bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD4-01: A new additive diagnostic assay for breast cancer screening - Biochemical infrared analysis of immune cells and plasma
Authors: Allweis TM , Schmitt J , Zelig U 
Published: May 2019

Abstract
Background:
Screening for early detection of breast cancer is currently based on breast imaging. Screening mammography, the most commonly used imaging modality, has limited sensitivity, especially in dense breast tissue, and a significant rate of false positive results. An adjuvant blood-test based assay may improve breast cancer detection irrespective of breast density. In previously reported studies, Total Biochemical Infrared Analysis (TBIA) of peripheral blood mononuclear cells (PBMCs) and plasma was able to differentiate between patients with breast cancer and healthy controls or patients with benign breast disease. The TM-B1TM assay is based on TBIA technology and is intended for breast cancer screening. In the present study, the performance of the TM-B1TM assay was evaluated for cancer detection across breast densities.
Patients and Methods:
A total of 220 women were recruited to this IRB approved study: 50 women with newly diagnosed breast cancer, and two control groups – 79 patients with benign findings and 61 patients with no detectable abnormality. Twenty-nine women were withdrawn from the study (for eligibility or technical reasons), and the data presented refer to 190 cases. Breast cancer patients included 6 cases of DCIS, 1 of LCIS, 42 of IDC and 1 of ILC. Ten milliliters of blood were drawn and separated by Ficoll gradient method into PBMCs and plasma. The samples were dried on a zinc selenide optical window and analyzed by a FTIR spectrometer. The spectra were analyzed by the proprietary software TodoSpectra to distinguish between infrared spectra of cancer patients vs. patients with benign findings and healthy controls. The influence of age and breast density on TM-B1TM results were evaluated.
Results:
The TM-B1 assay obtained a sensitivity of 86 % and specificity of 98 % for breast cancer detection. The positive predictive value (PPV) was 95.1% and the negative predictive value (NPV) was 93.5%. Dense breast tissue (BIRADS categories C&D) was present in 55 % of the subjects. The specificity and sensitivity for patients with dense breasts was 99 % and 83 % respectively. No major differences in accuracy of TM-B1 were found due to patients' age.
Conclusions:
TM-B1 in conjunction with current imaging techniques may contribute to early detection of breast cancer by increasing sensitivity and reducing false positive results and unnecessary biopsies. Further studies with larger patient numbers are required and under way to establish the utility of adding the TM-B1 assay to current standard screening for breast cancer.
Citation Format: Allweis TM, Schmitt J, Zelig U. A new additive diagnostic assay for breast cancer screening - Biochemical infrared analysis of immune cells and plasma [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-01.
Abstract PD4-12: Use of 64Cu-DOTA-trastuzumab positron emission tomography (PET) to predict response to ado-trastuzumab emtansine (TDM1)
Authors: Mortimer JE , Bading JR , Frankel P , Tumyan L , Tran TT , Rockne RC , Shively JE , Gidwaney N , Park J , Colcher DM 
Published: May 2019

