Laboratory Medicine Research This is an OPML file. It can be used to export all the MedWorm RSS feeds on this topic into your personal RSS reader (usually you have to save this file to your own computer before clicking on an Import OPML command in your own feed reader to upload the file which will then import all the feeds) or it can be used by webmasters to integrate MedWorm feeds with their own website. This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 34.

Discordant Estrogen and Progesterone Receptor Status in Breast Cancer
Conclusion: ER–/PR+ is by far the most rare and least reproducible subset of breast cancer cases. Given the lack of reproducibility of the ER–/PR+ group and the minimal reported benefit from hormonal therapy in these patients (2), these data question the clinical utility of assessment of PR, particularly in ER– breast cancer.1. Collins LC, Marotti JD, Baer HJ, Tamimi RM. Comparison of estrogen receptor results from pathology reports with results from central laboratory testing. Journal of the National Cancer Institute. 2008;100(3):218–21.2. Anderson H, Hills M, Zabaglo L, A'Hern R, Leary AF, Haynes ...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Hefti, M., Hu, R., Knoblauch, N., Collins, L., Tamimi, R., Beck, A. Tags: Poster Session 5 - Detection/Diagnosis: Diagnostic Pathology Source Type: research

Basement membrane localized tumor cells are protected from HER2-targeted therapy in vivo.
Drug resistance compromises the efficacy of HER2-targeted therapy. Results from our laboratory, and previous reports from others, indicate that tumor cell attachment to basement membrane (BM) and other extracellular matrix (ECM) proteins may confer drug resistance. We have discovered a differential drug response between the outer, matrix-attached cells and inner matrix-deprived cells comprising 3D tumor spheroids grown in reconstituted BM (Muranen 2012). The outer matrix-attached cells are resistant to multiple drug therapies due to upregulation of a multi-factor survival program including anti-apoptotic proteins and growt...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Zoeller, J., Bronson, R., Gilmer, T., Selfors, L., Lu, Y., Apple, S., Press, M., Hurvitz, S., Slamon, D., Mills, G., Brugge, J. Tags: Poster Session 4 - Tumor Cell and Molecular Biology: Drug Resistance Source Type: research

PI3K/mTOR inhibition overcomes in vitro and in vivo trastuzumab resistance independent of feedback activation of pAKT
In this study, we assessed the potential of targeting the PI3K/mTOR pathway in overcoming both de novo and acquired trastuzumab resistance.Materials and Methods: The in vitro activity of the pan-PI3K inhibitor BKM120, the mTORC1 inhibitor RAD001 and the dual PI3K/mTORC1/2 inhibitor BEZ235 were evaluated in a panel of 49 human breast cancer and immortalized cell lines. The in vivo activity of these molecules was assessed in six cell line xenografts models representing, ER+/HER2– (KPL-1, ZR75-1), ER+/HER2+ (UACC812, MDA361), ER–/HER2+ (SUM190), PIK3CA mutant (SUM190, MDA361), PTEN-null (ZR75-1) and trastuzumab re...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: O'Brien, N., McDonald, K., Tong, L., Von Euw, E., Conklin, D., Kalous, O., Di Tomaso, E., Schnell, C., Linnartz, R., Hurvitz, S., Finn, R., Hirawat, S., Slamon, D. Tags: Poster Session 4 - Tumor Cell and Molecular Biology: Drug Resistance Source Type: research

Rapamycin and Dalotuzumab in combination inhibit parental and endocrine resistant breast cancer cells.
The PI3K/Akt/mTOR pathway is involved in breast cancer resistance to endocrine therapy. Inhibitors of mTOR have been shown to have benefit for patients with ER positive tumors that have developed endocrine therapy resistance. Inhibition of mTOR triggers a negative feedback loop resulting in enhanced phosphorylation of Akt and subsequent breast cancer cell proliferation via the IGF signaling pathway. Therefore, blockade of both IGF-1R and mTOR may be necessary to completely suppress this pathway. Our laboratory studied the effect of dual inhibition of mTOR and IGF-1R with rapamycin and dalotuzumab respectively on parental a...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Beckwith, H., Fettig-Anderson, L., Yueh, N., Douglas, Y. Tags: Poster Session 4 - Tumor Cell and Molecular Biology: New Drugs and Mechanisms Source Type: research

The potential use of Optical Coherence Tomography for intraoperative breast tumour margin width estimation
Total mastectomy and lumpectomy with radiation have been shown to have equivalent patient outcomes, which has likely contributed to the more widespread adoption of breast conserving surgery (BCS) procedures. Assessment of breast lumpectomy margin widths in both an accurate and timely manner is essential to successful breast conservation procedures. Current BCS methodologies have been reported to result in reoperation rates of up to 20–60%, which represents a significant and unmet need for improved margin assessment. High reoperation rates present both increased treatment risk to patients and increased burden on healt...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Wilson, B., Akens, M., Niu, C. Tags: Poster Session 4 - Detection/Diagnosis: Breast Imaging - Other Methods Source Type: research

