bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B16: The detection of ductal carcinoma using noninvasive hyperspectral imaging
Authors: Khouj Yasser , Dawson Jeremy , Coad James , Vona-Davis Linda 
Published: March 2017

Abstract
Introduction: Hyperspectral imaging (HSI) technology is an optical medical imaging modality that has great potential for noninvasive tissue analysis in breast cancer. This imaging method may be able to enhance the detection of cancer tissue and lead to advances in the optical diagnosis of patients. Objective: The goal of this study was to use high resolution hyperspectral imaging microscopy to differentiate marked biopsies of normal and breast cancer tissues. Methods: For our hyperspectral imaging platform, we obtained stained (n=10) and unstained (n=10) pathology slides from ductal carcinomas of the breast and compared them. To capture the HSI, we used a hyperspectral camera that generates a spectral cube containing the spectra of each pixel between 460 to 640 nm and normalized the data to a gray scale to maximize data stability. The spectral signatures were graphed using MATLAB software. Results: The system was able to detect a clear spectral difference between cancer and normal tissues in hematoxylin and eosin stained slides. The spectrum of cancer tissue had a relatively lower intensity than that of normal tissue in the wavelength range between 480 and 610 nm. Conclusions: Our preliminary study showed a clear hyperspectral snapshot differentiating normal breast tissue from ductal carcinoma. Further HSI and quantitative analysis will demonstrate the feasibility of using this new imaging technique in breast cancer.
Citation Format: Yasser Khouj, Jeremy Dawson, James Coad, Linda Vona-Davis. The detection of ductal carcinoma using noninvasive hyperspectral imaging. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B16.
Abstract B26: A novel applicator for endoscopic gene electrotransfer
Authors: Bahrami Arya J. , Connolly Richard J. , Campbell Jean S. , Pierce Robert H. 
Published: March 2017

Abstract
Intratumoral gene delivery is a novel immunotherapy showing promise in cutaneous cancers such as melanoma. However, the broad application of this technology is limited by delivery efficiency and tumor accessibility. Efficient gene delivery requires intimate association of DNA and cells and a coincident electric field. Due to the low diffusion of plasmid DNA combined with the single bolus injection provided by a standard syringe, conventional electrogene transfer yields a small volume of transfected tissue. Our novel use of a corkscrew delivery needle provides the dual benefit of increased DNA-tissue interface and anchoring of the device necessary for endoscopic use. This device has yielded efficient and repeatable delivery of cytokine-encoding plasmid DNA and reporter genes in several tumor models including spontaneous mammary carcinomas (MMTV-PyVT) as well as syngeneic tumor models. Anchoring associated with the action of corkscrew deployment ensures co-localization of the electric field with the injected tissue volume. The small form factor of this device makes it compatible with standard medical devices, including trocars, endoscopes and other catheter based devices, enabling intratumoral gene immunotherapy of previously inaccessible cancers, including breast cancer, lung cancer, and hepatocellular carcinoma.
Citation Format: Arya J. Bahrami, Richard J. Connolly, Jean S. Campbell, Robert H. Pierce. A novel applicator for endoscopic gene electrotransfer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B26.
Abstract B31: Development of an implanted pump for metronomic delivery of chemotherapy and biological compounds: the virtue of local delivery
Authors: Chen Thomas C. , Adell Frank , Schachar Joshua 
Published: March 2017

Abstract
The development of an implanted pump that can locally and metronomically deliver drugs and biological agents is crucial in the treatment of cancer. For the last eight years, we have worked on an implanted pump that can deliver precisely at microliter doses. The Ipsum pump (Cognos Therapeutics) has three components: a double lumen catheter, a sampling reservoir, and a pump. The drug is pumped out of the bellows (5 ml) via a hermetically sealed MRI compatible piezoelectric pump. The drug is delivered via the delivery catheter lumen into the target. The sampling lumen can draw from the target to determine levels of drug delivered, allowing for in-vivo pharmacokinetic measurements. The reservoir is connected to the catheter and can be used to sample fluid. An optical sensor (embedded spectrophotometer) is set a specific frequency to determine absorbance for pharmacokinetic measurements of drug delivered. The pump is powered by a long term battery (good for up to five years) and is wirelessly controlled externally by the physician operator. Our first disease model will be delivery of methotrexate to the cerebrospinal fluid in the treatment of leptomeningeal carcinomatosis.
Citation Format: Thomas C. Chen, Frank Adell, Joshua Schachar. Development of an implanted pump for metronomic delivery of chemotherapy and biological compounds: the virtue of local delivery. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B31.
Abstract B32: Feedback optimized gene electrotransfer for immunotherapy
Authors: Brown Douglas W. , Bahrami Arya J. , Canton David A. , Xu Yi , Tse Gavin Y. , Campbell Jean S. , Pierce Robert H. , Connolly Richard J. 
Published: March 2017

