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Auswahl der wissenschaftlichen Literatur zum Thema „Human thorax surrogate“
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Zeitschriftenartikel zum Thema "Human thorax surrogate"
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Van Baelen, Karen, Gitte Zels, Maxim De Schepper, Marion Maetens, Josephine Van Cauwenberge, Tatjana Geukens, Kristien Borremans et al. „Abstract PO1-06-06: Underestimation of metastatic spread in patients with lobular breast cancer: results from the post-mortem tissue donation program UPTIDER“. Cancer Research 84, Nr. 9_Supplement (02.05.2024): PO1–06–06—PO1–06–06. http://dx.doi.org/10.1158/1538-7445.sabcs23-po1-06-06.
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Abstract Background: Invasive lobular carcinoma (ILC) accounts for 15% of all invasive breast cancers (BC) and has a peculiar metastatic spread in comparison to BC of no-special type. Since ILC is less likely to disrupt normal tissue architecture and is usually non-mass forming, imaging of ILC lesions entails many challenges. Insights into pathologic versus radiological metastatic invasion can lead to better diagnostic and monitoring tools for patients with ILC. Here, we compare microscopical findings during autopsy with clinical findings prior to death in patients with metastatic ILC included in our post-mortem tissue donation program UPTIDER (NCT04531696). Methods: UPTIDER was started in November 2020 in University Hospitals Leuven/KU Leuven with inclusion of patients with stage IV BC who were willing to participate. One of the predefined subgroups consisted of patients with primary pure (i.e. not mixed) ILC. Samples were taken from different macroscopically invaded and non-invaded sites. Clinical data on disease progression, imaging, biochemistry and treatment regimens were extracted from patient files. The number of samples that were preregistered as pathological served as a surrogate for lesions that were seen on imaging performed during the treatment of the patient. These samples are compared to microscopical findings of the autopsy. Results: Since the start of UPTIDER, an autopsy has been performed on 6 patients with pure ILC (26.1% of all autopsies). Median age at initial diagnosis was 52 years (range: 37 – 80 years). Three patients (50.0%) had stage IV disease at diagnosis, the others relapsed on average 162.7 months (range: 55 – 358 months) after initial diagnosis. The average time between clinical occurrence of metastases and death was 44.8 months (range: 15 – 83 months). Median number of treatment lines for stage IV disease was 5 (median endocrine lines 2; median chemotherapy regimens 3.5). To follow disease evolution, computed tomography of thorax and abdomen was used for 4 (66.7%) patients and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) for the remaining 2 (33.3%). Median time between last premortem imaging and death was 5.9 weeks (range: 1.6 – 16.6 weeks). At autopsy, a median of 26 unique metastases (range: 12-36) were sampled per patient. Table 1 gives an overview on the unique microscopically invaded metastases that were sampled per patient. Only 47.3% of the sampled unique metastases was preregistered. Of all unique metastases, 26.7% appeared macroscopically normal during autopsy. Tissues that appeared normal but turned out to be microscopically infiltrated included liver, stomach, adrenal glands, heart, pericardium, visceral and subcutaneous fat tissue. There were 2 patients with normal appearing, microscopically infiltrated livers. In these patients, elevation of γGT and transanimases was seen in the months prior to death. Conclusions: The disease burden of metastatic ILC reported on premortem imaging does not reflect the microscopical findings at autopsy. One of the priorities of metastatic ILC research should be the development of diagnostic tools to better estimate the extent of the disease. Future analyses of the performed postmortem MRIs in our study can aid in improving the interpretation of WB-DWI/MRI for patients with ILC. For now, clinicians should consider that unexplained clinical and/or biochemical findings might indicate progression of ILC. Table 1: patient overview on performed imaging and unique metastases sampled during autopsy CT = computed tomography; ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; pt = patient; WB-DWI MRI = whole-body diffusion-weighted magnetic resonance imaging *exclusion of samples of patient 2012 since no preregistration was performed for this patient due to unexpected death Citation Format: Karen Van Baelen, Gitte Zels, Maxim De Schepper, Marion Maetens, Josephine Van Cauwenberge, Tatjana Geukens, Kristien Borremans, François Richard, Amena Mahdami, Ha-Linh Nguyen, Sophia Leduc, Anirudh Pabba, Ann Smeets, Ines Nevelsteen, Patrick Neven, Hans Wildiers, Vincent Vandecaveye, Wouter Van Den Bogaert, Giuseppe Floris, Christine Desmedt. Underestimation of metastatic spread in patients with lobular breast cancer: results from the post-mortem tissue donation program UPTIDER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-06.
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Hamel, Ronald P. „Surrogate Motherhood: The Ethics of Using Human Beings. By Thomas A. Shannon. New York: Crossroad, 1989. xi + 191 pages. $17.95.“ Horizons 16, Nr. 2 (1989): 408–9. http://dx.doi.org/10.1017/s0360966900040937.
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Yoganandan, Narayan, Alok Shah, Lewis Somberg, Jamie Baisden, Brain D. Stemper, Cameron Bass, Robert S. Salzar, Valeta Carol Chancey und Joseph McEntire. „A Novel Paradigm to Develop Regional Thoracoabdominal Criteria for Behind Armor Blunt Trauma Based on Original Data“. Military Medicine 188, Supplement_6 (01.11.2023): 598–605. http://dx.doi.org/10.1093/milmed/usad272.