Safety and Efficacy of Zoledronic Acid Beyond 24 Months in Breast Cancer Patients
Conclusion: Prolonged treatment with Zoledronic acid seems to be well tolerated and should be studied in prospective, randomized studies to document prolonged skeletal efficacy and survival.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-02.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Suzuki, Y., Saito, Y., Ogiya, R., Oshitanai, R., Terao, M., Terada, M., Morioka, T., Tsuda, B., Niikura, N., Okamura, T., Tokuda, Y. Tags: Poster Session 3 - Treatment: Bone Metastases Source Type: research

Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases.
Brain metastases remain a serious obstacle in the treatment of patients with human epidermal growth factor receptor-2 (HER2)-amplified breast cancer. Unlike HER2-amplified breast tumors growing in extra-cranial locations, brain metastases do not respond well to HER2 inhibitors and are often the reason for treatment failure. One of the major challenges in studying brain metastases is the lack of preclinical models. We developed a HER2-amplified mouse model of brain metastasis using an orthotopic xenograft of BT474 cells in mice. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib failed to contain brain metas...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Kodack, D., Chung, E., Yamashita, H., Incio, J., Peters, A., Song, Y., Ager, E., Huang, Y., Farrar, C., Lussiez, A., Goel, S., Snuderl, M., Kamoun, W., Hiddingh, L., Tannous, B., Fukumura, D., Engelman, J., Jain, R. Tags: Poster Session 3 - Treatment: Brain Metastases Source Type: research

Regulation of inflammatory breast cancer cell invasion through Akt1/PKB{alpha} phosphorylation of RhoC GTPase
With a 42% and 18% 5- and 10-year respective disease-free survival rate, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. IBC invades the dermal lymphatic vessels of the skin overlying the breast and as a consequence nearly all women have lymph node involvement and ~1/3 have gross distant metastases at the time of diagnosis. One year after diagnosis ~90% of patients have detectable metastases, making IBC a paradigm for lymphovascular invasion. Understanding the underlying mechanisms of the IBC metastatic phenotype is essential for new therapies. Work from our laboratory and others show dist...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Lehman, H., Van Laere, S., van Golen, C., Vermeulen, P., Dirix, L., van Golen, K. Tags: Poster Session 3 - Treatment: Inflammatory Breast Cancer Source Type: research

Use of the MiCK drug-induced apoptosis assay improves clinical outcomes in recurrent breast cancer (BRCA)
Conclusions: Use of the MiCK assay to determine chemotherapy was associated with a higher response rate and a longer time to relapse in pts with recurrent or metastatic BRCA. It is possible that OS is also improved, but longer follow up is needed. There was a trend for improved outcomes if the best chemotherapy based on the MiCK assay was used.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-28.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Bosserman, L., Rogers, K., Davidson, D., Whitworth, P., Karimi, M., Upadhyaya, G., Rutledge, J., Hallquist, A., Perree, M., Presant, C. Tags: Poster Session 3 - Prognostic and Predictive Factors: Response Predictions - Biomarkers and Other Factors Source Type: research

Effect of TOP2A and cMYC gene copy number on outcome in a Phase II trial of adjuvant TC (Docetaxel/Cyclophosphamide) plus trastuzumab (HER TC) in HER2-positive early stage breast cancer
Conclusion: Outcome (DFS + OS) in a phase II study of a nonanthracycline regimen (TC) coupled with H was unaffected by cMYC or TOP2A gene copy number status. Only ER and nodal status showed an effect in a multivariate analysis.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-12.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Jones, S., Collea, R., Paul, D., Sedlacek, S., Favret, A., Gore, I., Lindquist, D., Holmes, F., Allison, M., Steinberg, M., Stokoe, C., Portillo, R., Crockett, M., Wang, Y., Lina, A., Robert, N., O'Shaughnessy, J. Tags: Poster Session 3 - Prognostic and Predictive Factors: Response Predictions - Biomarkers and Other Factors Source Type: research

Molecular subtyping improves stratification of patients into diagnostically more meaningful risk groups
Conclusions: This retrospective study showed that Molecular Subtyping with BluePrint and MammaPrint leads to clinically significant prognostic and molecular stratification. The use of MammaPrint and BluePrint in the management of patients with primary breast cancer should be considered for a more accurate selection of adjuvant therapies in this era of personalized medicine.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-01.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Cristofanilli, M., Turk, M., Kaul, K., Weaver, J., Wesseling, J., Stork-Sloots, L., de Snoo, F., Yao, K. Tags: Poster Session 3 - Tumor Cell and Molecular Biology: Tumor Heterogeneity/Molecular Subclassification Source Type: research

Survival impact of early detection of recurrence after surgery in early breast cancer patients
Conclusions: Our data may support the hypothesis that early detection of breast cancer recurrences has beneficial impact on survival. Randomized clinical trial would be warranted to prove this hypothesis, and we are currently planning this.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-06.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Hojo, T., Tamura, K., Masuda, N., Inoue, K., Kinoshita, T., Fujisawa, T., Hara, F., Saji, S., Asaga, S., Anan, K., Yamamoto, N., Wada, N., Takahashi, M., Nakagami, K., Kuroi, K., Iwata, H. Tags: Poster Session 3 - Detection/Diagnosis: Screening Source Type: research