Abstract
Intratumoral electroporation of proinflammatory cytokine-encoding plasmid DNA promotes innate and adaptive immune responses that correlate with abscopal effects. The conditions selected to electroporate tumors are typically fixed parameters optimized in preclinical tumor models. These conditions have little translatability to clinically relevant tumors, as idealized models fail to capture the variability encountered in clinical tumors. Variables that affect treatment outcome include tumor size, degree of vascularization, fibrosis, and necrosis. These variables can result in sub-optimal gene transfer and variable therapeutic outcomes. To address the need to advance the practice of electroporation, a feedback controlled electroporation generator has been developed, which is capable of assessing the electrophysiological properties of tissue in real-time. Determination of these properties is accomplished by electrochemical impedance spectroscopy and model parameter estimation. Model parameters that estimate membrane integrity are used to adjust electroporation parameters for each applied pulse and stop the process when optimum gene transfer conditions are identified. Studies performed in syngeneic colon carcinoma tumors (MC38) and spontaneous mammary tumors (MMTV-PyVT) have demonstrated feedback-based electroporation is capable of achieving maximum expression of reporter genes with minimal collateral cell death. These findings represent an unprecedented advancement to the practice of gene electro-transfer, as retaining the viability of transfected cells is paramount to treatment success.
Citation Format: Douglas W. Brown, Arya J. Bahrami, David A. Canton, Yi Xu, Gavin Y. Tse, Jean S. Campbell, Robert H. Pierce, Richard J. Connolly. Feedback optimized gene electrotransfer for immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B32.
Abstract B45: Silencing ß3 integrin by targeted ECO/siRNA nanoparticles inhibits EMT and metastasis of triple-negative breast cancer
Authors: Parvani Jenny G. , Gujrati Maneesh D. , Mack Margaret A. , Schiemann William P. , Lu Zheng-Rong 
Published: March 2017

Abstract
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGFβ;-mediated EMT and invasion, restore TGFβ-mediated cytostasis, and inhibit three-dimensional organoid growth. Modification of ECO/siβ3 nanoparticles with an RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous injections of RGD-targeted ECO/siβ3 nanoparticles in vivo alleviated primary tumor burden and, more importantly, significantly inhibited metastasis. In the span of 16 weeks of the experiments and observations, including primary tumor resection at week 9 and release from the treatment for 4 weeks, the mice bearing orthotopic, TGFβ-prestimulated MDA-MB-231 tumors that were treated with RGD-targeted ECO/siβ3 nanoparticles were free of metastases and relapse, in comparison with untreated mice. Collectively, these results highlight ECO/siβ3 nanoparticles as a promising therapeutic regimen to combat TNBC.
Citation Format: Jenny G. Parvani, Maneesh D. Gujrati, Margaret A. Mack, William P. Schiemann, Zheng-Rong Lu. Silencing ß3 integrin by targeted ECO/siRNA nanoparticles inhibits EMT and metastasis of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr B45.
Abstract IA16: Spherical nucleic acids as a powerful new platform for cancer immunotherapy
Authors: Mirkin Chad A. 
Published: March 2017

Abstract
Spherical nucleic acids (SNAs) are nanoparticle-oligonucleotide conjugates characterized by a dense, spherical shell of radially oriented oligonucleotides. SNAs enter cells without the need for auxiliary transfection reagents, are more resistant to nuclease degradation than their linear counterparts, and show minimal toxicity and off-target immunogenicity. These emergent properties of the SNA platform enable the design of powerful immunotherapy agents against cancer cells.
The SNA platform allows simultaneous delivery of Toll-like receptor (TLR) agonist oligonucleotides and cancer-associated antigen peptides to antigen-presenting cells (APCs). The oligonucleotides on the surface of the SNAs activate of the innate immune system through TLRs to mature the APCs, which in turn activates effector immune cells to target cell displaying the cancer-associated peptide. Compared to mixtures of free peptides and oligonucleotides, SNAs exhibit up to 80-fold increase in potency, 400-fold higher cellular response to antigens and improve median survival in mice with lymphomas through antigen-specific targeting of cancer cells. The enhancement of the immune properties arises from a combination of increase in cellular uptake, polyvalent binding of SNAs to TLRs and the co-delivery of the TLR agonist oligonucleotides and peptide to the same cell. Additionally, the SNA architecture enables the control of oligonucleotide to peptide ratio, subcellular release location of the peptide and release kinetics. Combined with their high serum stability, at-scale synthesis and minimal toxicity profile, SNAs hold great promise for the development of cancer vaccines.
Citation Format: Chad A. Mirkin. Spherical nucleic acids as a powerful new platform for cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA16.
Abstract BS3-1: Unfolding the unfolded protein response in breast cancer
Authors: Chen X 
Published: March 2017