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ABSTRACT Introduction For behind armor blunt trauma (BABT), recent prominent BABT standards for chest plate define a maximum deformation distance of 44 mm in clay. It was developed for soft body armor applications with limited animal, gelatin, and clay tests. The legacy criterion does not account for differing regional thoracoabdominal tolerances to behind armor-induced injury. This study examines the rationale and approaches used in the legacy BABT clay criterion and presents a novel paradigm to develop thoracoabdominal regional injury risk curves. Materials and Methods A review of the original military and law enforcement studies using animals, surrogates, and body armor materials was conducted, and a reanalysis of data was performed. A multiparameter model analysis describes survival–lethality responses using impactor/projectile (mass, diameter, and impact velocity) and specimen (weight and tissue thickness) variables. Binary regression risk curves with ±95% confidence intervals (CIs) and peak deformations from simulant tests are presented. Results Injury risk curves from 74 goat thorax tests showed that peak deflections of 44.7 mm (±95% CI: 17.6 to 55.4 mm) and 49.9 mm (±95% CI: 24.7 to 60.4 mm) were associated with the 10% and 15% probability of lethal outcomes. 20% gelatin and Roma Plastilina #1 clay were stiffer than goat. The clay was stiffer than 20% gelatin. Penetration diameters showed greater variations (on a test-by-test basis, difference 36-53%) than penetration depths (0-12%) across a range of projectiles and velocities. Conclusions While the original authors stressed limitations and the importance of additional tests for refining the 44 mm recommendation, they were not pursued. As live swine tests are effective in developing injury criteria and the responses of different areas of the thoracoabdominal regions are different because of anatomy, structure, and function, a new set of swine and human cadaver tests are necessary to develop scaling relationships. Live swine tests are needed to develop incapacitation/lethal injury risk functions; using scaling relationships, human injury criteria can be developed.
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Kleine-Kohlbrecher, Daniela, Nadia Viborg Petersen, Michail Angelos Pavlidis, Thomas Trolle, Stine Friis, Jens Kringelum, Anders Bundgaard Soerensen et al. „Abstract LB199: A personalized neoantigen vaccine is well tolerated and induces specific T-cell immune response in patients with resected melanoma“. Cancer Research 83, Nr. 8_Supplement (14.04.2023): LB199. http://dx.doi.org/10.1158/1538-7445.am2023-lb199.
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Abstract Tumor mutations giving rise to neoantigens have recently emerged as promising targets for cancer immunotherapy. Vaccines delivering tumor-specific neoantigens have demonstrated favorable efficacy and safety results in numerous preclinical and early clinical studies. However, selecting therapeutically relevant neoantigens amongst the myriad of cancer mutations has proven challenging. To overcome this, we have developed a proprietary AI-based target discovery platform, PIONEER, with enhanced predictive performance and increased precision. The PIONEER top-ranked neoantigens were selected and included in the personalized DNA vaccine candidate EVX-02. To assess the ability of the PIONEER designed neoantigen vaccine candidate to induce neoantigen immunogenicity and anti-tumor effect in preclinical models, mice were immunized with a mouse surrogate EVX-02 molecule, mEVX-02. mEVX-02 vaccination completely prevented establishment of tumors and induced neoantigen-specific, polyfunctional CD4+ and CD8+ T cells in the blood and spleen of immunized mice. An enhanced antitumor effect was obtained when combining mEVX-02 with anti-PD-1 mAb treatment. Encouraged by the preclinical results, we conducted a first-in-human multicenter Phase I clinical study of EVX-02 in combination with nivolumab in patients with resected malignant melanoma. The objectives of the trial were to investigate safety and tolerability, operational and clinical feasibility, and immunogenicity of the applied personal neoantigens. Each patient received a fully personalized drug that was produced in a complex process, from biopsy, through genome sequencing, AI-profiling, vaccine design, manufacturing, quality testing, and drug product release. This was succeeded with every single step for each patient. In all patients, EVX-02 treatment was well tolerated, and only very mild adverse events (AEs) have been observed in relation to immunization with EVX-02. Interim data demonstrated neoantigen-specific T-cell immune responses upon EVX-02 treatment and that the responses were mediated by activated CD4+ and CD8+ T cells. The measured T-cell responses were robust and long lasting. Together, these findings validate the precision and predictive power of our proprietary AI platform, PIONEER, and provide proof of mechanism for the DNA-delivery technology in that the encoded neoantigens gave rise to significant immune reactions. Citation Format: Daniela Kleine-Kohlbrecher, Nadia Viborg Petersen, Michail Angelos Pavlidis, Thomas Trolle, Stine Friis, Jens Kringelum, Anders Bundgaard Soerensen, Thomas Strandet Jepsen, Camilla Højgaard, Anders Jespersen, Erik D. Heegaard, Britt Winding Lauenborg, Birgitte Rønø. A personalized neoantigen vaccine is well tolerated and induces specific T-cell immune response in patients with resected melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB199.
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Monteiro Crozier, Thomas W., Martha Lopez-Yrigoyen, Helena Engman, Moritz Haneklaus, Samuel Witham, Krzystof B. Wicher, Steven Myatt, Luca Cassetta und Carola Ries. „Abstract LB201: ENIGMAC platform enables at-scale CRISPRi screenings for macrophage target discovery“. Cancer Research 84, Nr. 7_Supplement (05.04.2024): LB201. http://dx.doi.org/10.1158/1538-7445.am2024-lb201.