Insulin, Insulin-like Growth Factor-1 and cycling estrogen predict premenopausal mammographic density.
Conclusion: Our study supports that insulin, IGF-1 and IGFBP-3 independently, and in combination with cycling estrogen, predicts premenopausal mammographic density. These hormones may be important biomarkers in breast cancer control and clinical practice.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-01.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Frydenberg, H., Flote, V., Iversen, A., Finstad, S., Furberg, A.-S., Fagerland, M., Wist, E., Schlichting, E., Ellison, P., McTiernan, A., Ursin, G., Thune, I. Tags: Poster Session 3 - Detection/Diagnosis: Breast Imaging - Mammography Source Type: research

An efficient resource to accelerate research into the cause and prevention of breast cancer: the Love/Avon Army of Women
Conclusions: The AOW has proved to be a successful resource for scientists to accelerate accrual, expand the number and diversity of their subject population and to obtain exactly the type of specimens they need when they need it. This partnership between women and scientists has revolutionized research and accelerated efforts to eradicate breast cancer. The public is ready and willing to partner with the research community to find the answer to urgent clinical problems. The DSLRF will launch a new initiative this fall to harness the public's desire to be active research participants: The Health of Women (HOW) Study, an on...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Love, S. Tags: Poster Session 2 - Treatment: Patient Resources Source Type: research

Evaluation of Aromatase Inhibitor failure and total healthcare expenditures among post-menopausal women with metastatic ER+/HER2- breast cancer in the US
Aromatase Inhibitors (AIs) have replaced tamoxifen as first-line therapy for post-menopausal women with metastatic, ER+ breast cancer (BC). However, little information is available on the real-world use of AIs. This retrospective administrative claims study compared healthcare expenditures of post-menopausal women with metastatic ER+/HER2– BC treated with AIs and experiencing 0 or ≥ 1 AI failures (AIF).Women ≥ 55 years of age newly diagnosed with stage IV BC (index) were identified in the 2006–2010 Thomson Reuters MarketScan databases and followed until the earliest of chemotherapy, combination therapy, e...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Namjoshi, M., Landsman-Blumberg, P., Thomson, E., Chu, B. Tags: Poster Session 2 - Treatment: Endocrine Therapy - Advanced Disease Source Type: research

A phase II study of combined fulvestrant and RAD001 (everolimus) in metastatic estrogen receptor (ER) positive breast cancer after aromatase inhibitor (AI) failure.
Conclusions: Combined everolimus with fulvestrant is feasible and has manageable toxicities in this cohort of women with metastatic ER-positive breast cancer. Detailed efficacy analysis along with updated toxicity data will be presented at the meeting.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-14-05.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Croley, J., Black, E., Romond, E., Chambers, M., Waynick, S., Slone, S., Waynick, C., Stevens, M., Weiss, H., Massarweh, S. Tags: Poster Session 2 - Treatment: Endocrine Therapy - Advanced Disease Source Type: research

Pharmacological impact of endoxifen in a laboratory simulation of tamoxifen therapy in postmenopausal breast cancer patients
This study (PYM) was supported by Susan G. Komen for the Cure International Postdoctoral Fellowship under Award number SAC100009(VCJ), and the Department of Defense Breast Program under Award number W81XWH-06-1-0590 (VCJ).Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-09.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Maximov, P., McDaniel, R., Bhatta, P., Brauch, H., Jordan, V. Tags: Poster Session 2 - Treatment: Endocrine Therapy - Adjuvant Source Type: research

Continuous association of a 200-gene prognostic risk score with probability of neoadjuvant chemotherapy response and translation from fresh frozen to FFPE tissue for clinical use.
BreastPRS is a suite of complimentary gene signatures that resolves several of the significant limitations of current gene expression signatures in breast cancer. Notably, BreastPRS can accurately provide prognosis prediction, histological grade resolution and molecular subtyping of invasive breast cancer. The 200-gene prognostic component was previously validated in an independent retrospective series of 1,016 previously published fresh-frozen breast cancers and has now been applied to data from over 6,000 patients.In part one of this study, a meta-analysis of 890 previously published neoadjuvant treated breast cancer pat...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: van Laar, R., DiPaola, J., Carbaugh, H., Murphy, T., DiRamio, A., Flinchum, R., Brown, N., Albino, T. Tags: Poster Session 2 - Prognostic and Predictive Factors: Prognostic Factors - Clinical Source Type: research