Abstract
Background: We have demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent for HER2 positive breast cancer and are now seeking to evaluate the methodology for prediction of response and benefit to ado-trastuzumab emtansine (TDM1) in women with metastatic disease.
Methods: Patients with metastatic breast cancer were eligible if they had biopsy confirmed HER2 + disease, at least 1 site of metastasis 2.0 cm or larger outside the biopsy site, and were to receive TDM1 as therapy. Pretreatment staging included 18F-FDG/PET. Prior to injection of 64Cu-DOTA-trastuzumab, patients received 45 mg of cold trastuzumab to reduce liver uptake. PET-CT scans were obtained at 21-25 h and 47-48 h over fields of view chosen in reference to 18F-FDG scans. TDM1 was administered at a dose of 3.6 mg/kg every 3 weeks. Restaging 18F-FDG/PET was performed every 2 cycles, and response to therapy was determined by PERCIST criteria. The radiolabel uptake was measured in terms of maximum voxel standardized uptake value (SUVmax).
Results: Ten women enrolled on study and are evaluable for response; three continue on TDM1 for 22-40 months and four patients remained on treatment for at least 1 year. The median age was 54.5 years (48-83 years); seven received prior trastuzumab-containing chemotherapy 3 wks to 55 months prior to study entry. HER2 was positive by IHC in 5 and by FISH in 5 (3 were 2+ by IHC; 1 was 1+ and 1 indeterminate). Complete or partial metabolic response was observed in 5 patients. Patients had their average SUVmax on 64Cu-DOTA trastuzumab PET (aSUVmax) assessed in addition to individual assessments on up to 8 lesions on both Day1 and Day2. The mean aSUVmax was (6.3, 8.8) for responding patients and (4.4, 5.2) for non-responder (day1, day2). The difference between responders and non-responders on Day1 aSUVmax was marginally significant (p=0.06), but significant on Day2 (p=0.04). The three highest aSUVmax on both day1 and day2 were three of the four patients with PFS&gt;1 year. Data on the relationship of 64Cu-DOTA trastuzumab PET to IHC and FISH, and individual lesion SUVmax including evidence suggesting a potential threshold effect will be presented.
Conclusions: In women with biopsy confirmed HER2 positive metastatic disease, 64Cu-DOTA-trastuzumab PET imaging is predictive for response to TDM1.
Citation Format: Mortimer JE, Bading JR, Frankel P, Tumyan L, Tran TT, Rockne RC, Shively JE, Gidwaney N, Park J, Colcher DM. Use of 64Cu-DOTA-trastuzumab positron emission tomography (PET) to predict response to ado-trastuzumab emtansine (TDM1) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-12.
Abstract TS2-1: The complexity of targeting PI3K for cancer therapy
Authors: Cantley L 
Published: May 2019

Abstract
Phosphoinositide 3-Kinase (PI3K) is activated by insulin and other growth factors to mediate cell growth. The PI3K enzyme encoded by the PIK3CA gene is one of the most frequently mutated oncogenes in human cancer. This same enzyme mediates insulin responses in liver, muscle, fat and other tissues. The most common mutations in this gene enhance the ability of PI3K to be activated by insulin. Since breast cancers typically express relatively high levels of the insulin receptor, high serum insulin levels are likely to enhance activation of PI3K in breast cancers. PI3K inhibitors that target PIK3CA have the expected physiological effect of raising serum glucose and insulin levels and the elevated insulin is likely to compromise the effectiveness of therapy. Data will be presented showing that in mouse models of human breast cancers and other cancers, dietary interventions and pharmaceutical interventions that limit elevation of serum insulin during PI3K therapy improve responses to PI3K inhibitors.
Citation Format: Cantley L. The complexity of targeting PI3K for cancer therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS2-1.
Abstract TS3-2: Modulation of anti-tumor immunity using CDK4/6 inhibitors
Authors: Goel S 
Published: May 2019

Abstract
Several pharmacological inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have now been approved for the treatment of metastatic estrogen receptor-positive breast cancer. Although CDK4/6 inhibitors were initially developed to prevent cancer cell proliferation, preclinical studies have now demonstrated that they can also exert other biological effects in solid tumors including augmentation of anti-tumor immunity. The detailed mechanisms underlying this are currently under investigation, and likely include enhanced antigen presentation by tumor cells as well as an increase in the ratio of effector to regulatory T lymphocytes. In this presentation, I will discuss our current understanding of how CDK4/6 inhibitors might stimulate anti-tumor immune responses, focusing on breast cancer. I will also discuss if and how this unexpected phenomenon might be leveraged for therapeutic benefit.
Citation Format: Goel S. Modulation of anti-tumor immunity using CDK4/6 inhibitors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS3-2.
Abstract A06: Novel NF-kB reporter murine model of spontaneous, metastatic breast cancer for spatiotemporal monitoring of local and systemic therapeutic response
Authors: Dockery Mary , Poorman Megan , Dudzinski Stephanie , Barham Whitney , Chaplin Vandiver , Spears Ryan , Kusunose Jiro , Yull Fiona , Caskey Charles , Grissom William , Giorgio Todd 
Published: May 2019