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Abstract RNA sequencing has improved our understanding of cellular heterogeneity by providing in-depth transcriptome information at the single cell level. However, this “dataset infodemic” did not translate into an abundance of new validated targets due to the difficulties in performing gene-to-function studies. The main goal of the ENIGMAC™ discovery platform is to support gene-to-function studies and to deliver new validated macrophage targets. ENIGMAC™ combines custom, disease relevant assays and unique genome editing methods supported by multi-omics bioinformatics analyses yielding selected gene sets for interrogation. We use a human Induced Pluripotent Stem Cell (iPSC) line that yields macrophages phenotypically and functionally similar to MDM. By employing this iPSC system, we can produce millions of macrophages per week, which allows multiple high throughput assays to support target validation and drug discovery. Furthermore, we developed several proprietary technologies allowing fast and reliable gene editing of macrophages, including gene Knock In (KI), Knock Out (KO) and Knock Down (KD) with high efficiency both at iPSC and macrophage level while maintaining expression/silencing during macrophage differentiation. Here we report preliminary results of the CRISPRi screen, aiming to identify novel regulators of INFg-mediated PD-L1 upregulation on macrophages, a surrogate readout for a suppressive phenotype. To this aim, we developed a proprietary human iPSC line that constitutively expresses dCAS9-KRAB protein, allowing for a highly gene specific guide RNA (sgRNA)-mediated method of silencing of gene transcription. Notably, our proprietary anti-silencing system allows to maintains dCAS9-KRAB expression throughout the entire macrophage differentiation process. During the screen, 100 million iPSC-derived microphages were transduced with a 6500 gRNAs library targeting 1300 genes selected from disease-relevant macrophage datasets. Macrophages were subsequently stimulated with INFg and sorted for loss of PD-L1 expression using flow cytometry. Sequencing of the PD-L1 low macrophage population successfully identified PD-L1 regulators such as IFNGR1, IFNGR2, JAK1, STAT1 and IRF1 among other hits. The novel hits are being now individually validated, and selected ones will be progressed to drug discovery. Importantly, this macrophage CRISPRi screen provides technical proof of concept for the ENIGMAC™ platform to perform screens at scale and to identify novel hits. In conclusion, the ENIGMAC™ platform represents a unique tool for gene to function studies using human macrophages. Furthermore, it is disease agnostic and can be integrated with a variety of disease-specific conditions and phenotypic readouts. Citation Format: Thomas W. Monteiro Crozier, Martha Lopez-Yrigoyen, Helena Engman, Moritz Haneklaus, Samuel Witham, Krzystof B. Wicher, Steven Myatt, Luca Cassetta, Carola Ries. ENIGMAC platform enables at-scale CRISPRi screenings for macrophage target discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB201.
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Duvall, Jeremy R., Raghida A. Bukhalid, Naniye M. Cetinbas, Kalli C. Catcott, Kelly Lancaster, Keith W. Bentley, Suzanna Clark et al. „Abstract 3503: XMT-2056, a HER2-targeted Immunosynthen STING-agonist antibody-drug conjugate, binds a novel epitope of HER2 and shows increased anti-tumor activity in combination with trastuzumab and pertuzumab“. Cancer Research 82, Nr. 12_Supplement (15.06.2022): 3503. http://dx.doi.org/10.1158/1538-7445.am2022-3503.
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Abstract We present here a novel therapeutic agent, XMT-2056, that results in robust anti-tumor activity mediated by an immune response through targeted delivery of a STING agonist to the tumor microenvironment. By leveraging an antibody-drug conjugate (ADC) strategy, systemic administration of a STING agonist with tumor-targeted delivery can be achieved, potentially overcoming limitations of either intratumoral or intravenous administrations of unconjugated, small molecule STING agonists. XMT-2056 was generated through conjugation of Immunosynthen, a platform that employs a novel STING agonist payload specifically designed for ADCs, to HT-19, a HER2-targeting antibody which binds to a novel epitope and does not compete for binding with either trastuzumab or pertuzumab. Initial results showed XMT-2056 has target-dependent anti-tumor activity in vivo and is well tolerated in non-human primates at significantly higher exposure levels than those required for anti-tumor activity. To evaluate the impact of HER2 expression level on the activity of XMT-2056, in vivo studies in gastric and breast cancer models with varying HER2 expression levels were conducted, and XMT-2056 showed potent anti-tumor activity in a dose dependent and target dependent manner including in models with very low expression of HER2. Because the antibody employed in XMT-2056 does not compete for binding with trastuzumab or pertuzumab, we hypothesized that there could be benefit in combining with such approved HER2-targeted therapies. This advantage was demonstrated in vivo as the combination of XMT-2056 and trastuzumab or pertuzumab showed greater anti-tumor activity compared to the administration of either agent alone. Further efforts to elucidate the mechanism(s) of the observed benefit of these combinations will be discussed. Given the innate immune activation by XMT-2056, there is also a strong rationale for combination with immune checkpoint inhibitors. To this end, administration of an XMT-2056 surrogate ADC in combination with an anti-PD1 agent improved anti-tumor activity in a ratHER2-engineered EMT-6 syngeneic mouse model. Together these data support the potential of XMT-2056 both as a monotherapy and in combination with other HER2 targeted agents as well as checkpoint inhibitors. Citation Format: Jeremy R. Duvall, Raghida A. Bukhalid, Naniye M. Cetinbas, Kalli C. Catcott, Kelly Lancaster, Keith W. Bentley, Suzanna Clark, Susan Clardy, Scott D. Collins, Anouk Dirksen, Elizabeth Ditty, Bingfan Du, Eugene W. Kelleher, Travis Monnell, Marina Protopopova, Caitlin Routhier, Cheri Stevenson, Elena Ter-Ovanesyan, Joshua D. Thomas, Alex Uttard, Jason Wang, Phonphimon Wongthida, Ling Xu, Annika Yau, Jeffrey Zurita, Dorin Toader, Marc Damelin, Timothy B. Lowinger. XMT-2056, a HER2-targeted Immunosynthen STING-agonist antibody-drug conjugate, binds a novel epitope of HER2 and shows increased anti-tumor activity in combination with trastuzumab and pertuzumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3503.