Clinical validation of the PAM50 risk of recurrence (ROR) score for predicting residual risk of distant-recurrence (DR) after endocrine therapy in postmenopausal women with ER+ early breast cancer (EBC): An ABCSG study
Discussion: This large clinical trial serves both as a clinical validation study of the PAM 50 test and as a demonstration that a complex multi-analyte gene-expression test can be performed in a routine hospital pathology laboratory while meeting the same quality metrics as a central referral laboratory. The results of the primary analysis, when combined with the results already reported from the Trans ATAC population, yield Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC and form the basis of the design of the clinical utility studies of the PAM 5...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Gnant, M., Filipits, M., Mlineritsch, B., Dubsky, P., Jakesz, R., Kwasny, W., Fitzal, F., Rudas, M., Knauer, M., Singer, C., Greil, R., Ferree, S., Storhoff, J., Cowens, J., Schaper, C., Liu, S., Nielsen, T., the ABCSG Tags: Poster Session 2 - Prognostic and Predictive Factors: Prognostic Factors - Clinical Source Type: research

HER2 gene status change after taxanes based chemotherapy: be a ware of miss-interpretation of polyploidization! Impact for patient management.
Conclusions and recommendations: As a result of taxane administration, polyploid cells are formed and that most (if not all) chromosomes have been replicated simultaneously because of absent chromosomal segregation secondary to microtubule inhibition by taxanes. This HER2 copy increase is distinct from the mechanisms accounting for a more restricted gene amplification during carcinogenesis. The viability of giant polyploid cells is particularly low and most if not all of these cells succumb to mitotic catastrophe, an onco-suppressive mechanism causing cell cycle arrest and cell death. Irrespective of this consideration, it...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Valent, A., Penault-Llorca, F., Cayre, A., Kroemer, G. Tags: Poster Session 2 - Tumor Cell and Molecular Biology: Genetics - Somatic Changes Source Type: research

Preferential Activation of BP1 and c-Myc in Breast Cancer of African American Women Compared with Caucasian American Women
Conclusions: c-Myc is a potent oncogene known to increase transformation and proliferation. We show here that c-Myc is upregulated by BP1, a gene which is preferentially activated in breast tumors of AAW. Furthermore, we have identified an interesting mechanism by which BP1 and c-Myc may co-activate transcription involving a positive feedback loop, an attractive therapeutic target. The proposed mechanism could partially explain the aggressiveness of tumors of AAW.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-22.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Berg, P., Ghimbovschi, S., Grizzle, W., Nguyen, T. Tags: Poster Session 2 - Tumor Cell and Molecular Biology: Biomarkers Source Type: research

Quantitative measurement of HER2 expression in breast cancers: comparison with "real world" HER2 testing in a multi-center Collaborative Biomarker Study (CBS) and correlation with clinicopathological features
Conclusions: H2T by HERmark yields a continuum of quantitative HER2 protein measurements that shows an excellent correlation with central HER2 IHC retesting and confirms the known correlations between HER2 expression with tumor grade and ER/PR status. OS results of concordant HER2 positive or negative groups (between local HER2 testing and HERmark H2T) confirmed that HER2 positive patients (excluding adjuvant trastuzumab therapy) have worse OS than patients with HER2 negative disease. However, in the HERmark and local HER2 discordant groups, OS appeared to track better with H2T by HERmark and not with the local HER2 status...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Yardley, D., Kaufman, P., Adams, J., Krekow, L., Savin, M., Lawler, W., Zrada, S., Starr, A., Einhorn, H., Schwartzberg, L., Huang, W., Weidler, J., Lie, Y., Paquet, A., Haddad, M., Anderson, S., Brigino, M., Bosserman, L. Tags: Poster Session 2 - Tumor Cell and Molecular Biology: Biomarkers Source Type: research

Identification of cancer stem cells (CD44+CD24-/lo) in bone marrow as a prognostic factor in early breast cancer patients
Conclusions: Our data indicate that the presence of BM metastasis is correlated to CSCs, and CSCs irrespective of ALDH activity are independent adverse prognostic factors in EBC patients. Moreover, the presence of CTCs was a strong independent predictor of DFS.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-03-01.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Giordano, A., Gao, H., Cohen, E., Anfossi, S., Hess, K., Krishnamurthy, S., Tin, S., Cristofanilli, M., Hortobagyi, G., Woodward, W., Ueno, N., Lucci, A., Reuben, J. Tags: Poster Session 2 - Detection/Diagnosis: Micrometastases Source Type: research

Accurate identification of metastatic breast cancer using methylated gene markers in circulating free DNA in peripheral blood
Conclusion: Our results suggest that methylated DNA in serum accurately discriminates between blood samples from normal women and from metastatic breast cancer patients. Also, early changes after therapy initiation for metastatic disease may correlate with subsequent clinical outcome. Assay analytical validation studies are ongoing. Studies examining a potential role in surveillance in the adjuvant setting and therapeutic benefit in the metastatic setting are warranted.1. Fackler MJ et al. Genome-wide methylation analysis identifies genes specific to breast cancer hormone receptor status and risk of recurrence. Cancer Res....
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Sukumar, S., Fackler, M., Lopez-Bujanda, Z., Teo, W., Jeter, S., Umbricht, C., Visvanathan, K., Wolff, A. Tags: Poster Session 2 - Detection/Diagnosis: Circulating Markers Source Type: research