Abstract
Characterization of therapeutic response in primary and metastatic tumors is limited by endpoint studies and tissue collection. We have successfully developed a unique double-transgenic mouse model, which combines the polyoma virus middle T oncogene (PyVT), a model of human breast cancer, with a nuclear factor-kappaB (NF-kB) reporter model (NGL). PyVT mice spontaneously form primary mammary fat pad tumors, with 80% of mice developing metastatic lesions in the lungs. The reporter is luciferase, driven by NF-kB activation, to provide quantitative bioluminescent measurements of spatially-specific NF-kB activity. The resulting double transgenic (PyNGL) mice were monitored using in vivo imaging systems (IVIS) multiple times, before and after treatment, to quantitatively and spatially characterize NF-kB therapeutic response, both locally and systemically.
High intensity focused ultrasound (HIFU) was guided by magnetic resonance (MR) thermometry for tumor-localized hyperthermia which was dosage-controlled by the thermal feedback MR guided HIFU (MRgHIFU) system. A single primary mammary tumor in each PyNGL was treated with sub-ablative hyperthermia of 42⁰ for up to 25 minutes. Pre-treatment IVIS measurements were collected to determine baseline NF-kB activity within each mouse, followed by IVIS imaging every twelve hours after treatment until tissue collection. Treated tumor, contralateral (untreated) tumors, and spleens were collected for immunophenotyping and cytokine analysis using flow cytometry. PyNGL mice exhibited decreased NF-kB activity, spatially correlated with HIFU treatment, as early as 12 hours. In contrast, NF-kB increased in contralateral tumors as early as 24 hours following treatment. Immunophenotyping reveals changes in tumor infiltrating leukocyte populations in HIFU-treated and contralateral tumors, including quantity and phenotype of T cells.
The unique murine model developed allowed quantitative, temporal characterization of local and distant tumor response to MFgHIFU. The spontaneous, metastatic nature of PyVT tumor formation in concert with the non-destructive, spatiotemporal imaging capabilities of the NF-kB reporter transgene make the PyNGL model an unparalleled tool for research in metastatic disease.
Citation Format: Mary Dockery, Megan Poorman, Stephanie Dudzinski, Whitney Barham, Vandiver Chaplin, Ryan Spears, Jiro Kusunose, Fiona Yull, Charles Caskey, William Grissom, Todd Giorgio. Novel NF-kB reporter murine model of spontaneous, metastatic breast cancer for spatiotemporal monitoring of local and systemic therapeutic response. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A06.
Abstract A17: TRPM7 kinase domain is involved in breast tumor cell metastasis
Authors: Kaoud Tamer S. , Xie Xuemei , Park Jihyun , Tavares Clint D.J. , Mitra Shreya , Cano Micael , Radwan Mohamed F. , Bartholomeusz Chandra , Dalby Kevin N. 
Published: May 2019