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Schwenck, Johannes, Dominik Sonanini, Walter Ehrlichmann, Gabriele Kienzle, Gerald Reischl, Pascal Krezer, Ian Wilson et al. „Abstract LB058: Imaging of CD8+ cytotoxic T-cells by Zr-89-Df-IAB22M2C PET/MRI: First clinical experience in patients with metastatic cancer“. Cancer Research 82, Nr. 12_Supplement (15.06.2022): LB058. http://dx.doi.org/10.1158/1538-7445.am2022-lb058.
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Abstract CD8+ cytotoxic T cells are key players in anti-cancer immune responses as they destroy MHC class I-dependent tumor cells. Therefore, the spatial distribution of CD8+ cytotoxic T cells might represent an important surrogate for the response to cancer immunotherapy including immune checkpoint inhibitor therapy ICT. The radiolabeled minibody [89Zr]Zr-Df-IAB22M2C is characterized by a high affinity to human CD8 and was already investigated in a phase I study. Here, we present our first experience with the non invasive in vivo assessment of the whole body CD8 T cell distribution in cancer patients using clinical [89Zr]Zr-Df-IAB22M2C PET/MRI. In total 8 patients with metastasized cancers (5 x malignant melanoma; 1 x choroidal melanoma, 1 x NSCLC and 1 x sarcoma) were studied before (n = 3) or during (n = 5) ICT. Multiparametric PET/MRI was performed 24 h after injection of 74.2±17.9 MBq [89Zr]Zr-Df-IAB22M2C (1.1 - 1.8 mg Df-IAB22M2C) on a Siemens Biograph mMR System (SiemensHealthineers, Erlangen, Germany). The whole body distribution of the [89Zr]Zr-Df-IAB22M2C tracer was analyzed with a special focus on tumors/metastases as well as primary and secondary lymphatic organs. The PET tracer [89Zr]Zr-Df-IAB22M2C was well tolerated without any reported side effects. The PET/MRI acquisitions 24h p.i. of [89Zr]Zr-Df-IAB22M2C revealed a comparably low background signal with only a minor blood pool and unspecific tissue retention. Regarding the primary and secondary lymphoid organs we observed a high interpatient variability of the tracer uptake. Four out of five patients with previous ICT exhibited a relatively high [89Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Also a large number of non metastatic lymph nodes yielded a pronounced [89Zr]Zr-Df-IAB22M2C uptake in four patients. Strikingly, a low [89Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver (liver/spleen ratio < 10) was observed in 4 out of the 5 patients with cancer progression during ICT. Interestingly, only one metastasis with an intense tracer was detected in this patient cohort. This first clinical experiences revealed the feasibility to assess potential immune-related changes by [89Zr]Zr-Df-IAB22M2C PET/MRI. Considering these results we hypothesize that the whole body distribution of CD8+ cytotoxic T-cells assessed by non-invasive in vivo [89Zr]Zr-Df-IAB22M2C PET/MRI might be associated with the response to cancer immunotherapy which needs to be investigated in subsequent prospective trials. Citation Format: Johannes Schwenck, Dominik Sonanini, Walter Ehrlichmann, Gabriele Kienzle, Gerald Reischl, Pascal Krezer, Ian Wilson, Ron Korn, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Ferdinand Seith, Andrea Forschner, Thomas Eigentler, Lars Zender, Martin Röcken, Bernd Pichler, Lukas Flatz, Manfred Kneilling, Christian la Fougere. Imaging of CD8+ cytotoxic T-cells by Zr-89-Df-IAB22M2C PET/MRI: First clinical experience in patients with metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB058.
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Updyke, Joel, Shubhmita Bhatnagar, Nitu Bhaskar, Rachel Parise, Swati Nagar, John Schultz, David Ferguson et al. „Abstract 1993: Sulfobutylether-β-cyclodextrin hydrogel microspheres delivering TLR 7/8 agonist for transarterial immunoembolization“. Cancer Research 83, Nr. 7_Supplement (04.04.2023): 1993. http://dx.doi.org/10.1158/1538-7445.am2023-1993.
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Abstract Drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) is a treatment procedure for liver cancer that involves the selective catheterization and subsequent embolization of tumor-feeding arteries with drug-eluting beads (DEBs). DEB-TACE elicits ischemic cell death in the embolized tumor while simultaneously delivering a local, sustained release of chemotherapy. We hypothesize that the application of DEBs loaded with an immunostimulatory adjuvant in the DEB-TACE procedure will promote local antigen presenting cells to utilize the antigens released by dying tumor cells to generate a systemic, adaptive anti-tumor immune response. This approach represents a novel form of transarterial immunoembolization (TIE). 558 is a highly potent, small molecule Toll-like receptor 7/8 agonist that activates both innate and adaptive immune responses to eliminate tumor cells in various preclinical tumor models. Hydrogel microspheres composed of cross-linked sulfobutylether-β-cyclodextrin (SBE-βCD) were investigated as DEBs for 558 in the current study. SBE-βCD hydrogel microspheres (SBE-βCDMS) of 10 - 300 μm diameter were synthesized via suspension polymerization of SBE-βCD and ethylene glycol diglycidyl ether followed by wet sieving. 558 loading was achieved by incubating blank SBE-βCDMS in aqueous solutions of 558. Under non-saturating conditions, SBE-βCDMS absorbed almost the entirety of 558 from loading solutions in 4 h. The dose of 558 loaded in SBE-βCDMS was tuned by altering the initial amount of 558 in solution, up to a maximum loading of 0.28 mg 558/mg dry SBE-βCDMS determined under saturating conditions. The time to 50% release of 558 from loaded SBE-βCDMS was less than 30 min when phosphate buffered saline was used as release media. However, the release of 558 was negligible when deionized water was used as release media. The released drug was as effective as free 558 in stimulating cytokine response from human peripheral blood mononuclear cells in vitro. As a surrogate for TIE, we evaluated plasma and tumor pharmacokinetics upon intratumoral injection of 558-loaded SBE-βCDMS (50 - 100 μm diameter) or free 558 at a dose of 100 μg in C57BL/6 mice bearing B16F10-OVA flank tumors. The gradual release of 558 from loaded SBE-βCDMS prevented an initial spike in plasma concentration that was observed for mice administered with free 558, and maintained constant tumor concentrations for at least 4 h post-injection. High-resolution MALDI mass spectrometry imaging of 15 μm-thick tumor cryosections indicated that 558 was initially concentrated within SBE-βCDMS after intratumoral injection, and extensively released into the surrounding tumor tissue 24 h post-injection. Taken together, these results suggest that 558-loaded SBE-βCDMS are a promising platform for local drug delivery and immune cell stimulation via TIE. Citation Format: Joel Updyke, Shubhmita Bhatnagar, Nitu Bhaskar, Rachel Parise, Swati Nagar, John Schultz, David Ferguson, Tamara Kucaba, Thomas Griffith, Ronald Siegel, Jayanth Panyam. Sulfobutylether-β-cyclodextrin hydrogel microspheres delivering TLR 7/8 agonist for transarterial immunoembolization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1993.