Prognostic relevance of statistically standardized estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in tamoxifen(TAM)-treated NCIC CTG MA.14 patients
Discussion: In MA.14, all women received TAM. Local ER/PR status using categorical or semi-quantitative values did not impact RFS. A statistically standardized approach using continuous centralized ER, PR, HER2 by RT-PCR demonstrated that increasing PR values were associated with better RFS. Evaluation in other trials may provide support for this methodology.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-13.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Chapman, J.-A., Sgroi, D., Goss, P., Richardson, E., Binns, S., Zhang, Y., Schnabel, C., Erlander, M., Pritchard, K., Han, L., Shepherd, L., Pollak, M., NCIC Clinical Trials Group Tags: Poster Session 1 - Prognostic and Predictive Factors: Biomarkers - Methods Source Type: research

Attainment of extremely high concordance rates between fluorescence in situ hybridization and immunohistochemistry in testing for human epidermal growth factor receptor 2 (HER2) in breast cancer using a normalized scoring system for immunohistochemistry: a four year experience with over 9000 cases
Discussion: Extremely high concordance rates, with elimination of the vast majority of false IHC positive cases, can be attained in a clinical laboratory examining tissues from divergent sources, even in the absence of controlling pre-analytical variables, by employing a normalized scoring system for IHC.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-01.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Gown, A., Goldstein, L., Tse, C., Hwang, H., Kandalaft, P. Tags: Poster Session 1 - Prognostic and Predictive Factors: Biomarkers - Methods Source Type: research

Evaluation of the stage IB designation of the 7th edition of the AJCC staging system: Biologic factors are more important
Conclusion: Differentiating patients with micrometastases (stage IB) from node negative patients (stage IA) does not stratify patients well with respect to survival. Biologic factors including ER status and grade are better discriminants of survival than the presence of small volume nodal metastases in patients with early stage breast cancer. Breast cancer staging should include biologic factors from the primary tumor.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-06.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Mittendorf, E., Ballman, K., McCall, L., Hansen, N., Lucci, A., Gabram, S., Urist, M., Crow, J., Hurd, T., Hunt, K., Giuliano, A. Tags: Poster Session 1 - Detection/Diagnosis: Axillary Staging and Sentinel Nodes Source Type: research

ADAPT - Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early breast cancer
Background: Appropriate indication for chemotherapy (CTx) in patients with hormone receptor (HR) positive breast cancer (BC), prediction of CTx response, and addition of novel targeted therapies are the most important questions in adjuvant therapy of early BC. Few well evaluated prognostic tests identify patients (pts) with a low-risk profile resulting in a low enough CTx benefit to justify omission of CTx. Several clinical trials with results still pending have already addressed this question such as TAILORx, MINDACT, NNBC-3, WSG-planB.However, proliferation seems to be a key part of all prognostic genomic signatures. Mor...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Gluz, O., Hofmann, D., Kates, R., Harbeck, N., Nitz, U. Tags: Ongoing Trials 3 - Chemotherapy Source Type: research

Predictive value of a proliferation score (MS) in postmenopausal women with endocrine-responsive breast cancer: results from International Breast Cancer Study Group (IBCSG) Trial IX
Conclusions: Low MS was associated with differential benefit favoring those women receiving CMF->T vs T alone for both DFS and BCFI in the first 7 years. The effect was independent of traditional risk factors including Ki67. Hence this study, which is unconfounded by chemotherapy-induced ovarian ablation in younger women, identifies a subset of postmenopausal women with ER+, HER2– tumors that benefit from CMF chemotherapy. This seemingly incongruous observation is consistent with a) the prior observation that only the low-proliferation subgroup by PAM50 11-gene signature benefits from the addition of weekly paclit...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Sninsky, J., Wang, A., Gray, K., Lagier, R., Christopherson, C., Rowland, C., Chang, M., Kammler, R., Viale, G., Kwok, S., Regan, M., Leyland-Jones, B. Tags: Poster Discussion 10 - Prognostic / Predictive Source Type: research

Development of a highly reproducible clinical test for Ki67 using AQUA technology
Discussion: The use of image analysis has been shown to be of significant value in expression assessment due to increased objectivity and the potential for broader standardization. We have demonstrated that the use of advanced image analysis when coupled with fluorescence immunohistochemistry can produce a system with greatly improved precision over traditional IHC methods in clinically relevant samples. These results indicate that image analysis of Ki67 is advantageous over manual IHC in clinical diagnostic assessment.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD06-03.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Murphy, D., Pacia, E., Beruti, S., Lamoureux, J., Dabbas, B., Diver, J., Christiansen, J. Tags: Poster Discussion 6 - Ki67 Source Type: research