Abstract
During tumor development and progression, cancer cells encounter cytotoxic conditions such as hypoxia, nutrient deprivation, and low pH due to inadequate vascularization. To maintain survival and growth in the face of these physiologic stressors, a set of adaptive stress response pathways are induced. One adaptive pathway well studied in other contexts is the unfolded protein response (UPR), which is induced by factors affecting the endoplasmic reticulum (ER). Triple negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options and TNBC-targeted therapies do not yet exist. We found that XBP1, a key component of the UPR, is activated in TNBC and plays a pivotal role in the tumorigenicity and progression of this human breast cancer subtype. Depletion of XBP1 blocked primary tumor growth, inhibited tumor relapse and reduced the population of chemotherapy-resistant tumor initiating cells (TICs). Genome-wide mapping of the XBP1 transcriptional regulatory network revealed that XBP1 regulates the hypoxia response through controlling HIF1α transcriptional activity and the expression of HIF1α targets. Notably, we identified a gene expression signature indicative of XBP1 pathway activation that is associated with poor prognosis in two independent cohorts of patients with TNBC. Our findings reveal a key function for this branch of the UPR in TNBC, opening new therapeutic avenues for patients with TNBC.
Citation Format: Chen X. Unfolding the unfolded protein response in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr BS3-1.
Abstract CS1-2: CS1-2 Clinical utility of multi-gene testing in metastatic breast cancer
Authors: Bedard P 
Published: March 2017

Abstract
The goal of many ongoing precision medicine initiatives is to match patients to targeted treatment(s) based upon the identification of specific driver mutations in their tumors. Although large-scale research projects have elucidated the genomic landscape of breast cancer, they have not provided insight into the clinical utility of genomic testing. Institutional studies of small, targeted sequencing panel-based testing approaches involving patients with advanced, metastatic disease demonstrate that only a small proportion of patients ultimately receive genotype-matched treatment. The reasons for this low treatment matching rate include: institutional and/or geographic barriers to access to genotype-matched clinical trials; patient deterioration after testing results are reported; and the limited range of somatic mutations that are “druggable” with approved or investigational drug therapies. While there are promising signals of activity from early phase clinical trials with novel drug treatments targeting specific genomically defined subpopulations - including AKT1, ERBB2, ESR1 and PIK3CA mutations as well as FGFR1 amplification - and advances in circulating tumor DNA technology may allow for greater integration at the point of care, further evidence is needed before multi-gene testing can be recommended in routine clinical practice.
Citation Format: Bedard P. CS1-2 Clinical utility of multi-gene testing in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr CS1-2.
Abstract ES6-1: ES6-1 Assessment of residual disease and treatment implications post neoadjuvant therapy
Authors: Chang JC 
Published: March 2017

Abstract
Breast cancer is a highly heterogeneous disease with various molecular subtypes that differ in regard to treatment approach as well as unresolved treatment issues.
In women with HER2-amplified breast tumors, standard neoadjuvant therapy consisting of dual HER2 blockade with trastuzumab/pertuzumab plus chemotherapy can induce a high pathologic complete response (pCR) rate (60%), which translates into better overall survival (&gt;90% at 3 years). A critical unresolved issue in the neoadjuvant treatment of HER2-amplified tumors is minimizing toxicity in select patients. Selection of non-cardiogenic regimens and chemotherapy-free or lighter chemotherapy regimens should be the focus for women whose disease is highly addicted to the HER2 pathway. New research directions are also exploring ways to minimize the extent of local surgery in the breast and axilla.
Approximately 30% of patients with triple-negative breast cancer (TNBC) achieve pCR after neoadjuvant chemotherapy. While these patients tend to have a favorable prognosis, those with residual disease (RD) at the time of surgical resection may expect significantly worse outcomes and, at present, do not have targeted therapeutic options. Molecular analysis of tumor tissue from such patients may be used to identify the genetic alterations responsible for disease recurrence and to help individualize treatment with available agents. Transcriptome and sequencing analyses have identified important pathways and aberrations in the majority of residual tumors. Targeting these molecular abnormalities in conjunction with the tumor immune microenvironment may represent an effective therapeutic avenue to improve the outcomes of TNBC patients who have RD after standard neoadjuvant therapy. Adaptive clinical trials investigating neoadjuvant treatments directed against key pathways active in residual tumors are underway.
Citation Format: Chang JC. ES6-1 Assessment of residual disease and treatment implications post neoadjuvant therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES6-1.
Abstract ES6-2: ES6-2 Surgical considerations in patients receiving neoadjuvant therapy
Authors: King TA 
Published: March 2017