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McKeon, Thomas P., Vicky Tam, Wei-Ting Hwang, Paul Wileyto, Karen Glanz und Trevor M. Penning. „Abstract PR06: Geocoding and integrating multiple environmental exposomics sources: Assessing population hazard to lung carcinogens in 421 zip codes of a cancer center catchment area“. Cancer Epidemiology, Biomarkers & Prevention 29, Nr. 9_Supplement (01.09.2020): PR06. http://dx.doi.org/10.1158/1538-7755.modpop19-pr06.
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Abstract To assess risk factors that contribute to lung cancer burden in the Abramson Cancer Center (ACC) catchment area, we integrated geospatial data of exposure to pollutants from publicly available EPA and NASA datasets. The study area covers the 421 zip codes that make up the 12 counties of the catchment area from which most of the ACC patients come. The counties include 5 that surround Philadelphia, 6 in New Jersey, and 1 in Delaware. Environmental exposure data, sourced from US-EPA Air Quality System (AQS) Data Mart, were focused on air pollutants since air pollution is recognized by the International Agency on Cancer (IARC) as a Group 1 human carcinogen. Exposomics data included: hourly, daily, and annual (1980 -2018) PM2.5, PM10, NO2; Hazardous Air Pollutants (HAPS); Volatile Organic Compounds (VOCs); (Air Quality Index) AQI; NONOxNOy monitoring; and annual Toxic Release Inventory (TRI) air emissions by chemical classifier and point source (1987 -2017). Annual NASA satellite-derived grids were incorporated for PM2.5 (1998-2016; 1 km resolution) and NOx (1997 - 2012; 10 km resolution). ESRI’s ArcGIS was used to develop programming scripts to automate the process of data integration, geocoding, and classifying chemical parameters by (1) status as a lung carcinogen with sufficient evidence of lung carcinogenesis; (2) status as one of the priority 16 EPA polycyclic aromatic hydrocarbons, as a surrogate marker of exposure to carcinogens; (3) status in the IARC rankings for Cancer Group; (4) status as a component of diesel exhaust; and (5) status as a VOC. 1-km search radius kernel density grids were generated for each air pollutant. We sliced the density estimates into ordinal rankings ranging from “10 = high” to “1 = low.” A hazard index may be generated by summing data layers of cumulative environmental exposomics in a process called map algebra. Spatial sorting and merging of exposome releases by facility, year, chemical and zip code concentration allow for addressing “low-hanging fruit” through summary statistics. Although the focus of this investigation is on lung cancer, the utility of the methodology may be applied to probe exposures related to other cancers. Incorporating more years or larger geographic areas of study may make exploring the risk of exposure possible for less prevalent cancers. In future studies, we are conducting statistical analysis to determine whether geocoded exposure data predict lung cancer risks in those vulnerable zip codes using electronic health record data of geolocations of lung cancer patients. This novel approach will help determine whether geocoded exposomics data are associated with cancer incidence. The hazard index was used to identify zip codes that are the most vulnerable to carcinogen exposure. Zip codes 19720, 19061, 08066, 08027, 19153, and 19145 scored highest on the hazard index based on cumulative exposure. (Supported by P30-CA-016520 and P30-ES013508.) This abstract is also being presented as Poster A08. Citation Format: Thomas P. McKeon, Vicky Tam, Wei-Ting Hwang, Paul Wileyto, Karen Glanz, Trevor M. Penning. Geocoding and integrating multiple environmental exposomics sources: Assessing population hazard to lung carcinogens in 421 zip codes of a cancer center catchment area [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr PR06.
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van den Bruele, Astrid Botty, Morgan Paul, Samantha M. Thomas, Sarah L. Sammons, Maggie L. DiNome, Jennifer K. Plichta, Akiko Chiba, Laura H. Rosenberger und E. Shelley Hwang. „Abstract P3-05-20: Low 21-Gene Recurrence Score Is Not Associated with a High Axillary Nodal Burden in Post-Menopausal Women Presenting with a Clinically Negative Axilla“. Cancer Research 83, Nr. 5_Supplement (01.03.2023): P3–05–20—P3–05–20. http://dx.doi.org/10.1158/1538-7445.sabcs22-p3-05-20.