Abstract
Introduction: TRPM7 (transient receptor potential melastatin 7) is a non-selective cation channel fused to protein kinase domain at the C-terminal whose activity is linked to the control of actomyosin contractility. TRPM7 mediates adhesion and migration of breast cancer cells and promotes breast tumor metastasis. The lack of cell-permeable inhibitors of the kinase domain represents a barrier to understand the kinase function.
Methods: Herein, we discover the first small molecule (KD-1) that targets TRPM7 kinase activity and characterize its mechanism of action in-vitro, in-cells and in-vivo. By using this inhibitor, we are investigated the involvement of TRPM7 kinase domain in breast tumor cell metastasis.
Results: Mg2+ starvation, which promotes TRPM7 kinase activity, induces phosphorylation of eEF2. Treatment of Mg2+-starved HEK293 cells with KD-1 decreased eEF2 phosphorylation, consistent with TRPM7 kinase activity suppression in-cells. KD-1 decreased the binding of Myosin IIB to TRPM7 in HEK293 and MDA-MB-231 cells. And when MDA-MB-231 and BT 549 cells were treated with increasing doses of KD-1, no change in cell viability was seen. Interestingly, KD-1 inhibited migration and invasion in the MDA-MB-231 and BT 549 cells that is reportedly regulated by TRPM7 kinase activity. Finally, the bioluminescent signals (to assess lung metastasis) were significantly lower in KD-1-treated mice (25 and 50 mg/kg/day) than in mice treated with vehicle control (P ≤0.05, 2-sided t-test.).
Conclusion: The discovered compound represents the first inhibitor that targets the kinase activity of transient receptor potential melastatin 7 (TRPM7). Inhibition of TRPM7 kinase activity may reduce or block breast tumor progression and/or metastasis.
Citation Format: Tamer S. Kaoud, Xuemei Xie, Jihyun Park, Clint D.J. Tavares, Shreya Mitra, Micael Cano, Mohamed F. Radwan, Chandra Bartholomeusz, Kevin N. Dalby. TRPM7 kinase domain is involved in breast tumor cell metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A17.
Abstract A18: Development of a novel peptide therapeutic that targets ovarian cancer via the tumor microenvironment
Authors: Wang Suming , Blois Anna , Rayes Tina EI , Liu Joyce F. , Hirsch Michelle S. , Gravdal Karsten , Bielenberg Diane R. , Akslen Lars A. , Drapkin Ronny , Mittal Vivek , Watnick Randolph S. 
Published: May 2019

Abstract
Ovarian cancer is the most lethal gynecologic malignancy and the fourth leading cause of cancer deaths in women. Pathologically, ovarian cancer is categorized into multiple subtypes, with epithelial ovarian cancer (EOC) representing 90% of cases. Despite our increased understanding of the biology governing the progression of EOC the survival rate for patients with stage IV EOC is only 17%. The vast majority of ovarian cancer-related deaths are caused by metastatic dissemination of cells from the primary tumor resulting in subsequent organ failure. Tragically, there are no clinically approved drugs that have shown significant efficacy at treating advanced, metastatic, ovarian cancer. As such, there is a dire need for efficacious therapies that can specifically treat advanced, metastatic ovarian cancer. We were the first to identify prosaposin (psap) as a potent inhibitor of tumor metastasis via stimulation of the anti-tumorigenic protein thrombospondin-1 (Tsp-1) in bone marrow-derived cells that are recruited to metastatic sites. We report here that virtually 100% of human serous ovarian tumors tested express CD36, the receptor that mediates the pro-apoptotic activity of Tsp-1. Accordingly, we developed a novel cyclic peptide with drug-like properties derived from the active sequence in psap. Strikingly, this cyclic psap peptide was able to significantly regress metastatic tumors in a patient-derived tumor xenograft (PDX) model of metastatic ovarian cancer. Thus, our findings suggest that development of a therapeutic agent based on this psap peptide would have significant efficacy in treating patients with metastatic ovarian cancer.
Citation Format: Suming Wang, Anna Blois, Tina EI Rayes, Joyce F. Liu, Michelle S. Hirsch, Karsten Gravdal, Diane R. Bielenberg, Lars A. Akslen, Ronny Drapkin, Vivek Mittal, Randolph S. Watnick. Development of a novel peptide therapeutic that targets ovarian cancer via the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A18.
Abstract A21: Hypoxia preconditioning affects metastatic seeding and proliferation through vascular and immune function, in a process regulated by lung endothelial HIFa
Authors: Branco Cristina , Rundqvist Helene , Colaco Renato , Johnson Randall S. 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR03) of the Conference Proceedings.
Citation Format: Cristina Branco, Helene Rundqvist, Renato Colaco, Randall S. Johnson. Hypoxia preconditioning affects metastatic seeding and proliferation through vascular and immune function, in a process regulated by lung endothelial HIFa. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A21.
Abstract A30: The role of neutrophil extracellular traps in promoting metastatic cancer following surgical stress
Authors: Tohme Samer , Huang Hai , Chidi Alexis , Simmons Richard , Tsung Allan 
Published: May 2019