Pre-surgical Trial of Metformin in Overweight and Obese, Multi-ethnic Patients with Newly Diagnosed Breast Cancer
Conclusions: Our study is unique to other pre-surgical metformin trials due to the enrichment of overweight/obese BC patients and the ethnically diverse population. We observed a significant decrease in serum cholesterol and leptin with metformin, and a trend toward lower insulin, HOMA, and adiponectin. No significant changes in glucose or IGFP-3 levels are noted. We are awaiting tumor-based biomarker evaluation. Pre-surgical trials can assess an agent's biological effect prior to long-term intervention trials.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD03-03.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Kalinsky, K., Crew, K., Refice, S., Wang, A., Feldman, S., Taback, B., Hibshoosh, H., Maurer, M., Hershman, D. Tags: Poster Discussion 3 - Metformin / Statins Source Type: research

Automated Quantitative RNA In Situ Hybridization for Resolution of Equivocal and Heterogeneous ERBB2 (HER2) Status in Invasive Breast Carcinoma
Conclusion: RNAscope analysis of HER2 mRNA is an effective means to resolve HER2 status in double equivocal cases and cases that demonstrate heterogeneity. Automation and image analysis-based quantification minimize analytical and post-analytical variability. Quantification of single RNA transcripts in situ at single-cell level demonstrates superiority over qRTPCR and great potential in predictive biomarker analysis. Further studies of larger cohorts correlating clinical response with HER2 mRNA expression in situ are warranted.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-04.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Wang, Z., Portier, B., Gruver, A., Bui, S., Wang, H., Su, N., Vo, H.-T., Ma, X.-J., Luo, Y., Budd, G., Tubbs, R. Tags: Poster Discussion 2 - HER2 Source Type: research

Her2 expression measured by AQUA analysis on BCIRG-005 and BCIRG-006 predicts the benefit of Herceptin therapy
Conclusions: Analysis of the cases in this study originally determined to be HER2+ by FISH indicates that AQUA may improve predictions of which patients will benefit from Herceptin therapy.Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-01.
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Christiansen, J., Barakat, N., Murphy, D., Rimm, D., Dabbas, B., Nerenberg, M., Beruti, S., Quinaux, E., Hall, J., Press, M., Slamon, D. Tags: Poster Discussion 2 - HER2 Source Type: research

Investigating Breast Cancer with Single-Cell Sequencing
Tumors evolve from single cells. As they evolve, they acquire complex somatic mutations and diversify, forming distinct subpopulations of cells. This intratumor heterogeneity confounds basic research and clinical practice because tools do not exist to resolve it. Standard genomic methods are limited to reporting an average signal from a complex population of cells, because they require a large amount of input material. These bulk methods may mask population diversity and rare cells in the tumor - that may be the most malignant. To address this limitation my laboratory has developed single-cell sequencing tools to delineate...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Navin, N. Tags: Educational Session 5 - Mammary Cell Lineages and Breast Cancer Subtypes Source Type: research

Navigating the Genome: Quandaries and Approaches to Dealing with Genomic Information
Recent technological advances have made large-scale DNA sequencing, including whole genome sequencing, a practical reality. The ability to sequence tumor genomes as well as the germ-line genome of individuals holds considerable promise for the practice of oncology. Broad assessment of cancer risk in individuals, identification of those at extreme risk for cancer who might benefit from specific interventions and pharmacogenomic guidance regarding therapy are possible benefits of assessing an individual's genome. Likewise, analysis of genomic information in tumors is poised to begin helping to guide highly specific treatment...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Evans, J. Tags: Mini-Symposium 3 - SNPs: Germline Polymorphisms in Breast Cancer Susceptibility and Treatment Toxicity Source Type: research

Prolactin-humanized mice: an improved animal recipient for therapy response-testing of patient-derived breast cancer xenotransplants
Eighty percent of newly diagnosed breast cancer represents estrogen receptor(ER)-positive luminal subtypes. Many patients with luminal breast cancer develop antiestrogen resistant disease. It has historically been particularly difficult to establish ER-positive breast cancer lines from primary breast cancer in the laboratory or in mice. Murine and bovine prolactins, the major lactogens in current laboratory experimental in vivo and in vitro conditions, fail to activate human prolactin receptors because of species incompatibility. In fact, murine prolactin is a potent antagonist for human prolactin receptors. Because ER-pos...
Source: Cancer Research - December 17, 2012 Category: Cancer & Oncology Authors: Rui, H., Utama, F., Yanac, A., Xia, G., Peck, A., Liu, C., Rosenberg, A., Wagner, K.-U., Yang, N. Tags: General Session 1 Source Type: research

Efficient nucleus detector in histopathology images
Summary In traditional cancer diagnosis, (histo)pathological images of biopsy samples are visually analysed by pathologists. However, this judgment is subjective and leads to variability among pathologists. Digital scanners may enable automated objective assessment, improved quality and reduced throughput time. Nucleus detection is seen as the corner stone for a range of applications in automated assessment of (histo)pathological images. In this paper, we propose an efficient nucleus detector designed with machine learning. We applied colour deconvolution to reconstruct each applied stain. Next, we constructed a large feat...
Source: Journal of Microscopy - December 17, 2012 Category: Laboratory Medicine Authors: J.P. VINK, M.B. VAN LEEUWEN, C.H.M. VAN DEURZEN, G. DE HAAN Source Type: research