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Abstract Background: The predictive and prognostic value of the 21-gene recurrence score (RS) has emphasized the importance of tumor biology and minimized the credence of a limited (1-3 positive) nodal burden. The practice changing results of RxPonder demonstrated that post-menopausal women with 1-3 positive lymph nodes (pN1) and a RS of ≤25 did not necessarily benefit from adjuvant chemotherapy. Given that RS influences adjuvant therapy decision-making more significantly than nodal status, it is unclear whether axillary staging with sentinel lymph node biopsy (SLNB) has a continued role in the surgical care of post-menopausal patients otherwise presenting with early stage, clinically node negative (cN0) hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer. In this context, the de-escalation of axillary staging, especially in the presence of a low RS, is an area of active investigation. To help elucidate this further, we sought to estimate the association of RS with pathologic nodal stage. Methods: Using the 2004-2019 National Cancer Database (NCDB) Patient User File (2022 release), we evaluated the association of RS with the incidence of pN0, pN1 and pN2-3 disease. Only female patients diagnosed who were age 50 and older with HR+/HER2- invasive breast cancer were eligible, and only those presenting with cT1-T2N0 who underwent upfront surgery with a SLNB comprised our study population. Those with Oncotype DX testing performed with an available RS were included. Given the limitations within the dataset, age 50 and over was selected as a surrogate for post-menopausal status. Categorical variables were compared between RS groups (≤25 vs. >25) using chi-square tests and continuous variables were compared using t-tests. A logistic regression analysis was performed to estimate the association between RS (≤25 vs. >25) and nodal burden (pN2-3 vs pN0-1). Results: There were 151,447 patients with an invasive breast cancer diagnosis between 2015 and 2019 who met inclusion criteria. The average age at diagnosis was 64.1 (IQR 58-69) and almost 75% of tumors displayed ductal histology. There were 130,568 (86.2%) patients with a RS≤25 and 20,879 (13.8%) with a RS >25. On final pathology, 85.2% were pN0 and 14.8% were pN1-3. For those with a RS ≤25, 84.9% were pN0, 14.8% were pN1 and 0.3% were pN2-3. For those with a RS >25, 86.8% were pN0, 12.9% were pN1 and 0.3% were pN2-3. Overall, 14.5% demonstrated pN1 disease, of which 12.3% yielded a RS >25. Of the 461 patients with pN2-3 disease for whom RS was available, 12.4% (57 patients) had RS >25. After adjustment, RS >25 was associated with reduced incidence of pN2-3 compared to pN0-1 (OR=0.64, 95% CI 0.47-0.87, p=0.004). Conclusion: In this population of post-menopausal patients with cT1-T2N0, HR+/HER2- invasive breast cancer and an available RS, almost 86% displayed pN0 or pN1 disease in conjunction with a RS ≤25. Based on the current available literature, less than 5% of cT1-2N0 patients are thought to harbor >pN1 disease. These data add further support, suggesting that this patient population is unlikely to harbor a higher than limited nodal burden given a clinically negative axilla. Though less than 0.5% of the studied patient population demonstrated pN2-3 disease, an important caveat to make is that these patients would not have met criteria for RS, and it’s likely this low number reflects the absence of testing. Given that RS has not been validated for this higher nodal stage, we cannot make recommendations to omit axillary surgery in this cohort of patients. The data presented here provides further rationale for the two large prospective studies addressing whether SLNB could be eliminated in patients with otherwise small HR+/HER2- tumors which are currently ongoing. Table 1: Pathologic Nodal Staging Based on Recurrence Score Citation Format: Astrid Botty van den Bruele, Morgan Paul, Samantha M. Thomas, Sarah L. Sammons, Maggie L. DiNome, Jennifer K. Plichta, Akiko Chiba, Laura H. Rosenberger, E Shelley Hwang. Low 21-Gene Recurrence Score Is Not Associated with a High Axillary Nodal Burden in Post-Menopausal Women Presenting with a Clinically Negative Axilla [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-20.
Dissertationen zum Thema "Human thorax surrogate"
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Chaufer, Martin. „Développement d’un substitut physique de thorax humain et de son jumeau numérique dédiés à la prédiction du risque lésionnel lors d'impacts balistiques non pénétrants“. Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. http://www.theses.fr/2023UBFCA015.
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Au cours des dernières années, l'utilisation d'armes à létalité réduite a augmenté. Ces armes, conçues pour neutraliser des individus présentant un comportement dangereux, peuvent causer des blessures, voire la mort. Des mécanismes de lésions similaires sont observés lors de la déformation arrière des gilets pare-balles au cours d'impact avec projectiles d’arme à feu. Afin de protéger les citoyens et les forces de l’ordre, il est nécessaire de prévenir de tels scénarios. Or aujourd'hui peu d'outils sont disponibles pour aider au dimensionnement de tel équipements. Dans cette optique, ce travail de thèse vise à développer des outils de prédiction du risque de lésion thoracique lors d'impact balistique non pénétrant. Ainsi, un substitut physique de thorax humain et son jumeau numérique sont développés. Dans un premier temps, le modèle numérique HUByx est utilisé comme référence pour construire un modèle numérique simplifié pouvant être fabriqué avec des matériaux disponibles dans le commerce. Les différents matériaux sont caractérisés et leurs lois de comportement sont établies. Une fois validé, ce modèle numérique sert de base pour construire le substitut physique appelé SurHUByx. Celui-ci est équipé de différents capteurs permettant d'enregistrer les données au niveau des côtes et des organes internes lors d'impact. Des cas d'impact précisément décrits dans des rapports sont reproduits sur SurHUByx pour relier les données issues des capteurs à un bilan lésionnel. Enfin, une approche statistique est utilisée pour développer des courbes de probabilité de lésion, permettant d'estimer le risque de lésion suite à un impact sur SurHUByx ou son jumeau numérique SurHUByx FEMIn recent years, the use of less-lethal weapons has increased. These weapons, designed to neutralise individuals exhibiting dangerous behaviour, can cause injuries or even death. Similar injury mechanisms are observed in the rear deformation of bulletproof vests during impacts. To protect citizens and law enforcement personnel, it is necessary to prevent such scenarios. However, today there are few tools available to assist in the sizing of such equipment. In this context, this thesis aims to develop tools for predicting thoracic injury risk during non-penetrating ballistic impacts. Accordingly, a physical substitute of the human thorax and its numerical twin are developed. Initially, the HUByx numerical model is used as a reference to construct a simplified numerical model that can be manufactured using readily available materials. Different materials are characterised, and their material laws are established. Once validated, this numerical model serves as a basis for constructing the physical substitute called SurHUByx. It is equipped with various sensors to record data over the rib and in internal organs during ballistic impacts. Specific impact cases described in case reports are replicated on SurHUByx to correlate sensor data with injury assessments. Finally, a statistical approach is used to develop injury prediction curves, allowing to estimate of the risk of injury following an impact on SurHUByx or its numerical twin, SurHUByx FEM
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Albert, Devon Lee. „Biomechanical Responses of Human Surrogates under Various Frontal Loading Conditions with an Emphasis on Thoracic Response and Injury Tolerance“. Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/100947.