Abstract
Background: Surgical removal of malignancies may enhance the risk of recurrence but mechanisms remain poorly understood. Neutrophils, first line responders after surgical stress, can facilitate cancer progression. Neutrophils can expel nuclear DNA studded with proteins to form web-like structures known as Neutrophil Extracellular Traps (NETs) in response to stress. Here we aim to characterize the role of NETs in promoting metastatic cancer growth after surgical stress that is currently entirely unknown.
Methods: We used a standardized mouse model of partial hepatic ischemia reperfusion, to stimulate surgical stress, directly or five days after splenic injection of MC38 colon carcinoma cells.
Results: We found that NET formation is significantly increased in the immediate post-operative period in humans undergoing curative liver resection for colorectal cancer metastases. The risk of liver metastases recurrence was 4.22 times higher in patients with increased post-operative NET formation. In the murine model, we demonstrated increased NET deposition after surgical stress and this was associated with both increased formation of metastases and growth of already established micrometastatic disease. In vitro, NETs increase growth, invasion, migration and adhesion in multiple cancer cell lines. All the above effects were abrogated by NET inhibition with DNAse. NETs exert their pro-tumorigenic effects by releasing HMGB1 and activating TLR-9 dependent pathways in the cancer cells. In addition, as metastatic tumors continue to grow, hypoxia within the tumor microenvironment induces further neutrophil recruitment and NET formation that further accelerates tumor growth.
Conclusions: These findings implicate NETs in the process of cancer metastasis progression and recurrence after surgery and identifies NETs as potential therapeutic targets.
Citation Format: Samer Tohme, Hai Huang, Alexis Chidi, Richard Simmons, Allan Tsung. The role of neutrophil extracellular traps in promoting metastatic cancer following surgical stress. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A30.
Abstract A33: The regulation of extracellular acidosis and cell survival by the TIMP-1/CD63 axis in breast carcinoma
Authors: Najy Abdo J. , Jung Young Suk , Kim Hyeong-Reh Choi 
Published: May 2019

Abstract
Breast Cancer (BrCa) resistance to conventional therapies often leads to more aggressive and metastatic disease highlighting the importance of understanding the resistance pathway. The Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) is among the most reliable prognostic markers for therapy resistance as well as metastasis of breast cancer via promotion of breast cancer cell survival through its unique interaction with the tetraspanin CD63. Recent work has shown that levels of TIMP-1 and the carbonic anhydrase family member CAIX in circulating tumor cells (CTCs) predict BrCa progression-free and overall survival. Since CAIX is known to play a critical role in the regulation of extracellular acidosis that contributes to therapy resistance, we investigated whether TIMP-1/CD63 signaling regulates extracellular acidosis involving CAIX. We utilized the murine 4T1 and human MCF10A progression models of breast cancer and demonstrated increased CAIX and TIMP-1 expression in the more aggressive 4T1 and MCF10CA1h cells. When we monitored pH change using a digital pH reader and the pH sensitive DF fluorescein dye, the more aggressive human MCF10Ca1h cells exhibited marked extracellular acidosis compared to the minimally malignant MCF10A and MCF10AneoT cells. Importantly, downregulation of TIMP-1 or CD63 in MCF10CA1h cells specifically reduced CAIX expression and its associated extracellular acidosis. To determine the functional significance of CAIX in TIMP-1/CD63-mediated extracellular acidosis, we attenuated CAIX expression and demonstrated a significant reduction of the acidosis phenotype observed in MCF10CA1h cells. Importantly, CAIX knockdown drastically reduced BrCa cell survival in a clonogenic cell survival assay. Taken together, we have identified a unique TIMP-1/CD63-mediated signaling pathway, resulting in extracellular acidosis and cell survival of BrCa cells involving CAIX. This study further provides salient information as to TIMP-1-specific function in breast cancer.
Citation Format: Abdo J. Najy, Young Suk Jung, Hyeong-Reh Choi Kim. The regulation of extracellular acidosis and cell survival by the TIMP-1/CD63 axis in breast carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A33.