Low‐temperature‐SEM study of dihedral angles in the ice‐I/sulfuric acid partially molten system
Summary The transport and mechanical properties of partially molten materials are influenced by the wetting behaviour of the melt with respect to the crystalline solid. The equilibrium microstructure of an ice + melt system was examined using low‐temperature scanning electron microscopy. The samples were prepared by spraying a liquid solution of H2O‐H2SO4 into liquid nitrogen and packing the frozen particulates into aluminium capsules. Samples were then sintered at –35 °C or –55 °C (above the eutectic temperature, TE=–62 °C) for various durations and were quenched in liquid nitrogen to capture the equili...
Source: Journal of Microscopy - December 17, 2012 Category: Laboratory Medicine Authors: C. McCARTHY, J.R. BLACKFORD, C.E. JEFFREE Source Type: research

KL-6, a Human MUC1 Mucin, as a prognostic marker for diffuse alveolar hemorrhage syndrome
Conclusions: Peak serum KL-6 level >=700 U/ml may become a clinically useful marker of poor prognosis for diffuse alveolar hemorrhage.
Source: Orphanet Journal of Rare Diseases - December 17, 2012 Category: Internal Medicine Authors: Yoshiko KidaShinichiro OhshimoKohei OtaTomoko TamuraTadatsugu OtaniKazunobu UneTakuma SadamoriYasumasa IwasakiFrancesco BonellaNoboru HattoriNobuyuki HirohashiJosune GuzmanUlrich CostabelNobuoki KohnoKoichi Tanigawa Source Type: research

Electrostatic simulations of a local electrode atom probe: The dependence of tomographic reconstruction parameters on specimen and microscope geometry.
Abstract We electrostatically model a local electrode atom probe microscope using the commercial software IES LORENTZ 2D v9.0 to investigate factors affecting the reconstruction parameters. We find strong dependences on the specimen geometry and voltage, and moderate dependences on the tip-aperture separation, which confirm that the current approach to atom probe reconstruction overlooks too many factors. Based on our data, which are in excellent agreement with known trends and experimental results, we derive a set of empirical relations which predict the values of the reconstruction parameters. These may be used t...
Source: Ultramicroscopy - December 16, 2012 Category: Laboratory Medicine Authors: Loi ST, Gault B, Ringer SP, Larson DJ, Geiser BP Tags: Ultramicroscopy Source Type: research

The effects of season and soil type on microbial degradation of gasoline residues from incendiary devices.
Abstract The primary task of a fire debris chemist is to determine if there is an ignitable liquid present in a fire debris sample and, if so, to classify it according to its boiling point and carbon number range. However, in organic-rich substrates such as soil, the ignitable liquid residue is subject to microbial degradation due to the ease with which bacteria can metabolize the various hydrocarbons present. This is a rapid process which is problematic in many forensic laboratories as fire debris is often stored for extended periods of time due to case backlog. Although microbial degradation has been studied in l...
Source: Analytical and Bioanalytical Chemistry - December 16, 2012 Category: Chemistry Authors: Turner DA, Goodpaster JV Tags: Anal Bioanal Chem Source Type: research

NEMs Induce Tumor Vessel Stabilization
Improving tumor perfusion, thus tempering tumor-associated hypoxia, is known to impair cancer progression. Previous work from our laboratory has shown that VEGF-A165 and semaphorin 3A (Sema3A) promote vessel maturation through the recruitment of a population of circulating monocytes expressing the neuropilin-1 (Nrp1) receptor (Nrp1-expressing monocytes; NEM). Here, we define the characteristics of bone marrow NEMs and assess whether these cells might represent an exploitable tool to induce tumor vessel maturation. Gene expression signature and surface marker analysis have indicated that NEMs represent a specific subset of ...
Source: Cancer Research - December 16, 2012 Category: Cancer & Oncology Authors: Carrer, A., Moimas, S., Zacchigna, S., Pattarini, L., Zentilin, L., Ruozi, G., Mano, M., Sinigaglia, M., Maione, F., Serini, G., Giraudo, E., Bussolino, F., Giacca, M. Tags: Microenvironment and Immunology Source Type: research

Variants of the HNF1α gene: a molecular approach concerning diabetic patients from southern Brazil
Maturity Onset Diabetes of the Young (MODY) presents monogenic inheritance and mutation factors which have already been identified in six different genes. Given the wide molecular variation present in the hepatocyte nuclear factor-1α gene (HNF1α) MODY3, the aimof this study was to amplify and sequence the coding regions of this gene in seven patients from the Campos Gerais region, Paraná State, Brazil, presenting clinical MODY3 features. Besides the synonymous variations, A15A, L17L, Q141Q, G288G and T515T, two missense mutations, I27L and A98V, were also detected. Clinical and laboratory data obtained from patients wer...
Source: Genetics and Molecular Biology - December 15, 2012 Category: Genetics & Stem Cells Source Type: research