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Frontal motor vehicle collisions (MVCs) resulted in 10,813 fatalities and 937,000 injuries in 2014, which is more than any other type of MVC. In order to mitigate the injuries and fatalities resulting from MVCs, new safety restraint technologies and more biofidelic anthropomorphic test devices (ATDs) have been developed. However, the biofidelity of these new ATDs must be evaluated, and the mechanisms of injury must be understood in order to accurately predict injury. Evaluating the biomechanical response, injury mechanisms, and injury threshold of the thorax are particularly important because the thorax is one of the most frequently injured body regions in MVCs. Furthermore, sustaining a severe thoracic injury in an MVC significantly increases mortality risk.
The overall objective of this dissertation was to evaluate the biomechanical responses of human surrogates under various frontal loading conditions. This objective was divided into three sub-objectives: 1) to evaluate the biofidelity of the current frontal impact ATDs, 2) to evaluate the effect of different safety restraints on occupant responses, and 3) to evaluate rib material properties with respect to sex, age, structural response, and loading history.
In order to meet sub-objectives 1 and 2, full-scale frontal sled tests were performed on three different human surrogates: the 50th percentile male Hybrid III (HIII) ATD, the 50th percentile male Test Device for Human Occupant Restraint (THOR-M) ATD, and approximately 50th percentile male post-mortem human surrogates (PMHS). All surrogates were tested under three safety restraint conditions: knee bolster (KB), KB and steering wheel airbag (KB/SWAB), and knee bolster airbag and SWAB (KBAB/SWAB). The kinematic, lower extremity, abdominal, thoracic, and neck responses were then compared between surrogates and restraint conditions. In order to assess biofidelity, the ATD responses were compared to the PMHS responses. For both the kinematic and thoracic responses, the HIII and THOR-M had comparable biofideltiy. However, the HIII responses
were slightly more biofidelic. The ATDs experienced similar lower extremity kinetics, but very different kinetics at the upper and lower neck due to differences in design. Evaluation of the different restraint conditions showed that the SWAB and KBAB both affected injury risk. The SWAB decreased head injury risk for all surrogates, and increased or decreased thoracic injury risk, depending on the surrogate. The KBAB decreased the risk of femur injury, but increased or decreased tibia injury risk depending on the surrogate and injury metric used to predict risk.
In order to meet sub-objective 3, the tensile material properties of human rib cortical bone and the structural properties of whole ribs were quantified at strain rates similar to those observed in frontal impacts. The rib cortical bone underwent coupon tension testing, while the whole ribs underwent bending tests intended to simulate loading from a frontal impact. The rib material properties accounted for less than 50% of the variation observed in the whole rib structural properties, indicating that other factors, such as rib geometry, were also influencing the structural response of whole ribs. Age was significantly negatively correlated with the modulus, yield stress, failure strain, failure stress, plastic strain energy density, and total strain energy density. However, sex did not significantly influence any of the material properties. Cortical bone material properties were quantified from the ribs that underwent the whole rib bending tests and subject-matched, untested (control) ribs in order to evaluate the effect of loading history on material properties. Yield stress and yield strain were the only material properties that were significantly different between the previously tested and control ribs.
The results of this dissertation can guide ATD and safety restrain design. Additionally, this dissertation provides human surrogate response data and rib material property data for the validation of finite element models, which can then be used to evaluate injury mitigation strategies for MVCs.PHD
Buchteile zum Thema "Human thorax surrogate"
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Chaufer, Martin, Rémi Delille, Benjamin Bourel, Christophe Marechal, Franck Lauro, Olivier Mauzac und Sebastien Roth. „The Use of Human Surrogate for the Assessment of Ballistic Impacts on the Thorax“. In Dynamic Behavior of Materials, Volume 1, 121–28. Cham: Springer Nature Switzerland, 2024. http://dx.doi.org/10.1007/978-3-031-50646-8_18.
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Chaufer, Martin, Rémi Delille, Benjamin Bourel, Christophe Maréchal, Franck Lauro, Olivier Mauzac und Sébastien Roth. „Toward a Physical Human Thorax Surrogate Dedicated to Blunt Ballistic Impacts Based on FE Simulations“. In Computer Methods in Biomechanics and Biomedical Engineering II, 233–41. Cham: Springer Nature Switzerland, 2024. http://dx.doi.org/10.1007/978-3-031-55315-8_26.
