.3 were calculated. These K1:1 and CE values indicate a weak complex, but the UCD shows that HPbetaCD can be very useful as solubilizer in the desired formulation. Furthermore, a positive effect of HPbetaCD on the chemical stability of EO-9 in solution was seen. Subsequently, complexation in the freeze-dried products was studied more thoroughly using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses. HPbetaCD was found to be an excellent pharmaceutical complexing agent for application in formulations for EO-9 bladder instillations. Reconstitution before use of the developed freeze-dried products can be simply accomplished with water for injection.



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Fwd: Intrafraction changes of prostate position and geometrical errors studied by continuous electronic portal imaging.

---------- Forwarded message ----------
From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: Intrafraction changes of prostate position and geometrical errors studied by continuous electronic portal imaging.
To: mesothelioma77@gmail.com


[1]Acta Oncol. 2008 Jul 29; 1-7
Haskå TM, Honore H, Muren LP, Høyer M, Poulsen PR

Purpose. The use of marker-based on-line image guided radiotherapy for prostate cancer has considerably reduced the treatment margins to sub-cm. In this study we have quantified the residual set-up errors remaining after isocenter correction, studied their development during beam delivery and estimated their impact on margins. Methods and materials. After initial on-line patient set-up based on orthogonal kV x-ray images of implanted fiducial markers, continuous electronic portal imaging was performed during treatment delivery in 10 of 39 treatment sessions for 20 prostate cancer patients. The cranio-caudal (CC) position of the centre-of-mass of the three markers was found using a threshold technique on every single image frame for all patients, typically 12 - 14 images for 5 treatment beams in every fraction. The CC prostate position was determined relative to its initial position at treatment onset and relative to its planned position within the field aperture. These results allowed determination of the CC intrafraction prostate motion and the intrafraction progression of the geometrical CC error, respectively. Results. At treatment onset the standard deviation (SD) of the set-up error was 1.0mm in the lateral direction and 1.5mm in the cranio-caudal (CC) direction. It did not depend significantly on the duration of the set-up procedure (mean: 3.0min, span 1.2-14.6min). The distribution of CC prostate positions relative to the position at treatment onset broadened from 0 to 1.4mm during the treatment session, while the corresponding CC setup error distribution broadened from 1.5 to 1.9mm. This broadening means that the necessary CC setup margin increased by around 1mm during the treatment fraction. Conclusions. Large differences in the intrafraction CC prostate motion patterns were found, however, intrafraction motion only results in a modest additional CC set-up margin of around 1mm relative to the margins needed for the residual set-up error at treatment start.



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Fwd: Meta-analysis of gene-expression profiles in breast cancer: toward a unified understanding of breast cancer sub-typing and prognosis signatures.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: Meta-analysis of gene-expression profiles in breast cancer: toward a unified understanding of breast cancer sub-typing and prognosis signatures.
To: mesothelioma77@gmail.com


[1]Breast Cancer Res. 2008 Jul 28; 10(4): R65
Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, Haibe-Kains B, Desmedt C, Ignatiadis M, Sengstag T, Schutz F, Goldstein DR, Piccart M, Delorenzi M

ABSTRACT: INTRODUCTION: Breast cancer sub-typing and prognosis have been extensively studied by gene expression profiling, resulting in disparate signatures with little overlap in their constituent genes. Although a previous study demonstrated a prognostic concordance among gene-expression signatures, it was limited to only one dataset and did not fully elucidate how the different genes were related to one another, nor examined the contribution of well-known biological processes of breast cancer tumorigenesis to their prognostic performance. METHODS: To address the above issues and to further validate these initial findings, we performed the largest meta-analysis of publicly available breast cancer gene-expression and clinical data totaling 2833 breast tumors. Gene co-expression modules of three key biological processes in breast cancer, namely proliferation, estrogen receptor and HER2 signaling, were used to dissect the role of constituent genes of 9 prognostic signatures. RESULTS: Using meta-analytical approach, we consolidated the signatures associated with ER signaling, ERBB2 amplification and proliferation. Previously published expression-based nomenclature of breast cancer "intrinsic" subtypes can be mapped to the three modules, namely, the ER-/HER2- (basal-like), the HER2+ (HER2-like) and the low and high proliferation ER+/HER2- subtypes (luminal A and B). We showed that all 9 prognostic signatures exhibited similar prognostic performance in the entire dataset. Their prognostic abilities are due mostly to detection of proliferation activity. Although ER- (basal-like) and ERBB2+ amplification status correspond to bad outcome, they seem to act through elevated expression of proliferation genes, and thus contain only indirect information about prognosis. Clinical variables measuring the extent of tumor progression, such as tumor size and nodal status, still add independent prognostic information to proliferation genes. CONCLUSIONS: This meta-analysis unifies various results of previous gene-expression studies in breast cancer. It reveals connections between traditional prognostic factors, expression-based sub-typing and prognostic signatures, highlighting the important role of proliferation in breast cancer prognosis.



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Fwd: Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer.

---------- Forwarded message ----------
From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Jul 30, 2008 at 9:30 PM
Subject: Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer.
To: mesothelioma77@gmail.com


[1]Cancer. 2008 Jul 25;
Ali SM, Carney WP, Esteva FJ, Fornier M, Harris L, Köstler WJ, Lotz JP, Luftner D, Pichon MF, Lipton A,

BACKGROUND.: Previous reports based on small patient numbers suggested that changes in serum HER-2/neu levels may predict response or lack of response to trastuzumab-based therapies in metastatic breast cancer (MBC). The objectives of this study were to pool data from 307 patients with MBC from 7 medical institutions to validate that the serum HER-2/neu profile predicts patient resistance to trastuzumab and to establish a clinically relevant cutoff. METHODS.: This was an international, multicenter, retrospective analysis of individual pooled data from 307 patients with MBC who were treated with first-line trastuzumab-based therapy. Serum was collected at baseline and 30 to 120 days after the initiation of trastuzumab therapy. A serum HER-2/neu decrease >/=20% (receiver operating curve analysis) was defined as a significant HER-2/neu change. RESULTS.: Of the 307 patients with MBC, 191 patients (62%) had a significant decline (>20%) in serum HER-2/neu and 116 patients (38%) did not. The objective response rate was 57% for patients who achieved this decline in serum HER-2/neu (>20%) compared with 28% for patients who did not. Patients who achieved this decline in serum HER-2/neu also had a significantly longer time to disease progression (320 days vs 180 days; P /=20%) in serum HER-2/neu levels had decreased benefit from trastuzumab-based therapy, and these patients should be considered for clinical trials evaluating additional HER-2/neu-targeted interventions. Cancer 2008. (c) 2008 American Cancer Society.



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Source: http://www.hubmed.org/display.cgi?uids=18661530
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