Laboratory diagnosis of neurocysticercosis: review and perspectives
A neurocisticercose é causada por Cysticercus cellulose, a forma larval de Taenia solium, quando este se aloja no sistema nervoso central. O seu diagnóstico é realizado com base em dados clínicos, epidemiológicos, demonstração do agente etiológico pelas técnicas de imagem e testes laboratoriais. No presente estudo, apresentamos uma revisão do diagnóstico laboratorial, com ênfase no desempenho dos testes para pesquisa de anticorpos específicos e detecção de antígenos circulantes, utilização de antígeno homólogo ou heterólogo, nativo e recombinante, bem como a aplicação de métodos moleculares.Neurocys...
Source: Jornal Brasileiro de Patologia e Medicina Laboratorial - December 15, 2012 Category: Pathology Source Type: research

Antifungal susceptibility of Candida spp. in vitro among patients from Regional University Hospital of Maringá-PR
CONCLUSION: In the comparison between broth microdilution and disk diffusion (DD) methods, fluconazole showed good correlation for most Candida spp., which corroborates the usefulness of DD in the screening of main antifungal agents used in clinical practice. Nonetheless, cases of resistance detected by DD need to be confirmed by MD method, which avoids false-resistant results and maximizes the treatment efficacy and reliability.
Source: Jornal Brasileiro de Patologia e Medicina Laboratorial - December 15, 2012 Category: Pathology Source Type: research

[Increasing awareness of Clostridium difficile infection among patients with acute gastroenteritis admitted to a department of infectology].
Conclusion: The results confirm the increasing importance of Clostridium difficile infection among patients with acute gastroenteritis. Orv. Hetil., 2012, 153, 1992-1997. PMID: 23220365 [PubMed - in process]
Source: Orvosi Hetilap - December 15, 2012 Category: Journals (General) Authors: Fodor D, Ume KL, Matkó M, Nacsa E, Urbán E, Hajdú E Tags: Orv Hetil Source Type: research

Percutaneous Paravalvular Leak Closure.
Abstract Paravalvular leak (PVL) is a known complication of surgical and transcatheter valve replacement procedures. Patients most commonly present with congestive heart failure and/or hemolysis, and repeat surgical procedures to correct the PVL carries increased risk with reduced likelihood of success. As a result, percutaneous approaches to PVL closure have been developed, with a considerable emphasis on multimodality imaging for both diagnosis and procedural guidance in the cardiac catheterization laboratory. Several large series of percutaneous PVL closure have been recently published, with encouraging results ...
Source: Circulation Journal - December 15, 2012 Category: Cardiology Authors: Krishnaswamy A, Kapadia SR, Tuzcu EM Tags: Circ J Source Type: research

Significant steps in the evolution of analytical chemistry-Is the today's analytical chemistry only chemistry?
Abstract In this review the history of chemistry and specifically the history and the significant steps of the evolution of analytical chemistry are presented. In chronological time spans, covering the ancient world, the middle ages, the period of the 19th century, and the three evolutional periods, from the verge of the 19th century to contemporary times, it is given information for the progress of chemistry and analytical chemistry. During this period, analytical chemistry moved gradually from its pure empirical nature to more rational scientific activities, transforming itself to an autonomous branch of chemistr...
Source: Talanta - December 15, 2012 Category: Chemistry Authors: Karayannis MI, Efstathiou CE Tags: Talanta Source Type: research

Influence of precursor solvent extraction on stable isotope signatures of methylamphetamine prepared from over-the-counter medicines using the Moscow and Hypophosphorous routes.
Abstract A number of methods of clandestine manufacture of methylamphetamine involve the extraction and subsequent reaction of pseudoephedrine hydrochloride with other essential chemicals. The precursor can be easily extracted from over-the-counter medication widely available in the UK and elsewhere. Essential chemicals such as iodine and red phosphorous are also readily available and can be extracted from iodine tinctures and matchboxes, respectively. This work reports the repetitive preparation of methylamphetamine using two popular routes (the Moscow and Hypophosphorous synthesis). The focus was on the extractio...
Source: Analytical and Bioanalytical Chemistry - December 15, 2012 Category: Chemistry Authors: Nicdaéid N, Jayamana S, Kerr WJ, Meier-Augenstein W, Kemp HF Tags: Anal Bioanal Chem Source Type: research

Psychiatric Illness of Systemic Lupus Erythematosus in Childhood: Spectrum of Clinically Important Manifestations.
CONCLUSION: Cognitive dysfunction was present in all and additional psychosis present in 75% of pediatric patients with psySLE. Visual distortion and early preservation of insight were unique features of psychosis observed in this cohort of children/adolescents with psySLE. PMID: 23242179 [PubMed - as supplied by publisher]
Source: J Rheumatol - December 15, 2012 Category: Rheumatology Authors: Lim LS, Lefebvre A, Benseler S, Peralta M, Silverman E Tags: J Rheumatol Source Type: research