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„Outblooming Human Rights Violations in Surrogacy: Thorns Beneath the Rose“. In Advancement of Human Rights in India: Contemporary and Emerging Challenges, 210–21. B1/I-1 Mohan Cooperative Industrial Area, Mathura Road New Delhi 110 044: SAGE Publications Pvt. Ltd, 2021. http://dx.doi.org/10.4135/9789354793134.n16.
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Shah, Chirag S., Jong B. Lee, Warren N. Hardy und King H. Yang. „A Partially Validated Finite Element Whole-Body Human Model for Organ Level Injury Prediction“. In ASME 2004 International Mechanical Engineering Congress and Exposition. ASMEDC, 2004. http://dx.doi.org/10.1115/imece2004-61844.
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A finite element whole-body human model, which represents a 50th percentile male, was developed by integrating three detailed human component models previously developed at Wayne State University (WSU): a thorax model with detailed representation of the great vessels [1], an abdomen model [2], and a shoulder model [3]. This new model includes bony structures such as scapulae, clavicles, the vertebral column, rib cage, sternum, sacrum, and illium and soft tissue organs such as the heart, lungs, trachea, esophagus, diaphragm, kidneys, liver, spleen, and all major blood vessels including the aorta. In addition to model validations already reported at the component level, the new whole-body model was further validated against two sets of experimental data reported by Hardy [4]. In these experiments, human cadavers were loaded either by a seatbelt or by a surrogate airbag about the mid-abdomen, approximately at the level of umbilicus. It is believed that exercising a validated human model is an inexpensive and efficient way to examine potential injury mechanisms. In some cases, this can provide insight into the design of subsequent laboratory experiments.
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Cesari, Dominique, und Robert Bouquet. „Behaviour of Human Surrogates Thorax under Belt Loading“. In Stapp Car Crash Conference. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, 1990. http://dx.doi.org/10.4271/902310.
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Yoganandan, Narayan, John R. Humm, Frank A. Pintar, Karen H. Brasel, Rodney W. Rudd und Stephen A. Ridella. „Thoraco-Abdominal Deflection Responses of Post Mortem Human Surrogates in Side Impacts“. In 56th Stapp Car Crash Conference. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, 2012. http://dx.doi.org/10.4271/2012-22-0002.
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Serres, Jennifer L., Dan V. Jones, Rabih E. Tannous, Nathan Dau und Cynthia A. Bir. „Evaluation of Lower Limb Injury Mitigation Techniques for High Velocity Impacts With the Mil-LX“. In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53269.
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Improvised Explosive Devices (IED) and landmines present a significant threat to mounted troops currently serving in Iraq and Afghanistan. As a result of these threats, a substantial number of lower limb injuries are sustained by service members. Due to this reality, a critical factor in military vehicle design is the mitigation of lower limb trauma. Past studies have shown that the standard Hybrid III and THOR-LX are not biofidelic in military axial loading conditions (up to 12 m/s). Both of these surrogates over predict axial forces compared to Post Mortem Human Specimens (PMHS) [1]. As a result, a new surrogate was developed, Mil-LX (Military Lower Extremity), that matches the PMHS response for axial loading of the lower leg up to 12 m/s [2,3]. While injury mitigation techniques, such as energy absorbing mats, foot rests, and isolation floors, have been effective in reducing lower extremity injuries in live fire test events, there are several variants of each of these methods. Additionally, it has also been suggested that the positioning of the lower limbs may affect the load sustained by these extremities [4].
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Jaradat, Waseem, Joseph Hassan, Guy Nusholtz, Khalil Taraman und Sanaa Taraman. „A Comparison Between Head Impact Response of Hybrid III and THOR-NT Dummy Heads in FMVSS201 Tests“. In ASME 2006 International Mechanical Engineering Congress and Exposition. ASMEDC, 2006. http://dx.doi.org/10.1115/imece2006-16322.
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The impact response of the forehead of both the Hybrid III dummy and THOR dummy was designed to the same human surrogate data. Therefore, when the forehead of either dummy is impacted with the same initial conditions, the acceleration response and consequently the head impact criterion HIC should be similar. If the THOR dummy is used in the FMVSS 201 free motion headform tests, then when it strikes the interior trim of the vehicle, as prescribed by the FMVSS 201 procedure, the acceleration response should be similar to that of the Hybrid III, as long as only the forehead engages the vehicle interior. To compare and contrast the response of the two dummy heads under FMVSS 201 testing, a design of experiments (DOE), that is a function of seven variables, is utilized to develop a mathematical model of the Head Impact Response. These independent parameters include five trim manufacturing process variables that relate to the interior that the dummy head hits in 201 testing: mold temperature, melt temperature, packing pressure, hold pressure, and injection speed. Two operational variables were also considered: free motion Headform approach angle and the dummy head drop calibration. An incomplete block design approach is utilized in order to significantly reduce the number of experiments. The DOE approach determines the response in the form of the Head Impact Criterion (HIC) with respect to the seven variables at 99% confidence level. The results describe the response data of both dummy heads. The response data of the dummy heads is described. Results indicate that the Hybrid III dummy head and the THOR dummy head have significantly different response characteristics in terms of magnitude of response, variation to different input conditions, repeatability, HIC values, and acceleration time history.
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Albert, Devon L., Stephanie M. Beeman und Andrew R. Kemper. „Assessment of Thoracic Response and Injury Risk Using the Hybrid III, THOR-M, and Post-Mortem Human Surrogates under Various Restraint Conditions in Full-Scale Frontal Sled Tests“. In 62nd Stapp Car Crash Conference. 400 Commonwealth Drive, Warrendale, PA, United States: SAE International, 2018. http://dx.doi.org/10.4271/2018-22-0001.
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