Abstract
Early randomized trials of neoadjuvant chemotherapy failed to show an improvement in overall survival compared to adjuvant therapy, yet it reduces the need for mastectomy and axillary lymph node dissection, thus decreasing the morbidity of surgery, without increasing the risk of locoregional recurrence. It is also now increasingly clear that the impact of neoadjuvant chemotherapy varies by molecular subtype; whereby patients with high-grade estrogen receptor negative and/or HER2 positive breast cancers are more likely to experience pathologic complete response to NAC that those with low-grade, estrogen receptor positive cancers. The increasing rates of pCR following neoadjuvant chemotherapy have had a significant impact on local-regional treatment considerations. However, patient selection for this approach remains critical.
Sentinel node biopsy after neoadjuvant chemotherapy accurately stages the axilla and is associated with a low rate of nodal recurrence in patients presenting with a clinically negative axilla. Sentinel node biopsy after neoadjuvant chemotherapy in patients with proven axillary metastases prior to neoadjuvant chemotherapy who become clinically node negative has a false negative rate of less than 10% only when 3 or more sentinel nodes are identified and there are no data on nodal recurrence rates after sentinel node biopsy alone in this population. Hence, strategies to ensure a low false negative rate are critical if sentinel node biopsy is offered to patients with proven axillary metastases prior to neoadjuvant chemotherapy. The relative contribution of pre-treatment stage and post-treatment stage (degree of pathologic response) to local control is also uncertain and tailoring of local therapy based on the degree of response is the subject of ongoing trials.
Citation Format: King TA. ES6-2 Surgical considerations in patients receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES6-2.
Abstract OT2-01-16: Evaluating targets in localized and advanced breast cancer by sequencing tumor DNA at diagnosis and after progression (ELSA)
Authors: Gaba AG , Powell SF , Jennifer WL , Megan LL , Chun-Hung C , Lora BJ , Ford JM 
Published: March 2017

Abstract
Background: Breast cancer therapy exerts strong selection pressure that shapes the evolution of the cancer. Despite the importance of these treatment-induced changes for the success of subsequent therapy, tumors have been rarely resampled and reanalyzed, with the exception of hematopoietic malignancies. The availability of next generation sequencing (NGS) has made it possible to get highly accurate sequencing that allows detection of mutations and other genetic alterations not only from tumor biopsies but also from circulating DNA fragments.
Objectives: To demonstrate the evolution of the molecular genotype of breast cancer as patients are diagnosed, treated, and upon relapse. This will be accomplished by NGS of the tumor at key time points during the natural history of the disease. The molecular profile at diagnosis will be compared to the profile at recurrence/metastasis and after treatment for metastasis. Correlation with treatment response and adverse clinical outcomes will be determined.
Study Design and Eligibility: We have initiated a prospective observational study in patients with a new diagnosis of Stage I, II and III breast cancer and an ECOG performance status of 0, 1 or 2. Patients should be medically suitable to give informed consent for a biopsy or surgical procedure. Enrollment will occur at community-based cancer centers with inclusion of under-served populations.
Methodology: Tumor samples and blood samples are collected at - initial diagnosis/definitive surgery, first local relapse, diagnosis of metastasis and at first progression after treatment for metastatic disease. Molecular genotype will be analyzed from the tumor samples and from the circulating tumor DNA (ctDNA) in blood samples at each of the time points. ctDNA will also be assessed on blood samples collected annually till the diagnosis of metastasis and then more frequently at 3-6 month intervals in patients with high risk breast cancer.
Statistical Design/Size of study sample: Formal sample size calculations are not required for this study as by design, it is based on participation. There is no discrete endpoint that can be powered by sample size calculation for this study. We are screening all patients who are diagnosed with breast cancer at our facility. The proposed enrollment is 300 patients per year. The study launched in December 2015 at 4 of our community-based cancer centers. Current enrollments is 46 patients.
Citation Format: Gaba AG, Powell SF, Jennifer WL, Megan LL, Chun-Hung C, Lora BJ, Ford JM. Evaluating targets in localized and advanced breast cancer by sequencing tumor DNA at diagnosis and after progression (ELSA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-16.