HNBR and its MWCNT reinforced nanocomposites : Crystalline morphology and electrical response

Morphology and electrical response of hydrogenated acrylonitrile butadiene rubber (HNBR) and its multiwall carbon nanotube (MWCNT) reinforced nanocomposites were studied by means of x-ray diffraction and broadband dielectric spectroscopy. HNBR systems were found to be semi-crystalline, with their crystallinity to increase with the addition of MWCNTs. In their dielectric spectra, four relaxation processes were detected. Ascending in relaxation time, these were attributed to: (i) interfacial polarization at the interface of crystalline and amorphous regions of HNBR and at the interface between HNBR and MWCNTs, (ii) glass to rubber transition of the amorphous part of HNBR, (iii) rearrangement of polar side groups, such as –CN, and (iv) local motions of small segments of the main elastomer chain. Electrical conductivity increases with MWCNT content and frequency increasing. The effect of temperature, on the electrical response, is more pronounced at low frequencies. The temperature dependence of the electrical conductivity strongly deviates from a pure Arrhenius behavior, signifying that the occurring conductance mechanisms do not correspond to a single thermally activated process. Relaxation dynamics imply that crystalline regions exert motion restrictions to large segments of the macromolecules in the amorphous phase and to polar parts of the systems

TBCRC 019: A phase II trial of nanoparticle albumin-bound paclitaxel with or without the anti-death receptor 5 monoclonal antibody tigatuzumab in patients with triple negative breast cancer

Purpose: Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in DR5+ human tumor cells without crosslinking. TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple-negative breast cancer (TNBC). Experimental Design: Randomized 2:1 phase II trial of albumin-bound paclitaxel (nab-PAC) ± TIG in patients with TNBC stratified by prior chemotherapy. Patients received nab-PAC weekly × 3 ± TIG every other week, every 28 days. Primary objective was within-arm objective response rate (ORR). Secondary objectives were safety, progression-free survival (PFS), clinical benefit, and TIG immunogenicity. Metastatic research biopsies were required. Results: Among 64 patients (60 treated; TIG/nab-PAC n = 39 and nab-PAC n = 21), there were 3 complete remissions (CR), 8 partial remissions (PR; 1 almost CR), 11 stable diseases (SD), and 17 progressive diseases (PD) in the TIG/nab-PAC arm (ORR, 28%), and no CRs, 8 PRs, 4 SDs, and 9 PDs in the nab-PAC arm (ORR, 38%). There was a numerical increase in CRs and several patients had prolonged PFS (1,025+, 781, 672, 460, 334) in the TIG/nab-PAC arm. Grade 3 toxicities were 28% and 29%, respectively, with no grade 4–5. Exploratory analysis suggests an association of ROCK1 gene pathway activation with efficacy in the TIG/nab-PAC arm. Conclusions: ORR and PFS were similar in both. Preclinical activity of TIG in basal-like breast cancer and prolonged PFS in few patients in the combination arm support further investigation of anti-DR5 agents. ROCK pathway activation merits further evaluation

Contraindications of sentinel lymph node biopsy: Áre there any really?

BACKGROUND: One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient. METHODS: In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery. RESULTS: Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure. CONCLUSION: When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers

Phase III Trial Results Comparing Lymphoseek with Blue Dye in Detection of the Sentinel Lymph Node in Breast Cancer

Abstract Background: Lymphoseek (99mTc-DTPA–mannosyl-dextran) is a novel radiopharmaceutical specifically designed for intra-operative sentinel lymph node (SLN) detection. It is the first radiopharmaceutical to target lymphatic tissue by a specific molecular interaction of the drug with receptors found on macrophages. We report the results of a multi-center, open-label within-patient comparative study of Lymphoseek and vital blue dye in the detection of sentinel lymph nodes in patients with known breast cancer.Materials and Methods: A phase III clinical trial was conducted. The protocol received the consent of the Food and Drug Administration as well as the institutional review boards of each enrolling institution. Patients with known breast cancer were screened. Entrance criteria were age >18, ECOG= 0-2, clinically negative nodes, non-pregnant status. Exclusion criteria were metastatic disease, bilateral breast cancer, need for bilateral mastectomy, reduction mammaplasty, previous axillary basin surgery or irradiation. Each patient provided written informed consent.Baseline labs and electrocardiograms were performed for each patient. Patients underwent intra-operative SLN mapping with 0.5- 1.0 mCi of Lymphoseek and blue dye. Surgery was performed to identify the SLN. The primary objective of efficacy was the concordance between Lymphoseek and vital blue dye in the in-vivo detection of the excised lymph node(s) as confirmed by pathology. The requirements for designating a lymph node as identified by Lymphoseek were: >50 counts per 2 seconds, lymph nodes containing >3 standard deviations of the mean background counts or nodes containing >10% of the activity of the hottest node. All identified SLNs were removed for analysis, disease free SLNs were subjected to enhanced pathologic evaluation. Follow-up safety labs, electrocardiograms and physical examinations were performed 6-30 hours post injection. All patients were monitored for adverse events.Results: A total of 8 centers participated in the trial and consented 77 female patients (age 31-78 years) for enrollment into the trial. Of the 71 patients who met all entrance criteria and went on to lymphatic mapping surgery, 131 SLNs (mean 1.8) were identified by Lymphoseek and 94 (mean 1.3) were identified by blue dye. There were 13 positive axillary basins (18%), all of which were identified by Lymphoseek. Overall concordance rate of Lymphoseek with blue dye was 98%. There were 68 adverse events (4 serious); none were attributed to the study drug.Discussion: The primary endpoint, in-vivo concordance of Lymphoseek with blue dye in the detection of the SLN was achieved with a 98% concordance rate. The high in-vivo concordance rate demonstrates Lymphoseek's ability to detect SLNs when compared to the “gold standard” treatment. In addition, Lymphoseek correctly identified metastatic disease in all of the 13 axillary basins containing disease and did so while demonstrating an acceptable safety profile throughout the study. No adverse events were considered to be due to the administration of the study drug. The use of Lymphoseek, the first in-kind agent specifically designed for lymph node mapping, was validated as safe and effective in this multi-center phase III trial. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 304